Diaphragmatic hernia: formation mechanisms, clinical picture, treatment tactics

The article presents current data on etiology, pathogenesis of diaphragmatic hernia. Types of diaphragmatic hernia are described in detail, namely: axial, paraesophageal, mixed; transient and fixed. Pathogenesis of the formation of hiatal hernia includes: failure of the connective tissue structures involved in the formation of the esophago-gastric junction; significant increase in intra-abdominal pressure; increase in motor activity of the esophagus (hypermotor dyskinesia). Clinical manifestations and peculiarities of pain, including pseudo-coronary pain, differential diagnosis, are described. Recommendations for non-drug treatment, including lifestyle and nutritional changes, are presented. Particular attention is paid to pantoprazole as a means of choice for therapy of patients. Advantages of pantoprazole as compared with other proton pump inhibitors are presented: selectivity of action depending on pH, absence of “decussation” with the metabolism of other drugs, efficacy, duration of acid suppressive action, safety, favorable pharmacoeconomic characteristics.

AMP-activated protein kinase fortifies epithelial tight junctions during energetic stress via its effector GIV/Girdin

Loss of epithelial polarity impacts organ development and function; it is also oncogenic. AMPK, a key sensor of metabolic stress stabilizes cell-cell junctions and maintains epithelial polarity; its activation by Metformin protects the epithelial barrier against stress and suppresses tumorigenesis. How AMPK protects the epithelium remains unknown. Here, we identify GIV/Girdin as a novel effector of AMPK, whose phosphorylation at a single site is both necessary and sufficient for strengthening mammalian epithelial tight junctions and preserving cell polarity and barrier function in the face of energetic stress. Expression of an oncogenic mutant of GIV (cataloged in TCGA) that cannot be phosphorylated by AMPK increased anchorage-independent growth of tumor cells and helped these cells to evade the tumor-suppressive action of Metformin. This work defines a fundamental homeostatic mechanism by which the AMPK-GIV axis reinforces cell junctions against stress-induced collapse and also provides mechanistic insight into the tumor-suppressive action of Metformin.

Rebamipide suppresses mite-induced asthmatic responses in NC/Nga mice

Allergic asthma caused by continuous allergen exposure evokes allergen-specific Th2 responses and is characterized by chronic airway inflammation and hyperresponsiveness. A previous report showed that rebamipide improved asthmatic symptoms in an ovalbumin/trypsin mice model. However, it is still unclear how rebamipide exerts its effects in asthma. In this study, rebamipide improved the asthmatic responses induced by mite exposure in NC/Nga mice, revealing the mechanism of this therapeutic effect. Rebamipide suppressed the infiltration of eosinophils into the airways and lung as well as attenuating the production of reactive oxygen species in tissues. In addition to these anti-inflammatory effects, rebamipide inhibited the production of IL-33, a member of the IL-1 family that drives the subsequent production of Th2-associated cytokines. These observations identify the point where rebamipide exerts its suppressive action on asthma and suggest that rebamipide has therapeutic potential in preventing mite-induced asthma.