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Biomedical subjects

K L Davison

Publications and source records attributed to K L Davison.

At least 37 records · Page 2Linked to original sources

Propachlor-S-glutathione metabolism by kidneys and ureters of calves.

Six anesthetized 2- to 21-d-old male Guernsey calves weighing 28 to 61 kg were used in experiments in which either the left kidney was perfused, via the left renal artery, or the left ureter was perfused with metabolites of propachlor (2-chloro-N-acetylacetanilide, a herbicide). The glutathione conjugate of propachlor (2-S-glutathionyl-N-acetylacetanilide) was metabolized by both kidney and ureter to the cysteine conjugate (2-S-cysteinyl-N-isopropylacetanilide). The glutathione conjugate was not metabolized to the mercapturic acid conjugate (2-S-[N-acetyl]cysteinyl-N-isopropylacetanilide). When the mercapturic acid conjugate of propachlor was presented to the kidney, it was eliminated in urine. First-pass metabolism and elimination of the glutathione conjugate by the kidney was 16% of the dose, whereas first-pass elimination of the mercapturic acid was 33%. Absorption of the glutathione conjugate of propachlor, or its metabolites, or of glycine by the ureter was nil. The bovine species may be unable to form mercapturic acids from glutathione conjugates of some xenobiotics, which may make cattle more easily poisoned by these xenobiotics than chickens, pigs, and rats.

Acetanilides↗

Metabolism of the glutathione conjugate of propachlor by in situ perfused kidneys and livers of rats.

1. [1-14C]Propachlor-GSH was perfused at 0.34, 3.4 and 34 mumol/h through the portal vein or the right renal artery of anaesthetized rats with biliary and ureteral cannulas. Urine was the predominant route for elimination of the 14C regardless of the route of perfusion. 2. Mercapturic acid conjugates were found to be the end-products of metabolism of the 14C-propachlor-GSH by rat kidneys and liver, indicating that all enzymes necessary for the catabolism of GSH conjugates to mercapturates were present in each of these tissues. 3. Perfusion of 14C-propachlor-GSH at 34 mumol/h appeared to exceed the metabolic capacity of both liver and kidneys for this substrate. At this dose, parent compound was detected in the bile of portally perfused rats, and the amounts of 14C recovered in bile, kidneys and carcasses of renally perfused rats were greater than when smaller dosages were perfused.

Acetanilides↗

Evidence for the absence of cysteine S-conjugate N-acetyltransferase activity in the metabolism of propachlor, naphthalene, and dichlobanil in calves.

1. The glutathione conjugate of 2-chloro-N-isopropyl[1-14C]acetanilide (14C-propachlor) was perfused through a calf kidney in situ; 23% of the dose was excreted in the perfused kidney urine as the cysteine conjugate, no mercapturic acid was detected. 2. A 5-day-old calf dosed orally with 14C-propachlor excreted 70% dose in the urine as the cysteine conjugate; no mercapturic acid was detected. Rumen microflora were established in the calf (5 weeks older) and the experiment was repeated with the same results. 3. When the same calf was dosed 1 week later with 14C-naphthalene, 99% dose was excreted in the urine, mostly as the dihydrodiol-glucuronide (34%) and the dihydrohydroxy-cysteine conjugate (47%); no mercapturate was detected. 4. A 9-day-old calf dosed orally with 2,6,-dichlorobenzo[14C]nitrile (14C-dichlobanil) excreted 67% dose in the urine as cysteine conjugates (34%), and products of cysteine conjugate beta-lyase cleavage of cysteine conjugates (30%); no mercapturates were detected. 5. Cysteine S-conjugate N-acetyltransferase activity in calf kidney and liver was about 10% of that in the corresponding rat tissues.

Acetanilides↗

A comparison study of vecuronium bromide and atracurium besylate for rapid sequence induction.

Rapid sequence induction is necessary in emergency surgical operations to lessen the chance of aspiration of stomach contents. Succinylcholine usually is the relaxant of choice, because of its rapid onset. However, succinylcholine has side effects which may result in potentially life-threatening conditions. The purpose of this study was to compare two short-acting non-depolarizing muscle relaxants-vecuronium and atracurium, using the priming principle, with a depolarizing muscle relaxant, succinylcholine. The comparison may determine if a more suitable method for rapid sequence induction can be identified. Conditions at intubation and at the time to 80-90% neuromuscular blockade were evaluated. Subjects were intubated when the train of four revealed an 80-90% twitch depression. In Group I, the control group using succinylcholine, the mean time to 80-90% neuromuscular block was 74.8 seconds. In Group II subjects, who had received vecuronium, the mean time was 149.4 seconds. Subject in Group III, who received atracurium, had a mean time of 163.7 seconds. There was statistical significance within all three groups (ANOVA, p less than 0.01). Group I subjects showed a significantly faster time to 80-90% neuromuscular block when compared with subjects in Group II and III, but no difference in the time to 80-90% block was revealed between Group II and Group III subjects. Conditions for intubation at 80-90% neuromuscular blockade were the same for all three groups. It was concluded that the administration of vecuronium and atracurium using the priming principle did not allow onset times similar to succinylcholine and that the intubating conditions were similar among all three groups at 80-90% neuromuscular blockade.

Adolescent↗

A kidney perfusion method for metabolism studies with chickens using propachlor as a model.

1. A procedure for directly perfusing chicken kidneys in situ with xenobiotics is described. 2. When propachlor (2-chloro-N-isopropylacetanilide) or the glutathione, cysteine and mercapturic acid conjugates of propachlor were individually perfused through chicken kidneys, propachlor mercapturate was isolated from the urine and identified as an end product, indicating that all enzymes necessary for mercapturic acid formation were present in chicken kidney.

Acetanilides↗

Metabolism of naphthalene in roosters.

1. The metabolism of naphthalene in roosters was similar to that in rats. At least 45% of the dose was isolated from the urine as metabolites that could be formed from arene oxide precursors. 2. Urine was the major route for excretion (79%) of 14C-naphthalene from colostomized roosters. Roosters with cannulated bile ducts excreted about 24% of the dose in bile. 3. Roosters excreted tetrahydrotrihydroxy mercapturic acids of naphthalene as major urinary metabolites which indicates either the formation of diepoxide intermediates or sequential epoxidation-conjugation processes. 4. The major biliary metabolites in rooster bile were characterized as cysteine and cysteinylglycine conjugates of tetrahydrotrihydroxynaphthalenes.

Animals↗

Intermediary metabolism of 2,6-dichlorobenzonitrile (dichlobenil) in chickens and growth of chickens fed dichlobenil.

1. Ten 14C-labelled metabolites were isolated from either bile (6 metabolites) or urine (7 metabolites) from chickens given single oral doses of 2,6-dichlorobenzo[14C]nitrile (14C-dichlobenil). All metabolites were benzonitriles with the following ring substituents: two Cl, OH (two isomers); Cl, two OH; Cl, OH, SH; Cl, OH, S-glutathione; Cl, OH, S-cysteinylglycine; Cl, OH, S-cysteine; and Cl, OH, S-(N-acetyl)cysteine. 2. 2-(S-Glutathionyl)-3-hydroxy-6-chlorobenzo[14C]nitrile perfused through chicken kidneys in situ was excreted in urine from the perfused kidney (44% dose) as 2-mercapto-3-hydroxy-6-chlorobenzonitrile. 3. Dichlobenil (2,6-dichlorobenzonitrile) was fed at 0, 75, 150 or 225 p.p.m. in the diet to broiler and laying strains of cockerels to determine biological activity. Feed consumption and growth were not affected, but liver and kidney weights were higher in chicks fed the dichlobenil. The percentage of lipid or nitrogen in the livers and kidneys from chicks fed dichlobenil did not differ from controls and histological or ultrastructural changes were not observed in these tissues.

Animals↗

[14C]monensin balance in bile-fistulated ponies.

To measure absorption of monensin or its metabolites and its elimination from the body, [14C]monensin sodium was given orally (1 mg/kg body wt) to two bile-fistulated ponies and iv (8.7 mg) to one bile-fistulated pony. For one orally-dosed pony, 4.7% of the 14C was eliminated in bile, 52% in feces, .7% in urine and 33% remained in the gastrointestinal (GI) tract after 3 d. Total 14C recovery was 90%. For the other orally-dosed pony, 18.3% of the 14C was eliminated in bile, 69% in feces, 1.7% in urine and 7% remained in the GI tract after 4 d. Total 14C recovery was 98%. For the iv-dosed pony, 72% of the 14C was eliminated in bile, .5% in feces, 4.9% in urine and 15% remained in the GI tract after 23 h. Total 14C recovery was 96%. Maximum rate of 14C elimination in feces from the orally-dosed ponies occurred on the third and fourth days, and the maximum rate of biliary elimination occurred between 16 and 24 h for one pony and 48 and 56 h for the other. For the iv-dosed pony, 14C became immeasurable in plasma within 12 h after dosing and appeared in bile within 30 min, with maximum biliary concentration occurring at about 1 h. Monensin accounted for a minimum of 19% of the 14C in a 56- to 72-h sample of feces for one orally-dosed pony and a minimum of 25% of the 14C in feces from the same time period for the other.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Dieldrin-14C elimination from turkeys.

A series of experiments were conducted to find ways of removing dieldrin2 residues from tissues of broiler-type turkeys (Meleagris gallopavo). The turkeys were contaminated with dieldrin and dieldrin-14C by oral dosing. Elimination was measured by assaying for 14C in the droppings. Carcass retention was measured by assaying the tissue for 14C, and in one experiment, dieldrin residues were measured by electron capture gas-liquid chromatography. Charcoal, Colestipol, and cholestyramine at dosages approximately equal to an intake of 5% of the diet were ineffective gastrointestinal adsorbants for removing dieldrin residues from the turkeys. Starvation accelerated the elimination of dieldrin from the turkeys, but only if the body lipids were reduced to approximately 10% or less of the carcass dry matter.

Aging↗

Calcium-45 uptake by shell gland, oviduct, plasma and eggshell of DDT-dosed ducks and chickens.

Experiments were conducted with ducks and chickens to determine the effects of acute doses of DDT and DDE on calcium-45 balance and calcium-45 distribution among plasma, femur, tibia, oviduct, shell gland, and eggshell. Species differences in distribution of calcium-45 were evident between control ducks and control chickens. Ducks contained more radiocalcium in plasma, shell glands, tibias, and femurs than chickens and eliminated less radiocalcium in their droppings than chickens. The percentage of radiocalcium deposited in eggshells by control birds of either species was about equal. Ducks and chickens treated with DDT or DDE contained more radiocalcium in their shell glands than their respective controls. Treatment with DDT or DDE caused eggshell thinning in ducks but not in chickens; however, treatment with DDT or DDE did not alter significantly the percentage of radiocalcium that appeared in eggshells of either species.

Animals↗

Dieldrin-14C elimination from chickens.

A series of experiments was conducted with chickens contaminated with dieldrin-14C to find ways of accelerating the elimination of dieldrin from their bodies. The results of these experiments indicated that charcoal, imbiber beads, and the anion exchanges resins, Dowex XFS-4022 and Dowex SBR-C1, would not be useful agents for increasing the amount of dieldrin eliminated via feces (droppings) of chickens. Further, imbiber beads coalesced in the gizzard of the chickens and reduced their appetites. The anion exchange resin, cholestyramine, might be useful as gastrointestinal absorbant for increasing dieldrin elimination in chickens because it increased carbon-14 elimination in droppings, but its effect on carbon-14 residues in carcasses was not clear. We elected not to investigate this compound further. Probucol, investigated because it might alter gastrointestinal absorption or blood physiology that would affect dieldrin elimination, did not increase dieldrin elimination. Severe starvation was the only method investigated that clearly was useful for increasing dieldrin elimination because it increased carbon-14 elimination in droppings and reduced carbon-14 residues in carcasses.

Animals↗

Methoxychlor effects on hepatic storage of vitamin A in rats.

Sixty Sprague-Dawley rats were fed diets containing 0, 10, 100, 1,000, and 10,000 ppm of methoxychlor for 16 weeks under ad libitum- and restricted-feeding regimens. Methoxychlor at 10,000 ppm was lethal to some rats, reduced food consumption and growth, and increased liver weight relative to body weight. Methoxychlor at 1,000 ppm reduced food consumption and growth of rats fed ad libitum but did not reduce growth of restricted-fed rats. Reduced hepatic storage of vitamin A was detectable when methoxychlor was fed at levels of 100 ppm or higher.

Animals↗

P,p-DDT and p,p'-DDE effects on egg production, eggshell thickness, and reproduction of Japanese quail.

p,p' -DDT and p,p' -DDE were investigated for effects on egg production and eggshell thickness in Japanese quail. p,p' -DDT was examined for effects on hatchability and fertility. DDE was tested at 0, 2, 10, 40, and 200 ppm in the diet. No evidence suggested that DDE affected number of eggs laid, egg weight, or eggshell thickness at any level of DDE tested. DDT was tested at 1,2.5, 10 and 40 ppm in the diet. In one experiment, quail fed DDT at 40 ppm and caged in male-female pairs broke more eggs than quail caged similarly but fed lower amounts of DDT or than quail fed an equal amount of DDT but caged alone. DDT did not detectably reduce eggshell thickness, number of eggs laid, fertility, or hatchability. However, paired quail laid fewer eggs than did single quail in two experiments and laid eggs with thinner shells in one experiment.

Animals↗

Mirex-induced hepatic changes in chickens, Japanese quail, and rats.

Mirex was fed in the diet to chickens at 0 to 160 ppm for 12 and 16 weeks, to Japanese quail at 0 to 80 ppm for 12 weeks, and to rats at 0 to 100 ppm for 2 and 4 weeks. Mirex did not affect the concentration of protein or cytochrome P450 in hepatic microsomes of chickens or Japanese quail, nor did it affect hydroxylation of aniline or demethylation of aminopyrine. However, structural changes were apparent in livers of chickens fed mirex at 10 ppm and above and included regions of necrosis and nonspecific cellular aberrations and alterations of sinusoids and bile canaliculi. Mirex caused liver enlargement in rats and increased microsomal protein and cytochrome P450 but did not affect hydroxylation of aniline or demethylation of aminopyrine. Hepatic structural changes in rats that were associated with mirex included proliferation of smooth endoplasmic reticulum and degeneration of some bile canaliculi.

Animals↗