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The Journal of Veterinary Medical... Oct 2022The aim of this study was to investigate the anti-hepcidin effect of pentosan polysulfate (PPS) in Mongolian horses. Twenty-six healthy horses were randomly allocated in...
The aim of this study was to investigate the anti-hepcidin effect of pentosan polysulfate (PPS) in Mongolian horses. Twenty-six healthy horses were randomly allocated in to two-groups; one group was treated with a PPS once a week for 4-weeks while another group keeping as placebo. Blood samples at day 0 (D0), before race (BR; day 28) and after race (AR; day 28) were analyzed for serum biochemistry, hepcidin and iron concentrations. Significant reduction of hepcidin was observed at AR in PPS group when compared with BR placebo (P<0.05) and AR placebo (P<0.01). Mean hepcidin concentration difference of D0-BR and BR-AR in PPS was greater than the placebo whereas the iron concentration difference is reduced compared to placebo. Results indicate a novel therapeutic application of PPS as an anti-hepcidin compound to control hepcidin in horses while emphasizing further molecular studies.
Topics: Animals; Horses; Iron; Pentosan Sulfuric Polyester
PubMed: 36047165
DOI: 10.1292/jvms.22-0113 -
Investigative Ophthalmology & Visual... Nov 2020Individuals with pentosan polysulfate sodium (PPS) maculopathy commonly report symptoms of prolonged dark adaptation and difficulty reading. We hypothesize that PPS...
PURPOSE
Individuals with pentosan polysulfate sodium (PPS) maculopathy commonly report symptoms of prolonged dark adaptation and difficulty reading. We hypothesize that PPS maculopathy causes degradation of visual function not fully captured with visual acuity testing.
METHODS
Subjects with PPS maculopathy underwent multimodal evaluation of retinal structure and function. Structural changes were graded as moderate or advanced. Patient-reported visual function was assessed with the National Eye Institute Visual Function Questionnaire 39 (NEI-VFQ-39) and Low Luminance Questionnaire (LLQ). Objective functional evaluations included Early Treatment of Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), Pelli-Robson contrast sensitivity, mesopic microperimetry, and dark adaptometry. Functional testing results were correlated with structural disease category.
RESULTS
Thirteen patients (26 eyes), median age 62 years (range, 37-76), completed the study. Median ETDRS letter score was 82 (Snellen equivalent 20/25). Median NEI-VFQ-39 and LLQ composite scores were 65 (range, 33-88) and 41 (range, 20-92), respectively. Median contrast sensitivity was 1.65 (range, 0.15-1.95), and median mesopic microperimetry average thresholds and percent reduced thresholds were 26 decibels (range, 0.4-28.6) and 21.6% (range, 0-100%), respectively. Median rod intercept time was 14.1 minutes (range, 4.4-20.0). Eyes with advanced disease based on retinal structure had significantly worse retinal function for several testing modalities.
CONCLUSIONS
PPS maculopathy causes considerable visual function degradation that is not fully captured with BCVA testing. There was good correlation between other measures of visual function and disease severity. These findings deepen our concern regarding this patient safety issue.
Topics: Adult; Aged; Anticoagulants; Contrast Sensitivity; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Pentosan Sulfuric Polyester; Retinal Diseases; Sickness Impact Profile; Surveys and Questionnaires; Vision Disorders; Visual Acuity; Visual Field Tests; Visual Fields
PubMed: 33231621
DOI: 10.1167/iovs.61.13.33 -
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 -
Veterinary Sciences Apr 2024Musculoskeletal injuries such as equine osteoarthritis, osteoarticular defects, tendonitis/desmitis, and muscular disorders are prevalent among sport horses, with a fair... (Review)
Review
Musculoskeletal injuries such as equine osteoarthritis, osteoarticular defects, tendonitis/desmitis, and muscular disorders are prevalent among sport horses, with a fair prognosis for returning to exercise or previous performance levels. The field of equine medicine has witnessed rapid and fruitful development, resulting in a diverse range of therapeutic options for musculoskeletal problems. Staying abreast of these advancements can be challenging, prompting the need for a comprehensive review of commonly used and recent treatments. The aim is to compile current therapeutic options for managing these injuries, spanning from simple to complex physiotherapy techniques, conservative treatments including steroidal and non-steroidal anti-inflammatory drugs, hyaluronic acid, polysulfated glycosaminoglycans, pentosan polysulfate, and polyacrylamides, to promising regenerative therapies such as hemoderivatives and stem cell-based therapies. Each therapeutic modality is scrutinized for its benefits, limitations, and potential synergistic actions to facilitate their most effective application for the intended healing/regeneration of the injured tissue/organ and subsequent patient recovery. While stem cell-based therapies have emerged as particularly promising for equine musculoskeletal injuries, a multidisciplinary approach is underscored throughout the discussion, emphasizing the importance of considering various therapeutic modalities in tandem.
PubMed: 38787162
DOI: 10.3390/vetsci11050190 -
Asia-Pacific Journal of Ophthalmology...Pentosan polysulfate (PPS) sodium (Elmiron) is the only Food and Drug Administration (FDA)-approved oral medication to treat interstitial cystitis, also known as bladder... (Review)
Review
Pentosan polysulfate (PPS) sodium (Elmiron) is the only Food and Drug Administration (FDA)-approved oral medication to treat interstitial cystitis, also known as bladder pain syndrome. A symptomatic pigmentary maculopathy associated with PPS was reported in 2018. Since then, recognition of this unique drug toxicity has increased rapidly. This potentially sight-threatening side effect prompted the FDA in June 2020 to update the label for PPS to warn about "retinal pigmentary changes." A challenging feature of pentosan maculopathy is its ability to mimic many other retinal conditions, including inherited retinal dystrophies such as pattern dystrophy, mitochondrially inherited diabetes and deafness, and Stargardt disease, and age-related macular degeneration. In this review, we discuss the history of PPS maculopathy and its implications for thousands of at-risk interstitial cystitis patients. We use published literature and an illustrative case from our institution to highlight the importance of diagnosing PPS maculopathy. We also compare PPS maculopathy to age-related macular degeneration, explain why differentiating between the 2 is clinically important, and highlight avenues for further research. Finally, we highlight the paucity of data on patients of color and why this lack of understanding may impact patient care.
Topics: Anticoagulants; Cystitis, Interstitial; Female; Humans; Macular Degeneration; Male; Pentosan Sulfuric Polyester; Retinal Dystrophies
PubMed: 35533330
DOI: 10.1097/APO.0000000000000504 -
Journal of Virology Aug 2019Human T-cell leukemia virus type 1 (HTLV-1) infection causes T-cell leukemia and inflammatory diseases, most notably including HTLV-1-associated myelopathy/tropical...
Human T-cell leukemia virus type 1 (HTLV-1) infection causes T-cell leukemia and inflammatory diseases, most notably including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The underlying mechanism for the pathogenesis of HAM/TSP remains unclear. According to a recent clinical trial, a humanized antibody that targets CCR4 cells ameliorates inflammation by reducing the number of infected cells in the central nervous system; this result suggests that the transmigration of HTLV-1-infected cells plays a crucial role in HAM/TSP. Partly due to the blood-brain barrier, current treatments for HAM/TSP are mostly palliative. Pentosan polysulfate (PPS), a semisynthetic glycosaminoglycan, has recently been used to treat HAM/TSP and was found to alleviate the symptoms. In this study, we investigated the effect of PPS on HTLV-1-infected cells and provide evidence for its efficacy in HAM/TSP. PPS was cytotoxic to certain HTLV-1-infected cells and significantly suppressed HTLV-1 virion production. PPS also efficiently inhibited HTLV-1 cell-cell transmission in T cells. In addition, PPS blocked HTLV-1 infection of primary endothelial cells (human umbilical vascular endothelial cells) and suppressed the subsequent induction of proinflammatory cytokine expression. Furthermore, PPS was found to inhibit the adhesion and transmigration of HTLV-1-infected cells. We also confirmed the anti-HTLV-1 effect of PPS using two mouse models. PPS blocked HTLV-1 infection in a mouse model with peripheral blood mononuclear cell (PBMC)-humanized NOD-scid IL2Rgamma (huPBMC NSG) mice. PPS was also found to suppress the development of dermatitis and lung damage in HTLV-1 bZIP factor (HBZ)-transgenic (HBZ-Tg) mice, an HTLV-1 transgenic mouse model in which the mice develop systemic inflammation. HTLV-1 is the first human retrovirus to have been identified and is endemic in certain areas worldwide. HTLV-1 infection leads to the development of an inflammatory disease called HAM/TSP, a myelopathy characterized by slowly progressive spastic paraparesis. There have been no effective therapeutics available for HAM/TSP, but recently, a semisynthetic glycosaminoglycan, named pentosan polysulfate (PPS), has been found to alleviate the symptoms of HAM/TSP. Here we conducted a comprehensive study on the effect of PPS both and PPS demonstrated anti-HTLV-1 potential in infected cell lines, as shown by its suppressive effects on HTLV-1 replication and transmission and on the transmigration of infected T cells. Moreover, results obtained from two HTLV-1 mouse models demonstrate that PPS inhibits HTLV-1 infection and inflammation development Our work offers insights into the treatment of HAM/TSP by PPS and also suggests its possible use for treating other HTLV-1-induced inflammatory diseases.
Topics: Animals; Antineoplastic Agents; Cell Adhesion; Cell Line, Tumor; Disease Models, Animal; Endothelial Cells; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Leukocytes, Mononuclear; Mice; Mice, Inbred NOD; Mice, Knockout; Mice, Transgenic; Pentosan Sulfuric Polyester; T-Lymphocytes; Virus Replication
PubMed: 31167921
DOI: 10.1128/JVI.00413-19 -
Journal of Vitreoretinal Diseases 2023We investigated the potential for indication bias to be present in previous studies of pentosan polysulfate sodium (PPS) pigmentary retinopathy by comparing the...
We investigated the potential for indication bias to be present in previous studies of pentosan polysulfate sodium (PPS) pigmentary retinopathy by comparing the incidence and risk of retinopathy in patients with interstitial cystitis (IC) to matched controls. Adult women with IC from a multicenter database of electronic medical record data were matched to non-IC controls at a 1:4 ratio. The IC cohort was subdivided according to duration of PPS use: never, <5 years, and ≥5 years. Incidence and risk (estimated by Cox proportional hazards models) of retinopathy (defined by 6 , Ninth and Tenth Revision codes) were compared between groups. There were 22 060 women with IC and 88 240 women without IC. Average age was 53.92 years (SD, 16.22 years), and 96 110 (87.14%) patients were non-Hispanic White. Incidence of retinopathy per 100 000 person-years was 173.88 (95% CI, 162.78-185.53) for patients without IC, 226.63 (95% CI, 197.73-258.56) for IC without PPS use, 293.02 (95% CI 230.86-366.75) for IC with <5 years of PPS use, and 558.91 (95% CI, 399.29-761.07) for IC with ≥5 years of PPS use. Adjusted hazard ratios were 1.31 (95% CI, 1.13-1.51, < .001) for IC without PPS use, 1.70 (95% CI, 1.35-2.15, < .001) for IC with <5 years of PPS use, and 3.10 (95% CI, 2.26-4.27, < .001) for IC with ≥5 years of PPS use. Patients with IC had greater incidence and risk of retinopathy. PPS use further increased the incidence and risk of retinopathy.
PubMed: 37706083
DOI: 10.1177/24741264231190978 -
Retinal Cases & Brief Reports Nov 2023The purpose of this study was to report a unique case of pentosan polysulfate sodium (PPS) maculopathy with remarkable rapid progression over 2 years. These findings...
PURPOSE
The purpose of this study was to report a unique case of pentosan polysulfate sodium (PPS) maculopathy with remarkable rapid progression over 2 years. These findings show the importance of early detection of macular disease to limit toxic exposure and reduce the risk of progression.
METHODS
Multimodal retinal imaging including fundus autofluorescence, near-infrared reflectance with pseudocolor, and spectral domain optical coherence tomography was performed in an elderly patient with a history of PPS therapy (cumulative dose of 1,205 g) at baseline and 2 years later.
RESULTS
Baseline multimodal retinal imaging failed to show significant macular findings of PPS toxicity in either eye, but on repeat evaluation 2 years later, advanced features of PPS maculopathy were detected in both eyes with fundus autofluorescence, near-infrared reflectance, pseudocolor, and spectral domain optical coherence tomography.
CONCLUSION
This report describes a remarkable case of rapid progression of PPS maculopathy as documented with multimodal retinal imaging. The dramatic progression of macular findings over just 2 years underscores the importance of early detection and prompt withdrawal of therapy, if systemically feasible, to retard the development and rate of progression of PPS maculopathy.
Topics: Humans; Aged; Pentosan Sulfuric Polyester; Retinal Diseases; Macular Degeneration; Retina; Tomography, Optical Coherence; Fluorescein Angiography
PubMed: 35385434
DOI: 10.1097/ICB.0000000000001273 -
Ophthalmology Apr 2020To determine the association and cumulative dose-response pattern between pentosan polysulfate sodium (PPS) use for interstitial cystitis (IC) and maculopathy.
PURPOSE
To determine the association and cumulative dose-response pattern between pentosan polysulfate sodium (PPS) use for interstitial cystitis (IC) and maculopathy.
DESIGN
Large, multicenter, retrospective cohort study of commercially insured patients in the MarketScan database (Truven Health Analytics, San Jose, CA).
PARTICIPANTS
Two hundred twenty-seven thousand three hundred twenty-five patients with IC who were enrolled continuously in the MarketScan database.
METHODS
Cox proportional hazards models (controlling for patient gender, age at index diagnosis of IC, and diagnosis with diabetes mellitus) followed up patients from index diagnosis of IC for 5 years, or until patients discontinued insurance coverage, or until patients' first diagnosis with a maculopathy. As a sensitivity analysis, we re-estimate all models after excluding all patients with diabetes. To assess for dose response, we calculated the total days of PPS prescriptions filled and created a categorical variable indicating total exposure.
MAIN OUTCOME MEASURES
The primary outcome measure was association between binary PPS exposure and any maculopathy. Secondary outcome measures included exposure between binary and categorical, time-dependent, exposure to PPS and to drusen, nonexudative age-related macular degeneration (AMD), exudative AMD, hereditary maculopathy, and toxic maculopathy.
RESULTS
The most common diagnoses of maculopathy in patients with IC were exudative AMD (1.5%), drusen (0.8%), nonexudative AMD (0.3%), toxic maculopathy (0.1%), and hereditary dystrophy (0.04%). In unadjusted analyses, the percentage of patients who filled a PPS prescription and were diagnosed later with a maculopathy (2.37%) was very similar to the percentage of patients who did not fill a prescription (2.77%). Survival models using a binary variable indicating PPS exposure showed no significant associations between PPS exposure and diagnosis of drusen, nonexudative AMD, exudative AMD, toxic maculopathy, hereditary dystrophy, or an aggregate variable of any maculopathy. Similarly, there was no dose-dependent relationship between PPS exposure and diagnosis of any maculopathy. These findings remained stable in sensitivity analysis models that excluded patients with diabetes mellitus.
CONCLUSIONS
In this large, commercial claims database analysis, no association was found between PPS exposure and subsequent diagnosis of maculopathy.
Topics: Adult; Aged; Anticoagulants; Cystitis, Interstitial; Databases, Factual; Drug Prescriptions; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Insurance, Health; Macula Lutea; Male; Middle Aged; Pentosan Sulfuric Polyester; Proportional Hazards Models; Retinal Diseases; Retrospective Studies; Risk Factors; United States
PubMed: 31899034
DOI: 10.1016/j.ophtha.2019.10.036 -
Journal of Oncology Pharmacy Practice :... Oct 2022Hemorrhagic cystitis can commonly occur following an allogeneic hematopoietic cell transplant and treatment options are currently limited. Pentosan polysulfate, a...
INTRODUCTION
Hemorrhagic cystitis can commonly occur following an allogeneic hematopoietic cell transplant and treatment options are currently limited. Pentosan polysulfate, a heparin-like, sulfated polysaccharide, is used to relieve bladder pain and discomfort associated with interstitial cystitis. Initial reports in patients with hemorrhagic cystitis demonstrate that pentosan polysulfate may hasten hemorrhagic cystitis resolution and control symptoms.
METHODS AND RESULTS
This report includes a retrospective case series of six patients who received pentosan polysulfate for the treatment of hemorrhagic cystitis following an allogeneic hematopoietic cell transplant. Pentosan polysulfate was initiated at a median of 4.5 days (range: 3-18) following hemorrhagic cystitis onset and continued for a median duration of 17.5 days (range: 7-64). Four patients were tested for BK virus and all were found to have BK viremia and viruria around the time of pentosan polysulfate initiation. The median number of red blood cell transfusions seemed to decrease in the patients initiated on pentosan polysulfate. All patients received a multi-agent treatment regimen, which included pentosan polysulfate, and half the patients had symptom resolution. The median time to symptom resolution from pentosan polysulfate initiation was 9 days (range: 7-10).
CONCLUSION
Pentosan polysulfate was well-tolerated and seemed to assist with symptom resolution. Future studies are needed to confirm the impact of pentosan polysulfate on the treatment of hemorrhagic cystitis.
Topics: Cystitis; Cystitis, Interstitial; Hematopoietic Stem Cell Transplantation; Hemorrhage; Humans; Pentosan Sulfuric Polyester; Retrospective Studies
PubMed: 35642262
DOI: 10.1177/10781552221105295