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Biomedical subjects

J P Gibson

Publications and source records attributed to J P Gibson.

9 recordsLinked to original sources

Three-month effects of MDL 19,660 on the canine platelet and erythrocyte.

Nine male and nine female Beagle dogs were divided into three groups and administered orally 0, 15, or 30 mg/kg/day of the antidepressant compound MDL 19,660(5-(4-chlorophenyl)-2,4-dihydro-2,4-dimethyl-3H-1,2,4-triazole-3-t hione) for 3 months to determine the long-term effects on hemopoietic cells. Compared to a control platelet range of 353,000-452,000/microliters, a thrombocytopenia reached lowest mean levels of 135,000/microliters in the 15 mg/kg/day dogs after 2 weeks and 81,000/microliters in the 30 mg/kg/day dogs after 1 week. Subsequently, platelet numbers progressively increased and by the end of the study averaged 222,000/microliters and 203,000/microliters in dogs administered 15 and 30 mg/kg/day. Ultrastructural study of the platelet increase in the 30 mg/kg/day dogs revealed more smaller discoid platelets but no change in percentage platelets with vacuolar degeneration. Histologically, megakaryocyte hyperplasia was present in the sternal marrows and spleens of treated dogs. These observations suggest that increased thrombopoiesis rather than reduced destruction was involved in this partial recovery of platelet numbers during continuous treatment. Concurrently, cyclic formation of reticulocytes and Heinz bodies occurred in dogs given 30 mg/kg/day of MDL 19,660. These dogs had slightly lower erythrocyte counts, hemoglobin levels, and hematocrits in association with hemosiderosis (spleen, liver), extramedullary hematopoiesis (spleen), and bone marrow hypercellularity. These findings indicate that both destructive and regenerative processes followed MDL 19,660-induced Heinz body formation.

Animals

Effect on production traits of bovine somatotropin for up to three consecutive lactations.

Thirteen (control) cows were injected daily with saline and 22 with bST (12 at 10.3 mg/d and 10 at 20.6 mg/d) through wk 5 to 42 of lactation. Nine of the treated cows had received bST in the previous lactation, and 7 cows received bST in the previous two lactations. All control cows and 6 treated cows had not previously received bST. Treatment with bST caused substantial increases in milk production, feed intake, and efficiency of feed conversion in the current lactation, which is consistent with previous trials. Increases in feed intake were established fully within 9 wk of starting bST administration, somewhat earlier than usually reported. Treatment with bST in one or two previous lactations caused a statistically significant 14% reduction in production and 8% reduction in efficiency of feed conversion during the first 9 wk of bST treatment in the current lactation; reductions observed later in lactation were not statistically significant. Differences for other traits were not statistically significant. In combination with earlier trials, these results suggest that, although bST has beneficial effects on production and efficiency traits, these benefits may be considerably lower in the second and subsequent lactations of bST use. However, carry-over effects on cows not receiving bST in the current lactation were not explored in this trial.

Animals

The effects of genetic and phenotypic production potential on response to recombinant bovine somatotropin.

Evidence was sought for an interaction between both phenotypic and genetic production potential and response of milk production to administration of bST in three trials of 38, 43, and 35 cows. In each trial, bST was administered in doses of 0, 10.3, 20.6, and, in trial 1 only, 41.2 mg/d for 38 wk from wk 4 of lactation. Data were analyzed for each experiment separately and combined across experiments. Analyses included separate regressions for treated and untreated animals for milk production during the production period on pretreatment production and estimated breeding value for milk production. Breeding value was estimated as the sire's estimated transmitting ability plus one-half of the maternal grandsire's estimated transmitting ability. With the exception of regression on estimated breeding value in trial 1 and in combined data, differences between treated and untreated animals in the regression of milk production on pretreatment milk production or on estimates of breeding value were not statistically significant. However, regressions on pretreatment production were substantially lower for treated than for untreated animals in each of the three trials. Regressions on breeding value estimated from sire and maternal grandsire estimated transmitting abilities were substantially, but not significantly, lower for untreated than for treated animals in all three trials. The results suggest that cows with high production potential for nongenetic reasons may show diminished response to bST, whereas cows with genetically high production potential show enhanced response. However, borderline statistical significance argues for considerable further examination before drawing firm conclusions.

Animals

Genetic value of herd life adjusted for milk production.

Cow herd life adjusted for lactational milk production was investigated as a genetic trait in the breeding objective. Under a simple model, the relative economic weight of milk to adjusted herd life on a per genetic standard deviation basis was equal to CVY/dCVL where CVY and CVL are the genetic coefficients of variation of milk production and adjusted herd life, respectively, and d is the depreciation per year per cow divided by the total fixed costs per year per cow. The relative economic value of milk to adjusted herd life at the prices and parameters for North America was about 3.2. An increase of 100-kg milk was equivalent to 2.2 mo of adjusted herd life. Three to 7% lower economic gain is expected when only improved milk production is sought compared with a breeding objective that included both production and adjusted herd life for relative value changed +/- 20%. A favorable economic gain to cost ratio probably exists for herd life used as a genetic trait to supplement milk in the breeding objective. Cow survival records are inexpensive, and herd life evaluations from such records may not extend the generation interval when such an evaluation is used in bull sire selection.

Animals

Effects of high-dose gamma-vinyl GABA (vigabatrin) administration on visual and somatosensory evoked potentials in dogs.

gamma-Vinyl GABA (GVG, vigabatrin) is a GABA transaminase-inhibiting antiepileptic agent. In dogs, chronic GVG administration produces reversible microvacuolation (intramyelinic edema) in discrete brain regions and slowing in central afferent transmission as measured by somatosensory evoked potentials (SEPs). Because this microvacuolation is especially prominent in the optic tract, this study tested the sensitivity of visual evoked potentials (VEPs) to GVG-induced changes in conduction. We also replicated the earlier SEP findings. Eight beagles received daily oral vigabatrin at the maximum tolerated dose (300 mg/kg/day); four were placebo controls. Cortical VEPs and SEPs were recorded using scalp needle electrodes at baseline and every 2 weeks throughout treatment. One treatment dog died at 2 weeks. The remainder showed an increase in central latencies beginning at 6 weeks, attaining significance (p < 0.05) at 8 and 10 weeks for SEPs and VEPs, respectively. No changes occurred in peripheral or spinal conduction in treated dogs, or in any measure in control dogs. Three GVG and two control dogs were followed after drug was withdrawn; both VEP and SEP measures returned to baseline values within 5 weeks. These findings support the use of VEPs and SEPs to monitor patients receiving vigabatrin therapy.

Aminocaproates

Effect of tilorone hydrochloride on the lymphoid and interferon responses of athymic mice.

Nude athymic mice, which lack T-lymphocytes and are unable to mount a cellular immune response, failed to develop the lymphopenia so characteristically produced by a 100 mg/kg oral dose of tilorone hydrochloride in normal mice. The antiviral activity detected in athymic mice 18 hr after a 150 mg/kg oral dose of tilorone was significant, although somewhat less than that found in treated normal mice. These findings suggest that tilorone hydrochloride has a specific effect on T-lymphocytes that accounts for its effect on cellular immunity, but that its antiviral activity is not primarily mediated by T-lymphocytes.

Animals

Decrease in the activity of the drug-metabolizing enzymes of rat liver following the administration of tilorone hydrochloride.

Tilorone hydrochloride, 2,7-bias(2-(diethylamino)ethoxy(fluoren-9-one dihydrochloride, has been studied to determine its effect on the drug-metabolizing enzymes of the liver of male Charles River CD strain rats. Single and multiple doses of tilorone-HCl, 100 mg/kg/day po, were used. Most experiments were performed 24 hr after the last dose, except for a study 5 hr after dosing, and those in which the duration of effects of tilorone hydrochloride were determined. The hexobarbital sleeping time was prolonged after both single doses and four doses of tilorone hydrochloride. The 4-dose regimen prolonged the zoxazolamine paralysis time but the single dose did not. A decrease in microsomal protein was observed after the single- and 4-dose regimens but not after 21 daily doses of tilorone-HCl. Cytochrome P-450 content of microsomes was decreased by the single doses, 100 and 250 mg/kg po, and by 4 and 21 doses of 100 mg/kg/day po. Activities of aminopyrine demethylase and hexobarbital oxidase also were decreased by the above regimens, but the activity of hexobarbital oxidase was affected more markedly. Electron micrographs of rat liver, after treatment with tilorone-HCl, 100 mg/kg/day for 21 days, revealed many membranous structures in the form of whorls.

Aminopyrine N-Demethylase