Ciliary activity

Naitoh, Y., Eckert, R. Control of Ciliary Activity in Protozoa, in Cilia and Flagella (Sleigh, M.A., ed.), pp. 305-352. London Academic Press 1974... 

Rylander, R. (1966). Current techniques to measure alterations in the ciliary activity of intact respiratory epithelium. Am. Rev. Respir. Dis. 93 (Suppl) 67-85. 

Dalhamn, T. Mucous flow and ciliary activity in the trachea of healthy rats exposed to respiratory irritant gases (SOj. H,N, and HCHO). A functional and morphologic (light microscopic and electron microscopic) study with special reference to technique. Acta Physiol. Scand. 36 (Suppl. 123) 1-161, 1956. 

Among the specific enzymes whose activity has been reported to be decreased after in vitro ozone exposure are papain, glyceraldehyde-3-phosphate dehydrogenase, lysozyme, ribonuclease, and acetylcholinesterase. The latter enzyme appears to be particulady susceptible to free-radical and oxidative states. A loss in acetylcholinesterase activity has been reported in the red cells of humans and mice that inhaled ozone. However, there are only minimal amounts of this enzyme in lupg tissue, and, although it has been suggested that acetylcholinesterase is important in bronchial tract ciliary activity, there is no direct evidence to support this conjecture. 

Dust particles inhaled in tobacco smoke, together with bronchial mucus, must be removed from the airways by the ciliated epithelium. Ciliary activity, however, is depressed by tobacco smoke mucociliary transport is impaired. This depression favors bacterial infection and contributes to the chronic bronchitis associated with regular smoking. Chronic injury to the bronchial mucosa could be an important causative factor in increasing the risk in smokers of death from bronchial carcinoma. 

In vitro exposure of chicken trachea cells to 2,3-benzofuran results in substantial inhibition of ciliary activity (Pettersson et al. 1982), which may indicate that ciliotoxicity is involved in the respiratory effects seen in mice. Certain other furan derivatives exhibit pulmonary toxicity due to metabolic activation by lung P-450 oxygenases (Boyd 1981), but 2,3-benzofuran... 

Pettersson B, Curvall M, Enzell CR. 1982. Effects of tobacco smoke compounds on the ciliary activity of the embryo chicken trachea in vitro. Toxicol 23 41-55. 

Inhalation of 400 ppm [1000 ing/m ] isopropanol by guinea-pigs for 24 h reduced the ciliary activity in the nasal mucosa, but recovery was complete within two weeks. Higher concentrations produced damage that required longer to repair (Ohashi et al., 1987, 1988). 

Increased ambient particulate load (54) or metallic inhibitors of ciliary activity (14) promote retention and accumulation. 

Side effects associated with narcotics include nausea, anorexia, and constipation most of them also diminish ciliary activity and produce a drying effect on the respiratory tract mucosa. 

The synthesis of dextromethorphan is an outgrowth of eady efforts to synthesize the morphine skeleton. IV-Methylmorphinan(40) was synthesized in 1946 (58,59). The 3-hydroxyl and the 3-methoxy analogues were prepared by the same method. Whereas the natural alkaloids of opium are optically active, ie, only one optical isomer can be isolated, synthetic routes to the morphine skeleton provide racemic mixtures, ie, both optical isomers, which can be separated, tested, and compared pharmacologically. In the case of 3-methoxy-IV-methylmorphinan, the levorotatory isomer levorphanol [77-07-6] (Levorphan) was found to possess both analgesic and antitussive activity whereas the dextrorotatory isomer, dextromethorphan (39), possessed only antitussive activity. Dextromethorphan, unlike most narcotics, does not depress ciliary activity, secretion of respiratory tract fluid, or respiration. 

The coordination of cilia motility is controlled by neural innervation, chemical pacemaking, and hormonal stimulation, and the effects of ions such as calcium and potassium. Cilia beat in a coordinated fashion to achieve the unidirectional propulsion of mucus with the frequency of the ciliary beat, which is dependent upon the environment. Human nasal cilia have been reported to beat, in vitro, with an average frequency of 10 Hz. Any rheological abnormalities in the mucus gel, particularly those that alter the elastic properties of mucus, can greatly affect clearance and undermine ciliary activity in the nasal cavity. In such circumstances, the adhesiveness of the mucus layer may allow it to remain in contact with the underlying cell layers and retain any substances introduced into the nasal cavity. 

Major determinants of the efficiency of mucociliary clearance are cilia density, periciliary fluid, and composition of mucus. Some drugs and excipients, such as preservatives in drug formulations, may diminish the ciliary movement in the nasal cavity and trachea. A suggested adverse effect of ciliostasis (permanently or momentarily arrest or impairment of ciliary activity) is lower respiratory tract infection as a result of impaired nasal microbiological defense. 

Figure 9.6 Diagram showing the infrastructure of an airway cilium. CM, central microtubules NX, nexin link RS, radial spoke SH, spoke head CP, projections of the central microtubules, (redrawn from Sanderson, M.J. (1997) Mechanisms controlling airway ciliary activity. In Rogers, D.F. andLethem, M.I. (eds.) Airway Mucus Basic Mechanisms and Clinical Perspectives. Birkhauser Verlag, Basel).

Kensler CJ, Battista SP. 1966. Chemical and physical factors affecting mammalian ciliary activity. 

Agu, R. U., Jorissen, M., Willems, T., Van Den Mooter, G., Kinget, R., Verbeke, N., and Augustijns, R (2000), Safety assesment of selected cyclodextrins Effect on ciliary activity using a human cell suspension model exhibiting in vitro ciliogenesis, Int. J. Pharm., 193, 219-226. 

Ciliary activity, after transient stimulation, is depressed, and particles are removed from the lungs more slowly. 

The surface of the nasal cavity is approximately 150 cm. Inside the cavity, the mucosa is covered with the ciliary epithelium. The ciliary activity is the driving force of the secretory transport in the nose. Approximately 1 L of mucus is transported from the anterior part to the posterior part of the nose per day. The mucus in the rear of the cavity is removed by swallowing. The function of the ciliary activity is to remove any particles that are trapped on the mucus blanket during inhalation. It takes approximately 20-30 min for the whole mucus layer to be renewed. 

There has been concern that ipratropium and other antimuscarinics may cause drying and inspissation of sputum with resulting sputum retention. In vitro studies show no effect on ciliary activity. In healthy subjects and patients with chronic bronchitis, inhaled ipratropium did not affect the rate of tracheobronchial clearance of a previously inhaled radioactive carrier aerosol. In studies using therapeutic doses for 2-14 days sputum volume and viscosity did not change (1). 

Hastie, A.T., Loegering, D.A., Gleich, G.J. and Kueppers, F. (1987). The effect of purified human eosinophil major basic protein on mammalian ciliary activity. Am. Rev. Respir. Dis. 135, 848-853. 

Di Benedetto, G., Marara-Shediac, F.S. and Mehta, S. (1991). Eflect of cyclic AMP on ciliary activity of human respiratory epithelium. Eur. Bespir. J. 4, 789-795. 

The oral LD50 in rats for tetrahydrofuran is 2.3 ml kg A single 4h inhalation study of tetrahydrofuran in rabbits at 100-12 000 ppm produced a transient dose-related decrease of tracheal ciliary activity. Concentrations of tetrahydrofuran 25 000 ppm produced anesthesia. Tetrahydrofuran was irritating to rabbit skin when applied topically in solutions exceeding a 20% concentration. No lasting acute adverse effects on neurological endpoints were seen with THF exposures of 0, 500, 2500, or 5000 ppm for 6 h in rats except for sedation. The no-observed-effect level (NOEL) for the acute neurotoxicity in rats was 500 ppm. 

The rate of removal of mucus from the airways is determined by such factors as mucus viscosity, the amount of mucus produced, and the degree of ciliary activity. These processes may be influenced by a variety of diseases, including asthma, cystic fibrosis, and chronic bronchitis [82,83], In patients suffering from cystic fibrosis or chronic bronchitis, mucus hypersecretion is evident and mucociliary function is impaired. The failure to clear mucus from the airways leads to airway obstruction and to chronic colonization of the airways with bacterial organisms (which leads to lung infections and airway inflammation and damage). In asthmatic subjects, airway mucus is more viscous and ciliary transport mechanisms are inhibited [82,83]. In these diseases, the therapeutic objective is to improve mucus clearance from the airways. For example, aerosols of water or saline (especially hypertonic saline) promote clearance of mucus by... 

M (decreased nasal mucous flow and ciliary activity)... 

Braga PC. 1989. Agents that affect ciliary activity. In Braga PC, Allegra L, ed. Drugs in bronchial mucology. New York, NY Raven Press Ltd., 335-348. 

Hastie AT. 1986. Inhibition of mammalian ciliary activity by formaldehyde [Abstract]. Am Rev Respir Dis 133 A-84. 

Myometrium Estrogen decreases the resting membrane potential of the myometrium and increases ciliary activity of the endometrial epithelium. Rising levels of estradiol prior to ovulation cause the smooth muscle of the fallopian tubes to become increasingly contractile at about the time of ovulation. This and the increased activity of cilia on the endometrial lining facilitate entry of the oocyte-cumulus complex into the lumen of the fallopian tube at the time of ovulation. In the pregnant uterus shortly before parturition, estradiol stimulates the formation of gap junctions and the production of myometrial receptors for oxytocin, PGF, and PGE, and thereby promotes the myometrial contractions that facilitate parturition. 

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