chondroitin-sulfates and Calcinosis

Calcific aortic valve disease (CAVD), has been characterized as a cascade of cellular changes leading to leaflet thickening and valvular calcification. In diseased aortic valves, glycosaminoglycans (GAGs) normally found in the valve spongiosa migrate to the collagen I-rich fibrosa layer near calcified nodules. Current treatments for CAVD are limited to valve replacement or drugs tailored to other cardiovascular diseases.. Porcine aortic valve interstitial cells and porcine aortic valve endothelial cells were seeded into collagen I hydrogels of varying initial stiffness or initial stiffness-matched collagen I hydrogels containing the glycosaminoglycans chondroitin sulfate (CS), hyaluronic acid (HA), or dermatan sulfate (DS). Assays were performed after 2 weeks in culture to determine cell gene expression, protein expression, protein secretion, and calcification. Multiple regression analyses were performed to determine the importance of initial hydrogel stiffness, GAGs, and the presence of endothelial cells on calcification, both with and without osteogenic medium.. High initial stiffness hydrogels and osteogenic medium promoted calcification, while for DS or HA the presence of endothelial cells prevented calcification. CS was found to increase the expression of pro-calcific genes, increase activated myofibroblast protein expression, induce the secretion of collagen I by activated interstitial cells, and increase calcified nodule formation.. This study demonstrates a more complete model of aortic valve disease, including endothelial cells, interstitial cells, and a stiff and disease-like ECM. In vitro models of both healthy and diseased valves can be useful for understanding the mechanisms of CAVD pathogenesis and provide a model for testing novel therapeutics.

Topics: Animals; Aortic Valve; Aortic Valve Stenosis; Calcinosis; Cells, Cultured; Chondroitin Sulfates; Collagen; Endothelial Cells; Glycosaminoglycans; Hydrogels; Swine

To determine the effect of intraoperative ophthalmic viscosurgical devices (OVDs) on late opacification of the Hydroview hydrogel intraocular lens (IOL) (Bausch & Lomb Surgical).. Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada.. A retrospective study of 949 cases of Hydroview IOL implantations from February 1998 to September 2000 was conducted. Of the 949 implantations, 462 were performed by 1 surgeon (J.H.S.) using Viscoat (sodium chondroitin sulfate 4.0%-sodium hyaluronate 3.0%) and 487 were performed by a second surgeon (W.A.N.) using Biolon (sodium hyaluronate 1.0%). Surgical techniques were identical with the exception of surgeon OVD preference. The number of IOLs opacifying and requiring explantation was determined in each group.. Seventy-one Hydroview IOLs had surface calcification deposits that presented a mean of 39 months postoperatively. Twenty-two IOLs opacified sufficiently to warrant a recommendation of IOL explantation; 20 IOLs were explanted, and 2 surgeries were cancelled due to death or disability. In all cases of opacification, Viscoat had been used intraoperatively. This represented a 15.4% incidence of opacification in the Viscoat group, with 31.0% cases severe enough to warrant a recommendation of explantation.. The results suggest that the intraoperative use of Viscoat has a facilitating role in the development of late calcification and opacification of the Hydroview IOL.

Topics: Adult; Aged; Aged, 80 and over; Calcinosis; Chondroitin; Chondroitin Sulfates; Device Removal; Drug Combinations; Female; Humans; Hyaluronic Acid; Hydrogel, Polyethylene Glycol Dimethacrylate; Incidence; Lens Implantation, Intraocular; Lenses, Intraocular; Male; Middle Aged; Prosthesis Failure; Reoperation; Retrospective Studies

Chemical modification of biological materials used in the manufacture of cardiac valves tends to reduce the relatively high degree of biodegradation and calcification of the implanted bioprostheses. The most widely used treatment to reduce biodegradability of the valves is glutaraldehyde fixation. However, this treatment is potentially toxic and induces tissue calcification. In order to minimize these undesirable effects, we have analyzed the effect of a pre-fixation of endogenous proteoglycans and exogenous glycosaminoglycans, as well as the borohydride reduction influence on the different modified ostrich pericardium implants after subcutaneous implantation in rats. The presence of calcific deposits was detected in all implanted GA-fixed samples; however, calcification was highly reduced in both groups of periodate-prefixed materials, which showed also a very low Ca/P molar ratio. Borohydride post-treatment of these biomaterials resulted in a significant increase in calcium phosphate precipitation, with the appearance of calcium deposits mainly in an amorphous form even though X-ray diffraction allowed the detection of brushite- and apatite-like crystals. Regarding tissue stability, no significant differences were found among the borohydride-untreated implants but higher levels of matrix metalloproteinases were observed by gelatin zymography in the periodate pre-fixed materials. This increase was partially reduced by pre-fixation of exogenous chondroitin 4-sulfate. On the other hand, borohydride post-treatment not only increased calcification, but also reduced tissue stability and increased the presence of matrix-degrading activities.

Topics: Animals; Biocompatible Materials; Bioprosthesis; Calcinosis; Chondroitin Sulfates; Graft Rejection; In Vitro Techniques; Materials Testing; Pericardium; Periodic Acid; Prosthesis Failure; Proteoglycans; Rats; Rats, Wistar; Struthioniformes; Tissue Fixation

The effect of removal of glycosylaminoglycans on the mineralization of sheep periodontal ligament was determined using enzyme digests followed by incubation in solutions supersaturated with respect to hydroxyapatite at pH 7.4. TEM revealed that control periodontal ligament remained unmineralized. However, tissue from which glycosylaminoglycans had been removed contained plate-like crystals arranged parallel to and within the collagen fibrils. Electron probe and electron diffraction studies suggested that the crystals were apatitic with a similar order of crystallinity to dentine, and a Ca:P ratio of 1.61. In addition, the glycosylaminoglycan content of periodontal ligament, cementum and alveolar bone was compared using cellulose acetate electrophoresis. Periodontal ligament contained predominantly dermatan sulfate while cementum and alveolar bone contained mostly chondroitin sulfate. A role for glycosylaminoglycans in maintaining the unmineralized state of the periodontal ligament is suggested. Control of expression of specific proteoglycan species on a spatially restricted basis is presumably central to this role.

Topics: Alveolar Process; Animals; Apatites; Calcinosis; Calcium; Chondroitin Sulfates; Collagen; Crystallization; Dental Cementum; Dentin; Dermatan Sulfate; Electron Probe Microanalysis; Electrophoresis, Cellulose Acetate; Female; Glycosaminoglycans; Microscopy, Electron; Minerals; Periodontal Ligament; Phosphorus; Sheep

The causative mechanism of tendon calcification ('calcifying tendinitis') is unknown. In this report, pathological human tendon samples were examined to give morphological and ultrastructural detail of the calcified regions and these findings were compared with those from normal tendon. Selected specimens were cryosectioned to enable histochemical and immunohistochemical comparison of the occurrence and distribution of specific matrix molecules in diseased and normal tendon tissues. The lack of collagen type II and alkaline phosphatase in the pathological regions suggests that the calcification process is not mediated through an endochondral transition. In contrast, the pathological areas were characterised by widespread labelling for chondroitin-4-sulphate/dermatan sulphate and intense pericellular localisation of chondroitin-6-sulphate.

Topics: Adult; Calcinosis; Chondroitin Sulfates; Collagen; Dermatan Sulfate; Female; Humans; Male; Microscopy, Electron; Middle Aged; Rotator Cuff; Tendinopathy

Glutaraldehyde crosslinking of native or reconstituted collagen fibrils and tissues rich in collagen significantly reduces biodegradation. Other aldehydes are less efficient than glutaraldehyde in generating chemically, biologically, and thermally stable crosslinks. Tissues crosslinked with glutaraldehyde retain many of the viscoelastic properties of the native collagen fibrillar network which render them suitable for bioprostheses. Implants of collagenous materials crosslinked with glutaraldehyde are subject long-term to calcification, biodegradation, and low-grade immune reactions. We have attempted to overcome these problems by enhancing crosslinking through bridging of activated carboxyl groups with diamines and using glutaraldehyde to crosslink the epsilon-NH2 groups in collagen and the unreacted amines introduced by aliphatic diamines. This crosslinking reduces tissue degradation and nearly eliminates humoral antibody induction. Covalent binding of diphosphonates, specifically 3-amino-1-hydroxypropane-1, 1-diphosphonic acid (3-APD), and chondroitin sulfate to collagen or to the crosslink-enhanced collagen network reduces its potential for calcification. Platelet aggregation is also reduced by glutaraldehyde crosslinking and nearly eliminated by the covalent binding of chondroitin sulfate to collagen. The cytotoxicity of residual glutaraldehyde--leaching through the interstices of the collagen fibrils or the tissue matrix--and of reactive aldehydes associated with the bound polymeric glutaraldehyde can be minimized by neutralization and thorough rinsing after crosslinking and storage in a nontoxic bacteriostatic solution.

Topics: Adenosine Diphosphate; Animals; Biocompatible Materials; Bioprosthesis; Calcinosis; Calcium; Chondroitin Sulfates; Collagen; Diphosphonates; Glutaral; Heparin; Hydroxyapatites; Microbial Collagenase; Phosphates; Platelet Aggregation; Pronase; Proteoglycans; Rats

Band keratopathy developed rapidly in two patients following uneventful phacoemulsification and intraocular lens implantation using BSS Plus (balanced salt solution enriched with glutathione, bicarbonate, and glucose) infusion and Viscoat (chondroitin sulfate-sodium hyaluronate), which was left in the anterior chamber at the conclusion of the procedure. Histopathologic evaluation of corneal tissue obtained from one patient at the time of edetic acid chelation revealed histochemical findings consistent with anterior stromal calcification. To investigate a possible relationship between Viscoat and the rapid onset of band keratopathy, Viscoat formulated with varying concentrations of phosphate buffer was injected intracamerally into 42 rabbit eyes. Within 48 hours, clinically obvious corneal opacification developed in nine (47%) of 19 eyes injected with the commercial preparation of Viscoat. Also, similar opacification developed in ten (77%) of 13 eyes that received Viscoat formulated with twice the phosphate concentration of the commercial preparation. Band keratopathy did not develop any of ten eyes that received Viscoat with one fourth the commercial phosphate concentration. In selected opacified corneas, the presence of phosphorus in the subepithelial and posterior corneal stroma was confirmed by histochemical stains and energy-dispersive x-ray analysis.

Topics: Aged; Aged, 80 and over; Animals; Anterior Chamber; Calcinosis; Chondroitin; Chondroitin Sulfates; Corneal Diseases; Drug Combinations; Female; Humans; Hyaluronic Acid; Instillation, Drug; Male; Rabbits

Topics: Adult; Age Factors; Aged; Calcinosis; Chondroitin Sulfates; Endocrine System Diseases; Humans; Joint Diseases; Middle Aged; Nervous System Diseases; Vascular Diseases

Analyses of the cystic fluid from a patient with massive tissue calcification showed a significant amount of acid mucopolysaccharides (mainly hyaluronic acid) and phospholipid-polypeptide complexes. The possible role of those molecules in this type of calcinosis is discussed.

Topics: Calcinosis; Calcium; Chondroitin Sulfates; Cysts; Female; Glycosaminoglycans; Humans; Hyaluronic Acid; Hyperparathyroidism, Secondary; Kidney Diseases; Middle Aged; Phospholipids; Proteins

Specimens of different intracranial tumors as well as samples of normal brain have been studied for calcium, magnesium, phosphorus, phospholipids and glycosaminoglycans contents. Tumor tissue showed calcium and magnesium concentrations higher than normal tissue. Brain tumors exhibit a decreased phospholipid concentration than normal brain, and its ability to complex divalent cations (specially magnesium) appears impaired. The glycosaminoglycans contents show no correlation with the concentration of calcium but in cases of observable calcification (meningiomas) a preponderance of chondroitin sulfate was observed.

Topics: Binding Sites; Brain Neoplasms; Calcinosis; Calcium; Chondroitin Sulfates; Glycosaminoglycans; Humans; Magnesium; Meningioma; Phospholipids; Phosphorus

Topics: Calcification, Physiologic; Calcinosis; Chondroitin; Chondroitin Sulfates; Humans