Search

Background: In recent years, the positive effect of topically applied estriol nose ointment in the adjuvant therapy of Morbus-Rendu-Osler (HHT) has been proven. Due to the induced metaplasia, a complete destruction of the ciliated cells may be expected. However, data regarding the ciliary function of HHT patients with and without the use of topical estriol application are currently lacking., Methodology/principal: Ciliated samples were obtained by gently brushing the inferior nasal turbinate of 19 healthy volunteers and 15 patients with known HHT (8 of them regularly using 0.1% estriol nose ointment for 2 years (HHTwE) and 7 of them not using the ointment in the last 12 months (HHTwoE)). Analysis was done with an inverted phase contrast microscope connected to a high-speed digital camera. Recorded parameters were the visual integrity (VI) of the ciliary beat and its frequency (CBF) in Hz., Results: The VI index of all samples showed an undisrupted, even beating pattern with a difference between the three groups. The mean CBF in all HHT patients was reduced compared to the control group`s mean CBF. Within the HHT group itself, the mean CBF was reduced in the HHTwE group compared to the HHTwoE group., Conclusions: The ciliary beat frequency of HHT patients is impaired compared to the control group and even more so if the HHT patients topically apply estriol more than 6 months. An undisrupted beating pattern is found in the HHTwE group despite the fact that estrogens induce a transformation of the ciliated columnar into a keratinizing squamous epithelium. This data may justify the adjuvant application of estriol as a nose ointment in the treatment of epistaxis in HHT patients without the fear of damage to the nose`s mucus clearance.

Objective: The use of tampons after nasal septum surgery is important for both prevention of postoperative bleeding and stabilization of the nasal flaps and the septum. One of the most important factors in achieving rapid postoperative recovery is the choice of the nasal tampon material, among many, to produce minimal damage on the nasal mucosa. In this study, the histopathological effects of the glove finger and merocel tampons, which are commonly used in clinical applications, have been investigated on the nasal mucosa of rabbits., Materials and Methods: In this study, merocel and glove finger tampons were used for nasal packing in one-sided nasal cavities of 16 adult New Zealand rabbits. The animals were randomized into two groups, each consisting of eight animals. The tampons were removed after 48 hours., Results: Histological examination showed that if the merocel was in a glove finger, it did not create any damage to mucosal integrity and lamina propria. However, in the group where merocel was used directly, the epithelium of the nasal mucosa was shortened and demonstrated loss of cilia and in four of the eight specimens, it was partly from lamina propria., Conclusion: It is concluded that the use of merocel in glove finger tampon leads to a lesser degree of damage in the lamina propria, and may facilitate rapid mucosal wound healing postoperatively.

Statement of Problems: To determine whether topical prednisolone affected sinus mucosal healing in a sheep animal model., Methods of Study: A standardised sheep model with concurrent Oestrus ovus infection was utilised. Following full thickness nasal mucosal injuries, hyaluronic acid packs soaked with prednisolone were applied to one side of the nasal cavity, with hyaluronic acid packs without prednisolone, to the other. At four weekly intervals, for 16 weeks, mucosal biopsies were taken and analysed for epithelial thickness and length, for cilial height and percentage of ciliated mucosa and mucosal inflammation., Results: Eighteen sheep were utilised, with each acting as its own control. At completion of the study there was no statistical difference between the control or treatment group for the percentage of mucosal epithelialisation (mean: 86.5% vs 92.2%), epithelial thickness (mean: 39.7 microns vs 39.3 microns or the percentage of epithelium ciliated (mean: 26.5% vs 30.8%). Furthermore prednisolone had no effect on mucosal inflammation with the control arm mean score of 3.44 (SD .022) and treatment arm mean of 3.77 (SD 0.21)., Conclusion: Hyaluronic acid nasal packs soaked in prednisolone failed to improve the speed of mucosal healing or re-ciliation in the sheep model of eosinophilic rhinosinusitis.

Muscarinic receptors are believed to play an important role in modulation of ciliary action in respiratory system. We studied the in vitro effect of methacholine, a beta-methyl ester of acetylcholine, on the ciliary beat frequency (CBF). Adenoid explants were cultured in Minimum Essential Medium Eagle (MEM). CBF was determined using microphotometry. Methacholine (10(-6) M) increased CBF a maximum of 10.34 +/- 0.42% (p < 0.001). The non-selective muscarinic antagonist atropine (10(-6) M) significantly inhibited the ciliostimulatory effects of methacholine (p < 0.001). To characterize the muscarinic receptor subtypes in nasal mucosa, the selective M1-, M2- and M3-muscarinic antagonists pirenzepine dihydrochloride (PZ), gallamine triethiodide (gallamine), and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) were used prior to addition of methacholine, PZ and 4-DAMP, at concentrations of 10(-6) to 10(-8) M, significantly inhibited the ciliostimulatory effects of methacholine (p < 0.0001). There was no significant inhibition of methacholine-induced ciliostimulation by gallamine (p > 0.3). Our study showed that ciliostimulation by methacholine in human upper airway mucosa involves M1- and M3- muscarinic receptor subtypes, but not the M2-receptor subtype. The identification of the muscarinic receptor subtypes and intracellular signalling mechanisms involved in CBF modulation will permit the selection appropriate of pharmacological agents for treating the cholinergic symptoms of rhinitis.

Prostaglandins and histamine released during inflammatory and allergic reactions can affect the mucociliary system in different ways. By studying the effect of these mediators on ciliary beat frequency (CBF) with a photo-electrical technique in airway explants from different species, i.e. guinea-pig trachea, rabbit maxillary sinus, and human adenoid, the mechanisms underlying the effects of prostaglandin and histamine were further elucidated. Prostaglandin E1 (PGE1) produced a modest increase in CBF in preparations from guinea-pig trachea. The maximum response was 12.9 +/- 3.4% for the dose of 0.1 micrograms/ml, corresponding with 0.28 microM. Prostaglandin E1 produced a dose-dependent increase in explants from rabbit maxillary sinus, the maximum effect was 35.9 +/- 14.1% at a dose of 1.0 micrograms/ml. PGE1 produced a lesser increase in CBF in explants from human adenoids. A maximum increase of 4.1 +/- 1.6% was observed at a dose of 0.1 mg/ml. Histamine produced a moderate increase in CBF in explants from human adenoid at concentrations of 0.01-0.1 mM, corresponding with 1.84-18.4 micrograms/ml. In contrast, histamine did not significantly alter CBF in explants from the rabbit maxillary sinus or guinea-pig trachea. These results indicate that there are interspecies differences in the responsiveness to prostaglandins, and that PGE1 seems to have more powerful effects on CBF in the upper than in the lower airways.(ABSTRACT TRUNCATED AT 250 WORDS)

A method to study the effects of airborne pollutants on ciliary activity of isolated human respiratory cells is presented. Human respiratory cells were scraped from nasal cavities of 25 healthy volunteers and washed in Ringer's solution. The cells were placed on polycarbonate membranes (3 microns pore size) and kept in macroplate holders swimming on Ringer's solution. Cells were thus kept humid and were supplied with nutrients through the pores of the membrane by capillary forces, while their surface was exposed to the gaseous environment. Isolated respiratory cells were exposed to SO2, NO2, and mixtures of SO2 and NO2 in various concentrations for 30 min and for 2 h. Exposure to synthetic air served as control. Ciliary beat frequency was measured using video-interference contrast microscopy, before and after exposure to the various gases. Exposure of isolated respiratory cells to a non-toxic gaseous environment resulted in a 20% reduction of ciliary beat frequency. A concentration-dependent decrease of ciliary beat frequency following exposure to SO2 in concentrations ranging between 2.5 and 12.5 ppm was found. Exposure to NO2 up to 2 h in concentrations ranging between 3 ppm and 15 ppm did not decrease ciliary beat frequency. No cumulative effect was found, if a mixture of SO2 (2.5 ppm) and NO2 (12 ppm) was applied.

Ciliated cells from the nasal mucosa of normal persons were collected in culture medium and exposed to either oxymetazoline without preservatives, oxymetazoline with preservatives, xylometazoline with preservatives, or sham (culture medium). There was a significant decrease in ciliary beat frequency only by the two drugs with preservatives after 20 min. After substitution of the test media with culture medium ciliary action did not recover in any group.

This study was designed to investigate the possible pharmacological effect of S-carboxy-methylcysteine (S-CMC) on the ciliary activity, using an in vitro experimental system after removing mucus. Ciliary activity from healthy rabbit maxillary sinus and from healthy human nasal mucosa demonstrated no significant change in RPMI 1640 containing S-CMC. On the other hand, the effect of S-CMC on the reduced ciliary activity from patients with chronic sinusitis was quite varied among the cases examined. S-CMC demonstrated no stimulatory effect on the beating activity of cilia that have a baseline activity of less than 400 beats/min. However, S-CMC was able to enhance the beating activity of cilia that demonstrated a baseline activity of more than 400 beats/min. S-CMC at 0.5% induced a larger ciliostimulatory effect than 0.05% S-CMC. In conclusion, our study has clearly demonstrated that S-CMC could directly enhance ciliary activity of chronic sinusitis in the absence of significant organic change of ciliated cells.

The effect of autonomic substances on ciliary beat in mucosal biopsies from the normal human nose was studied. The influence on ciliary beat frequency (CBF) as well as on ciliary beat harmony was measured photoelectrically. The sympathetic beta-agonist isoprenaline was found to have a stimulatory effect on CBF, whereas the alpha-agonist xylometazoline reduced CBF and ciliary beat harmony. The parasympathetic agonist carbachol had a positive effect on CBF. The sympathetic antagonists timolol (beta) and phentolamine (alpha) as well as the parasympathetic antagonist atropine had no effect. The effect of the agonists on ciliary beat was absent when they were administered in combination with their specific antagonists. These experiments indicate that, in clinical concentrations, the autonomic substances modify ciliary beat by a direct effect on the ciliated cells.

Adenosine triphosphate (ATP) has been shown to revitalize the disturbed nasal mucociliary function in man. We investigated the effects of ATP on the ciliary beat frequency (CBF) in animals by immersing tracheal explants from rats in various concentrations of ATP, and by infusing ATP intravenously to guinea pigs. CBF was measured with a photodetector technique from the surface of the explants or from the incised trachea. ATP (from 0.01 to 1 mg/ml) in vitro increased CBF in rat tracheal explants up to 10.5% (p less than 0.05). In vivo ATP (1 mg/kg) increased the CBF by 29% (p less than 0.01) in the guinea pig trachea. As the CBF was increased by ATP, both in vitro and in vivo, it can be suggested that the improvement in mucociliary transport by exogenous ATP as shown in previous studies is caused by the ciliostimulatory effect of ATP.

Cystic fibrosis is a systemic disease where symptoms from the respiratory tract are important. The frequent infections in paranasal sinuses as well as in the lower respiratory tract are related to the occurrence of thick, viscous secretions. Spock et al. (1967) described an abnormal serum factor in patients with cystic fibrosis. This cystic fibrosis factor has been associated with dyskinetic ciliary motion induced by serum and cell culture media from patients with cystic fibrosis. In this study a sensitive method for photoelectric recording of the mucociliary function was used to examine the effect of sera, cell culture media and bronchial lavage fluids from patients with cystic fibrosis. No sign of decreased mucociliary activity was found. Electron microscopy showed morphologically normal cilia.

An in vivo test model has been developed to measure the influence of pharmacological substances on mucociliary activity in the rabbit maxillary sinus. Test solutions are administered via the feeding vessel to the investigated mucous membrane. The model permits administration of test substances and simultaneous recording of the obtained effects under conditions that closely mimic the normal situation. The parasympathomimetic agonist methacholine accelerates the mucociliary wave frequency dose-dependently. Atropine has no influence on the resting mucociliary activity but reduces or abolishes the effect of methacholine. The sympathomimetic beta 2-adrenoceptor agonist salbutamol accelerates the mucociliary activity dose-dependently whereas beta 1-adrenoceptor stimulation with prenalterol is without effect. Agonists acting on alpha 1- and alpha 2-adrenoceptors, phenylephrine and oxymetazoline, retard the mucociliary activity dose-dependently. beta- and alpha-adrenoceptor antagonists (propranolol and phentolamine, respectively) have no influence on the resting mucociliary activity but reduce the effect of beta- and alpha-adrenoceptor agonists, respectively. It is concluded that the resting mucociliary activity during anesthesia functions independently of parasympathetic and sympathetic nervous activity, and that the role of the parasympathetic and sympathetic innervation is to increase the mucociliary activity.

Ipratropium bromide is a parasympatholytic drug. After application to the nose, the nasal mucociliary transport time was measured using the method of the saccharin test. This compound did not cause any changes in the nasal mucociliary transport function.

Eosinophils are frequently associated with the manifestation of nasal allergy in the nasal mucosa and nasal secretion. The role of eosinophils in hypersensitivity diseases, however, is still obscure, whether it protects or damages tissues and activates mast cells. The effects of two kinds of human eosinophil extract (biological and physical extracts) on human nasal mucosa by applying them in nasal provocation test and cilia beating test, and also in tracheal ring incubation and skin test in the guinea-pig were measured. The results of the study suggest that eosinophil major protein and other protein components may produce damage to the function of human nasal mucosa and tracheal mucosa of the guinea-pig.

Human neutrophil granulocytes contain proteolytic enzymes. In purulent bronchial and paranasal secretions these enzymes have been found extra cellulary in complex with enzyme inhibitors as well as in free form indicating saturation of the inhibiting capacity. Isolated human leukocyte enzymes, elastase and neutral protease, were found to arrest the mucociliary activity and subsequently cause superficial tissue destruction. Elastase was found to be the most potent of the enzymes. Experimental studies with elastase together with specific inhibitor indicated the importance of the enzyme inhibitors for the integrity of the mucous membrane.

The effect of topical budesonide on the human mucociliary transport in the nose was investigated utilizing the saccharin-dye test in 10 healthy volunteers. Measurements were made before treatment, after a single dose and after one week continuous treatment with either placebo or active substance. The design of the study was double blind, randomized and cross-over. A single dose of placebo or budesonide did not alter the mucociliary transport as compared to pretreatment values. A trend towards decrease of mucociliary transport was noted after one week treatment with the active drug, a trend that reached statistical significance in the comparison between the 1 h value and the 1 week value.

The effects of preservatives on the ciliary beat frequency of chicken embryo tracheas are determined, Polar compounds like benzalkonium chloride in commonly used concentrations, decrease the frequency less than 30% after a 20 minutes' exposure. The effect is not reversible after rinsing with Locke-Ringer solution. Lipophilic compounds however, like chlorbutol, cause an arrest of the cilary movement with 10 minutes. The effect, different from the polar compounds, is reversible; but only after a limited exposure-time. Mercuric compounds, like thiomersal, decrease the frequency non-reversibly 30 to 90% after a 20 minutes' exposure. EDTA decreases the frequency 40 to 50%, independent of the exposure-time and in a reversible way. The combination of benzalkonium chloride 0.01% and EDTA 0.05% is recommended to preserve nasal drops.

The effects of benzalkonium chloride, chlorbutol,xylometazoline and naphazoline on the ciliary beat frequency of human adenoids and chicken embryo tracheas have been determined and compared. Chlorbutol 0.5% appeared to arrest ciliary motion in both tissues within 5 minutes. Rinsing with Locke Ringer solution (LR) restored the ciliary motion almost completely in both cases. Benzalkonium chloride 0.006% +EDTA 0.1% decreased the ciliary beat frequency 35% for the human tissues and 50% for the chicken tissues after a contact of 20 minutes. In both cases the frequency hardly changed after rinsing with LR. Naphazoline nitrate 0.1% and xylometazoline HCl 0.05% have reversible effects on the ciliary beat frequency of both human adenoids and chicken embryo tracheas. Cilia of human adenoids appeared to be more sensitive for xylometazoline than for naphazoline; whereas cilia of chicken embryo tracheas were more affected by naphazoline than by xylometazoline. The results with human adenoids and chicken embryo tracheas show a correlation (correlation coeff. = 0.82, p less than 0.005). In the initial response the differences in sensitivity to preservatives and drugs were in many cases statistically significant, but the final effects were similar.

The effects of proprietary preparations in the Netherlands and nasal preparations according to the F.N.A. (Formulary of the Netherlands' Pharmacists Association) on the ciliary beat frequency of chicken embryo tracheas have been determined. In general the preservatives, used in the nasal drops, turned out to have a more decisive influence on the ciliary motion than the pharmacologically active constituents. The average time, necessary to decrease the frequency 50% with 1=5 diluted nasal drops (average t 50%(1=5) containing a mercury compound or chlorbutol, is 0.4 h. Quaternary ammonium compounds containing preparations, however, have less influence, average t 50%(1=5) greater than 1.22 h. They are to be used preferably. Nasal drops, used as decongestants, provided that they are preserved with quaternary ammonium compounds, have little influence on the ciliary motion (average t50%(1=5) greater than 1.38 h). Nasal drops containing antihistamines, in contrast, inhibit the ciliary motion largely and almost independently of the preservatives (average t50%(1=5)=0.22 h); the cromoglycate containing preparation, on the contrary, has only little effect in this respect (t50%(1=5) greater than 2 h). Antimicrobial preparations are not preserved and have an intermediate ciliotoxic effect (average t50%(1=5)=0.7 h).

The three substances bromhexine, NA 872 (bromhexine metabolite VIII) and the beta 2-receptor agonist NAB 365 (clenbuterol) and their effect on the mucociliary activity have been studied in vivo in rabbits. The substances were given parenterally in increasing dosages and 519 records were obtained from 12 rabbits. Not even at dosages in excess of recommended human dosages has any effect on the mucociliary activity been observed for any of the substances during the first 30 minutes after administration. The conclusion to be drawn is that the three substances have no effect on the mucociliary activity in rabbit in vivo, but that this does not exclude an effect on mucociliary transport or clearance.