Desmoplakin and periplakin genetically and functionally contribute to eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease with a complex underlying genetic etiology. Herein, we conduct whole-exome sequencing of a multigeneration EoE pedigree (discovery set) and 61 additional multiplex families with EoE (replication set). A series of rare, heterozygous, missense variants are identified in the genes encoding the desmosome-associated proteins DSP and PPL in 21% of the multiplex families. Esophageal biopsies from patients with these variants retain dilated intercellular spaces and decrease DSP and PPL expression even during disease remission. These variants affect barrier integrity, cell motility and RhoGTPase activity in esophageal epithelial cells and have increased susceptibility to calpain-14–mediated degradation. An acquired loss of esophageal DSP and PPL is present in non-familial EoE. Taken together, herein, we uncover a pathogenic role for desmosomal dysfunction in EoE, providing a deeper mechanistic understanding of tissue-specific allergic responses.

Modern concepts on the state of esophagus epithelial barrier at gastroesophageal reflux disease and possibilities of correction with alginates

Gastroesophageal reflux disease (GERD) remains an urgent problem in clinical medicine. The search for ways of effective treatment leads to the need to set new accents in the multifactorial pathogenesis of the disease. According to current trends, special attention is paid to the epithelial barrier of the esophagus. The article presents considerations of the structure of the mucosal epithelial layer, the features of transport routes and intercellular interactions of the esophageal epithelium. Special attention is paid to the phenomenon of the Dilated Intercellular Spaces (DIS) and the syndrome of increased epithelial permeability (SІEP) at GERD. An interpretation of these concepts is given, their role in the implementation of inflammatory processes and the formation of clinical manifestations of the disease, such as heartburn and pain, is revealed. The data on the possible mechanisms of the formation of the DIS and SІEP phenomenon, methods of their diagnosis and aspects that are discussed in the scientific world are presented. The possibilities of cytoprotective therapy using alginate preparations have been shown. Among the alginates, available on the pharmaceutical market of Ukraine, the pharmacological line Gaviscon® (LLC Reckitt Benckiser Ukraine, Great Britain) is presented. The results of experimental studies with the use of the latest technologies, and data from randomized clinical trials confirming the alginates’ clinical efficacy, have been outlined. The phenomenon of DIS of the esophageal epithelium and SІEP for aggression factors is one of the leading links in GERD pathogenesis, in particular, its non‑erosive form, and to some extent determines the features of the clinical manifestations of the disease. Treatment of GERD with the use of alginates is logically justified, successfully used in clinical practice, and continues to be actively studied. The use of Gaviscon® products is expedient due to their unique mechanism of action to increase the resistance of the esophagus.

Protective Effects of Trehalose on the Corneal Epithelial Cells

Purpose.Aim of the present work was to evaluate the effects of the trehalose on the corneal epithelium undergoing alcohol delamination.Methods.Twelve patients undergoing laser subepithelial keratomileusis (LASEK) were consecutively included in the study. The right eyes were pretreated with 3% trehalose eye drops, whilst left eyes were used as control. Epithelial specimens were processed for cells vitality assessment, apoptosis, and light and transmission electron microscopy; a morphometric analysis was performed in both groups.Results.In both trehalose-untreated eyes (TUE) and trehalose-treated eyes (TTE), the percentage of vital cells was similar and no apoptotic cells were observed. In TUE, the corneal epithelium showed superficial cells with reduced microfolds, wing cells with vesicles and dilated intercellular spaces, and dark basal cells with vesicles and wide clefts. In TTE, superficial and wing cells were better preserved, and basal cells were generally clear with intracytoplasmatic vesicles. The morphometric analysis showed statistically significant differences between the two groups: the TTE epithelial height was higher, the basal cells showed larger area and clearer cytoplasm. The distribution of desmosomes and hemidesmosomes was significantly different between the groups.Conclusions.Trehalose administration better preserved morphological and morphometric features of alcohol-treated corneal epithelium, when compared to controls.