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The Medical Journal of Australia May 2023
Topics: Humans; Pentosan Sulfuric Polyester; General Practitioners; Ophthalmologists; Optometrists; Urologists; Macular Degeneration; Retinal Diseases
PubMed: 36990107
DOI: 10.5694/mja2.51913 -
Pharmaceuticals (Basel, Switzerland) Mar 2023Pentosan polysulfate (PPS), a small semi-synthetic highly sulfated heparan sulfate (HS)-like molecule, shares many of the interactive properties of HS. The aim of this... (Review)
Review
Pentosan polysulfate (PPS), a small semi-synthetic highly sulfated heparan sulfate (HS)-like molecule, shares many of the interactive properties of HS. The aim of this review was to outline the potential of PPS as an interventional therapeutic protective agent in physiological processes affecting pathological tissues. PPS is a multifunctional molecule with diverse therapeutic actions against many disease processes. PPS has been used for decades in the treatment of interstitial cystitis and painful bowel disease, it has tissue-protective properties as a protease inhibitor in cartilage, tendon and IVD, and it has been used as a cell-directive component in bioscaffolds in tissue engineering applications. PPS regulates complement activation, coagulation, fibrinolysis and thrombocytopenia, and it promotes the synthesis of hyaluronan. Nerve growth factor production in osteocytes is inhibited by PPS, reducing bone pain in osteoarthritis and rheumatoid arthritis (OA/RA). PPS also removes fatty compounds from lipid-engorged subchondral blood vessels in OA/RA cartilage, reducing joint pain. PPS regulates cytokine and inflammatory mediator production and is also an anti-tumor agent that promotes the proliferation and differentiation of mesenchymal stem cells and the development of progenitor cell lineages that have proven to be useful in strategies designed to effect repair of the degenerate intervertebral disc (IVD) and OA cartilage. PPS stimulates proteoglycan synthesis by chondrocytes in the presence or absence of interleukin (IL)-1, and stimulates hyaluronan production by synoviocytes. PPS is thus a multifunctional tissue-protective molecule of potential therapeutic application for a diverse range of disease processes.
PubMed: 36986536
DOI: 10.3390/ph16030437 -
Asia-Pacific Journal of Ophthalmology...This study will provide a thorough review of systemic (and select intravitreal) medications, along with illicit drugs that are capable of causing various patterns of...
This study will provide a thorough review of systemic (and select intravitreal) medications, along with illicit drugs that are capable of causing various patterns of retinal toxicity. The diagnosis is established by taking a thorough medication and drug history, and then by pattern recognition of the clinical retinal changes and multimodal imaging features. Examples of all of these types of toxicity will be thoroughly reviewed, including agents that cause retinal pigment epithelial disruption (hydroxychloroquine, thioridazine, pentosan polysulfate sodium, dideoxyinosine), retinal vascular occlusion (quinine, oral contraceptives), cystoid macular edema/retinal edema (nicotinic acid, sulfa-containing medications, taxels, glitazones), crystalline deposition (tamoxifen, canthaxanthin, methoxyflurane), uveitis, miscellaneous, and subjective visual symptoms (digoxin, sildenafil). The impact of newer chemotherapeutics and immunotherapeutics (tyrosine kinase inhibitor, mitogen-activated protein kinase kinase, checkpoint, anaplastic lymphoma kinase, extracellular signal-regulated kinase inhibitors, and others), will also be thoroughly reviewed. The mechanism of action will be explored in detail when known. When applicable, preventive measures will be discussed, and treatment will be reviewed. Illicit drugs (cannabinoids, cocaine, heroin, methamphetamine, alkyl nitrite), will also be reviewed in terms of the potential impact on retinal function.
Topics: Humans; Retina; Retinal Diseases; Macular Edema; Uveitis; Illicit Drugs; Retinal Vein Occlusion; Intravitreal Injections; Tomography, Optical Coherence
PubMed: 36971705
DOI: 10.1097/APO.0000000000000605 -
Osteoarthritis and Cartilage Open Jun 2023To evaluate the efficacy and safety of pentosan polysulfate sodium (PPS, Elmiron®) for dyslipidaemia and knee osteoarthritis (OA) related symptoms. (Clinical Trial)
Clinical Trial
OBJECTIVE
To evaluate the efficacy and safety of pentosan polysulfate sodium (PPS, Elmiron®) for dyslipidaemia and knee osteoarthritis (OA) related symptoms.
METHOD
This was a single-arm, open-label, prospective, non-randomised pilot study. People with painful knee OA and a history of primary hypercholesterolemia were included. PPS was taken orally in a dosage of 10 mg/kg once every 4 days for 5 weeks for two cycles. There was 5 weeks of no medication between the cycles. The main outcomes included the change in lipidemia levels, the change in knee OA-related symptoms assessed by pain numerical rating scale (NRS) and Knee Osteoarthritis Outcome Score (KOOS), and knee MRI semi-quantitative score. The changes were analysed using paired t-tests.
RESULTS
38 participants were included, with a mean age of 62.2 years. We found a statistically significant decrease in total cholesterol (from 6.23 ± 0.74 to 5.95 ± 0.77 mmol/L; = 0.01) and low-density lipoprotein (from 4.03 ± 0.61 to 3.82 ± 0.61 mmol/L; = 0.009) from baseline to week 16. Knee pain NRS was significantly reduced at weeks 6, 16 and 26 from 6.39 ± 1.33 to 4.18 ± 1.99, 3.63 ± 2.28 and 4.38 ± 2.55, respectively ( < 0.001). However, there was no significant difference in terms of the primary outcome of triglyceride levels before and after treatment. The most common AEs were positive faecal occult blood tests, followed by headache and diarrhoea.
CONCLUSION
The findings suggest that PPS has promising effects on improving dyslipidaemia and symptomatic pain relief in people with knee OA.
PubMed: 36879559
DOI: 10.1016/j.ocarto.2023.100343 -
Canadian Journal of Ophthalmology.... Apr 2024Pentosan polysulfate (PPS; ELMIRON, Janssen Pharmaceuticals, Titusville, NJ) is a U.S. Food and Drug Administration-approved oral medication for interstitial cystitis....
OBJECTIVE
Pentosan polysulfate (PPS; ELMIRON, Janssen Pharmaceuticals, Titusville, NJ) is a U.S. Food and Drug Administration-approved oral medication for interstitial cystitis. Numerous reports have been published detailing retinal toxicity with the use of PPS. Studies characterizing this condition are primarily retrospective, and consequently, alert and screening systems need to be developed to actively screen for this disease. The goal of this study was to characterize ophthalmic monitoring trends of a PPS-using patient sample to construct an alert and screening system for monitoring this condition.
METHODS
A single-institution retrospective chart review was conducted between January 2005 and November 2020 to characterize PPS use. An electronic medical record (EMR) alert was constructed to trigger based on new PPS prescriptions and renewals offering ophthalmology referral.
RESULTS
A total of 1407 PPS users over 15 years was available for characterization, with 1220 (86.7%) being female, the average duration of exposure being 71.2 ± 62.6 months, and the average medication cumulative exposure being 669.7 ± 569.2 g. A total of 151 patients (10.7%) had a recorded visit with an ophthalmologist, with 71 patients (5.0%) having optical coherence tomography imaging. The EMR alert fired for 88 patients over 1 year, with 34 patients (38.6%) either already being screened by an ophthalmologist or having been referred for screening.
CONCLUSIONS
An EMR support tool can improve referral rates of PPS maculopathy screening with an ophthalmologist and may serve as an efficient method for longitudinal screening of this condition with the added benefit of informing pentosan polysulfate prescribers about this condition. Effective screening and detection may help determine which patients are at high risk for this condition.
Topics: Humans; Female; Male; Pentosan Sulfuric Polyester; Retrospective Studies; Eye; Retinal Diseases; Face
PubMed: 36878265
DOI: 10.1016/j.jcjo.2023.01.019 -
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 -
JAMA Ophthalmology Mar 2023
Topics: Humans; Pentosan Sulfuric Polyester; Macular Degeneration; Retinal Diseases
PubMed: 36729463
DOI: 10.1001/jamaophthalmol.2022.6158 -
JAMA Ophthalmology Mar 2023Prior retrospective studies have provided limited evidence on disease progression following drug cessation in patients with maculopathy associated with pentosan...
IMPORTANCE
Prior retrospective studies have provided limited evidence on disease progression following drug cessation in patients with maculopathy associated with pentosan polysulfate (PPS).
OBJECTIVE
To evaluate the 2-year evolution of maculopathy associated with PPS use after drug cessation.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study prospectively evaluated the natural history of patients with maculopathy associated with PPS use. Participants seen at the Emory Eye Center were enrolled between December 1, 2018, and December 1, 2019, and data were collected through November 30, 2021.
MAIN OUTCOMES AND MEASURES
The main outcomes were changes in visual function and structure. Visual function was assessed annually with refraction and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), mesopic microperimetry, and dark adaptometry. Structural outcomes included presence and extent of complete retinal pigment epithelium and outer retinal atrophy (cRORA), macular central subfield thickness (CST), and subfoveal choroidal thickness (SFCT).
RESULTS
Of the 12 participants (23 eyes), 11 (91.7%) were female (1 [8.3%] male), 11 (91.7%) were White (1 [8.3%] Black), and median (IQR) age at enrollment was 58 (47-64) years. Median (IQR) time from PPS discontinuation to initial visit was 0.6 (0.4-1.9) years. Median baseline ETDRS BCVA letter score was 83 (Snellen equivalent, 20/20) (IQR, 80-86.5 [20/25-20/20]), with a median 2-year change of -3 (IQR, -6 to -0.5; P = .08). Four eyes (17.4%) had a letter score decline of 15 or more, all associated with progressive cRORA. Median change in microperimetry average threshold was -3.5 dB (IQR, -4.1 to -2.5 dB; P = .001), and percent reduced threshold was 32.5% (IQR, 20.3%-52.8%; P = .004). Nine eyes (39%) had macular cRORA at baseline, with a median linearized growth rate of 0.23 mm/y (IQR, 0.22-0.25 mm/y). Two eyes (8.7%) without atrophy at baseline developed new-onset cRORA. Median baseline CST was 284 μm (IQR, 253-291 μm), with a median 2-year change of -5 μm (IQR, -13 to 0.5 μm; P = .0497). Median 2-year change in SFCT was 1 μm (IQR, -18 to 16 μm; P = .91).
CONCLUSIONS AND RELEVANCE
The findings of this cohort study suggest that functional and structural deficits continue to progress in PPS-associated maculopathy even after drug cessation. Additional study is needed to determine whether these findings can be generalized to other patients with PPS-associated maculopathy and whether longer follow-up could determine subsequent disease course.
Topics: Humans; Male; Female; Middle Aged; Pentosan Sulfuric Polyester; Cohort Studies; Retrospective Studies; Tomography, Optical Coherence; Macular Degeneration; Diabetic Retinopathy; Retinal Degeneration; Atrophy
PubMed: 36729449
DOI: 10.1001/jamaophthalmol.2022.6093 -
The American Journal of Gastroenterology May 2023This study evaluates the potential association of pentosan polysulfate (PPS) with inflammatory bowel disease (IBD) or dysplasia.
INTRODUCTION
This study evaluates the potential association of pentosan polysulfate (PPS) with inflammatory bowel disease (IBD) or dysplasia.
METHODS
We searched electronic medical records to identify patients with IBD using PPS.
RESULTS
Ten of 30 identified patients (33.3%) had colonic dysplasia. Six of them (60%) underwent colectomy for endoscopically unresectable dysplasia. Three (10%) discontinued PPS, each with an apparent benefit.
DISCUSSION
Patients with IBD at 2 institutions who had taken PPS had high rates of colonic dysplasia leading to surgery. Patients who stopped PPS showed improvement in their colitis. PPS may play a causal role in the development of colitis and dysplasia.
Topics: Humans; Pentosan Sulfuric Polyester; Inflammatory Bowel Diseases; Colitis
PubMed: 36689730
DOI: 10.14309/ajg.0000000000002137 -
American Journal of Ophthalmology Case... Mar 2023To report the development of type 3 macular neovascularization (MNV) in a patient with pentosan polysulfate sodium (PPS) maculopathy one year after PPS cessation.
PURPOSE
To report the development of type 3 macular neovascularization (MNV) in a patient with pentosan polysulfate sodium (PPS) maculopathy one year after PPS cessation.
OBSERVATION
A 72-year-old woman presented for decreased visual acuity in the left eye. Medical history was significant for interstitial cystitis treated with PPS for 11 years (cumulative dose of 1205 g) and PPS maculopathy. PPS was discontinued 1 year prior to presentation. Blue-light fundus autofluorescence and spectral domain optical coherence tomography confirmed the diagnosis of bilateral PPS maculopathy. OCT-angiography illustrated the development of type 3 MNV with intraretinal fluid in the left eye. Intravitreal injections of aflibercept were initiated with a good visual and anatomical response.
CONCLUSION AND IMPORTANCE
This report describes the development of type 3 MNV in a patient with PPS macular toxicity one year after PPS cessation. This complication emphasizes the need for regular retinal surveillance even after discontinuation of the inciting drug.
PubMed: 36561881
DOI: 10.1016/j.ajoc.2022.101771