Objective-Insulin promotes adhesion of leukocytes to the endothelium through increased expression of surface adhesion molecules. We determined whether src-homology domain-2-containing protein tyrosine phosphatase 2 (SHP2), a downstream effecter of insulin signaling, is involved in insulin-induced endothelial inflammation. Methods and Results-In human umbilical vein-derived endothelial cells, treatment with insulin (100 nmol/L) increased Tyr 542 phosphorylation, activity, and subsequently expression of SHP2. Increase in SHP2 accompanied a parallel decrease in the availability of the anti-inflammatory molecule, NO. This consequently enhanced the expression of cell adhesion molecules. Decrease in NO index was caused by endothelial NO synthase (eNOS) uncoupling and increased arginase activity. Among the 2 isoforms, insulin treatment induced the expression of arginase II. Inactivation of endogenous SHP2 via NSC87877 [8-hydroxy-7-(6-sulfonapthalen-2-yl)-diazenyl-quinoline-5-sulfonic acid] and its knockdown by small interfering RNA decreased arginase activity by blocking arginase II expression; however, it failed to restore eNOS coupling. Inactivation of SHP2 also abrogated insulin-mediated leukocyte adhesion by blocking the expression of adhesion molecules. Finally, downregulation of endogenous arginase II blocked insulin-mediated endothelial inflammation. Conclusion-SHP2

Mechanism of thrombin–induced inflammation is not fully understood. Thrombin induced monocyte adhesion and barrier loss require Angiopoietin‐2 (Ang‐2). Ang‐2 mediates vessel leakage and monocyte adhesion through SHP‐2/p38MAPK pathway. Calcium dependent SHP2/p38MAPK activation regulates Ang‐2 expression through a feedback loop. Summary BackgroundThrombin imparts an inflammatory phenotype to the endothelium by promoting increased monocyte adhesion and vascular permeability. However, the molecular players that govern these events are incompletely understood. ObjectiveThe aim of this study was to determine whether Angiopoietin‐2 (Ang‐2) has a role, if any, in regulating inflammatory signals initiated by thrombin. MethodsAssessment of vascular leakage by Miles assay was performed by intra‐dermal injection on the foot paw. Surface levels of intercellular adhesion molecule‐1 (ICAM‐1) were determined by flow cytometry. Overexpression, knockdown and phosphorylation of proteins were determined by Western blotting. ResultsIn time‐course experiments, thrombin‐stimulated Ang‐2 up‐regulation, peaked prior to the expression of adhesion molecule ICAM‐1 in human umbilical vein‐derived endothelial cells (HUVECs). Knockdown of Ang‐2 blocked both thrombin‐induced monocyte adhesion and ICAM‐1 expression. In addition, Ang‐2−/− mice displayed defective vascular leakage when treated with thrombin. Introducing Ang‐2 protein in Ang‐2−/− mice failed to recover a wild‐type phenotype. Mechanistically, Ang‐2 appears to regulate the thrombin‐activated calcium spike that is required for tyrosine phosphatase SHP2 and p38 MAPK activation. Further, down‐regulation of SHP2 attenuated both thrombin‐induced Ang‐2 expression and monocyte adhesion. Down‐regulation of the adaptor protein Gab1, a co‐activator of SHP2, as well as overexpression of the Gab1 mutant incapable of interacting with SHP2 (YFGab1), inhibited thrombin‐mediated effects, including downstream activation of p38 MAPK, which in turn was required for Ang‐2 expression. ConclusionsThe data establish an essential role of the Gab1/SHP2/p38MAPK signaling pathway and Ang‐2 in regulating thrombin‐induced monocyte adhesion and vascular leakage.

Abstract This paper from India describes anxieties that pregnant and postpartum women reported to obstetricians during the COVID-19 pandemic. Of the 118 obstetricians who responded to an online survey, most had been contacted for concerns about hospital visits (72.65%), methods of protection (60.17%), the safety of the infant (52.14%); anxieties related to social media messages (40.68%), contracting the infection (39.83%). Obstetricians felt the need for resources such as videos, websites and counselling skills to handle COVID related anxiety among perinatal women.

ObjectiveTo report our experience and evaluate outcomes in monochorionic pregnancies with Twin Reversed Arterial Perfusion sequence with intrafetal laser therapy.MethodsRetrospective review of records of all pregnancies with TRAP sequence treated by intrafetal laser therapy between 2011 January and 2015 December that were retrieved and analysed.ResultsElectronic search of the scan database retrieved 57 cases of TRAP sequence during the study period, 7 triplets and 50 monochorionic twins. Intrafetal laser was done in 27 cases, 22 cases of twins and 5 cases of triplets. In the twins group, median gestational age at intervention was 22.5 weeks, the earliest done at 16.3 weeks. The median gestational age at delivery and birth weight was 37 weeks and 2.5 Kgs. The median procedure and delivery interval was 14 weeks. Live birth rate was 17/22 (77%) the pump survival rate was 16/22 (73%). Pregnancies with non‐surviving pump were 5 in numbers (5/22). A repeat procedure was warranted in one case. In the triplet group, median gestational age at intervention, delivery and procedure delivery interval was 18, 35 and 17 weeks.ConclusionIntrafetal laser is simple, effective and the treatment of choice to interrupt the vascular supply to acardiac twin.