Previous studies have indicated that administration of glycosaminoglycans can prevent some of the morphological and physiological alterations which occur in experimental diabetic nephropathy. The aims of this study were to further elucidate the effect of these drugs on glomerular basement membrane permeability by dextran clearance studies, to test the ability of glycosaminoglycans to revert established diabetic nephropathy and to examine the effect of glycosaminoglycans on renal extracellular matrix synthesis. Five groups of Sprague-Dawley rats were studied for 12 months: two control groups (treated or untreated non-diabetic), three streptozotocin diabetic animal groups, two of which received a glycosaminoglycan formulation, one from the induction of diabetes and the other after the fifth month of diabetes. At five months the 35S-sulfate glomerular incorporation, albuminuria, glomerular basement membrane thickness and anionic charge density were determined. At 12 months albuminuria, renal collagen IV and perlecan mRNA levels, anionic and neutral dextran clearances, glomerular basement membrane morphometry, and mesangial cell proliferation were evaluated. We demonstrate that long-term administration of glycosaminoglycans prevents renal morphological and functional alterations in diabetic rats and appears to revert established diabetic renal lesions. Glycosaminoglycan administration modified renal matrix composition by the normalization of collagen gene expression and increasing glomerular 35S-sulfate incorporation.

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Ge(IV) phthalocyanine (GePc) with two axially ligated cholesterol moieties was prepared by chemical synthesis and incorporated in a monomeric state into small unilamellar liposomes (CGP 55398). Upon photoexcitation with light wavelengths around its intense absorption peak at 680 nm, GePc shows an efficient photosensitising activity towards biological substrates through a mechanism which largely involves the intermediacy of singlet oxygen. GePc injected systemically into mice bearing an intramuscularly implanted MS-2 fibrosarcoma is quantitatively transferred to serum lipoproteins and localises in the tumour tissue with good efficiency: at 24 h post injection the GePc content in the tumour is 0.74 and 1.87 micrograms per g of tissue with a tumour/peritumoral ratio of 4.35 and 5.67 for injected doses of 0.76 and 1.52 mg kg-1 respectively. At this time the red-light irradiation of the GePc-loaded fibrosarcoma causes a fast and massive tumour necrosis involving both malignant cells and blood vessels. Images Figure 8 Figure 9 Figure 10 Figure 11 Figure 12