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PloS One 2021Chikungunya virus (CHIKV) is an arthropod-borne virus that causes large outbreaks world-wide leaving millions of people with severe and debilitating arthritis....
Chikungunya virus (CHIKV) is an arthropod-borne virus that causes large outbreaks world-wide leaving millions of people with severe and debilitating arthritis. Interestingly, clinical presentation of CHIKV arthritides have many overlapping features with rheumatoid arthritis including cellular and cytokine pathways that lead to disease development and progression. Currently, there are no specific treatments or vaccines available to treat CHIKV infections therefore advocating the need for the development of novel therapeutic strategies to treat CHIKV rheumatic disease. Herein, we provide an in-depth analysis of an efficacious new treatment for CHIKV arthritis with a semi-synthetic sulphated polysaccharide, Pentosan Polysulfate Sodium (PPS). Mice treated with PPS showed significant functional improvement as measured by grip strength and a reduction in hind limb foot swelling. Histological analysis of the affected joint showed local inflammation was reduced as seen by a decreased number of infiltrating immune cells. Additionally, joint cartilage was protected as demonstrated by increased proteoglycan staining. Using a multiplex-immunoassay system, we also showed that at peak disease, PPS treatment led to a systemic reduction of the chemokines CXCL1, CCL2 (MCP-1), CCL7 (MCP-3) and CCL12 (MCP-5) which may be associated with the reduction in cellular infiltrates. Further characterisation of the local effect of PPS in its action to reduce joint and muscle inflammation was performed using NanoString™ technology. Results showed that PPS altered the local expression of key functional genes characterised for their involvement in growth factor signalling and lymphocyte activation. Overall, this study shows that PPS is a promising treatment for alphaviral arthritis by reducing inflammation and protecting joint integrity.
Topics: Animals; Anticoagulants; Arthritis, Rheumatoid; Chikungunya Fever; Chikungunya virus; Cytokines; Disease Models, Animal; Female; Inflammation; Intercellular Signaling Peptides and Proteins; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Pentosan Sulfuric Polyester
PubMed: 34492036
DOI: 10.1371/journal.pone.0255125 -
Retinal Cases & Brief Reports Nov 2022To describe a potential case of pentosan polysulfate maculopathy that seemed to manifest nearly 3 years after drug cessation.
PURPOSE
To describe a potential case of pentosan polysulfate maculopathy that seemed to manifest nearly 3 years after drug cessation.
METHODS
Complete ophthalmic examination, including multimodal fundus imaging, electroretinography, automated perimetry, and molecular testing, was performed.
RESULTS
A 44-year-old woman with a 435 g cumulative exposure to pentosan polysulfate sodium presented 38 months after drug cessation with 6 months of worsening metamorphopsia and prolonged dark adaptation. Fundus examination and multimodal fundus imaging demonstrated characteristic features of pentosan polysulfate maculopathy, and molecular testing was unremarkable. By contrast, color fundus photographs of the same patient acquired at an outside facility 25 months before did not display features consistent with pentosan polysulfate sodium maculopathy.
CONCLUSION
This case suggests that new-onset clinically detectable pentosan polysulfate maculopathy may develop years after drug cessation. If corroborated, this finding has important ramifications for pentosan polysulfate sodium dosing and surveillance guidelines.
Topics: Female; Humans; Adult; Pentosan Sulfuric Polyester; Macular Degeneration; Retinal Diseases; Electroretinography; Vision Disorders
PubMed: 33229920
DOI: 10.1097/ICB.0000000000001090 -
Ophthalmology. Retina Jan 2020
Topics: Choroid; Choroidal Neovascularization; Cystitis, Interstitial; Female; Fluorescein Angiography; Fundus Oculi; Humans; Middle Aged; Pentosan Sulfuric Polyester; Tomography, Optical Coherence
PubMed: 31570285
DOI: 10.1016/j.oret.2019.08.006 -
Investigative and Clinical Urology Sep 2022Intravesical Bacillus Calmette-Guérin (BCG) instillation, although an important treatment for non-muscle-invasive bladder cancer, exerts local and systemic adverse...
PURPOSE
Intravesical Bacillus Calmette-Guérin (BCG) instillation, although an important treatment for non-muscle-invasive bladder cancer, exerts local and systemic adverse effects. Pentosan polysulfate (PPS) is a bladder mucosal protective drug that acts by replacing mucus in the glycosaminoglycan layer of the damaged urothelium. We hypothesized that co-administration of oral PPS with BCG instillation would relieve BCG-related adverse effects without affecting its efficacy.
MATERIALS AND METHODS
A total of 217 patients receiving BCG instillation were enrolled. They were placed in two groups and analyzed retrospectively: group A (n=122) received BCG instillation only and group B (n=95) received 100 mg of PPS thrice daily during the BCG treatment.
RESULTS
After BCG instillation, the rate of BCG-treatment discontinuation owing to adverse effects was 15.6% in group A and 6.3% in group B (p=0.034). The proportion of patients with bacteriuria after BCG was higher in group B; however, no statistical difference was observed (28.7% vs. 41.1%; p=0.057). The proportion of patients with pyuria was significantly higher in group B (81.1% vs. 91.6%; p=0.029). The proportion of patients using antibiotics was significantly higher in group A (73.8% vs. 43.2%; p=0.001). The recurrence rate within 1 year was 29 (23.8%) in group A vs. 19 (20.0%) in group B (p=0.507). Univariate and multivariate analyses showed that antibiotic use had a statistically significant effect on BCG discontinuation.
CONCLUSIONS
Oral PPS effectively decreased the discontinuation rate and antibiotic use without affecting the BCG efficacy.
Topics: Anti-Bacterial Agents; BCG Vaccine; Humans; Pentosan Sulfuric Polyester; Retrospective Studies; Urinary Bladder Neoplasms
PubMed: 36067999
DOI: 10.4111/icu.20220179 -
Ophthalmic Epidemiology Feb 2023We describe a retrospective cohort study investigating the prevalence of pentosan polysulfate sodium (PPS) maculopathy in patients with PPS exposure, as well as the...
PURPOSE
We describe a retrospective cohort study investigating the prevalence of pentosan polysulfate sodium (PPS) maculopathy in patients with PPS exposure, as well as the relationship between cumulative PPS exposure and the presence of PPS-maculopathy.
METHODS
Patients were identified through review of the electronic medical record system. Available diagnostic imaging was reviewed for signs of PPS-maculopathy. Patients were also contacted to determine cumulative exposure.
RESULTS
Of the 335 identified eligible patient records, 84 had sufficient diagnostic imaging. Sixteen patients had definitive signs of PPS-maculopathy, 6 had likely signs of PPS-maculopathy, and 62 had no signs. The mean cumulative PPS exposure and standard error of the mean (SEM) for patients with any signs of PPS-maculopathy was 1946.0 g (396.0 g), significantly higher than the mean cumulative PPS exposure for patients without such signs of 782.3 g (105.3 g). No significant difference in BCVA was noted. The odds ratio (OR, 95% confidence interval (95% CI)) of PPS-maculopathy was significantly elevated in patients with cumulative PPS exposures of 1500-2000 g [OR 4.72 (0.856-26.02 95% CI)] and greater than 2000 g [OR 28.33 (2.388-336.1, 95% CI)]. Logistic regression analysis confirmed a positive dose response relationship.
CONCLUSIONS
We describe the concerning incidence of PPS-maculopathy in a multispecialty ophthalmology practice's patient population and investigate the dose-dependency of PPS-maculopathy. Patients with PPS-maculopathy were shown to have a higher average exposure to PPS than those without the maculopathy. Patients with cumulative PPS exposures greater than 1500 g were shown to have an increased risk of PPS-maculopathy.
Topics: Humans; Pentosan Sulfuric Polyester; Prevalence; Retrospective Studies; Retinal Diseases; Macular Degeneration
PubMed: 35081852
DOI: 10.1080/09286586.2022.2031227 -
Retinal Cases & Brief Reports Jul 2022To report a case of nonleaking cystoid macular edema (CME) associated with pentosan polysulfate sodium (PPS)-induced pigmentary maculopathy.
PENTOSAN POLYSULFATE SODIUM-INDUCED PIGMENTARY MACULOPATHY WITH NONLEAKING CYSTOID MACULAR EDEMA SUCCESSFULLY TREATED WITH ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.
PURPOSE
To report a case of nonleaking cystoid macular edema (CME) associated with pentosan polysulfate sodium (PPS)-induced pigmentary maculopathy.
METHODS
Multimodal imaging, including optical coherence tomography, fundus photography, autofluorescence, and fluorescein angiography, was used to substantiate our diagnosis, further characterize the cystoid macular edema showed by our patient and to monitor the response to treatment.
RESULTS
A 59-year-old woman was referred for decreased visual acuity and bilateral macular edema. She had been treated for interstitial cystitis with PPS for 10 years. Multimodal imaging showed the characteristic features of PPS-induced pigmentary maculopathy. Moreover, fluorescein angiogram showed nonleaking cystoid macular edema in both eyes. She was treated successfully with intravitreal injections of bevacizumab.
CONCLUSION
To our knowledge, this report is the first to demonstrate that PPS-associated cystoid macular edema can be nonleaking on fluorescein angiography and responds well to intravitreal anti-vascular endothelial growth factor injections.
Topics: Female; Fluorescein Angiography; Humans; Intravitreal Injections; Macular Degeneration; Macular Edema; Middle Aged; Pentosan Sulfuric Polyester; Tomography, Optical Coherence; Visual Acuity
PubMed: 32541441
DOI: 10.1097/ICB.0000000000001013 -
The Journal of Urology Mar 2015We compared the efficacy and safety of the currently recommended dose of pentosan polysulfate sodium with a third of the daily dose and with placebo. (Comparative Study)
Comparative Study Randomized Controlled Trial
PURPOSE
We compared the efficacy and safety of the currently recommended dose of pentosan polysulfate sodium with a third of the daily dose and with placebo.
MATERIALS AND METHODS
In this multicenter, double-blind, randomized, placebo controlled study 368 adults with interstitial cystitis/bladder pain syndrome, defined as an ICSI total score of 8 or greater and a score of greater than 0 on the 4 ICSI component items, received pentosan polysulfate sodium 100 mg once daily or 3 times daily, or matching placebo for 24 weeks. Study eligibility was not based on cystoscopy findings. ICSI was administered at baseline, and at weeks 4, 8, 12, 18 and 24. Unblinded interim analysis performed at 6 years with 54% of the target number of 645 patients enrolled resulted in early study termination.
RESULTS
There was no statistically significant difference between the pentosan polysulfate sodium group and the placebo group or between the 2 pentosan polysulfate sodium groups for the primary end point, defined as responder achieving a 30% or greater reduction from the baseline ICSI total score at study end. This primary end point was achieved by 48 of 118 patients (40.7%) in the placebo group, and by 51 of 128 (39.8%) and 52 of 122 (42.6%) in the pentosan polysulfate sodium 100 mg once daily and 3 times daily groups, respectively. Pentosan polysulfate sodium was well tolerated with a similar percent of patients (range 10.2% to 13.3%) across the groups discontinuing due to an adverse event.
CONCLUSIONS
Results of this study in a broad population of patients with symptoms consistent with interstitial cystitis revealed no treatment effect vs placebo for pentosan polysulfate sodium at the currently established dose or at a third of the daily dose.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cystitis, Interstitial; Double-Blind Method; Female; Humans; Male; Middle Aged; Pentosan Sulfuric Polyester; Young Adult
PubMed: 25245489
DOI: 10.1016/j.juro.2014.09.036 -
Military Medicine Mar 2023In 2018, a unique maculopathy associated with chronic pentosan polysulfate sodium (PPS) use for the treatment of interstitial cystitis (IC) was described, where the...
INTRODUCTION
In 2018, a unique maculopathy associated with chronic pentosan polysulfate sodium (PPS) use for the treatment of interstitial cystitis (IC) was described, where the authors detailed macular retinal pigment epithelial abnormalities in six patients. In this paper, a retrospective study of a larger patient pool at one large tertiary retina practice was undertaken to evaluate patients taking PPS and their macular findings.
MATERIALS AND METHODS
A retrospective chart review was performed on all patients presenting to a single large retina practice between 2011 and 2019. Patient's macular diagnosis, findings, optical coherence tomography scans, and macular auto-fluorescent scans were assessed. This project was Institutional Review Board (IRB) approved by the St Luke's Hospital IRB board (St Louis, MO, USA).
RESULTS
Fifty-five patients were identified as taking PPS for IC. Fifty-three patients were found to have a diagnosis consistent with changes attributable to known macular diseases to include macular degeneration and pattern dystrophies. Two (4%) of fifty-five patients had macular findings suggestive of PPS toxicity. The first was a 58-year-old female with subtle retinal pigment epithelium (RPE) deposits on optical coherence tomography that exhibited hyper-autofluorescence. The second was a 72-year-old female with 14 years of PPS use who exhibited RPE excrescences and parafoveal areas of atrophy.
CONCLUSIONS
Pentosan polysulfate sodium may be the cause of macular findings in a small percentage of patients referred to a tertiary retina practice. Although causation of macular changes with PPS use has yet to be elucidated, clinicians should be aware of this possibility when assessing patients with atypical macular findings. Future longitudinal studies are necessary to evaluate a definitive relationship. This paper should remind all clinicians of the importance of a throughout review of the patient's medication list as novel toxicities may become apparent years after initial FDA trials. The strength of this study is the larger patient population compared to earlier studies, and the main weaknesses include the retrospective nature of the study, lack of family and genetic testing, and lack of multimodal imaging for all patients.
Topics: Female; Humans; Middle Aged; Aged; Pentosan Sulfuric Polyester; Retrospective Studies; Retinal Diseases; Cystitis, Interstitial; Genetic Testing; Tomography, Optical Coherence
PubMed: 34296258
DOI: 10.1093/milmed/usab301 -
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 -
Journal of Pharmaceutical and... Oct 2023Several publications have recently proposed NMR spectroscopy to evaluate the critical quality attributes (CQA) of pentosan polysulfate sodium (PPS), the active...
Several publications have recently proposed NMR spectroscopy to evaluate the critical quality attributes (CQA) of pentosan polysulfate sodium (PPS), the active ingredient of Elmiron™ approved to treat interstitial cystitis. PPS is a polymer of sulfated β(1-4)-d-xylopyranose residues randomly substituted by 4-O-methyl-glucopyranosyluronic acid, containing, beyond the main xylose-2,3-O-disulfate repetitive unit, some minor residues that can be marker of both the starting material and preparation process. In the present study we assigned some previously unknown cross-peaks in H-C HSQC NMR of PPS related to its minor sequences adding additional details to its CQA. Four anomeric cross-peaks related to glucuronate-branched xylose and different sulfation pattern as well as the preceding xyloses were identified. Two minor process-related signals of monosulfated xyloses (unsubstituted in position 2 or 3) were also assigned. The isolation of a disaccharide fraction allowed the assignment of the reducing end xylose-α/β as well as the preceding xylose residues to be corrected. Additionally, the oversulfation of PPS allowed detection of the reducing end xylose-tri-1,2,3-O-sulfate. The newly identified cross-peaks were integrated into an updated quantitative NMR method. Finally, we demonstrated that an in-depth PPS analysis can be obtained using NMR instruments at medium magnetic fields (500 MHz/600 MHz), commonly available in pharmaceutical industries.
Topics: Pentosan Sulfuric Polyester; Monosaccharides; Xylose; Magnetic Resonance Imaging; Sulfates; Magnetic Resonance Spectroscopy
PubMed: 37619291
DOI: 10.1016/j.jpba.2023.115672