Could the Oxidation of α1-Antitrypsin Prevent the Binding of Human Neutrophil Elastase in COVID-19 Patients?

Human neutrophil elastase (HNE) is involved in SARS-CoV-2 virulence and plays a pivotal role in lung infection of patients infected by COVID-19. In healthy individuals, HNE activity is balanced by α1-antitrypsin (AAT). This is a 52 kDa glycoprotein, mainly produced and secreted by hepatocytes, that specifically inhibits HNE by blocking its activity through the formation of a stable complex (HNE-AAT) in which the two proteins are covalently bound. The lack of this complex, together with the detection of HNE activity in BALf/plasma samples of COVID-19 patients, leads us to hypothesize that potential functional deficiencies should necessarily be attributed to possible structural modifications of AAT. These could greatly diminish its ability to inhibit neutrophil elastase, thus reducing lung protection. The aim of this work was to explore the oxidation state of AAT in BALf/plasma samples from these patients so as to understand whether the deficient inhibitory activity of AAT was somehow related to possible conformational changes caused by the presence of abnormally oxidized residues.

Roux-en-Y reconstruction at greater curvature in biliopancreatic diversion: effects on early postoperative functional recovery.

Delayed gastric emptying after distal gastrectomy and reconstruction of alimentary tract with a gastroenteric anastomosis can significantly influence early and late postoperative course and the length of hospital stay. The purpose of this study was to compare the effect on postoperative functional recovery of two different Roux-en-Y reconstructions: at the gastric greater curvature and at the transected gastric staple line in the Scopinaro's biliopancreatic diversion. We conducted comparative study; 80 patients were enrolled and divided in two groups: group A (RY-GC) and group B (RY-SL) with 40 patients in each group. We compared the early postoperative functional recovery for both groups measuring four parameters: gastric stasis indicated with the volume of the gastric fluid collected per 24 h, day of removal of the nasogastric tube, day of starting the oral intake, and day of hospital discharge. There was statistically significant (p < 0.001) reduction in gastric fluid volume in favor of the RY-GC group starting from the first postoperative day resulting in earlier removal of nasogastric tube with earlier starting of oral feeding than RY-SL group, with no symptoms of stasis required nutrition suspension; while three patients in RY-SL group experienced persistence of nausea and vomiting and needed nutrition suspension for several days. There was statistically significant (p < 0.001) reduction in the hospital stay for RY-GC group. Roux-en-Y reconstruction at the greater curvature ensures a rapid functional recovery with early hospital discharge. The use of stapler devices made this method easier and safer and no complications have arisen with mechanical anastomoses.

Activation of smooth muscle and myenteric plexus cells of jejunum via Toll-like receptor 4.

The cell types of the gut expressing Toll-like receptor 4, which recognizes specifically bacterial lipopolysaccharides, as well as the functionality of this receptor, have remained controversial. We aimed to clarify these issues. Mouse and human intestinal specimens were stained immunohistochemically to detect Toll-like receptor 4 expression. Smooth muscle and myenteric plexus cells but not enterocytes revealed receptor expression. Murine intestinal smooth muscle and myenteric plexus cells but not enterocytes showed nuclear translocation of nuclear factor-kappaB after in vivo stimulation with lipopolysaccharide. Moreover, lipopolysaccharide added to human jejunum biopsies free of epithelial cells induced release of interleukin-8 (IL-8). We can conclude that Toll-like receptor 4 is not expressed in epithelial layer, but rather on smooth muscle and myenteric plexus cells and that expression is functional. The expression of Toll-like receptor 4 on smooth muscle and myenteric plexus cells is consistent with the possibility that these cells are involved in intestinal immune defense; the low or absent expression of Toll-like receptor 4 on enterocytes might explain the intestinal epithelium hyporesponsiveness to the abundance of LPS in the intestinal lumen.