Biomedical subjects

J G Castillo

Publications and source records attributed to J G Castillo.

18 recordsLinked to original sources

PubMed1991

Mechanism of ketotifen action in hypersensitivity reactions. Its effect on cellular enzymatic activities.

In this study we observed that asthmatics had less methyltransferase activity and greater phosphodiesterase activity than healthy individuals. These enzymatic activities were nearer to values obtained in healthy individuals when we preincubated cells with ketotifen. The modulator effect of this drug on these two enzymes permits, on the one hand, to re-establish the beta-receptor numbers expressed on the membrane, and on the other hand, to inhibit mediator secretion provoked by antigenic stimulus. With its action on adenylate cyclase and phosphodiesterase activities, it allows cAMP intracellular accumulation and hinders the secretory process. Through its action on methyltransferase activity, it is responsible for the normalization of beta-receptor expression observed in asthmatic patients treated with ketotifen.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1991

Number of beta-receptors in patients allergic to Dermatophagoides pteronyssinus.

This study was carried out on 96 atopic patients with monosensitization against Dermatophagoides pteronyssinus and 30 control individuals. The patients were divided into 3 subgroups: 27 asymptomatic patients, 27 patients who only presented nasal symptomatology, and 27 patients with marked bronchial symptomatology. Total serum IgE, antigen-specific histamine release, and the number of beta 2-adrenergic receptors in peripheral blood lymphocytes in all patients were determined. The control group presented the highest number of beta-receptors in comparison with the bronchial symptomatic and nasal symptomatic patients. However, asymptomatic patients presented numbers of beta-receptors similar to controls, with no significant differences between both groups. No significant correlation was found between beta-adrenergic receptors and levels of total serum IgE. On the other hand, correlation between beta-receptors and specific histamine release was detected only in symptomatic nasal patients. It can be postulated that the decrease in beta-receptors is a consequence, and not the cause, of atopy.

Adult↗

PubMed1991

Number of beta-receptors in rhinitic pollinic patients.

The study was carried out on venous blood from 67 patients with seasonal rhinoconjunctivitis caused by sensitization to grass pollen and 30 control individuals. Total IgE determination, antigen-specific histamine release test against two concentrations of Phleum pratense, and quantification of beta 2-adrenergic receptor numbers in lymphocyte membrane of peripheral blood were done on all patients. Those pollinic patients who were asymptomatic at the time of the study had 500.07 +/- 237.27 receptors/cell; no significant differences were established with the control group, with 541.53 +/- 123.63 receptors/cell. However, both the control group and asymptomatic patients had receptor numbers which were significantly higher than those of symptomatic pollinic patients, with 376.81 +/- 158.65 receptors/cell (p < 0.01 and p < 0.05, respectively). The average decrease in number of receptors in symptomatic pollinic patients was 30.42% in relation to controls and 24.65% in relation to asymptomatic patients. Within the subgroup of pollinic patients, studied both in and out of season, the number of beta 2-adrenergic receptors had an average decrease of 13.22% during pollination, with 363.7 receptors/cell. Once the pollination season was over, this figure increased to 419.1 receptors/cell, establishing significant differences with p < 0.025. The number of beta 2-adrenergic receptors did not correlate with total seric IgE figures or with antigen-specific histamine release. These data indicate that the decrease of these receptors does not constitute the causal factor of atopic diseases; it seems more likely to be a consequence of the same.

Adolescent↗

PubMed1990

Seasonal influence on serum and receptor-bound IgE in pollinosis.

Analysis of the correlation between bound and free IgE in 32 patients with pollinosis before and during the pollen season disclosed no correlation between bound and free IgE in rhinitic patients before the pollen season, while there was correlation during the season. In the asthmatic patients there was good correlation before the pollen season rather than during it.

Antigens, Differentiation, B-Lymphocyte↗

PubMed1989

Results of the in vitro follow-up of immunotherapy.

With the advances made in allergological diagnosis, thanks to the application of various in vitro immunological techniques, we have also learnt more about the immunological modifications produced during the course of the immunotherapy. Among the techniques which will detect immunological changes is the histamine release test, which will show a decrease in antigen-specific histamine release. On the other hand, both total IgE and IgG4 are modified in the course of this immunotherapeutic treatment.

Follow-Up Studies↗

PubMedDate not supplied

Effect of ketotifen on phosphodiesterase activity from asthmatic individuals.

It was demonstrated, in this study, that phosphodiesterase activity was elevated in asthmatic patients compared to healthy individuals. This may be reason why various authors found higher intracellular cAMP levels in healthy individuals than in asthmatic patients. We also demonstrated that the efficacy of ketotifen in inhibiting antigen-specific histamine release is due to the potent inhibitor effect of ketotifen on cellular phosphodiesterase activity which then allowed intracellular cAMP accumulation, and as a consequence prevented mediators release.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMedDate not supplied

Membrane IgE and adenyl cyclase activity in the dynamics of bronchospasm. Ketotifen as a blocker of antigen action.

A continuous exposition to antigen provokes an increase of IgE synthesis in individuals sensitized to that antigen. This increase in the synthesis is hardly seen to be reflected in seric levels; however, it is clearly seen in the quantity of IgE associated with membranes as this value increases considerably. This fact is due to the characteristic of IgE which tends to fix itself to basophil membrane. On the other hand, although no difference exists in basal adenyl cyclase activity of asthmatic and healthy individuals, the sensitivity of this enzyme to isoproterenol (beta-agonist) is greater in healthy than in asthmatic individuals. The antigenic stimulus makes adenyl cyclase activity descend in these individuals; this does not happen when the cells are treated with ketotifen before stimulating them with the antigen.

Adenylyl Cyclase Inhibitors↗

PubMedDate not supplied

Does ketotifen act by directly stimulating beta-adrenergic system?

Through this study we proved that the inhibitory effect ketotifen has on antigen-specific histamine release (ASHR) does not have any relation with beta-adrenergic system stimulation. However, it increases the inhibitory effect of histamine release caused by isoproterenol. Therefore, although ketotifen does not directly stimulate beta-adrenergic receptors to inhibit mediator secretion, its action correlates with the response produced through the stimulation of these receptors.

Allergens↗

PubMedDate not supplied

Effect of ketotifen on the methyltransferase activity of asthmatic patients.

The results of this study have revealed that asthmatic individuals have less methyltransferase activity, compared to healthy individuals. This is reflected in a less fluidity of the plasmatic membrane and thus, presents with less beta-receptors compared to healthy subjects. Ketotifen is capable of partially reversing this situation where it stimulates methyltransferase activity of asthmatic individuals approaching the enzyme activity to healthy individuals.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMedDate not supplied

Action of ketotifen on histamine release and intracellular cAMP levels in basophil cultures from pollinic subjects.

Basophils from peripheral blood of 22 pollinic patients were isolated and were cultured in the presence of different concentrations of ketotifen. We studied the effect of this drug on the specific histamine release (Technicon autoanalyzer) and the levels of intracellular cAMP during days 1, 6 and 12 of culture period. We observed that ketotifen induced an inhibition of specific histamine release throughout the culture days, but was greater on the 12th day. The cAMP levels likewise increased during the period of culture in the presence of ketotifen.

Adult↗

PubMedDate not supplied

Late asthmatic reaction in a hairdresser, due to the inhalation of ammonium persulphate salts.

Persulphate salts are among the various chemical substances that can cause occupational diseases in hairdressers. We present the case of a 21 year-old female who worked in a hairdressing salon for five and a half years. Five years prior to consultation, she presented with rhinitic symptoms and wheezing dyspnea which were related with her working environment. The routine laboratory examinations carried out on the patient were found to be normal. Among the various allergic exams performed there was an elevated total IgE. The provocation test with histamine was positive at the concentration of 10 mg/ml, demonstrating mild bronchial hyperreactivity. The test of bronchial exposure to ammonium persulphate was positive with bronchospasm 3-4 hours after this test. With a prior inhalation of betamethasone we were able to block this reaction, but with disodium cromoglycate we were able to block it only partially. We conclude that the patient presented with late onset bronchial asthma due to sensitivity to ammonium persulphate. It has to be pointed out that this patient was a rare case as generally persulphate salts choose to invade and affect the skin. The rarity of this pathology is reflected by the scarce bibliography on this subject.

Adult↗

PubMedDate not supplied

Variations of histamine release in an atopic population. I. Clinical situation and seasons.

Two hundred and twenty-six patients (195 asthmatics and 31 rhinitics) sensitive to D. pteronyssinus were studied. Histamine release tests were performed on them and the results obtained were analyzed with respect to 3 variables: clinical situation (symptomatic and asymptomatic), diagnosis (asthma or rhinitis), and the month of extraction. There were no significant differences between the total and basal histamine in the various groups. The symptomatic individuals (48.66 +/- 29.66 ng/ml) released a greater amount of histamine than the asympomatic group (39.47 +/- 21.07 ng/ml) (p less than 0.05). There was no difference with regards to the diagnosis, although symptomatic asthmatics released more histamine than active rhinitics (p less than 0.01). These patients released more histamine during spring and autumn than during the other two seasons.

Adolescent↗

PubMedDate not supplied

Variations in antigen-specific histamine release related with immunotherapeutic treatment.

The present study analyzes the variations in the percentage of histamine release of 34 allergic patients receiving immunotherapy; the determinations were realized at two different periods of their immunotherapeutic treatment, that is, at an average of 18 months (mite allergy group) and 12 months (grass allergy group) after the first determination. We found that the percentage of histamine release decreased significantly in the second determination in relation to the first, and that this decrease was more intense when more time elapsed between both determinations.

Allergens↗

PubMedDate not supplied

Basophil degranulation test in house dust mite allergy: diagnostic value.

After reviewing the experience of various authors we applied the Basophil Degranulation Test (BDT) in the study of sensitization to Dermatophagoides pteronyssinus, so as to evaluate its diagnostic use. Fifty-five patients with asthma and/or rhinitis and a positive skin test to the mentioned antigen, as well as 20 control subjects were studied. The results demonstrated a sensitivity of 65.5% and a specificity of 80% with an efficiency index of 69.5%. We did not find any significant correlation with the histamine release test (r = 0.236). The data obtained and the proper limitations of the technique led us to consider the BDT to have a limited application in routine allergy diagnosis.

Adolescent↗

PubMedDate not supplied

Variations of histamine release in an atopic population. II. Clinical situation according to age and duration of immunotherapy.

Mediators released as a consequence of allergen-IgE interaction constitute the elements responsible for the clinical manifestations of allergic diseases. To date, numerous mediators have been described although histamine is the fundamental agent in the majority of these reactions. In the present work, we analyzed the influence of 3 different factors (sex, age and duration of immunotherapy) on "in vitro" antigen-specific histamine release. The study was done on 226 individuals mono-sensitized to Dermatophagoides. Of these patients, 195 were asthmatics and 31 rhinitics; their ages ranged between 1 and 72 years, with an average of 21.87 +/- 15.36. There were no significant differences in histamine release capacity in relation to the patient's sex. As to age, there were marked differences in patients older than 40 years; these patients released less histamine (in percentage as well as in total levels) than those patients with less than 20 years of age, with a probability of less than 0.05. When comparing the different groups studied in relation to the time of immunotherapy, we found a statistically significant decrease in histamine release percentages between those patients with less than 1 year of immunotherapy and those with more than 3 years (p less than 0.05), reaching a reduction of 16.33%.

Adolescent↗

PubMedDate not supplied

IgE receptors and serum IgE in pollinosis. The influence of season and action of ketotifen.

In the present study we have analyzed the correlation between bound and free IgE in two groups of patients with sensitization to grass pollen; 15 of these patients only presented symptoms of rhinitis, while the other 17 patients had symptoms associated with bronchial asthma. The study was carried out after, and during the pollen season. We observed that no correlation existed between bound and free IgE in the rhinitic group after pollen season, while there was correlation with the same group of patients during the pollen season. On the contrary, the asthmatic group obtained a good correlation between bound and free IgE after the pollen season, rather than within the pollinization period. In view of these results, we can affirm that the relationship which exists between free and membrane-associated IgE varies, depending on the type of individual and the seasonal period at the time the measurements were carried out. At the same time and in order to analyze the dynamics of action of ketotifen, we studied the effect of this drug on the amount of membrane-associated IgE, for which we employed an enriched population of basophils maintained in culture. From the results obtained we deduced that in no way does ketotifen affect the receptor expression for IgE. Therefore, the possible mechanism of action of ketotifen could be directed toward the interior of, rather than the exterior of the plasmatic membrane.

Asthma↗

PubMedDate not supplied

Decrease of beta-receptors in asthmatic and rhinitic patients.

The number of beta-receptors was determined in 60 atopic patients: 30 asthmatics with sensitization to domestic inhalant allergens and 30 rhinitic patients with sensitization to pollen and/or Dermatophagoides antigens. A L-iodocyanopindolol radio-active marker was used. Our control population (20 healthy individuals) showed 908 +/- 396 receptors/cell. The rhinitic individuals showed a 24% decrease in receptors in relation to the control population. On the other hand, within the asthmatic patients there existed 2 differentiated groups: inactive asthmatics whose receptors were found to be within the normal limits and active asthmatics with a 36% decrease in receptors in relation to the healthy individuals (673 receptors/cell) establishing a significant statistical difference (p less than 0.005). As a consequence these data seem to support Szentivanyi's B-adrenoreceptor theory.

Asthma↗

PubMedDate not supplied

Effect of ketotifen on adenyl cyclase activity in asthmatic patients.

Employing peripheral blood leucocytes as the model of the study, we proved how ketotifen blocks the inhibiting effect that the antigen induces over the adenyl cyclase activity in asthmatic individuals with sensitization to Dermatophagoides pteronyssinus. The strength of the Ketotifen effect is comparable to that produced on beta-receptor stimulation by isoproterenol. On the other hand, we found that within the same age range, the activity of adenyl cyclase in asthmatic individuals is comparable to healthy individuals, although the response is not the same to isoporoterenol which is greater in the control group. This is probably due to the diminished number of beta-receptors in asthmatic individuals as compared to healthy ones.

Adenylyl Cyclases↗