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Biomedical subjects

W R Campbell

Publications and source records attributed to W R Campbell.

At least 19 recordsLinked to original sources
PubMed1995

Centrally mediated ocular hypotension: potential role of imidazoline receptors.

These experiments sought to: (1) determine if alpha 2/I1 agonists that are topically active on the eye have similar effects on intraocular pressure when applied to the CNS and (2) ascertain whether these agents lower IOP, in part, via central alpha 2 receptors and/or imidazoline (I1) receptors. New Zealand White rabbits were fitted with chronic indwelling stainless-steel guide cannulas in several brain regions including the lateral ventricle, third ventricle (3V), or medullary intermediate reticular zone. Animals were allowed 5 days' recovery time prior to experiments measuring the effects of drugs on IOP via applanation pneumatonometry. Some animals were also pretreated with 400 micrograms of 6-hydroxydopamine injected into the lateral ventricle to determine the site of action of these alpha 2/I1 agonists. In initial experiments involving microinjection into the lateral ventricle, UK-14,304-18 evoked ocular hypotension that was inhibited by the alpha 2-antagonist rauwolscine but not by the I1-receptor antagonist efaroxan. Conversely, moxonidine and oxymetazoline were preferentially inhibited by efaroxan rather than by rauwolscine. Subsequently, experiments have shown that moxonidine and oxymetazoline, but not UK-14,304-18 will lower intraocular pressure when microinjected into the medullary intermediate reticular zone region and that efaroxan, but not rauwolscine, will inhibit ocular hypotension induced by moxonidine and oxymetazoline. Pretreatment with 6-hydroxydopamine (48 hours) completely eliminated the ocular hypotension induced by moxonidine. These preliminary data demonstrate that alpha 2- and I1-receptors in the brain mediate ocular hypotension induced by UK-14,304-18 and moxonidine/oxymetazoline, respectively. Moreover, the medullary intermediate reticular zone area of the brain stem is the probable presynaptic site mediating ocular hypotension induced by moxonidine and oxymetazoline.

Administration, Topical↗
PubMed1994

The central effects of moxonidine on intraocular pressure and its antagonism by L-659, 066 and L-657, 743 in the rabbit.

1) The imidazoline, moxonidine (MOX), injected icvt into the anterior lateral ventricle of NZW rabbits induced ocular hypotension (> 7.0 mmHg) that persisted for two hrs. 2) L-659, 066 injected i.v. or icvt inhibited MOX-induced ocular hypotension, significantly. 3) L-657, 743, injected icvt at 100-fold lower concentration than icvt L-659, 066, significantly inhibited MOX-induced ocular hypotension. 4) Alpha-2-adrenoceptors, located in the CNS, play a role in MOX-induced ocular hypotension, as evidenced by the ability of the relatively selective alpha-2 antagonists, L-659, 066 and L-657, 743 to inhibit icvt MOX-induced ocular hypotension.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1992

One-year dietary toxicity study with methidathion in beagle dogs.

The purpose of this study was to determine the chronic toxicity of methidathion, an organophosphate insecticide, in dogs. Groups of beagle dogs, four/sex/dose, were fed methidathion at constant dietary concentrations of 0, 0.5, 2, 4, 40, or 140 ppm for 1 year. The equivalent daily dosages were approximately 0, 0.02, 0.07, 0.15, 1.4, and 4.7 mg/kg. There were no deaths or adverse clinical signs associated with the treatment. Weekly body weights and weight gains were not affected. Mean daily food consumption was reduced in male dogs given the 140-ppm diet. Major treatment-related effects were cholestasis, chronic inflammation in the liver, and cholinesterase (ChE) inhibition. The liver effects were indicated by gross and microscopic pathologic findings as well as moderate increases in serum bile acids and enzyme activities (alanine aminotransferase, aspartate aminotransferase, sorbitol dehydrogenase, and alkaline phosphatase) in all dogs receiving greater than or equal to 40 ppm. RBC ChE was inhibited in males at greater than or equal to 40 ppm and in females and 140 ppm. Brain ChE was inhibited in both sexes at 140 ppm; the magnitude of inhibition relative to control was slightly greater with the cerebellar fraction than with the cerebral fraction. Serum ChE was not affected at any dose level. In conclusion, liver was the target organ in beagle dogs given greater than or equal to 40 ppm (equivalent to 1.4 mg/kg/day) methidathion in diet for 1 year. The no-observable-effect level was 4 ppm (0.15 mg/kg/day) for both liver cholestasis and ChE inhibition.

Animals↗
PubMed1991

Direct vasoconstriction as a possible cause for amphotericin B-induced nephrotoxicity in rats.

In anesthetized rats we tested the hypothesis that amphotericin B (AmB) reduces glomerular filtration rate (GFR) by activating the tubuloglomerular feedback (TGF) mechanism. Infusion of 1 mg/kg AmB over 50 min was followed by a reduction in kidney GFR (from 0.47 +/- 0.03 to 0.39 +/- 0.02 ml/min per 100 g body wt during the second hour after infusion; P less than 0.05) and by an increase in urine flow and urinary chloride excretion. Single-nephron GFR (SNGFR) measured in proximal (TGF interrupted) or distal tubules (TGF intact) decreased to a similar degree from 33.4 +/- 1.8 and 30.6 +/- 1.2 nl/min in the control period to 19.7 +/- 1.9 and 21.2 +/- 1.6 nl/min during the second hour after AmB infusion (P less than 0.05). Distal chloride concentrations and TGF responses to changes in loop of Henle flow rate were not significantly altered by AmB. AmB at 10(-5) M reduced the diameter of isolated perfused afferent arterioles from rabbit kidneys. In isometrically contracting rings of rabbit aorta and renal artery in vitro AmB produced endothelium-independent constriction, with half-maximal contraction (EC50) being achieved by 1.8 x 10(-6) and 2.6 x 10(-6) M in intact vessels and 1.3 x 10(-6) and 1.7 x 10(-6) M in endothelium-denuded vessels respectively. Tension development did not occur in Ca-free media or in the presence of Ca channel blockers. Pretreatment with ouabain or Bay K 8644 potentiated the effect of AmB. The vasoconstrictive effect of AmB was counteracted by aminophylline and atrial natriuretic peptide. We conclude that the AmB-induced reduction in GFR is not caused by TGF activation and that AmB has a direct vasoconstrictor effect that is probably initiated by depolarization-induced opening of Ca channels. This effect may be an important component of the nephrotoxic actions of AmB.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Retention of larvicidal activity after feeding cyromazine (Larvadex) for the initial 20 weeks of life of single comb White Leghorn layers.

Single Comb White Leghorn pullets were fed cyromazine (Larvadex) continuously at levels of 0, 25, 250, and 1,000 mg/kg diet (ppm) from hatch to 20 wk of age. Fresh manure was bioassayed for toxicity to housefly, Musca domestica, larvae beginning at the 6th wk after removal of cyromazine from the feed, and at weekly intervals thereafter. At 6 wk after removal of the feed additive there was 51.6% fly mortality at 25 ppm, 75.7% at 250 ppm, and 86.5% at 1,000 ppm relative to the 0-ppm control. Fly mortality decreased to less than 10.7% mortality at 13 and 15 wk postremoval for hens grown on 25 ppm and 250 ppm cyromazine, respectively. Hens grown on 1,000 ppm cyromazine produced manure that was still exhibiting more than 50% fly mortality 20 wk after removal of the feed additive. These data demonstrate retention of cyromazine in laying hens for up to 20 wk after feeding the chemical to the birds at 5 to 200 times greater than the maximum recommended rate for the initial 20 wk of life.

Administration, Oral↗
PubMed1989

Effects of CGA-72662 (Larvadex) in turkeys during rearing and reproduction.

Turkeys were fed CGA-72662 (Larvadex) at treatment levels of 0, 500, 1,000, and 2,000 mg/kg diet from hatch to 16 wk of age, when the 500 mg/kg level was reduced to 250 mg/kg because of a significant reduction in feed intake. All diets continued through 40 wk of age. Body weight, feed consumption, livability, egg production, fertility, hatchability, and progeny performance were examined. Turkeys fed a treatment level of 2,000 mg CGA-72662/kg diet exhibited reduced growth rate and feed consumption prior to sexual maturity and decreased fertility and poult weight after sexual maturity. Necropsies suggested that the kidney was the primary site of lesions at the 1,000 and 2,000 mg/kg diet treatment levels. The kidneys were characterized as enlarged, nodular, and cystic, containing urate deposits and areas of necrosis. These data indicate that dosage levels of CGA-72662 at 250 mg/kg diet produced no deleterious effects on growth, feed consumption, egg production, fertility, hatchability, livability, or progeny performance.

Age Factors↗
PubMed1987

Cardiovascular effects of microinjections of adenosine analogs into the fourth ventricle of rats.

Rats were implanted with chronic indwelling cannulae into the posterior region of the fourth ventricle. After recovery from surgery, acute experiments on blood pressure were conducted under urethane anesthesia. The blood pressure and heart rate responses following administration of two adenosine analogs, NECA and L-PIA were examined. Microinjections of both analogs produced dose-dependent reductions in blood pressure and heart rate. NECA was approximately 20-fold more potent than L-PIA in reducing blood pressure and depressing heart rate. The cardiovascular effects of both analogs were antagonized by parenteral injections of caffeine. These findings show that microinjections of analogs of adenosine into the fourth ventricle can influence areas of the central nervous system involved in cardiovascular control.

Adenosine↗
PubMed1987

The effects of parenteral injections of adenosine and its analogs on blood pressure and heart rate in the rat.

The dose-response effects of adenosine and its analogs on cardiovascular parameters were examined in rats following intravenous administration. 5'-N-ethylcarboxamidoadenosine (NECA) was by far the most potent analog in reducing mean arterial blood (PA) pressure while N6-(3-pentyl)-adenosine exerted the most potent bradycardic action. The N6-substituted (S)-diastereoisomers were substantially less potent in reducing PA and heart rate than NECA and the N6-substituted (R)-diastereoisomers. The cardiovascular effects of adenosine analogs persist, to varying degrees, much longer than those of adenosine itself.

Adenosine↗
PubMed1987

Central effects of adenosine analogs on blood pressure and heart rate in the mouse.

Mice implanted with chronic indwelling cannulae were injected into the lateral cerebral ventricle with two adenosine analogs, NECA and L-PIA, and the effects on blood pressure and heart rate recorded. Both analogs produced dose-related reductions in blood pressure and heart rate. NECA exhibited approximately 10 fold more potency than L-PIA on mean arterial blood pressure. The effects of both drugs on blood pressure and heart rate were antagonized by parenteral injections of caffeine. These results show that injections of adenosine analogs into the lateral ventricle of mice can influence the areas of the central nervous system involved in the control of cardiovascular function.

Adenosine↗
PubMed1986

The effects of central injections of adenosine analogs on blood pressure and heart rate in the rat.

Rats were implanted with chronic indwelling cannulae into the lateral cerebral ventricle. After recovery from surgery, acute experiments on blood pressure were conducted under methoxyflurane/nitrous oxide anesthesia. Rats were injected intracerebroventricularly with two adenosine analogs, 5'-N-ethylcarboxaminidoadenosine (NECA) and (-)-N-(1-methyl-2-phenylethyl)adenosine(L-phenylisopropyladenosine) (L-PIA), and the effects on blood pressure and heart rate recorded. Both analogs produced dose-related reductions in blood pressure and heart rate with L-PIA producing a more potent depression of heart rate than NECA. These effects on blood pressure and heart rate were antagonized by parenteral injections of caffeine. In separate experiments, the responses of blood pressure and heart rate to microinjection of NECA into the brainstem of rats anaesthetized with methoxyflurane/nitrous oxide were also examined. Microinjection of 2.7 nmol/kg into the fourth ventricle in the region of the area postrema produced a profound and long-lasting depression of blood pressure and heart rate. These results show that central injections of analogs of adenosine can influence the areas of the central nervous system involved in the control of cardiovascular function.

2-Chloroadenosine↗
PubMed1985

Therapeutic alternatives in patients with esophageal cancer.

The records of 52 patients treated either with surgery alone (Group A), preoperative radiotherapy (Group B), or combined preoperative chemotherapy and radiotherapy (Group C) were reviewed to determine the optimal management of patients with squamous cell carcinoma of the esophagus. There was a significant difference in the number of patients with stage III disease between Groups A and C (100 percent and 48 percent, respectively). With the decrease in patients with stage III disease, both resectability rates in Groups A and C (21 percent and 62 percent) and 2 year cumulative survival (0 and 52 percent) increased. Eleven patients in Group C (53 percent) had apparent total resolution of the primary tumor after preoperative therapy. Microscopic tumor was present but was not detected by repeat endoscopy in 35 percent of these patients. The survival rate was higher in patients with apparent total tumor regression who underwent esophageal resection. These results suggest that patients with squamous cell carcinoma of the esophagus are best treated with preoperative chemotherapy and radiotherapy followed by esophagectomy regardless of their response to preoperative therapy.

Adult↗
PubMed1983

Effect of high levels of Larvadex on reproduction in Leghorn breeders.

The insect growth inhibitor, Larvadex, was fed to egg type breeder hens for 8 weeks at levels of 0, 50, 100, 500, 1000, and 2000 ppm and to the same strain of males at 0 and 2000 ppm. All birds were kept in individual cages. Fertility was determined following artificial insemination. Egg production was significantly increased in Experiment 1 but numerically decreased in Experiment 2 by feeding 1000 ppm Larvadex. Feeding 2000 ppm significantly decreased egg production in both experiments. Egg weight was highest at 100 ppm and decreased with higher treatment levels. Specific gravity of eggs was improved with all Larvadex treatments. Fertility was not affected by treatment of females or males. Hatchability was reduced by the 1000 and 2000 ppm levels in the hen's diet. Semen quality was not significantly affected by feeding Larvadex at 2000 ppm.

Animals↗