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Journal of Endourology Dec 2003The clinical role for pentosan polysulfate (PPS) in the prevention of calcium oxalate urolithiasis is not known. Crystallization and aggregation are important steps in... (Comparative Study)
Comparative Study Review
The clinical role for pentosan polysulfate (PPS) in the prevention of calcium oxalate urolithiasis is not known. Crystallization and aggregation are important steps in calcium oxalate stone formation, and PPS has been shown to inhibit these steps, both in vitro and in vivo. In addition, PPS has a role in repairing injured urothelium and inhibiting adhesion to epithelial defects. A randomized double-blind placebo-controlled study appears warranted to assess the utility of PPS in the prevention of recurrent calcium oxalate stones.
Topics: Administration, Oral; Biological Availability; Calcium Oxalate; Clinical Trials as Topic; Female; Humans; Infusions, Intravenous; Male; Pentosan Sulfuric Polyester; Sensitivity and Specificity; Treatment Outcome; Urinary Calculi
PubMed: 14744348
DOI: 10.1089/089277903772036136 -
Carbohydrate Polymers Apr 2020Rapid advances have been made in developing analytical technologies for characterization of highly heterogeneous active ingredients of complex drugs, such as pentosan...
Rapid advances have been made in developing analytical technologies for characterization of highly heterogeneous active ingredients of complex drugs, such as pentosan polysulfate (PPS), active ingredient of the drug Elmiron®, approved by the Food and Drug Administration and marketed in the United States to treat interstitial cystitis. PPS sulfated polysaccharides comprise of a repeat unit of β(1-4)-D-xylopyranoses randomly substituted by 4-O-methyl-glucopyranosyluronic acid. To define the critical quality attributes (CQAs) of such a complex drug, it is critical to develop an approach that integrates data from orthogonal analytical methodologies. Here, we developed an approach integrating diverse analytical tools including gel permeation chromatography, LC/ESI-MS and NMR to measure CQAs of PPS. The proposed mathematical framework integrates the data from these diverse analytical methods as function of PPS chain length and building blocks. Our approach would facilitate in establishing a scientific foundation for comparative characterization of drug products with complex active ingredients.
Topics: Carbohydrate Conformation; Chromatography, Gel; Cystitis, Interstitial; Humans; Magnetic Resonance Spectroscopy; Molecular Weight; Pentosan Sulfuric Polyester; Spectrometry, Mass, Electrospray Ionization
PubMed: 32070534
DOI: 10.1016/j.carbpol.2020.115913 -
Minerva Surgery Jun 2023
Topics: Rats; Animals; Cystitis, Interstitial; Urinary Bladder; Hyaluronic Acid; Pentosan Sulfuric Polyester; Mast Cells; Perfusion
PubMed: 35708444
DOI: 10.23736/S2724-5691.22.09557-0 -
The Journal of Veterinary Medical... Aug 2020Pentosan polysulfate (PPS) is a semi-synthetic sulfated polysaccharide compound which has been shown the benefits on therapeutic treatment for osteoarthritis (OA) and...
Pentosan polysulfate (PPS) is a semi-synthetic sulfated polysaccharide compound which has been shown the benefits on therapeutic treatment for osteoarthritis (OA) and has been proposed as a disease modifying osteoarthritis drugs (DMOADs). This study investigated the effects of PPS on cell proliferation, particularly in cell cycle modulation and phenotype promotion of canine articular chondrocytes (AC). Canine AC were treated with PPS (0-80 µg/ml) for 24, 48 and 72 hr. The effect of PPS on cell viability, cell proliferation and cell cycle distribution were analyzed by MTT assay, DNA quantification and flow cytometry. Chondrocyte phenotype was analyzed by quantitative real-time PCR (qPCR) and glycosaminoglycan (GAG) quantification. PPS significantly reduced AC proliferation through cell cycle modulation particularly by maintaining a significantly higher proportion of chondrocytes in the G1 phase and a significantly lower proportion in the S phase of the cell cycle in a concentration- and time-dependent manner. While the proportion of chondrocytes in G1 phase corresponded with the significant downregulation of cyclin-dependent kinase (CDK) 1 and 4. Furthermore, the study confirms that PPS promotes a chondrogenic phenotype of AC through significant upregulation of collagen type II (Col2A1) mRNA and GAG synthesis. The effect of PPS on the inhibition of chondrocyte proliferation while promoting a chondrocyte phenotype could be beneficial in the early stages of OA treatment, which transient increase in proliferative activity of chondrocytes with subsequent phenotypic shift and less productive in an essential component of extracellular matrix (ECM) is observed.
Topics: Animals; Cartilage, Articular; Cell Cycle; Cell Proliferation; Cell Survival; Cells, Cultured; Chondrocytes; Chondrogenesis; Cyclin-Dependent Kinases; Dogs; Gene Expression Regulation; Osteoarthritis; Pentosan Sulfuric Polyester
PubMed: 32641601
DOI: 10.1292/jvms.20-0091 -
The Journal of Urology Oct 1984Pentosan polysulfate was studied as a calcium oxalate crystal growth inhibitor. The inhibition from pentosan polysulfate at concentrations ranging from 3.5 to 110 mg./l....
Pentosan polysulfate was studied as a calcium oxalate crystal growth inhibitor. The inhibition from pentosan polysulfate at concentrations ranging from 3.5 to 110 mg./l. was measured in simple inorganic calcium oxalate solutions at pH 5, 6 and 7. Pentosan polysulfate also was mixed with urine at concentrations from 10 to 350 mg./l. and inhibition determined. Measurement of calcium oxalate crystal growth inhibition was performed in a seeded crystal growth system. One inhibitory unit (concentration of pentosan polysulfate necessary to give a 50 per cent reduction in the rate of crystal growth) was 5.7 +/- 2 mg./l. at pH 5, 7.2 +/- 1.1 mg./l. at pH 6 and 6.0 +/- 2.1 mg./l. at pH 7. Urine-pentosan polysulfate mixtures showed more inhibitory activity than the predicted inhibition present. Addition of pentosan polysulfate to urine at a concentration of 10 mg./l. increased the inhibitory activity from 45 +/- 3 to 59 +/- 3 IU/l. Pentosan polysulfate is a potent calcium oxalate crystal growth inhibitor in urine at physiologic pH levels. If the urinary concentration of pentosan polysulfate after oral administration reaches 10 mg./l., the increase in inhibitory activity in urine that may occur might be important in the treatment of patients who form calcium oxalate calculi within the urinary tract.
Topics: Calcium Oxalate; Crystallization; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Pentosan Sulfuric Polyester; Polysaccharides; Urine
PubMed: 6206244
DOI: 10.1016/s0022-5347(17)49873-9 -
Journal of Virology Aug 2015Arthritogenic alphaviruses such as Ross River virus (RRV) and chikungunya virus (CHIKV) cause large-scale epidemics of severe musculoskeletal disease and have been...
UNLABELLED
Arthritogenic alphaviruses such as Ross River virus (RRV) and chikungunya virus (CHIKV) cause large-scale epidemics of severe musculoskeletal disease and have been progressively expanding their global distribution. Since its introduction in July 2014, CHIKV now circulates in the United States. The hallmark of alphavirus disease is crippling pain and inflammation of the joints, a similar immunopathology to rheumatoid arthritis. The use of glycans as novel therapeutics is an area of research that has increased in recent years. Here, we describe the promising therapeutic potential of the glycosaminoglycan (GAG)-like molecule pentosan polysulfate (PPS) to alleviate virus-induced arthritis. Mouse models of RRV and CHIKV disease were used to characterize the extent of cartilage damage in infection and investigate the potential of PPS to treat disease. This was assessed using histological analysis, real-time PCR, and fluorescence-activated cell sorting (FACS). Alphaviral infection resulted in cartilage destruction, the severity of which was alleviated by PPS therapy during RRV and CHIKV clinical disease. The reduction in cartilage damage corresponded with a significant reduction in immune infiltrates. Using multiplex bead arrays, PPS treatment was found to have significantly increased the anti-inflammatory cytokine interleukin-10 and reduced proinflammatory cytokines, typically correlated with disease severity. Furthermore, we reveal that the severe RRV-induced joint pathology, including thinning of articular cartilage and loss of proteoglycans in the cartilage matrix, was diminished with treatment. PPS is a promising new therapy for alphavirus-induced arthritis, acting to preserve the cartilage matrix, which is damaged during alphavirus infection. Overall, the data demonstrate the potential of glycotherapeutics as a new class of treatment for infectious arthritis.
IMPORTANCE
The hallmark of alphavirus disease is crippling pain and joint arthritis, which often has an extended duration. In the past year, CHIKV has expanded into the Americas, with approximately 1 million cases reported to date, whereas RRV continues to circulate in the South Pacific. Currently, there is no licensed specific treatment for alphavirus disease, and the increasing spread of infection highlights an urgent need for therapeutic intervention strategies. Pentosan polysulfate (PPS) is a glycan derivative that is orally bioavailable, has few toxic side effects, and is currently licensed under the name Elmiron for the treatment of cystitis in the United States. Our findings show that RRV infection damages the articular cartilage, including a loss of proteoglycans within the joint. Furthermore, treatment with PPS reduced the severity of both RRV- and CHIKV-induced musculoskeletal disease, including a reduction in inflammation and joint swelling, suggesting that PPS is a promising candidate for drug repurposing for the treatment of alphavirus-induced arthritis.
Topics: Animals; Cartilage; Chikungunya Fever; Chikungunya virus; Disease Models, Animal; Glycosaminoglycans; Humans; Joint Diseases; Mice; Mice, Inbred C57BL; Pentosan Sulfuric Polyester
PubMed: 26018160
DOI: 10.1128/JVI.00224-15 -
The Journal of Urology Sep 1987
Clinical Trial
Topics: Clinical Trials as Topic; Cystitis; Humans; Pentosan Sulfuric Polyester
PubMed: 2442420
DOI: 10.1016/s0022-5347(17)43268-x -
Ophthalmology Jul 2019
Topics: Humans; Macular Degeneration; Pentosan Sulfuric Polyester
PubMed: 31229011
DOI: 10.1016/j.ophtha.2018.12.038 -
The Biochemical Journal Apr 2012The semi-synthetic sulfated polysaccharide PPS (pentosan polysulfate) increases affinity between the aggrecan-degrading ADAMTSs (adamalysins with thrombospondin motifs)...
The semi-synthetic sulfated polysaccharide PPS (pentosan polysulfate) increases affinity between the aggrecan-degrading ADAMTSs (adamalysins with thrombospondin motifs) and their endogenous inhibitor, TIMP (tissue inhibitor of metalloproteinases)-3. In the present study we demonstrate that PPS mediates the formation of a high-affinity trimolecular complex with ADAMTS-5 and TIMP-3. A TIMP-3 mutant that lacks extracellular-matrix-binding ability was insensitive to this affinity increase, and truncated forms of ADAMTS-5 that lack the Sp (spacer) domain had reduced PPS-binding ability and sensitivity to the affinity increase. PPS molecules composed of 11 or more saccharide units were 100-fold more effective than those of eight saccharide units, indicating the involvement of extended or multiple protein-interaction sites. The formation of a high-affinity trimolecular complex was completely abolished in the presence of 0.4 M NaCl. These results suggest that PPS enhances the affinity between ADAMTS-5 and TIMP-3 by forming electrostatically driven trimolecular complexes under physiological conditions.
Topics: ADAM Proteins; ADAMTS5 Protein; Amino Acid Substitution; Chromatography, Gel; HEK293 Cells; Humans; Pentosan Sulfuric Polyester; Protein Binding; Protein Structure, Tertiary; Recombinant Proteins; Sequence Deletion; Sodium Chloride; Tissue Inhibitor of Metalloproteinase-3
PubMed: 22299597
DOI: 10.1042/BJ20112159 -
The Urologic Clinics of North America May 2022Interstitial cystitis/bladder pain syndrome (IC/BPS) is defined as persistent or chronic discomfort perceived to be related to the urinary bladder accompanied by urinary... (Review)
Review
Interstitial cystitis/bladder pain syndrome (IC/BPS) is defined as persistent or chronic discomfort perceived to be related to the urinary bladder accompanied by urinary urgency or frequency. Pharmacotherapies used to treat IC/BPS include oral and intravesical agents. Oral therapies include amitriptyline, hydroxyzine, cyclosporine A, and pentosan polysulfate sodium (PPS), although the recent finding of pigmented maculopathy with chronic PPS is very concerning and must be discussed with patients, many of whom will choose to either come off this medicine or not even start it. Certolizumab pegol is a pharmacologic therapy that is currently in clinical development for treatment of IC/BPS symptoms.
Topics: Cystitis, Interstitial; Female; Humans; Male; Pentosan Sulfuric Polyester; Urinary Bladder
PubMed: 35428433
DOI: 10.1016/j.ucl.2022.01.003