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Biomedical subjects

B A Spicer

Publications and source records attributed to B A Spicer.

At least 19 recordsLinked to original sources
PubMed1993

Effects of dexamethasone in a model of lung hyperresponsiveness in the rat.

In rats, Sephadex treatment on days 0, 2 and either 4 or 5 resulted in a blood and lung eosinophilia, an increase in lung cell fragility, an increase in the functional activity of peritoneal eosinophils in vitro and a sustained increased responsiveness of lung parenchymal strips to KCl, 5-hydroxytryptamine (5-HT) and carbachol that was not associated with oedema or gross fibrosis. The corticosteroid dexamethasone, when given before each injection of Sephadex, reduced all these effects of Sephadex. When given 30 min after the last injection of Sephadex, dexamethasone had no effect on the number of blood and lung eosinophils but it did reduce the functional activity of peritoneal eosinophils, the increased lung cell fragility and the hyperresponsiveness to 5-HT. Repeated administration of dexamethasone to rats with an established hyperresponsiveness that was no longer associated with cellular inflammation had minimal effects on this hyperresponsiveness.

Animals↗
PubMed1990

The effect of drugs on lung hyperreactivity in Sephadex treated rats.

The injection of Sephadex G200 intravenously into rats induced a blood eosinophilia and an hyper-reactivity of lung parenchymal strips to 5-hydroxytryptamine (5HT) and carbachol. The blood eosinophilia and the hyper-reactivity to 5HT reached a maximum at the same time and before that to carbachol. It was shown previously that the reduction of the blood eosinophilia by treatment with dexamethasone, dapsone, phenidone, isoprenaline and aminophylline also reduced the hyper-reactivity to 5HT. In this study we found that only dexamethasone reduced the hyper-reactivity to carbachol.

Animals↗
PubMed1990

The effects of drugs on Sephadex-induced eosinophilia and lung hyper-responsiveness in the rat.

1. Rats given an intravenous injection of Sephadex particles (0.5 mg of G200 in 1 ml of saline) on days 0, 2 and 5 had a blood eosinophilia which was maximal on day 7. 2. On day 7, broncho-alveolar lavage (BAL) fluids taken from the rats contained an increased number of eosinophils and fewer mononuclear cells but there was no change in the small number of neutrophils. In addition the rats were hyper-sensitive to the increase in resistance to artificial respiration produced by 5-hydroxytryptamine (5-HT), given intravenously, with a shift to the left of the log dose-response curve. Lung parenchymal strips, taken from the rats on days 6, 7 and 8, were hyper-reactive to 5-HT with an increase in slope of the log dose-response curve. 3. Compounds with a wide variety of activities were evaluated for their effects on the blood eosinophilia on day 7 when given before each injection of Sephadex. The eosinophilia was reduced by glucocorticosteroids, beta-adrenoceptor agonists, aminophylline, dapsone and phenidone. 4. Dexamethasone, isoprenaline, dapsone and phenidone at doses that reduced the blood eosinophilia also reduced the changes in number of leucocytes in the BAL fluids and the hyper-responsiveness to 5-HT in vivo and in vitro, except that the effects of dapsone on the hyper-sensitivity to 5-HT in vivo did not reach significance. Aminophylline was the least effective of the drugs at reducing the blood eosinophilia and its effects on the other changes did not reach significance. Sodium cromoglycate reduced the BAL eosinophilia but had no effect on the other changes produced by Sephadex. 5. The correlation coefficients between blood eosinophil numbers and reactivity to 5-HT in vitro and sensitivity in vivo were r = 0.76, (n = 88; P < 0.001) and r = 0.53, (n = 61; P < 0.001) respectively. 6. Doses of dexamethasone, isoprenaline, dapsone and phenidone that reduced the blood eosinophilia when given before each injection of Sephadex were inactive when given up to 8 h after the Sephadex. 7. These data show an association between blood eosinophilia and hyper-responsiveness of the lung. The blood eosinophilia in the rats was triggered within the first few hours of injecting the Sephadex and drugs have been identified which inhibit this trigger.

Animals↗
PubMed1989

Correlation between blood eosinophilia and airways hyper-responsiveness in rats.

The injection of Sephadex particles intravenously into rats produced a specific blood eosinophilia and an hyper-responsiveness of the airways to 5-hydroxytryptamine (5-HT). The rats given Sephadex had an hyper-sensitivity to the respiratory effects of 5-HT in vivo with a shift to the left of the intravenous dose response curve. In vitro lung strips from rats given Sephadex were hyper-reactive to 5-HT in that the strips from these rats and control rats responded over the same dose range of 5-HT but the slope of the dose response curve and the maximum response were greater in the strips from the Sephadex treated rats. The levels of hyper-sensitivity in vivo and of hyper-reactivity in vitro both correlated with the numbers of blood eosinophils.

Animals↗
PubMed1988

Changes in leucocyte numbers without diapedesis in rats given platelet-activating factor (PAF-acether).

Changes occurring in the blood and the peritoneal cavity following the intraperitoneal injection of platelet-activating factor (PAF-acether) into rats were compared with those when antigen was injected intraperitoneally into actively sensitised rats. A blood eosinophilia had been produced in the rats by an intravenous injection of Sephadex G200 6 days before either challenge. 5 min after PAF-acether, the total number of cells in the peritoneal washings had decreased and the concentration of extravasated dye-labelled plasma protein had increased with no change in histamine levels. On the other hand, antigen at this time produced nor only a decrease in cells and an increase in dye but also an increase in histamine concentration. Only antigen produced a cellular infiltration into the peritoneal cavity with an increase in numbers of neutrophils in the peritoneal washings at 4 h and of mononuclear cells and eosinophils at 24 h. In the blood at 4 h after either challenge, there was a neutrophilia and an eosinopenia. When PAF-acether and antigen were injected together into actively sensitised rats, leucocyte counts in the peritoneal washings increased by a similar amount, both at 4 and 24 h, as those in rats given antigen alone.

Animals↗
PubMed1987

Airway hyper-reactivity and eosinophilia in rats treated with Sephadex particles.

The intravenous injection of Sephadex particles (G200) into rats produced a specific increase in numbers of blood eosinophils, peaking 7 days later. A second injection, given on day 14 when the numbers of blood eosinophils had fallen to control levels, produced a dose-dependent increase in numbers, greater than the first, and peaking 5 days later. At this time, there was a dose-dependent increase in numbers of eosinophils, but not of other leucocytes, in broncho-alveolar lavage fluids and lung tissue, together with an increase in sensitivity of the rats to the respiratory effects produced by the intravenous injection of 5-hydroxytryptamine.

Animals↗
PubMed1986

The effects of drugs on leucocyte changes following the injection of antigen into the peritoneal cavities of actively sensitised rats.

The injection of antigen into the peritoneal cavities of actively sensitised rats produced an immediate reaction characterised by an increase in concentrations in the peritoneal fluids, collected 5 min later, of extravasated dye labelled plasma proteins, histamine and slow reacting substance of anaphylaxis (SRS-A). Changes were also produced in the numbers of leucocytes in the blood and peritoneal cavity. 5 min after antigen challenge there was a reduction in the number of cells that could be washed from the peritoneal cavity. 4 h after antigen there was an increase in numbers of neutrophils both in the blood and peritoneal washings and these fell to the levels in control rats at 24 h. 24 h after antigen, and continuing for 72 h, there was an increase in numbers of eosinophils and mononuclear cells in the peritoneal washings. The rats were injected intravenously with sephadex particles to produce a blood eosinophilia at the time of antigen challenge, this increased the numbers of eosinophils migrating into the peritoneal cavity but had no effect on antibody levels, the numbers of other leucocytes or on the immediate reaction. An inhibitor of lipoxygenase and cyclo-oxygenase metabolism of arachidonic acid, phenidone, at 100 mg/kg p.o., inhibited SRS-A release to control levels, in the immediate reaction, but had no effect on the leucocyte changes. The glucocorticosteroid, dexamethasone, at doses of 0.1 and 1 mg/kg p.o., produced little inhibition of SRS-A release but significantly inhibited neutrophil, eosinophil and mononuclear cell infiltration into the peritoneal cavity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophylline↗
PubMed1986

Studies on 1,2,3-triazoles. 13. (Piperazinylalkoxy) [1]benzopyrano[2,3-d]-1,2,3-triazol-9(1H)-ones with combined H1-antihistamine and mast cell stabilizing properties.

Several N-benzylpiperazino derivatives of [1]benzopyrano[2,3-d]-1,2,3-triazol-9(1H)-one and its 5-methyl homologue have been prepared and evaluated for H1-antihistamine activity on guinea pig ileum. The most potent compounds were also evaluated for their ability to stabilize mast cells in the rat passive peritoneal anaphylaxis (PPA) system and were shown to inhibit histamine release at concentrations below those required to inhibit extravasation, suggesting that this might be relevant to their antianaphylactic activity in this system. The compound tested with the most potent H1-antihistamine activity was 6-[3-[4-(4-chlorobenzyl)-1-piperazinyl]propoxy][1]benzopyrano[2,3- d]-1,2,3-triazol-9(1H)-one, 28, which had a pA2 of 9.1 against histamine on guinea pig ileum, comparable to that of mepyramine, and inhibited histamine release in the rat PPA system with an IC50 value of 5.4 X 10(-6) M.

Anaphylaxis↗
PubMed1986

Effect of drugs on the increase in cell numbers in the peritoneal cavity of the actively sensitised mouse after intraperitoneal challenge with antigen.

The injection of antigen into the peritoneal cavity of actively sensitised mice produced an increase in the number of neutrophils in peritoneal washings collected 4 h later but after 1 day the numbers had returned to control levels. The increase in numbers of mononuclear cells and eosinophils in the peritoneal washings peaked at 2 days and persisted for at least 5 days. Dosing the mice with phenidone, a dual inhibitor of the cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism, potentiated the neutrophil infiltration at 4 h but had no significant effect upon the subsequent mononuclear cell and eosinophil infiltration. In contrast, treatment with the corticosteroid, dexamethasone, reduced the infiltration by all three types of cells, providing further evidence that the corticosteroids can inhibit immune-induced cellular infiltrations by mechanisms other than the inhibition of arachidonic acid metabolism. Isoprenaline, given to the mice before antigen challenge, had no effect on the subsequent neutrophil infiltration, but repeated doses did inhibit the mononuclear cell and eosinophil infiltration measured 4 days later. Aminophylline, disodium cromoglycate and cyproheptadine had no effect upon the cellular changes.

Animals↗
PubMed1986

Airway hyper-reactivity and blood, lung and airway eosinophilia in rats treated with Sephadex particles.

The intravenous injection of Sephadex particles (G200) into rats produced a specific increase in numbers of blood eosinophils peaking 7 days later. A second injection, given on day 14 when the numbers of blood eosinophils had fallen to control levels, produced a dose-dependent increase in numbers, greater than the first, and peaking 5 days later. At this time there was a dose-dependent increase in numbers of eosinophils, but not of other leucocytes, in broncho-alveolar lavage fluids and lung tissue, together with an increase in sensitivity of the rats to the respiratory effect produced by the intravenous injection of 5-hydroxytryptamine.

Animals↗
PubMed1985

An investigation of the involvement of platelet activating factor in the non-histamine immediate hypersensitivity reaction in the rat peritoneal cavity.

Synthetic PAF-acether injected intraperitoneally (i.p.) into sham-sensitized rats, caused dose-dependent extravasation of plasma proteins into the peritoneal fluids. Platelet aggregating activity was detected in the peritoneal fluids. In rats that had been passively sensitized for a non-histamine mediated immediate hypersensitivity reaction, antigen challenge caused extravasation of plasma proteins into the peritoneal fluids. No platelet aggregating activity was detected in these fluids. PAF is unlikely to be the mediator of extravasation in the non-histamine mediated immediate hypersensitivity reaction in the rat.

Animals↗
PubMed1984

Studies on 1,2,3-triazoles. 10. Synthesis and antiallergic properties of 9-oxo-1H,9H-benzothiopyrano[2,3-d]-1,2,3-triazoles and their S-oxides.

Selected derivatives of 9-oxo-1H,9H-benzothiopyrano[2,3-d]-1,2,3-triazole, a new heterocyclic ring system, and their S-oxides have been prepared and evaluated for antiallergic activity in the rat passive cutaneous anaphylaxis screen. Several of the compounds show intravenous potencies similar to or greater than that of disodium cromoglycate, the most potent being 6,7-dimethyl-9-oxo-1H,9H-benzothiopyrano[2,3-d]-1,2,3-triazole and its 4,4-dioxide.

Animals↗
PubMed1984

N-benzylpiperazino derivatives of 3-nitro-4-hydroxycoumarin with H1 antihistamine and mast cell stabilizing properties.

In a small range finding study a number of N-benzylpiperazino derivates of 3-nitro-4-hydroxycoumarin have been shown to combine potent H1-antihistamine activity with that of mast cell stabilization as demonstrated by their activity as antagonists of histamine on guinea pig ileum and by their inhibition of the release of histamine in rat passive peritoneal anaphylaxis (PPA). The most potent compound, 1-[2-hydroxy-3-[(4-hydroxy-3-nitrocoumarin-7-yl)oxy]propyl]-4- (4-chlorobenzyl)piperazine, 30, had a pA2 of 9.0 against histamine on guinea pig ileum and inhibited histamine release in the rat PPA test with a potency similar to that of disodium cromoglycate.

4-Hydroxycoumarins↗
PubMed1983

Studies on v-triazoles. 7. Antiallergic 9-oxo-1H,9H-benzopyrano[2,3-d]-v-triazoles.

A series of the little compounds was prepared by cyclization of the appropriate 5-(aryloxy)-v-triazole-4-carboxylic acids and evaluated for antiallergic activity by the rat passive cutaneous anaphylaxis (PCA) screen. The most potent compounds were 6-(mesyloxy)-9-oxo-1H,9H-benzopyrano[2,3-d]-v-triazole and its 5-methyl homologue, which were some tenfold more potent than disodium cromoglycate. Dialkyl derivatives, especially those substituted at C-5 and C-6 or C-6 and C-7, and 6-methoxy compounds were also among the more potent compounds. One compound, 6,7-dimethyl-9-oxo-1H,9H-benzopyrano[2,3-d]-v-triazole, was further evaluated and shown to be a potent inhibitor of rat PCA when given orally.

Animals↗
PubMed1983

Studies on v-triazoles. 9. Antiallergic 4,9-dihydro-4,9-dioxo-1H-naphtho[2,3-d]-v-triazoles.

A short series of the title compounds was prepared and evaluated for antiallergic activity in the rat passive cutaneous anaphylaxis screen. All but the two N-methylated derivatives were active in this screen by the intravenous route, the most potent being the symmetrical dimethyl compound, 4,9-dihydro-6,7-dimethyl-4,9-dioxo-1H-naphtho[2,3-d]-v-triazole, and its 5-nitro derivative. The latter two compounds were noticeably more potent than disodium cromoglycate, and one of these, the unnitrated material, was selected for further evaluation as a potential antiasthmatic drug.

Animals↗
PubMed1980

Rat passive peritoneal anaphylaxis following sensitisation with guinea pig antiserum: an immediate hypersensitivity reaction without histamine release.

Antigen challenge of rats, sensitised by an intraperitoneal injection of guinea pig antiserum, produced an antibody-dependent increase in concentrations, in the peritoneal fluids. of slow-reacting substance of anaphylaxis (SRS-A) and of extravasated, dye-labelled, plasma proteins but not of histamine or 5-hydroxytryptamine. The SRS-A released may not be the main mediator of the extravasation since pre-treatment of the rats with the SRS-A antagonists FPL 55712 and BRL 19880 had no effect on extravasation, and a number of compounds, given in a similar way, were more potent as inhibitors of SRS-A release than of extravasation. Rat passive peritoneal anaphylaxis (PPA), following sensitisation with guinea pig antiserum, provides an example of an immediate hypersensitivity reaction in which there is no antibody-dependent release of histamine and in which the SRS-A released may not mediate all of the extravasation produced.

Anaphylaxis↗