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Archives of Internal Medicine Oct 2007More than 180 different types of therapy have been used in the treatment and management of painful bladder syndrome/interstitial cystitis (PBS/IC), yet evidence from... (Review)
Review
BACKGROUND
More than 180 different types of therapy have been used in the treatment and management of painful bladder syndrome/interstitial cystitis (PBS/IC), yet evidence from clinical trials remains inconclusive. This study aimed to evaluate the efficacy of pharmacologic approaches to PBS/IC, to quantify the effect size from randomized controlled trials, and to begin to inform a clinical consensus of treatment efficacy for PBS/IC.
METHODS
We identified randomized controlled trials for the pharmacologic treatment of patients with PBS/IC diagnosed on the basis of National Institute of Diabetes and Digestive and Kidney Diseases or operational criteria. Study limitations include considerable patient heterogeneity as well as variability in the definition of symptoms and in outcome assessment.
RESULTS
We included a total of 1470 adult patients from 21 randomized controlled trials. Only trials for pentosan polysulfate sodium had sufficient numbers to allow a pooled analysis of effect. According to a random-effects model, the pooled estimate of the effect of pentosan polysulfate therapy suggested benefit, with a relative risk of 1.78 for patient-reported improvement in symptoms (95% confidence interval, 1.34-2.35). This result was not heterogeneous (P = .47) and was without evidence of publication bias (P = .18). Current evidence also suggests the efficacy of dimethyl sulfoxide and amitryptyline therapy. Hydroxyzine, intravesical bacille Calmette-Guérin, and resiniferatoxin therapy failed to demonstrate efficacy, but evidence was inconclusive owing to methodological limitations.
CONCLUSIONS
Pentosan polysulfate may be modestly beneficial for symptoms of PBS/IC. There is insufficient evidence for other pharmacologic treatments. A consensus on standardized outcome measures is urgently needed.
Topics: Adult; Aged; Cystitis, Interstitial; Female; Humans; Male; Middle Aged; Pentosan Sulfuric Polyester; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 17923590
DOI: 10.1001/archinte.167.18.1922 -
Clinical Ophthalmology (Auckland, N.Z.) 2021To investigate the prevalence of retinal pathology in patients with a history of exposure to pentosan polysulfate sodium (PPS).
AIM
To investigate the prevalence of retinal pathology in patients with a history of exposure to pentosan polysulfate sodium (PPS).
METHODS
Patients exposed to PPS and seen in the ophthalmology clinic at Northwestern University during 1/1/2002 to 1/1/2019 were identified from electronic health records (EHR) by an electronic data warehouse (EDW) search. Visual acuity (VA), reasons for clinic visit, ocular conditions, and duration of exposure to PPS were noted. Chart review was performed for fundus exam findings and ophthalmologic imaging, specifically fundus photography, fundus autofluorescence, and ocular coherence tomography (OCT) images. When OCT or fundus photography was available, studies were evaluated by two independent graders.
RESULTS
A total of 131 patients who were exposed to PPS and seen at the Northwestern Ophthalmology clinic were identified in the EHR. Forty patients of 131 had imaging. Patients with imaging or fundus examination suspicious for PPS maculopathy were placed into the suspect group. Of the 40 patients that had imaging, 5 (12.5%) had features suspicious for PPS maculopathy. Of the remaining 91, 5 (5.4%) had macular pigmentary changes described on fundus exam. Among the 10 patients in the suspect group, the average duration of PPS use was 4.2 years (range 0.3-11.6 years, interquartile range 5.5 years) and the average cumulative dose was 380g (range 29-1092g, interquartile range 132g).
CONCLUSION
A novel drug-induced maculopathy has been associated with PPS use with a distinct clinical constellation that can be accurately identified with multimodal imaging.
PubMed: 33603329
DOI: 10.2147/OPTH.S285013 -
Minerva Surgery Jun 2023
Topics: Rats; Animals; Cystitis, Interstitial; Urinary Bladder; Hyaluronic Acid; Pentosan Sulfuric Polyester; Mast Cells; Perfusion
PubMed: 35708444
DOI: 10.23736/S2724-5691.22.09557-0 -
Laboratory Investigation; a Journal of... Feb 2012Pentosan polysulfate (PPS), a heparinoid compound essentially devoid of anticoagulant activity, modulates cell growth and decreases inflammation. We investigated the...
Pentosan polysulfate (PPS), a heparinoid compound essentially devoid of anticoagulant activity, modulates cell growth and decreases inflammation. We investigated the effect of PPS on the progression of established atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits. After severe atherosclerosis developed on an atherogenic diet, WHHL rabbits were treated with oral PPS or tap water for 1 month. The aortic intima-to-media ratio and macrophage infiltration were reduced, plaque collagen content was increased, and plaque fibrous caps were preserved by PPS treatment. Plasma lipid levels and post-heparin hepatic lipase activity remained unchanged. However, net collagenolytic activity in aortic extracts was decreased, and the levels of matrix metalloproteinase (MMP)-2 and tissue inhibitor of metalloproteinase (TIMP) activity were increased by PPS. Moreover, PPS treatment decreased tumor necrosis factor α (TNFα)-stimulated proinflammatory responses, in particular activation of nuclear factor-κB and p38, and activation of MMPs in macrophages. In conclusion, oral PPS treatment prevents progression of established atherosclerosis in WHHL rabbits. This effect may be partially mediated by increased MMP-2 and TIMP activities in the aortic wall and reduced TNFα-stimulated inflammation and MMP activation in macrophages. Thus, PPS may be a useful agent in inhibiting the progression of atherosclerosis.
Topics: Animals; Atherosclerosis; Cell Line; Enzyme Activation; Female; Humans; Hyperlipidemias; Immunohistochemistry; Lipids; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mitogen-Activated Protein Kinases; NF-kappa B; Pentosan Sulfuric Polyester; Rabbits; Tumor Necrosis Factor-alpha
PubMed: 22042083
DOI: 10.1038/labinvest.2011.154 -
American Family Physician May 2011Interstitial cystitis/painful bladder syndrome affects more than 1 million persons in the United States, but the cause remains unknown. Most patients with interstitial...
Interstitial cystitis/painful bladder syndrome affects more than 1 million persons in the United States, but the cause remains unknown. Most patients with interstitial cystitis/painful bladder syndrome are women with symptoms of suprapubic pelvic and/or genital area pain, dyspareunia, urinary urgency and frequency, and nocturia. It is important to exclude other conditions such as infections. Tests and tools commonly used to diagnose interstitial cystitis/painful bladder syndrome include specific questionnaires developed to assess the condition, the potassium sensitivity test, the anesthetic bladder challenge, and cystoscopy with hydrodistension. Treatment options include oral medications, intravesical instillations, and dietary changes and supplements. Oral medications include pentosan polysulfate sodium, antihistamines, tricyclic antidepressants, and immune modulators. Intravesical medications include dimethyl sulfoxide, pentosan polysulfate sodium, and heparin. Pentosan polysulfate sodium is the only oral therapy and dimethyl sulfoxide is the only intravesical therapy with U.S. Food and Drug Administration approval for the treatment of interstitial cystitis/painful bladder syndrome. To date, clinical trials of individual therapies have been limited in size, quality, and duration of follow-up. Studies of combination or multimodal therapies are lacking.
Topics: Administration, Intravesical; Administration, Oral; Antidepressive Agents, Tricyclic; Clinical Trials as Topic; Cystitis, Interstitial; Cystoscopy; Diagnosis, Differential; Dimethyl Sulfoxide; Drug Approval; Dyspareunia; Feeding Behavior; Female; Heparin; Histamine Antagonists; Humans; Immunologic Factors; Male; Pelvic Pain; Pentosan Sulfuric Polyester; Practice Guidelines as Topic; Syndrome; United States; United States Food and Drug Administration; Urination Disorders
PubMed: 21568251
DOI: No ID Found -
European Journal of Biochemistry Oct 1989Four sulfated polysaccharides (unfractioned heparin, low-molecular-mass heparin, heparan sulfate and pentosan polysulfate) were investigated for their abilities (a) to...
Four sulfated polysaccharides (unfractioned heparin, low-molecular-mass heparin, heparan sulfate and pentosan polysulfate) were investigated for their abilities (a) to bind antithrombin, (b) to induce conformational change of the inhibitor and (c) to potentiate antithrombin inhibition of thrombin. The binding capacity was reflected by the shielding of the heparin binding site. This was characterized by the extent to which a polysaccharide could protect chemical modification of Lys-125 and Lys-136, two lysyl residues of antithrombin which have been implicated in heparin binding. The conformational change was measured by fluorescence enhancement and the increased accessibility of Lys-236 to chemical modification. Our results reveal that the events of polysaccharide binding, conformational change and the enhancement of inhibitory activity are not quantitatively interlinked. Compared to the unfractionated heparin on an equal mass basis, the low-molecular-mass heparin (molecular mass 4-6 kDa) binds more strongly to antithrombin, induces a greater conformational change (about twofold), but is less potent in accelerating the inhibitory activity. Both heparin and heparan sulfate shield Lys-125 and Lys-136 and induce a conformational change that leads to exposure of Lys-236 and an increased fluorescence. On the other hand, pentosan polysulfate protects only Lys-125 and causes no appreciable conformational change, although it is also capable of enhancing the antithrombin-thrombin interaction. These data clearly demonstrate that the heparin and pentosan polysulfate binding sites of antithrombin overlap (at Lys-125) but are not identical.
Topics: Antithrombins; Binding Sites; Heparin; Heparitin Sulfate; Humans; Pentosan Sulfuric Polyester; Polysaccharides; Protein Conformation
PubMed: 2478364
DOI: 10.1111/j.1432-1033.1989.tb15106.x -
BMC Musculoskeletal Disorders Mar 2021Alphaviruses, such as Ross River (RRV) and chikungunya virus (CHIKV), cause significant global morbidity, with outbreaks of crippling joint inflammation and pain,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Alphaviruses, such as Ross River (RRV) and chikungunya virus (CHIKV), cause significant global morbidity, with outbreaks of crippling joint inflammation and pain, leaving patients incapacitated for months to years. With no available vaccine or specific therapeutic for any alphaviral disease, and a growing economic and public health burden, there is a serious need for the development of specific therapies.
METHODS
This study evaluated the safety and efficacy of pentosan polysulfate sodium (PPS) in subjects with RRV-induced arthralgia in a double-blind, placebo-controlled trial. Twenty subjects were randomized 2:1 to subcutaneous PPS (2 mg/kg) or placebo (sodium chloride 0.9%) twice weekly for 6 weeks. Safety evaluation included physical examination, concomitant medications, and laboratory findings. Efficacy assessments included change from baseline in joint function (hand grip strength and RAPID3) and quality of life (SF-36) at Days 15, 29, 39 and 81 after treatment initiation. Inflammatory and cartilage degradation biomarkers were exploratory endpoints.
RESULTS
PPS was well tolerated, with a similar proportion of subjects reporting at least one treatment-emergent adverse event (TEAE) in the treatment and placebo groups. Injection site reactions were the most common TEAE and occurred more frequently in the PPS group. Dominant hand grip strength and SF-36 scores improved with PPS at all time points assessed, with hand grip strength improvement of 6.99 kg (p = 0.0189) higher than placebo at Day 15. PPS showed significant improvements versus placebo in adjusted mean relative change from baseline for RAPID3 Pain (p = 0.0197) and Total (p = 0.0101) scores at Day 15. At the conclusion of the study overall joint symptoms, assessed by RAPID3, showed near remission in 61.5% of PPS subjects versus 14.3% of placebo subjects. Additionally, PPS treatment improved COMP, CTX-II, CCL1, CXCL12, CXCL16 and CCL17 biomarker levels versus placebo.
CONCLUSIONS
Overall, the improvements in strength and joint symptoms warrant further evaluation of PPS as a specific treatment for RRV-induced and other forms of arthritis.
TRIAL REGISTRATION
This trial is registered at the Australian New Zealand Clinical Trials Registry # ACTRN12617000893303 .
Topics: Arthralgia; Australia; Double-Blind Method; Hand Strength; Humans; Pentosan Sulfuric Polyester; Quality of Life; Ross River virus; Treatment Outcome
PubMed: 33711991
DOI: 10.1186/s12891-021-04123-w -
Canadian Family Physician Medecin de... Dec 2000To review current knowledge about the epidemiology, etiology, diagnosis, and treatment of interstitial cystitis, with special emphasis on management of this condition by... (Review)
Review
OBJECTIVE
To review current knowledge about the epidemiology, etiology, diagnosis, and treatment of interstitial cystitis, with special emphasis on management of this condition by family physicians.
QUALITY OF EVIDENCE
Articles were identified through MEDLINE and review of abstracts presented at Urology and Interstitial Cystitis meetings during the last decade. Recent reviews were further searched for additional studies and trials. Data were summarized from large epidemiologic studies. Etiologic theories were extracted from current concepts and reviews of scientific studies. Diagnostic criteria described in this review are based on clinical interpretation of National Institutes of Health (NIH) research guidelines, interpretation of data from the NIH Interstitial Cystitis Cohort Study, and recent evidence on use of the potassium sensitivity test. Treatment suggestions are based on six randomized placebo-controlled clinical treatment trials and best available clinical data.
MAIN MESSAGE
Interstitial cystitis affects about 0.01% to 0.5% of women. Its etiology is unknown, but might involve microbiologic, immunologic, mucosal, neurogenic, and other yet undefined agents. The diagnosis of interstitial cystitis is a diagnosis of exclusion. It is impossible to provide a purely evidence-based treatment strategy, but review of available evidence suggests that conservative supportive therapy (including diet modification); oral treatment with pentosan polysulfate, amitriptyline, or hydroxyzine; and intravesical treatments with heparinlike medications, dimethyl sulfoxide, or BCG vaccine could benefit some patients.
CONCLUSION
Family physicians should have an understanding of interstitial cystitis and be able to make a diagnosis and formulate an evidence-based treatment strategy for their patients.
Topics: Administration, Intravesical; Algorithms; Autoimmune Diseases; Bacterial Infections; Cystitis, Interstitial; Cystoscopy; Female; Glycosaminoglycans; Humans; Male; Potassium; Quality of Life; Urinary Bladder; Urinary Bladder, Neurogenic
PubMed: 11153410
DOI: No ID Found -
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 -
PloS One 2019Gaucher and Fabry diseases are the most prevalent sphingolipidoses. Chronic inflammation is activated in those disorders, which could play a role in pathogenesis....
Gaucher and Fabry diseases are the most prevalent sphingolipidoses. Chronic inflammation is activated in those disorders, which could play a role in pathogenesis. Significant degrees of amelioration occur in patients upon introduction of specific therapies; however, restoration to complete health status is not always achieved. The idea of an adjunctive therapy that targets inflammation may be a suitable option for patients. PPS is a mixture of semisynthetic sulfated polyanions that have been shown to have anti-inflammatory effects in mucopolysaccharidosis type I and II patients and animal models of type I, IIIA and VI. We hypothesized PPS could be a useful adjunctive therapy to inflammation for Gaucher and Fabry diseases. The objective of this work is to analyze the in vitro effect of PPS on inflammatory cytokines in cellular models of Gaucher and Fabry diseases, and to study its effect in Gaucher disease associated in vitro bone alterations. Cultures of peripheral blood mononuclear cells from Fabry and Gaucher patients were exposed to PPS. The secretion of proinflammatory cytokines was significantly reduced. Peripheral blood cells exposed to PPS from Gaucher patients revealed a reduced tendency to differentiate to osteoclasts. Osteoblasts and osteocytes cell lines were incubated with an inhibitor of glucocerebrosidase, and conditioned media was harvested in order to analyze if those cells secrete factors that induce osteoclastogenesis. Conditioned media from this cell cultures exposed to PPS produced lower numbers of osteoclasts. We could demonstrate PPS is an effective molecule to reduce the production of proinflammatory cytokines in in vitro models of Fabry and Gaucher diseases. Moreover, it was effective at ameliorating bone alterations of in vitro models of Gaucher disease. These results serve as preclinical supportive data to start clinical trials in human patients to analyze the effect of PPS as a potential adjunctive therapy for Fabry and Gaucher diseases.
Topics: Cell Differentiation; Cell Line; Fabry Disease; Gaucher Disease; Humans; Inflammation; Leukocytes, Mononuclear; Lysosomal Storage Diseases; Lysosomes; Osteoblasts; Osteoclasts; Osteocytes; Pentosan Sulfuric Polyester
PubMed: 31150494
DOI: 10.1371/journal.pone.0217780