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Biomedical subjects

I Herjavecz

Publications and source records attributed to I Herjavecz.

At least 19 recordsLinked to original sources

The effect of allergic rhinitis on adenosine concentration in exhaled breath condensate.

BACKGROUND: Patients with allergic rhinitis (AR) frequently develop asthma. This initiating inflammation in the lower airways may result in increased levels of inflammatory mediators such as adenosine in the exhaled breath. OBJECTIVE: We compared adenosine levels in exhaled breath condensate (EBC) and both exhaled and nasal nitric oxide (NO) levels of AR patients and healthy control subjects. We also tested whether inhalation through inflamed nasal cavity during EBC sampling influences adenosine concentrations in exhaled air. METHODS: Exhaled and nasal NO levels were measured and EBC samples (at oral inhalation) were collected from 27 patients and 15 healthy controls. EBC collection was repeated after 15 min with subjects inhaling through their nose. Adenosine was measured by HPLC and NO was determined by chemiluminescence. RESULTS: The concentration of EBC adenosine was higher in patients with AR than in healthy controls (12.4+/-1.3 nM vs. 6.5+/-0.7 nM, P=0.0019) and this was accompanied by an increase in the concentration of exhaled NO (10.2+/-1.3 ppb vs. 5.3+/-0.5 ppb; P=0.0099, respectively). No difference in nasal NO was detected. EBC adenosine concentration showed a significant positive correlation with the level of exhaled NO. In contrast to healthy control subjects, patients with rhinitis had higher levels of exhaled adenosine when inhaling via the nose instead of the mouth (17.7+/-2.8 nM, P=0.007). CONCLUSION: When compared with healthy subjects, patients with AR exhibit an increased concentration of exhaled adenosine and a related increase in exhaled NO concentration. EBC adenosine is further increased when rhinitis patients inhale through their nose than via their mouth. Our data suggest that non-asthmatic patients with rhinitis may have subclinical inflammation in their lower airways.

Adenosine↗

Comparative measurement of thromboxane A2 metabolites in exhaled breath condensate by different immunoassays.

OBJECTIVE: Differences between detection techniques may be partly responsible for variable mediator concentrations reported in exhaled breath condensate (EBC). We compared two types of immunoassays to estimate thromboxane A(2) (TxA(2)) concentration. MATERIALS AND METHODS: Thromboxane B(2) (TxB(2)) levels were measured by enzyme immunoassay (EIA) and TxB(2)/2,3-dinor TxB(2) by radioimmunoassay (RIA) in 10 healthy subjects and 13 asthmatic patients. 2,3-Dinor TxB(2) was also determined by a separate EIA. RESULTS: Thromboxane was detected in all samples by RIA, but only in about 75% of samples by EIA. 2,3-Dinor TxB(2) was detected in most samples. There was no agreement between the results of the different immunoassays. As compared to healthy subjects, exhaled breath condensates of asthmatic patients contained significantly more immunoreactivity by RIA and TxB(2) EIA (but not by 2,3-dinor TxB(2) EIA). CONCLUSION: RIA and EIA resulted in vastly different absolute values. The difference found between healthy volunteers and asthmatic patients however, suggests an increased level of TxA(2) in the airways of asthmatics.

Adult↗

Adenosine level in exhaled breath increases during exercise-induced bronchoconstriction.

In asthmatic patients, airway obstruction provoked by exercise challenge is accompanied by an increase in plasma adenosine level. In this study, the current authors investigated if exercise-induced bronchoconstriction was associated with local changes of adenosine concentration in the airways. Oral exhaled breath condensate (EBC) collection (5-min duration) and forced expiratory volume in one second (FEV1) measurements were performed at rest (baseline) and 4-8 times after treadmill exercise challenge in healthy and asthmatic subjects. Adenosine concentration in EBC was determined by HPLC. Observations indicated that physical exercise results in bronchoconstriction together with a significant increase of adenosine level in EBC in asthmatic patients (mean+/-sd maximal fall in FEV1 27+/-13%; associated increase in adenosine 110+/-76% as compared to baseline), but not in healthy control subjects. Exercise-induced changes in adenosine concentration correlated significantly with the fall in FEV1 values in asthmatic patients. In conclusion, the observed increase in adenosine concentration of oral exhaled breath condensate most probably reflects changes in the airways during exercise-induced bronchoconstriction. Due to its known bronchoconstrictor property in asthma, adenosine may contribute to the development of bronchospasm.

Adenosine↗

Adenosine in exhaled breath condensate in healthy volunteers and in patients with asthma.

Persistent airway inflammation may require the use of different markers for monitoring airway inflammation. In this study, the authors investigated whether adenosine, which may be produced in allergic inflammatory conditions, could be measured with good reproducibility in exhaled breath condensate (EBC), and whether its concentration was elevated in patients with asthma. EBC adenosine and exhaled nitric oxide (eNO), a noninvasive marker of asthmatic airway inflammation, were measured in 40 healthy volunteers and 43 patients with allergic bronchial asthma. Repeatability of adenosine measurement was checked in 20 pairs of samples collected from healthy control subjects. Adenosine was detectable in all EBC samples by the applied high-performance liquid chromatographic method. The mean difference between repeated measurements of adenosine was -0.1 nM and all differences were within the coefficient of repeatability. Adenosine concentration was higher in steroid-naive patients (n=23) compared with healthy control subjects and steroid-treated patients (n=20). In patients with worsening symptoms of asthma (n=23), adenosine concentration was elevated compared with those in a stable condition (n=20). Furthermore, adenosine concentrations were related to eNO levels in asthmatic patients. These results, showing good reproducibility of adenosine measurements and increased adenosine concentrations in steroid-naive patients and in patients with worsening of asthmatic symptoms, indicate that adenosine measurement in exhaled breath condensate might be an acceptable novel method to investigate the role of local production of adenosine in the airways.

Adenosine↗

[Effectiveness and tolerability of the glucocorticoid mometasone furoate given as nasal spray in seasonal allergic rhinitis].

The clinical effect and tolerance of momethasone furoate (MF) glucocorticoid nasal spray (MFNS) were studied in 14-70 year-old patients suffering from seasonal allergic rhinitis. The patients administered daily one (morning) dose, 100 micrograms each, of MF into both nostrils, for a period of 14 days. They did not use other medicines affecting nasal symptoms. Nasal symptoms (nasal discharge, nasal obstruction, nasal itching, sneezing) and non-nasal symptoms (lacrimation, eye itching/burning sensation, palatal itching, ear itching, general itching), scored 0 to 3, and serving as a basis for evaluating the effect, were registered before treatment (day 1) and at visits on 3, 7 and 14th day. Of the 196 patients involved in the open multicentric study, 188 completed the study. The total average nasal symptom scores decreased, already after 3 days of treatment, from 8.7 to 4.1 and to 1.6 by the 14th day. Decrease of non-nasal symptoms was also conspicuous, however, lacrimation persisted in 57 of 188 cases, while eye itching--mainly in moderate and mild form--in 90 cases. The general condition of rhinitis before the treatment was evaluated by the examiners as severe or very severe in 155 cases (82%), as symptom-free (99 cases) on day 14 in, and mild (71 cases), in 170 cases (90%). The therapeutic effect was considered by both, patients and physician, as excellent, in 106 (56%) and 115 (61%) cases, resp. and as good in 63 (34%) and 56 cases (30%). Side-effects were mostly mild and transitory. Treatment was not discontinued due to side-effect in any of the cases. Based on the results, MFNS, administered in a single daily dose of 200 micrograms, has proved to be an effective and safe glucocorticoid preparation, also easy to use locally, in the treatment of allergic rhinitis.

Administration, Intranasal↗

Efficacy of once- and twice-daily administration of budesonide via Turbuhaler as initial therapy in patients with mild persistent asthma.

Inhaled glucocorticosteroids such as budesonide have an important role in the management of asthma. Although these agents have traditionally been given twice daily, evidence is accumulating that once-daily treatment may be as effective as twice-daily administration. The efficacy of budesonide Turbuhaler (Astra, Lund, Sweden), 400 micrograms once daily in the evening or 200 micrograms twice daily, was compared in a randomized, double-blind study involving 181 patients (75 men, 106 women; mean age 30.8 years) with mild asthma [mean forced expiratory volume in 1 s (FEV1) 92.8% pred.] who had not previously been treated with inhaled glucocorticosteroids. After a 2-week run-in period, patients were randomized to either regimen and treated for 6 weeks. This was followed by two 8-week open treatment periods, during which all patients received budesonide Turbuhaler, 200 micrograms once daily during the first period and 100 micrograms once daily during the second period. The mean change in morning peak expiratory flow (PEF) during the double-blind treatment period was 16.9 l min-1 in patients receiving once-daily treatment and 17.2 l min-1 in those receiving twice-daily treatment. Similarly, there were no significant differences in evening PEF, symptom scores, bronchodilator use or spirometry data between patients receiving once- and twice-daily treatments. The improvements in morning PEF, symptom scores and bronchodilator use seen during the double-blind treatment period were maintained during the two open treatment periods. It is concluded that once-daily treatment with budesonide Turbuhaler is as effective as an initial therapy twice-daily treatment in patients with mild persistent asthma and that the initial dose can be reduced to maintenance levels (including 100 micrograms) without loss of asthma control.

Administration, Topical↗

Elevated circulating adenosine level potentiates antigen-induced immediate bronchospasm and bronchoconstrictor mediator release in sensitized guinea pigs.

BACKGROUND: Adenosine causes bronchoconstriction in asthmatic patients, and it is also accepted that adenosine influences histamine release from activated human mast cells and basophils in vitro. OBJECTIVE: In this study we tested the hypothesis that adenosine potentiates both the airway narrowing and the release of bronchoconstrictor mediators induced by ovalbumin challenge in sensitized guinea pigs. METHODS: After ovalbumin sensitization, 4 groups were studied: control group, adenosine group (ADO), ovalbumin group (OA), and adenosine plus ovalbumin group (ADO + OA). Changes in airway resistance were assessed from continuously recorded pulmonary insuffilation pressure (PIP). The concentration of histamine, PGD2, and thromboxane B2 were determined from bronchoalveolar lavage fluids. RESULTS: Adenosine alone (6 mg/kg intravenously) did not influence baseline values of PIP and the mediator concentrations; however, ovalbumin (10 mg/kg intravenously) increased both the PIP and the levels of the measured mediators compared with the control and ADO groups. When ovalbumin challenge was preceded by adenosine administration, both PIP and mediator levels were significantly enhanced compared with values obtained after simple ovalbumin provocation (ADO + OA vs OA: P <.05). CONCLUSION: These results suggest that adenosine potentiates the airway narrowing induced by ovalbumin challenge and that this effect may develop through facilitation of the release of bronchoconstrictor mediators during the immediate airway response.

Adenosine↗

Relation between bronchial and cardiac vagal tone in healthy humans.

A generally increased vagal nervous activity was suggested to exist in bronchial asthma; however, this contention has never been fully tested. Before studying vagal activity in asthma, we raised the question if there existed any relation between vagal outflows to different target organs in the physiologic state. The specific aim of this study was to determine the relation between the resting level of bronchial and cardiac vagal activity in healthy volunteers. Bronchial and cardiac vagal tone were measured in 12 subjects as the change of airway resistance (Raw) and heart period (HP) in response to complete cholinergic blockade. It was found that after intravenous atropine administration, Raw was reduced from 1.30 +/- 0.41 cm H2O/L/s to 0.51 +/- 0.22 cm H2O/L/s and HP was reduced from 789 +/- 84 ms to 506 +/- 41 ms. All the values are given as mean +/- SD. Both the bronchial and cardiac responses exhibited considerable interindividual variability, but there was no significant correlation between them (R = 0.22, p = 0.50). It was concluded that under resting conditions, vagal control of bronchial tone and HP were not related in healthy human subjects.

Adult↗

Comparative clinical examination of Loderix (setastinum) and astemizole in pollenosis.

The action and side-effects of Loderix (EGIS) were examined in comparison with Hismanal (Janssen) containing the non-sedative H1-receptor antagonist astemizole, by double-blind, cross-over, self-controlled method. On the basis of the changes observed in response to the two drugs in the symptoms of rhinoconjunctivitis and asthma of 21 patients suffering from pollenosis Loderix proved to be of the same value as Hismanal considering both clinical effectivity and side-effects.

Adult↗

Effects of ketotifen and clenbuterol on beta-adrenergic receptor functions of lymphocytes and on plasma TXB-2 levels of asthmatic patients.

Clinical observations indicate that beta-adrenergic drugs may increase bronchial reactivity in asthmatics. To find out possible reasons for this phenomenon the beta-adrenergic receptor function of isolated lymphocytes of asthmatic patients treated with clenbuterol alone or with ketotifen and clenbuterol together were studied. The cAMP levels of lymphocytes stimulated by different doses of isoproterenol were measured by radioimmunoassay and have been compared in the groups of healthies, and asthmatic patients after 3-months running of clenbuterol (Spiropent, Sandoz), as well as in the same asthmatics after one-week running of parallel administration of ketotifen and clenbuterol. There was no difference between the beta-adrenergic receptor function in asthmatic patients treated with clenbuterol alone vs. untreated healthies. Applying ketotifen and clenbuterol together the beta-adrenergic receptor function increased compared to the values obtained after application of clenbuterol alone (intraindividual-control) as well as vs. the group of healthies (control). Data presented support the view that therapeutic doses of selective beta 2-agonists do not lead to damage of the beta-adrenoceptor function. The improvement of receptor function after parallel administration of clenbuterol and ketotifen may be a consequence of the participation of ketotifen in the control of beta-adrenergic receptor system. Thus it seems unlikely that down-regulation of beta-adrenergic receptors is responsible for the beta-agonist induced bronchial hyperreactivity. That's why TXB-2 levels in the plasma of the same asthmatic patients and healthy volunteers were determined by RIA.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗

Effects of drugs on aminophylline elimination in rats.

Effects of phenobarbital, phenytoin, carbamazepine, cimetidine, erythromycin, combination of sulfamethoxazole + trimethoprim (5:1), and rifampicin (rifampin) on the elimination of aminophylline were examined in female rats. Aminophylline was administered i.p. in a dose of 13.33 mg/kg. Blood samples were collected 0.5, 2, 4 and 7 h after the administration of the injection; one measurement was performed from one blood sample. Plasma aminophylline levels were measured by a modified HPLC method. The elimination half-life of the untreated control group (n = 27) was 4.62 h. The pretreatments with drugs examined were carried out by a gastric tube. The half-life of aminophylline after phenobarbital (10 mg/kg, 7 days, n = 29) was 2.09 h; after phenytoin (10 mg/kg, 7 days, n = 29), 2.47 h; after carbamazepine (400 mg/d, 7 days, n = 25), 2.19 h; after cimetidine (in cimetidine-treated group the blood samples were collected 0.5, 4 and 7 h after the aminophylline injection) (40 mg/kg, 7 days, n = 13), 1.77 h; after erythromycin (800 mg/d, 7 days, n = 28), 2.51 h; after the combination of sulfamethoxazole + trimethoprim in ratio of 5:1 (50 mg/kg, 7 days, n = 23), 2.85 h; and after rifampicin (300 mg/kg, 21 days, n = 23), 2.74 h. Sulfamethoxazole presumably interfered with the HPLC examination of aminophylline.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophylline↗

The beta-adrenoceptors of lymphocytes in asthmatic patients treated with beta-agonists.

Numbers of beta-adrenoceptors in intact human lymphocytes of asthmatics treated continuously with the usual doses of beta-agonists have been estimated. Lymphocytes were isolated by density gradient centrifugation as described by BOYUM [4]. The binding experiment was performed with (-)3H-dihydroalprenolol which is a high affinity beta-adrenoceptor antagonist. There was no difference between the mean values of the binding sites of asthmatic patients and those of the normal volunteers. In asthmatic patients, a significant correlation was found between the density of receptors and the percentage increase of FEV1 after salbutamol inhalation. Symptoms of drug tolerance were not observed in patients treated with therapeutic doses of beta-agonists.

Adrenergic beta-Agonists↗

Development of drug tachyphylaxis in asthmatic patients treated with beta-adrenergic drugs.

The development of drug tolerance in two groups of asthmatics treated with beta-adrenergic bronchodilators was studied by respiratory function methods. During one-year treatment with conventional therapeutic doses of selective beta-2-receptor stimulant aerosols, none of the patients showed subsensitivity to the bronchodilatory effect of terbutaline. Dose-response curves were plotted upon the inhalation of salbutamol in two-week intervals in patients treated with betamimetics. There was no decrease in the airways beta-adrenergic receptor function as compared to the untreated control group. The results show that prolonged treatment with therapeutic doses of inhaled beta-adrenergic bronchodilators does not result in drug tachyphylaxis, which is in accord with the clinical experience that there is no loss of effect of the preparations during their continuous administration.

Adrenergic beta-Agonists↗

Effect of enzyme inducer flumecinolum (Zixoryn) on aminophylline metabolism in rats.

The effect of the enzyme inducer flumecinolum, m-trifluoromethyl-alpha-ethylbenzhydrol (Zixoryn), on aminophylline metabolism was examined in rats. Aminophylline plasma levels were determined by HPLC. Aminophylline T1/2 was 2.85 hours (r = 0.9353) in the pretreated group and 3.75 hours (r = 0.9471) in the untreated control group. Flumecinolum was found to accelerate the elimination of aminophylline and the effect became significant 3.92 hours after the administration of aminophylline.

Aminophylline↗