Evaluation of rat neutrophil beta-adrenergic receptors by microphysiometry.
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Adrenergic beta-Agonists↗
Biomedical subjects
P Eyre
Publications and source records attributed to P Eyre.
Professing change. The veterinary profession.
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Accreditation↗
The R.G. Thomson Lecture. Partnerships: an academic imperative.
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Canada↗
Functional characterization of equine neutrophils in response to calcium ionophore A23187 and phorbol myristate acetate ex vivo.
Equine neutrophils (PMN) play a critical role in inflammatory processes in horses. The objective of this study was to characterize equine PMN function ex vivo following stimulation with calcium ionophore A23187 (A23187) and phorbol myristate acetate (PMA). These stimulants trigger different branches of the PMN activation process that occurs in vivo. Equine PMN were isolated from the whole blood of six clinically normal geldings using a one-step discontinuous Percoll gradient technique. Neutrophil aggregation, degranulation, and superoxide anion production were evaluated in assay systems which had previously been established to quantitate PMN function. Dose-response curves for A23187 and PMA were derived for the three functions. Results indicate that equine PMN aggregation and superoxide anion production are more responsive to activation by PMA as the maximum change in percent transmittance and maximum nanomoles of superoxide anion produced following PMA stimulation (60.8% and 10.4 nmol per 10(6) cells, respectively) were greater than those values stimulated by A23187 (41.5% and 5.2 nmol per 10(6) cells, respectively). However, degranulation was found to be more responsive to A23187 stimulation (maximum percent degranulation: 56.1%) than to PMA stimulation (maximum percent degranulation: 30.7%). Dose-response curves following A23187 and PMA stimulation revealed that superoxide anion production had the lowest threshold concentration among the three functions. Degranulation had the highest threshold concentration among the three functions for both stimulants. Results indicate that equine PMN functions differ in their dependence on second messengers in the activation pathway. These functions also occur in a dose-dependent manner and differ in the threshold concentrations required for their stimulation.
Animals↗
Altered endothelium-dependent alpha-adrenergic vascular reactivity following exposure to Pasteurella haemolytica antigens.
Rats were injected with sterile saline (controls), 10(5) cfu of Pasteurella haemolytica (biotype A) obtained from a commercial vaccine, or a commercial Pasteurella leukotoxoid vaccine. Three days after vaccination, the animals were killed and the thoracic aorta was removed. In some experiments the vascular endothelium was mechanically removed. Each isolated aorta was placed in a tissue bath and the biophysical responses to methoxamine (alpha-1 agonist) were determined. In separate experiments the endothelial surface was examined by scanning electron microscopy. In endothelium-intact vessels both vaccines appeared to enhance the contractile response to methoxamine. On the other hand, in endothelial-denuded vessels, the methoxamine-mediated contractile response was enhanced in the P. haemolytica-treated group but not in animals vaccinated with leukotoxoid. Furthermore, scanning electron microscopy revealed deposition of a fibrin-like material on the endothelial surface of vaccinated animals. These results suggest that exposure to vaccine-derived P. haemolytica antigens alters the morphology and adrenergic responsiveness of vascular smooth muscle.
Animals↗
Classification and biological distribution of histamine receptor sub-types. 1975.
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Animals↗
Schultz-Dale reaction in isolated perfused calf ear and its inhibition by isoproterenol.
Calf ears which were sensitised to horse serum and others which were unsensitised were catheterised and perfused at a constant flow rate of 2 ml min-1 with Krebs-Henseleit solution using a peristalic pump. The ear preparations were then challenged with whole horse serum, the sensitising antigen. Vascular responses were monitored as changes in perfusion pressure. Weight changes were determined to indicate the extent of oedema formation. Unsensitised ear preparations responded to 0.1 ml whole horse serum with 43.3 +/- 0.8 per cent (n = 5) and 10.7 +/- 0.3 per cent (n = 5) increases in perfusion pressure and weight, respectively. Sensitised ear preparations responded to 0.05 ml whole horse serum by increases of 280.8 +/- 32.9 per cent (n = 5) and 27.2 +/- 1.4 per cent (n = 5) in perfusion pressure and bodyweight, respectively. Isoproterenol (10(-5) M) inhibited the vascular responses by 81.4 +/- 7.6 per cent (n = 5) while the increases in weight were reduced by 20.0 +/- 1.5 per cent (n = 5). The Schultz-Dale reaction has thus been demonstrated in an isolated whole organ, the pinna.
Anaphylaxis↗
Vaccine-derived Pasteurella haemolytica alter the responses of ovine pulmonary artery and vein to drugs acting on adenylate cyclase.
Sheep were vaccinated with a live, vaccine-derived strain of Pasteurella haemolytica. The ex vivo response of isolated pulmonary artery and vein to isoproterenol, cholera toxin, sodium fluoride and calcium were examined three days after vaccination. In the pulmonary artery (endothelium intact), vaccination did not alter the response to isoproterenol, or sodium fluoride whereas the relaxation response to cholera toxin was impaired. In the pulmonary artery (endothelium removed), the maximum relaxation attained in response to isoproterenol was reduced and the response to exogenous calcium, sodium fluoride and cholera toxin not altered. In the pulmonary vein (endothelium intact), the response to isoproterenol and sodium fluoride was unchanged whereas the response to cholera toxin was impaired. In the pulmonary vein (endothelium removed), the response to isoproterenol and sodium fluoride was not altered following P haemolytica vaccination whereas the relaxation response to cholera toxin was enhanced and the response to exogenous calcium slightly impaired. These experiments suggest that vaccination with live strains of P haemolytica cause subclinical disturbances in the pulmonary circulation and may potentially alter the animals' response to pathogens.
Animals↗
Morphological and functional disturbances in pulmonary vascular endothelium following exposure of sheep to an "avirulent" strain of Pasteurella haemolytica.
Sheep were vaccinated with a live attenuated strain of Pasteurella haemolytica and killed 3 days later. Segments of main intrapulmonic artery and vein were removed for biophysical and scanning electron microscopic studies. In the pulmonary artery, vaccination with Pasteurella haemolytica caused an increase in the number of endothelial cell surface blebs and, in some cases, those blebs appeared to be splitting open, suggesting cell damage or irritation. There was a surprising lack of platelet adherence to the lesions, suggesting that an antiplatelet factor is released by the damaged endothelium. The endothelial-dependent relaxant response to bradykinin was enhanced following vaccination. In the pulmonary vein, ultrastructural lesions similar to those in the artery were present in vaccinated animals. Bradykinin caused a contraction, an effect that was reduced following vaccination with Pasteurella haemolytica. These experiments demonstrate that a live, vaccine-derived strain of Pasteurella haemolytica causes both morphological and functional changes in the pulmonary vascular endothelium.
Animals↗
Disturbances in ex vivo vascular smooth muscle responses following exposure to Pasteurella haemolytica vaccines.
Rats were vaccinated with saline (control) or one of the two commercially available Pasteurella haemolytica vaccines Presponse or Precon-PH. Animals were killed 3 days later and thoracic aorta removed for evaluation of the ex vivo biophysical responses to carbachol (CCh). In some experiments, vascular endothelium was mechanically removed. Vaccination of rats impairs the endothelial-dependent relaxation to CCh. In vessels with endothelium removed, the contractile response to CCh is converted into a relaxation following vaccination. Treatment of endothelial-denuded vascular rings ex vivo with methylene blue, a guanylate cyclase inhibitor, reduced the vaccination effect. Treatment of vascular rings with the superoxide dismutase inhibitor diethyldithiocarbamate, impairs the relaxant response of de-endothelialized vessels to CCh in Presponse vaccinated rats while enhancing the relaxation response of vessels from Precon-PH vaccinated rats. De-endothelialized vessels from vaccinated rats, but not control rats, relaxed in the presence of N-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of nitric oxide synthetase. Furthermore, in the presence of L-NMMA, the relaxant response to CCh is significantly enhanced by Precon-PH but not Presponse. The normal relaxant response to hydrogen peroxide is converted into a contraction following vaccination. Results suggest that exposure to commercially available P. haemolytica vaccines alters vascular smooth muscle reactivity to CCh and that several independent pathways may be altered.
Animals↗
Vaccination with live Pasteurella haemolytica alters vascular adrenergic reactivity.
Rats were injected with sterile saline (controls) or 0.7 x 10(5) c.f.u. of Pasteurella haemolytica (biotype A) obtained from a commercial vaccine. Three days following vaccination animals were killed and aortas removed from the heart base. Isolated aorta was placed in a tissue bath and the biophysical responses to phenylephrine (alpha-1 agonist), clonidine (alpha-2 agonist) and isoproterenol (beta agonist) determined. The results indicate that the alpha-2 adrenergic contractile response to clonidine is significantly enhanced while the response to phenylephrine is not significantly altered. The relaxant response to isoproterenol is eliminated following vaccination. These results suggest that exposure to vaccine-derived strains of P. haemolytica cause an imbalance in the adrenergic responsiveness of vascular smooth muscle.
Animals↗
Veterinary education with career emphasis: a partnership with private, public, and corporate veterinary practice.
The Virginia-Maryland Regional College of Veterinary Medicine responded to the Pew-sponsored National Veterinary Education Program by proposing a Center for Government and Corporate Veterinary Medicine. The Center is currently providing, through elective course offerings and practical experiences, a senior clinical curriculum that permits career emphasis in a number of species areas, in addition to a unique program for graduates wishing to enter the field of public and corporate veterinary medicine. The Center is also developing post-veterinary medicine. The Center is also developing post-veterinary school education for advanced degrees (PhD, MS) and residency training in public and corporate fields, and for midcareer updating and changes of career emphasis.
Career Choice↗
Altered spontaneous and histamine-induced in vitro suppressor-cell function in dogs with atopic dermatitis.
Spontaneous, histamine-induced and Concanavalin A (Con A)-induced suppression of Con A mitogenesis of autologous responder cells was studied in normal dogs and in dogs with atopic dermatitis. Histamine-induced suppression was significantly decreased in the atopic dogs, as was the Con A-induced suppression, at supraoptimal concentration of Con A, to a lesser extent. Total numbers of histamine type 1 or type 2 receptors were not different for cells from atopic or normal dogs. The spontaneous suppression was significantly greater for the atopic dogs and this was not accounted for by the effect of non-specific dermatitis, increased macrophage-induced suppression or increased induction by mitogenic factors in the culture medium. Some possible mechanisms for these results are discussed, and the similarities to suppressor cell function in humans with atopic disease are noted.
Animals↗
The vascular responses of the isolated perfused bovine external ear to exogenous histamine and 5-HT (serotonin).
The responses of the vasculature of isolated, non-sensitized, bovine external ears to histamine and serotonin (5-HT) were evaluated while they were being perfused with Krebs-Henseleit solution. Histamine (10(-5) mol/L to 5 x 10(-3) mol/L) and 5-hydroxytryptamine (5-HT) (10(-9) mol/L to 10(-2) mol/L) caused increased vascular resistance. Mepyramine (10(-7) mol/L), cimetidine (10(-5) mol/L) and atropine (10(-6) mol/L) inhibited the responses to histamine. The responses to 5-HT were inhibited by methysergide (10(-9) mol/L) and potentiated by morphine (10(-5) mol/L). These results suggest the presence of H1 and H2 histamine, and 5-HT receptors in bovine auricular vessels, all of which cause net vasoconstriction.
Animals↗
Increased numbers of duodenal mucosal mast cells in turkeys inoculated with hemorrhagic enteritis virus.
The relation between average duodenal mast cell count, duodenal mucosal mast cell numbers, duodenal connective tissue mast cell numbers, circulating basophil numbers, heterophil-to-lymphocyte ratio, and lesion score were studied to gain an understanding of the events that may lead to intestinal lesion formation associated with hemorrhagic enteritis virus (HEV) infection. Changes in vascular permeability in the duodenum in birds inoculated with HEV were examined, using colloidal carbon and ferritin as vascular markers. Turkeys inoculated with HEV had significantly (P less than 0.05) higher duodenal mast cell counts than did noninfected controls. Birds inoculated with HEV had significantly (P less than 0.05) more mucosal mast cells than did phosphate-buffered saline solution-inoculated birds. Connective tissue mast cell and basophil numbers were unaffected by viral inoculation. Thermal stress did not have significant effect on lesion severity, but did increase number of birds that developed the characteristic intestinal lesions. The heterophil-to-lymphocyte ratio was significantly (P less than 0.05) higher in HEV-inoculated birds, compared with phosphate-buffered saline solution-inoculated controls. Increase in vascular permeability was only detected in HEV-inoculated birds with intestinal lesions. Results indicate that mast cells, and the vasoactive mediators contained within mast cells, may be important in the early manifestation of HEV infection. They also provide a possible mechanism through which biochemical and physiologic changes characteristic of HEV infection can occur.
Adenoviridae Infections↗
The isolated, perfused bovine ear. A model for pharmacological study of cutaneous vasculature and anaphylaxis.
Bovine ears were catheterized and perfused with Krebs-Henseleit (K-H) solution at a constant flow rate. The perfusion pressure (PP) was monitored using a pressure transducer coupled to a carrier preamplifier, amplifier and a pen recorder. Dose-response curves to phenylephrine, histamine and 5-hydroxytryptamine were obtained. The ear preparations responded to these agonists dose-dependently by increases in perfusion pressure. Ear preparations from sensitized calves were challenged with 0.05 ml of horse serum which caused increased perfusion pressure. These preliminary results suggest that the perfused bovine ear represents a promising, simple, inexpensive model for the study of pharmacological mechanisms of the skin.
Animals↗
Exposure of sheep to Pasteurella haemolytica alters ex vivo pulmonary vascular smooth muscle alpha adrenergic responses: role of vascular endothelium.
Sheep were exposed to a live- vaccine derived strain of Pasteurella haemolytica (10(5) colony forming units/sheep, i.m.) and euthanized 3 days later. Pulmonary artery and vein ex vivo responses to cumulative doses of methoxamine were determined. In some experiments endothelium was removed. In the pulmonary artery, removal of the endothelium significantly impairs the potency of methoxamine as a contractile agent in control sheep. Also, in sheep exposed to P. haemolytica removal of the endothelium ex vivo impairs the efficacy of methoxamine as a contractile agent. In the pulmonary vein, removal of the endothelium significantly increases the maximum contractile response obtained in control sheep. Conversly, in the pulmonary vein from P. haemolytica exposed sheep, removal of the endothelium reduces the efficacy of methoxamine. These experiments suggest that vaccination with live P. haemolytica impairs pulmonary vascular alpha adrenergic responses. Such impairments may contribute to development of pulmonary edema and congestion during stressful periods such as post-vaccination.
Animals↗
Morphometric analyses of the skin of dogs with atopic dermatitis and correlations with cutaneous and plasma histamine and total serum IgE.
In order to improve the diagnostic value of histopathologic examination of skin biopsy samples from dogs with atopic dermatitis and, perhaps, to identify any differences from the normal state that may predispose to this skin condition, we compared the anatomic and cellular morphology of skin from three standard sites in 21 normal and 15 atopic dogs. The standard sites were lateral neck, dorsal rump, and craniolateral abdomen. No differences between the two groups were found in the means of area or thickness of the stratum corneum or the remainder of the epidermis at any site. The area of sebaceous glands, but not apocrine sweat glands, was larger in the atopic group (P less than or equal to 0.05 for the lateral neck skin and P less than or equal to 0.1 for the dorsal rump skin). The mean number of non-metachromatic mononuclear cells in combined skin samples (126 microns 2) in atopic dogs (91.0 +/- 28.7) was significantly greater (P less than or equal to 0.01) than for the control normal dogs (65.3 +/- 19.3); the mean number of mast cells in atopic dogs (12.39 +/- 6.44) was similarly greater than in the controls (8.48 +/- 5.14; P less than or equal to 0.1). Eosinophils were significantly increased in atopic dog skin (P less than or equal to 0.01). with the mean for all three sites combined of 0.81 +/- 0.90 compared with a mean of 0.06 +/- 0.15 for normal dogs. Numbers of circulating blood eosinophils were not significantly different in the atopic and normal group.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗