Biomedical subjects

N Tudoric

Publications and source records attributed to N Tudoric.

6 recordsLinked to original sources

PubMed2000

Allergen inhalation challenge induces decrease of serum neutral endopeptidase (NEP) in asthmatics.

There is accumulating evidence that tachykinins are implicated in inflammation, including asthma. Therefore, we hypothesized that the neutral endopeptidase (NEP), under challenge conditions, could be affected. Serum from 21 asthmatics and six healthy volunteers was sampled before, 30, and 120 min after allergen challenge. NEP-IR was determined using an ELISA and was found in all subjects. Compared to prechallenge, no difference was seen between asthmatics and controls; however, under challenge conditions, NEP-IR in asthmatics was significantly lower (30 min, P = 0.058; 120 min, P = 0.0017, respectively). This finding supports indirectly the hypothesis that tachykinins are released during allergen exposure, and suggests a regulatory role of NEP.

Administration, Inhalation↗

PubMed1999

Non-specific nasal and bronchial reactivity are not correlated in non-asthmatic subjects occupationally exposed to irritants and in healthy subjects.

BACKGROUND: Non-specific nasal and bronchial reactivity are frequently correlated in disease (rhinitis and asthma). It is not known whether such a correlation exists in subjects exposed to irritants and in healthy subjects. In order to test the hypothesis that a correlation between non-specific nasal and bronchial reactivity exists in non-asthmatic subjects, two groups of subjects were studied: 110 workers occupationally exposed to respiratory irritants, and 86 non-exposed healthy controls. METHODS: Allergy, non-specific nasal, and non-specific bronchial reactivity were tested, and smoking habits were categorized in each subject. RESULTS: Respiratory irritants cause a substantial increase in nasal and bronchial reactivity when compared with the group of healthy, non-exposed subjects (33.6% nasal hyperreactors and 20.0% bronchial hyperreactors vs. 4.7% nasal hyperreactors and 2.3% bronchial hyperreactors, respectively). But, occupational exposure to respiratory irritants does not induce a correlation between non-specific nasal and bronchial reactivity frequently found in asthmatic and rhinitic subjects. CONCLUSIONS: We found no correlation between non-specific nasal and bronchial reactivity either in subjects occupationally exposed to respiratory irritants or in the group of healthy subjects. This lack of correlation in both studied groups seems to be a feature of non-diseased airways. Smoking as an additional factor does not increase nasal and bronchial reactivity either in workers exposed to irritants or in healthy subjects. Smoking also does not strengthen the correlation between upper and lower airways' reactivity in both groups.

Adult↗

PubMed1996

Decrease in CD23+ B lymphocytes and clinical outcome in asthmatic patients receiving specific rush immunotherapy.

Rush immunotherapy (RIT) has been documented as useful in the treatment of patients with allergic bronchial asthma. To investigate the mechanisms of its action, we studied changes in the serum levels of total IgE, allergen-specific IgE and IgG4, and expression of CD23 on peripheral blood B cells in patients receiving RIT. Twenty patients with perennial bronchial asthma were evaluated before the beginning of RIT, as well as 6 weeks and 6 months later. Compared to pretreatment values, the level of Der-p-specific IgG4 and IgE significantly increased after 6 weeks and 6 months of RIT, while the total serum IgE remained unchanged. Furthermore, after 6 months of RIT, the percentage of CD23+B cells and its CD23 receptor density significantly decreased. Since the symptom score improved and the need for medication decreased, we evaluated RIT as a useful procedure. After 6 months, 30% of patients did not have an asthma attack, with no medication in the last month, while 10% of them were asthma free for the last 3 months. No significant correlation between the clinical improvement, and in vitro changes was found. Furthermore, the observed in vitro changes were not significantly different in patients who responded with clinical improvement, compared to those with unchanged intensity of asthma. In conclusion, during specific RIT we found a significant increase in Der-p-specific IgE and IgG4 antibodies, as well as a moderate decrease in CD23+ B cells and its CD23 receptor density. These findings suggest a change in the lymphokine profile of patients receiving specific immunotherapy, and that the inhibition of IL-4-induced B cell stimulation may be hypothesized as the most important mechanism.

Adolescent↗

PubMed1995

Effects of halothane and isoflurane on antigen- and leukotriene-D4-induced constriction of guinea pig trachea.

We investigated the mechanism of the action of volatile anesthetics on the airway smooth muscle constricted by an antigen and leukotriene-D4 (LTD4). Excised tracheal rings from ovalbumin-sensitized guinea pigs were suspended in eight tissue baths. Halothane or isoflurane was aerated into four tissue baths, while the remaining four served as time controls. To assess the antispasmogenic activity of halothane and isoflurane, concentration-response curves for antigen and LTD, were constructed exposed to anesthetics and compared to controls. The spasmolytic activity of halothane and isoflurane was measured in the tracheal rings constricted by a single antigen challenge or by EC50 of LTD. Both halothane and isoflurane produced significant rightward shifts of ovalbumin and LTD, concentration-response curve with corresponding increases in the EC50 values. Halothane increased the EC50 value for LTD, from 5.38 +/- 0.43 x 10-9 M to 1.2 +/- 0.18 x 10-8 M, and for ovalbumin from 1.2 +/- 0.06 x 10-4 mg/ml to 3.03 +/- 0.28 x 10-4 mg/ml. Isoflurane increased the EC50 value for LTD, from 5.17 +/- 0.64 x 10-9 M to 8.98 +/- 1.01 x 10-9 M, and for ovalbumin from 1.21 +/- 0.09 x 10-4 mg/ml to 2.61 +/- 0.19 x 10-4 mg/ml. Furthermore, halothane and isoflurane significantly reduced the magnitude of the antigen-and LTD4-induced constriction. In 30 min intervals, 1% and 2% halothane reduced the magnitude of the ovalbumin-induced constriction by 32% and 50%, respectively, while isoflurane (2% and 4%) caused relaxation of 16% and 35%, respectively. The magnitude of LTD4-induced constriction was reduced by 17% and 24%, with 1% and 2% halothane, respectively. Isoflurane (2% and 4%) reduced this constriction by 25% and 25% respectively. In conclusion, halothane and isoflurane attenuate and prevent the constrictive response of airway smooth muscle to allergen and LTD. A direct, nonspecific dilating effect is suggested as the mechanism responsible for the observed effects.

Anesthetics, Inhalation↗

PubMed1994

Inhibition of neutral endopeptidase potentiates compound 48/80-induced constriction of guinea-pig tracheal smooth muscle.

Our previous studies have shown that the inhibition of neutral endopeptidase, an enzyme which degrades tachykinins, increases anaphylactic construction of guinea-pig tracheal smooth muscle. To investigate this observation further, we examined the effects of phosphoramidon, an inhibitor of a neutral endopeptidase, on constriction induced by the non-immunological mast cell degranulator-compound 48/80. Phosphoramidon produced significant leftward shift of the compound 48/80 concentration-response curve with corresponding decrease in the EC50 value from 51 (28-80) micrograms/ml to 42 (20-72) micrograms/ml. When added during the compound 48/80-induced constriction, phosphoramidon significantly increased the magnitude of this constriction by 69.7% after 30 min, and 78.9% after 45 min. Phosphoramidon was ineffective in tracheal rings from tachykinin-depleted guinea pigs. The incubation of tracheal rings with H1-histamine receptor antagonist (diphenhydramine HCl, 10 microM) and leukotriene receptor antagonist (ICI 198.615, 5 microM) significantly diminished the contractile response to compound 48/80 and prevented a phosphoramidon-dependent increase of this constriction. These results suggest that compound 48/80 induces the release of tachykinins by the stimulatory activity of histamine and leukotrienes. Anaphylactic release of tachykinins would therefore not depend directly on the antigen-antibody reaction.

Anaphylaxis↗

PubMed1993

Inhibition of neutral endopeptidase augments anaphylactic constriction of guinea pig tracheal smooth muscle.

To determine whether tachykinins participate in antigen-induced constriction of tracheal smooth muscle, we examined the effects of a neutral endopeptidase inhibitor, phosphoramidon, the tachykinin antagonist (D-Pro4, D-Trp7,9,10)-substance P(4-11), and capsaicin-induced tachykinin depletion on the responses to antigen in tracheal rings from ovalbumin-sensitized guinea pigs. In these preparations, the antigen (ovalbumin, 0.1 microgram/ml) produced reproducible and durable constriction of tracheal smooth muscle. Incubation with phosphoramidon (10 min, 10 microM) prior to antigen challenge significantly augmented the magnitude of ovalbumin-induced constriction by 22% after 30 min and by 31% after 45 min. The addition of phosphoramidon at the plateau level of antigen-induced constriction produced a similar, significant increase in the magnitude of the constriction. Following incubation with tachykinin antagonist (D-Pro4,D-Trp7,9,10)-substance P(4-11) (5 microM), the contractile response of the tracheal rings to the antigen was not altered. Furthermore, the addition of phosphoramidon (10 microM) did not significantly affect this contraction. Similarly, neither tachykinin antagonist nor phosphoramidon altered the ovalbumin-induced constriction of the tracheal rings from capsaicin-treated guinea pigs. Based on these findings, we hypothesize that tachykinins or similar broncho-constricting neutral endopeptidase substrates were released from tachykinin-containing nerve endings during immediate hypersensitivity reaction in airways, manifesting a modest and delayed constrictive effect. Following alteration of endopeptidase activity, these substances could modulate the anaphylactic constriction of the airway smooth muscle.

Anaphylaxis↗