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Biomedical subjects

M Queralt

Publications and source records attributed to M Queralt.

12 recordsLinked to original sources
PubMed2000

Stem cell factor enhances IgE-mediated histamine and TNF-alpha release from dispersed canine cutaneous mast cells.

Stem cell factor (SCF), the c-kit receptor ligand, plays a critical role in mast cell (MC) development and differentiation. In addition, SCF has recently been found to both modulate and induce MC activation. To investigate the effect of SCF on canine cutaneous MC function, we have characterized the ability of SCF to modulate the release by mature canine MC of preformed (histamine) and newly generated (TNF-alpha) mediators. Mature MC were isolated from skin and cultured in the absence or presence of exogenous SCF (6 ng/ml) for up to 5 days and then challenged with anti-IgE (1 microg/ml) alone for 30 min or with a combination of SCF (50 ng/ml) and anti-IgE. SCF alone failed to trigger either histamine or TNF-alpha release at any time. However, we observed that SCF used as a co-stimulus significantly potentiated histamine and TNF-alpha release in canine MC activated through Fc epsilon RI regardless of whether or not SCF was added to the medium during culturing. Thus, the mean histamine release (%) and TNF-alpha production (pg/ml) were found to be significantly higher if cells were maintained in culture in SCF-supplemented medium compared with cells cultured in the absence of exogenous SCF. We also observed that MC responsiveness to immunological stimulation increased with culture time, the percentage of histamine released being higher in cells cultured for at least 3 days when compared to freshly isolated MC. Taken together these findings suggest that canine skin MC releasability can be enhanced independently either through prolonged incubation with SCF and/or through anti-IgE and SCF co-stimulation.

Animals↗
PubMed2000

In vitro inhibitory effect of rupatadine on histamine and TNF-alpha release from dispersed canine skin mast cells and the human mast cell line HMC-1.

OBJECTIVE AND DESIGN: To examine the inhibitory potential of rupatadine, a new H1-antihistamine and anti-PAF agent, on histamine and TNF-alpha release. Comparison with an H1-antihistamine (loratadine) and a PAF-antagonist (SR-27417A). MATERIAL: Dispersed canine skin mast cells were used to assess the effect of the drugs tested on FcepsilonRI-dependent and -independent histamine release; the human HMC-1 cell line was used to study TNF-alpha release. TREATMENT AND METHODS: Before stimulation mast cell populations were treated with increasing concentrations of rupatadine, loratadine and SR-27417A. Histamine and TNF-alpha release were measured following 15-30 min and 3 h activation, respectively. RESULTS: The IC50 for rupatadine in A23187, concanavalin A and anti-IgE induced histamine release was 0.7+/-0.4 microM, 3.2+/-0.7 microM and 1.5+/-0.4 microM, respectively whereas for loratadine the IC50 was 2.1+/-0.9 microM, 4.0+/-1.3 M and 1.7+/-0.5 microM. SR-27417A exhibited no inhibitory effect. Rupatadine, loratadine and SR-27417A inhibited TNF-alpha release with IC50 2.0+/-0.9 microM, 2.1+/-1.1 M and 4.3+/-0.6 microM, respectively. CONCLUSIONS: Rupatadine and loratadine showed similar inhibitory effect on histamine and TNF-alpha release, whereas SR-27417A only exhibited inhibitory effect against TNF-alpha.

Animals↗
PubMed1999

Clinical anti-inflammatory efficacy of arofylline, a new selective phosphodiesterase-4 inhibitor, in dogs with atopic dermatitis.

Forty atopic dogs were studied for 28 days after the oral administration of four randomised treatments: (A) arofylline (1 mg/kg) twice daily for four weeks; (B) prednisone (0.5 mg/kg) twice daily for the first week, once a day during the second week and every 48 hours for the remaining two weeks; (C) prednisone following the same protocol but at a dose of 0.25 mg/kg; or (D) arofylline (1 mg/kg) twice daily for four weeks plus prednisone (0.25 mg/kg) following the same protocol as in (B) and (C). The degree of pruritus and skin lesions and the side effects were evaluated and graded from 0 to 3 before and weekly during the treatments. In all cases there was a progressive clinical improvement in the clinical signs, with no statistical differences among the four treatments. However, many of the dogs treated with arofylline vomited and had adverse gastrointestinal signs.

Administration, Oral↗
PubMed1998

Comparative study of histamine release from skin mast cells dispersed from atopic, ascaris-sensitive and healthy dogs.

Atopic dermatitis results from the interaction between allergen and allergen-specific IgE bound to the mast cell surface receptors. This process triggers mast cell degranulation and accounts at least for early phase reaction. Furthermore, there is increasing in vitro and in vivo evidence that IgE has the ability to induce overexpression of the Fc epsilonRI receptor on the mast cell plasma membrane. In order to study the potential effect of an increase in serum IgE on mast cell activity, the histamine releasability of mature mast cells isolated from the skin of atopic, ascaris-sensitive and healthy dogs was analyzed. No histamine release was detected upon the immunological stimulation of cells that were not previously sensitized with atopic or ascaris-sensitive dog serum. However, when passively sensitized, skin mast cells were challenged with either Asc SI antigen or anti-IgE, the mast cell histamine release increased in a stimulus concentration-dependent manner. The amount of histamine released was significantly higher in response to anti-IgE than in response to Asc SI antigen. However. the difference in the percentage of mast cell histamine release between atopic (26.3+/-2.8%) and non-atopic (30.9+/-1.7%) dogs was not statistically significant, similar to what occurred when ascaris-sensitive (12.8+/-1.6%) and non-sensitive (13.2+/-1.7%) dogs were compared. Although these results could suggest that there is either little or no increase in the density of IgE receptors in atopic or ascaris-hypersensitive dogs versus controls, we strongly consider either the possibility that the digestion procedure might affect cell behaviour in vitro or that an underlying increase of receptors poorly affects the release of granule-stored mediators but influences mast cell activity in a different manner.

Animals↗
PubMed1997

Rupatadine, a new potent, orally active dual antagonist of histamine and platelet-activating factor (PAF).

Rupatadine (UR-12592, 8-chloro-6, 11-dihydro-11-[1-[(5-methyl3-pyridinyl) methyl]-4-piperidinylidene]-5H-benzo[5,6]-cyclohepta[1,2b]pyridine ) is a novel compound that inhibits both platelet-activating factor (PAF) and histamine (H1) effects through its interaction with specific receptors (Ki(app) values against [3H]WEB-2086 binding to rabbit platelet membranes and [3H]-pyrilamine binding to guinea pig cerebellum membranes were 0.55 and 0.10 microM, respectively). Rupatadine competitively inhibited histamine-induced guinea pig ileum contraction (pA2 = 9.29 +/- 0.06) without affecting contraction induced by ACh, serotonin or leukotriene D4 (LTD4). It also competitively inhibited PAF-induced platelet aggregation in washed rabbit platelets (WRP) (pA2 = 6.68 +/- 0.08) and in human platelet-rich plasma (HPRP) (IC50 = 0.68 microM), while not affecting ADP- or arachidonic acid-induced platelet aggregation. Rupatadine blocked histamine- and PAF-induced effects in vivo, such as hypotension in rats (ID50 = 1.4 and 0.44 mg/kg i.v., respectively) and bronchoconstriction in guinea pigs (ID50 = 113 and 9.6 micrograms/kg i.v.). Moreover, it potently inhibited PAF-induced mortality in mice (ID50 = 0.31 and 3.0 mg/kg i.v. and p.o., respectively) and endotoxin-induced mortality in mice and rats (ID50 = 1.6 and 0.66 mg/kg i.v.). Rupatadine's duration of action was long, as assessed by the histamine- and PAF-induced increase in vascular permeability test in dogs (42 and 34% inhibition at 26 h after 1 mg/kg p.o.). Rupatadine at a dose of 100 mg/kg p.o. neither modified spontaneous motor activity nor prolonged barbiturate-sleeping time in mice, which indicates a lack of sedative effects. Overall, rupatadine combines histamine and PAF antagonist activities in vivo with high potency, the antihistamine properties being similar to or higher than those of loratadine, whereas rupatadine's PAF antagonist effects were near those of WEB-2066. Rupatadine is therefore a good candidate for further development in the treatment of allergic and inflammatory conditions in which both PAF and histamine are implicated.

Administration, Oral↗
PubMed1994

Pharmacokinetic and pharmacodynamic studies of the histamine H1-receptor antagonist ebastine in dogs.

The pharmacokinetics and pharmacodynamics of ebastine at single oral doses of 10 and 20 mg were studied in six healthy beagle dogs. Plasma concentrations of the active metabolite of ebastine were measured at predetermined times after the dose. At these times an intradermal injection of 0.01 mL of a 0.2 mg mL-1 histamine diphosphate solution was given, and wheal areas were computed. The plasma elimination half-life of ebastine was 4.38 +/- 1.01 h after 10 mg ebastine and 4.09 +/- 0.74 h after 20 mg ebastine; the distribution volume was 3.99 +/- 0.88 and 3.65 +/- 0.75 L kg-1 after 10 and 20 mg of ebastine, respectively; the clearance after the 10 mg dose of ebastine was 0.67 +/- 0.24 L h-1 kg-1 and after 20 mg ebastine was 0.63 +/- 0.17 L h-1 kg-1. The mean histamine-induced wheal areas were significantly suppressed from 1 to 25 h after the 10 mg dose ebastine and from 1 to 32 h after the 20 mg dose ebastine, compared with the mean predose wheal areas (P < 0.001). Maximum suppression of the wheals was 75 and 82% from 10 and 20 mg ebastine, respectively. A combined pharmacokinetic-pharmacodynamic model was used to analyse the relationship between inhibition of wheal skin reaction and changes in the active metabolite of plasma concentration after ebastine administration. A significant delay of 3-4 h was present between the maximum effect and the peak plasma concentration. Calculated from mean data, the rate constant for equilibration of the drug between plasma and effect site was 0.17 and 0.22 h-1 after 10 and 20 mg ebastine with a half-life of 4.13 and 3.56 h, respectively, and the steady-state plasma concentration resulting in 50% of maximal effect was 18.9 +/- 4.8 ng mL-1 after 10 mg and 18.2 +/- 5.7 ng mL-1 after 20 mg ebastine.

Administration, Oral↗
PubMed1993

Risk factors associated with completed suicide in Latino adolescents.

This is the first study to explore potential psychosocial risk factors associated with completed suicide among Latino adolescents in the U.S. The sample (N = 14) included all the Latino adolescents aged 13 to 19 who committed suicide in Miami, Florida between January, 1988 and June, 1989. Data were derived from the medical examiner's records, family interviews, and a questionnaire completed by the school counselors of the victims and of an equal number of randomly selected Latino nonsuicidal matched-pair controls; t-tests were used to determine the significance of differences between victims and controls on the psychosocial risk variables explored. The victims had experienced significantly more school, personality, behavioral, and family stressors than had the controls. Implications for research and for suicide prevention are discussed.

Adolescent↗