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PubMed1981

The pH gradient across mucus adherent to rat fundic mucosa in vivo and the effect of potential damaging agents.

We investigated the possibility that a "mucus-bicarbonate" barrier might exist in the stomach in vivo. Using an antimony microelectrode a pH gradient was demonstrated across the mucus layer on the fundic mucosa of the rat stomach in vivo. When the luminal pH was 2.0 the maximum pH reached on traversing the mucus layer was 6.68 +/- 0.71 (n = 30) and a stable gradient could be maintained across the mucus for over 100 min. Introduction of luminal solutions with a pH of less than 1.5 caused a fall in the pH gradient and its abolition at pH 1.2. N-Acetyl-L-cysteine (5%) in pH 2.0 luminal HCl solution caused a fall in pH in 12 of 18 rats within 5 min. After 30 to 60 min exposure the maximum mean pH in 12 rats was reduced to 4.18 +/- 0.92 (p less than 0.001). Ten millimolar aspirin in pH 2.0 HCl also caused a fall in pH in 12 of 24 rats within 10 min and the maximum pH in 12 rats after 30-60 min exposure was 4.13 +/- 0.84 (p less than 0.001). These effects on the mucus pH gradient were local actions because in other, untreated areas of the same stomachs there was a normal maximum pH. Ten millimolar sodium taurocholate in pH 2.0 HCl produced a visible clouding of the mucus layer, but no fall in pH. However, gentle manipulation caused the mucus to "flake" off with a subsequent fall in underlying pH. These observations indicate the presence of a pH gradient in mucus in vivo which can be compromised by agents which interfere with mucus structure and/or bicarbonate secretion and by high intraluminal hydrogen ion concentrations. The results support a role for this barrier in gastric mucosal protection.

Acetylcysteine↗
PubMed1997

Stone formation after augmentation cystoplasty: the role of intestinal mucus.

PURPOSE: We evaluated the role of mucus in urine after bladder augmentation and hypothesize that mucus acts as a possible etiological factor in stone formation. MATERIALS AND METHODS: Mucus was collected via centrifugation from the 24-hour urine specimens of 8 stone forming and 10 nonstone forming patients who were randomly selected from our augmentation population. The mucus and stones were lyophilized, and then analyzed via scanning electron microscopy and energy dispersive x-ray spectrometry for calcium, phosphate, magnesium and sodium. The 24-hour urine collections were also analyzed to determine any metabolic differences between the 2 groups. RESULTS: Scanning electron microscopy and energy dispersive x-ray spectrometry spectra showed increased calcium, phosphate, and magnesium, and significantly higher (p < 0.05) calcium-to-phosphate ratios in the mucus of stone versus nonstone forming patients. Of the 8 stones examined all had viscous fluid (mucus) centers rich in calcium, phosphate and magnesium. Calcium-to-phosphate ratios in the corresponding mucus recovered from stone centers were similarly high. Urinary citrate levels were low in both groups, and calcium, phosphate and magnesium were within normal ranges. CONCLUSIONS: Mucus appears to have an important role in the genesis of bladder stones after augmentation, possibly acting as a nidus. Metabolic changes following augmentation were similar in stone and nonstone forming populations. Our data suggest that mucous calcium-to-phosphate ratios may be predictive of future stone formation. Furthermore, there may be a benefit in instituting more aggressive measures aimed at clearing mucus from the bladder.

Child↗
PubMed1997

Mucus and H. pylori.

A continuous, adherent mucus gel layer with mucosal bicarbonate secretion is the initial protective barrier in the stomach and duodenum against erosion by the gastric juice. H. pylori resides within the adherent mucus gel layer close to the epithelial surface. The barrier function of the mucus layer in vivo depends on (i) its thickness, and (ii) its gel structure, a property which is linearly dependent on the polymeric mucin content. We have shown in vivo that H. pylori colonisation alone did not decrease the thickness of the adherent gastric mucus barrier, although there was a mean 20% decrease in mucus thickness in those H. pylori positive subjects with underlying gastric atrophy. There was, however, a significant mean 18% reduction in the gel-forming polymeric mucin content of mucus from H. pylori subjects, independent of underlying atrophy. Studies in vitro suggest this loss of gel structure might arise from a H. pylori mediated, high local pH generated by urease activity rather than by proteolysis. This study shows that H. pylori infection alone does not compromise the overall integrity of the mucus barrier in vivo. However, in the immediate environment of the organism there appears to be a localised loss of mucus gel structure. The mucus barrier is compromised if H. pylori associated gastric atrophy or peptic ulceration follows.

Animals↗
PubMed1997

[Decreased quality of cervix mucus under the influence of clomiphene: a meta-analysis].

OBJECTIVE: To determine whether clomiphene (citrate) has a negative influence on cervical mucus qualities and whether administration of exogenous oestrogens has a favourable influence in that case. DESIGN: Meta-analysis. SETTING: Stichting Gezondheidszorg Oostelijk Zuid-Limburg, Midwifery School, Kerkrade, the Netherlands. METHOD: Relevant articles were searched using the Medline database for the years 1980-1996 and the Knowledge Finder search system. The reference lists of these articles were studied. All prospective, randomized and controlled clinical trials mentioning detailed figures were selected and analysed. RESULTS: Six articles met all criteria for analysis of the effect of clomiphene on cervical mucus. Clomiphene 50 mg/day had an unfavourable influence on cervical mucus (not significant), but clomiphene 100 and clomiphene 150 mg/day did have a significant effect, the relative risk of unfavourable cervical mucus being more than seven in comparison with women not using clomiphene (respective odds ratios 7.90 (95% confidence interval: 4.15-15.00) and 7.50 (1.97-28.60)). Four articles met all criteria for analysis of the effect of exogenous oestrogens on cervical mucus of women being treated with clomiphene. Exogenous oestrogens resulted in improvement of the cervical mucus qualities in these women (odds ratio: 2.87 (1.76-4.69)). CONCLUSION: The influence of clomiphene 50 mg/day on cervical mucus is not significantly unfavourable, unlike the influence of clomiphene 100 and 150 mg/day. Exogenous oestrogen administration improves this cervical mucus. In all patients being treated with clomiphene the cervical mucus qualities should be investigated.

Cervix Mucus↗
PubMed2004

Mucin core protein expression by colorectal mucinous carcinomas with or without mucus hyperplasia.

BACKGROUND: In the categorization of colorectal mucinous carcinomas, much attention has been paid to the amount of extracellular mucin, but little to that of intracellular mucin. Perhaps this factor would be useful in further categorization. METHODS: We estimated the amount of intracellular mucin morphologically, and classified colorectal tumors (tubular adenomas, mucinous carcinomas, and nonmucinous carcinomas) into two categories each, those with and without intracellular mucus hyperplasia. From preliminary results, we chose a range of 50% or more for the ratio of intracellular mucus to the total area of tumor cells for our definition of such hyperplasia. Then, mucin expression in the different categories was examined immunochemically with antibodies to the mucin core proteins MUC1, MUC2, MUC5AC, and MUC6. RESULTS: MUC1 expression was found in none of the 40 adenomas, 8 (17%) of the 48 mucinous carcinomas (with little difference in those with and without mucus hyperplasia), and 4 (16%) of the 25 nonmucinous carcinomas. MUC2 was found in all mucinous carcinomas. MUC5AC was found in 18 (86%) of the 21 mucinous carcinomas with mucus hyperplasia and 18 (90%) of the 20 adenomas with mucus hyperplasia, but in only 9 (33%) of the 27 mucinous carcinomas without mucus hyperplasia, 5 (20%) of the 25 nonmucinous carcinomas, and 2 (10%) of the 20 adenomas without mucus hyperplasia. CONCLUSIONS: Mucinous carcinomas with and without mucus hyperplasia may arise from adenomas with and without mucus hyperplasia, respectively. The amount of intracellular mucin may be a morphologic reflection of the origin of colorectal mucinous carcinomas.

Adenocarcinoma, Mucinous↗
PubMed1990

Impact of methodological factors on sperm penetration into cervical mucus in cattle.

The aim of this study was to investigate the influence of methodological factors on the interaction of bovine spermatozoa and homologous cervical mucus. Cervical mucus was obtained from three cows during estrus. To evaluate the penetration ability of frozen-thawed semen samples of five different bulls, fresh mucus as well as frozen-thawed mucus, stored for 1, 10 or 30 d in liquid nitrogen, were used. Penetration assays were performed at 38 degrees C for 10 min, and the most advanced spermatozoon was located and the distance determined. Semen parameters were examined by a computer-assisted videomicrographic system. Conservation of mucus in liquid nitrogen for up to 30 d did not influence the results of the penetration assay. In contrast, the mucus of individual cows showed significant differences in the migration distance of spermatozoa. Sperm concentration, mean velocity and number of forward moving spermatozoa were significantly correlated with mucus penetration. These results demonstrated that the mucus penetration assay in cattle can be performed by dividing a mucus sample from a cow into many portions and storing the sample in liquid nitrogen.

Journal Article↗
PubMed2002

Regional differences of H+, HCO3-, and CO2 diffusion through native porcine gastroduodenal mucus.

Gastroduodenal mucus may play a critical role in defending the epithelium from luminal acid and in the creation of a microenvironment suitable for H. pylori. We measured transmucus permeation of H+, HCO3-, and CO2 with an in vitro perfusion chamber through freshly harvested or partially purified porcine gastric mucin. pH and CO2 concentrations were measured with selective ion electrodes; HCO3- and CO2 concentrations were derived. Viscosity was measured by rotational microviscometry. Mucin viscosity was directly related to concentration. There was a large variation in viscosity among native mucus from antrum, corpus, and duodenum. The highest viscosity was found in the antral mucus; duodenal mucus had the lowest. Diffusion coefficients of duodenal mucus for H+ and HCO3- were significantly lower than those from corpus and antrum. CO2 diffusion coefficients were invariant. In conclusion, despite large variations in viscosity, antral and corpus gastric mucus were similar in terms of ion diffusion. Surprisingly, the low viscosity duodenal mucus was a more potent barrier to ion diffusion than was gastric mucus. Consequently, duodenal mucus may play a more important role in inhibiting ion diffusion than its gastric counterpart.

Animals↗
PubMed1998

In vitro inhibition of adhesion of enterotoxigenic Escherichia coli K88 to piglet intestinal mucus by egg-yolk antibodies.

The objective of the study was to determine if the adhesion of E. coli K88 to piglet intestinal mucus could be inhibited in vitro by spray-dried egg-yolk anti-K88 antibodies. Binding of E. coli was monitored using a radioactive assay. Four 14+/-2-day-old healthy piglets were used for the preparation of mucus from the small intestine. Competition and displacement phenomena were investigated by incubating (a) egg-yolk antibodies and E. coli together prior to adding to the mucus and (b) E. coli and mucus, followed by egg-yolk antibodies. The results demonstrated that egg-yolk antibodies inhibited the adhesion of 3H-labeled local strain of hemolytic E. coli K88+ (E. coli K88+ MB) to piglet small intestinal mucus by 84.6-97.0% when the egg-yolk antibodies were diluted 10, 20, 40 or 100 times. The adhesion inhibiting effects of egg-yolk antibodies declined dramatically when the antibody dilution was more than 250-fold. A similar adhesion inhibiting effect was observed when egg-yolk antibodies were incubated with E. coli K88+ MB for 15, 30 and 60 min prior to the adhesion test. Egg-yolk antibodies when diluted 50- and 100-fold had a very strong inhibiting ability against E. coli K88+ MB at a concentration of 10(9) colony forming units (cfu) ml(-1) (adhesion was < 6%). However, dilution of 100 times for egg yolk antibodies was insufficient to inhibit the adhesion of E. coli K88+ MB to intestinal mucus when the concentration of E. coli K88+ MB was 10(10) cfu ml(-1). The displacement test indicated that there was no significant reduction in the adhesion of E. coli K88+ MB to the small intestinal mucus when egg-yolk antibodies were added after adhesion of the organism to the mucus. These studies demonstrate that anti-K88+ MB fimbriae antibodies from chicken egg-yolk when added to E. coli K88+ MB prevented their binding to receptors in the mucus isolated from the intestine of piglets.

Animals↗
PubMed1986

Mucus colonization as a determinant of pathogenicity in intestinal infection by Campylobacter jejuni: a mouse cecal model.

Human isolates of the intestinal pathogen Campylobacter jejuni have been shown to colonize mucus on the outer surface and deep within the intestinal crypts of gnotobiotic or germfree mice. The cecal crypts are preferentially colonized. A model of mucus colonization by C. jejuni in the mouse cecum has been developed, using antibiotic- and magnesium sulfate-treated specific-pathogen-free animals. These spiral-shaped bacteria colonize the mucus in a similar manner to the normal spiral-shaped microbiota. No evidence of adhesion to the intestinal surface was found with a wide variety of microscopic techniques. The campylobacters were seen to be highly motile in living preparations of gut tissue and rapidly tracked along intestinal mucus. Just as many of the normal spiral-shaped bacteria of intestinal surfaces can achieve close association with the epithelium through mucus association and do not adhere to the surface, C. jejuni colonizes the intestinal mucosa via mucus colonization. Thus, a major determinant of pathogenicity in intestinal infection with C. jejuni is proposed to be an ability to colonize intestinal mucus. The possession of specific adhesins is unlikely to be a significant determinant of pathogenicity. Better understanding of the mechanism of mucus association and the properties of the bacterium that are responsible will provide a basis for the rational selection of preventative measures. The model of mucus association in adult antibiotic-treated mice provides an opportunity for colonization studies with variant organisms and immunization studies.

Adhesiveness↗
PubMed1989

Binding of Yersinia enterocolitica to rabbit intestinal brush border membranes, mucus, and mucin.

Mucus and its gel-forming glycoprotein component, mucin, are thought to protect the gastrointestinal tract from enteric pathogens by inhibiting their attachment to enterocytes. In this study, we investigated interactions between Yersinia enterocolitica (isogenic strains of virulent and nonvirulent organisms) and crude mucus, highly purified mucin, and brush border membranes (BBMs) isolated from the upper mid-, and distal small intestine and the proximal colon of the rabbit. Adherence of radiolabeled bacteria was assessed to BBMs, mucus, and mucin immobilized in polystyrene microtiter plate wells. Virulent Y. enterocolitica showed saturable binding to mucus, mucin, and BBMs from all four regions of the intestinal tract, although adherence to BBMs was appreciably greater than that to mucus or mucin. Maximal binding of bacteria was higher to BBMs from the distal small intestine and the proximal colon than to those from the upper and mid-small intestine, which may in part explain why the organism localizes to the ileo-caecal regions of the gut. Adherence of virulent Y. enterocolitica to BBMs was significantly reduced in the presence of homologous mucus or mucin preparations. Binding of virulent bacteria appears to depend on plasmid-encoded proteins located on the outer surface membrane, since (i) the isogenic strain lacking the virulence plasmid showed markedly less binding to all BBM, mucus, and mucin preparations; (ii) growth of the virulent strain at 25 degrees C, which inactivates its plasmid, significantly diminished binding to BBMs, mucus, and mucin; and (iii) mild proteolysis substantially decreased adherence of virulent bacteria to BBMs. Compared with rabbit intestinal and colonic mucins, binding of virulent Y. enterocolitica was significantly greater to purified human intestinal mucin and significantly less to rat intestinal mucin. These findings provide support for the role of mucus and mucin in host defense by preventing adherence of virulent Y. enterocolitica to epithelial cell membranes.

Animals↗
PubMed1998

Helicobacter pylori in vivo causes structural changes in the adherent gastric mucus layer but barrier thickness is not compromised.

BACKGROUND: It has been proposed that a pathogenic effect of Helicobacter pylori is a weakening of the protective mucus barrier; however, this remains controversial. AIMS: To clarify the effects of H pylori infection on the mucus gel barrier in vivo. METHODS: Mucus gel polymeric structure and the thickness of the adherent mucus barrier were measured in endoscopic biopsy samples in subjects with and without H pylori infection. RESULTS: There was a significant 18% reduction in the proportion of polymeric gel forming mucin in the adherent mucus layer in H pylori positive compared with negative subjects. There was no change in the adherent mucus thickness between H pylori positive and negative subjects without gastric atrophy (mean (SD): 104 (26) micron, 106 (30) micron, respectively). There was however a significant reduction in mucus thickness in those H pylori positive subjects with underlying gastric atrophy (84 (13) micron, p=0.03) compared with those without atrophy. CONCLUSIONS: A partial breakdown in gel forming structure of the gastric mucus barrier does occur in H pylori infection per se but this is insufficient to cause a collapse of the mucus barrier.

Aged↗
PubMed2005

Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin.

Secretion of bicarbonate into the adherent layer of mucus gel creates a pH gradient with a near-neutral pH at the epithelial surfaces in stomach and duodenum, providing the first line of mucosal protection against luminal acid. The continuous adherent mucus layer is also a barrier to luminal pepsin, thereby protecting the underlying mucosa from proteolytic digestion. In this article we review the present state of the gastroduodenal mucus bicarbonate barrier two decades after the first supporting experimental evidence appeared. The primary function of the adherent mucus gel layer is a structural one to create a stable, unstirred layer to support surface neutralization of acid and act as a protective physical barrier against luminal pepsin. Therefore, the emphasis on mucus in this review is on the form and role of the adherent mucus gel layer. The primary function of the mucosal bicarbonate secretion is to neutralize acid diffusing into the mucus gel layer and to be quantitatively sufficient to maintain a near-neutral pH at the mucus-mucosal surface interface. The emphasis on mucosal bicarbonate in this review is on the mechanisms and control of its secretion and the establishment of a surface pH gradient. Evidence suggests that under normal physiological conditions, the mucus bicarbonate barrier is sufficient for protection of the gastric mucosa against acid and pepsin and is even more so for the duodenum.

Animals↗
PubMedDate not supplied

Effects of omeprazole on rat gastric mucus glycoproteins with acetylsalicylic acid-induced gastric damage.

Investigations were carried out to determine the effects of omeprazole on mucus glycoprotein in rat gastric mucosa. Quantitative and qualitative changes in mucus glycoprotein, isolated from omeprazole-treated rats with or without acetylsalicylic acid-induced gastric damage, and the degree of gastric mucosal injury were studied. Omeprazole, in a dose-dependent manner, prevented macroscopical mucosal damage induced by acidified acetylsalicylic acid. A considerable decrease in corpus mucus glycoprotein (54%) and antral mucus glycoprotein (72%) was observed in acetylsalicylic acid-treated rats and acetylsalicylic acid reduced the amounts of fucose and galactose of corpus mucus glycoprotein. Pretreatment with omeprazole partially restored a quantitative reduction and a qualitative change of carbohydrate portion in corpus mucus glycoprotein induced by acetylsalicylic acid. A single administration of a high dose of omeprazole (200 mumol/kg) also induced the reduction of corpus mucus glycoprotein content (82%), although no changes in the carbohydrate component were observed. The decrease in corpus mucus glycoproteins induced by omeprazole might be due to a cause different from that of acetylsalicylic acid-induced mucus glycoprotein reduction.

Animals↗
PubMed1981

A review of cervical mucus and sperm interactions in humans.

Cervical mucus is an aqueous or gel mixture of fluids, ions and compounds, and cells, primarily produced by the endocervical epithelium. The amount secreted varies with menstrual phase and compositions changes under hormonal influence. Sodium shows the greatest concentration change at ovulation but does not change early enough to be of value in natural family planning practice. Dried mucus has a fern appearance due to NaCl crystals at ovulation. Other substances, less clearly related, are too difficult to analyze or in too low concentration. Soluble proteins, amino acids, and simple sugars show wide fluctuation and probably influence sperm penetration and nutrition. One function of mucus is antimicrobial activity of leukocytes, which decreases at midcycle. Another, sperm transport, is a function of estrogen's effect on mucus rather than ovulation. Sperm concentration in the mucus column is maximal from 15 minutes to 2 hours after vaginal deposition. Rapid penetration into cervical mucus favors sperm survival because of its optimal pH. Infertility may be caused by immunoglobulins or spermagglutinins in cervical mucus. To date, no constituent of cervical mucus has been identified which undergoes an easily detectable change 4 days before ovulation. Several potential methods for use in natural family planning are suggested.

Cervix Mucus↗
PubMed1982

Human ocular mucus. Scanning electron microscopic study.

Twenty biopsy specimens of the human conjunctival epithelial surface with its associated mucus from normal subjects and contact lens wearers with biomicroscopic evidence of excess mucus were studied by scanning electron microscopy. Mucus existed in strands, sheets, and granules; each morphologic type of mucus was observed in all samples. No qualitative difference in morphologic features of mucus was found between normal subjects and those with excess mucus. Mucous forms observed by scanning electron microscopy closely resembled structures previously shown by biomicroscopic and light microscopic techniques, providing evidence that careful scanning electron microscopic preparation of biopsy specimens containing mucus may not greatly alter in situ morphologic characteristics of mucus.

Conjunctiva↗
PubMed2001

Mucus hypersecretion in chronic obstructive pulmonary disease.

Most patients with chronic obstructive pulmonary disease (COPD) exhibit characteristics of airway mucus hypersecretion, namely sputum production, increased luminal mucus, submucosal gland hypertrophy and goblet cell hyperplasia. The clinical consequences of hypersecretion are impaired gas exchange and compromised mucociliary clearance, which encourages bacterial colonization and associated exacerbations. However, the extent of the contribution of mucus to pathophysiology of COPD is controversial. Early epidemiological studies found little evidence for the involvement of mucus in the age-related decline in lung function and mortality associated with COPD and concluded that chronic airflow obstruction and mucus hypersecretion were independent processes. Later studies found positive associations between phlegm production and decline in lung function, hospitalization and death. Thus, although not diagnostic for the condition, mucus hypersecretion contributes to morbidity and mortality in certain groups of patients with COPD. This suggests that it is important to develop drugs that inhibit mucus hypersecretion in these patients. Unfortunately, ambiguity in clinical studies of mucoactive drugs means that mucolytics are not recommended in clinical management. Future research should determine whether there is an intrinsic abnormality in mucus in COPD, which will determine development of appropriate inhibitors, which in turn can be used in 'proof of concept' and in treatment.

Humans↗
PubMed1984

Some non-mucin components of mucus and their possible biological roles.

Non-mucin components have essential roles in the protective functions of mucous secretions. Secretory IgA (SIgA) antibodies probably act by blocking the attachment of pathogenic microorganisms to mucosal cells. In addition SIgA1 may render bacteria more 'mucophilic', possibly by virtue of the 'mucus-like' stretch that the immunoglobulin molecule possesses. Lysozyme will attack cell walls of susceptible bacteria. As the enzyme associates strongly with mucus glycoproteins the mucus layer is provided with powerful bactericidal properties. Lactoferrin, normally unsaturated, sequesters any free iron in secretions, so exerting a bacteriostatic action on iron-requiring microorganisms. In addition it may protect mucus glycoproteins from iron-catalysed active oxygen species. This mucoprotective action would be overcome during infections. Attention is also directed towards a possible copper-mediated limited degradation by hydrogen peroxide. Surfactants and free lipid have long been recognized as components of normal bronchial mucus. For example, some lipid is tightly but non-covalently bound to a hydrophobic region of bronchial mucin. More intriguing is the presence of small amounts of covalently bound lipid in normal human gastric mucin. In addition, normal human gastric mucus contains significant amounts of a galactose-rich polysaccharide. The function of this is not known but it may act as a cross-linking strand in the mucus gel structure or as a renewable cell membrane component, perhaps interacting between glycocalyx and the mucus layer.

Gastric Mucosa↗
PubMed1996

Adhesion of Lactobacillus fermentum 104-S to porcine stomach mucus.

The adhesion to whole and fractionated porcine gastric mucus of both Lactobacillus fermentum 104-S cells and a saccharide extracted from this strain was investigated. It has been shown previously that this saccharide had affinity for nonsecreting gastric epithelium. The mucus component(s) with affinity the bacterial cells was partly characterized by gel filtration and treatment with protease or metaperiodate. L. fermentum 104-S extracts containing the saccharide were radioactively labeled, fractionated by gel filtration, and tested for affinity for the gastric mucus component showing receptor activity for the whole cells of strain 104-S. The mucus material with affinity for the bacterial cells had a relative molecular weight of 30-70 K. From the results of treatment with protease or metaperiodate, it is proposed that the mucus components(s) that adhered to the whole bacterial cells contained glycoprotein groups. The radioactively labeled saccharide extracted from L. fermentum 104-S cells did not bind to the mucus fraction that had affinity for the whole cells. Conclusively, we suggest that the mechanism by which cells of L. fermentum 104-S adhere to the gastric mucus is different from the mechanism mediating the adhesion of this strain to the nonsecreting gastric epithelium. Cells of L. fermentum 104-S adhere to a glycoproteinaceous mucus component with a relative molecular weight of 30-70 K.

Animals↗