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PubMed1989

Sucralfate interactions with gastric mucus.

Sucralfate protects the stomach against a number of experimental damaging agents and is efficacious in the treatment of peptic ulcer disease. It binds with acidity to the base of an ulcer to form a protective barrier. Sucralfate also enhances prostaglandin synthesis and release in the mucosa. In this study, the rat stomach was examined to determine sucralfate's interaction with gastric mucus. Mucus in the rat stomach forms a distinct and continuous blanket. In snap-frozen samples, pretreatment with phosphate-buffered saline as a control shows a layer of mucus of homogeneous structure thinner than the homogeneous layer after pretreatment with antibodies developed against rat gastric mucus. Pretreatment with the surface protective agent sucralfate shows some increase in the thickness of mucus with a thin dense sublayer adjacent to the epithelium and a less dense-appearing outer zone of variable thickness. Analysis of x-rays generated by the electron beam on windows of mucus and epithelium showed the expected gradients of sodium, potassium, chloride, and sulfur. The percentage of aluminum and sulfur in the mucus was higher in sucralfate-treated samples than in controls. Interaction between sucralfate and gastric mucus needs further investigation.

Animals↗
PubMed1982

Binding of [3H]quinuclidinyl benzilate to intestinal mucus. An artifact in identification of epithelial cell muscarinic receptors.

The widely used muscarinic receptor ligand [3H]quinuclidinyl benzilate ([3H]QNB) was found to bind in a site-specific but artifactual manner to rat intestinal mucus, obscuring specific binding to muscarinic receptors on intestinal epithelial cells. Atropine inhibited [3H]QNB binding to mucus with an apparent IC50 of 2.1 x 10(-7) M, compared to an IC50 of 1.4 x 10(-8) M obtained with a homogenate of intestinal epithelial cells. Unlabeled QNB also inhibited binding of [3H]QNB to mucus but the apparent IC50 (4 x 10(-7) M) was about 300-fold greater than the IC50 determined with a control tissue, heart muscle (IC50, 1.2 x 10(-9) M). [3H]QNB binding was saturable over the concentration range of 1-7 nM in the heart, with an apparent KD of 0.76 nM. As expected from the high IC50 for QNB in the mucus binding experiments, binding to mucus was not saturable over the 1-15 nM concentration range. Based on pH profiles and temperature dependency of binding, it seems unlikely that mucin, the primary component of mucus, was responsible for [3H]QNB binding to the mucus. The findings have implications for studies which involve binding of [3H]QNB in particular and other ligands in general to mucus-secreting epithelial tissues.

Animals↗
PubMed1994

P2 purinergic receptor regulation of mucus glycoprotein secretion by rabbit gastric mucous cells in a primary culture.

BACKGROUND/AIMS: Physiological regulation of gastric mucus secretion has not been well studied. The present study investigated the effects of adenosine 5'-triphosphate (ATP), a P2 purinergic receptor agonist, and its analogues on gastric mucus secretion using gastric mucous cells in a primary culture. METHODS: A monolayer culture of gastric mucous cells from adult rabbits were prepared after enzyme digestion. Mucus secretion was estimated from the release of [3H]glucosamine from prelabeled cells. Intracellular calcium concentration ([Ca2+]i) was monitored by a Ca(2+)-sensitive probe, indo-1. Prostaglandin E2 (PGE2) in the media was measured by an enzyme-linked immunoassay. RESULTS: ATP significantly stimulated mucus secretion by these cells at nontoxic doses in a dose-dependent fashion. The order of potency of ATP analogues stimulating mucus secretion was alpha beta-methylene ATP > ATP > 2-methylthio ATP, whereas adenosine, a P1 purinergic receptor agonist, had no effect. ATP also induced an elevation of [Ca2+]i in a dose-dependent fashion. The efficacy of ATP analogues to increase [Ca2+]i showed a similar potency to their actions on mucus secretion. ATP increased PGE2 at relatively higher concentrations, whereas indomethacin did not block ATP-induced increase of mucus secretion. CONCLUSIONS: These results suggest that ATP stimulates mucus secretion by gastric mucous cells through P2 purinergic receptors; this appears to be mediated by intracellular calcium not by endogenous PGE2.

Adenosine↗
PubMed1990

SCH 23390: D-1 modulation of oral dyskinesias induced in snakes by Xenopus skin mucus.

The granular gland skin secretion of Xenopus laevis induces seven involuntary oral dyskinesias and climbing behavior in the water snake Nerodia sipedon. In a previous study the D-2 receptor antagonist, haloperidol (HAL), selectively potentiated mucus-induced yawning and chewing but attenuated fixed gaping; other oral behaviors were unaffected; HAL alone induced no dyskinesias and failed to modify mucus-induced decreases in tongue flicking, cage climbing and activity. As skin compounds have neuroleptic properties known to induce human and animal dyskinesias, we hypothesized that D-1 receptor antagonism may modulate the four of seven mucus-induced dyskinesias and the climbing not altered by HAL. We found that, like HAL, SCH 23390 (SCH) potentiated mucus-induced yawning, attenuated fixed gaping and had no effect on climbing. Unlike HAL's potentiation of chewing, SCH attenuated chewing and potentiated writhing tongue movements. SCH alone, like skin mucus, attenuated tongue flicking and activity but, given with mucus, SCH increased tongue flicking and activity to control levels. Compared to the HAL study, results suggest that mucus-induced yawning and fixed gaping are similarly modulated by both HAL and SCH, while these drugs have opposite effects on writhing tongue and chewing. SCH given alone or with frog mucus had unique effects on activity and normal tongue flicking.

Animals↗
PubMed1985

Free amino acid content in the skin mucus of goldfish, Carassius auratus L.: influence of feeding.

Free amino acid contents in skin extracts and influence of food and starvation on free amino acid content in skin mucus were analysed in sexually immature goldfish. Free amino acid concentration in skin mucus (91.1 mumol/g dry wt) was higher than in deep skin (54 mumol/g) or in whole skin (56.6 mumol/g) extracts. Free amino acid compositions were very similar in the latter extracts. They both differed from skin mucus extract in taurine, glutamic acid, glycine and histidine relative contents. Free amino acid composition in zooplankton used to feed goldfish was close to the composition found in corresponding skin mucus extracts, except in taurine content. Goldfish weighing 3 g (6 months old) and 17 g (1 year old) reared on zooplankton showed similar patterns of free amino acid composition in skin mucus. Comparison with free amino acid composition in skin mucus from goldfish fed on commercial food had big differences in glutamic acid, valine, methionine and lysine relative contents. During fasting, we observed an increase in the amount of mucus secreted and a concomitant decrease of the free amino acid concentration in the secretion. The origin of free amino acids found in skin mucus and their possible role in pheromonal and allelochemical communications of goldfish are discussed.

Amino Acids↗
PubMed2006

Evaluation of effectiveness of prophylactic cerclage of a short cervix according to interleukin-8 in cervical mucus.

OBJECTIVE: This study was undertaken to compare rates of preterm delivery according to cervical mucus interleukin-8 (IL-8) among women who underwent cerclage because of a short cervix. STUDY DESIGN: This retrospective study included 16,508 patients whose cervical length and cervical mucus IL-8 concentrations were measured between 20 and 24 weeks. A short cervix was defined by a length of 25 mm or less, whereas IL-8 concentrations exceeding 360 ng/mL were considered high. Whether to perform cerclage was decided by clinicians without consideration of IL-8 concentrations. RESULTS: Among all subjects, a significantly smaller percentage of subjects avoided delivery before 37 weeks when cervical mucus IL-8 was elevated (P = .0302) or the cervix was short (P < .0001). Among patients with a short cervix, preterm delivery was more likely when cervical mucus IL-8 was elevated. Overall, risk of preterm delivery in patients with a short cervix did not differ between those undergoing and not undergoing cerclage. However, among patients with a short cervix, those with normal IL-8 concentrations in cervical mucus were less likely to have preterm delivery if they underwent cerclage (before 37 weeks, 33% vs 54.5%, P = .01; before 34 weeks, 4% vs 13.6%, P = .03). In contrast, when cervical mucus IL-8 was high, delivery before 37 weeks was more likely with than without cerclage (78% vs 54.1%, P = .03). CONCLUSION: With normal cervical mucus IL-8, cerclage treatment for cervical shortening may reduce the rate of preterm delivery, but with elevated cervical mucus IL-8 cerclage may be harmful.

Cerclage, Cervical↗
PubMed2004

The effect of synthetic polymers on the migration of monocytes through human cervical mucus.

The integrity of the vaginal mucosa is critical to protecting women from infection, particularly sexually transmitted diseases. For example, breakdown of the mucosa, including the cell lining and/or mucus layer, due to vaginal infections has been shown to increase the risk of HIV infection. There is considerable interest in the development of new topical microbicides for women; many of these topical agents contain polymers. One potential mechanism for altering the barrier properties of a three-dimensional fibrous gel, such as cervical mucus, to cell penetration is to alter the fiber structure. In previous studies, we have shown that addition of synthetic polymers, such as polyvinyl pyridine (PVP) and polyethylene glycol (PEG), modify the fiber structure and mechanical properties of human cervical mucus. Here we investigated the ability of peripheral blood monocytes to migrate through structurally altered mucus gels. Adding PVP to mucus increased both the average fiber spacing and the rate of random migration of monocytes; addition of PEG to mucus also caused an increased random migration rate, although changes in overall fiber spacing were not obvious. In both cases, the addition of small amounts of polymer to cervical mucus decreased the barrier property of mucus with respect to cell migration. This result raises questions about the safety of polymeric agents as ingredients in topical microbicides.

Biocompatible Materials↗
PubMed2005

Antioxidant properties of the mucus secreted by Laeonereis acuta (Polychaeta, Nereididae): a defense against environmental pro-oxidants?

Polychaeta species like Laeonereis acuta (Nereididae) usually secrete great amounts of mucus that wrap the animal inside. Taking into account that fungi action in the sediment and UV radiation acting on dissolved organic matter in the water produces reactive oxygen species (ROS) like hydrogen peroxide (H(2)O(2)), it was considered that the mucus secretion could represent an antioxidant defense against environmental ROS. Antioxidant enzymes (catalase-CAT; superoxide dismutase-SOD; glutathione peroxidase-GPx and glutathione-S-transferase-GST) and total antioxidant capacity (TOSC) were determined in worms and mucus secretion. Higher (p<0.05) CAT, GPx and TOSC values were registered in mucus samples respect worms, SOD activity was similar (p>0.05) in both kind of samples, and absence of GST activity was observed in mucus samples, suggesting absence of catalyzed phase II reactions. In assays conducted with hepatoma cell lines exposed to H(2)O(2), it was verified that: (1) mucus co-exposure significantly (p<0.05) lowered DNA damage induced by H(2)O(2); (2) ROS production was significantly (p<0.05) reduced when cells were exposed simultaneously with mucus samples and H(2)O(2) respect H(2)O(2) alone. It can be concluded that the mucus production contributes substantially to the antioxidant defense system of the worm against environmental ROS through the interception or degradation of H(2)O(2), peroxyl and hydroxyl radicals.

Animals↗
PubMed2004

Airway mucus hypersecretion in asthma: an undervalued pathology?

Airway mucus hypersecretion is a feature of many patients with asthma. It is indicative of poor asthma control and contributes to morbidity and mortality. Excess mucus not only obstructs airways but also contributes to airway hyperresponsiveness. Furthermore, asthma might have a specific mucus hypersecretory phenotype. Goblet cell hyperplasia and submucosal gland hypertrophy are shared with other hypersecretory diseases, such as chronic obstructive pulmonary disease; however, some features are different, including mucus plugging, mucus "tethering" to goblet cells, plasma exudation, and increased amounts of a low charge glycoform of mucin (MUC)5B and the presence of MUC2 in secretions. Experimentally, most of the inflammatory mediators and neural mechanisms implicated in the pathophysiology of asthma impact upon the mucus hypersecretory phenotype. There is currently huge research interest in identifying targets involved in inducing mucus abnormalities, which should lead to the rational design of anti-hypersecretory drugs for treatment of airway mucus hypersecretion in asthma.

Airway Obstruction↗
PubMed2005

Striking deposition of toxic eosinophil major basic protein in mucus: implications for chronic rhinosinusitis.

BACKGROUND: The mechanisms by which eosinophilic inflammation damages the epithelium and contributes to recurrent acute exacerbations in chronic rhinosinusitis (CRS) have not been fully elucidated. OBJECTIVE: We tested the hypotheses that eosinophils deposit toxic major basic protein (MBP) in the mucus and that MBP reaches concentrations able to damage the sinonasal epithelium. METHODS: Tissue specimens with mucus attached to the tissue were carefully collected from 22 patients with CRS and examined by using immunofluorescence staining for MBP. This immunofluorescence was digitally analyzed to determine the area covered by MBP and the intensity of the staining (estimating MBP concentration). Levels of MBP in extracts from nasal mucus were quantitated by means of RIA. RESULTS: Heterogeneous eosinophilia was evident within tissue and mucus specimens. All tissue specimens showed intact eosinophils, but diffuse extracellular MBP deposition, as a marker of eosinophil degranulation, was rare. In contrast, all mucus specimens showed diffuse MBP throughout and abundant diffuse extracellular MBP deposition within clusters of eosinophils. Digitized analyses of MBP immunofluorescence revealed increased area coverage (P < .0001) in mucus compared with that seen in tissue. Estimated concentrations of MBP within the clusters suggested toxic levels. MBP concentrations in mucus extract reached 11.7 microg/mL; MBP was not detectable in healthy control subjects. CONCLUSION: In patients with CRS, eosinophils form clusters in the mucus where they release MBP, which is diffusely deposited on the epithelium, a process not observed in the tissue. Estimated MBP levels far exceed those needed to damage epithelium from the luminal side and could predispose patients with CRS to secondary bacterial infections.

Adolescent↗
PubMed2006

Effect of fish skin mucus on the soluble proteome of Vibrio salmonicida analysed by 2-D gel electrophoresis and tandem mass spectrometry.

Vibrio salmonicida is the causative agent of cold-water vibriosis in farmed marine fish species. Adherence of pathogenic bacteria to mucosal surfaces is considered to be the first steps in the infective processes, and proteins involved are regarded as virulence factors. The global protein expression profile of V. salmonicida, grown with and without the presence of fish skin mucus in the synthetic media, was compared. Increased levels of proteins involved in motility, oxidative stress responses, and general stress responses were demonstrated as an effect of growth in the presence of mucus compared to non-mucus containing media. Enhanced levels of the flagellar proteins FlaC, FlaD and FlaE indicate increased motility capacity, while enhanced levels of the heat shock protein DnaK and the chaperonin GroEL indicate a general stress response. In addition, we observed that peroxidases, TPx.Grx and AhpC, involved in the oxidative stress responses, were induced by mucus proteins. The addition of mucus to the culture medium did not significantly alter the growth rate of V. salmonicida. An analysis of mucus proteins suggests that the mucus layer harbours a protein species that potentially possesses catalytic activity against DNA, and a protein with iron chelating activity. This study represents the first V. salmonicida proteomic analysis, and provides specific insight into the proteins necessary for the bacteria to challenge the skin mucus barrier of the fish.

Aliivibrio salmonicida↗
PubMed2005

Clinical evaluation of postpartum vaginal mucus reflects uterine bacterial infection and the immune response in cattle.

Bacteria contaminate the uterus of most dairy cattle after parturition and endometritis causes infertility. An endometritis score can be ascribed based on the vaginal mucus character and odour but it is not clear if the clinical score reflects the number of uterine bacteria or the inflammatory response. The present study tested the hypothesis that clinical evaluation of endometritis reflects the number of bacteria present in the uterus, and the acute phase protein response. Swabs (n = 328) were collected from the uterine lumen of dairy cattle, 21 and 28 days postpartum, vaginal mucus was scored for character and odour, and blood samples collected for acute phase protein measurement. Bacteria were identified following aerobic and anaerobic culture, and the bacterial growth density was scored semi-quantitatively. When bacteria were categorised by their expected pathogenic potential in the uterus, purulent or fetid odour vaginal mucus was associated with the growth density of pathogenic bacteria but not opportunist contaminants. When bacteria were analysed independently, Arcanobacterium pyogenes, Proteus and Fusobacterium necrophorum growth densities were associated with mucopurulent or purulent vaginal mucus. The bacterial growth densities for A. pyogenes, Escherichia coli, non-hemolytic Streptococci, and Mannheimia haemolytica were associated with a fetid mucus odour. Peripheral plasma concentrations of alpha(1)-acid glycoprotein were higher if there was a fetid compared with a normal vaginal mucus odour (1.50 +/- 0.09 mg/mL versus 1.05 +/- 0.02 mg/mL, P < 0.001), but did not differ significantly between vaginal mucus character scores. The evaluation of the character and odour of vaginal mucus reflects the number of bacteria in the uterus, and the acute phase protein response.

Actinomycetaceae↗
PubMed1988

Role of salivary epidermal growth factor in the maintenance of physicochemical characteristics of oral and gastric mucosal mucus coat.

The involvement of salivary epidermal growth factor (EGF) in the maintenance of oral and gastric mucosal mucus coat dimension and chemical characteristics was investigated using sialoadenectomized rats. Examination of the oral and gastric mucosal surface by phase contrast microscopy and Alcian blue uptake revealed that deprivation of salivary EGF caused a 31-36% reduction in mucus coat thickness and a 38-43% reduction in adherent mucin content. Chemical analyses indicated that the mucus coat of sialoadenectomized group exhibited a 21-28% increase in protein and a 67% decrease in covalently bound fatty acids, a 30% decrease in carbohydrates, and a 32-37% decrease in lipids. Sialoadenectomy also evoked changes in the chemical composition of mucus glycoprotein component of oral and gastric mucus coat reflected in the lower content of sulfate (25-26%), associated lipids (24-25%), and covalently bound fatty acids (67-75%). Intragastric supplementation of EGF had no effect on the physicochemical changes caused by sialoadenectomy in the oral mucosal mucus coat, while nearly complete restoration to normal characteristics occurred in the gastric mucosal mucus coat. The results suggest that salivary EGF is essential for the maintenance of mucus coat dimension and quality needed in the protection of alimentary tract epithelium.

Animals↗
PubMed2001

Diffusion of macromolecules and virus-like particles in human cervical mucus.

To determine whether or not large macromolecules and viruses can diffuse through mucus, we observed the motion of proteins, microspheres, and viruses in fresh samples of human cervical mucus using fluorescent recovery after photobleaching and multiple image photography. Two capsid virus-like particles, human papilloma virus (55 nm, approximately 20,000 kDa) and Norwalk virus (38 nm, approximately 10,000 kDa), as well as most of the globular proteins tested (15-650 kDa) diffused as rapidly in mucus as in saline. Electron microscopy of cervical mucus confirmed that the mesh spacing between mucin fibers is large enough (20-200 nm) for small viruses to diffuse essentially unhindered through mucus. In contrast, herpes simplex virus (180 nm) colocalized with strands of thick mucus, suggesting that herpes simplex virus, unlike the capsid virus particles, makes low-affinity bonds with mucins. Polystyrene microspheres (59-1000 nm) bound more tightly to mucins, bundling them into thick cables. Although immunoglobulins are too small to be slowed by the mesh spacing between mucins, diffusion by IgM was slowed by mucus. Diffusion by IgM-Fc(5 mu), the Fc pentamer core of an IgM with all 10 Fab moieties removed, was comparably slowed by mucus. This suggests that the Fc moieties of antibodies make low-affinity bonds with mucins.

Cervix Mucus↗
PubMed2002

Effects of chelating agents on the rheological property of cervical mucus.

As an ongoing effort to elucidate the mechanisms involved in the calcium-dependent fertility regulation process, the viscoelastic properties of the mucus obtained from lamb cervix and human semen, as well as their water and total protein contents after exposure to EDTA, a chelating agent, or Nonoxynol-9 (N-9), a spermicidal agent, were examined. The viscosity was measured using a Cone Plate Digital Viscometer, while the water and total protein contents were determined by the lyophilization process and the Lowry method, respectively. The significant changes in the rheological properties of mucus, such as its viscosity and the water content, upon exposure to EDTA were demonstrated. The viscosity of cervical mucus and human semen were significantly increased by EDTA treatment (as compared to the controls): lamb cervical mucus (2.9 +/- 0.3 vs. 2.2 +/- 0.3 cps) and human semen (5.0 +/- 0.3 vs. 4.3 +/- 0.3 cps), respectively. The hydration rate was decreased by EDTA treatment as compared with the control (93.6 +/- 0.7 vs. 96.8 +/- 0.8%). Among tested samples, the reduction in the percentage of sperm penetration through the cervical mucus was the highest in the mucus containing EDTA, which had the lowest water content (93.6 +/- 0.7%), indicating that there is a positive relationship between the hydration rate of the cervical mucus and its ability to permit the penetration of spermatozoa. This result indicates that spermicidal activity exerted by high concentrations of EDTA is in part due to its effect on the rheological properties of cervical mucus or semen.

Animals↗
PubMed1980

Spermagglutinating antibodies and sperm penetration of cervical mucus from infertile women with spermagglutinating antibodies in serum.

Spermagglutinins were demonstrated by the tray agglutination technique in cervical mucus collected during presumably-ovulatory cycles in 8 women among 21 patients with spermagglutinating antibodies in serum treated for infertility. A "poor" sperm penetration test was recorded exclusively in women with spermagglutinins in cervical mucus, and the results of the sperm-cervical mucus contact test were significantly correlated to the spermagglutinin titers in cervical mucus. The incidence of spermagglutinating antibodies in cervical mucus from infertile women was estimated to be 2.2% on the basis of the results in the present study. However, an inhibiting effect on sperm penetration in cervical mucus by spermagglutinins is expected to occur in less than 1% of women from infertile couples. A decrease in spermagglutinin titers in cervical mucus observed during estrogen medication was significantly associated with improved sperm penetration in vitro. The latter results may indicate a new approach to the treatment of infertility due to the presence of spermagglutinating antibodies in cervical mucus.

Antibody Formation↗
PubMed1988

Correlation of human sperm motility characteristics with an in vitro cervical mucus penetration test.

Semen analysis was performed on 226 ejaculates by an integrated microcomputerized system employing the multiple-exposure photography (MEP) method. Mucus penetration tests were performed in vitro using commercial preparations of bovine cervical mucus. A highly significant (P less than 0.001) correlation between mucus penetration distance and sperm count (r = 0.582), motility (r = 0.357), velocity (r = 0.569), motile density (r = 0.582), motility index (r = 0.467), and morphology (r = 0.383) was observed. Increased percentages of immature germ cells (r = -0.318) and bent-tailed sperm (r = -0.221) were the most strongly correlated with mucus penetration. Approximately 10% to 15% of patients with otherwise normal semen parameters displayed poor penetration of mucus. Conversely, 5% to 40% of patients with abnormal semen parameters displayed excellent penetration of the mucus. Motile density and velocity demonstrated the strongest relationship with the outcome of the mucus penetration test. These results suggest that a significant subpopulation of patients can be identified as having inadequate (or adequate) penetration of mucus with otherwise normal (or abnormal) motility characteristics.

Animals↗
PubMed1988

In vivo measurement of gastric mucus pH in canines: effect of high luminal acidity and prostaglandin E2.

We measured gastric mucus pH in vivo in a canine chambered stomach preparation using glass pH microelectrodes. The average maximum mucus pH was 6.52 at a luminal pH of 3.0, declining gradually as luminal pH was lowered; the mucus pH gradient was obliterated completely when luminal pH reached 1.1. At a luminal pH of 1.0, the average maximum mucus pH increased to 6.03, whereas transmural potential dropped from -50.3 to -31.8 mV. Prostaglandin E2 pretreatment (10 micrograms/ml) prevented epithelial injury during exposure to 100 mM HCl, but mucus pH was unchanged as compared with the acid-only group (4.77 vs. 4.72, p = 0.92). Histology on stomachs exposed to a luminal pH of 1.0 revealed characteristic changes of superficial epithelial injury without affecting the deeper gastric glands or disrupting the basal lamina. Prostaglandin E2 pretreatment prevented these histologic changes. These results indicate that although the mucus pH gradient can be overwhelmed by high luminal acidity, a newly formed mucus pH gradient may develop after disruption of epithelial integrity, possibly providing protection for the mucosa during the period of epithelial repair. The high mucus pH (4.77) accompanying normal histology and unchanged potential suggests that prostaglandin E2 may protect the surface epithelium by the stimulation of bicarbonate secretion.

Animals↗