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Use of glycosaminoglycan for restoring glycocalyx

A technology of glycosaminoglycan and glycocalyx, which is applied in the direction of medical preparations containing active ingredients, metabolic diseases, and extracellular fluid diseases, and can solve problems such as failure to recognize the cause of damage and the solution

Inactive Publication Date: 2010-01-27
MAASTRICHT UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] Palazzini and Gambaro disclosed the use of Sulodexide in the treatment of diabetic nephropathy in WO01 / 93850, for reducing the protein concentration in the blood, and they provided the safe concentration range of Sulodexide for human beings, but they did not realize the damage Causes and solutions to damage

Method used

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  • Use of glycosaminoglycan for restoring glycocalyx
  • Use of glycosaminoglycan for restoring glycocalyx
  • Use of glycosaminoglycan for restoring glycocalyx

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0112] M199 medium, L-glutamine, antibiotic-antimycotics and trypsin were obtained from Gibco-BRL, PBS pH: 7.4 from Fresenius Kabi and fetal bovine serum (FBS) from Biowhittaker. The following compounds were obtained from Sigma; Heparin, Endothelial Cell Growth Supplement (ECGS). D(+) glucose was obtained from Merck. Fibronectin was a gift from Central Laboratory for Bloodtransfusion (CLB), Amsterdam, Netherlands. Semi-permeable inserts 12-well 3 μm tube pores were purchased from Greiner.

[0113] HUVEC cells were isolated from human umbilical cords obtained from the Obstetrics Department of the AMC in Amsterdam. Briefly, the umbilical vein was cannulated and flushed with PBS before application of trypsin solution. The trypsin solution was incubated at 37°C to dissociate endothelial cells from the venous vessel wall. The trypsin solution was collected and the vein was flushed with PBS. The cell solution was centrifuged at 1100 rpm for 10 minutes, the supernatant was remov...

Embodiment 2

[0119] Determination of baseline parameters

[0120] Isolated HUVECs were cultured on a semi-permeable membrane under normoglycemic (5 mM) conditions for 5 days. After 5 days, monolayer formation was assessed by measuring endothelial transfer of FITC-labeled albumin through the monolayer. The baseline permeability of FITC albumin is very low, which is indicative of solid phase formation.

Embodiment 3

[0122] Determination of Permeability of Cell Monolayers Under Normoglycemia and Hyperglycemia

[0123] HUVECs were also cultured under hyperglycemia (25 mM) conditions for 5 days to evaluate whether this condition affects endothelial permeability. figure 1 Shows the permeability of HUVECs grown under normoglycemia and hyperglycemia. The albumin crossover rate of HUVECs grown under normoglycemic conditions was set at 100%. Hyperglycemia increased albumin permeability by 22% (p<0.01), indicating degradation of the barrier.

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Abstract

The invention is directed to the use of glycosaminoglycans for restoring glycocalyx functions or preventing glycocalyx damage. The effectiveness of glycosaminoglycans is directed in all pathologies where glycocalyx damage or this function may be etiologically cause of many pathologies such as: vascular disease, septic states, atherosclerosis syndrome, inflammation states and disease related to ischemia, peritoneal impairment, myocardial infarction, cerebrum- vascular events, alteration of enzymatic glycosylation in diabetes, kidney injury, intestinal disease as ulcerous colitis conditions, pneumoconiosis involving alteration of metabolic activity of pulmonary endothelium.

Description

Background technique [0001] The glycocalyx is a 0.5 micron thick gel layer that lines the inner walls of healthy blood vessels and is the first line of defense against many diseases. [0002] Currently, the glycocalyx is a complex and poorly understood structure. Recent studies have shown that hyperglycemia can alter the structure of the glycocalyx, and parallel findings have suggested that the marked increase in permeability exhibited in hyperglycemia may be due to increased permeability of blood vessels to water rather than to proteins increase. [0003] The question of restoring the functional integrity of the glycocalyx, or avoiding disruption of the glycocalyx, is a problem that involves more than one mechanism of endothelial permeability. [0004] Given this, there is an urgent need to uncover etiological factors and mechanisms related to these degenerative changes, as targeting such processes would provide further avenues to avoid and ameliorate vascular destruction a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/726A61P43/00A61P9/00A61P9/10A61P3/10A61P13/12A61P1/04A61P11/00A61P7/00
CPCA61K31/737A61K31/727A61K31/726A61P1/00A61P3/10A61P13/12A61P25/02A61P27/02A61P43/00
Inventor H·温科E·S·G·斯托丝
Owner MAASTRICHT UNIVERSITY
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