Biomedical subjects

D G Beasley

Publications and source records attributed to D G Beasley.

22 records · Page 2Linked to original sources

PubMed1986

Maintenance of cerebral circulation during hemorrhagic hypotension in newborn pigs: role of prostanoids.

The possibility that the prostanoid system contributes to the capability of the newborn piglet to maintain cerebral blood flow and cerebral metabolic rate during hypotension was investigated. The effect of hemorrhage on net (arterial-to-venous) cerebral prostacyclin production and the effects of indomethacin on cerebral hemodynamic response to hemorrhage and on the cerebral oxygen utilization following hemorrhage were determined in chronically instrumented, unanesthetized newborn pigs. Hemorrhage decreased arterial pressure about 35% but did not affect cerebral blood flow or cerebral O2 consumption. Hemorrhage was accompanied by an increase in net cerebral 6-keto-PGF1 alpha production from 4.0 +/- 1.1 to 15.3 +/- 4.9 ng/100g X min (mean +/- SEM). Indomethacin treatment of piglets following hemorrhage inhibited the net cerebral production of 6-keto-PGF1 alpha and caused a decrease in blood flow (approximately equal to 40%) to all brain regions within 20 minutes. The decrease in cerebral blood flow was the result of an increase in cerebral vascular resistance of 57 and 180%, 20 and 40 minutes post treatment, respectively. Cerebral O2 consumption was reduced from 2.5 +/- 0.3 ml/100 g X min to 1.5 +/- 0.3 ml/100 g X min 20 minutes following treatment of hemorrhaged piglets with indomethacin and to 1.1 +/- 0.3 ml/100 g X min 40 minutes after treatment. Six of 8 piglets for whom the data were recorded that were administered indomethacin following hemorrhage became comatose with cerebral O2 consumption of 0.4 +/- 0.1 ml O2/100 g X min by 40 minutes after treatment. These data are consistent with the hypothesis that the prostanoid system contributes to the maintenance of cerebral blood flow and cerebral metabolic rate during hypotension in the newborn.

6-Ketoprostaglandin F1 alpha↗

PubMed1986

Effects of leukotrienes C4, D4, and E4 on cerebral arteries of newborn pigs.

We examined effects of topical application of leukotrienes (LT) C4, D4, and E4 on cerebral arteries of newborn pigs in vivo. Diameters of pial arteries were measured using a cranial window method during application of artificial cerebrospinal fluid without drug, and cerebrospinal fluid containing LT C4, D4, and E4 (1, 10, 100, 1000, and 5000 ng/ml). Control diameters ranged from 51-345 micron. All three LT constricted pial arteries in a dose-dependent manner, with a threshold for detectable response at 10 ng/ml (7 +/- 3% for LTD4). The magnitude of constrictor response at the highest dose was 23 +/- 3% for LTC4, 17 +/- 2% for LTD4, and 17 +/- 3% for LTE4. The specific receptor antagonist FPL 55712 blocked the constrictor response to LT. We conclude that LT are potent constrictors of cerebral arteries in newborn pigs.

Animals↗

PubMed1985

Effects of indomethacin upon cerebral hemodynamics of newborn pigs.

Treatment of unanesthetized newborn pigs with indomethacin trihydrate (5 +/- 1 mg/kg, intravenous) decreased cerebral blood flow uniformly throughout the brain by 18-28% without changing cardiac output, arterial pressure, or arterial blood gases and pH. Breathing 10% O2, 9% CO2 with the balance N2 (hypoxia/hypercapnia) caused cerebral blood flow to increase from 102 +/- 12 to 218 +/- 19 ml/100 g . min. Intravenous administration of indomethacin during hypoxia/hypercapnia caused a uniform decrease in cerebral flow throughout the brain to levels (94 +/- 5 ml/100 g . min) indistinguishable from those when the piglet was breathing ambient air. Further, 2.5 h later, the cerebral hyperemia caused by hypoxia/hypercapnia was attenuated markedly (129 +/- 19 ml/100 g . min). Vehicle treatment did not alter resting cerebral blood flow or cerebral hyperemia in response to hypoxia/hypercapnia. Measurements of 6-keto-prostaglandin F1 alpha, thromboxane B2, and prostaglandin E2 demonstrated that intravenously administered indomethacin crossed the blood-brain barrier of newborn pigs in sufficient quantity to inhibit prostanoid release into the cerebrospinal fluid passing over the surface of the brain. The mechanism by which indomethacin reduces cerebral blood flow and attenuates cerebral hyperemia cannot be determined from the present experiments. We conclude that intravenous administration of indomethacin decreases cerebral blood flow and attenuates cerebral hyperemia induced by severe, combined hypoxia/hypercapnia in newborn pigs.

Animals↗

PubMedDate not supplied

Commercial sunscreen lotions prevent ultraviolet radiation-induced depletion of epidermal Langerhans cells in Skh-1 and C3H mice.

There is much controversy regarding the ability of sunscreens to prevent ultraviolet (UV)-induced immune suppression. Epidermal Langerhans cells (LC) play a key antigen-presenting role in the afferent limb of the immune system's response to antigens introduced through the skin. It has been suggested that depletion of LC in UV-exposed skin is a critical step toward the induction of immunosuppression by UV radiation. There are a number of disparate reports with inconsistent results concerning the ability of sunscreens to prevent UV-induced depletion of LC. The purpose of this study was to systematically evaluate the ability of sunscreens to prevent UV-induced LC depletion in mice. Epidermal sheets obtained from skin biopsies taken from mice exposed to UV radiation from Kodacel-filtered FS20 sunlamps, which do not emit UV power at wavelengths < 290 nm, were immunoperoxidase stained for LC using a rat monoclonal antibody against mouse Ia (major histocompatibility complex class II antigen). Time course and dose-response curves for LC depletion were generated for Skh-1 and C3H mice. Dose-response curves for acute UV exposure induced depletion of LC in Skh-1 and C3H mice were similar, but not identical. LC density in the skin of Skh-1 mice that received chronic UV exposure (3 days/week for 8 weeks) was reduced by 62% after 2 weeks of exposure, but returned to normal levels by 6 weeks. Five commercial sunscreen lotions with labeled sun protection factors (SPF) of 4, 8, 15, 30 and 45 were tested for their capacity to block UV-induced depletion of LC. LC were depleted approximately 75% in the skin of unprotected or placebo lotion treated Skh-1 mice exposed to UV given on two consecutive days. Conversely, LC depletion was prevented in similarly UV exposed Skh-1 mice protected with a SPF 30 sunscreen. In C3H mice the levels of protection against LC depletion provided by the five sunscreens were proportional to the level of protection predicted by their labeled SPF. Comparisons of dose-response curves showed that significantly higher doses of UV were required for LC depletion and induction of skin edema than for the induction of local suppression of contact hypersensitivity. Thus, at UV doses where sunscreens provide complete protection against immunosuppression of contact hypersensitivity, prevention of LC depletion and skin edema would be expected.

Animals↗