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Effects of a novel 5-HT1A receptor agonist, E4424, on gastric adherent mucus levels following restraint stress in rats.

Several novel arylpiperazine serotonin 1A receptor agonists, developed as anxiolytics, have antisecretory and gastroprotective effects in rats. E4424 (2-¿4-[4-(4-chloropyrazol-1-yl)butyl]-1-piperazinyl ¿pyrimidine; Lesopitron dihydrochloride), has potent anti-gastric secretory and antiulcer effects. Preliminary data indicated an enhancing effect of E4424 on gastric mucus that may underlie its gastroprotective actions. We therefore tested the effects of acute and chronic administration of E4424 and of a reference 5-HT1A receptor agonist, 8-OHDPAT [8-hydroxy-2-(di-n-propylamino)tetralin], on gastric mucus levels in rats subjected to cold-restraint stress, a procedure associated with depletion of gastric mucus and the development of mucosal injury. Acute oral administration of E4424 increased adherent mucus levels by 12%, 11%, and 13%, relative to controls. Chronic E4424 significantly increased gastric mucus relative to controls (69% increase). Acute oral treatment with 8-OHDPAT did not affect gastric mucus level. Acute intraperitoneal 8-OHDPAT slightly increased mucus levels. Chronic twice per day 8-OHDPAT did not affect mucus levels; however, chronic once per day treatment with 8-OHDPAT significantly elevated gastric mucus levels at the highest doses used. For E4424, there is a strong correlation between reduction of gastric mucosal injury and increase in gastric mucus level, suggesting that the action of E4424 on glandular mucus levels is an important mechanism underlying its gastroprotective effects.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

The viscosity and glycoprotein biochemistry of salmonid mucus varies with species, salinity and the presence of amoebic gill disease.

Fish mucus has previously been reported to change in appearance and composition among species and in response to changes in salinity and disease status. This study reports on the mucus viscosity and glycoprotein biochemistry of Atlantic salmon (Salmo salar L.), brown trout (Salmo trutta L.) and rainbow trout (Oncorhynchus mykiss Walbaum) in freshwater and seawater, both naive to and affected by amoebic gill disease (AGD). Cutaneous mucus viscosity was measured over a range of shear rates (11.5, 23, 46 and 115 s(-1)), and non-Newtonian behaviour was demonstrated for all three species. Mucus viscosity was significantly greater in seawater than in freshwater for all species, and significantly lower in AGD-affected Atlantic salmon and brown trout. Mucus glucose, total protein and osmolality data indicated that differences in viscosity due to salinity were mostly attributed to changes in mucus hydration, while differences due to disease were mostly attributed to changes in mucus composition. Trends in gill mucus cell histochemistry included shifts in glycoproteins from neutral mucins in freshwater to acidic mucins in seawater, and shifts towards neutral mucins, with an increase in mucus cell numbers, in response to AGD. Results suggested that Atlantic salmon and brown trout are more similar to one another in their mucus profile than to rainbow trout. Atlantic salmon and brown trout both exhibited a whole-body mucus response to AGD, whereas rainbow trout exhibited only a local gill response. Findings hold implications for fish physiology and pathology, and indicate that future fish-disease management strategies should be species and condition specific.

Adaptation, Physiological↗

MAO-A and -B inhibitors selectively alter Xenopus mucus-induced behaviors of snakes.

Skin mucus of the frog Xenopus laevis, contacted orally by snakes, induces dyskinetic oral movements and climbing behavior that promote escape. The mucus contains peptides and indoleamines known to produce drug-induced movement disorders in other species. We hypothesized that inhibition of monoamine oxidase-A (MAO-A) by N-methyl-N-propargyl-3-(2,4-dichlorophenoxy)-propylamine [clorgyline (CLG)] and MAO-B by R(-)-N, alpha-Dimethyl-N-2-propynyl-benzene-ethanamine [L-deprenyl (LDL)] would selectively modify mucus-induced behaviors by elevating norepinephrine and serotonin (with CLG), phenylethylamine (with LDL), or dopamine (with both drugs). In Experiment 1 (EXP1), adult snakes received mucus and/or 20 micrograms/g (IP) of both drugs. In EXP2, juveniles received mucus and/or 5, 10, and 20 micrograms CLG or LDL. CLG given alone had no effect on tongue flicking, activity, and climbing (EXP1,2). LDL alone decreased tongue flicking in EXP2 and increased climbing (EXP1,2). Given with mucus, both drugs further lowered the tongue flicking rates attenuated by mucus (EXP1,2); only LDL potentiated mucus-induced climbing. Yawning was the only mucus-induced dyskinesia attenuated (20 micrograms CLG, adults; 20 micrograms LDL, juveniles). We suggest that dopamine and/or phenylethylamine, the substrates for MAO-B, may promote mucus-induced climbing and tongue flicking but may have some protective role against mucus-induced yawning in water snakes.

Analysis of Variance↗

Antibody diffusion in human cervical mucus.

The mucosal immune system actively transports large quantities of antibodies into all mucus secretions, and these secreted antibodies help prevent infectious entry of many pathogens. Mucus is generally thought to protect epithelial cells by forming a diffusional barrier through which only small molecules can pass. However, electron microscopy indicates that the pore size in mucus is approximately 100 nm, which suggests that antibodies as well as other large molecules might also diffuse through mucus. We measured the diffusion coefficients for antibodies and other proteins within human midcycle cervical mucus using two techniques: fluorescence imaging of concentration profiles and fluorescence photobleaching recovery. The two techniques are complementary, since the rates of diffusion are observed over millimeter distances with fluorescence imaging of concentration profiles and micron distances with fluorescence photobleaching recovery. Both methods yielded essentially the same diffusion coefficients. In contrast to previous reports indicating mucus significantly impedes diffusion of small molecules, antibody diffusion in mucus was relatively unimpeded. In our observations IgG, IgG fragments, IgA, and IgM diffused almost as rapidly in cervical mucus as in water (1.0 > Dmucus/Dwater > 0.7). Simple models for diffusion through water-filled pores suggest that the hydrodynamic pore size for cervical mucus is approximately 100 nm, smaller than the approximately 1000 nm pore size of a collagen gel (at 1 mg/ml) and larger than the approximately 10 nm pore size of gelatin (at 100 mg/ml). This estimated pore size is consistent both with electron micrographs and geometric models of interfiber spacing. Based on these results, we predict that particles as large as viruses can diffuse rapidly through human midcycle cervical mucus, provided the particle forms no adhesive interactions with mucus glycoproteins.

Antibodies↗

A new quantitative test for sperm penetration into cervical mucus.

A new experimental and theoretical procedure is described for characterizing the penetration of spermatozoa into cervical mucus in vitro. Semen is introduced to a prescribed volume of mucus contained in a flat capillary tube. Use of the tube enables the surface area of semen-mucus contact to be fixed, and provides excellent visualization of sperm movement in the mucus. The time interval of semen-mucus contact is also controlled. The number of motile sperm and their swimming speeds are determined in both the semen and mucus by hemocytometer counts and simple time-exposure photomicrography. The assay provides two new measures of the sperm-mucus interaction. The number of successful sperm entries into the mucus is compared with the number of original collisions between seminal sperm and the semen-mucus interface. The comparison is expressed as a ratio of the numbers of sperm in these two groups, viz., PSC = percentage of successful collisions. The vitality of spermatozoa that do succeed in entering the mucus is assessed by comparing their swimming speeds with those of sperm in the semen. This second comparison is also expressed as a ratio, viz., VR = velocity ratio = mean swimming speed in mucus/mean swimming speed in semen. The clinical application of the method to human semen and cervical mucus is described, and sample results are presented.

Cervix Mucus↗

Differences in sperm migration through cervical mucus in vitro relates to sperm colonization of the oviduct and fertilizing ability in goats.

Sperm migration in estrous cervical mucus can be used to measure the ability of spermatozoa to migrate through the genital tract. The relationship of this test with the sperm colonization of the isthmus, and its impact on fertility has not been evaluated in goats. Our objectives were to determine the differences among spermatozoa of different bucks in their ability to penetrate homologous cervical mucus in vitro and to determine the relationship between sperm displacement through cervical mucus and the ability of spermatozoa to colonize the oviduct and penetrate IVM oocytes, in vivo. Sperm migration in cervical mucus was assessed in flat capillary tubes with a phase contrast microscope. In the first experiment, fresh semen was used to establish differences between males in the ability of their spermatozoa to migrate in cervical mucus. In the second experiment, goats in estrus were inseminated with fresh spermatozoa from males with significant differences in mucus migration ability, and sperm numbers were evaluated at the UTJ. In the third experiment, the fertilization efficiency of IVM oocytes transferred to the oviduct of estrous females inseminated with semen from the same males as earlier, was used to assess the relationship between the mucus migration test and the in vivo fertilization performance of their spermatozoa. Spermatozoa from different males varies significantly in sperm migration efficiency in cervical mucus (15.5a +/- 1.2; 14.9a +/- 1.4; 17.5ab +/- 1.2; 17.0ab +/- 1.5; 19.7b +/- 1.2; 20.1b +/- 1.4 mm; media +/- S.E.M. for males A-F, respectively, P < 0.05). Spermatozoa from males with different mucus migration efficiency values produced different sperm populations at the oviduct reservoir of inseminated females (1,233 +/- 92.3 versus 28.8 +/- 17.0 spermatozoa of males with high and low relative migration efficiency, respectively, P < 0.02). Spermatozoa from males with different mucus migration efficiency values have different fertilization rates of IVM oocytes transferred to oviduct (47/96 (49.0%) versus 25/91 (27.5%) for males with high and low relative migration efficiency, respectively, P < 0.05). Cumulative results suggest that sperm migration in cervical mucus is related to the ability of spermatozoa to colonize the oviduct and to fertilize matured oocytes in vivo.

Animals↗

Decreased colonic mucus in rats with loperamide-induced constipation.

Constipation is a risk factor of colorectal cancer. Mucin is a major component of lumenal mucus, which protects the colorectal mucosa against mechanical and chemical damage. The aim of this study was to evaluate mucus production and to quantitate lumen mucus in a rat model of spastic constipation. We induced constipation with loperamide (1.5 mg/kg), and histochemically evaluated mucus production and the thickness of the mucus layer at the fecal surface. We quantitated the mucus attached to the mucosal surface using colonic perfusion with N-acetylcysteine. While more feces remained in the colon, there was less fecal excretion and lower fecal water content in loperamide-administered rats than in control rats. Crypt epithelial cells contained less mucus in constipated rats than in control rats. The mucus layer at the fecal surface was thinner and less mucus was recovered from the mucosal surface in constipated rats than in control rats. Mucus production of crypt epithelial cells and mucus at the fecal and mucosal surface were reduced by loperamide-induced constipation.

Animals↗

Effect of bile salts on colonic mucus secretion in isolated vascularly perfused rat colon.

Mainly composed of mucins, mucus secreted by goblet cells in the intestinal epithelium is critically involved in the protection of the gastrointestinal mucosa. The hypothesis that bile and some bile salts can induce mucus secretion was tested in the isolated perfused rat colon. Mucus release was evaluated using enzyme-linked immunosorbent assays and supported by histological analysis. Luminal administration of bile extract (1%) provoked mucus secretion in the rat colon. Deoxycholate (0.5-10 mM) induced a dose-dependent increase in rat colonic mucus release. Chenodeoxycholate (10 mM) and hyodeoxycholate (10 mM) also evoked mucus discharge, whereas 10 mM cholate, 10 mM ursodeoxycholate, or Tween-20 did not release mucus. Taurine-conjugated bile salts (deoxycholate, hyodeoxycholate, and chenodeoxycholate) were less potent mucus secretagogues than the corresponding unconjugated forms. The deoxycholate-induced mucus discharge was not altered by pharmacological blockers (tetrodotoxin, atropine), indomethacin, mast cell stabilizers (ketotifen, doxantrazole), H1 histamine receptor antagonist (pyrilamine), or 5-HT receptor antagonists (ketanserin, ondansetron, SDZ 205-557). Our findings suggest that some bile salts, especially in the unconjugated form, may provoke colonic mucus secretion, probably through a direct action on mucus-secreting cells.

Animals↗

Factors affecting solubility and penetration of clarithromycin through gastric mucus.

BACKGROUND: Factors influencing the pharmacokinetics of clarithromycin in gastric mucus are poorly defined. AIM: To determine: (i) whether the clinical formulation of clarithromycin (Biaxin granules and powdered Biaxin tablets) affects the water solvency of the antibiotic or changes the barrier properties of pig gastric mucus (PGM), thereby influencing the penetration of clarithromycin through the gastric mucus layer; and (ii) whether topically active anti-ulcer agents affect clarithromycin penetration through gastric mucus. METHODS: Solubility of clarithromycin in aqueous solution was studied at pH 7. PGM viscosities were determined using a falling ball microviscometer. Permeability of clarithromycin through PGM with and without added anti-ulcer drugs at pH 7 was monitored using a microfiltration device and an agar diffusion bioassay. RESULTS: Clarithromycin showed the poorest solubility at pH 7, whereas both Biaxin formulations demonstrated identical solubility of their antibiotic ingredient. Clarithromycin and both Biaxin formulations markedly increased mucin viscosity over the pH range 2-7. PGM markedly retarded the penetration of clarithromycin: unformulated clarithromycin and Biaxin tablets penetrated more rapidly through mucus than Biaxin granules. Pre-treatment of PGM with aluminium-magnesium-containing antacids (Riopan and Talcid preparations) decreased the rate of clarithromycin penetration, whereas Carafate and Peptobismol had no significant effect on mucus penetration of clarithromycin. CONCLUSIONS: The availability of clarithromycin in gastric mucus is significantly influenced by its clinical formulation, which affects its solubility as well as the viscous properties of mucus. Pulverized Biaxin tablets provide better local distribution of clarithromycin in mucus than Biaxin granules. Pre-treatment of mucus with anti-ulcer medications does not increase the penetration of clarithromycin through mucus.

Absorption↗

Recovery from gastric mucus depletion in the intact guinea pig mucosa.

BACKGROUND: In developed countries one-third of the population is infected with the gastric pathogen Helicobacter pylori. In the early stages of H. pylori-induced gastritis, typical symptoms include gastric erosions and mucus depletions. Artificial mucus depletion was generated, demonstrating both consequent irritation and recovery processes in the mucosa. METHODS: The mucus depletion was examined by removing a small cylinder of mucus from the surface of the explanted guinea pig corpus mucosa, leaving the epithelial surface intact. pH microelectrodes were inserted into the mucosa in vitro, measuring the epicellular mucus pH, the pH(i) of the underlying epithelial cells and the pH inside the gastric glands during mucus regeneration. Using infrared microscopy, the same process of mucus layer renewal was followed in anaesthetized animals. RESULTS: The depletion exposed the tissue surface to low luminal pH levels. At a luminal pH of 2.5, a decrease was observed in the crypt outlet pH and surface cell pH(i), while deeper cells were less affected. However, a subsequent neutralization in the deep gland lumen was found. During the repair process, a quarter of the mucus layer was regenerated within the first 5 min. This newly secreted mucus formed a structure similar to that before depletion. Within 45 min, pH(i) and tissue-near pH values had fully recovered. CONCLUSION: Following mucus depletion, there is a decrease in surface cell pH(i) and crypt outlet pH values. The repair process is then characterized by extensive mucus secretion and local cessation of acid secretion.

Animals↗

Mucus and iron absorption regulation in rats fed various levels of dietary iron.

We tested two hypotheses: (1) that iron binding by secreted mucus enhances iron absorption (Quarterman, Digestion 37: 1, 1987) and (2) that iron binding by secreted mucus prevents excess iron absorption. Rats were fed diets containing 6, 200 or 500 mg Fe/kg diet (Fe-0, Fe-200 and Fe-500 rats, respectively) for 3 wk. Iron absorption was measured in fasted rats using 59FeCl3 in a 10-min in situ duodenal ligated-segment procedure. After draining the segment contents, the mucus layer was separated from the under-lying mucosal surface using Quarterman's agar cast technique. In comparison with that in Fe-200 rats, iron absorption in Fe-0 rats was markedly increased, but the 59Fe and the total mucus in the mucus layer were decreased. The 59Fe absorption and total mucus and total iron in the mucus layer were similar in Fe-500 rats and Fe-200 rats, but the 59Fe in the mucus layer was marginally lower in Fe-500 rats. There was no evidence that mucus enhanced iron absorption; it appeared to trap or bind iron proportionally to the amount of secreted mucus, suggesting protection against excess absorption. Mucus secretion and possibly synthesis were decreased in the Fe-0 rats.

Animals↗

Identification of tobacco-specific carcinogen in the cervical mucus of smokers and nonsmokers.

BACKGROUND: In 1996, an estimated 15,700 new cases of cancer of the uterine cervix and 4,900 deaths from this disease were expected to occur in the United States. In a recent international study, human papillomavirus DNA was found in more than 90% of cervical tumor specimens examined, irrespective of the nationality of the patients from whom the samples were obtained. Although infection with human papillomavirus is the major known risk factor for the development of cervical cancer, it alone is not sufficient. Other etiologic factors that have been associated with this disease include deficiencies in micronutrients, lower socioeconomic status, oral contraceptive use, and cigarette smoking. Several compounds from cigarette smoke (nicotine and its major metabolite, cotinine) have been identified in cervical mucus, and the occurrence of smoking-related DNA damage in the cervical epithelium has been documented. PURPOSE: This investigation was conducted to determine for the first time whether carcinogenic tobacco-specific N-nitrosamines are present in the cervical mucus of cigarette smokers and of nonsmokers (most likely as a result of environmental exposure). METHODS: Cervical mucus specimens from 15 smokers and 10 nonsmokers were subjected to supercritical fluid extraction with the use of carbon dioxide that contained 10% methanol, and the resultant extracts were analyzed for tobacco-specific nitrosamines by use of a very sensitive method that involved gas chromatography and mass spectroscopy analyses. RESULTS: In a total of 16 samples obtained from 15 women who were current smokers (two samples from the same woman), we detected the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) at concentrations that ranged from 11.9 to 115.0 ng/g of mucus. Only one of a total of 10 cervical mucus specimens obtained from 10 women who claimed to be nonsmokers did not contain detectable NNK, and NNK concentrations ranged from 4.1 to 30.8 ng/g of mucus in the specimens from the remaining nine women. The concentrations of NNK in specimens from cigarette smokers were significantly higher than those from nonsmokers (mean +/- standard deviation: 46.9 +/- 32.5 ng/g of mucus versus 13.0 +/- 9.3 ng/g of mucus; two-tailed Student's t test, P = .004). CONCLUSION: The cervical mucus of cigarette smokers contains measurable amounts of the potent carcinogen NNK. This compound represents the first tobacco-specific carcinogen identified in this physiologic fluid of women who smoke cigarettes. The presence of NNK in the cervical mucus of nonsmokers is likely due to environmental exposure or to the fact that some of the subjects in this study may not have revealed that they occasionally smoked cigarettes. IMPLICATIONS: The presence of NNK in human cervical mucus further strengthens the association between cervical cancer and tobacco smoking.

Adult↗

Post-partum cervical mucus: biological and rheological properties.

In this study we have evaluated the score, sperm migration and ultrastructural characteristics of cervical mucus present in amenorrhoeic women under exclusive breastfeeding at 30, 60, 90, 120, 150 and 180 days post-partum. Periovulatory mucus samples from seven normally cycling women were used as a control. The average scores of post-partum and periovulatory mucus were 4.6 +/- 0.4 and 14.1 +/- 0.5 respectively. Twenty-one (39%) of the 54 post-partum cervical mucus samples and all (100%) periovulatory mucus samples allowed sperm migration. Positive sperm migration into post-partum mucus was observed at all time intervals studied. The only parameter that correlated with sperm migration into post-partum mucus was ferning formation. Sperm migration was obtained in all post-partum mucus samples with a score greater than 8, but samples with scores between 2 and 7 also showed sperm penetration. Scanning electron microscopic studies showed the characteristic spongy appearance of periovulatory mucus. Post-partum mucus was formed by a dense mesh (rocky appearance), when samples were generally unable to sustain sperm migration, but samples where sperm migration occurred showed small areas of spongy mucus mixed with areas in which a dense mesh and high cellularity was observed.

Amenorrhea↗

Human cervical mucus: relationship between biochemical characteristics and ability to allow migration of spermatozoa.

Cervical mucus is produced throughout the menstrual cycle. Sperm migration, however, is possible only during the periovulatory period of the cycle. Cervical mucus is also produced during the amenorrhoeic post-partum period. Post-partum mucus is very similar to luteal phase mucus except that it can allow sperm migration. In this study, mucus samples obtained from all these periods were classified according to their capacity to allow sperm migration. The biochemical characteristics of mucus samples that did (peri-ovulatory and 40% of post-partum samples) and did not (luteal and 60% of post-partum samples) allow sperm migration were then compared. Mucus samples with positive sperm migration showed the highest percentage of water and lowest protein and glycoprotein concentration (per ml of mucus). In addition, post-partum mucus samples with positive sperm migration showed lower concentrations of proteins and glycoproteins than post-partum mucus samples that did not allow sperm migration. However, the amount of glycoproteins per mg of protein was similar between post-partum samples that were positive and negative for sperm migration. These data suggest that the carbohydrate composition of the glycoproteins is playing a key role in the ability of cervical mucus to accept spermatozoa.

Body Water↗

Induction of protease activity in Vibrio anguillarum by gastrointestinal mucus.

The effect of gastrointestinal mucus on protease activity in Vibrio anguillarum was investigated. Protease activity was measured by using an azocasein hydrolysis assay. Cells grown to stationary phase in mucus (200 microg of mucus protein/ml) exhibited ninefold-greater protease activity than cells grown in Luria-Bertani broth plus 2% NaCl (LB20). Protease induction was examined with cells grown in LB20 and resuspended in mucus, LB20, nine-salts solution (NSS [a carbon-, nitrogen-, and phosphorus-free salt solution]), or marine minimal medium (3M) ( approximately 10(9) CFU/ml). Induction of protease activity occurred 60 to 90 min after addition of mucus and was >/=70-fold greater than protease activity measured in cells incubated in either LB20 or 3M. Mucus was fractionated into aqueous and chloroform-methanol-soluble fractions. The aqueous fraction supported growth of V. anguillarum cells, but did not induce protease activity. The chloroform-methanol-soluble fraction did not support growth, nor did it induce protease activity. When the two fractions were mixed, protease activity was induced. The chloroform-methanol-soluble fraction did not induce protease activity in cells growing in LB20. EDTA (50 mM) inhibited the protease induced by mucus. Upon addition of divalent cations, Mg(2+) (100 mM) was more effective than equimolar amounts of either Ca(2+) or Zn(2+) in restoring activity, suggesting that the mucus-inducible protease was a magnesium-dependent metalloprotease. An empA mutant strain of V. anguillarum did not exhibit protease activity after exposure to mucus, but did grow in mucus. Southern analysis and PCR amplification confirmed that V. anguillarum M93 contained empA. These data demonstrate that the empA metalloprotease of V. anguillarum is specifically induced by gastrointestinal mucus.

Animals↗

Mucus rheology and transport in neonatal respiratory distress syndrome and the effect of surfactant therapy.

BACKGROUND: Neonatal respiratory distress syndrome (RDS) is caused by a deficiency of pulmonary surfactant. Alveolar collapse and obstruction of conducting airways leads to mismatch of ventilation and perfusion and profound hypoxemia. We postulated that surfactant deficiency could alter the properties of respiratory mucus in such a way that it would be poorly cleared from airways and promote airway luminal obstruction and that these changes might be reversed by the exogenous administration of a synthetic surfactant preparation. METHODS: Respiratory mucus coating an endotracheal tube (ETT) or suction catheter was collected from 14 neonates (gestational age, 24 to 36 weeks; birth weight, 600 to 2,400 g) with RDS who required tracheal intubation and ventilation. Eight of these neonates received 5 ml/kg of an intratracheal artificial surfactant preparation (Exosurf), given between 2 and 10 h of age and six neonates received 5 ml/kg of air. Mucus viscoelasticity, hydration (percentage of solid composition of mucus), and mucociliary clearability (NFPTR) were measured for each specimen. RESULTS: The total volume of mucus collected from the surfactant-treated and control infants was similar, but mucus hydration was significantly less in babies with RDS who did not receive Exosurf (percentage of solid composition of mucus 18.7 vs 11.4; p = 0.013). Ciliary transportability was also less in the untreated babies (NFPTR 0.39 vs 0.86; p = 0.018) and this mucus was more rigid (increased viscoelasticity: log G* 1 rad/s 2.28 vs 1.50; p = 0.0001). CONCLUSIONS: These data suggest that airway obstruction in RDS may be due, in part, to abnormal mucus properties and impaired ciliary transport. Surfactant therapy appears to improve mucus clearability. Exogenously administered surfactant may also be beneficial for the treatment of other selected respiratory conditions associated with impaired mucus clearance.

Drug Combinations↗

In situ variation of cervical mucus pH during exposure to atmospheric air.

The objective of the present study was to determine if exposure of cervical mucus to air during specular examination could modify mucus pH. Detection of changes is justified because of their possible interference with sperm-mucus interaction, since an acidic pH is unfavorable to sperm penetration and is associated with infertility due to the cervical factor. Twenty women with good quality mucus were evaluated. pH measurements of ecto- and endocervical mucus were made in situ using a glass electrode after 0-, 5- and 10-min exposure to air. There was a progressive alkalinization of mucus pH. Mean values of ectocervical mucus pH were 6.91, 7.16 and 7.27, while mean values of endocervical mucus pH were 7.09, 7.34 and 7.46 at 0, 5 and 10 min, respectively. Significant differences were found between the mean values obtained at 0 and 5 min, and at 0 and 10 min (P<0.05), whereas the differences in mean values at 5 and 10 min were not significant at either site. We conclude that 5 to 10 min of exposure to atmospheric air affects cervical mucus pH in a significant way. Since tests used to evaluate sperm-mucus interaction generally have not considered this possibility, we suggest that they should be performed immediately after mucus collection in order to avoid misinterpretation of the results.

Air↗

The role of mucus viscoelasticity in cough clearance.

The relationships between mucus rheology, depth of mucus layer and clearance by simulated cough were examined in a study employing a model plexiglass trachea lined with gels formed from locust bean gum crosslinked with sodium tetraborate. The viscoelastic properties of the mucus simulants were determined by magnetic rheometry at 100 rad/s and expressed as mechanical impedance (dynamic stress/strain ratio) and loss tangent. Cough was simulated by opening a solenoid valve connecting the model trachea to a pressurized tank, using an upstream flow-constrictive element to shape the flow profile to approximate the pattern seen in a normal adult. Mucus clearance was quantitated by observing the movement of contrasting marker particles placed in the mucus layer. The median particle displacement was defined as the clearance index, Cl. For any initial depth of mucus, Cl increased with driving pressure in the tank, and for a given driving pressure, Cl increased linearly with increasing mucus depth. For a given driving pressure and depth, Cl decreased with increasing mechanical impedance of the mucus. At constant mechanical impedance, Cl increased with increasing loss tangent, in other words, cough clearance was impeded more by elasticity than viscosity. Mucus clearance was associated with transient wave formation in the lining layer. Thus dependence on viscoelasticity is consistent with observations that airflow-mucus interaction and wave formation are impeded by elasticity. The clearance vs. loss tangent relationship for cough is opposite to that found for ciliary clearance (Biorheology 1980, 17, 249), suggesting a natural balance in viscosity and elasticity for mucus to be cleared by both mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗