Effect Of Pentosan Polysulphate Research Articles

The effects of pentosan polysulphate and polysulphated glycosaminoglycan on chondrogenic differentiation of canine bone marrow-derived mesenchymal stem cells in three-dimensional alginate cultures

The effects of pentosan polysulphate and polysulphated glycosaminoglycan on chondrogenic differentiation of canine bone marrow-derived mesenchymal stem cells in three-dimensional alginate cultures

The effect of pentosan polysulphate on bone healing of rat cranial defects

The purpose of the study was to determine the efficacy of pentosan polysulphate, used in combination with guided bone regeneration on rat skull defects. The study was conducted on 45 adult Wistar rats. On each animal two symmetrical 6 mm wide, full-thickness, skull defects were created in the parietal regions. The right defect was chosen as the experimental site and the left one was left empty to provide a control. Each experimental site was covered by an inner and outer polytetrafluoroethylene membrane. The 45 rats were divided into 3 groups: in group I (n=15), carboxymethyl cellulose, used as a delivery vehicle, was injected between the two membranes; in group II (n=15), 1 mg of pentosan polysulfate was added to the carboxymethyl cellulose vehicle; in group III (n=15), purified micronized eggshell powder was added to the mixture of pentosan polysulfate and carboxymethyl cellulose between the two membranes. In each group, the animals were sacrificed at 42 days. The harvested specimens were processed for contact radiography and standard histological examination. The results were assessed by a Fisher's exact test. All animals, except one, healed uneventfully. In group I, partial bone healing was observed in 14 out of 15 animals. In group II, partial bone healing was observed in 13 out of 15 animals, and complete bone healing in 1 out of 15 cases. In group III, partial resorption of the eggshell implant was observed with a partial bone healing in only 2 cases (P<0.001). In conclusion, significant bone regeneration was observed with the membranes alone. The use of pentosane polysulphate did not result in additional bone gain. The use of particulate material as a space maintainer is also questionable.

Effects of pentosan polysulphate and growth factors on cartilage integrity in animal models of osteoarthritis

Effects of pentosan polysulphate and growth factors on cartilage integrity in animal models of osteoarthritis

Heparin enhances the catalytic activity of des-ETW-thrombin

The thrombin mutant, des-ETW-thrombin, lacking Glu(146), Thr(147), and Trp(148) within a unique insertion loop located at the extreme end of the primary specificity pocket, has been shown previously to exhibit reduced catalytic activity with respect to macromolecular and synthetic thrombin substrates and reduced or enhanced susceptibility to inhibition. Investigation of the hydrolysis of peptidyl p-nitroanilide substrates by des-ETW-thrombin showed increased activity in the presence of heparin and other sulphated glycosaminoglycans. No effect was observed upon the activity of wild-type thrombin. Heparin was found to decrease the K(m) for cleavage of four thrombin-specific substrates by des-ETW-thrombin by 3-4-fold. Similarly, pentosan polysulphate (PPS) decreased the K(m) with these substrates by 8-10-fold. Heparin also increased the rate of inhibition of des-ETW-thrombin by antithrombin III and D-phenylalanyl-prolyl-arginylchloromethane (PPACK). The inhibition of des-ETW-thrombin by a number of thrombin-specific peptide boronic acids also showed significant reduction in the final K(i) in the presence of heparin, due to reduction in the off-rate. A peptide analogue of a sequence of hirudin which binds thrombin tightly to exosite I (fibrinogen recognition site) potentiated the activity of des-ETW-thrombin against peptide p-nitroanilide substrates in a manner similar to heparin. The K(i) for the inhibition of des-ETW-thrombin by p-aminobenzamidine was decreased by these ligands from 9.7 mM to 7.5 mM, 5.1 mM, and 2.5 mM in the presence of heparin, hirudin peptide and PPS respectively, suggesting the increased catalytic activity is due to enhanced access to the primary specificity pocket. The positive influence of these ligands on des-ETW-thrombin was reversed in the presence of ATP or ADP; the latter has previously been shown to inhibit thrombin activity by blocking initial interaction with fibrinogen at exosite 1. Because the effect of heparin and PPS is similar to that of hirudin peptide, it is proposed that the most likely mechanism is that binding at the heparin-binding site (thrombin exosite 2) facilitates interaction at exosite 1 causing a conformational change which partially corrects the defective ground-state binding of the mutant thrombin. Although no effect was observed upon the activity of wild-type thrombin, our findings do provide further evidence of an allosteric property of thrombin which may control the geometry of, and access to, the primary specificity pocket.

Effect of pentosan polysulphate, standard heparin and related compounds on protein kinase C activity

Ca2+/phospholipid-dependent protein kinase (PKC) was inhibited by sulphated polysaccharides. Pentosan polysulphate (PPS) and heparin were 8–10-times more potent than dextran sulphate or heparan sulphate. Steady-state studies revealed that PPS was a competitive inhibitor with respect to ATP with an apparent Ki value of 0.32 μg/ml and a non-competitive inhibitor with respect to histones. In contrast, the inhibition of PKC by heparin was competitive with substrate and non-competitive with respect to ATP. The interaction of sulphated polysaccharides with the catalytic domain of PKC was further demonstrated by the absence of effect on [3H]phorbol 12,13-dibutyrate binding to the regulatory domain of PKC. Furtermore, PPS and heparin inhibited equally cAMP-dependent protein kinase and tyrosine protein kinase. Structure-function relationships indicated that the Inhibition of protein kinases by PPS and heparin fractions was highly dependent on molecular weight. Additionally, PKC-affinity chromatography revealed that a high-molecular-weight heparin fraction with strong anti-PKC activity was eluted. We set out to demonstrate that heparin and PPS, which are potent antiproliferative agents on vascular smooth muscle cells (SMC), alter intracellular PKC activity (both membrane and cytosolic). Therefore, it is suggested that the mechanism by which sulphated polysaccharides inhibit SMC growth may be by direct inhibition of PKC in SMC.

Chondroprotection, myth or reality: An experimental approach

A CHARACTERISTIC feature of osteoarthritis (OA) and chronic rheumatoid arthritis (RA) is the progressive decline in the structural integrity of joint articular cartilage. The ability of a therapeutic substance to prevent this process has led to the concept of chondroprotection but the manner by which chondroprotection can be achieved in practise has not been adequately defined. The mechanisms responsible for failure of cartilage in osteoarthritic joints are still the subject of debate, particularly with regard to whether the primary lesion occurs within cartilage-a chondrocyte/matrix defect, in the subchondral bone-a decrease in compliance, or in the synovium-production of inflammatory mediators and/or proteinases. Irrespective of the initiating event, it is clear that once joint dysfunction is established all these tissues (cartilage, synovial fluid, synovium and subchondral bone) can contribute to progression of the disorder. The situation is summarised in Figure 1, and on these grounds, therapeutic intervention in OA should not be exclusively directed to articular cartilage but must also address the synovial inflammation”* and inadequacies which exist in the synovial fluid3 and subchondral blood s~pply.‘*~ Today, steroidal and nonsteroidal antiinflammatory drugs (NSAIDs) represent the mainstay of nonsurgical treatment of the arthritic patient. Evidence is accumulating to suggest that some of these agents may provide chondroprotection by attenuating the release from activated synovial cells of cytokines, oxygen derived free radicals, and proteinases that are capable of directly or indirectly degrading components of the cartilage matrix.‘-’ However, the effects that NSAIDs may have on the biosynthesis of hyaluronic acid (HA) by synovial fibroblasts has not been previously investigated. Recent studies’,’ with prednisone and triamcinolone hexacetonide have suggested that corticosteroids may provide a chondroprotective effect in OA, since in animal models cartilage lesions and osteophytes were reduced. Corticosteroids act by down regulating cell metabolism” and although this mode of action may be beneficial in the shortterm, by suppressing cell proliferation and the synthesis of proteinases and inflammatory mediators, the long-term consequences, particularly in relation to the inhibition of proteoglycan and HA synthesis by chondrocytes and synovial cells, has limited their application.” Polysulphated polysaccharides, such as glycosaminoglycan polysulphate ester (Arteparon@) and pentosan polysulphate (Cartrophen@) have been demonstrated to exhibit a chondroprotective effect in a variety of in vitro and in vivo systems ‘*‘l-13. however, the action of this class of drugs on synoviocyte proliferation and biosynthesis of HA has received only limited attention. In the present study, the effects of pentosan polysulphate (PPS) and three NSAIDs (tiaprofenic acid, diclofenac sodium, and piroxicam) on DNA and HA biosynthesis, by synovial fibroblast cultures obtained from OA and RA knee joints, were investigated.

132 Thrombolytic effect of pentosan poly-sulphate in animals

132 Thrombolytic effect of pentosan poly-sulphate in animals

The Effect of Pentosanpolysulphate and Carbenoxolone on Bacterial Adherence to the Injured Urothelium

The effect of the glycosaminoglycan (GAG) layer on the adherence of Escherichia coli to the bladder urothelium of rats has been studied. The study was performed by destroying the GAG layer and the changes were observed using the electron microscope. Bacterial adherence to the bladder with a destroyed GAG layer was much higher than to the normal bladder. Following the destruction of the GAG layer, the instillation of sodium pentosanpolysulphate significantly reduced the adhesion of bacteria. Prophylactic intramuscular administration of carbenoxolone increased the speed of regeneration of the destroyed GAG layer.

A Comparison of Pentosan Polysulphate and Heparin II: Effects of Subcutaneous Injection

A comparison has been made between the effects of pentosan polysulphate (SP54) and mucosal heparin following subcutaneous injection in man. Unlike heparin, pentosan polysulphate has relatively little effect in vivo as measured by anti-factor Xa clotting assay and none by an anti-Xa amidolytic assay (S-2222). However, pentosan polysulphate is at least as potent as heparin on a weight basis in producing activation of lipoprotein lipase, shortening of the euglobulin clot lysis time and impairing the generation of factor Xa. Our data indicate that pentosan polysulphate has more marked effects in vivo than in vitro, that the action of the drug on clotting is mediated mainly via an At III-independent pathway, and that its effects are not confined to the coagulation system.