ß2-Adrenoceptor signaling in airway epithelial cells promotes eosinophilic inflammation, mucous metaplasia, and airway contractility.

The mostly widely used bronchodilators in asthma therapy are ß2-adrenoreceptor (ß2AR) agonists, but their chronic use causes paradoxical adverse effects. We have previously determined that ß2AR activation is required for expression of the asthma phenotype in mice, but the cell types involved are unknown. We now demonstrate that ß2AR signaling in the airway epithelium is sufficient to mediate key features of the asthmatic responses to IL-13 in murine models. Our data show that inhibition of ß2AR signaling with an aerosolized antagonist attenuates airway hyperresponsiveness (AHR), eosinophilic inflammation, and mucus-production responses to IL-13, whereas treatment with an aerosolized agonist worsens these phenotypes, suggesting that ß2AR signaling on resident lung cells modulates the asthma phenotype. Labeling with a fluorescent ß2AR ligand shows the receptors are highly expressed in airway epithelium. In ß2AR-/- mice, transgenic expression of ß2ARs only in airway epithelium is sufficient to rescue IL-13-induced AHR, inflammation, and mucus production, and transgenic overexpression in WT mice exacerbates these phenotypes. Knockout of ß-arrestin-2 (ßarr-2-/-) attenuates the asthma phenotype as in ß2AR-/- mice. In contrast to eosinophilic inflammation, neutrophilic inflammation was not promoted by ß2AR signaling. Together, these results suggest ß2ARs on airway epithelial cells promote the asthma phenotype and that the proinflammatory pathway downstream of the ß2AR involves ßarr-2. These results identify ß2AR signaling in the airway epithelium as capable of controlling integrated responses to IL-13 and affecting the function of other cell types such as airway smooth muscle cells.

Odontogenic cyst with diverse histopathological features: report of an unusual case.

OBJECTIVE: It is a well established fact that all inflammatory and developmental cysts of odontogenic origin have squamous epithelial linings. They may show various forms of metaplasia from a stratified squamous to more highly differentiated ciliated columnar or mucous cells. Dentigerous cyst represents is the most common developmental odontogenic cyst usually associated with an impacted tooth after complete formation of the crown. A dentigerous cyst encloses is seen attached to the neck of the tooth at the cementoenamel junction associated with an unerupted/ impacted tooth and grows by expansion of the dental follicles. We report a similar case of dentigerous cyst associated with an impacted tooth, histologically demonstrates the characteristics of a glandular odontogenic cyst with pseudo- stratified ciliated columnar epithelium lining with goblet cells and mucous cells.

Metamorphosis of Dentigerous cyst: A case Series with Insight into Molecular Profiling.

The objective of this study was to review the clinical, radiologic, and histologic aspects of cases of dentigerous cysts metamorphosing into different entities along with comments on the molecular factors involved in the process. A series comprising 8 cases of dentigerous cysts was performed retrospectively along with a comprehensive literature review. Two cases of dentigerous cyst converting into mucous metaplasia were included, out of which one case was transformed into ameloblastoma after a year. The other two cases were reported as acanthomatous and unicystic ameloblastoma, whereas four transitioned to AOT. The complete review of cases and literature with molecular profiling concluded that the lining of dentigerous cysts has the potential for transforming into benign odontogenic tumors. Therefore, a careful clinical and histopathological examination is crucial for the correct diagnosis. Also, a thorough molecular understanding of the cystic lining is required.

Odontogenic Keratocyst with Diverse Variations: A Rare Case Report.

Rationale: An odontogenic keratocyst (OKC) is a developmental odontogenic cyst lined by squamous epithelium having intrinsic growth potential. Hence, metaplastic changes such as the formation of mucous cells, ciliated cells, and hyaline bodies with ortho/para keratinisation have been known to create unusual histopathological variations. Patient Concerns: A 34-year-old male patient reported with swelling on the lower right side of the face and numbness on the overlying skin. Diagnosis: Based upon the histopathological findings, a final diagnosis of glandular odontogenic cyst with OKC was confirmed presenting mixed features of basal layer palisading squamous epithelium with goblet cells and satellite cysts appeared to be entrapped in the connective tissue wall. Treatment: Surgical enucleation of the cyst was done. Outcomes: No recurrence was reported in 1 year of follow-up. Take-away Lessons: Diverse variations appear within odontogenic cysts and tumours. The high recurrence rate and aggressive nature of the cyst, divulges appropriate treatment and long-term follow-up.

Can Chromoendoscopy Improve the Early Diagnosis of Gastric Carcinoma in Dogs?

Chromoendoscopy has improved the early diagnosis of gastric cancer in humans but its usefulness in dogs is unknown. This study aimed at assessing whether adding narrow band imaging (NBI) or indigo carmine (IC) chromoendoscopy (CE) can improve the diagnostic yield of standard white light endoscopy (WLE). We compared the real-time findings of canine WLE, NBI-CE, and IC-CE and corresponding histology reports with endoscopic mucosal pattern assessment templates used in human medicine. Belgian Shepherd dogs are predisposed to gastric carcinoma. Therefore, 30 dogs of this breed served as the study population. According to histology, 17/30 dogs had mucosal changes (mucous metaplasia, glandular dysplasia, and gastric carcinoma). Diagnostic yield was best when targeted biopsies were taken with WLE and NBI-CE combined (15/17 cases). WLE alone positively identified only 8/17 cases and missed a gastric carcinoma in 3/6 cases. CE assessment templates based on macroscopic mucosal patterns, broadly used in human medicine, were not readily applicable in dogs. In conclusion, the study provides evidence that using CE in dogs has the potential to improve the diagnosis of precancerous gastric mucosal pathology and early gastric carcinoma. However, current image assessment templates from human medicine need major adjustments to the patterns of canine gastric mucosa.

Helicobacter pylori Colonization Drives Urokinase Receptor (uPAR) Expression in Murine Gastric Epithelium During Early Pathogenesis.

(1) Background: Persistent Helicobacter pylori infection is the most important risk factor for gastric cancer. The urokinase receptor (uPAR) is upregulated in lesions harboring cancer invasion and inflammation. Circumstantial evidence tends to correlate H. pylori colonization with increased uPAR expression in the human gastric epithelium, but a direct causative link has not yet been established in vivo; (2) Methods: In a mouse model of H. pylori-induced gastritis, we investigated the temporal emergence of uPAR protein expression in the gastric mucosa in response to H. pylori (SS1 strain) infection; (3) Results: We observed intense uPAR immunoreactivity in foveolar epithelial cells of the gastric corpus due to de novo synthesis, compared to non-infected animals. This uPAR induction represents a very early response, but it increases progressively over time as do infiltrating immune cells. Eradication of H. pylori infection by antimicrobial therapy causes a regression of uPAR expression to its physiological baseline levels. Suppression of the inflammatory response by prostaglandin E2 treatment attenuates uPAR expression. Notwithstanding this relationship, H. pylori does induce uPAR expression in vitro in co-cultures with gastric cancer cell lines; (4) Conclusions: We showed that persistent H. pylori colonization is a necessary event for the emergence of a relatively high uPAR protein expression in murine gastric epithelial cells.

Pleomorphic adenoma: a rare presentation in buccal salivary gland with extensive squamous and mucous metaplasia.

Pleomorphic Adenoma (PA) is the most common salivary gland tumor and accounts for about 60% of all salivary gland neoplasms. Intraorally, the hard palate is the most common presenting site (50-60%) followed by upper lip (15-20%) and rarely buccal mucosa (8-10%). Histopathologically, PA shows diverse morphology resulting from amalgamation of cellular and stromal components. The PA may show changes in the stromal and epithelial components, such as sebaceous, lipocytic and oncocytic metaplasia. A rare characteristic of PA is to show extensive squamous and mucous differentiation which poses diagnostic dilemma to the pathologist. Here, we present an unusual case of PA of buccal minor salivary gland with squamous and mucous metaplasia. The localization, gender and microscopic features of the presented case are unusual.

Multiwalled Carbon Nanotube Functionalization with High Molecular Weight Hyaluronan Significantly Reduces Pulmonary Injury.

Commercialization of multiwalled carbon nanotubes (MWCNT)-based applications has been hampered by concerns regarding their lung toxicity potential. Hyaluronic acid (HA) is a ubiquitously found polysaccharide, which is anti-inflammatory in its native high molecular weight form. HA-functionalized smart MWCNTs have shown promise as tumor-targeting drug delivery agents and can enhance bone repair and regeneration. However, it is unclear whether HA functionalization could reduce the pulmonary toxicity potential of MWCNTs. Using in vivo and in vitro approaches, we investigated the effectiveness of MWCNT functionalization with HA in increasing nanotube biocompatibility and reducing lung inflammatory and fibrotic effects. We utilized three-dimensional cultures of differentiated primary human bronchial epithelia to translate findings from rodent assays to humans. We found that HA functionalization increased stability and dispersion of MWCNTs and reduced postexposure lung inflammation, fibrosis, and mucus cell metaplasia compared with nonfunctionalized MWCNTs. Cocultures of fully differentiated bronchial epithelial cells (cultivated at air-liquid interface) and human lung fibroblasts (submerged) displayed significant reduction in injury, oxidative stress, as well as pro-inflammatory gene and protein expression after exposure to HA-functionalized MWCNTs compared with MWCNTs alone. In contrast, neither type of nanotubes stimulated cytokine production in primary human alveolar macrophages. In aggregate, our results demonstrate the effectiveness of HA functionalization as a safer design approach to eliminate MWCNT-induced lung injury and suggest that HA functionalization works by reducing MWCNT-induced epithelial injury.

Predominantly cystic central mucoepidermoid carcinoma developing from a previously diagnosed dentigerous cyst: case report and review of the literature.

Primary intraosseous mucoepidermoid carcinoma of the jawbones is an extremely rare malignant salivary gland tumour constituting 2-4.3% of all the reported mucoepidermoid carcinomas. We report a case of intraosseous mucoepidermoid carcinoma of the mandible in an 80-year old female patient developing from a previously diagnosed dentigerous cyst. An excisional biopsy was performed and the histopathological features confirmed low grade-cystic intraosseous mucoepidermoid carcinoma. The origin of central mucoepidermoid carcinoma could be suggested to be from the epithelial lining of previously diagnosed dentigerous cyst. Thus, emphasizing the need for careful examination of the entire excision specimen to rule out such neoplastic transformation of epithelial lining of odontogenic cyst and provide appropriate and effective treatment.

Short term retinol treatment in vitro induces stable transdifferentiation of chick epidermal cells into mucus-secreting cells.

Epidermal mucous metaplasia of cultured skin can be induced by treatment with excess retinol for several days (Fell 1957). In the induction of mucous metaplasia, retinol primarily affects the dermal cells and retinol-pretreated dermis can alter epidermal differentiation towards secretory epithelium (Obinata et al. 1987). In this work, we found that mucous metaplasia could be induced by culturing 13-day-old chick embryonic tarsometatarsal skin in medium containing retinol (20 µM) for only 8-24 h, followed by culture in a chemically defined medium (BGJb) without retinol or serum for 6 days. The application of cycloheximide together with retinol during the first 8 h of culture inhibited epidermal mucous metaplasia during subsequent culture for 6 days in BGJb, indicating that induction of a signal(s) in the dermis by excess retinol requires protein synthesis. However, the presence of 20 nM hydrocortisone (Takata et al. 1981) throughout the culture period did not inhibit retinol-induced epidermal mucous metaplasia of the epidermis. This indicates that a brief treatment of the skin with excess retinol determines the direction of epithelial differentiation toward secretory epithelium; this is a simpler in vitro system for the induction of epidermal mucous metaplasia than those established before.