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Bladder (San Francisco, Calif.) 2023Pentosan Polysulfate (PPS) is the only oral treatment for interstitial cystitis (IC)-bladder pain syndrome (BPS) approved by the World Health Organization....
OBJECTIVES
Pentosan Polysulfate (PPS) is the only oral treatment for interstitial cystitis (IC)-bladder pain syndrome (BPS) approved by the World Health Organization. Self-evaluation scales can provide more objective results on pre- and post-treatment satisfaction. The aim of this study was to investigate the effect of pentosan polysulfate treatment on symptoms in IC-BPS patients.
METHODS
This study included 37 adult male and female patients with IC-BPS who reported pain, urinary urgency, polyurea, and nocturia without urinary tract infection for a minimum of six months prior to the study and were taking 300 mg/day oral pentosan polysulfate. Pre- and post-treatment symptoms, Interstitial Cystitis Symptom Index (ICSI) Scores, quality of life (QoL) scores (1-4), and satisfaction conditions were examined.
RESULTS
Following the application of inclusion and exclusion criteria, mean age of 37 suitable patients was 46.0±11.9 years and 27% (10 individuals) of the patients were male. Pre-treatment, ICSI scores, and measures of satisfaction degree and QoL increased significantly after the treatment (p<0.001). Adverse reaction was detected in two patients (5.4%) among the patients treated with pentosan polysulfate.
CONCLUSIONS
Oral pentosan polysulfate for the treatment of interstitial cystitis/bladder pain syndrome treatment could achieve recovery in symptoms, increase Interstitial Cystitis Symptom Index score and improve quality of life and patient satisfaction.
PubMed: 37936582
DOI: 10.14440/bladder.2023.866 -
Stem Cell Research May 2020We evaluated the synergistic effects of pentosan polysulfate sodium (PPS) and mesenchymal stem cells (MSCs) in an interstitial cystitis (IC) rat model. After generation...
We evaluated the synergistic effects of pentosan polysulfate sodium (PPS) and mesenchymal stem cells (MSCs) in an interstitial cystitis (IC) rat model. After generation of the IC rat model, the rats were divided into 4 groups according to the treatment they received: phosphate-buffered saline injection into bladder submucosa, daily oral PPS feeding, MSC injection into bladder submucosa, or MSC injection into bladder submucosa with daily oral PPS feeding. After treatment, conscious cystometry and pain scale measurement were performed and their bladders were obtained for histological and proinflammatory-related gene expression analysis. On cystometric analysis, all treatment groups showed significantly increased intercontraction intervals and lower pain scores compared to those of the control group. Histological analysis revealed regenerated urothelium, less fibrosis, and decreased mast cell infiltration in all treatment groups compared to the control group. Significantly lower expression of TNF-α, IFN-γ, MCP, IL-6, TLR2, and TLR11 was observed in the PPS with MSC group compared to the other groups. Combination therapy with PPS and MSCs showed histological and functional effects in an IC rat model, including synergistic effects leading to increased intercontraction interval and decreased inflammatory reactions.
Topics: Adipose Tissue; Animals; Cystitis, Interstitial; Inflammation; Mesenchymal Stem Cells; Pentosan Sulfuric Polyester; Rats
PubMed: 32334368
DOI: 10.1016/j.scr.2020.101801 -
Clinical Ophthalmology (Auckland, N.Z.) 2021To investigate the prevalence of retinal pathology in patients with a history of exposure to pentosan polysulfate sodium (PPS).
AIM
To investigate the prevalence of retinal pathology in patients with a history of exposure to pentosan polysulfate sodium (PPS).
METHODS
Patients exposed to PPS and seen in the ophthalmology clinic at Northwestern University during 1/1/2002 to 1/1/2019 were identified from electronic health records (EHR) by an electronic data warehouse (EDW) search. Visual acuity (VA), reasons for clinic visit, ocular conditions, and duration of exposure to PPS were noted. Chart review was performed for fundus exam findings and ophthalmologic imaging, specifically fundus photography, fundus autofluorescence, and ocular coherence tomography (OCT) images. When OCT or fundus photography was available, studies were evaluated by two independent graders.
RESULTS
A total of 131 patients who were exposed to PPS and seen at the Northwestern Ophthalmology clinic were identified in the EHR. Forty patients of 131 had imaging. Patients with imaging or fundus examination suspicious for PPS maculopathy were placed into the suspect group. Of the 40 patients that had imaging, 5 (12.5%) had features suspicious for PPS maculopathy. Of the remaining 91, 5 (5.4%) had macular pigmentary changes described on fundus exam. Among the 10 patients in the suspect group, the average duration of PPS use was 4.2 years (range 0.3-11.6 years, interquartile range 5.5 years) and the average cumulative dose was 380g (range 29-1092g, interquartile range 132g).
CONCLUSION
A novel drug-induced maculopathy has been associated with PPS use with a distinct clinical constellation that can be accurately identified with multimodal imaging.
PubMed: 33603329
DOI: 10.2147/OPTH.S285013 -
BMC Musculoskeletal Disorders Mar 2021Alphaviruses, such as Ross River (RRV) and chikungunya virus (CHIKV), cause significant global morbidity, with outbreaks of crippling joint inflammation and pain,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Alphaviruses, such as Ross River (RRV) and chikungunya virus (CHIKV), cause significant global morbidity, with outbreaks of crippling joint inflammation and pain, leaving patients incapacitated for months to years. With no available vaccine or specific therapeutic for any alphaviral disease, and a growing economic and public health burden, there is a serious need for the development of specific therapies.
METHODS
This study evaluated the safety and efficacy of pentosan polysulfate sodium (PPS) in subjects with RRV-induced arthralgia in a double-blind, placebo-controlled trial. Twenty subjects were randomized 2:1 to subcutaneous PPS (2 mg/kg) or placebo (sodium chloride 0.9%) twice weekly for 6 weeks. Safety evaluation included physical examination, concomitant medications, and laboratory findings. Efficacy assessments included change from baseline in joint function (hand grip strength and RAPID3) and quality of life (SF-36) at Days 15, 29, 39 and 81 after treatment initiation. Inflammatory and cartilage degradation biomarkers were exploratory endpoints.
RESULTS
PPS was well tolerated, with a similar proportion of subjects reporting at least one treatment-emergent adverse event (TEAE) in the treatment and placebo groups. Injection site reactions were the most common TEAE and occurred more frequently in the PPS group. Dominant hand grip strength and SF-36 scores improved with PPS at all time points assessed, with hand grip strength improvement of 6.99 kg (p = 0.0189) higher than placebo at Day 15. PPS showed significant improvements versus placebo in adjusted mean relative change from baseline for RAPID3 Pain (p = 0.0197) and Total (p = 0.0101) scores at Day 15. At the conclusion of the study overall joint symptoms, assessed by RAPID3, showed near remission in 61.5% of PPS subjects versus 14.3% of placebo subjects. Additionally, PPS treatment improved COMP, CTX-II, CCL1, CXCL12, CXCL16 and CCL17 biomarker levels versus placebo.
CONCLUSIONS
Overall, the improvements in strength and joint symptoms warrant further evaluation of PPS as a specific treatment for RRV-induced and other forms of arthritis.
TRIAL REGISTRATION
This trial is registered at the Australian New Zealand Clinical Trials Registry # ACTRN12617000893303 .
Topics: Arthralgia; Australia; Double-Blind Method; Hand Strength; Humans; Pentosan Sulfuric Polyester; Quality of Life; Ross River virus; Treatment Outcome
PubMed: 33711991
DOI: 10.1186/s12891-021-04123-w -
BMC Veterinary Research May 2018Sodium pentosan polysulfate (NaPPS) was testified as a chondroprotective drug in with a detailed rationale of the disease-modifying activity. This study was undertaken...
BACKGROUND
Sodium pentosan polysulfate (NaPPS) was testified as a chondroprotective drug in with a detailed rationale of the disease-modifying activity. This study was undertaken to determine whether anti-osteoarthritis drug, NaPPS inhibited osteoclasts (OC) differentiation and function. Canine bone marrow mononuclear cells (n = 6) were differentiated to OC by maintaining with receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) for up to 7 days with the treatment of NaPPS at concentration of 0, 0.2, 1 and 5 μg/mL. Differentiation and function of OC were accessed using tartrate-resistant acid phosphate (TRAP) staining and bone resorption assay, while monitoring actin ring formation. Invasion and colocalization patterns of fluorescence-labeled NaPPS with transcribed gene in OC were monitored. Gene expression of OC for cathepsin K (CTK), matrix metallopeptidase-9 (MMP-9), nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), c-Fos, activator protein-1(AP-1) and carbonic anhydrase II was examined using real-time PCR.
RESULTS
Significant inhibition of OC differentiation was evident at NaPPS concentration of 1 and 5 μg/mL (p < 0.05). In the presence of 0.2 to 5 μg/mL NaPPS, bone resorption was attenuated (p < 0.05), while 1 and 5 μg/mL NaPPS achieved significant reduction of actin ring formation. Intriguingly, fluorescence-labeled NaPPS invaded in to cytoplasm and nucleus while colocalizing with actively transcribed gene. Gene expression of CTK, MMP-9 and NFATc1 were significantly inhibited at 1 and 5 μg/mL (p < 0.05) of NaPPS whereas inhibition of c-Fos and AP-1 was identified only at concentration of 5 μg/mL (p < 0.05).
CONCLUSIONS
Taken together, all the results suggest that NaPPS is a novel inhibitor of RANKL and M-CSF-induced CTK, MMP-9, NFATc1, c-Fos, AP-1 upregulation, OC differentiation and bone resorption which might be a beneficial for treatment of inflammatory joint diseases and other bone diseases associated with excessive bone resorption.
Topics: Actins; Animals; Bone Marrow Cells; Cell Differentiation; Cells, Cultured; Dogs; Humans; Macrophage Colony-Stimulating Factor; Osteoclasts; Pentosan Sulfuric Polyester; RANK Ligand; Transcription Factors
PubMed: 29720166
DOI: 10.1186/s12917-018-1466-4 -
PloS One 2017Osteoarthritic (OA) chondrocytes are shown to express inducible nitric oxide synthase (iNOS) which produces high concentrations of nitric oxide (NO), particularly when...
Osteoarthritic (OA) chondrocytes are shown to express inducible nitric oxide synthase (iNOS) which produces high concentrations of nitric oxide (NO), particularly when stimulated with proinflammatory cytokines. NO is involved in OA cartilage degradation. On the other hand, c-Jun N-terminal Kinase (JNK) pathway mediates the activation and transcription of c-Jun, which is required for interleukin-1 (IL-1)-induction of matrix metalloproteinases-13 (MMP-13) in OA pathogenesis. Therefore, the selective inhibition of iNOS and c-Jun is a promising target for treatment and prevention of OA. The purpose of the study was to investigate the inhibitory effects of pentosan polysulfate (PPS) on IL-1β-induced iNOS, c-Jun and HIF-α isoforms upregulation in canine articular chondrocytes (CACs). Primary (P0) chondrocytes were isolated and cultured from femoral head cartilages of three (3) dogs. First passage (P1) chondrocytes were preincubated with 0, 1, 5, 15 and 40 μg/mL of PPS for 4 hr before treatment with 10 ng/mL rhIL-1β for a further 8 hr. In addition, we evaluated the effects of single and multiple cytokine with or without LPS on iNOS protein induction. PPS significantly inhibited (P < 0.05) IL-1β-induced iNOS, c-Jun and HIF-1α mRNA upregulation in a dose-dependent pattern. iNOS mRNA was significantly inhibited at 15 and 40 μg/mL whereas c-Jun and HIF-1α were significantly downregulated at 5, 15 and 40 μg/mL of PPS compared to chondrocytes treated with only rhIL-1β. Intriguingly, CACs were recalcitrant to single IL-1β, TNF-α or LPS-induction of iNOS protein including to a combination of IL-1β+TNF-α, IL-1β+LPS except to TNF-α+LPS and IL-1β+TNF-α+LPS suggestive of a protective mechanism from iNOS detrimental effects on perpetuating OA. IL-1β+TNF-α+LPS-induced iNOS protein expression was significantly abrogated by PPS. We demonstrate for the first time that PPS is a novel inhibitor of IL-1β-induced iNOS, c-Jun, and HIF-1α mRNA upregulation and iNOS protein induction which may be beneficial for prevention and treatment OA.
Topics: Animals; Cartilage, Articular; Chondrocytes; Dogs; Genes, jun; Hypoxia-Inducible Factor 1, alpha Subunit; Interleukin-1beta; Nitric Oxide Synthase Type II; Pentosan Sulfuric Polyester; RNA, Messenger; Up-Regulation
PubMed: 28472120
DOI: 10.1371/journal.pone.0177144 -
Postgraduate Medical Journal Aug 2003The medical literature was reviewed from 1968-2002 using Medline and the key words "intra-articular" and "osteoarthritis" to determine the various intra-articular... (Review)
Review
The medical literature was reviewed from 1968-2002 using Medline and the key words "intra-articular" and "osteoarthritis" to determine the various intra-articular therapies used in the treatment of osteoarthritis. Corticosteroids and hyaluronic acid are the most frequently used intra-articular therapies in osteoarthritis. Other intra-articular substances such as orgotein, radiation synovectomy, dextrose prolotherapy, silicone, saline lavage, saline injection without lavage, analgesic agents, non-steroidal anti-inflammatory drugs, glucosamine, somatostatin, sodium pentosan polysulfate, chloroquine, mucopolysaccharide polysulfuric acid ester, lactic acid solution, and thiotepa cytostatica have been investigated as potentially therapeutic in the treatment of arthritic joints. Despite the lack of strong, convincing, and reproducible evidence that any of the intra-articular therapies significantly alters the progression of osteoarthritis, corticosteroids and hyaluronic acid are widely used in patients who have failed other therapeutic modalities for lack of efficacy or toxicity. As a practical approach for a knee with effusion, steroid injections should be considered while the presence of symptomatic "dry" knees may favour the hyaluronic acid approach. The virtual absence of serious side effects, coupled with the perceived benefits, make these approaches attractive.
Topics: Adjuvants, Immunologic; Adrenal Cortex Hormones; Analgesics; Humans; Hyaluronic Acid; Injections, Intra-Articular; Osteoarthritis, Knee; Pain
PubMed: 12954956
DOI: 10.1136/pmj.79.934.449 -
American Family Physician Oct 2001Interstitial cystitis is a chronic, severely debilitating disease of the urinary bladder. Excessive urgency and frequency of urination, suprapubic pain, dyspareunia,... (Review)
Review
Interstitial cystitis is a chronic, severely debilitating disease of the urinary bladder. Excessive urgency and frequency of urination, suprapubic pain, dyspareunia, chronic pelvic pain and negative urine cultures are characteristic of interstitial cystitis. The course of the disease is usually marked by flare-ups and remissions. Other conditions that should be ruled out include bacterial cystitis, urethritis, neoplasia, vaginitis and vulvar vestibulitis. Interstitial cystitis is diagnosed by cystoscopy and hydrodistention of the bladder. Glomerulations or Hunner's ulcers found at cystoscopy are diagnostic. Oral treatments of interstitial cystitis include pentosan polysulfate, tricyclic antidepressants and antihistamines. Intravesicular therapies include hydrodistention, dimethyl sulfoxide and heparin, or a combination of agents. Referral to a support group should be offered to all patients with interstitial cystitis.
Topics: Administration, Intravesical; Administration, Oral; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Antidepressive Agents, Tricyclic; Cystitis, Interstitial; Cystoscopy; Decision Trees; Diagnosis, Differential; Dimethyl Sulfoxide; Drug Therapy, Combination; Heparin; Histamine H1 Antagonists; Humans; Pentosan Sulfuric Polyester; Recurrence
PubMed: 11601802
DOI: No ID Found -
The Journal of Veterinary Medical... Jul 2017Mesenchymal stem cells (MSC) are a potential alternative source of differentiated chondrocytes for cartilage tissue regeneration and repair of osteoarthritic (OA)...
Effects of pentosan polysulfate and polysulfated glycosaminoglycan on chondrogenesis of canine bone marrow-derived mesenchymal stem cells in alginate and micromass culture.
Mesenchymal stem cells (MSC) are a potential alternative source of differentiated chondrocytes for cartilage tissue regeneration and repair of osteoarthritic (OA) joints. We investigated the effects of pentosan polysulfate (PPS) and polysulfated glycosaminoglycan (PSGAG) on chondrogenesis of canine bone marrow-derived mesenchymal stem cells (cBMSC) in alginate and micromass cultures (MMC). Chondrogenic differentiation medium (CDM) was supplemented with PPS or PSGAG at concentrations of 0 (positive control; PC), 1, 3 and 5 µg/ml. 10% DMEM was used as negative control. Chondrocyte phenotype was analyzed by quantitative real-time PCR (qPCR) for alginate cultures and Alcian blue staining for proteoglycan (PG) synthesis for MMC. In alginate culture, PPS and PSGAG showed no significant effect on type II collagen, aggrecan and HIF-2α mRNA expression. PPS had no significant effect on type I collagen whereas PSGAG significantly upregulated (P<0.05) it at all concentrations relative to other treatments. PPS demonstrated a dose-dependent inhibitory effect on type X collagen mRNA with significant inhibition observed at 5 µg/ml compared to the NC. PSGAG showed an inverse effect on type X collagen with 1 µg/ml significantly inhibiting its expression while increase in the concentration correspondingly increased type X collagen expression. In MMC, PPS significantly enhanced chondrogenesis and PG deposition whereas PSGAG inhibited chondrogenesis and promoted a fibrocartilage-like phenotype with reduced PG deposition. While PPS enhances chondrogenesis of cBMSC in MMC, the response of MSC to chondroinductive factors is culture system-dependent and varies significantly between alginate and MMC.
Topics: Alginates; Animals; Cells, Cultured; Chondrocytes; Chondrogenesis; Dog Diseases; Dogs; Glucuronic Acid; Glycosaminoglycans; Hexuronic Acids; Mesenchymal Stem Cells; Osteoarthritis; Pentosan Sulfuric Polyester; Real-Time Polymerase Chain Reaction
PubMed: 28552861
DOI: 10.1292/jvms.17-0084 -
JIMD Reports 2019Overall Goal: This study was designed to evaluate the impact of pentosan polysulfate (PPS) treatment on mice with mucopolysaccharidosis (MPS) type IIIA (Sanfilippo A...
Overall Goal: This study was designed to evaluate the impact of pentosan polysulfate (PPS) treatment on mice with mucopolysaccharidosis (MPS) type IIIA (Sanfilippo A syndrome; OMIM 252900). Protocol: Three groups of MPS IIIA mice were evaluated: 1-week-old mice treated with subcutaneous (subQ) PPS at 25 mg/kg once weekly for 31 weeks (group 1); 5-month-old mice treated with subQ PPS once weekly at 50 mg/kg for 12 weeks (group 2); and 5-week-old mice treated by continual intracerebroventricular (ICV) PPS infusion for 11 weeks (60 μg/kg/day). Treated MPS IIIA mice and controls were assessed by measuring plasma cytokine levels, histologic analyses of systemic organs, and analyses of various neuroinflammatory, neurodegenerative, and lysosomal disease markers in their brains. Neurobehavioral testing also was carried out. Results: As seen in other MPS animal models, subQ PPS treatment reduced plasma cytokine levels and macrophage infiltration in systemic tissues. ICV administration did not elicit these systemic effects. SubQ PPS administration also significantly impacted brain neuropathology, inflammation, and behavior. The effect of early subQ treatment was more significant than dose. Surprisingly, ICV PPS treatment had intermediate effects on most of these brain markers, perhaps due to the limited dose and/or duration of treatment. Consistent with these neuropathological findings, we also observed significant improvements in the hyperactivity/anxiety and learning behaviors of the MPS IIIA mice treated with early subQ PPS.
PubMed: 29654542
DOI: 10.1007/8904_2018_96