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Biomedical subjects

J D Neill

Publications and source records attributed to J D Neill.

At least 91 records · Page 5Linked to original sources
PubMed1982

Comparison of a direct radioimmunoassay with virus isolation in cell culture for detection of pseudorabies virus in tissues of infected swine.

A direct radioimmunoassay (DRIA) was developed for detection of pseudorabies virus (PRV) in tissues of pigs with clinical disease. Homogenates of tissues prepared from 289 swine were tested for PRV with the DRIA and virus-isolation technique (VIT). The virus was detected in 53 (18%) of the homogenates by both DRIA and VIT. Fifteen (5%) others were positive for PRV by VIT, but negative by DRIA. There were no samples negative by VIT and positive by DRIA. A total of 221 (77%) pigs with clinical PRV infection were negative in both DRIA and VIT. Although the VIT is more sensitive than DRIA, the DRIA possesses certain advantages which include reduced requirement for aseptic procedures and cell cultures, rapidity, and increased objectivity. Moreover, high levels of confidence could be attributed to DRIA-positive results, since DRIA-positive/VIT-negative results were not obtained.

Animals↗
PubMed1981

Observation on the efficacy and pharmacokinetics of betaxolol (SL 75212), a cardioselective beta-adrenoceptor blocking drug.

1 Observations were made in five subjects who exercised before and at 2, 3, 6, 8, 24, 33 and 48 h after the oral administration of placebo and 5, 10, 20 and 40 mg betaxolol. 2 The exercise heart rate remained constant at all times after the placebo. All doses of betaxolol significantly reduced the exercise tachycardia at all times. The maximum effect (34.4 +/- 2.2%) occurred after 40 mg. 3 There was a small decline in effect from the peak to 24 h when 40 mg produced a 23.3 +/- 2.7% reduction and a further decline to 48 h when there was a 14.6 +/- 1.8% reduction. 4 Plasma levels of betaxolol were measured in these studies. The peak plasma concentration occurred between 3 and 8 h with different doses. The plasma elimination half-lives after 10, 20 and 40 mg were 11.4 +/- 2.5, 15.9 +/- 4.9 and 15.1 +/- 3.1 h. 5 The effects of 40 mg betaxolol, 200 mg atenolol, 160 mg propranolol, 160 mg oxprenolol, 400 mg sotalol and placebo on an exercise tachycardia were compared in five subjects who received all treatments in random order. 6 There was no significant difference in the maximum reduction produced in an exercise tachycardia by the different drugs. 7 The effect of all drugs decreased with time. The effect of oxprenolol had worn off at 24 h but at 48 h only atenolol and betaxolol produced significant reductions in the exercise tachycardia. 8 Plasma concentrations of the different drugs were measured and plasma elimination half-lives determined. The half-life for betaxolol was 24.5 h which was longer than that for any of the other drugs. 9 These observations show that betaxolol is a potent beta-adrenoceptor antagonist with a long duration of effect on an exercise tachycardia and a long plasma elimination half-life.

Adrenergic beta-Antagonists↗
PubMed1981

Increased LH secretory response to LHRH after hypophyseal stalk-transection of monkeys.

Luteinizing hormone-releasing hormone (LHRH) will evoke large increases of circulating LH in all species tested except for the rhesus monkey. Indeed, in the present study we found that an intravenous injection of a relatively large dose of LHRH (20 micrograms) evoked only a small (2.2-fold) increase in plasma LH levels, as measured by the dispersed interstitial cell bioassay in 4 intact follicular phase monkeys. In contrast, 4 stalk-transected animals exhibited a significantly greater (19.9-fold) increase in plasma LH levels when treated with 20 micrograms of LHRH within 1 week after surgery. Qualitatively similar differences in responsiveness also existed between the two treatment groups with respect to FSH secretion. 2 stalk-transected monkeys treated with LHRH at weekly intervals for the first 4 weeks after surgery showed progressive declines in the LH secretory response approaching, eventually, that observed in intact animals. In 3 additional monkeys, initiation of estrogen maintenance therapy within 3 h of stalk transection, to achieve mid-follicular phase plasma levels of estradiol, totally abolished hyperresponsiveness to LHRH. Thus, the results of this study demonstrate that a transient increase in pituitary responsiveness to LHRH occurs after hypophyseal stalk transection in rhesus monkeys. Although the results indicate that this phenomenon can be accounted for, in large part, by the absence of estrogen feedback, they do not preclude the possibility that factors other than LHRH and gonadal steroids regulate gonadotropin secretion in monkeys.

Animals↗
PubMed1981

Dopamine levels in hypophysial stalk plasma and prolactin levels in peripheral plasma of the lactating rat: effects of a simulated suckling stimulus.

Secretion of prolactin is tonically inhibited by hypothalamic release of dopamine into the hypophysial portal system. However, the role that changes in dopamine secretion play in altering prolactin secretion after physiologic stimuli is still unknown. The present study was designed to investigate changes in dopamine release into stalk blood during sucking-induced release of prolactin. An increase in prolactin secretion was induced in urethane-anesthetized, lactating rats by a 15-min electrical stimulation of an isolated mammary nerve trunk. This procedure induced a rapid increase in prolactin secretion, and a 7-fold increase in prolactin concentrations was observed within 20-30 min after stimulation began. In unstimulated control rats, prolactin levels remained at baseline values during the period of observation. Then, we measured the effect of this stimulus on the concentration of dopamine in hypophysial stalk plasma. Dopamine concentrations in hypophysial stalk plasma, collected at 15-min intervals before, during and after mammary nerve stimulation, decreased significantly by 20% during stimulation, returned to prestimulation values, and then increased significantly by 20% at 45-60 min. In control rats, no changes in dopamine concentrations were observed. These results demonstrate that a simple, inverse relationship between dopamine secretion and prolactin secretion does not exist during suckling. However, the observed decrease in dopamine secretion during mammary nerve stimulation may be an integral part of a complex mechanism, including other hypothalamic hormones, that lead to the release of prolactin.

Animals↗
PubMed1981

Stimulation of prolactin secretion in rhesus monkeys by vasoactive intestinal polypeptide.

Vasoactive intestinal polypeptide (VIP) is a potent stimulus for prolactin (PRL) release in rats. The purpose of this study was to test the effect of VIP on PRL secretion in rhesus monkeys and to identify its site of action. Three experimental models were used: (1) intact monkeys during the follicular phase of the menstrual cycle; (2) female, hypophyseal stalk-transected, ovariectomized monkeys (St-OVX), and 93) monkey pituitary tissue perifused in vitro. Initial serum concentrations of immunoreactive PRL were more than 10-fold higher for ST-OVX monkeys (52.4 +/- 10.4 ng/ml, X +/- SEM; n = 6) than for intact monkeys (4. 79 +/- 1.0 ng/ml; n = 10). Intravenous administration of VIP (20 micrograms/kg body weight) induced an elevation of circulating PRL in each of the intact and ST-OVX monkeys tested. On the average, VIP treatment evoked more than a 9-fold rise in serum PRL in intact monkeys (p less than 0.01) and more than a 2-fold increase in ST-OVX monkeys (p less than 0.01), while injection of vehicle alone did not affect PRL levels in either experimental group. Addition of VIP (5 x 10(-9) - 5 x 10 (-6) M) to medium perifusing monkey pituitary tissue in vitro stimulated PRL secretion both in the presence and in the absence of dopamine (2.5 x 10(-6) M). Furthermore, the in vitro potency of VIP was comparable, on a molar basis, with that of thyrotropin releasing hormone. Collectively, these results indicate that VIP is a potent stimulus for PRL secretion in monkeys which exerts its effect, at least in part, by a direct action at the pituitary level. Therefore, VIP should now be considered as a possible PRL releasing factor in primates.

Animals↗
PubMed1981

Dopamine in hypophysial stalk blood of the rhesus monkey and its role in regulating prolactin secretion.

Numerous studies are suggestive of dopamine serving as the hypothalamic PRL-inhibiting factor in the monkey. In the present study, we measured dopamine concentrations in plasma collected from the hypophysial stalk and determined whether those concentrations were sufficient to account for the inhibiting effect on PRL secretion exerted by the hypothalamus. First, we collected hypophysial stalk blood from seven follicular phase monkeys (four anesthetized with pentobarbital and three with phencyclidine) using a transorbital surgical approach. Dopamine concentrations, measured with a liquid chromatographic-electrochemical procedure, averaged 0.76 ng/ml in stalk plasma and less than 0.1 ng/ml in peripheral plasma collected contemporaneously. Next, we determined the rate of dopamine infusion required to produce peripheral plasma concentrations of dopamine similar to those measured in hypophysial stalk plasma. In seven monkeys, a dopamine infusion rate of 0.1 microgram/kg BW . min produced plasma dopamine concentrations of 0.62 ng/ml, whereas a 10-fold higher rate (1.0 microgram/kg . min) produced plasma concentrations of 1.95 ng/ml. Then, we infused these doses of dopamine into intact follicular phase animals, stalk-transected animals, and estrogen-treated stalk-transected animals to determine their effect on PRL release. The physiological dose of dopamine (0.1 microgram/kg . min) significantly suppressed plasma PRL levels in intact follicular phase animals and estrogen-treated stalk-transected animals but not in untreated stalk-transected animals. The higher rate of dopamine infusion (1.0 microgram/kg . min) was required to inhibit PRL release in the latter group. These results demonstrate that dopamine is secreted by the hypothalamus into hypophysial portal blood in quantities sufficient to account for much of the PRL-inhibiting activity known to be caused by the hypothalamus. Moreover, the results suggest that estrogen reinforces the inhibitory effect of dopamine on PRL release in primates, in contrast to its antagonistic effect in rodents. (Endocrinology 108: 489, 1981)

Animals↗
PubMed1981

The effect of dopamine on thyrotropin-releasing hormone-induced prolactin secretion in vitro.

The direct effects on PRL release of acute changes in dopamine (DA) and TRH concentrations were measured in an in vitro perifusion system. Hemisected anterior pituitaries of lactating rats were perifused with medium that received a coinfusion of DA at 20 ng/ml. These tissues released PRL at 35% of the release rate of controls in the absence of DA. Interruption of the DA coinfusion for 9 min caused a 2-fold increase in PRL release, which was resuppressed when the DA treatment was resumed. During continuous Da exposure, TRH administration (10 ng/ml for 12 min) induced a gradual but slight increase in PRL release. However, when this TRH treatment was administered immediately after the end of the DA interruption, it evoked an immediate 2-fold increase in PRL release to 4 times the initial release rate in the presence of DA. This pronounced effect of TRH after the brief DA interruption was also observed when an 18 min interval was imposed between the two manipulations. During continuous coinfusion of DA at 100 ng/ml, TRH was totally ineffective in eliciting PRL release. However, even after this DA treatment had been interrupted briefly and an increase in PRL release had been evoked, TRH still was not an effective stimulus for PRL release. T was imposed between the two manipulations. During continuous coinfusion of DA at 100 ng/ml, TRH was totally ineffective in eliciting PRL release. However, even after this DA treatment had been interrupted briefly and an increase in PRL release had been evoked, TRH still was not an effective stimulus for PRL release. T was imposed between the two manipulations. During continuous coinfusion of DA at 100 ng/ml, TRH was totally ineffective in eliciting PRL release. However, even after this DA treatment had been interrupted briefly and an increase in PRL release had been evoked, TRH still was not an effective stimulus for PRL release. These data indicate that DA not only can serve as a PRL-inhibiting factor for tonic release of PRL but also may determine by its presence or brief absence, and concentration whether acute release occurs in the presence of a PRL-releasing factor. The direct effect of DA on PRL release and its interference with the action of a PRL-releasing factor appear to be independent of each other.

Animals↗
PubMed1980

Comparison of the activity and plasma levels of oxprenolol, slow release oxprenolol, long acting propranolol and sotalol.

Observations were made in 5 healthy subjects who exercised before and 1, 3, 6, 8 and 24 h after the oral administration on separate occasions of 160 mg oxprenolol, 160 mg slow release oxprenolol, 160 mg long acting propranolol and 400 mg sotalol. Blood samples were obtained before and at 1, 2, 3, 6, 8, 10 and 24 h after drug administration and assayed for drug concentration. Although the plasma concentration of oxprenolol after S.R. oxprenolol was significantly less at 1 and 2 h and significantly greater at 24 h than after conventional oxprenolol, there was little difference between the effects of the two drugs on an exercise tachycardia. The plasma level of propranolol and the reduction in an exercise tachycardia after L.A. propranolol increased slowly to reach a peak at 6 h and then declined gradually to 24 h. The maximum plasma concentration and effect after sotalol occurred at 3 h and then declined with an elimination half-life of 12.1 h. At 24 h the percentage reduction in an exercise tachycardia was 8.3 +/- 2.5 after oxprenolol, 10.0 +/- 2.3 after S.R. oxprenolol, 18.0 +/- 3.2 after L.A. propranolol and 14.7 +/- 3.4% after sotalol.

Adult↗
PubMed1980

Effects of thyroid dysfunction on propranolol kinetics.

Propranolol kinetics was studied in six hyperthyroid and six hypothyroid patients who received single oral and intravenous doses of propranolol when they had thyroid dysfunction and again when they had become euthyroid. Change in thyroid status from hyperthyroid to euthyroid produced no change in the elimination half-life (t 1/2) of oral propranolol (3.2 +/- 0.5 to 4.1 +/- 0.7 hr), the oral clearance (38.4 +/- 7.3 to 27.4 +/- 2.4 ml/min/kg), the elimination t 1/2 of intravenous propranolol (2.5 +/- 0.3 to 3.5 +/- 0.7 hr), and the apparent volume of distribution (4.8 +/- 0.4 to 3.8 +/- 0.5 l/kg). The systemic clearance of propranolol, however, was greater when the patients were hyperthyroid (20.8 +/- 2.5 ml/min/kg) than when they had become euthyroid (11.7 +/- 1.7 ml/min/kg). The elimination t 1/2 after oral propranolol was longer in the hypothyroid (3.7 +/- 0.5 hr) than in the euthyroid state (2.0 +/- 0.1 hr). No other changes were observed in the kinetic parameters measured when these hypothyroid patients had become euthyroid. Adequate beta-adrenoceptor blockade in hyperthyroid patients may require higher propranolol dosage than expected.

Adult↗