Biomedical subjects

J S Lacroix

Publications and source records attributed to J S Lacroix.

At least 19 recordsLinked to original sources

PubMed2003

Somato-sympathetic vasoconstriction to intranasal fluid administration with consecutive decrease in nasal nitric oxide.

AIM: Patients suffering from non-allergic chronic rhinosinusitis (NACRS) increasingly use intranasal saline sprays. They report better nasal comfort. METHODS: In order to better understand this phenomenon, we studied intranasal laser Doppler flowmetry (LDF) and nasal nitric oxide (NO) variations evoked by local administration of saline, histamine, N-acetylcysteine (NAC) and lidocaine at room temperature (22 degrees C). RESULTS: There was a significant (P < 0.05) 14 +/- 3.8% decrease in LDF signal after 30 s, which lasted for 60-90 s, for all the substances applied at 22 degrees C. This pharmaco-independent vasoconstriction was further studied in patients under general anaesthesia (GA), with saline at 37 degrees C and after intranasal adrenaline treatment. While GA did not influence the vasoconstriction, saline at 37 degrees C and adrenaline pre-treatment abolished it. Nasal NO is influenced by vasoconstriction. Therefore we investigated, whether the observed vasoconstriction also changes nasal NO. A significant (P < 0.001) 8.03 +/- 0.59% decrease in nasal NO was recorded 60 s after administration of all the substances, and under GA after 22 degrees C saline application. This NO decrease was absent after intranasal adrenaline pre-treatment. An additional experiment tested the effect of nose blowing on nasal NO concentration. We registered an NO decrease with a similar pattern than observed with the other substances. CONCLUSIONS: Intranasal fluid nebulization at 22 degrees C induces a sympathetic mediated, transient vasoconstrictor reflex response. This somato-sympathetic vasoconstriction induces a decrease in nasal NO. Both could be related to the subjective comfort experienced by NACRS patients using intranasal saline sprays.

Acetylcysteine↗

PubMed2002

Comparison of once- versus twice-daily use of beclomethasone dipropionate aqueous nasal spray in the treatment of allergic and non-allergic chronic rhinosinusitis.

The aim of the study was to assess the efficacy and safety of nasal aqueous beclomethasone dipropionate (BDP), 400 micro g/day, given via a metered pump in a once-daily or twice-daily regimen following a double-blind, parallel group design over a 12-week period. Adult patients (n=112) with allergic or non-allergic chronic rhinosinusitis recorded their nasal and ocular symptoms for the 7-day run-in period and for the first 4 weeks of treatment. At baseline and after 4 weeks the airways' resistance via active anterior rhinomanometry and the volume and area section via acoustic rhinometry were measured. Morning serum cortisol was measured at baseline and at week 12. Adverse events were to be reported at each visit. Of the 112 randomised patients, three did not enter the ITT analysis and another 13 in total discontinued the treatment. Significant improvements over the baseline were reported in both groups for the primary variable sum of nasal scores (-53.7% in the once-daily group and -59.7 in the twice-daily group), as well as for each nasal and ocular symptoms, without differences between the groups. Because of a wider variability than expected, the 95% confidence interval (C.I.) for the difference between the least square means exceeded the pre-defined limit of +/-10% of the reference mean. Similar improvements in both groups were also reported for the nasal airway patency's parameters. The total number of drug-related adverse events was 26 in the once-daily group and 32 in the twice-daily group, with most of the events consisting of local effects at the site of application. No signs of adrenal suppression were observed, and serum morning cortisol values did not significantly change. The once-daily BDP dosing (400 micro g/day) therefore has a similar efficacy and safety profile as the same daily dose given in a twice-daily regimen.

Administration, Intranasal↗

PubMed2002

Histological comparison of nasal polyposis in black African, Chinese and Caucasian patients.

We have compared the histological aspects of nasal mucosa biopsies (n = 130) obtained during bilateral polypectomy and ethmoidectomy performed in black African (n = 50), Chinese (n = 30) and Caucasian patients (n = 50) suffering from bilateral nasal polyposis (NP). The three groups of patients were matched for age and sex. The African and Chinese patients did not receive any medical treatment before endoscopic nasal surgery (ENS). All Caucasian patients were treated with corticosteroid nasal spray (400 mg/day) for 6 months. In the absence of subjective and objective clinical improvement, ENS was performed after antibiotic treatment for 10 days and prednisolone 1 mg/kg/day for 5 days. Clinical staging of the NP was graded from I to III (I = polyps limited to the middle meatus, II = polyps extending beyond the middle meatus, and III = polyps occupying the entire nasal cavity). Stage I NP was present in 22% of the Caucasians and 30% of the Chinese. Stage II was found in 58% of the Caucasians, 56% of the Chinese and 8% of the Africans. Stage III was found in 92% of the Africans, while only 20% of the Caucasians and 14% of the Chinese patients had stage III. The extent of submucosal oedema and number of mast cells were similar for the three groups of patients. A significantly greater number of eosinophils were observed in African polyps. Lymphocytes as well as plasmocytes were rare in African but abundant in polyps from both Chinese and Caucasian. Ulceration of the overlying epithelium of the polyps was observed in 20% of the African and 10% of both Chinese and Caucasians patients. We did not find any significant thickening of the basal membrane. We cannot exclude the possibility that the histological difference observed between African and Chinese polyps is related to the very common use among the Chinese population of topical intranasal treatment according to their traditional medicine practices. Since no major histological difference was found in the nasal mucosa and polyps obtained from the three groups of patients, NP in African, Chinese and Caucasian patients is very probably a similar inflammatory disease in all three ethnic groups.

Adolescent↗

PubMed2001

Modulatory effect of two novel CGRP receptor antagonists on nasal vasodilatatory responses to exogenous CGRP, capsaicin, bradykinin and histamine in anaesthetised pigs.

Calcitonin gene-related peptide (CGRP) is a 37-amino acid peptide and potent vasodilatator agent located in sensory C fibres. Several functional studies suggest that CGRP could be involved in the vasodilatation of different vascular beds during neurogenic inflammation. We have studied, in pentobarbital anaesthetised pigs, the antagonistic effect of local intra-arterial (i.a.) pretreatment with the analogues CGRP 8-37, [D31, P34, F35]CGRP 27-37 and [N31, P34, F35]CGRP 27-37 on the vasodilatation of the nasal vascular bed induced by exogenous CGRP, capsaicin, bradykinin (BK) and histamine. The attenuating effect of CGRP 8-37 analogue on exogenous CGRP-induced vasodilatation, previously described in other in vivo animal models, was confirmed in the pig nasal mucosa. It also interfered with BK-and, to a lesser extent, with capsaicin-and histamine-induced decrease in vascular resistance. CGRP 27-37 analogues reduced the duration of CGRP-, capsaicin- and BK-induced vasodilatation by more than 50%. Peak values of vasodilatation were attenuated by more than 25% overall. Attenuation of histamine-induced decrease in vascular resistance was less pronounced. It is concluded that CGRP 27-37 analogues antagonise the action of exogenous CGRP, capsaicin, BK and histamine by attenuating their vasodilatation effect, both in intensity and duration. These results strongly suggest that BK- and histamine-induced vasodilatation is partly mediated by CGRP. CGRP 8-37 and 27-37 appear to be potential contributors to the study of CGRP and its physiological role in neurogenic inflammation. In addition, they may have putative therapeutic applications in the treatment of rhinitic patients suffering from chronic nasal obstruction.

Anesthesia↗

PubMed2001

Assessing cerebrospinal fluid rhinorrhea: a two-dimensional electrophoresis approach.

Assessment of nasal cerebrospinal fluid (CSF) fistula commonly relies on the determination of CSF markers in an aqueous rhinorrhea, such as the beta2-transferrin immunofixation assay. While generally reliable, false positive and false negative results have been reported for most of the laboratory tests yet available. Based on the hypothesis that the simultaneous assessment of several CSF markers may yield an increased sensitivity and specificity, we used a proteomics, two-dimensional electrophoresis 2-DE based approach to study samples of nasal secretions obtained from 18 patients suspected of CSF rhinorrhea. Since CSF, nasal mucus and plasma may coexist in the nasal cavities, we first defined five specific markers for each of these biological fluids (transferrin, prostaglandin-D synthase, transthyretin, and two unknown trains of spots for CSF, immunoglobulin A (IgA) S-chain, lipocortin-1, lipocalin-1, prolactine-inducible protein and palatal lung nasal epithelium clone protein for mucus, haptoglobin alpha1/2- and beta-chains, fibrinogen alpha-, beta- and gamma-chains for plasma). Gels from the rhinorrhea patients were then compared to these 2-DE reference maps to determine the presence or absence of the defined markers, and clinical data were independently compared to the results of the 2-DE study. In all cases, the biological fluid(s) anticipated to be present in the nasal secretions based on clinical data were correctly identified by 2-DE. Moreover, an excellent correlation was found in nine patients who underwent extensive workup for suspected CSF rhinorrhea, since CSF was found by the 2-DE method in four patients in whom a CSF fistula was confirmed, whereas the test was negative in five patients in whom a CSF fistula was excluded. In the remaining patients, mucus, sometimes contamined with blood, was found to be the major component of the nasal secretions, confirming that clear mucus may mimick CSF rhinorrhea. These preliminary results suggest that a 2-DE-based multimarker approach is a valid, sensitive, and specific method to assess the presence of CSF in occult rhinorrhea.

Adult↗

PubMed2001

Role of nasopharyngeal culture in antibiotic prescription for patients with common cold or acute sinusitis.

The aim of the present study was to assess the hypothesis that, when present in nasopharyngeal secretions, Streptococcus pneumoniae. Haemophilus influenzae, and Moraxella catarrhalis play a pathogenic role early in the course of an upper respiratory tract infection. Adults with a clinical diagnosis of acute sinusitis or common cold were enrolled. Participants were randomly assigned in a double-blind manner to receive azithromycin 500 mg daily or placebo for 3 days. The effect of treatment on symptom evolution in the predefined subset of patients with Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis in their nasopharyngeal secretions was assessed. Of 265 patients enrolled, 132 received placebo and 133 azithromycin. Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis was identified in nasopharyngeal secretions of 77 patients (29%). In this predefined subgroup of patients with Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, resolution of symptoms by day 7 occurred in 73% of those treated with azithromycin compared with 47% of those who received placebo (P=0.007). The median time before resolution of symptoms was 5 days in the azithromycin group compared to 7 days in the placebo group. Respiratory complications requiring antibiotic treatment occurred in 19% of patients in the placebo group and in 3% of the azithromycin group (P=0.025). In the remaining 188 patients without Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, resolution of symptoms by day 7 was similar in both groups (69% in the placebo group vs. 64% in the azithromycin group [P=0.75]). Antibiotic treatment is of clinical benefit for patients with acute sinusitis or common cold when Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis is present in nasopharyngeal secretions. This observation provides new insights into the pathogenic role of these bacteria in the early stage of the common cold.

Acute Disease↗

PubMed2000

Effect of intranasal treatment with capsaicin on the recurrence of polyps after polypectomy and ethmoidectomy.

The aim of this study was to evaluate the influence of five intranasal applications of capsaicin, performed after endoscopic polypectomy associated with partial middle turbinectomy and anterior ethmoidectomy, on the recurrence of nasal polyps and the intensity of nasal obstruction and rhinorrhea. Fifty-one patients (19 females, 32 males, mean age 43 years) suffering from nasal polyposis for more than 1 year were included in this double blind, randomized, placebo-controlled study. During post-surgical controls, local anaesthesia and vasoconstriction of the middle meatus area were performed in all patients with a cotton pellet soaked with lidocain and adrenaline. In 29 patients, the same type of cotton pellet soaked with capsaicin (3 x 10(-6) mol. dissolved in 70% ethanol) was left into the middle meatus of both nostrils for 20 min. As a control group, 22 patients, matched for age and sex, were treated with the capsaicin vehicle alone (70% ethanol). All patients studied received the intranasal treatment once a week for 5 weeks. Subjective evaluations of nasal airway resistance (NAR) and rhinorrhea were recorded by means of a visual analogue scale. Clinical staging of the nasal polyposis (graded from stage 0 = absence of polyp to stage 3 = polyps occupying the entire nasal cavity) was evaluated by the same ENT specialist (ZW) using a 0 degrees endoscope. All parameters were recorded for each patient 1 week before surgery, then once a month for 9 months. Patients treated by endoscopic surgery followed by intranasal capsaicin application, reported a marked reduction in their NAR compared with the pretreatment evaluation (p<0.001). In contrast, patients treated with the vehicle alone did not have any significant improvement of their subjective NAR. Subjective rhinorrhea was not modified by either treatment. Patients treated with capsaicin showed a significant smaller staging of their nasal polyposis compared with the control group (p<0.001). These observations suggest that endoscopic surgery followed by intranasal capsaicin application reduces polyps and nasal obstruction recurrence and could be an alternative treatment to expensive corticosteroids in developing countries.

Administration, Intranasal↗

PubMed2000

Modulation of capsaicin-sensitive nerve activation by low pH solutions in guinea-pig lung.

We have studied the stimulation of airways sensory nerves by low pH solutions and concomitantly induced bronchoconstriction. The effect of low pH buffer and lactic acid solutions at the same pH (5 and 6) were compared and the influence of low pH on the capsaicin effect was recorded. We have used the isolated guinea-pig perfused lung model taking the insufflation pressure as an indicator of bronchial smooth muscle tone while the calcitonin gene-related peptide-like immunoreactivity measured in the lung perfusate represented sensory nerves activation. Low pH buffer and lactic acid solution (3 and 4.1 mM) at the same pH of 5 and 6 induced pH-dependent bronchoconstriction and peptides release which were completely abolished after systemic pretreatment with capsaicin. Both responses were significantly inhibited after Ca2+-free infusion. Capsazepine (10(-6) M), a selective capsaicin antagonist, significantly reduced the calcitonin gene-related peptide-like immunoreactivity overflow evoked by all the solutions studied. Diclofenac (10(-5) M), a cyclooxygenase blocker, inhibited pH 5, pH 6 and lactic acid 3 mM (pH 6)-evoked peptide release, but not lactic acid 4.1 mM (pH 5). The functional response was not significantly modified after diclofenac while only the lactic acid 3 mM response was significantly reduced by capsazepine. There was a synergistic interaction between capsaicin and low pH buffer on calcitonin gene-related peptide-like immunoreactivity release and an additive effect on bronchoconstriction. It is concluded that in the isolated perfused guinea-pig lung, lactic acid and low pH buffer induced calcitonin gene-related peptide-like immunoreactivity release and bronchoconstriction by stimulation of capsaicin-sensitive C fibres via a pathway partly dependent of extracellular Ca2+. The mechanism of calcitonin gene-related peptide-like immunoreactivity release seems to be the same at pH 6, while differences are evident at pH 5 between low pH buffer and lactic acid. Our results also suggest that proton activity could exert a modulatory role on the capsaicin-sensitive sensory nerves by a mechanism which remains to be clarified.

Animals↗

PubMed2000

[Correlation between objective criteria and subjective evaluation of symptoms in chronic rhinosinusitis].

INTRODUCTION: We evaluated the possible correlations between the extent of inflammatory infiltration of the nasal mucosa caused by mechanical irritation (septal deviation and hypertrophy of the middle turbinate) and nasal airway resistance measured by rhinomanometry and acoustic rhinometry. Subjective evaluation of the nasal obstruction, rhinorrhoea and headache was done by visual analogic scale and compared with the inflammation. PATIENTS AND METHODS: 40 patients with a more than 18 months' history of chronic rhinosinusitis associated with septal deviation and/or hypertrophy of the middle turbinate were included in the study. The density of inflammatory cells (graded from + to +3, where + means few and +3 abundant inflammatory cells) in the mucosa of the middle turbinate was evaluated histopathologically. RESULTS: We found a significant correlation between subjective intensity of nasal obstruction and inflammation (mainly lymphocytes) of the middle turbinate mucosa and the value of nasal airway resistance measured by rhinomanometry. No correlation was found between the other parameters studied. CONCLUSION: Mechanical stimulation at the level of turbinoseptal contact causes inflammation in the mucosa which correlates with both subjective nasal airway resistance and rhinomanometry values.

Adolescent↗

PubMed2000

[Symptoms and clinical and radiological signs predicting the bacterial origin of acute rhinosinusitis].

A minority of patients with common cold and upper respiratory tract infections have a bacterial infection and may benefit from antibiotic therapy. The present analysis set out to determine whether there were clinical symptoms or signs which could help the clinician to identify a subset of patients with moderate forms of acute rhinosinusitis who are infected with pathogenic bacteria. Detailed clinical history and medical examination were obtained from 265 patients (mean age 35 years, 138 females and 127 males) presenting symptoms of upper respiratory tract infections but no fever above 38 degrees C. The presence of three pathogenic bacteria (S. pneumoniae, H. influenzae or M. catarrhalis) was determined in all patients by culture of nasopharyngeal secretions. Aggravating factors for severity of rhinosinusitis, such as severe nasal obstruction, inferior and/or middle turbinate hypertrophy, oedema of the middle meatus mucosa and septal defects, were not associated with the presence of bacteria. Pathogenic bacteria were found in 77 patients (29%). The clinical signs and symptoms which were significantly associated in a multivariate model with the presence of bacteria included facial pain (p < 0.003), coloured nasal discharge (p < 0.003) and radiological maxillary sinusitis (complete opacity, air-fluid level or mucosal thickening greater than 10 mm) (p < 0.002). This, the best predictive model, had a sensitivity of 69% and a specificity of 64% and therefore could not be used either as a screening tool or as a diagnostic criterion for bacterial rhinosinusitis. We conclude that signs and symptoms of acute rhinosinusitis in patients with a mild to moderate clinical presentation are poor predictors of the presence of bacteria. In agreement with previous studies, culture of nasopharyngeal secretions may identify patients who would benefit from antibiotic treatment. Thus, antibiotic therapy should not be prescribed in the absence of bacteriological evidence.

Adolescent↗

PubMed2000

[Evaluation of various antagonists of CGRP, a neuromediator implicated in the inflammatory mechanisms of nasal mucosa].

INTRODUCTION: This article presents a review of the literature addressing the role of different neuropeptides involved in neurogenic inflammation at the level of the nasal mucosa. DISCUSSION: Calcitonin gene-related peptide (CGRP) is a vasodilator peptide located in sensory C fibres. It plays an important role during neurogenic inflammation by controlling both tonicity and permeability of different vascular beds. Its release can be produced by capsaicin, bradykinin (BK) or histamine. In turn, CGRP appears to play an important role in modulating histamine-induced vascular responses. Different CGRP analogues are used to investigate the mechanisms of neurogenic inflammation. Some of them antagonise exogenous substances such as CGRP, capsaicin or bradykinin, attenuating the vasodilatation induced both in intensity and duration. They can contribute to the study of CGRP and its physiological involvement in neurogenic inflammation. Moreover, they may have therapeutic applications in the treatment of patients with nasal hyperreactivity.

Bradykinin↗

PubMed2000

[Study of the enzyme peptidyl peptidase IV in nasal mucosa].

INTRODUCTION: The endothelial serine protease dipeptidyl peptidase IV (DPP IV) cleaves the tyrosin-prolin dipeptide of several inflammatory mediators and neuropeptides, including neuropeptide Y (NPY), yielding the endogenous Y2-receptor agonist NPY (3-36) which modulates sensory and parasympathetic nerve activity. The aims of the study were to investigate the localisation of DPP IV in human nasal mucosa and to measure in vitro activity of DPP IV in nasal mucosa biopsies from patients suffering from chronic rhinosinusitis. PATIENTS AND METHODS: Using immunohistochemistry we have studied the localisation of DPP IV in human nasal biopsies. The activity of DPP IV was measured in vitro in nasal mucosa samples obtained from 45 patients suffering from chronic rhinosinusitis and compared with the density of inflammatory cell infiltration. RESULTS: Positive immunoreactivity for DPP IV was observed in the human nasal mucosa. Low activity of DPP IV was associated with high density of inflammatory cells in the mucosa of patients suffering from chronic rhinosinusitis. The regressive correlation was statistically significant (p < 0.001). CONCLUSION: Low level DPP IV activity is associated with inflammation of the nasal mucosa. This enzyme may be involved in the pathophysiological mechanism of nasal hyperreactivity and chronic rhinosinusitis.

Adolescent↗

PubMed2000

[Effect of intranasal treatment with capsaicin on polyp recurrence after polypectomy and ethmoidectomy].

OBJECTIVE: To evaluate the influence of polypectomy and anterior ethmoidectomy associated with intranasal applications of capsaicin on the recurrence of nasal polyps. METHOD: Fifty one patients (19 females, 32 males, mean age 43) undergoing polypectomy and anterior ethmoidectomy were included in the study. In 29 patients, a cotton pellet soaked with capsaicin (3 x 10(-6) mol, dissolved in 70% ethanol) was left into the middle meatus for 20 min under local anaesthesia. As a control group, 22 patients were treated with the capsaicin vehicle alone (70% ethanol). All patients studied received the intranasal capsaicin or vehicle treatment once a week for 5 weeks. The clinical objective examination and the subjective evaluation of nasal obstruction, rhinorrhea were recorded by means of a visual analogic scale graded from 0 to 4 throughout the study. RESULT: Patients treated with intranasal capsaicin application reported 9 months later and 55 months later separately, a marked reduction of their subjective evaluation of nasal obstruction when compared to the pretreatment evaluation (P < 0.01). In contrast, patients treated with the capsaicin vehicle alone did not have any significant improvement of their subjective evaluation of nasal obstruction. Subjective rhinorrhea was not modified by either treatment. Of 29 patients with capsaicin treatment, 25 (86.2%) patients (9 months later) and 20 (69%) patients (55 months later) showed satisfactory result, compared to 10 (45.4%) patients and 8 (36.4%) patients separately in the control group, the difference was significant (P < 0.01). CONCLUSION: Intranasal capsaicin application can reduce polyp recurrence and nasal obstruction after polypectomy and ethmoidectomy.

Administration, Intranasal↗

PubMed1999

CGRP 27-37 analogues with high affinity to the CGRP1 receptor show antagonistic properties in a rat blood flow assay.

CGRP Y0-28-37 is known as a selective CGRP1 receptor antagonist. We succeeded in optimising the CGRP1 receptor affinity of this fragment by multiple amino acid replacement. The analogues [p34, F35]CGRP 27-37 and [D31, p34, F35]CGRP 27-37 exhibit a 100-fold increased affinity compared to the unmodified segment. Receptor binding studies were performed with human neuroblastoma cells SK-N-MC, which selectively express the hCGRP1 receptor. Blood flow, which is increased by exogenous CGRP, was measured in the right femoral artery. Preincubation of the rats with [p34, F35]CGRP 27-37 and [D31, p34, F35]CGRP 27-37 led to a significant decrease in CGRP induced increase in vascular conductance indicating the antagonistic properties of these compounds. Interestingly, an exchange of the amino acid Asn31 to Asp31 in [p34, F35]CGRP 27-37 shortened the period of the antagonistic effect significantly, suggestive of a different rate of metabolism for the two ligands. Secondary structure investigations obtained by circular dichroism measurements revealed that an increase in ordered structure correlates with high binding affinity.

Animals↗

PubMed1999

Influence of TASP-V, a novel neuropeptide Y (NPY) Y2 agonist, on nasal and bronchial responses evoked by histamine in anaesthetized pigs and in humans.

1. In nine anaesthetized pigs we have studied the influence of intranasal or intrabronchial pretreatment with TASP-V, a neuropeptide Y (NPY) Y2 agonist formed by the attachment of NPY 21-36 to a template-assembled synthetic peptide (TASP), on the functional responses to subsequent intranasal or intrabronchial histamine challenge. 2. In a parallel study, subjective and objective nasal airway resistance (NAR) increase following intranasal histamine challenge was evaluated in 11 healthy volunteers after TASP-V or placebo pretreatment. 3. In pigs, increase in sphenopalatine blood flow induced by histamine dihydrochloride nasal spray (0.25 mg kg(-1) in 3 ml of saline) was significantly reduced by 65% (P<0.05) following intranasal pretreatment with 10 microg kg(-1) of TASP-V. Bronchoconstriction induced by histamine dihydrochloride nebulization (0.5 mg kg(-1) in 3 ml of saline) was significantly attenuated by 25 and 55% following aerosolized pretreatment with TASP-V analogue at 10 and 20 microg kg(-1), respectively. 4. In healthy volunteers, objective increase in NAR and reduction in nasal minimal cross section area (MCSA) induced by intranasal spray of histamine dihydrochloride (15 microg kg(-1) in 200 microl of saline) were significantly attenuated by 50% following local pretreatment with 1.275 microg kg(-1) of TASP-V when compared with saline. 5. It is concluded that intranasal or intrabronchial pretreatment with TASP-V reduced nasal obstruction and bronchoconstriction evoked by histamine challenge in the pig. In healthy human volunteers, this agent attenuated NAR increase and MCSA reduction induced by intranasal application of histamine.

Adult↗

PubMed1999

Nasonasal reflex mechanisms in anaesthetized dogs.

In dogs anaesthetized with pentobarbitone, we recorded bilateral vascular and secretory responses to unilateral stimulation of intranasal afferent nerves. Nasonasal reflexes evoked by intranasal light mechanical stimulation, intranasal application of cold saline (2 ml at 3 degrees C), capsaicin (0.003-0.3 mmol) and antidromic electrical stimulation (15 V, 0.2 ms) of the trigeminal nerve at 10 Hz for 45 s were recorded. Vascular and secretory responses were studied before and after atropine pre-treatment, after ipsilateral section of the post-ganglionic parasympathetic fibres and the trigeminal nerve, and after administration of the ganglionic nicotinic receptor antagonist chlorisondamine. All stimuli studied induced bilateral increases in nasal arterial blood flow and secretion, although the contralateral responses were smaller under control conditions (p < 0.05). Bilateral vasodilatation evoked by mechanical stimulation, capsaicin and antidromic trigeminal nerve stimulation was resistant to atropine. The ipsilateral non-cholinergic vasodilatation evoked by mechanical stimulation or capsaicin was reduced by 50% (p < 0.05) after section of both trigeminal and post-ganglionic parasympathetic fibres. The remaining ipsilateral vasodilatation induced by these two stimuli was significantly reduced after chlorisondamine. The ipsilateral secretory responses to all stimuli studied were significantly reduced (p < 0.05), but not abolished by atropine. Contralateral secretory responses to all stimuli studied were not affected by atropine, the section of either the parasympathetic or trigeminal nerves, or chlorisondamine, suggesting the activation of local axon reflexes only. We conclude that unilateral intranasal stimulation of primary afferent neurons with light pressure, cold saline and capsaicin induces bilateral vascular and secretory responses via axon reflex mechanisms, as well as the activation of local and central sensory-parasympathetic reflex arcs.

Anesthesia, General↗

PubMed1999

Different ion channel control pH6-induced bronchoconstriction and calcitonin gene-related peptide release in the guinea-pig lung.

We have studied the bronchoconstriction and the release of calcitonin gene-related peptide-like immunoreactivity induced by perfusion of pH6 buffer in the isolated guinea-pig perfused lung. Both bronchoconstriction and peptide release were completely abolished after systemic capsaicin pretreatment. Ca(2+)-free pH6 buffer infusion also completely inhibited the bronchial response, whereas the calcitonin gene-related peptide-like immunoreactivity overflow was significantly reduced. omega-Conotoxine and omega-agatoxin IVA known as N-, L- and P-type Ca2+ channel blocker, respectively, and the Na+ channel blocker tetrodotoxin decreased significantly the pH6-induced bronchial response and calcitonin gene-related peptide like immunoreactivity overflow. Nifedipine was without influence suggesting the involvement of both P- and N-type Ca2+ channel as well as the activation of an axon reflex. Ruthenium red had a more pronounced reduction effect on the functional response than on the peptide release. Ryanodine and caffeine are both agents known to influence Ca2+ release from sarcoplasmic reticulum. Ryanodine significantly reduced both bronchoconstriction and calcitonin gene-related peptide-like immunoreactivity overflow. Caffeine as well as theophylline and the Na(+)-H+ blocker, dimethylamiloride, largely depressed the functional response while producing a significant increase of calcitonin gene-related peptide-like immuno-reactivity basal value. The pH6-induced peptide overflow was slightly inhibited after caffeine and dimethylamiloride pre-treatment whereas no significant change was observed after theophylline. It is concluded that multiple ion channels including different type of Ca2+ channels appear to participate in pH6-induced bronchoconstriction and calcitonin gene-related peptide-like immunoreactivity release in the guinea-pig lung.

Animals↗

PubMed1999

[Environment and nasal hyperreactivity].

The nasal mucosa is densely innervated by sensory nerve fibres which play an important part in the protection of the lower airways. Protective reflexes such as sneezing, secretion and nasal congestion can be elicited by exogenous noxious particles and numerous airborne irritants. The functions of the nasal mucosa is influenced at least in part, by biologically active neuropeptides that are released from sensory nerves endings. These sensory neuropeptides are involved in local vasodilatation, vascular permeability and mucus secretion. In addition, these neuropeptides are chemotactic for inflammatory cells such as eosinophiles and granulocytes. Therefore, neuropeptides of sensory origin are most likely involved in the pathophysiological mechanisms of specific (allergy) as well as non specific nasal hyperreactivity.

Capillary Permeability↗