Eosinophilic esophagitis is a chronic disease whose incidence and prevalence are increasing, based on a genetic-driven interaction between environment and immune system. Several gene loci involved in the development of the disease have been identified. A two-step mechanism has been hypothesized: a thymic stromal lymphopoietin-induced allergic sensitization followed by upregulation of CAPN14-related esophageal-specific pathways. Environment seems to have a larger effect than genetic variants. Factors that could play a role are allergens, drugs, colonizing bacteria and possibly Helicobacter Pylori infection. Acting on these modifiable risk factors may be a tool to prevent the disease. EoE is characterized by a typical eosinophilic infiltrate limited to the esophageal epithelium, supported by a Th2-mediated immune response, found in other atopic conditions. The key of the pathogenesis is the disfunction of the epithelial barrier which allow the interaction between allergens and inflammatory cells. Eosinophilic-predominant inflammation leads to the typical wall remodeling, histologically characterized by epithelial and smooth muscle hyperplasia, lamina propria fibrosis and neo-angiogenesis. These alterations find their clinical expression in the pattern of symptoms: dysphagia, food impaction, chest pain, heartburn.
BACKGROUND Liver is one of the first organs to be exposed to reactive oxygen species (ROS). But the data about the levels of redox homeostasis parameters in the patients with liver cirrhosis (LC) are contradictory. We hypothesized that the levels of malondialdehide and catalase should change in accordance with the LC severity causing the endothelial dysfunction. METHODS In a randomized way with the preliminary startification by the presence of LC 81 patients and 20 healthy volunteers were examined. To determine the contents of catalase, malondialdehide, cyclic guanosine monophosphate, endothelin-1, renin, aldosterone, natriuretic peptide, the routine standartized methods were used. The results were processed in Statistica 6.0, RStudio v. 1.1.442 and R Commander v.2.4-4. RESULTS Patients with LC revealed the statistically significant increase of malondialdehide and decrease of catalase levels in parallel with the increase of cyclic guanosine monophosphate, endothelin-1, renin, aldosterone, natriuretic peptide contents and disease course worsening according to C. H. Child-R. N. Pugh criteria. It testifies the huge oxidative stress impact on the organism. Initially, at the stage of LC compensation, it slightly stimulates the activation of antioxidant system, followed by its gradual suppression at the stages of sub- and decompensation. Disorders of redox homeostasis lead to the endothelial dysfunction that becomes the background of extrahepatic comorbid disorders. CONCLUSIONS The cirrhotic patients have the significant abnormalities in the redox homeostasis that becomes the background of the endothelial dysfunction - common trigger mechanism for the syntropic comorbid diseases and early pathophysiologic symptom of the unfavorable prognosis for such patients.
Therapeutic drug monitoring (TDM) is a useful tool for decision-making process in patients with Inflammatory Bowel Disease (IBD) treated with anti TNF-α drugs, especially when experiencing loss of response. Growing evidences support the existence of exposure-response relationship with Vedolizumab, but the utility and the appropriate use of TDM in clinical practice is still under debate. In this review, we summarize all evidences supporting a TDM-guided approach for patients treated with Vedolizumab, suggesting three potential scenarios: 1) early prediction of long-term outcomes; 2) verifying the best strategy in case of loss of response, 3) maximizing therapeutic efficacy during maintenance treatment. Vedolizumab through concentrations < 20 μg/ml at week 6 and > 12 μg/ml seem to be associated with more favourable outcomes. No comparative studies have been conducted so far to demonstrate the advantage of adopting a TDM-guided versus an empirical approach for managing primary or secondary non responses.The frequency of antibodies to Vedolizumab detection is quite low (up to 4% in pivotal trials), suggesting, unlike of anti TNF-α agents, a low probability of experiencing an immune-mediated pharmacokinetic failure in clinical practice. Future prospective and controlled studies are warranted to establish the guidance on the use of a TDM-guided approach with Vedolizumab in clinical practice.
