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Ophthalmology. Retina Sep 2022There is growing evidence of a direct association between pentosan polysulfate (PPS) therapy and the development of macular changes. Using standardized visual acuity...
PURPOSE
There is growing evidence of a direct association between pentosan polysulfate (PPS) therapy and the development of macular changes. Using standardized visual acuity (VA) testing and multimodal imaging, we investigated the impact of PPS therapy on vision and described an expanded spectrum of imaging findings among PPS users.
DESIGN
Cross-sectional screening study.
PARTICIPANTS
Thirty-nine patients who were current or recent users of PPS.
METHODS
The participants underwent a brief eye examination and answered a comprehensive medical and ophthalmic history questionnaire. Color fundus photography, fundus autofluorescence (FAF), and spectral-domain OCT (SD-OCT) were performed. The images were evaluated by expert graders at Wisconsin Reading Center. Abnormalities were categorized as definite toxicity (DT) if seen on both FAF and SD-OCT and as questionable toxicity (QT) if seen on either FAF or SD-OCT.
MAIN OUTCOME MEASURES
ETDRS and Snellen VA, the dosage and duration of PPS exposure, and the prevalence of retinal toxicity on imaging.
RESULTS
The mean ETDRS and Snellen VA of the study cohort were 85 letters and 20/22, respectively. The mean PPS daily dose was 282 mg (range, 88-400 mg), whereas the mean cumulative dose was 915 g (range, 19-3650 g) over a mean period of 8.8 years (range, 2 months-25 years). There was evidence of retinopathy in 41% of the eyes; DT was identified in 24 eyes (31%) and QT in 8 eyes (10%). Retinal pigment epithelium (RPE) abnormalities (thickening or thinning or both) were present in all eyes with DT. Retinal pigment epithelium atrophy was seen in 7 eyes (9%). In addition to well-established findings, the unique SD-OCT features of this cohort included interdigitation zone abnormalities and the presence of a flying saucer-type defect. Fundus autofluorescence abnormalities were seen in 24 eyes (30.8%), with 20 (66.7%) of these exhibiting abnormalities located outside the central subfield and extending beyond the arcades.
CONCLUSIONS
Findings from the masked grading of multimodal imaging at a centralized reading center suggest a wider phenotypic spectrum of structural abnormalities among patients taking PPS. Macular changes selectively involve the RPE and outer retina, with a range of findings often seen beyond the arcades. The subtle and atypical findings in this cohort should prompt clinicians to consider lowering the threshold for diagnosing PPS retinopathy.
Topics: Cross-Sectional Studies; Fluorescein Angiography; Humans; Multimodal Imaging; Pentosan Sulfuric Polyester; Retinal Degeneration; Tomography, Optical Coherence
PubMed: 35339727
DOI: 10.1016/j.oret.2022.03.016 -
Medical Hypotheses Dec 2021Osteoarthritis is still a disease burden for pharmaceutical scientists and strategy makers. It is associated with the chronic inflammation of joints especially...
Osteoarthritis is still a disease burden for pharmaceutical scientists and strategy makers. It is associated with the chronic inflammation of joints especially weight-bearing joints like knee, hip, backbone, and phalanges. NSAIDs that are used for the management of inflammation associated with osteoarthritis have high side effects related to gastric upset, gastric ulcer, and long term treatment associated with liver and kidney damage. Nanotechnology has gained a huge scope for the management of arthritis as it can reach out to the deep inside the cell and alter cellular physiology as desired. The present study hypothesizes the use of polyion complex nanoparticles of hyaluronic acid linked Pentosan polysulfate sodium, a disease-modifying agent for the treatment of osteoarthritis administered through transdermal route. The hypothesis involves the use of drug repurposing as the drug was initially approved for interstitial cystitis, a condition of the urinary bladder associated with pain and swelling. Being very low oral bioavailability and gastric irritation profile, the transdermal route would be beneficial. To overcome the problem associated with the oral route, there is a need for the targeted approach that will particularly reach at inflammatory sites. Thereby transdermal delivery of hyaluronic acid linked Pentosan polysulfate sodium through polyion complex nanoparticle therapy will be a novel therapeutic approach to combat osteoarthritis.
Topics: Cystitis, Interstitial; Drug Repositioning; Humans; Hyaluronic Acid; Nanoparticles; Osteoarthritis; Pentosan Sulfuric Polyester
PubMed: 34710749
DOI: 10.1016/j.mehy.2021.110713 -
The Analyst Aug 2019Pentosan polysulfate (PPS) is a semi-synthetic glycosaminoglycan (GAG) mimetic. PPS, synthesized through the chemical sulfonation of a plant-derived β-(1 → 4)-xylan,...
Pentosan polysulfate (PPS) is a semi-synthetic glycosaminoglycan (GAG) mimetic. PPS, synthesized through the chemical sulfonation of a plant-derived β-(1 → 4)-xylan, is the active pharmaceutical ingredient of the drug Elmiron™ used to treat interstitial cystitis. Unlike natural GAGs that can be enzymatically broken down into oligosaccharides for analysis, PPS is an unnatural polyanionic polysaccharide and is not amenable to such an analytical approach. Instead reactive oxygen species were used for the controlled depolymerization of PPS and the resulting oligosaccharide fragments were then analyzed by liquid chromatography-mass spectrometry (LC-MS) to obtain bottom-up information on its composition. Because PPS has an average molecular weight ranging from 4000 to 6000 Da, similar to that of low molecular weight heparin, this suggested that it might be possible to use LC-MS on its intact chains and perform top-down analysis. The bottom-up and top-down analysis of PPS provides the first detailed compositional and structural information on PPS. Finally, we examined whether PPS would interfere with polysaccharide lyases and hydrolases, used in the analysis of natural GAGs such as chondroitin sulfates, heparan sulfate, and keratan sulfates. We found that PPS did not interfere with GAG analysis, suggesting that a combination of chemical and enzymatic treatment could be used to analyze samples containing both natural GAGs and PPS.
Topics: Chromatography, Liquid; Glycosaminoglycans; Hydrogen Peroxide; Mass Spectrometry; Oligosaccharides; Organometallic Compounds; Oxidation-Reduction; Pentosan Sulfuric Polyester
PubMed: 31287456
DOI: 10.1039/c9an01006h -
Research in Veterinary Science Feb 2019Pentosan polysulfate (PPS) is currently under investigation as a potential disease-modifying antiarthritic agent. In the present study the effects of PPS on arthritic...
Pentosan polysulfate (PPS) is currently under investigation as a potential disease-modifying antiarthritic agent. In the present study the effects of PPS on arthritic profiles based on clinical score, ankle size, histological changes, and activity of inflammatory mediators using collagen-induced arthritic rat are reported. Model of arthritis was developed in Sprague Dawley rats by intradermal injection of bovine type II collagen emulsified with incomplete Freund's adjuvant. The rats were randomly divided into four groups: normal control, arthritic control, arthritic rats treated with PPS (at dose level 20 μg/g) and arthritic rats treated with meloxicam (2 μg/g). The treatment was continued daily until the day 30. Arthritic biomarkers (cartilage oligomeric matrix protein and tartrate-resistant acid phosphatase 5b) in synovial fluid, expression of inflammatory mediators (interleukin-1β, and tumor necrosis factor-α) and osteoclast marker genes (cathepsin K, tartrate-resistant acid phosphatase) in synovial membrane were measured. Daily administration of PPS to the arthritic rats significantly decreased the severity of arthritis by effectively suppressing the symptoms of arthritis and improving the functional recovery based on clinical score and histopathological evidence. Intriguingly, identical downregulation pattern of arthritis profiles, biological markers as well as relative mRNA levels of osteoclast markers and cytokines were monitored in arthritic rats treated with PPS. In conclusion, PPS exerted protective effects against collagen-induced arthritis in rats. The results suggest that PPS acts as an anti-inflammatory and anti-arthritic agent in decreasing the arthritic effects in collagen-induced arthritic rats.
Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Cattle; Collagen Type II; Cytokines; Freund's Adjuvant; Gene Expression Regulation; Lipids; Pentosan Sulfuric Polyester; Random Allocation; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha
PubMed: 30529273
DOI: 10.1016/j.rvsc.2018.11.028 -
Der Ophthalmologe : Zeitschrift Der... Dec 2020Toxic retinopathies are most frequently induced by external stimulants (e.g. nicotine, poppers, methanol) and are less frequently undesired side effects of systemic...
Toxic retinopathies are most frequently induced by external stimulants (e.g. nicotine, poppers, methanol) and are less frequently undesired side effects of systemic drugs (e.g. hydroxychloroquine, ethambutol, MEK, ERK, FLT3 or checkpoint inhibitors, didanosine, pentosan polysulfate sodium) or intravitreally applied drugs. The clinical symptoms of undesired side effects of drugs are often similar to retinal diseases from other causes, which interferes with the recognition of the undesired side effects of drugs. Clinical findings, pathophysiological mechanisms and if advisable strategies for screening are discussed. The focus is on the presentation of confirmed undesirable side effects with established associations for medications which have long been approved. For novel medications, in addition potential but not proven associations are presented to facilitate the recognition of additional cases with side effects for these medications.
Topics: Humans; Pentosan Sulfuric Polyester; Retinal Diseases
PubMed: 33211161
DOI: 10.1007/s00347-020-01260-w -
Pentosan polysulfate, a sulfated oligosaccharide, is a potent and selective anti-HIV agent in vitro.Antiviral Research Sep 1988Several sulfated oligo- or polysaccharides such as pentosan polysulfate, fucoidan, dextran sulfate, heparin and iota-, kappa- and lambda-carrageenans proved to be potent...
Several sulfated oligo- or polysaccharides such as pentosan polysulfate, fucoidan, dextran sulfate, heparin and iota-, kappa- and lambda-carrageenans proved to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) in vitro. The most potent anti-HIV-1 activity was recorded for the oligosaccharide pentosan polysulfate, its 50% antiviral effective dose (ED50) being 0.19 microgram/ml in MT-4 cells. It inhibited HIV-1 antigen expression in HUT-78 cells at an ED50 of 0.02 microgram/ml, and complete inhibition of HIV-1 antigen expression was obtained at a concentration of 4.0 micrograms/ml. No toxicity for MT-4 cells was observed with pentosan polysulfate at a concentration of 2500 micrograms/ml. The anticoagulant activity of pentosan polysulfate was more than ten-fold lower than that of heparin (14.4 and 177 U/mg, respectively). In fact, pentosan polysulfate achieved its anti-HIV-1 activity at a concentration that is 370-fold below its anticoagulant threshold (1 U). Pentosan polysulfate inhibits virus adsorption to the cells, as was demonstrated by monitoring the association of radiolabeled HIV-1 virions with MT-4 cells.
Topics: Adsorption; Anticoagulants; Antiviral Agents; Blood Coagulation; Cell Line; Drug Evaluation, Preclinical; HIV-1; Humans; In Vitro Techniques; Pentosan Sulfuric Polyester; Polysaccharides; Reverse Transcriptase Inhibitors
PubMed: 2465736
DOI: 10.1016/0166-3542(88)90035-6 -
PloS One 2016We previously demonstrated the therapeutic benefits of pentosan polysulfate (PPS) in a rat model of mucopolysaccharidosis (MPS) type VI. Reduction of inflammation,... (Comparative Study)
Comparative Study
BACKGROUND
We previously demonstrated the therapeutic benefits of pentosan polysulfate (PPS) in a rat model of mucopolysaccharidosis (MPS) type VI. Reduction of inflammation, reduction of glycosaminoglycan (GAG) storage, and improvement in the skeletal phenotype were shown. Herein, we evaluate the long-term safety and therapeutic effects of PPS in a large animal model of a different MPS type, MPS I dogs. We focused on the arterial phenotype since this is one of the most consistent and clinically significant features of the model.
METHODOLOGY/PRINCIPAL FINDINGS
MPS I dogs were treated with daily oral or biweekly subcutaneous (subQ) PPS at a human equivalent dose of 1.6 mg/kg for 17 and 12 months, respectively. Safety parameters were assessed at 6 months and at the end of the study. Following treatment, cytokine and GAG levels were determined in fluids and tissues. Assessments of the aorta and carotid arteries also were performed. No drug-related increases in liver enzymes, coagulation factors, or other adverse effects were observed. Significantly reduced IL-8 and TNF-alpha were found in urine and cerebrospinal fluid (CSF). GAG reduction was observed in urine and tissues. Increases in the luminal openings and reduction of the intimal media thickening occurred in the carotids and aortas of PPS-treated animals, along with a reduction of storage vacuoles. These results were correlated with a reduction of GAG storage, reduction of clusterin 1 staining, and improved elastin integrity. No significant changes in the spines of the treated animals were observed.
CONCLUSIONS
PPS treatment led to reductions of pro-inflammatory cytokines and GAG storage in urine and tissues of MPS I dogs, which were most evident after subQ administration. SubQ administration also led to significant cytokine reductions in the CSF. Both treatment groups exhibited markedly reduced carotid and aortic inflammation, increased vessel integrity, and improved histopathology. We conclude that PPS may be a safe and useful therapy for MPS I, either as an adjunct or as a stand-alone treatment that reduces inflammation and GAG storage.
Topics: Administration, Oral; Animals; Biomarkers; Blood Vessels; Cervical Vertebrae; Dogs; Female; Glycosaminoglycans; Humans; Injections, Subcutaneous; Male; Mucopolysaccharidosis I; Pentosan Sulfuric Polyester; Rats; Safety
PubMed: 27064989
DOI: 10.1371/journal.pone.0153136 -
Frontiers in Immunology 2023There is an unmet medical need for effective anti-inflammatory agents for the treatment of acute and post-acute lung inflammation caused by respiratory viruses. The...
INTRODUCTION
There is an unmet medical need for effective anti-inflammatory agents for the treatment of acute and post-acute lung inflammation caused by respiratory viruses. The semi-synthetic polysaccharide, Pentosan polysulfate sodium (PPS), an inhibitor of NF-kB activation, was investigated for its systemic and local anti-inflammatory effects in a mouse model of influenza virus A/PR8/1934 (PR8 strain) mediated infection.
METHODS
Immunocompetent C57BL/6J mice were infected intranasally with a sublethal dose of PR8 and treated subcutaneously with 3 or 6 mg/kg PPS or vehicle. Disease was monitored and tissues were collected at the acute (8 days post-infection; dpi) or post-acute (21 dpi) phase of disease to assess the effect of PPS on PR8-induced pathology.
RESULTS
In the acute phase of PR8 infection, PPS treatment was associated with a reduction in weight loss and improvement in oxygen saturation when compared to vehicle-treated mice. Associated with these clinical improvements, PPS treatment showed a significant retention in the numbers of protective SiglecF+ resident alveolar macrophages, despite uneventful changes in pulmonary leukocyte infiltrates assessed by flow cytometry. PPS treatment in PR8- infected mice showed significant reductions systemically but not locally of the inflammatory molecules, IL-6, IFN-g, TNF-a, IL-12p70 and CCL2. In the post-acute phase of infection, PPS demonstrated a reduction in the pulmonary fibrotic biomarkers, sICAM-1 and complement factor C5b9.
DISCUSSION
The systemic and local anti-inflammatory actions of PPS may regulate acute and post-acute pulmonary inflammation and tissue remodeling mediated by PR8 infection, which warrants further investigation.
Topics: Mice; Animals; Pentosan Sulfuric Polyester; Alphainfluenzavirus; Mice, Inbred C57BL; Pneumonia; Anti-Inflammatory Agents; Disease Models, Animal
PubMed: 36845136
DOI: 10.3389/fimmu.2023.1030879 -
Ophthalmology Jun 2020
Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Cystitis, Interstitial; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Macular Degeneration; Male; Middle Aged; Pentosan Sulfuric Polyester; Prevalence; Retina; Retrospective Studies; Tomography, Optical Coherence
PubMed: 32085877
DOI: 10.1016/j.ophtha.2020.01.017 -
Optometry and Vision Science : Official... Jun 2021Pentosan polysulfate sodium (PPS) maculopathy is a clinical entity characterized by a pigmentary maculopathy in the setting of chronic exposure to PPS. Pentosan...
SIGNIFICANCE
Pentosan polysulfate sodium (PPS) maculopathy is a clinical entity characterized by a pigmentary maculopathy in the setting of chronic exposure to PPS. Pentosan polysulfate sodium is indicated for discomfort related to interstitial cystitis/painful bladder syndrome. Given a reported interstitial cystitis/painful bladder syndrome prevalence up to 2%, recognition is critical to mitigate visual sequelae.
PURPOSE
We present an observational case report demonstrating typical findings of PPS maculopathy in a patient originally diagnosed with a pattern macular dystrophy. We demonstrate the importance of medical history, medication profile review, and multimodal imaging in the diagnosis and management. The patient provided written informed consent for medical information and images to be published.
CASE REPORT
A 55-year-old White woman presented with a painless, bilateral loss of vision and bilateral pigmentary maculopathy that was initially diagnosed as pattern macular dystrophy. Detailed review of medical history, medication profile, and subsequent studies, including optical coherence tomography, near-infrared reflectance imaging, fundus autofluorescence, fluorescein angiography, and genetic studies, ultimately led to the diagnosis of PPS maculopathy. Pentosan polysulfate sodium was discontinued, and ongoing surveillance with multimodal imaging was encouraged.
CONCLUSIONS
Because toxic maculopathies are an uncommon diagnosis, screening and recognition of PPS maculopathy are critical in the primary eye care setting. Discontinuation of the insulting agent may be necessary to prevent potentially severe and irreversible vision loss in the at-risk population.
Topics: Anticoagulants; Female; Fluorescein Angiography; Humans; Macular Degeneration; Middle Aged; Pentosan Sulfuric Polyester; Retinal Dystrophies
PubMed: 34039907
DOI: 10.1097/OPX.0000000000001702