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Biomedical subjects

A P Foster

Publications and source records attributed to A P Foster.

At least 37 records · Page 2Linked to original sources
PubMed1999

Characterisation of lymphocyte subpopulations in the skin and circulation of horses with sweet itch (Culicoides hypersensitivity).

Circulating lymphocyte numbers are elevated in horses with the allergic skin disease sweet itch and skin lesions are typified by an infiltrate of eosinophils and mononuclear cells, the latter of which have not been fully characterised. The aim of the present study was to characterise the lymphocyte subpopulations in the circulation and skin of ponies with sweet itch by flow cytometry and a newly developed modified alkaline phosphatase immunohistochemical technique. Sweet itch ponies were found to have significantly greater numbers of circulating CD5+ and CD4+ T-lymphocytes than normal animals. Increased numbers of CD3+ T-lymphocytes, most of which were CD4+, and eosinophils were present in the skin of these animals following intradermal injection of a Culicoides antigen extract (97 +/- 21 vs. 449 +/- 49 CD3+ T-lymphocytes/mm2 in deep dermis of vehicle vs. antigen injected sites; 83 +/- 8% CD4+ T-lymphocytes at antigen injected site). T-lymphocytes, which are thought to be important in the pathogenesis of human allergic skin disease, may therefore contribute to the development of sweet itch lesions via the release of cytokines which can cause eosinophil accumulation and activation. An understanding of the pathology of this disease may lead to a more rational approach to therapy.

Alkaline Phosphatase↗
PubMed1998

Inhibition of antigen-induced cutaneous responses of ponies with insect hypersensitivity by the histamine-1 receptor antagonist chlorpheniramine.

A whole-body extract of Culicoides impunctatus induced a biphasic increase in oedema formation in ponies with insect hypersensitivity, with maxima after one and eight hours. The Culicoides antigen did not induce similar responses in ponies with no previous history of the disease. In insect-hypersensitive ponies the local administration of chlorpheniramine (12 micrograms) completely inhibited oedema formation in response to histamine (0.04 microgram) and to Culicoides antigen (0.5 microgram) at one hour, and the response to Culicoides antigen at eight hours was inhibited by 63 per cent. Chlorpheniramine also partially inhibited the accumulation of eosinophils and neutrophils induced by Culicoides antigen after two hours.

Animals↗
PubMed1998

Histamine-induced adherence and migration of equine eosinophils.

OBJECTIVES: To examine effects of histamine on equine eosinophil adherence in vitro and to determine the histamine receptor subtype(s) and cell surface adhesion molecules that mediate this response. In addition, to determine the receptor subtypes involved in histamine-induced eosinophil migration. ANIMALS: 8 healthy ponies. PROCEDURE: Effects of histamine on equine eosinophil adherence to serum- or fibronectin-coated plastic, and migration in a microchemotaxis assay were examined. In some experiments, eosinophils were pretreated with histamine receptor antagonists or monoclonal antibodies raised against cell adhesion molecules. For comparison, the effect of histamine on equine neutrophil adherence and migration was studied. RESULTS: Histamine induced adherence of equine eosinophils, but not neutrophils, to serum- and fibronectin-coated plastic (P < 0.01). Histamine also caused migration of equine eosinophils, but not neutrophils (P < 0.01). Histamine-induced adherence and migration of equine eosinophils were inhibited by histamine, (H,)-receptor antagonists chlorpheniramine and mepyramine (P < 0.01), but not H2- or H3-receptor antagonists cimetidine and thioperamide. Monoclonal antibodies raised against CD18, but not very late antigen 4, reduced histamine-induced equine eosinophil adherence to serum- and fibronectin-coated plastic (P < 0.01). CONCLUSIONS: When released from mast cells or basophils, histamine could stimulate adherence and migration of equine eosinophils via H, receptor activation and induce adherence of equine eosinophils to opsonized surfaces or dermal connective tissue matrix proteins via CD18 activation. CLINICAL RELEVANCE: Histamine may have a part in regulating equine eosinophil function during parasitic killing or antigen-induced responses in horses with insect hypersensitivity.

Animals↗
PubMed1997

Agonist-induced adherence of equine eosinophils to fibronectin.

Eosinophils are believed to play an important part in the pathogenesis of equine diseases such as helminth infestation and the allergic skin disease, sweet itch. It has been shown that adherence of human eosinophils to the connective tissue matrix protein fibronectin enhances cell activation and survival time. If adherence causes similar changes in the properties of equine eosinophils, cell-induced tissue damage at a site of parasitic infestation or allergic response would be exacerbated. However, investigation of this hypothesis requires identification of mediators that cause equine eosinophil adherence. Since the equivalent recombinant equine proteins were not available, the present study reports the effects of recombinant human (rh) C5a and IL-5 on the adherence of equine peripheral blood eosinophils (EPBEs) to fibronectin in vitro. The effects of LTB4 and PAF on EPBE adherence to fibronectin were also examined and phorbol myristate acetate (PMA) was used as a positive control. PMA caused a dose-related increase in EPBE adherence to fibronectin-coated plastic. In comparison, rh C5a produced a much smaller response which was only evident at the highest dose tested. On the other hand, rhIL-5 induced a small, but significant dose-related increase in EPBE adherence. Moreover, this response was in part dependent on the beta 1 integrin Very Late Antigen-4 (VLA4). Since adherence to serum-coated plastic was also increased by IL-5, beta 2 integrins may be activated and/or up-regulated on EPBEs by the cytokine. Neither LTB4 nor PAF caused EPBE adherence to fibronectin but prior incubation with these mediators increased the response of cells to IL-5. There were no differences between the responses of EPBEs isolated from horses with clinical signs of sweet itch and normal animals. Thus, whilst up-regulation of IL-5-induced adherence may occur locally in tissues in vivo, it does not appear to take place in the circulation. Finally, C5a, PAF and LTB4, but not IL-5, caused equine neutrophil adherence to fibronectin demonstrating the different responses of granulocytes to these mediators. The results obtained in the present study have shown that mediators which may be released at sites of inflammatory or allergic reactions can induce or enhance eosinophil adherence to tissue matrix protein. Thus, these mediators can now be used in future studies to determine if cell adherence may alter eosinophil activation or survival time.

Animals↗
PubMed1997

Differential superoxide anion generation by equine eosinophils and neutrophils.

Equine eosinophils and neutrophils are believed to play an important part in the protection of horses against parasitic and bacterial invasion. Eosinophils may also play a key role in the pathogenesis of equine inflammatory conditions such as the allergic skin disease, insect hypersensitivity. The factors which stimulate the respiratory burst of equine eosinophils and neutrophils are poorly understood. The first aim of the present study was to determine the effects of the phorbol ester, phorbol myristate acetate (PMA), which is believed to activate intracellular protein kinase C, and opsonised particles of serum-treated zymosan (STZ), on the production of superoxide anions by equine eosinophils and neutrophils. Since histamine has been detected after antigen challenge in the skin of horses with insect hypersensitivity, the second aim was to establish the effects of this mediator on superoxide anion production by equine eosinophils and the receptor sub-type(s) that mediate histamine-induced responses. For comparison, responses of neutrophils from the same horses were also examined. PMA and STZ induced significant increases in superoxide anion generation by equine eosinophils and neutrophils. The estimated maximum (EMAX) superoxide anion production by eosinophils in the presence of PMA was significantly greater than that of neutrophils; the estimated concentration of PMA inducing 50% of the maximum response (EC50) by eosinophils was significantly less. The EMAX values for superoxide anion production by neutrophils in the presence of STZ were significantly greater than those for eosinophils. Histamine induced superoxide anion generation by equine eosinophils which was inhibited by the histamine-1 receptor antagonists chlorpheniramine and mepyramine, but not the histamine-2 and histamine-3 receptor antagonists, cimetidine and thioperamide, respectively. Histamine did not cause superoxide anion production by equine neutrophils. These studies demonstrate that equine granulocytes vary in their ability to produce a respiratory burst in the presence of different stimuli, with eosinophils being more responsive to protein kinase C activators and neutrophils to opsonised particles. They also show that histamine selectively induced the generation of superoxide anions by equine eosinophils via histamine-1 receptor activation. Thus, in horses with insect hypersensitivity, histamine released from cutaneous mast cells after antigen challenge could activate eosinophils which have migrated into the dermis.

Animals↗
PubMed1996

Pharmacodynamics and chiral pharmacokinetics of carprofen in calves.

The non-steroidal anti-inflammatory drug, carprofen, was administered intravenously as the racemate at a dose rate of 0.7 mg kg-1 to six Friesian bull calves aged 8-10 weeks. Anti-inflammatory properties were indicated by attenuation of temperature rise at sites of intradermal injection of the irritants, carrageenin and dextran, but responses were not statistically significant at most recording times. Carrageenin- and dextran-induced swelling were not significantly reduced by carprofen. Carprofen reduced ex vivo serum thromboxane B2 synthesis but this effect was also not significant at most sampling times. Enantioselective pharmacokinetics of carprofen was demonstrated, plasma concentrations of the R(-) enantiomer predominating at all sampling times. It is concluded that inhibition of cyclo-oxygenase is unlikely to be the sole mechanism of action of carprofen in calves.

Animals↗
PubMed1996

Evaluation of carprofen in calves using a tissue cage model of inflammation.

The arylpropionate anti-inflammatory drug, carprofen, was administered intravenously as the racemate at a dose rate of 0.7 mg kg-1 body weight to six Friesian bull calves aged 16-17 weeks. Anti-inflammatory and pharmacokinetic properties were investigated using a tissue cage model of inflammation based on intracaveal injection of the mild irritant, carrageenin. Carprofen displayed enantioselective pharmacokinetics, with the R(-) enantiomer predominating in plasma at all measuring times. Elimination half-life and mean residence time were shorter and volume of distribution and clearance were greater for the S(+) than for the R(-) enantiomer. Penetration of both enantiomers into transudate (non-stimulated tissue cage) was poor but penetration into exudate (carrageenin-stimulated tissue cage) was good. Carprofen failed to reduce exudate concentration of prostaglandin E2 and the reductions in 12-hydroxyeicosatetraenoic acid were non-significant at most sampling times. The long elimination half-life of both R(-) and S(+) carprofen enantiomers and their ready penetration into and slow clearance from inflammatory exudate indicate that the drug is likely to have a long duration of action in calves. The mechanism of action is unknown but it is unlikely to involve inhibition of either cyclooxygenase or 12-lipoxygenase.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1995

Actions of PAF receptor antagonists in horses with the allergic skin disease sweet itch.

Platelet activating factor (PAF) mimics the effects of Culicoides antigen by inducing oedema and inflammatory cell accumulation in the dermis of horses with the allergic skin disease, sweet itch. PAF could therefore contribute to antigen-induced inflammatory changes in these horses. We now report that intravenous administration of the PAF receptor antagonist WEB 2086 (3 mg kg-1), at a dose that inhibited the vascular and cellular responses to PAF in sweet itch horses, reduced Culicoides antigen-induced oedema at 1 h by 73% and at 8 h by 71% (p < 0.05). Neutrophil accumulation and eosinophil recruitment were not significantly reduced by WEB 2086 or a second hetrazepine PAF receptor antagonist WEB 2170 (0.1 mg kg-1). These findings suggest a key role for PAF in oedema formation, but not inflammatory cell accumulation, induced by Culicoides antigen in the skin of sweet itch horses.

Animals↗
PubMed1995

Studies on the isolation and characterisation of a reaginic antibody in a cat.

A reaginic antibody has been demonstrated, by passive cutaneous anaphylaxis (PCA), in the serum of a cat infected with the microfilariae of Brugia pahangi. Recipient cats and pigs were challenged with an extract of Ascaris suum after either a four-hour or a 72-hour period of sensitisation. When the serum was heat treated at 56 degrees C it lost its PCA activity. Gel filtration of the serum revealed a pattern of positive PCA fractions similar to that observed in other species. Attempts to purify the PCA-positive material by Superose gel filtration and ion exchange chromatography by fast protein liquid chromatography (FPLC) were unsuccessful. Affinity chromatography of PCA-positive material by FPLC on protein A demonstrated two bound peaks, the second of which was PCA-positive and eluted as a single peak by ion exchange chromatography. The PCA-positive material from gel filtration did not bind to protein G. The protein A, PCA-positive peak provides a partially purified reaginic antibody for further study.

Animals↗
PubMed1995

Platelet activating factor mimics antigen-induced cutaneous inflammatory responses in sweet itch horses.

Hypersensitivity responses to biting flies such as Culicoides are believed to be the cause of sweet itch, a seasonal intensely pruritic skin condition of horses. Little is known about the mediators released by antigen in the skin of affected horses. In the present study the cutaneous vascular and cellular responses to intradermally injected platelet activating factor (PAF) have been characterised in sweet itch cases during the active phase of the disease and compared with those of Culicoides antigen extract. Histamine was used as a positive control in vascular permeability studies. Responses were also examined in 4 of the 5 sweet itch cases during the inactive phase of the disease. Normal ponies were used as controls. PAF-induced increases in vascular permeability that were dose-related (0.001-1 micrograms per site) and of a similar magnitude in sweet itch and normal animals. Antigen (0.5-50 micrograms per site) also caused dose-related wheal formation in sweet itch cases during the active, but not the inactive, phase of the disease. This effect was biphasic, with maximal responses occurring at 1 and 8 h. An increase in vascular permeability occurred in normal ponies only after administration of the highest dose of antigen tested. Interestingly, histamine (0.02 micrograms per site) induced wheals were significantly smaller in the affected, compared with the normal, group, both during the active and inactive phases. PAF and antigen caused neutrophil accumulation in the skin of sweet itch and normal animals during both the active and inactive phases of the disease. Eosinophil recruitment was also observed but only in the affected group and, in the case of PAF, during the active, but not the inactive, phase. Antigen additionally caused the accumulation of mononuclear cells in the skin of sweet itch cases during the active phase, PAF induced a small increase in mononuclear cell numbers in these animals but the increase was not statistically significant. These findings demonstrate that PAF mimics the effects of Culicoides antigen during the active phase of the disease. Hence, PAF, like histamine, may play a role in the pathogenesis of antigen-induced responses in the skin of sweet itch horses.

Animals↗
PubMed1995

Focal and generalized alopecia.

Focal or generalized alopecia is defined as hair loss affecting the ventral, lateral, perineal, and dorsal aspects of the trunk of the cat, usually in a symmetric pattern. This may be attributable to failure of hair coat production, excess loss of hair due to self trauma, or excess shedding of whole hairs. Self trauma is the most common cause of hair loss and is associated particularly with flea allergy dermatitis. Other causes of hair loss are reviewed.

Alopecia↗
PubMed1993

A comparison of the actions of platelet activating factor (PAF) antagonists WEB 2170 and WEB 2086 in the horse.

The effects of the selective platelet activating factor (PAF) receptor antagonist WEB 2170 on PAF-induced responses in equine cells and tissues have been examined and compared with those of WEB 2086. In initial experiments WEB 2170 was shown to inhibit in vitro platelet aggregation in a dose-dependent, competitive reversible manner (pA2 = 7.21). Co-administration of the antagonists with either PAF or histamine also inhibited PAF, but not histamine, induced wheal formation and PAF-induced neutrophil accumulation in vivo in equine skin. Intravenous (i.v.) administration of both drugs at a dose of 0.1 mg/kg blocked PAF-induced ex vivo platelet aggregation. The inhibition produced by WEB 2170 was greater and, at 30 min, this drug also reduced the slope and maximal response. Wheal formation in the skin was significantly inhibited for up to 6 h by WEB 2170 administered i.v., the reduction being more prolonged than that obtained with WEB 2086. Neutrophil accumulation in the skin was also significantly reduced for up to 24 h by WEB 2170, whilst no significant inhibition was produced by WEB 2086. These results demonstrate that WEB 2170, like WEB 2086, is an effective antagonist of PAF in the horse. Moreover, when given i.v., WEB 2170 appears to be a more potent PAF inhibitor than WEB 2086.

Animals↗
PubMed1992

Platelet activating factor is a mediator of equine neutrophil and eosinophil migration in vitro.

Platelet activating factor (PAF) is known to be a chemoattractant for equine neutrophils in vivo and in vitro. In this study the in vitro migratory response of equine eosinophils and neutrophils to PAF has been examined and compared with that to leukotriene (LT)B4. PAF (10(-8) to 10(-5) M), but not lyso-PAF (10(-6) M), caused dose related migration of both equine eosinophils and neutrophils, maximal responses occurring at 10(-6) M. Responses to PAF were inhibited by the receptor antagonist WEB 2086. LTB4 (10(-8) to 10(-6) M) also induced migration of both cell types, although the maximum effect was observed with a 10-fold lower concentration. Moreover, the maximum response of equine eosinophils to LTB4 was significantly greater than to PAF. It is concluded that LTB4 and PAF, if released in vivo at sites of allergic or inflammatory reactions, could mediate the recruitment of leucocytes to the involved tissue.

Animals↗
PubMed1992

Effects of WEB 2086, an antagonist to the receptor for platelet-activating factor (PAF), on PAF-induced responses in the horse.

Platelet-activating factor (PAF) causes oedema and neutrophil accumulation when injected into the skin of normal horses. PAF is also known to induce aggregation of horse platelets in vitro. The selective PAF receptor antagonist WEB 2086 has now been used to determine whether these effects are mediated by PAF receptor activation. Addition of WEB 2086 to equine platelets in vitro inhibited PAF-induced aggregation in a competitive reversible manner (pA2 = 7.14). Inhibition of in vivo inflammatory responses to PAF occurred after local administration of WEB 2086: wheal formation induced by 0.1 micrograms PAF/site was reduced by 1-10 micrograms WEB 2086/site. PAF (1 micrograms/site)-induced neutrophil accumulation was also inhibited by co-administration of 10 micrograms WEB 2086/site. Systemic administration of WEB 2086 (3 mg/kg iv) to 4 normal ponies inhibited PAF-induced wheal formation and ex vivo platelet aggregation. At 30 min after drug administration the concentration of PAF required to produce a half maximal aggregation response was increased 496 +/- 137 fold. At 6 h the degree of inhibition was markedly reduced and responses had returned to pre-treatment values by 24 h. PAF-induced increases in cutaneous vascular permeability were also reduced by 80% as early as 30 min after iv administration of WEB 2086 in these animals, the inhibition persisting for at least 6 h. These results suggest that in vitro and in vivo responses to PAF in the horse are mediated via activation to PAF receptors. WEB 2086 will therefore be a useful agent for studying the role of PAF in the pathogenesis of equine inflammatory conditions.

Animals↗
PubMed1992

Inflammatory effects of platelet activating factor (PAF) in equine skin.

Intradermal administration of PAF (0.001-1 micrograms/site), but not lyso-PAF (10 micrograms/site), in the horse caused an increase in cutaneous vascular permeability which was maximal by 32 min. Responses to PAF and histamine were reduced by coadministration of the histamine 1 receptor antagonist chlorpheniramine, although only the inhibition of histamine-induced responses was dose-related and statistically significant. The cyclo-oxygenase inhibitor indomethacin was without effect on PAF-induced increases in vascular permeability. These findings suggest that the actions of PAF on equine skin microvasculature may be partly due to histamine release but not to prostanoid formation. Coadministration of prostaglandin (PG) E2 enhanced the oedematous responses to both PAF and histamine, although PGE2 failed to exert direct permeability-increasing activity. In addition, and in contrast to PAF and histamine, PGE2 increased cutaneous blood flow and skin surface temperature. PAF, but not lyso-PAF, also caused neutrophil infiltration into the skin which was maximal at 2 h. No significant effects on eosinophil or mononuclear cell numbers were apparent up to 24 h after injection of PAF. These results are consistent with the concept that PAF may be a mediator of inflammatory disorders of the skin in the horse.

Animals↗
PubMed1992

Influence of feeding schedule on the absorption of orally administered flunixin in the horse.

The effects of access to hay and of restricted feeding on the pharmacokinetics of flunixin administered orally to six healthy ponies were compared in a cross-over study. No access to feed for a few hours before and after flunixin administration resulted in rapid absorption with a mean peak plasma concentration of 2.84 +/- 0.28 micrograms/ml attained in an average time of 0.76 +/- 0.18 h, followed by an exponential decline in plasma concentration. A lower peak plasma concentration was obtained when ponies had free access to hay before and after drug dosing. The mean maximum concentration (Cmax) was 1.30 +/- 0.23 micrograms/ml and maximum time (tmax) was prolonged to a mean time of 7.66 +/- 1.74 h. Free access to hay reduced and delayed the peak plasma concentration resulting in two or three separate concentration peaks in some ponies. The mean area under the plasma concentration-time curve was not significantly different for the two feeding regimens.

Administration, Oral↗
PubMedDate not supplied

Allergen-specific IgG antibodies in cats with allergic skin disease.

An enzyme-linked immunosorbent assay was developed for quantifying feline serum allergen-specific IgG directed against selected house dust, pollen and flea allergens. The assay was used to compare allergen-specific IgG concentrations in sera from healthy cats, cats with non-dermatologic illness, confirmed allergic cats and undiagnosed pruritic cats. Our results demonstrate that cats with confirmed allergic skin disease have significantly more IgG directed against house dust, flea and ryegrass allergens than other cat groups examined. These results support the theory that cats with allergic skin disease have an underlying TH2 lymphocyte response that directs production of both allergen-specific IgG and IgE.

Allergens↗