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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 -
Ophthalmology Oct 2019
Topics: Aged; Cystitis, Interstitial; Female; Humans; Macular Degeneration; Male; Middle Aged; Pentosan Sulfuric Polyester; Retinal Pigment Epithelium
PubMed: 31004677
DOI: 10.1016/j.ophtha.2019.04.024 -
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 -
PloS One 2017Osteoarthritic (OA) chondrocytes are shown to express inducible nitric oxide synthase (iNOS) which produces high concentrations of nitric oxide (NO), particularly when...
Osteoarthritic (OA) chondrocytes are shown to express inducible nitric oxide synthase (iNOS) which produces high concentrations of nitric oxide (NO), particularly when stimulated with proinflammatory cytokines. NO is involved in OA cartilage degradation. On the other hand, c-Jun N-terminal Kinase (JNK) pathway mediates the activation and transcription of c-Jun, which is required for interleukin-1 (IL-1)-induction of matrix metalloproteinases-13 (MMP-13) in OA pathogenesis. Therefore, the selective inhibition of iNOS and c-Jun is a promising target for treatment and prevention of OA. The purpose of the study was to investigate the inhibitory effects of pentosan polysulfate (PPS) on IL-1β-induced iNOS, c-Jun and HIF-α isoforms upregulation in canine articular chondrocytes (CACs). Primary (P0) chondrocytes were isolated and cultured from femoral head cartilages of three (3) dogs. First passage (P1) chondrocytes were preincubated with 0, 1, 5, 15 and 40 μg/mL of PPS for 4 hr before treatment with 10 ng/mL rhIL-1β for a further 8 hr. In addition, we evaluated the effects of single and multiple cytokine with or without LPS on iNOS protein induction. PPS significantly inhibited (P < 0.05) IL-1β-induced iNOS, c-Jun and HIF-1α mRNA upregulation in a dose-dependent pattern. iNOS mRNA was significantly inhibited at 15 and 40 μg/mL whereas c-Jun and HIF-1α were significantly downregulated at 5, 15 and 40 μg/mL of PPS compared to chondrocytes treated with only rhIL-1β. Intriguingly, CACs were recalcitrant to single IL-1β, TNF-α or LPS-induction of iNOS protein including to a combination of IL-1β+TNF-α, IL-1β+LPS except to TNF-α+LPS and IL-1β+TNF-α+LPS suggestive of a protective mechanism from iNOS detrimental effects on perpetuating OA. IL-1β+TNF-α+LPS-induced iNOS protein expression was significantly abrogated by PPS. We demonstrate for the first time that PPS is a novel inhibitor of IL-1β-induced iNOS, c-Jun, and HIF-1α mRNA upregulation and iNOS protein induction which may be beneficial for prevention and treatment OA.
Topics: Animals; Cartilage, Articular; Chondrocytes; Dogs; Genes, jun; Hypoxia-Inducible Factor 1, alpha Subunit; Interleukin-1beta; Nitric Oxide Synthase Type II; Pentosan Sulfuric Polyester; RNA, Messenger; Up-Regulation
PubMed: 28472120
DOI: 10.1371/journal.pone.0177144 -
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 -
Stem Cell Research May 2020We evaluated the synergistic effects of pentosan polysulfate sodium (PPS) and mesenchymal stem cells (MSCs) in an interstitial cystitis (IC) rat model. After generation...
We evaluated the synergistic effects of pentosan polysulfate sodium (PPS) and mesenchymal stem cells (MSCs) in an interstitial cystitis (IC) rat model. After generation of the IC rat model, the rats were divided into 4 groups according to the treatment they received: phosphate-buffered saline injection into bladder submucosa, daily oral PPS feeding, MSC injection into bladder submucosa, or MSC injection into bladder submucosa with daily oral PPS feeding. After treatment, conscious cystometry and pain scale measurement were performed and their bladders were obtained for histological and proinflammatory-related gene expression analysis. On cystometric analysis, all treatment groups showed significantly increased intercontraction intervals and lower pain scores compared to those of the control group. Histological analysis revealed regenerated urothelium, less fibrosis, and decreased mast cell infiltration in all treatment groups compared to the control group. Significantly lower expression of TNF-α, IFN-γ, MCP, IL-6, TLR2, and TLR11 was observed in the PPS with MSC group compared to the other groups. Combination therapy with PPS and MSCs showed histological and functional effects in an IC rat model, including synergistic effects leading to increased intercontraction interval and decreased inflammatory reactions.
Topics: Adipose Tissue; Animals; Cystitis, Interstitial; Inflammation; Mesenchymal Stem Cells; Pentosan Sulfuric Polyester; Rats
PubMed: 32334368
DOI: 10.1016/j.scr.2020.101801 -
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 -
Ophthalmology. Retina Sep 2022There is growing evidence of a direct association between pentosan polysulfate (PPS) therapy and the development of macular changes. Using standardized visual acuity...
PURPOSE
There is growing evidence of a direct association between pentosan polysulfate (PPS) therapy and the development of macular changes. Using standardized visual acuity (VA) testing and multimodal imaging, we investigated the impact of PPS therapy on vision and described an expanded spectrum of imaging findings among PPS users.
DESIGN
Cross-sectional screening study.
PARTICIPANTS
Thirty-nine patients who were current or recent users of PPS.
METHODS
The participants underwent a brief eye examination and answered a comprehensive medical and ophthalmic history questionnaire. Color fundus photography, fundus autofluorescence (FAF), and spectral-domain OCT (SD-OCT) were performed. The images were evaluated by expert graders at Wisconsin Reading Center. Abnormalities were categorized as definite toxicity (DT) if seen on both FAF and SD-OCT and as questionable toxicity (QT) if seen on either FAF or SD-OCT.
MAIN OUTCOME MEASURES
ETDRS and Snellen VA, the dosage and duration of PPS exposure, and the prevalence of retinal toxicity on imaging.
RESULTS
The mean ETDRS and Snellen VA of the study cohort were 85 letters and 20/22, respectively. The mean PPS daily dose was 282 mg (range, 88-400 mg), whereas the mean cumulative dose was 915 g (range, 19-3650 g) over a mean period of 8.8 years (range, 2 months-25 years). There was evidence of retinopathy in 41% of the eyes; DT was identified in 24 eyes (31%) and QT in 8 eyes (10%). Retinal pigment epithelium (RPE) abnormalities (thickening or thinning or both) were present in all eyes with DT. Retinal pigment epithelium atrophy was seen in 7 eyes (9%). In addition to well-established findings, the unique SD-OCT features of this cohort included interdigitation zone abnormalities and the presence of a flying saucer-type defect. Fundus autofluorescence abnormalities were seen in 24 eyes (30.8%), with 20 (66.7%) of these exhibiting abnormalities located outside the central subfield and extending beyond the arcades.
CONCLUSIONS
Findings from the masked grading of multimodal imaging at a centralized reading center suggest a wider phenotypic spectrum of structural abnormalities among patients taking PPS. Macular changes selectively involve the RPE and outer retina, with a range of findings often seen beyond the arcades. The subtle and atypical findings in this cohort should prompt clinicians to consider lowering the threshold for diagnosing PPS retinopathy.
Topics: Cross-Sectional Studies; Fluorescein Angiography; Humans; Multimodal Imaging; Pentosan Sulfuric Polyester; Retinal Degeneration; Tomography, Optical Coherence
PubMed: 35339727
DOI: 10.1016/j.oret.2022.03.016 -
Biomedicines Dec 2021As with many other pathogens, SARS-CoV-2 cell infection is strongly dependent on the interaction of the virus-surface Spike protein with the glycosaminoglycans of target...
As with many other pathogens, SARS-CoV-2 cell infection is strongly dependent on the interaction of the virus-surface Spike protein with the glycosaminoglycans of target cells. The SARS-CoV-2 Spike glycoprotein was previously shown to interact with cell-surface-exposed heparan sulfate and heparin in vitro. With the aim of using Enoxaparin as a treatment for COVID-19 patients and as prophylaxis to prevent interpersonal viral transmission, we investigated GAG binding to the Spike full-length protein, as well as to its receptor binding domain (RBD) in solution by isothermal fluorescence titration. We found that Enoxaparin bound to both protein variants with similar affinities, compared to the natural GAG ligand heparan sulfate (with Kd-values in the range of 600-680 nM). Using size-defined Enoxaparin fragments, we discovered the optimum binding for dp6 or dp8 for the full-length Spike protein, whereas the RBD did not exhibit a significant chain-length-dependent affinity for heparin oligosaccharides. The soluble ACE2 receptor was found to interact with unfractionated GAGs in the low µM Kd range, but with size-defined heparins with clearly sub-µM Kd-values. Interestingly, the structural heparin analogue, pentosan polysulfate (PPS), exhibited high binding affinities to both Spike variants as well as to the ACE2 receptor. In viral infection experiments, Enoxaparin and PPS both showed a strong inhibition of infection in a concentration range of 50-500 µg/mL. Both compounds were found to retain their inhibitory effects at 500 µg/mL in a natural biomatrix-like human sputum. Our data suggest the early topical treatment of SARS-CoV-2 infections with inhaled Enoxaparin; some clinical studies in this direction are already ongoing, and they further imply an oral or nasal prophylactic inactivation of the virus by Enoxaparin or PPS for the prevention of inter-personal viral transmission.
PubMed: 35052728
DOI: 10.3390/biomedicines10010049 -
BMC Veterinary Research May 2018Sodium pentosan polysulfate (NaPPS) was testified as a chondroprotective drug in with a detailed rationale of the disease-modifying activity. This study was undertaken...
BACKGROUND
Sodium pentosan polysulfate (NaPPS) was testified as a chondroprotective drug in with a detailed rationale of the disease-modifying activity. This study was undertaken to determine whether anti-osteoarthritis drug, NaPPS inhibited osteoclasts (OC) differentiation and function. Canine bone marrow mononuclear cells (n = 6) were differentiated to OC by maintaining with receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) for up to 7 days with the treatment of NaPPS at concentration of 0, 0.2, 1 and 5 μg/mL. Differentiation and function of OC were accessed using tartrate-resistant acid phosphate (TRAP) staining and bone resorption assay, while monitoring actin ring formation. Invasion and colocalization patterns of fluorescence-labeled NaPPS with transcribed gene in OC were monitored. Gene expression of OC for cathepsin K (CTK), matrix metallopeptidase-9 (MMP-9), nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), c-Fos, activator protein-1(AP-1) and carbonic anhydrase II was examined using real-time PCR.
RESULTS
Significant inhibition of OC differentiation was evident at NaPPS concentration of 1 and 5 μg/mL (p < 0.05). In the presence of 0.2 to 5 μg/mL NaPPS, bone resorption was attenuated (p < 0.05), while 1 and 5 μg/mL NaPPS achieved significant reduction of actin ring formation. Intriguingly, fluorescence-labeled NaPPS invaded in to cytoplasm and nucleus while colocalizing with actively transcribed gene. Gene expression of CTK, MMP-9 and NFATc1 were significantly inhibited at 1 and 5 μg/mL (p < 0.05) of NaPPS whereas inhibition of c-Fos and AP-1 was identified only at concentration of 5 μg/mL (p < 0.05).
CONCLUSIONS
Taken together, all the results suggest that NaPPS is a novel inhibitor of RANKL and M-CSF-induced CTK, MMP-9, NFATc1, c-Fos, AP-1 upregulation, OC differentiation and bone resorption which might be a beneficial for treatment of inflammatory joint diseases and other bone diseases associated with excessive bone resorption.
Topics: Actins; Animals; Bone Marrow Cells; Cell Differentiation; Cells, Cultured; Dogs; Humans; Macrophage Colony-Stimulating Factor; Osteoclasts; Pentosan Sulfuric Polyester; RANK Ligand; Transcription Factors
PubMed: 29720166
DOI: 10.1186/s12917-018-1466-4