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JAMA Ophthalmology Jan 2022Case series have identified a macular condition hypothesized to be associated with the use of pentosan polysulfate sodium (PPS). Observational studies seeking to...
IMPORTANCE
Case series have identified a macular condition hypothesized to be associated with the use of pentosan polysulfate sodium (PPS). Observational studies seeking to quantify this association have yielded equivocal results.
OBJECTIVE
To estimate the association between PPS exposure and maculopathy.
DESIGN, SETTING, AND PARTICIPANTS
This disproportionality analysis was conducted using the US Food and Drug Administration Adverse Event Reporting System from January 2013 through June 2020.
EXPOSURE
Adverse event reports for pentosan polysulfate were selected and compared with adverse event reports associated with drugs taken for the following indications: interstitial cystitis, cystitis, bladder disorder, or bladder pain.
MAIN OUTCOME MEASURES
Retinal adverse events were identified using the retinal disorders Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query, which includes conditions associated with retinal damage attributable to blockage of its blood supply, nutritional deficiencies, toxins, and diseases affecting the retina.
RESULTS
There were 2775 reports available for analysis in the PPS group (of which 1966 were for women [70.9%]) and 6833 reports in the other drugs group (of which 4036 [59.1%] were for women). The proportion of adverse events for any macular event relative to all other events was elevated for the users of PPS compared with those using other interstitial cystitis and bladder pain drugs (proportionate reporting ratio [PRR], 1.21 [95% CI, 1.01-1.44]). With respect to specific retinal conditions, macular degeneration (20 [0.8%] vs 15 [0.2%]), maculopathy (83 [3.4%] vs 2 [0.03%]), retinal dystrophy (3 [0.1%] vs 0), retinal injury (5 [0.2%] vs 0), and retinal toxicity (3 [0.1%] vs 0) were proportionately more common among users of PPS compared with those using other interstitial cystitis and bladder pain drugs, respectively.
CONCLUSIONS AND RELEVANCE
The results of the current study add to the growing evidence that PPS use is associated with an increased risk of maculopathy. Studies that rule out prevalent retinal abnormalities prior to the initiation of PPS would strengthen the current body of literature.
Topics: Anticoagulants; Cystitis, Interstitial; Female; Humans; Macular Degeneration; Male; Pain; Pentosan Sulfuric Polyester; Retinal Dystrophies
PubMed: 34792558
DOI: 10.1001/jamaophthalmol.2021.4778 -
JFMS Open Reports 2021A 14-year-old male castrated Cornish Rex cat was referred for lethargy progressing rapidly to collapse in the hours following a subcutaneous injection of a product...
CASE SUMMARY
A 14-year-old male castrated Cornish Rex cat was referred for lethargy progressing rapidly to collapse in the hours following a subcutaneous injection of a product containing 100 mg/ml pentosan polysulfate sodium and 168 mg/ml glucosamine. Physical examination revealed the cat to be in hypotensive shock with swelling and interstitial oedema around the cranial thorax and caudal cervical regions without cutaneous haemorrhage. Initial diagnostics revealed a severe anaemia (packed cell volume 11%) which later deteriorated further, necessitating a blood transfusion and aggressive fluid therapy. Post-transfusion, the patient remained dyspnoeic and subsequent diagnostics found evidence of pre-existing cardiomyopathy and congestive heart failure. The cat was euthanased 24 h following presentation due to increasing dyspnoea. Post-mortem findings were of severe subcutaneous and intermuscular haemorrhage over the neck and thorax, among other changes. There were no detectable levels of coumarin anticoagulants in the liver.
RELEVANCE AND NOVEL INFORMATION
This is the first reported case of acute subcutaneous and intermuscular haemorrhage of this severity suspected to be related to the off-label use of an injectable product containing pentosan polysulfate in a cat. Given the popularity of its use for feline arthritis, there is a need for large-scale clinical trials to evaluate the safety and efficacy of products containing pentosan polysulfate for cats, and any side effects to be reported.
PubMed: 34777848
DOI: 10.1177/20551169211058650 -
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 -
Central European Journal of Urology 2021Bladder pain syndrome/interstitial cystitis (BPS/IC) is a condition that is characterized by urgency, frequency and/or pelvic pain. The disease occurs mainly in women....
Safety and efficacy of pentosan polysulfate in patients with bladder pain syndrome/interstitial cystitis: a multicenter, double-blind, placebo-controlled, randomized study.
INTRODUCTION
Bladder pain syndrome/interstitial cystitis (BPS/IC) is a condition that is characterized by urgency, frequency and/or pelvic pain. The disease occurs mainly in women. BPS/IC can be severe enough to have a significant impact on patients' quality of life, but it can also be associated with moderate symptoms that are equally debilitating.The aim of this article was to evaluate the possibility of the use of pentosan polysulfate sodium in patients in the complex treatment of BPS/IC.
MATERIAL AND METHODS
A multicenter, double-blind, placebo-controlled, randomized study was conducted in parallel groups in 7 Russian medical centers.
RESULTS
Efficacy and safety have been established as the main criteria. A total of 93 patients were screened. Statistical analysis was performed. It has been shown that pentosan therapy is more effective than in the placebo. Average change in the number of points on the scale O'Leary-Santa Interstitial Cystitis Symptom Index compared to baseline data in the pentosan group 4.93 ±3, 03, in the placebo group 1.66 ±3.19 (p = 0.014), and the adverse events and safety of pentosan are comparable to the placebo group.
CONCLUSIONS
Oral glycosaminoglycan (pentosan polusulfate sodium) is an effective and safe drug and should be included in the complex treatment of patients with bladder pain syndrome/interstitial cystitis.
PubMed: 34336239
DOI: 10.5173/ceju.2021.0340.R1 -
Journal of Vitreoretinal Diseases 2022This work describes characteristics of pentosan polysulfate sodium (PPS)-associated maculopathy and its similarities with common maculopathies in a retina practice...
PURPOSE
This work describes characteristics of pentosan polysulfate sodium (PPS)-associated maculopathy and its similarities with common maculopathies in a retina practice cohort.
METHODS
Thirty-two patients were identified through electronic medical record query who were exposed to PPS. One patient was excluded for lack of retinal imaging. Thirty-one patients (62 eyes) were included. A retrospective review was used to obtain patient characteristics, examination findings, and retinal imaging of the study patients. Classification into "likely," "unlikely," or "possible" to have PPS-associated maculopathy groups was based on the fundus photography and retinal imaging. Main outcome measures were best-corrected visual acuity, age, sex, diagnosis of reason for referral, allocation into designated maculopathy group, and presence of choroidal neovascularization.
RESULTS
Of 31 patients (62 eyes), the median age was 70 years (range, 24-104 years) and the majority were women (87%). Mean best-corrected visual acuity was 0.3 ± 0.4 logMAR at presentation. The most common reason for referral was age-related macular degeneration (29%). Maculopathy grades were "likely" (29%, 9 total patients), "possible" (26%, 8 total patients), or "unlikely" (45%, 14 total patients). Choroidal neovascularization was noted in 9.7% of all eyes and 11% of eyes in the "likely" group. The "possible" and "likely" groups had older ages of presentation ( < .05) compared with the "unlikely" group.
CONCLUSIONS
A high percentage (55%) of patients with a history of chronic PPS exposure showed features of "likely" or "possible" maculopathy. Similarities with common maculopathies such as age-related macular degeneration and the importance of screening and recognizing at-risk patients are highlighted.
PubMed: 37008666
DOI: 10.1177/24741264211020259 -
CMAJ : Canadian Medical Association... Jul 2021
Review
Topics: Humans; Macular Degeneration; Pentosan Sulfuric Polyester
PubMed: 34312174
DOI: 10.1503/cmaj.201900-f -
Thrombosis Research Aug 2021Heparin-induced thrombocytopenia (HIT) is characterized clinically by thrombocytopenia, hypercoagulability, and increased thrombosis risk, and serologically by... (Review)
Review
Heparin-induced thrombocytopenia (HIT) is characterized clinically by thrombocytopenia, hypercoagulability, and increased thrombosis risk, and serologically by platelet-activating anti-platelet factor 4 (PF4)/heparin antibodies. Heparin-"induced" acknowledges that HIT is usually triggered by a proximate immunizing exposure to heparin. However, certain non-heparin medications (pentosan polysulfate, hypersulfated chondroitin sulfate, fondaparinux) can trigger "HIT". Further, naturally-occurring polyanions (bacterial lipopolysaccharide, DNA/RNA) can interact with PF4 to recapitulate HIT antigens. Indeed, immunologic presensitization to naturally-occurring polyanions could explain why HIT more closely resembles a secondary, rather than a primary, immune response. In 2008 it was first reported that a HIT-mimicking disorder can occur without any preceding exposure to heparin or polyanionic medications. Termed "spontaneous HIT syndrome", two subtypes are recognized: (a) surgical (post-orthopedic, especially post-total knee arthroplasty, and (b) medical (usually post-infectious). Recently, COVID-19 adenoviral vector vaccination has been associated with a thrombotic thrombocytopenic disorder associated with positive PF4-dependent enzyme-immunoassays and serum-induced platelet activation that is maximal when PF4 is added. Vaccine-induced immune thrombotic thrombocytopenia (VITT) features unusual thromboses (cerebral venous thrombosis, splanchnic vein thrombosis) similar to those seen in spontaneous HIT syndrome. The emerging concept is that classic HIT reflects platelet-activating anti-PF4/heparin antibodies whereas spontaneous HIT syndrome and other atypical "autoimmune HIT" presentations (delayed-onset HIT, persisting HIT, heparin "flush" HIT) reflect heparin-independent platelet-activating anti-PF4 antibodies-although the precise relationships between PF4 epitope targets and the clinical syndromes remain to be determined. Treatment of spontaneous HIT syndrome includes non-heparin anticoagulation (direct oral Xa inhibitors favored over direct thrombin inhibitors) and high-dose immunoglobulin.
Topics: Anticoagulants; Arthroplasty, Replacement, Knee; COVID-19; Heparin; Humans; Platelet Factor 4; SARS-CoV-2; Syndrome; Thrombocytopenia; Thrombosis; Vaccines
PubMed: 34144250
DOI: 10.1016/j.thromres.2021.05.018 -
CMAJ : Canadian Medical Association... May 2021
Topics: Anticoagulants; Cystitis, Interstitial; Humans; Macular Degeneration; Pentosan Sulfuric Polyester; Time Factors; Vision Disorders
PubMed: 33941523
DOI: 10.1503/cmaj.201900 -
Angewandte Chemie (International Ed. in... Jul 2021Here we report that negatively charged polysulfates can bind to the spike protein of SARS-CoV-2 via electrostatic interactions. Using a plaque reduction assay, we...
Here we report that negatively charged polysulfates can bind to the spike protein of SARS-CoV-2 via electrostatic interactions. Using a plaque reduction assay, we compare inhibition of SARS-CoV-2 by heparin, pentosan sulfate, linear polyglycerol sulfate (LPGS) and hyperbranched polyglycerol sulfate (HPGS). Highly sulfated LPGS is the optimal inhibitor, with an IC of 67 μg mL (approx. 1.6 μm). This synthetic polysulfate exhibits more than 60-fold higher virus inhibitory activity than heparin (IC : 4084 μg mL ), along with much lower anticoagulant activity. Furthermore, in molecular dynamics simulations, we verified that LPGS can bind more strongly to the spike protein than heparin, and that LPGS can interact even more with the spike protein of the new N501Y and E484K variants. Our study demonstrates that the entry of SARS-CoV-2 into host cells can be blocked via electrostatic interactions, therefore LPGS can serve as a blueprint for the design of novel viral inhibitors of SARS-CoV-2.
Topics: A549 Cells; Animals; Antiviral Agents; Chlorocebus aethiops; Heparin; Humans; Molecular Dynamics Simulation; Pentosan Sulfuric Polyester; Polymers; Protein Binding; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Static Electricity; Vero Cells; Virus Internalization
PubMed: 33860605
DOI: 10.1002/anie.202102717 -
Scientific Reports Mar 2021Creutzfeldt-Jakob Disease (CJD) is a fatal, currently incurable, neurodegenerative disease. The search for candidate treatments would be greatly facilitated by the...
Creutzfeldt-Jakob Disease (CJD) is a fatal, currently incurable, neurodegenerative disease. The search for candidate treatments would be greatly facilitated by the availability of human cell-based models of prion disease. Recently, an induced pluripotent stem cell derived human cerebral organoid model was shown to take up and propagate human CJD prions. This model offers new opportunities to screen drug candidates for the treatment of human prion diseases in an entirely human genetic background. Here we provide the first evidence that human cerebral organoids can be a viable model for CJD drug screening by using an established anti-prion compound, pentosan polysulfate (PPS). PPS delayed prion propagation in a prophylactic-like treatment paradigm and also alleviated propagation when applied following establishment of infection in a therapeutic-like treatment paradigm. This study demonstrates the utility of cerebral organoids as the first human 3D cell culture system for screening therapeutic drug candidates for human prion diseases.
Topics: Cell Culture Techniques; Cell Line; Cerebral Ventricles; Creutzfeldt-Jakob Syndrome; Drug Discovery; Drug Evaluation, Preclinical; Humans; Organoids; Pentosan Sulfuric Polyester
PubMed: 33727594
DOI: 10.1038/s41598-021-84689-6