Inhibition of heparanase-mediated degradation of extracellular matrix heparan sulfate by non-anticoagulant heparin species

Incubation of human platelets, human neutrophils, or highly metastatic mouse lymphoma cells with sulfate-labeled extracellular matrix (ECM) results in heparanase-mediated release of labeled heparan sulfate cleavage fragments (0.5 less than Kav less than 0.85 on Sepharose 6B). This degradation was inhibited by native heparin both when brought about by intact cells or their released heparanase activity. Degradation of heparan sulfate in ECM may facilitate invasion of normal and malignant cells through basement membranes. The present study tested the heparanase inhibitory effect of nonanticoagulant species of heparin that might be of potential use in preventing heparanase mediated extravasation of bloodborne cells. For this purpose, we prepared various species of low-sulfated or low-mol-wt heparins, all of which exhibited less than 7% of the anticoagulant activity of native heparin. N-sulfate groups of heparin are necessary for its heparanase inhibitory activity but can be substituted by an acetyl group provided that the O-sulfate groups are retained. O-sulfate groups could be removed provided that the N positions were resulfated. Total desulfation of heparin abolished its heparanase inhibitory activity. Heparan sulfate was a 25-fold less potent heparanase inhibitor than native heparin. Efficiency of low-mol-wt heparins to inhibit degradation of heparan sulfate in ECM decreased with their main molecular size, and a synthetic pentasaccharide, representing the binding site to antithrombin III, was devoid of inhibitory activity. Similar results were obtained with heparanase activities released from platelets, neutrophils, and lymphoma cells. We propose that heparanase inhibiting nonanticoagulant heparins may interfere with dissemination of bloodborne tumor cells and development of experimental autoimmune diseases.     

Modified anthropometry in prepubertal Israeli children while excluding the head’s weight and height

Aim: A methodological inadequacy in anthropometric measurements of children exists because of an age‐dependent decelerating contribution of the head to body weight (Wt) and height (Ht). Hence, we aimed to assess the contribution of head measurements to anthropometry (Ht, Wt and BMI) in healthy prepubertal children. Methods: This prospective study was conducted in 300 2‐ to 9‐year‐old typically growing children. Head‐excluded (HE) Ht was determined by a stadiometer that measured the distance from the foot plate to the lower margin of protuberance occipitalis externa. Head’s weight was calculated from the head volume using three different measurements of the head circumference. Results: In the typically growing children, the HE/standard (STD) ratios for Wt and Ht increased significantly with age (p < 0.001 for both), but the HE/STD ratio for BMI did not increase with age. Conclusion: Measurement of body Wt and Ht while excluding the head’s Wt and Ht provides a new dimension to standard anthropometry by eliminating the age‐dependent head bias with its unique pattern of growth and minimal adipose tissue.