The Development of a Unified Balance of Fuel and Power

Considerable experience has been acquired in our country in the development of balances of material goods, including balances for fuel, electric power, light, petroleum, etc. These balances make it possible to determine the economy's needs for resources of fuel and power, the methods and means of satisfying these needs, and establish the proportions of development that have to be maintained between the fuel and power branches of the economy on the one hand, and the branches consuming their products, on the other. The experience acquired in developing these balances is of major scientific and practical value, and makes it possible now to proceed to new and more advanced methods of planning the development of the fuel-and-power base for the country.

PI-88 and related heparan sulfate mimetics

The heparan sulfate mimetic PI-88 (muparfostat) is a complex mixture of sulfated oligosaccharides that was identified in the late 1990s as a potent inhibitor of heparanase. In preclinical animal models it was shown to block angiogenesis, metastasis and tumor growth, and subsequently became the first heparanase inhibitor to enter clinical trials for cancer. It progressed to Phase III trials but ultimately was not approved for use. Herein we summarize the preparation, physicochemical and biological properties of PI-88, and discuss preclinical/clinical and structure-activity relationship studies. In addition, we discuss the PI-88-inspired development of related HS mimetic heparanase inhibitors with improved properties, ultimately leading to the discovery of PG545 (pixatimod) which is currently in clinical trials

Heparanase: roles in cell survival, extracellular matrix remodelling and the development of kidney disease

Item does not contain fulltextHeparanase has regulatory roles in various processes, including cell communication, gene transcription and autophagy. In addition, it is the only known mammalian endoglycosidase that is capable of degrading heparan sulfate (HS). HS chains are important constituents and organizers of the extracellular matrix (ECM), and have a key role in maintaining the integrity and function of the glomerular filtration barrier. In addition, HS chains regulate the activity of numerous bioactive molecules, such as cytokines and growth factors, at the cell surface and in the ECM. Given the functional diversity of HS, its degradation by heparanase profoundly affects important pathophysiological processes, including tumour development, neovascularization and inflammation, as well as progression of kidney disease. Heparanase-mediated degradation and subsequent remodelling of HS in the ECM of the glomerulus is a key mechanism in the development of glomerular disease, as exemplified by the complete resistance of heparanase-deficient animals to diabetes and immune-mediated kidney disease. This Review summarizes the role of heparanase in the development of kidney disease, and its potential as a therapeutic target

Heparanase Involvement in Exosome Formation

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