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The high-risk α-type papillomaviruses have a C-terminal PDZ-binding motif (PBM) on one of the two major oncoproteins E6 or E7; the vast majority on E6. The PBM is essential for the high-risk HPV life cycle, for episomal maintenance of the virus genome, and for maintaining the mitotic stability of the infected cell. The question is why only these viruses have PBMs - are there specific constraints imposed by the mucosal epithelium in which these viruses replicate? However the low-risk α-HPVs, such as HPV-6 and HPV-11 replicate extremely efficiently without a PBM, while viruses of the alpha8 group, such as HPV-40, replicate well with a very primitive PBM. So what does PDZ-binding capacity contribute to the fitness of the virus?

Background Nattokinase (NK) is a promising alternative in the prevention and treatment of cardiovascular diseases due to its potent fibrinolytic activity. In this study, we investigated the effect of crude nattokinase extract on the healing of acetic acid-induced oral mucositis in mice. Methods Bacillus subtilis culture media (BSCM) was isolated into the supernatant, named nattokinase crude extract (NCE), and the pellet was named Bacillus subtilis mass (BSM). An oral mucositis model was established in mice by applying 50% glacial acetic acid to the buccal mucosa. According to the treatment conditions, the mice were divided into BSCM, NCE, BSM and phosphate buffered saline (PBS) groups. The weight of the mice, oral mucositis healing score and histopathological examination were used to evaluate the treatment. Results Fibrinolytic activities of BSCM, NCE and BSM were approximately 8069, 10,800 and 80 U/ml, respectively. The weight gain of mice in the NCE group was significantly different from the PBS group after three days’ treatment (p p p Conclusions NCE could possess remarkable potential to reduce pain and promote oral mucositis healing with minimal safety concerns. In this study, we first report that NCE from the supernatant of Bacillus subtilis can promote the healing of oral mucositis, which extends the application scope of NK.

Chronis rhinosinusitis is considered as a widespread public health issue with a prevalence of 10%. The disease significantly reduces quality of life and increases the risk of cardiovascular diseases as well as certain forms of cancer. Alteration of mucociliary clearance frequently observed in the patients and plays a significant role in disease pathogenesis. Certain studies have demonstrated that patients with chronic rhinosinusitis are characterized by significant reduction of essential trace elements and toxic metal overload. However, the particular mechanisms of the role of trace element dysbalance in chronic rhinosinusitis are unclear. We hypothesize that exposure to toxic trace elements (arsenic, nickel, cadmium) damages ciliary mucosal epithelium thus affecting mucociliary transport. In turn, altered mucociliary transport results in reduced removal of the inhaled metal-containing particles from nasal mucosa leading to their absorption and further aggravation of toxicity. Essential trace elements (zinc, selenium) play a significant role in regulation of mucociliary transport and immunity, thus their deficiency (either dietary or due to antagonism with toxic metals) may be associated with impaired functions and increased toxic metal toxicity. Therefore, a vicious circle involving metal accumulation and toxicity, essential element deficiency, impairment of mucociliary transport and metal particle removal, resulting in further accumulation of metals and aggravation of toxic effects is formed. The present hypothesis is supported by the findings on the impact of trace elements especially zinc and arsenic on mucociliary clearance, the role of mucociliary transport in heavy metal particles elimination from the airways, trace element dysbalance in chronic rhinosinusitis, as well as toxic and essential metal antagonism. The data from hypothesis testing and its verification may be used for development of therapeutic approach for management of chronic rhinosinusitis. Particularly, the use of essential elements (zinc, selenium) may reduce toxic metal toxicity thus destroying the vicious circle of heavy metal exposure, toxicity, alteration of mucociliary clearance, and aggravation of chronic rhinosinusitis. Essential element supplementation may be considered as a tool for management of chronic refractory rhinosinusitis. In addition, analysis of essential and toxic trace element status may provide an additional diagnostic approach to risk assessment of chronic rhinosinusitis in highly polluted environments.

Transplantation of the autologous cultured corneal limbal epithelium and oral mucosal epithelium is a standard technique for ocular surface reconstruction under corneal limbal stem cell deficiency. As an option for bilateral cases, we recommend utilization of autologous conjunctivae for ocular surface reconstruction. Autologous conjunctival epithelium sheet transplantation was effective for bilateral corneal limbal stem cell deficiency without symblepharon or severe keratinization. Moreover, we established a feeder-free and serum-free culture system of the limbal epithelium. This system can be applied for culturing conjunctival epithelia. Autologous cultured conjunctival epithelium transplantation is a practical option for treating bilateral corneal limbal stem cell deficiency.

Sucralfate is effective for the treatment of gastric and duodenal ulcers owing to its protective gel-forming ability. However, the mechanism by which sucralfate protects the oesophageal mucosa against reflux oesophagitis has not been clarified. We aimed to investigate the mechanisms of action of sucralfate and sucrose octasulfate (SOS), a component of sucralfate. SOS and sucralfate were administered to oesophagitis-induced rats, and the ulcer lesion size was macroscopically examined and scored. Effective pepsin activity in the gastric juices obtained from the animal model was evaluated by a casein digestion test. Sucralfate and SOS improved the pathology scores in a dose-dependent manner, whereas gastric juice pepsin activity was not impaired by therapeutic doses of SOS. As SOS lacks the ability to form a thick gel layer by polymerisation, we examined the distribution of SOS in the mucosal lumen by imaging mass spectrometry (IMS) to determine whether SOS directly adheres to the mucosal surface. A clear homogeneous thin-layer SOS film (>100 μm thick) was visualized on the oesophageal mucosal surface. Moreover, this SOS film formation was enhanced at ulcer lesion sites. Taken together, SOS appears to protect oesophageal mucosa against reflux oesophagitis via thin-layer formation on the mucosal surface.

The present study was designed to envisage the antigiardial efficacy of killed probiotic and probiotic protein (PP) of Lactobacillus rhamnosus GG in murine giardiasis. Experimentally, it was observed that animal administered either with probiotic protein emulsified with adjuvant (PP(E) + Giardia) or killed probiotic (killed probiotic (i/p) + Giardia) had significantly reduced Giardia cycle with respect to observed severity and duration of giardiasis compared with Giardia-infected mice. Further, it was found that animals belonging to PP(E) + Giardia and killed probiotic (i/p) + Giardia had significantly high levels of antigiardial IgA antibody and nitric oxide both in serum and in intestinal fluid compared with Giardia-infected and counter control mice. Histopathologyically, also animals belonging to PP(E) + Giardia and killed probiotic (i/p) + Giardia animals had intact mucosal epithelium lining, basal crypts, and normal villi along with increased goblet cells compared with severe microvillus atrophy, vacuolated epithelial cells, and ileitis in Giardia-infected mice. This is the first-ever study to demonstrate that prior administration of either killed probiotics or probiotic protein of effective probiotic reduced both the severity and the duration of giardiasis mainly by modulating the gut microbiome and morphology along with mucosal immunity, but animals belonging to PP(E) + Giardia had better response than killed probiotic (i/p) + Giardia suggesting that probiotic components do have adjuvant potential and may be used as the vaccine candidate for gastrointestinal diseases.

Mucosal epithelium maintains tissue homeostasis through many processes, including epithelial barrier function, which separates the environment from the tissue. The barrier hypothesis of type 2 inflammatory disease postulates that epithelial and epidermal barrier dysfunction, which cause inappropriate exposure to the environment, can result in allergic sensitization and development of type 2 inflammatory disease. The restoration of barrier dysfunction once it's lost, or the prevention of barrier dysfunction, have the potential to be exciting new therapeutic strategies for the treatment of type 2 inflammatory disease. Neutrophil-derived Oncostatin M has been shown to be a potent disrupter of epithelial barrier function through the induction of epithelial-mesenchymal transition (EMT). This review will discuss these events and outline several points along this axis at which therapeutic intervention could be beneficial for the treatment of type 2 inflammatory diseases.

Microplastic (MP) vector effects have been well described in the literature but surprisingly little is in known about the impact of MPs on the intestinal uptake of contaminants. The present study aimed to determine whether the intestinal fate of Ag was affected by the presence of polyethylene MP beads. Ag (added as 110mAg) was introduced into the lumen of rainbow trout (Oncorhynchus mykiss) anterior/mid-intestine gut sac preparations as Ag only, Ag and MPs (co-exposure) and Ag-incubated MPs (where Ag was adsorbed to the MP). Results show that after 3 h exposure the distribution of accumulated Ag between the four intestinal compartments (mucus layer, mucosal epithelium, muscle layer and serosal saline) was not affected by either MP condition when compared to Ag alone (p > 0.05, One way ANOVA). Across all treatment groups mucus layer binding dominated (54.2–72.6%) whereas relatively little Ag was transported to the blood compartment (i.e. combined muscle layer and serosal saline compartments, 8.5–15.0%). Accompanying adsorption/desorption studies were performed in relevant media. Over 24 h, 60.6± 2.9% of the available Ag in artificial freshwater adhered to the surface of the PE MPs. In pH adjusted luminal fluids (pH 2.2, 4.1, 7.4 and 9.8) that span the range of conditions encountered within the rainbow trout digestive tract, there was almost complete dissociation at acidic pHs within 3 h (

Most pathogens invade body through the mucosal epithelium, which is a primary target to prevent the infectious diseases. Mucosal vaccine has been considered to be an effective strategy to establish immunosurveillance against pathogens by the induction of antigen-specific immune responses at both mucosal and systemic immune compartments. The development of antigen delivery system and mucosal adjuvants are required for the sufficient induction of protective immunity in the development of mucosal vaccine. In this review, we shed light on the recent advances in the development of antigen delivery system using microbial functions for mucosal vaccines.

Mucosal barriers encounter an environment that is rich in pathogens that possess mechanisms for invading mucosal tissues. These barriers also encounter innocuous antigens, such as foods, airborne antigens, and microbiota. The mucosa has developed a sophisticated immune system that can mount robust immune responses against pathogenic antigens, while maintaining mucosal tolerance against non-pathogenic antigens. Accumulating evidence indicates that the mucosal epithelium, dendritic cells, and a subtype of T cells with regulatory properties play important roles in the development and maintenance of mucosal tolerance. Moreover, the micribiota also contribute to regulating the mucosal immune system. A failure to develop or the breakdown of mucosal tolerance can result in allergic diseases, such as food allergy and asthma. By taking advantage of the unique characteristics of the mucosal immune system, strategies that induce regulatory cells in vivo and, thereby, reconstitute mucosal tolerance may be used to develop novel therapies that are suitable for treating or preventing of allergic diseases.

Mucosal epithelial cells express an autonomous innate immune response that controls the overgrowth of invaded bacteria, mitigates the harmful effects of the bacteria carried within, and does not rely on other external arms of the immune response. Epithelial cell autonomous innate immunity "respects" the social biology of invading bacteria to achieve symbiosis, and is the primary protective mechanism against pathogens.

Buccal delivery of the desired drug using mucoadhesive polymers has been the subject of interest since the early 1980s. Advantages associated with buccal drug delivery have rendered this route of administration useful for a variety of drugs. This review highlights the use of mucoadhesive polymers in buccal drug delivery. Starting with a review of the oral mucosa, mechanism of drug permeation, and characteristics of the desired polymers, this article then proceeds to cover the theories behind the adhesion of bioadhesive polymers to the mucosal epithelium. Additionally, we focus on the new generation of mucoadhesive polymers such as thiolated polymers, followed by the recent mucoadhesive formulations for buccal drug delivery.

We previously reported that a loss of contraction in the mucosal tissue of the palate arch is effectively induced by ethanol injections of moderate concentration and dosage. The present study was performed to obtain more information on how such ethanol injections induce contraction loss in mucosa tissue. Guinea pigs of both sexes were used in this study. The left arch of the palate mucosa was injected with 2 microliters of 70% ethanol and used as the experimental group. The right arch of the palate mucosa of the same animal was injected with saline and used as a control. One, three, five, eight, 10, 30, 50, and 90 days after injection, the mucosal tissues that received the injection were resected under anesthesia and processed for light microscopy using standard procedures. One day after the ethanol injection, severe coagulative degeneration of the mucosal tissue of the palate was seen. However, the damaged area was strictly restricted to the arch of the palate. Coagulative degeneration of the tissue peaked three days after the injection. Thereafter, the mucosal epithelial and mucosal connective tissues regenerated, and the damaged mucosal tissue quickly began to repair. An apparent cicatricial contraction loss was observed 10 days after the ethanol injection, along with the progression of fibrotic changes in the submucosal connective tissue of the arch of the palate. The regenerative action of the mucosal arch of the palate abated 30 days after the ethanol injection, and the reduced mucosal tissue appeared to have become denser as a result of an increase in dense fibrous connective tissue in the submucosal layer. No cell malignancies were seen throughout the entire 90-day observation period. In conclusion, cicatricial contraction loss of the mucosal arch of the palate resulting from the injection of an appropriate concentration and dosage of ethanol leads to the regeneration of the mucosal epithelium and fibrotic changes in the submucosa. The ethanol injection described here seems to be extremely safe, since it exerted no malignant effects on the cells and tissues either morphologically or functionally.

The influence of epithelial damage on mucociliary transport was studied in relation to the amount of mucus. The mucosal epithelium of mucus-depleted frog palate was dissected and mounted on a plastic plate. Mechanical damages were created on the frog mucosa by pressing a different thickness of boards (2, 3, 5, and 8 mm). Two different amounts of frog mucus (7.9 L [small amount of mucus {S-mucus}]) and 51.0 L [large amount of mucus {L-mucus}])were applied on the frog mucosa with and without mucosal damage. There was no difference in mucociliary transport rate (MTR) on undamaged frog mucosa between S-mucus and L-mucus. However, on the damaged mucosa, MTR of S-mucus was significantly decreased compared with that of L-mucus. Moreover, capability of mucus transportation across the mucosal damage was significantly lower in S-mucus than in L-mucus. Results indicate that the larger the mucus amount becomes, the more the mucus travels the damaged epithelium. Moreover, MTR of L-mucus was decreased with increasing the degree of epithelial damage. This study indicates that the degree of loss of cilia is an important factor of mucociliary deceleration. (American Journal of Rhinology 16, 215–219, 2002)

The reliability of methods for nutrient uptake measurements across the intestinal epithelium relies on the integrity of the mucosal epithelium and the enterocytes. We tested effects of tissue handling during the "everted sleeves method" on the length of intestinal villi, the surface magnification, the circumference of the gut, and the thickness of the muscle layer in sunbirds (Nectarinia osea), chicken (Gallus gallus), and mice (Mus domesticus). The sunbird has thin and delicate intestinal villi that are greatly affected by the everted sleeves method. After eversion and incubation, villi lost 30% of their original length. The severe tissue damage coincides with uptake measurements for glucose that were an order of magnitude lower than in other nectar-feeding (nectarivorous) birds of similar body size. Tissue handling during the everted sleeves method had significant effects on morphometric parameters of chicken and mouse intestines, but on a light-microscopical level, the tissue integrity and the cytology of the enterocytes were not altered. Therefore, we think that the everted sleeves method renders reliable and reproducible measurements of nutrient uptake in those species. We conclude that a histological evaluation is necessary to assess the reliability of the method before it is applied to adults or to the developmental stage of any species.

Gastrointestinal disorders are a major cause of morbidity in the elderly population. The gastrointestinal tract is the most complex organ system; its diverse cells perform a range of functions essential to life, not only secretion, digestion, absorption and excretion, but also, very importantly, defence. The gastrointestinal tract acts not only as a barrier to harmful materials and pathogens but also contains the vast number of beneficial bacterial populations that make up the microbiota. Communication between the cells of the gastrointestinal tract and the central nervous and endocrine systems modifies behaviour; the organisms of the microbiota also contribute to this brain–gut–enteric microbiota axis. Age-related physiological changes in the gut are not only common, but also variable, and likely to be influenced by external factors as well as intrinsic aging of the cells involved. The cellular and molecular changes exhibited by the aging gut cells also vary. Aging intestinal smooth muscle cells exhibit a number of changes in the signalling pathways that regulate contraction. There is some evidence for age-associated degeneration of neurons and glia of the enteric nervous system, although enteric neuronal losses are likely not to be nearly as extensive as previously believed. Aging enteric neurons have been shown to exhibit a senescence-associated phenotype. Epithelial stem cells exhibit increased mitochondrial mutation in aging that affects their progeny in the mucosal epithelium. Changes to the microbiota and intestinal immune system during aging are likely to contribute to wider aging of the organism and are increasingly important areas of analysis. How changes of the different cell types of the gut during aging affect the numerous cellular interactions that are essential for normal gut functions will be important areas for future aging research.

We investigated morphological changes after transplantation of cultured mucosal epithelium using a modified Barrandon's method (1988). Serially cultivated human mucosal epithelium was transplanted onto the reverse side of rectangular dorsal skin flaps in hairless mice. The morphological changes in the epithelium were studied using paraffin sections. The modified Barrandon's method used in this study has advantages such as minimum external trauma and less chance of infection. The cultured epithelium was taken within 1 week and gradually increased its epithelial thickness. Keratinized epithelium arises after 3 weeks. At 4 weeks after grafting, the grafted epithelium comprised 7-10 cell layers. The structure of transplanted tissue, in conjunction with surrounding connective tissues, showed dermis-like features at day 7 after transplantation. From these results, it was confirmed that cultured mucosal epithelium could be successfully transplanted and its morphology was similar to that of normal mucosal tissue.

Prosthogonimus ovatus infection was detected in 5 of 130 chickens in the oviduct and 4 chickens in the bursa of Fabricius. Scanning electron microscopy (SEM) revealed that the spines of the P. ovatus were densely distributed on the cuticula of the entire dorsal surface of body, but on the ventral surface, they were densely present to the level of ventral sucker but gradually decreased in density posteriorly, and they could not be seen in the posterior 1/3 area. The spines were finger-shaped and denticulate at the tip. Histopathological examination showed that polypous elevations, degeneration and exfoliation of the mucosal epithelium were detected in the bursa of Fabricius possibly by the suction of flukes, in addition to the stratification of the mucosal epithelium, and interstitial cell infiltration.

Rabbits are born blind and deaf and receive unusually limited maternal care. Consequently, their suckling young heavily rely on the olfactory cue for nipple attachment. However, the postnatal morphofunctional adaptations of olfactory mucosa (OM) are not fully elucidated. To clarify on the extent and the pattern of refinement of the OM following birth in the rabbit, morphologic and morphometric analysis of the mucosa were done at neonatal (0-1 days), suckling (2 weeks), weanling (4 weeks), and adult (6-8 months) stages of postnatal development. In all the age groups, the basic components of the OM were present. However, proliferative activity of cells of the mucosal epithelium decreased with increasing age as revealed by Ki-67 immunostaining. Diameters of axon bundles, packing densities of olfactory cells, and cilia numbers per olfactory cell knob increased progressively with age being 5.5, 2.1, and 2.6 times, respectively, in the adult as compared with the neonate. Volume fraction values for the bundles increased by 5.3% from birth to suckling age and by 7.4% from weaning to adulthood and the bundle cores were infiltrated with blood capillaries in all ages except in the adult where such vessels were lacking. The pattern of cilia projection from olfactory cell knobs also showed age-related variations, that is, arose as a tuft from the tips of the knobs in neonates and sucklings and in a radial pattern from the knob bases in weanlings and adults. These morphological changes may be attributed to the high olfactory functional demand associated with postnatal development in the rabbit.

Immunohistochemical characterizations of motilin-immunoreactive cells were examined in gastric and duodenal mucosae of nine species of birds from seven orders using five different region-specific motilin antisera. Motilin-immunoreactive cells appeared as open-type cells in the mucosal epithelium and showed varying immunoreactivities to antisera used in all the birds examined except for the cormorant and penguin, which did not show any kinds of immunoreactivity to motilin. Motilin-immunoreactive cells of the emu duodenum were detected by all the motilin-antisera used. The present results suggest that there is a wide range of heterogeneity between motilin molecules among avian species, or perhaps alternatively the existence of a family of motilin-like peptide. Furthermore, the present results should prove useful for a molecular biological study on the evolution of avian motilin.

We describe a case of zoonotic anatrichosomiasis in a patient from Illinois. A 44-year-old immigrant from Mexico originally presented with a history of multiple oral ulcers and two submucosal nodules on the dorsal surface of the tongue. An incisional biopsy was taken to assist with diagnosis. Examination of stained sections revealed the presence of a coiled nematode. The histologic examination displayed trichuroid features. Anatomic structures that aided in the identification included esophagus embedded in a prominent stichosome in the anterior end, paired bacillary bands, and small size. The location of the worm within the oral mucosal epithelium also facilitated the diagnosis.

SUMMARY Passerine birds migrating long distances arrive at stopover sites to refuel having lost as much as 50% of their initial body mass (mb), including significant losses to digestive organs that may serve as a reservoir of protein catabolised for fuel during flight. Birds newly arrived at a stopover show slow or no mb gain during the initial 2–3 days of a stopover, which suggests that energy assimilation may be limited by reduced digestive organs. Measurements of migrants and captive birds subjected to simulated migratory fasts have shown reductions in intestine mass, morphological changes to the mucosal epithelium, and reductions in food intake and assimilation rate upon initial refeeding. We found that blackcaps (Sylvia atricapilla, Linnaeus) newly arrived at a migratory stopover after crossing the Sahara and Sinai deserts had significantly increased paracellular nutrient absorption (non-carrier mediated uptake occurring across tight junctions between enterocytes) that may provide partial compensation for reduced digestive capacity resulting from changes to intestinal tissues. Indeed, newly arrived birds also had a slightly reduced capacity for absorption of a glucose analogue (3-O-methyl-d-glucose) transported simultaneously by both carrier-mediated and non-mediated mechanisms. Increased paracellular absorption coupled with extended digesta retention time may thus allow migratory blackcaps to maintain high digestive efficiency during initial stages of refuelling while digestive organs are rebuilt.

In rats, we examined the effect of an omentum wrapping on the vascularization of the trachea and on regeneration of the mucosal epithelium in the very early stage after free tracheal grafting. Two pieces of trachea were obtained from each donor rat. One piece was transplanted into the peritoneal cavity of the recipient rat and wrapped with omentum. The other piece was transplanted subcutaneously into the abdominal wall, without omentopexy. Recipients were sacrificed at random on days 1, 2, 3, and 4 after operation (5 rats/day). The increase of blood vessels rose significantly earlier in the omentopexy tracheas than in those without omentopexy (p less than 0.01), with all the former showing a normal ciliated, columnar epithelium in the membranous region of the trachea on day 4, accompanied by excellent epithelial regeneration in the cartilaginous region. These results suggest that omentopexy causes revascularization to occur earlier and to be completed in a shorter time, and that it also promotes epithelial regeneration following free tracheal grafting.

1. 1. The cloacal and bucco-pharyngeal regions of three species of Australian freshwater turtles were experimentally compared for their ability to take up radiocalcium directly from the aquatic medium. 2. 2. The cloacal route was at least 4 times more important than the bucco-pharyngeal route for radiocalcium uptake, in each of the three species investigated. 3. 3. Histological examination of anatomical regions in the cloaca showed that the cloacal bursae of three species (E. dentata, C. longicollis and E. signala) had abundant villi and infolded mucosal epithelia that increase the surface area of the epithelium exposed to the aquatic medium. 4. 4. Electron microscoplc studies on the mucosal epithelium of the cloacal bursae showed that it contained many structural characteristics indicative of an exchange function and consistent with the cloacal bursae being an important site of radiocalcium uptake within the cloaca.

To clarify the functions of the equine guttural pouch, the distribution of various immunoglobulin isotypes and subisotypes in the guttural pouch mucosa were examined in healthy horses. IgGa was present in the mucosa of guttural pouch, mucosal lymph nodules and submucosal lymph nodules. IgM was scattered in the mucosal lymph nodules and in the germinal centers of the submucosal lymph nodules. IgGc was recognized only in the submucosal lymph nodules. These immunoglobulin isotypes and subisotypes were found in lymphocytes and plasma cells. On the other hand, IgA was detected in glandular epithelial cells and the surface layer of the mucosal epithelium, as well as in free cells. This finding suggests that IgA is secreted through the glandular epithelium. Based on the above findings, we conclude that the guttural pouch has phylactic ability.

The paper presents a comparison of the microscopic structure and morphometric traits of gustatory and mechanical lingual papillae in newborn and adult frugivorous Egyptian fruit bats (Rousettus aegyptiacus). All of the four types of lingual papillae found in adult animals were observed on the tongue surface in the newborn Egyptian fruit bats. After the birth, the gustatory papillae (fungiform and vallate papillae) were especially well-developed, as their structural characteristics, such as morphology of the epithelium and presence of the taste buds, indicate that they have reached almost complete functional traits. Mechanical papillae, particularly filiform papillae, in newborns are still fetal in character. Keratinization processes in the epithelium of these papillae are not advanced and specific structures, such as elongated processes, are missing. The morphometric analysis of the size of papillae and thickness of the mucosal epithelium showed that a complete development of keratinized structures in Egyptian fruit bats occurs at later stages of postnatal development.

Bioartificial mucosa can be fabricated with living cells in vitro and used for mucosal grafting. In this report, we describe our culturing methods for preparation of bioartificial mucosa and its morphological characteristics. Bioartificial mucosa has bilayered components, namely, mucosal epithelium and submucosal tissue. Submucosal tissue was composed of fibroblasts and type I collagen lattice. Mucosal epithelium was formed by an epithelial segment grafted on the submucosal tissue surface. Between epithelial and submucosal tissues, basement membrane was observed under a transmission electron microscope. In animal experiments, the bioartificial mucosa was well vascularized and survived completely without immunological rejections. Based on the findings from these animal experiments, we applied this bioartificial mucosa to humans and succeeded in reconstructing their mucosal defects. We also present an overview of the problems relevant to the use of such methods.

Although effectiveness of photodynamic therapy (PDT) after application of 5-aminolevulinic acid ointment to oral mucosal lesions has been reported, a consensus regarding recontact time of ALA applied to a lesion has been unreached. Hence, we determined the contact time of ALA required for protoporphyrin IX (PpIX) production efficient for full-blown PDT reaction. ALA ointment was topically applied to healthy rabbits’ tongues for different periods and then washed out. On the surface of the tongue, 10-min contact of ALA maximized the PpIX-derived fluorescence. PpIX yield in a tissue specimen with 10-min contact of ALA reached 73% of that in a tissue specimen with 240-min contact. Histological observation showed that PpIX accumulation predominated in the basal layer, and the PDT effects were confined in the mucosal epithelium regardless of contact time. These results suggest that 5-aminolevulinic-acid-ointment-mediated PDT with short contact of ALA is potentially applicable for treating tongue epithelial lesions.

The aim of this study was to use immunohistochemistry with morphometry to investigate COX-1 and COX-2 expression in the normal rat gastrointestinal (GI) tract and examine if sites of ulceration previously observed with long-term COX-2 inhibitor administration in mice correlate with differential COX-1/COX-2 expression. COX-2 positive cells were observed predominantly in the apical lamina propria of intestinal villi with fewer cells in the mucosal epithelium. The highest level of COX-2 expression was observed at the ileocaecal junction (ICJ). COX-2 expression was also present in parasympathetic ganglia of the submucosa and muscularis. In the stomach, the highest grade of COX-2 expression was observed in the apical lamina propria of the fundus adjacent to the junctional ridge. In contrast, COX-1 positive cells within the lamina propria were evenly distributed along the GI tract but were present in higher numbers than COX-2 positive cells. The mean level of COX-1 expression at the ICJ was not significantly different from the ileum and caecum. Evidence that the highest level of COX-2 expression in normal rats is located on the ileal side of the ICJ provides the first mechanism to explain spontaneous ulceration and perforation of the distal ileum in COX-2−/− animals.

Small bowel is one of the organs that can in principle be transplanted. Optimum preservation of the organ is essential for the success of transplantation. The aim of the present study is the investigation of time-related morphological changes of rat small bowel during preservation in hypothermic Euro-Collins (EC) and Ringer's lactate (RL) solution using light microscopy and transmission electron microscopy to evaluate the integrity of intercellular complexes of mucosal epithelium, one of the tissues of the intestine that is most susceptible to ischemia. Small bowels were perfused with either EC, RL solution or physiological saline solution and were placed in the different preservation solutions at 4°C for 0, 3, 6 and 12 h. The results of our study suggest that both preservation solutions are suitable for short-term preservation of the small bowel although RL solution is more effective than EC solution. However, we conclude that further improvement of preservation solutions and/or techniques are needed to perform long-term preservation.

Contents A reservoir of sperm in the initial segment of the oviduct has been found in several species of domestic and laboratory mammals. Evidently, the reservoir serves to ensure successful fertilization by providing the appropriate number of sperm in the appropriate physiological state for fertilizing oocytes soon after they enter the oviduct. Recent evidence indicates that sperm are trapped in the reservoir by binding to specific carbohydrate moieties on the surface of the mucosal epithelium of the oviduct. A bovine seminal plasma protein has been identified that associates with sperm and confers on them the capacity to bind to the carbohydrate moiety.

The developing lung of the brushtail possum, Trichosurus vulpecula, was studied by light microscopy, and transmission electron microscopy was used to study the morphology of the conducting airways in the adult. Bronchi did not extend beyond the hilus of each of the six lobes of the lung, and lobules were supplied by major bronchioles. By 105 days post partum, bronchi and bronchioles were fully formed, coinciding with the emergence of mucosal associated lymphoid tissue (MALT), which preceded alveolar maturation by approximately 20 days. In the adult lung, goblet cells were rarely observed in the mucosal epithelium of bronchi, whereas Clara cells were present in the mucosa of all airways, increasing proportionately as the conducting and respiratory portions narrowed distally. Although the airways of the possum lung have a poorly developed mucociliary blanket, this may be compensated for by the large numbers of Clara cells and adequate supply of MALT.

The aim of this study was to localize macrophages in the hen oviduct and determine the effects of age and gonadal steroids on their population. Cryostat sections of oviducal tissues from immature hens (60 d of age), virgin young (175 d of age), and old (620 d of age) laying hens, and immature hens (84 d of age) treated with gonadal steroids were immunostained for macrophages. The population of macrophages was analyzed by an image analysis system under a light microscope. Macrophages were observed in the stroma and mucosal epithelium of all oviducal segments of immature and laying hens. The population of macrophages in the oviducal stroma increased with age. Young laying hens had a significantly higher population of macrophages than immature hens in the vagina. Old laying hens had a significantly higher population than immature hens in the infundibulum, magnum, and vagina, and than young laying hens in the magnum. In the immature hens treated with gonadal steroids, the macrophage population increased only in the stroma of shell gland of the progesterone-treated birds. These results indicate that macrophage population in the oviducal stroma increases in association with sexual maturation and aging. Their population in the stroma may be partially affected by progesterone.

1. Movement of thallium (I) ions across the mucosal epithelium of descending rat colon, stripped of the muscularis externa in vitro was determined under voltage clamp conditions. 2. The unidirectional fluxes of thallium (I) ions from mucosal to serosal side (M → S) and in the opposite direction (S → M) were measured at 0 mV. A net flux of thallium (I) ions was observed from serosal to mucosal side (0.216 nmoles · cm−2 · h−1) in other words, the mucosal epithelium is apparently asymmetric for the movement of thallium (I) ions. 3. The investigations were carried out on the range of −30 mV up to +30 mV from mucosal to serosal side. Thallium (I) ions move from mucosal to serosal side (M → S) by diffusion only (Pi = 0.119 cm · h−1), whereas into the opposite direction (S → M) thallium (I) ions in addition to a voltage-dependent component are transported against an electrical gradient.

The stomach contains plasminogen activators localized to submucosal vessels and to the mucosa. To study the release of plasminogen activators from mucosal cells, we induced mucosal damage by pyloric ligature and instillation of 0.5 mol/l HCl in rats. After 4 h, all rats developed focal necrotic lesions and a diffuse mucosal damage, as studied both by light microscopy and by scanning electron microscopy. Diffuse mucosal damage was accompanied by significant increase (P less than 0.001) in mucosal fibrinolytic activity based on plasminogen activators. This activity was probably derived from injured mucosal cells since focal necrotic lesions (erosions and ulcers) with total denudation of the mucosal epithelium lacked fibrinolytic activity. The results obtained in this study support the hypothesis that plasminogen activators are released during cellular degeneration.

This review summarizes recent information about immune responses in the intestinal mucosa, with emphasis on the role of orally-administered antigens from the external environment. The intestinal mucosa provides an extensive surface for potential absorption of pathogenic environmental antigens, such as microbes, chemicals, and food. The intestinal mucosa is densely populated by IgA-producing plasma cells. The humoral immune responses to antigens in the intestinal mucosa are largely of the IgA class in secretory form (sIgA). This sIgA provides an immunological barrier to absorption of antigens on the mucosal epithelium and to penetration into the body. The cell-mediated immune mechanism is also equipped in the mucosal sites. In addition, the mucosal immune response induces hyporesponsiveness of nonmucosal (systemic) immune reactions, and the liver is an integral part of the mucosal immune system. Thus we consider that the mucosal immune system plays a central role in the maintenance of the homeostasis of the total immune system.

Mucosal defects in the oral cavities of 35 dogs were repaired with reversed dermal grafts, full-thickness skin grafts, and dermal grafts. Comparative observations were made for up to two years to analyze the healing processes. The reversed dermal grafts were covered by surrounding mucosal epithelium and formed normal mucosal tissue that maintained its characteristics for two years. Histologic and scanning electron microscopic examination revealed that the epithelial appendages underwent degeneration, presumably through being embedded by the grafting of the dermis inside out. Epithelialization of the dermal grafts occurred from both surrounding mucosal epithelium and ancillary skin appendages. The full-thickness skin grafts maintained their original structure and function over the two-year observation period. It appears from this investigation that the reversed dermal graft method has definite advantages over full-thickness skin grafting and dermal grafting.

The development of colon mucosa during postnatal growth was analyzed in male BD IX rats using histological and radioautographic methods. Newborn animals already exhibited clearly recognizable crypts of Lieberkühn. DNA synthesis activity predominated in the lower two thirds of those crypts, as it constantly did during subsequent growth and in adult colons. The height of crypts at birth was already half the adult size. There was, in contrast, a dramatic increase in their number (more than 1,000% from birth to the 10th week, as observed on transverse sections). The mechanism by which new glands derive from the mucosal epithelium implies a longitudinal fission of preexisting glands.

The penetration of tritiated bacterial endotoxin through nonkeratinized oral mucosal epithelium was studied using an in vitro model system and radioautographic tracer techniques. The basement membrane region of the epithelium was the rate-limiting barrier to penetration, and this barrier effect was independent of the direction and duration of penetration as well as any clearance effects of the vasculature.

SummaryEnriched preparations of the two major cell types of the mucosal epithelium of the turtle's urinary bladder can be obtained by density gradient centrifugation. Carbonic anhydrase activity is much greater in the mitochondria-rich than in the granular cell, suggesting the former cell type is the site of acetazolamide-sensitive transport. This technique should be useful in further defining the biochemical and transport properties of epithelial tissues composed of heterogeneous mucosal cells.

The transfer rates of lidocaine and five derivatives were measured across the everted rat intestine. No obvious relationship was observed between the first-order rate constants for transfer and the lipophilicity of the compounds as measured by their apparent partition coefficients. The intestinal mucosal epithelium also did not appear to be the rate-limiting barrier for the passage of these agents across the intestinal membrane regardless of the respective clearance of the compound. It is suggested that the ionized form of these agents may be capable of crossing the intestinal barrier at substantial rates, although it is not known if a similar situation exists in vivo. The transfer rate is believed to be due to the passage of intact drug and not the metabolite.

Using microsurgical techniques and two layers of sutures, we reanastomosed 66 rabbit oviducts; 35 had been divided in the isthmic region and 31 in the ampullary region. With light microscopy as well as transmission and scanning electron microscopy we studied anastomosed segments and the rest of the oviducts 1 day, 1 week, and 4--12 weeks after operation. -- In the vicinity of the sutures we found slight scarring, some flattening of the mucosal epithelium with loss of differentiation and, most important, displacement of the mucosa into the muscle wall of the tube with the development of irregular diverticuli. The significance of these alterations and their possible relation to the occurrence of tubal ectopic pregnancy is discussed. We recommend that care should be taken to avoid the mucosa during total anastomosis.

SummaryTo substantiate our previous hypothesis in explanation of the inhibitory effect of EA, furosemide, and amiloride on mouse intestine, the intracellular potential, Vmc, and transmural potential, Vsm, of the intestinal mucosal epithelium were measured simultaneously with a 0.5-μm diameter microelectrode. It was found when glucose was present in the Ringer bathing solution, an average Vsm of 22.5 ± 0.87 mV was recorded and Vsm was 2.68 ± 0.09 mV. EA, furosemide, and amiloride at 0.5 mM produced an hyperpolarization of Vmc and a reduction of Vsm. The Vmc increased to 34.8 ± 0.68, 31.9 ± 2.6, and 31.2 ± 0.92 mV, respectively. When the bathing fluid contained no glucose, the average Vmc was 29.5 ± 0.53 mV and the average Vsm was 1.28 ± 0.10 mV. Addition of EA in the glucose-free bathing media caused no significant change in Vmc, but a decrease in Vsm. However, addition of furosemide or amiloride did cause further hyperpolarizations of Vmc, to 40.7 ± 0.64 and 39.8 ±1.2 mV, respectively. These results suppo...

We have used suspensions of isolated cells to study the metabolism of the mucosal epithelium and to compare its activity with that of other tissues in the intestinal wall of guinea pig. Only 4% of the total glycolytic activity of the intestinal wall could be attributed to the mucosal epithelium. In contrast, about 76% of the activity was located in the intestinal muscle and the remaining 20% in the intervening tissue. Clearly the view that the major proportion of the glycolytic activity of the small intestine resides in the mucosal epithelium does not apply to the guinea pig. In the light of our results, it would be prudent to re-examine any conclusions about the distribution of metabolic activity throughout the gut wall if the supporting evidence has been drawn from experiments with mucosal homogenates.

The length of the oviduct, the thickness of its wall, and the height of its mucosal epithelium and cilia were measured in (a) 0-, 2-, 4- and six-month-old rabbits, (b) rabbits ovariectomized at birth and (c) ovariectomized, estrogen-treated rabbits. The length and external diameter of the oviduct increased progressively until four months of age, after which their rates of increase declined. The thickness of the oviductal wall at the uterotubal junction was twice as large as that of the isthmus at two months of age and six times as large at four and six months of age. The height of the mucosal epithelium in the fimbriae was less than that in other oviductal segments at birth, but exceeded that in other segments at six months of age. Ciliated cells and motile cilia were absent 24 hours after birth; they were first observed two months after birth. The cilia of fimbriae were shorter than cilia elsewhere in the oviduct. Neonatal ovariectomy retarded the development of the oviduct and the mesotubarium and caused pyknosis of ciliated and non-ciliated cells of the oviductal mucosa. Cells with scarcely motile cilia were present five and one-half months after neonatal ovariectomy.

SummaryTwo anionics, a cationic and a nonionic synthetic surfactant, were examined in an in vitro phloridzinized preparation for their effects on passive intestinal permeability to glucose. These agents increased intestinal permeability to glucose in a dose-related manner with the anionic surfactant, linear alkylate sulfonate, producing this effect at lower concentrations than any of the other surfactants tested. Histologic observations demonstrated that the mucosal epithelium was not altered by low surfactant concentraions which increased intestinal permeability. Increased glucose permeability could account, in part, for decreased glucose uptake by the intestine when exposed to detergents due to the production of a “leak” at the mucosal surface preventing a glucose gradient to be established between the mucosal cell and the serosal border.

Ultrastructural evidence is presented indicating an increase in membrane-bound ATPase activity of the mucosal epithelium of the toad urinary bladder following exposure of its serosal surface to aldosterone. Although no conclusion could be made as to whether the observed increase in ATPase activity was a direct affect of AIP, or an event secondary to an effect of AIP on other components of the cells, various possibilities are discussed in terms of current physiological information regarding the effects of aldosterone on the epithelium of the isolated toad urinary bladder.