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Frontiers in Immunology 2023There is an unmet medical need for effective anti-inflammatory agents for the treatment of acute and post-acute lung inflammation caused by respiratory viruses. The...
INTRODUCTION
There is an unmet medical need for effective anti-inflammatory agents for the treatment of acute and post-acute lung inflammation caused by respiratory viruses. The semi-synthetic polysaccharide, Pentosan polysulfate sodium (PPS), an inhibitor of NF-kB activation, was investigated for its systemic and local anti-inflammatory effects in a mouse model of influenza virus A/PR8/1934 (PR8 strain) mediated infection.
METHODS
Immunocompetent C57BL/6J mice were infected intranasally with a sublethal dose of PR8 and treated subcutaneously with 3 or 6 mg/kg PPS or vehicle. Disease was monitored and tissues were collected at the acute (8 days post-infection; dpi) or post-acute (21 dpi) phase of disease to assess the effect of PPS on PR8-induced pathology.
RESULTS
In the acute phase of PR8 infection, PPS treatment was associated with a reduction in weight loss and improvement in oxygen saturation when compared to vehicle-treated mice. Associated with these clinical improvements, PPS treatment showed a significant retention in the numbers of protective SiglecF+ resident alveolar macrophages, despite uneventful changes in pulmonary leukocyte infiltrates assessed by flow cytometry. PPS treatment in PR8- infected mice showed significant reductions systemically but not locally of the inflammatory molecules, IL-6, IFN-g, TNF-a, IL-12p70 and CCL2. In the post-acute phase of infection, PPS demonstrated a reduction in the pulmonary fibrotic biomarkers, sICAM-1 and complement factor C5b9.
DISCUSSION
The systemic and local anti-inflammatory actions of PPS may regulate acute and post-acute pulmonary inflammation and tissue remodeling mediated by PR8 infection, which warrants further investigation.
Topics: Mice; Animals; Pentosan Sulfuric Polyester; Alphainfluenzavirus; Mice, Inbred C57BL; Pneumonia; Anti-Inflammatory Agents; Disease Models, Animal
PubMed: 36845136
DOI: 10.3389/fimmu.2023.1030879 -
JIMD Reports 2019Overall Goal: This study was designed to evaluate the impact of pentosan polysulfate (PPS) treatment on mice with mucopolysaccharidosis (MPS) type IIIA (Sanfilippo A...
Overall Goal: This study was designed to evaluate the impact of pentosan polysulfate (PPS) treatment on mice with mucopolysaccharidosis (MPS) type IIIA (Sanfilippo A syndrome; OMIM 252900). Protocol: Three groups of MPS IIIA mice were evaluated: 1-week-old mice treated with subcutaneous (subQ) PPS at 25 mg/kg once weekly for 31 weeks (group 1); 5-month-old mice treated with subQ PPS once weekly at 50 mg/kg for 12 weeks (group 2); and 5-week-old mice treated by continual intracerebroventricular (ICV) PPS infusion for 11 weeks (60 μg/kg/day). Treated MPS IIIA mice and controls were assessed by measuring plasma cytokine levels, histologic analyses of systemic organs, and analyses of various neuroinflammatory, neurodegenerative, and lysosomal disease markers in their brains. Neurobehavioral testing also was carried out. Results: As seen in other MPS animal models, subQ PPS treatment reduced plasma cytokine levels and macrophage infiltration in systemic tissues. ICV administration did not elicit these systemic effects. SubQ PPS administration also significantly impacted brain neuropathology, inflammation, and behavior. The effect of early subQ treatment was more significant than dose. Surprisingly, ICV PPS treatment had intermediate effects on most of these brain markers, perhaps due to the limited dose and/or duration of treatment. Consistent with these neuropathological findings, we also observed significant improvements in the hyperactivity/anxiety and learning behaviors of the MPS IIIA mice treated with early subQ PPS.
PubMed: 29654542
DOI: 10.1007/8904_2018_96 -
The Cochrane Database of Systematic... Nov 2015Although superficial thrombophlebitis of the upper extremity represents a frequent complication of intravenous catheters inserted into the peripheral veins of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although superficial thrombophlebitis of the upper extremity represents a frequent complication of intravenous catheters inserted into the peripheral veins of the forearm or hand, no consensus exists on the optimal management of this condition in clinical practice.
OBJECTIVES
To summarise the evidence from randomised clinical trials (RCTs) concerning the efficacy and safety of (topical, oral or parenteral) medical therapy of superficial thrombophlebitis of the upper extremity.
SEARCH METHODS
The Cochrane Vascular Group Trials Search Co-ordinator searched the Specialised Register (last searched April 2015) and the Cochrane Register of Studies (2015, Issue 3). Clinical trials registries were searched up to April 2015.
SELECTION CRITERIA
RCTs comparing any (topical, oral or parenteral) medical treatment to no intervention or placebo, or comparing two different medical interventions (e.g. a different variant scheme or regimen of the same intervention or a different pharmacological type of treatment).
DATA COLLECTION AND ANALYSIS
We extracted data on methodological quality, patient characteristics, interventions and outcomes, including improvement of signs and symptoms as the primary effectiveness outcome, and number of participants experiencing side effects of the study treatments as the primary safety outcome.
MAIN RESULTS
We identified 13 studies (917 participants). The evaluated treatment modalities consisted of a topical treatment (11 studies), an oral treatment (2 studies) and a parenteral treatment (2 studies). Seven studies used a placebo or no intervention control group, whereas all others also or solely compared active treatment groups. No study evaluated the effects of ice or the application of cold or hot bandages. Overall, the risk of bias in individual trials was moderate to high, although poor reporting hampered a full appreciation of the risk in most studies. The overall quality of the evidence for each of the outcomes varied from low to moderate mainly due to risk of bias and imprecision, with only single trials contributing to most comparisons. Data on primary outcomes improvement of signs and symptoms and side effects attributed to the study treatment could not be statistically pooled because of the between-study differences in comparisons, outcomes and type of instruments to measure outcomes.An array of topical treatments, such as heparinoid or diclofenac gels, improved pain compared to placebo or no intervention. Compared to placebo, oral non-steroidal anti-inflammatory drugs reduced signs and symptoms intensity. Safety issues were reported sparsely and were not available for some interventions, such as notoginseny creams, parenteral low-molecular-weight heparin or defibrotide. Although several trials reported on adverse events with topical heparinoid creams, Essaven gel or phlebolan versus control, the trials were underpowered to adequately measure any differences between treatment modalities. Where reported, adverse events with topical treatments consisted mainly of local allergic reactions. Only one study of 15 participants assessed thrombus extension and symptomatic venous thromboembolism with either oral non-steroidal anti-inflammatory drugs or low-molecular-weight heparin, and it reported no cases of either. No study reported on the development of suppurative phlebitis, catheter-related bloodstream infections or quality of life.
AUTHORS' CONCLUSIONS
The evidence about the treatment of acute infusion superficial thrombophlebitis is limited and of low quality. Data appear too preliminary to assess the effectiveness and safety of topical treatments, systemic anticoagulation or oral non-steroidal anti-inflammatory drugs.
Topics: Anti-Inflammatory Agents; Anticoagulants; Catheterization, Peripheral; Dalteparin; Diclofenac; Drug Combinations; Drugs, Chinese Herbal; Escin; Gels; Heparin; Heparinoids; Humans; Ibuprofen; Nitroglycerin; Pentosan Sulfuric Polyester; Phospholipids; Polydeoxyribonucleotides; Randomized Controlled Trials as Topic; Thrombophlebitis; Upper Extremity
PubMed: 26588711
DOI: 10.1002/14651858.CD011015.pub2 -
Pakistan Journal of Medical Sciences 2019In the present study, we investigated the efficacy of bladder hydrodistension combined with pentosan polysulfate (PPS) treatment in interstitial cystitis (IC)/bladder...
OBJECTIVE
In the present study, we investigated the efficacy of bladder hydrodistension combined with pentosan polysulfate (PPS) treatment in interstitial cystitis (IC)/bladder pain syndrome (BPS).
METHODS
In this study, 339 patients diagnosed with IC/BPS were categorized into two groups. The first group only received 300 mg/day PPS, while the second group received 300 mg/day PPS following bladder hydrodistension. The results were evaluated at the 3rd, 6th, and 12th months after the first dose using the interstitial cystitis symptom index (ICSI), international cystitis problem index (ICPI), visual analog scale (VAS), and female sexual function index (FSFI).
RESULTS
PPS treatment started just after hydrodistension was significantly more effective than PPS treatment alone and combined treatment significantly reduced the rate of non-compliance such that, at the end of the 3rd month, 12.1% patients in Group-1 did not continue their treatment whereas only 1.9% of patients in Group-2 did not continue.
CONCLUSIONS
The study results indicate that PPS treatment started just after hydrodistension yields significantly better results in terms of both symptom improvement and treatment compliance in patients with IC/BPS.
PubMed: 30881421
DOI: 10.12669/pjms.35.1.172 -
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 -
The Canadian Journal of Urology Jun 2024
Topics: Humans; Pentosan Sulfuric Polyester; Macular Degeneration; Cystitis, Interstitial; Anticoagulants
PubMed: 38912936
DOI: No ID Found -
Frontiers in Molecular Biosciences 2023The unexpected surge of respiratory syncytial virus (RSV) cases following pandemic phase of COVID-19 has drawn much public attention. Drawing on the latest antiviral...
The unexpected surge of respiratory syncytial virus (RSV) cases following pandemic phase of COVID-19 has drawn much public attention. Drawing on the latest antiviral research, revisiting this heightened annual outbreak of respiratory disease could lead to new treatments. The ability of sulfated polysaccharides to compete for a variety of viruses binding to cell surface heparan sulfate, suggests several drugs that might have therapeutic potential for targeting RSV-glycosaminoglycan interactions. In the current study, the binding affinity and kinetics of two RSV glycoproteins (RSV-G protein and RSV-F protein) to heparin were investigated by surface plasmon resonance. Furthermore, solution competition studies using heparin oligosaccharides of different lengths indicated that the binding of RSV-G protein to heparin is size-dependent, whereas RSV-F protein did not show any chain length preference. The two RSV glycoproteins have slightly different preferences for heparin sulfation patterns, but the -sulfo group in heparin was most critical for the binding of heparin to both RSV-G protein and RSV-F protein. Finally, pentosan polysulfate and mucopolysaccharide polysulfate were evaluated for their inhibition of the RSV-G protein and RSV-F protein-heparin interaction, and both highly negative compounds showed strong inhibition.
PubMed: 37122559
DOI: 10.3389/fmolb.2023.1151174 -
Investigative and Clinical Urology Sep 2022Intravesical Bacillus Calmette-Guérin (BCG) instillation, although an important treatment for non-muscle-invasive bladder cancer, exerts local and systemic adverse...
PURPOSE
Intravesical Bacillus Calmette-Guérin (BCG) instillation, although an important treatment for non-muscle-invasive bladder cancer, exerts local and systemic adverse effects. Pentosan polysulfate (PPS) is a bladder mucosal protective drug that acts by replacing mucus in the glycosaminoglycan layer of the damaged urothelium. We hypothesized that co-administration of oral PPS with BCG instillation would relieve BCG-related adverse effects without affecting its efficacy.
MATERIALS AND METHODS
A total of 217 patients receiving BCG instillation were enrolled. They were placed in two groups and analyzed retrospectively: group A (n=122) received BCG instillation only and group B (n=95) received 100 mg of PPS thrice daily during the BCG treatment.
RESULTS
After BCG instillation, the rate of BCG-treatment discontinuation owing to adverse effects was 15.6% in group A and 6.3% in group B (p=0.034). The proportion of patients with bacteriuria after BCG was higher in group B; however, no statistical difference was observed (28.7% vs. 41.1%; p=0.057). The proportion of patients with pyuria was significantly higher in group B (81.1% vs. 91.6%; p=0.029). The proportion of patients using antibiotics was significantly higher in group A (73.8% vs. 43.2%; p=0.001). The recurrence rate within 1 year was 29 (23.8%) in group A vs. 19 (20.0%) in group B (p=0.507). Univariate and multivariate analyses showed that antibiotic use had a statistically significant effect on BCG discontinuation.
CONCLUSIONS
Oral PPS effectively decreased the discontinuation rate and antibiotic use without affecting the BCG efficacy.
Topics: Anti-Bacterial Agents; BCG Vaccine; Humans; Pentosan Sulfuric Polyester; Retrospective Studies; Urinary Bladder Neoplasms
PubMed: 36067999
DOI: 10.4111/icu.20220179 -
The Biochemical Journal Apr 2012The semi-synthetic sulfated polysaccharide PPS (pentosan polysulfate) increases affinity between the aggrecan-degrading ADAMTSs (adamalysins with thrombospondin motifs)...
The semi-synthetic sulfated polysaccharide PPS (pentosan polysulfate) increases affinity between the aggrecan-degrading ADAMTSs (adamalysins with thrombospondin motifs) and their endogenous inhibitor, TIMP (tissue inhibitor of metalloproteinases)-3. In the present study we demonstrate that PPS mediates the formation of a high-affinity trimolecular complex with ADAMTS-5 and TIMP-3. A TIMP-3 mutant that lacks extracellular-matrix-binding ability was insensitive to this affinity increase, and truncated forms of ADAMTS-5 that lack the Sp (spacer) domain had reduced PPS-binding ability and sensitivity to the affinity increase. PPS molecules composed of 11 or more saccharide units were 100-fold more effective than those of eight saccharide units, indicating the involvement of extended or multiple protein-interaction sites. The formation of a high-affinity trimolecular complex was completely abolished in the presence of 0.4 M NaCl. These results suggest that PPS enhances the affinity between ADAMTS-5 and TIMP-3 by forming electrostatically driven trimolecular complexes under physiological conditions.
Topics: ADAM Proteins; ADAMTS5 Protein; Amino Acid Substitution; Chromatography, Gel; HEK293 Cells; Humans; Pentosan Sulfuric Polyester; Protein Binding; Protein Structure, Tertiary; Recombinant Proteins; Sequence Deletion; Sodium Chloride; Tissue Inhibitor of Metalloproteinase-3
PubMed: 22299597
DOI: 10.1042/BJ20112159 -
FEBS Letters Jan 2020Extracellular levels of soluble TIMP-3 are low, reflecting its binding by extracellular matrix (ECM) components including sulfated glycosaminoglycans (SGAGs) and...
Extracellular levels of soluble TIMP-3 are low, reflecting its binding by extracellular matrix (ECM) components including sulfated glycosaminoglycans (SGAGs) and endocytosis via low density lipoprotein receptor-related protein 1. Since TIMP-3 inhibits ECM degradation, the ability of SGAGs to elevate extracellular TIMP-3 is significant for osteoarthritis treatment. Previous studies of such interactions have utilized immobilized TIMP-3 or ligands. Here, we report the thermodynamics of the interactions of the sGAG-binding N-domain of TIMP-3 with chondroitin sulfate, pentosan polysulfate, and suramin in solution using isothermal titration calorimetry. All three interactions are driven by a favorable negative enthalpy change combined with an unfavorable decrease in entropy. The heat capacity changes (ΔC ) for all of the interactions are zero, indicating an insignificant contribution from hydrophobic interactions.
Topics: Binding Sites; Chondroitin Sulfates; Humans; Molecular Docking Simulation; Pentosan Sulfuric Polyester; Protein Binding; Suramin; Tissue Inhibitor of Metalloproteinase-3
PubMed: 31359422
DOI: 10.1002/1873-3468.13556