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International Urogynecology Journal Mar 2019
Topics: Cystitis, Interstitial; Humans; Pentosan Sulfuric Polyester
PubMed: 30612180
DOI: 10.1007/s00192-018-3850-9 -
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 -
International Urogynecology Journal Apr 2017Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic inflammatory condition of the submucosal and muscular layers of the bladder. So far, there is no... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION AND HYPOTHESIS
Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic inflammatory condition of the submucosal and muscular layers of the bladder. So far, there is no effective and targeted treatment strategy for IC/PBS. This study aimed to assess the efficacy and safety of intravesical instillation treatment in IC/PBS patients.
METHODS
We searched various databases up to October 2015. A network meta-analysis was performed to compare global response assessment (GRA) for different treatment strategies, including botulinum toxin A (BoNTA), bacillus Calmette-Guerin (BCG), resiniferatoxin (RTX), lidocaine, chondroitin sulfate (CS), oxybutynin, and pentosan polysulfate (PPS). A traditional meta-analysis was also performed.
RESULTS
Sixteen trials evaluating 905 patients were included. Network meta-analysis indicated that BoNTA had the highest probability of being the best treatment course according to GRA assessment results (probability 81.7 %). BCG or BoNTA therapy yielded significant improvement in GRA incidence according to traditional meta-analysis. Patients who received PPS showed higher urinary frequency results compared with the placebo groups. BCG- and PPS-treated patients had elevated urinary urgency treatment effects compared with placebo groups. Bladder capacity restoration results also showed significant improvements in patients who received BoNTA compared with placebo-treated individuals.
CONCLUSIONS
These findings indicate that BoNTA therapy has the highest probability of being the best therapy according to GRA, and significantly improves bladder capacity in IC/PBS patients. BCG treatment also significantly increases the incidence of GRA and improves the symptoms of urinary urgency. PPS can significantly improve urinary frequency and urgency symptoms in IC/PBS patients.
Topics: Administration, Intravesical; BCG Vaccine; Botulinum Toxins, Type A; Cystitis, Interstitial; Humans; Neurotoxins
PubMed: 27614759
DOI: 10.1007/s00192-016-3079-4 -
Research and Reports in Urology 2023Hemorrhagic cystitis (HC) can be one of the most challenging clinical scenarios for urologists to manage. It most commonly occurs as a toxicity of pelvic radiation... (Review)
Review
Hemorrhagic cystitis (HC) can be one of the most challenging clinical scenarios for urologists to manage. It most commonly occurs as a toxicity of pelvic radiation therapy or in patients treated with the oxazaphosphorine class of chemotherapy. Successful management of HC necessitates a stepwise approach with a thorough understanding of the various treatment options. Once ensuring hemodynamic stability, conservative management includes establishing bladder drainage, manual clot evacuation, and continuous bladder irrigation through a large-bore urethral catheter. If gross hematuria persists, operative cystoscopy with bladder clot evacuation is often required. There are multiple intravesical options for treating HC, including alum, aminocaproic acid, prostaglandins, silver nitrate, and formalin. Formalin is an intravesical option that has caustic effects on the bladder mucosa and is most often reserved as a last-line intravesical treatment. Non-intravesical management tools include hyperbaric oxygen therapy and oral pentosan polysulfate. If needed, nephrostomy tube placement or superselective angioembolization of the anterior division of the internal iliac artery can be performed. Finally, cystectomy with urinary diversion is a definitive, albeit invasive, treatment option for refractory HC. While there is no standardized algorithm, treatment modalities typically progress from less to more invasive. Clinical judgement and shared decision-making with the patient are required when choosing therapies for managing HC, as success rates are variable and some treatments may have significant or irreversible effects.
PubMed: 37404838
DOI: 10.2147/RRU.S320684 -
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 -
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 -
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 -
Current Opinion in Urology Mar 2024Despite available treatments, many bladder pain syndrome/interstitial cystitis (BPS/IC) patients continue to have poor quality of life. Thus, there is an urge for new... (Review)
Review
PURPOSE OF REVIEW
Despite available treatments, many bladder pain syndrome/interstitial cystitis (BPS/IC) patients continue to have poor quality of life. Thus, there is an urge for new therapies. Our manuscript aims to review papers about BPS/IC treatments published in the last 2 years.
RECENT FINDINGS
During this period, several treatments were tested, most of them new and others combining treatments already used. Pentosan polysulfate, interleukin 1 antagonist, low energy shock wave, physical therapy, hypnosis, acupuncture, clorpactin, dimethyl sulfoxide and hyaluronic acid plus botulinum toxin-A showed positive results. ASP3652 and lidocaine-releasing intravesical systems failed to prove their efficacy.
SUMMARY
Validation of these studies is arduous due to the broad spectre of BPS/IC phenotypes, small number of patients enrolled, distinct outcome measures and short-term follow-up. It is also important to highlight that some authors combined therapies, and others split central and peripheric phenotypes before treatment. Therefore, soon, phenotyping and combining therapies with a step-by-step approach will be needed in BPS/IC treatment.
Topics: Humans; Cystitis, Interstitial; Quality of Life; Administration, Intravesical; Botulinum Toxins, Type A; Lidocaine
PubMed: 38168016
DOI: 10.1097/MOU.0000000000001159 -
Journal of Feline Medicine and Surgery Jun 2016Obstructive feline idiopathic cystitis is a common emergency in small animal practice. There is evidence for a defective glycosaminoglycan layer in the urinary bladder... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Obstructive feline idiopathic cystitis is a common emergency in small animal practice. There is evidence for a defective glycosaminoglycan layer in the urinary bladder of affected cats. The aim of this study was to investigate the effect of intravesical pentosan polysulfate sodium (PPS) in cats with obstructive feline idiopathic cystitis in a randomised, placebo-controlled, blinded clinical study.
METHODS
Thirty-five cats with obstructive feline idiopathic cystitis were enrolled into the study. On day 0, cats were randomised to receive either 30 mg PPS in saline (18 cats) or saline alone as placebo (17 cats) at the time of indwelling urinary catheter placement and then after 24 and 48 h. The catheter was clamped for 30 mins after administration before connecting it to a sterile urine collection system. The procedure was repeated after 24 and 48 h, and then the indwelling catheter was removed. Treatment success was assessed via the incidence of recurrent urethral obstruction, results of a scoring system for physical examination and daily urinalysis from day 0 to 5.
RESULTS
Recurrent urethral obstruction occurred in 3/18 cats of the verum group and 3/17 of the placebo group (P = 1.000). The verum group showed a significantly lower degree of microscopic haematuria between day 5 and day 0 (P ⩽0.05). The placebo group showed a significantly lower degree of dipstick haematuria between day 5 and day 0 (P ⩽0.05). There was no difference in the clinical score between the groups in the investigated time period.
CONCLUSIONS AND RELEVANCE
Intravesical instillation of PPS three times within 48 h in the chosen dose had no influence on the incidence of recurrent urethral obstruction and clinical signs in cats with obstructive feline idiopathic cystitis.
Topics: Administration, Intravesical; Animals; Cat Diseases; Cats; Cystitis; Double-Blind Method; Glycosaminoglycans; Male; Pentosan Sulfuric Polyester; Physical Examination; Treatment Outcome; Urethral Obstruction; Urinary Catheterization
PubMed: 26116618
DOI: 10.1177/1098612X15588934 -
BMJ Clinical Evidence Aug 2015Chronic prostatitis can cause pain and urinary symptoms, and can occur either with an active infection (chronic bacterial prostatitis [CBP]) or with only pain and no... (Review)
Review
INTRODUCTION
Chronic prostatitis can cause pain and urinary symptoms, and can occur either with an active infection (chronic bacterial prostatitis [CBP]) or with only pain and no evidence of bacterial causation (chronic pelvic pain syndrome [CPPS]). Bacterial prostatitis is characterised by recurrent urinary tract infections or infection in the prostate with the same bacterial strain, which often results from urinary tract instrumentation. However, the cause and natural history of CPPS are unknown and not associated with active infection.
METHODS AND OUTCOMES
We conducted a systematic overview and aimed to answer the following clinical questions: What are the effects of treatments for chronic bacterial prostatitis? What are the effects of treatments for chronic pelvic pain syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).
RESULTS
At this update, searching of electronic databases retrieved 131 studies. After deduplication and removal of conference abstracts, 67 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 51 studies and the further review of 16 full publications. Of the 16 full articles evaluated, three systematic reviews and one RCT were included at this update. We performed a GRADE evaluation for 14 PICO combinations.
CONCLUSIONS
In this systematic overview, we categorised the efficacy for 12 interventions based on information relating to the effectiveness and safety of 5 alpha-reductase inhibitors, allopurinol, alpha-blockers, local injections of antimicrobial drugs, mepartricin, non-steroidal anti-inflammatory drugs (NSAIDs), oral antimicrobial drugs, pentosan polysulfate, quercetin, sitz baths, transurethral microwave thermotherapy (TUMT), and transurethral resection of the prostate (TURP).
Topics: Humans; Male; Prostatitis
PubMed: 26313612
DOI: No ID Found