Fragrances as a trigger of immune responses in different environments.

Fragrances can cause allergic skin reactions, expressed as allergic contact dermatitis and reactions in the respiratory tract that range from acute temporary upper airway irritation to obstructive lung disease. These adverse health effects may result from the stimulation of a specific (adaptive) immune response. Th1 cells, which essentially produce interleukin-2 (IL-2) and interferon-γ (IFN-γ), play a key role in allergic contact dermatitis and also on allergic sensitization to common allergens (e.g., nickel and fragrance). It has been shown that fragrance allergy leads to Th2/Th22 production of IL-4, IL-5 and IL-13, controlling the development of IgE and mediating hypersensitivity reactions in the lung, such as asthma. Cytokines released during immune response modulate the expression of cytochrome P450 (CYPs) proteins, which can result in alterations of the pharmacological effects of substances in inflammatory diseases. The mechanisms linking environment and immunity are still not completely understood but it is known that aryl hydrocarbon receptor (AhR) is a sensor with conserved ligand-activated transcription factor, highly expressed in cells that controls complex transcriptional programs which are ligand and cell type specific, with CYPs as targeted genes. This review focuses on these important aspects of immune responses of the skin and respiratory tract cells, describing some in vitro models applied to evaluate the mechanisms involved in fragrance-induced allergy.

[Working overseas and cardiovascular diseases: application of a screening method on Oil&Gas employees]. / Lavoro all'estero e malattie cardiovascolari: applicazione di un protocollo di screening su un gruppo di lavoratori del settore Oil&Gas.

Working overseas is a reality for decades in the Oil&Gas Industry and many noxae impact on the cardiovascular system. In fitness to work evaluation the physician should consider besides the conventional risk factors, the presence of cardiovascular diseases, and prevent their evolution. A cardiovascular screening and follow up after 2 years was carried out on 42 Oil&Gas employees, over 45 of age, during medical fitness to work. The main tests were ECG, exercise tolerance test (ETT) and echocardiocolordoppler, completed with other instrumental tests. Cardiovascular diseases causing unfitness to working overseas occurred in 7%, blood hypertension in 23%. The screening permitted to diagnose and correct acute cardiovascular diseases, that caused unfitness to work, and disease that can get worse related to occupational risk. Moreover it was fundamental for evaluation of fitness and timing of health surveillance.

Subchronic effects of nasally instilled diesel exhaust particulates on the nasal and airway epithelia in mice.

Diesel exhaust is the major source of ultrafine particles released during traffic-related pollution. Subjects with chronic respiratory diseases are at greater risk for exacerbations during exposure to air pollution. This study evaluated the effects of subchronic exposure to a low-dose of diesel exhaust particles (DEP). Sixty male BALB/c mice were divided into two groups: (a) Saline: nasal instillation of saline (n = 30); and (b) DEP: nasal instillation of 30 microg of DEP/10 microl of saline (n = 30). Nasal instillations were performed 5 days a week, over 30 and 60 days. Animals were anesthetized with pentobarbital sodium (50 mg/kg intraperitoneal [i.p.]) and sacrificed by exsanguination. Bronchoalveolar lavage (BAL) fluid was performed to evaluate the inflammatory cell count and the concentrations of the interleukin (IL)-4, IL-10, and IL-13 by enzyme-linked immunosorbent assay (ELISA). The gene expression of oligomeric mucus/gel-forming (Muc5ac) was evaluated by real-time polymerase chain reaction (PCR). Histological analysis in the nasal septum and bronchioles was used to evaluate the bronchial and nasal epithelium thickness as well as the acidic and neutral nasal mucus content. The saline group (30 and 60 days) did not show any changes in any of the parameters. However, the instillation of DEP over 60 days increased the expression of Muc5ac in the lungs and the acid mucus content in the nose compared with the 30-day treatment, and it increased the total leukocytes in the BAL and the nasal epithelium thickness compared with saline for 60 days. Cytokines concentrations in the BAL were detectable, with no differences among the groups. Our data suggest that a low-dose of DEP over 60 days induces respiratory tract inflammation.

Mapping Cell Membrane Organization and Dynamics Using Soft Nanoimprint Lithography.

Membrane shape is a key feature of many cellular processes, including cell differentiation, division, migration, and trafficking. The development of nanostructured surfaces allowing for the in situ manipulation of membranes in living cells is crucial to understand these processes, but this requires complicated and limited-access technologies. Here, we investigate the self-organization of cellular membranes by using a customizable and benchtop method allowing one to engineer 1D SiO2 nanopillar arrays of defined sizes and shapes on high-performance glass compatible with advanced microscopies. As a result of this original combination, we provide a mapping of the morphology-induced modulation of the cell membrane mechanics, dynamics and steady-state organization of key protein complexes implicated in cellular trafficking and signal transduction.

Gold decoration of silica by decomposition of aqueous gold(iii) hydroxide at low temperatures.

The decomposition of gold hydroxide to give metallic gold is known to take place around 300 °C in dry environments. However, little information about the gold hydroxide stability in wet environments has been recorded. Here, we present experimental evidence which shows that aqueous/water-enriched gold(iii) hydroxide colloids decompose spontaneously to form gold nanoparticles at temperature values above the freezing point of water. Based on this reaction, we developed a method to decorate silica spheres with gold nanoparticles by precipitation and decomposition of gold(iii) hydroxide onto the silica surface in wet media by a simple one-pot/one-step protocol. The silica|gold nanostructures are prepared in high yield and with a low level of by-products.

Effects of an individually ventilated cage system on the airway integrity of rats (Rattus norvegicus) in a laboratory in Brazil.

The ventilation method used in the management of laboratory rats is important in maintaining their health. Rats kept under general diluting ventilation (GDV) are exposed to high levels of pollutants present in the environment (dust, airborne bacteria, etc.) or those pollutants produced by animal metabolism and excretion inside the boxes (e.g. ammonia and carbon dioxide). These pollutants may contribute to respiratory pathologies. An alternative experimental ventilation system for laboratory animal housing using intracage ventilation technology (individually ventilated cage system, IVC) was developed. In this system, ammonia levels decreased and rats exhibited better reproductive performance and a lower incidence of pneumonia than rats maintained under GDV. Using two different levels of air speed (0.03-0.26 m/s: IVC(1); 0.27-0.80 m/s: IVC(2)), the effects of IVC were compared with GDV (control) in Wistar rats in terms of respiratory mucus properties, on the nasal epithelium (as measured by quantitative morphometry) and on the lungs (as determined by the cellular composition obtained by bronchoalveolar lavage). Mucus of the respiratory system was evaluated using the following techniques: rheology (viscoelasticity) by microrheometer, in vitro mucociliary transportability (frog palate) and contact angle (an indicator of adhesivity). Also, membrane transepithelial potential difference was measured as a biomarker of airway integrity. After bedding was changed, ammonia concentrations inside the cages on day 3 were significantly higher for GDV than for IVC(1) and IVC(2). The potential-difference values for IVC(1), IVC(2) and GDV in the epiglottis and in the trachea also showed differences. Although some significant differences were observed across the three groups in counts of some cell types, the intragroup results were highly variable among individuals and inconsistent between sexes. No significant differences in the other parameters were found across groups. These results establish that rats maintained under GDV in relatively unregulated conditions are exposed to factors that can lead to deleterious effects on the ciliated epithelium of the airways, and that these effects can be prevented by the use of IVC.

The effects of urban particulate matter on the nasal epithelium by gender: An experimental study in mice.

Nose is the first portion of the respiratory system into contact with air pollution particles, including organic compounds that could act as endocrine releasers. The objective was to identify and quantify estrogenic receptor-ß (ERß), aryl hydrocarbon receptor (AhR), the cytochrome P450 enzymes CYP1A1, 1A2, 1B1, and mucus profile in the nasal epithelium of mice. BALB/c mice male (n = 32) and female (n = 82) in proestrus, estrus and diestrus were divided into two groups: 1) exposed to ambient air; 2) concentrated ambient particles (CAPs) to achieve an accumulated dose (concentration vs. time product) of 600 µg/m(3), the time of the exposure was controlled to ensure the same concentration for all groups (5 days per week for 40-51 days). RT-PCR (Erß-1, Erß-2, Ahr, Cyp1a1, Cyp1a2, Cyp1b1), immunohistochemistry and morphometry (ERß, AhR) were used to analyze. The mucus profiles were examined using acid (Alcian Blue) and neutral (periodic acid Schiff's) stains. Exposed females had significantly lower levels of Erß-2 mRNA than exposed males (p = 0.036). Cyp1b1 mRNA in diestrus females was significantly lower in the CAP-exposed group compared with the ambient air group (p ≤ 0.05). ERß expression in the epithelium and submucosa nucleus was lower in estrus exposed to CAPs compared with ambient air. CAPs increases AhR in the epithelium (p = 0.044) and submucosa (p = 0.001) nucleus of female when compared with male mice. Exposure to CAPs, also led to relatively increased acidic content in the mucus of males (p = 0.048), but decreased acidic content in that of females (p = 0.04). This study revealed sex-dependent responses to air pollution in the nasal epithelium that may partially explain the predisposition of females to airway respiratory diseases.

Morphological Evolution of Noble Metal Nanoparticles in Chloroform: Mechanism of Switching on/off by Protic Species.

The morphological stability/morphological reshaping of noble metal nanoparticles are studied experimentally in order to unravel the chemical mechanisms lying beneath. Gold and silver nanoparticles (AuNPs and AgNPs, respectively) formed in chloroformic environment are used, as model synthetic systems, to study phenomena of morphological change. The morphological evolution of NPs that follows their formation, is characterized by spectroscopy (UV-Visible, Raman and FTIR) and TEM (Transmission Electron Microscopy). The change of NP morphology involves the increase of the average NP size and the broadening of size distribution, in a close resemblance with the effect characteristically obtained from the Ostwald ripening. The effect of the poor solvating properties of chloroform in stabilizing small charged species (H+, Ag+, Au+) as well as the principle of electroneutrality of matter are analyzed in order to formulate a feasible reaction scheme consisting of a three-step processes: the generation of soluble intermediary species by corrosion of nanoparticles, the diffusion of intermediary species from one nanoparticle to another, and the re-deposition process involving the reduction of intermediary species. This basic reaction scheme is used as hypothesis to plan and perform experiments, which reveal that molecular oxygen dissolved in the dispersive medium can drive NP corrosion, however, protic species are also required as co-reactant. The polarity of the hydrogen bond and the ligand properties of the anions produced by deprotonation are feature of the protic species that enable/disable the corrosion and, in turn, the NP morphological evolution.

The use of the frog palate preparation to assess the effects of oxidants on ciliated epithelium.

This work was designed to develop a simple method based on the frog palate preparation to study the effects of hydrogen peroxide (H2O2) on ciliated epithelium. For this purpose, five sets (n = 10 per set) of frog palate preparations (Rana catesbeiana) were studied during 35 min after immersion in increasing concentrations of H2O2: 1, 8, 16, 32, and 64 microM. The effects of H2O2 on ciliated epithelium were assessed by measuring transepithelial potential difference (PD) and mucociliary transport (MT). Measurements were performed at 5-min intervals. In addition, the palates submitted to the 64 microM dose were immersed in Ringer's solution and followed by another 30 min to assess the possible recovery after maximal injury. Transepithelial potential difference (PD) was measured by means of agar-filled microelectrodes connected to the high input of a grounded electrometer. Mucociliary transport (MT) was determined by directly monitoring the movement of autologous mucus along the palate surface. Significant decrease in MT was observed in 16 microM and beyond and significant change in PD was observed in 32 microM and 64 microM. Palates submitted to 64 microM of H2O2 returned to their baseline levels of PD and MT within 30 min of recovery in Ringer's solution. In conclusion, the frog palate preparation was shown to be an efficient experimental tool to assess the deleterious effects of H2O2 on the ciliated epithelium.

Acute effects of inhalable particles on the frog palate mucociliary epithelium.

This work was designed to evaluate the toxicity of inhalable particles [less than/equal to] 10 microm in aerodynamic diameter (PM(10)) collected from the urban air in São Paulo, Brazil, to the mucociliary apparatus using the frog palate preparation. Seven groups of frog palates were immersed in different concentrations of PM(10) diluted in Ringer's solution during 120 min: 0 (control, n = 31); 50 (n = 10); 100 (n = 9); 500 (n = 28); 1,000 (n = 10); 5,000 (n = 11); and 10,000 microg/m(3) (n = 10). Mucociliary transport and transepithelial potential difference were determined at 0, 30, 60, and 120 min exposure. Additional groups (control and 500 microg/m(3)) were studied by means of morphometric analyses (quantification of the amount of intraepithelial and surface mucins), measurement of cilia beat frequency, and quantification of total glutathione. Mucociliary transport and transepithelial potential difference were significantly decreased at higher concentrations of PM(10) (p = 0.03 and p = 0.02, respectively). Exposure to PM(10) also elicited a significant decrease of total glutathione (p = 0. 003) and depletion of neutral intraepithelial mucins (p = 0.0461). These results show that PM(10) can promote significant alterations in ciliated epithelium in vitro.

Tumor and serum beta-2-microglobulin expression in women with breast cancer.

To investigate whether the tumor expression of beta-2-microglobulin (beta 2-M) could serve as a marker of tumor biologic behavior, the authors studied specimens of breast carcinomas from 60 consecutive female patients. Presence of beta 2-M was analyzed by immunohistochemistry. No significant correlations were found between tumor beta 2-M expression and several histologic attributes such as type, histologic and nuclear grades, mitotic index, necrosis, vascular invasion, and lymphocytic infiltration. Likewise, beta 2-M was not associated with markers of disease extension such as TNM, (UICC, classification of malignant tumors) staging and axillary lymph node involvement or with estrogen, progesterone, and glucocorticoid receptor levels. However, there was a significantly positive association between tumor beta 2-M expression and the degree of lymphocytic infiltration in the tumor tissue. Beta 2-M serum levels were determined by an enzyme-linked immunosorbent assay in samples from 22 of the above women. Although some of the highest values had been obtained in women with larger (T4) primary tumors, the authors failed to detect any statistical relationship between beta 2-M expression in the tumor with serum levels or between serum beta 2-M and the above histologic, laboratory, and clinical factors.

Methods for studying respiratory mucus and mucus clearance.

We describe some basic procedures for studying the properties of mucus. These techniques can be applied in both clinical and physiological studies to improve the understanding of the mechanisms related to epithelial defense in health and disease. Mucus collection--A major difficulty is the lack of simple and noninvasive methods for collecting normal mucus in sufficient quantity for later analysis. Physical properties of mucus--A. Rheology: Mucus exhibits both solid and liquid properties and the important factor governing the actual behavior is time. The magnetic microrheometer provides an elegant method for measuring rheological properties of microsamples. B. Adhesivity: It characterizes the forces of attraction between an adherent surface and an adhesive system and can be calculated by measuring the contact angle between a mucus drop and a surface. Mucus Transport--A. Mucus transport by cilia: Mucus is primarily cleared by the continuous ciliary beating, which can be studied using techniques such as the frog palate preparation as well as direct measurement, i.e., in situ mucus clearance. B. Cough clearance: It is essential for elimination of secretions in diseases leading to hypersecretory states. The cough machine simulates the flow-time profile of human coughing. Transepithelial potential difference--A potential difference exists between the epithelial surface and the submucosa and is the net result of the activity of the ion-transport system of the pulmonary epithelium. The potential can be measured using appropriate microelectrodes. Quantitative morphology--Methods may be used to characterize the epithelial surface condition that continuously changes during aggressive conditions.

Effects of formaldehyde on the frog's mucociliary epithelium as a surrogate to evaluate air pollution effects on the respiratory epithelium.

The increasing use of alcohol as an alternative fuel to gasoline or diesel can increase emission of formaldehyde, an organic gas that is irritant to the mucous membranes. The respiratory system is the major target of air pollutants and its major defense mechanism depends on the continuous activity of the cilia and the resulting constant transportation of mucous secretion. The present study was designed to evaluate the effects of formaldehyde on the ciliated epithelium through a relative large dose range around the threshold limit value adopted by the Brazilian legislation, namely 1.6 ppm (1.25 to 5 ppm). For this purpose, the isolated frog palate preparation was used as the target of toxic injury. Four groups of frog palates were exposed to diluted Ringer solution (control, N = 8) and formaldehyde diluted in Ringer solution at three different concentrations (1.25, 2.5 and 5.0 ppm, N = 10 for each group). Mucociliary clearance and ciliary beat frequency decreased significantly in contact with formaldehyde at the concentrations of 2.5 and 5.0 ppm after 60 min of exposure (P<0.05). We conclude that relatively low concentrations of formaldehyde, which is even below the Brazilian threshold limit value, are sufficient to cause short-term mucociliary impairment.

Effects of water pollution on the gill apparatus of fish.

The study was designed to investigate the influence of water pollution on gill apparatus. Specimens of Nile tilapia were collected from a polluted site in the São Paulo metropolitan area (Billings reservoir) and from a "clean" area. Fish from the polluted site showed a chronic inflammatory process in the distal region of the gill filaments, with epithelial hyperplasia. The raker length was increased and hypersecretion occurred, with a considerable volume of alcian blue-positive mucin on the epithelium of the rakers and a smaller volume of periodic acid-Schiff-positive mucin on the epithelial surface of the filaments. The rigidity of mucus in fish from the polluted site was increased, but no abnormalities in the viscosity to elasticity ratio or in mucus "wettability" were observed.

Somatomedin levels in the diagnosis and therapy of growth hormone deficiency.

Serum somatomedin-C (SM-C) and somatomedin (SM) concentrations were measured by, respectively, radioimmuno (SM-C RIA) and radioreceptor assays (SM RRA) in 3 groups of children with short stature. The patient population was different from previously reported series in that it was urban Brazilian, low income, and significantly older. Group A consisted of 6 male and 3 female children, aged 7.7-16.0 years, whose average peak plasma immunoreactive growth hormone (GH) was above 10 ng/ml. Group B contained 8 male and 5 female untreated GH-deficient patients, ranging in age from 9.5 to 21.0 years. In Group C there were 4 male and 1 female GH-deficient subjects treated with I.M. injections of GH (0.1 U/kg) from 1 month to 7 years. The mean +/- SE basal RIA SM-C (ng/ml) concentrations were significantly lower in groups B (34.2 +/- 8.8) and C (43.8 +/- 13.7) than A (214.3 +/- 42.7): A X B, P less than 0.001 and A X C, P less than 0.02. Likewise the mean +/- SE basal RRA SM (ng/ml) concentrations were significantly lower in groups B (78.9 +/- 17.6) and C (90.8 +/- 19.3) than group A (316.3 +/- 43.0): A X B, P less than 0.001 and A X C, P less than 0.002. A significant linear correlation was observed between RIA and RRA in group B (r = 0.84; P less than 0.001) and C (r = 0.96; P less than 0.01), but not for A (r = 0.61; P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Criteria for the cure of acromegaly: comparison between basal growth hormone and somatomedin C plasma concentrations in active and non-active acromegalic patients.

Fasting plasma growth hormone (GH) and somatomedin C (SmC) levels were compared as criteria for the cure of acromegaly in 7 untreated and 16 treated acromegalic patients studied 1 to 16 yr after pituitary surgery and/or radiotherapy. The patients without active disease presented a significant correlation between GH and SmC. Only when basal GH was lower than 2.5 ng/ml were SmC values within the normal range. The subjects with active acromegaly (both treated and untreated) presenting GH higher than 5 ng/ml did not show any correlation between GH and SmC levels.

Quantitative pathology of nasal passages in rats exposed to urban levels of air pollution.

In order to assess the adverse effects of urban levels of air pollution, rats were used as biological indicators in a chronic exposure experiment. Animals were housed for 6 months in the center of São Paulo (the largest South American town) and compared to controls kept for the same period in a clean area. Pollution levels were obtained from a state air pollution monitoring station, 200 m distant from exposure location, which provided the levels of CO, SO2, particulates, and ozone. The nasal septum was submitted to quantitative analysis of morphological and histochemical parameters, comprising the measurement of volume of epithelium and lamina propria per unity of surface of basal lamina, the amount of mucus stored in the surface epithelium, the volume densities of neutral and acidic mucus in the lamina propria glands, and the densities of secretory and ciliated cells in the epithelium. The results obtained in the present investigation suggest that chronic exposure to urban levels of air pollution induces secretory hypertrophy, combined with a shift toward acidic mucus secretion and ciliary damage. The results are consistent with the idea that prolonged exposure to low levels of air pollution deteriorates respiratory defenses against infectious agents and may cause an increase in respiratory morbidity and perhaps mortality.

Rheological determinants of mucociliary transport in the nose of the rat.

The present work was designed to investigate whether the rheological determinants for nasal mucociliary transport are the same in the intact preparation (in situ), as they are when the mucus is added exogenously to the isolated, mucus-depleted frog palate (in vitro). We evaluated the association between estimators of mucociliary transport in both conditions and rheological parameters using multiple regression techniques. Two kinds of rats were used: (a) specific pathogen free (SPF) rats, representing the normal condition of respiratory epithelium; (b) non-SPF rats (NSPF), which have a chronic inflammatory process in the airways. In situ mucociliary clearance (MCC) was determined by measuring the displacement of charcoal particles placed in the nasal septum. In vitro mucociliary transport (MCT) of rat nasal mucus was measured using the isolated frog palate preparation. Mucus rheologic properties were determined by magnetic microrheometry, in oscillatory deformations performed at 1, 10 and 100 radians/sec. No differences were detected between SPF and NSPF rats in terms of rheological parameters. A decreased MCC was found in NSPF in comparison with the SPF group, but no differences were observed between groups in terms of MCT, as could be predicted by rheological data. When all animals were pooled, in situ transport was significantly associated with the viscosity/elasticity ratio, whereas in vitro transport was dependent on the total mechanical impedance of the mucus sample. In conclusion, in situ mucus transport is influenced by other rheological parameters than those associated with in vitro transportability.

Effects of a heat and moisture exchanger and a heated humidifier on respiratory mucus in patients undergoing mechanical ventilation.

OBJECTIVE: To evaluate the effects of a heat and moisture exchanger and a heated humidifier on respiratory mucus and transportability by cilia and cough in patients undergoing invasive mechanical ventilation (up to 72 hrs). DESIGN: Prospective, randomized, clinical study. SETTING: General intensive care unit and university research laboratory. PATIENTS: A total of 32 consecutive patients with acute respiratory failure, who were intubated and mechanically ventilated in the intensive care unit setting, were enrolled in the study. INTERVENTIONS: Patients were randomly assigned to receive as a humidifying system a heat and moisture exchanger (HME) or heated humidified water (HHW) at the onset of mechanical ventilation (time 0). Respiratory mucus samples were collected by suction using a sterile technique at time 0, 24, 48, and 72 hrs of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Eleven patients were excluded from this study because of either extubation or death before 72 hrs of mechanical ventilation, leaving 12 patients in the HME group and nine patients in the HHW group. Ventilatory variables including minute volume, mean airway pressure, positive end-expiratory pressure, Fio2, as well as Pao2/Fio2 ratio, fluid balance (last 6 hrs), furosemide, and inotrope administration (last 4 hrs) were recorded. In vitro mucus transportability by cilia was evaluated on the mucus-depleted frog palate model, and the results were expressed as the mucus transport rate. Cough clearance (an estimation of the interaction between the flow of air and the mucus lining the bronchial walls) was measured using a simulated cough machine, the results being expressed in millimeters. Mucus wettability was measured by the contact angle between a mucus sample drop and a flat glass surface. Mucus rheologic properties (mechanical impedance [log G*] and the ratio between viscosity and elasticity [tan delta]) were measured using a magnetic microrheometer at 1 and 100 cGy/sec deformation frequency. The two humidification groups were comparable in terms of the Acute Physiology and Chronic Health Evaluation II score, age, gender, ventilatory variables, fluid balance, use of inotropes, and furosemide. CONCLUSION: Ours results indicate that air humidification with either HME or HHW at 32 degrees C (89.6 degrees F) has similar effects on mucus rheologic properties, contact angle, and transportability by cilia in patients undergoing mechanical ventilation, except for transportability by cough, which diminished after 72 hrs of mechanical ventilation in the HME group (p = .0441).

Nasal mucus clearance in rats: differences with sex and phase of the oestrous cycle.

We studied the changes in airway mucus rheology and clearability, as well as in morphometric indices, between male rats and females in either the oestrous or dioestrous phases of the oestrous cycle. Three-month-old Wistar rats were studied and the phases of the oestrous cycle were determined based on analysis of vaginal smears stained by a modified Shorr's procedure. Nasal mucus samples were analysed by means of magnetic rheometry and determination of in vitro transport rate in the frog palate preparation. In situ clearance on the exposed nasal septum was also determined. The mucociliary velocity in situ was significantly affected by both sex and the oestrous cycle phase. In female rats, dioestrous phase clearance was significantly slower than the oestrous phase one. Clearance in male rats was faster than that of both the phases studied in females. Mucus rigidity of females in the oestrous phase was more rigid than that of females in the dioestrous phase and that of males. Mucus viscosity/elasticity ratio for deformations performed at high frequencies was greater for females in comparison with males. Cough clearability computed on the basis of rheological parameters was predicted to be more favourable in females. There were no significant differences between the three groups in mucociliary clearance in vitro. Morphometric studies of the nasal epithelium showed that epithelial and glandular volumes did not exhibit sex- or oestrous-phase-related differences, but the amount of epithelial acidic glycoproteins was lower in females in the oestrous phase in comparison with males and those in the dioestrous phase, the same trend being observed in the glands of the lamina propria.(ABSTRACT TRUNCATED AT 250 WORDS)