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Urology Annals 2019Treatment of chronic idiopathic scrotal pain is a dilemma and challenge. Many men with this condition undergo multiple therapies and surgeries with no improvement in...
OBJECTIVE
Treatment of chronic idiopathic scrotal pain is a dilemma and challenge. Many men with this condition undergo multiple therapies and surgeries with no improvement in their symptoms. Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) have a variable clinical presentation and initially complain of only one symptom of urinary urgency, frequency, or pain. We report on patients with chronic idiopathic scrotal pain treated with standard therapy for IC/BPS.
PATIENTS AND METHODS
Patients with chronic idiopathic scrotal content pain were evaluated, determined to have chronic idiopathic scrotal content pain, and were treated with either pentosan polysulfate sodium (PPS) or bladder instillations of alkalinized lidocaine and heparin.
RESULTS
Sixteen males were determined to have chronic idiopathic scrotal pain. Eight males received PPS and eight males received a bladder instillation of alkalinized lidocaine and heparin. All patients had improvement of their scrotal pain to a self-reported acceptable level.
CONCLUSIONS
Chronic idiopathic scrotal pain may be one of the variable presenting symptoms of IC/BPS. This scrotal pain may actually be referred pain from the bladder. Standard therapies for IC/BPS may be a treatment option for chronic idiopathic scrotal pain.
PubMed: 31413503
DOI: 10.4103/UA.UA_161_17 -
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 -
The Analyst Aug 2019Pentosan polysulfate (PPS) is a semi-synthetic glycosaminoglycan (GAG) mimetic. PPS, synthesized through the chemical sulfonation of a plant-derived β-(1 → 4)-xylan,...
Pentosan polysulfate (PPS) is a semi-synthetic glycosaminoglycan (GAG) mimetic. PPS, synthesized through the chemical sulfonation of a plant-derived β-(1 → 4)-xylan, is the active pharmaceutical ingredient of the drug Elmiron™ used to treat interstitial cystitis. Unlike natural GAGs that can be enzymatically broken down into oligosaccharides for analysis, PPS is an unnatural polyanionic polysaccharide and is not amenable to such an analytical approach. Instead reactive oxygen species were used for the controlled depolymerization of PPS and the resulting oligosaccharide fragments were then analyzed by liquid chromatography-mass spectrometry (LC-MS) to obtain bottom-up information on its composition. Because PPS has an average molecular weight ranging from 4000 to 6000 Da, similar to that of low molecular weight heparin, this suggested that it might be possible to use LC-MS on its intact chains and perform top-down analysis. The bottom-up and top-down analysis of PPS provides the first detailed compositional and structural information on PPS. Finally, we examined whether PPS would interfere with polysaccharide lyases and hydrolases, used in the analysis of natural GAGs such as chondroitin sulfates, heparan sulfate, and keratan sulfates. We found that PPS did not interfere with GAG analysis, suggesting that a combination of chemical and enzymatic treatment could be used to analyze samples containing both natural GAGs and PPS.
Topics: Chromatography, Liquid; Glycosaminoglycans; Hydrogen Peroxide; Mass Spectrometry; Oligosaccharides; Organometallic Compounds; Oxidation-Reduction; Pentosan Sulfuric Polyester
PubMed: 31287456
DOI: 10.1039/c9an01006h -
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 -
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 -
Revista Da Associacao Medica Brasileira... May 2019The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to...
The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.
Topics: Administration, Intravesical; Botulinum Toxins, Type A; Brazil; Chondroitin Sulfates; Clinical Decision-Making; Cystitis, Interstitial; Dimethyl Sulfoxide; Diterpenes; Humans; Hyaluronic Acid; Lidocaine; Mycobacterium bovis; Pentosan Sulfuric Polyester; Treatment Outcome
PubMed: 31066806
DOI: 10.1590/1806-9282.65.4.535 -
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 -
International Journal of Surgery... Mar 2019BK virus is a major cause of late onset haemorrhagic cystitis in patients undergoing Haematopoietic Cell Transplantation (HCT). The evidence for the management of BK...
BACKGROUND
BK virus is a major cause of late onset haemorrhagic cystitis in patients undergoing Haematopoietic Cell Transplantation (HCT). The evidence for the management of BK Virus Associated Haemorrhagic Cystitis (BKV-HC) is limited. Much of the published data consists of non-randomised case series and case reports. To our knowledge this is the first systematic review for the management of BKV-HC in both paediatric and adult populations. Our primary outcome was to examine the evidence for strategies of 1) prevention and 2) cessation of haematuria associated with BKV. Secondary outcomes were to assess the toxicity of treatment strategies and devise management recommendations for clinicians.
MATERIALS AND METHODS
We performed a systematic review of the PubMed and Central databases to evaluate the current evidence. A search protocol was prepared and registered with the PROSPERO database (CRD42017082442). The review was conducted in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement and AMSTAR (Assessing the methodological quality of systematic reviews) guidelines. Results were classified by treatment type. Qualitative analysis of included articles was performed, and grades of recommendations were devised for each treatment.
RESULTS
Of 896 titles screened, 44 articles were included for qualitative analysis. The overall quality of evidence was low. There is insufficient evidence to recommend prophylactic quinolones. 40 studies evaluated treatments for established BKV-HC. There are no high-quality comparative studies. Cidofovir is the most studied treatment but quality of evidence is low, and grade of recommendation is weak. Hyperbaric oxygen therapy, Fibrin glue, Leflunomide, Sodium Pentosan Polysulfate, Intravesical Alum and Radiological embolisation have all been described but the effectiveness of these treatments is unclear.
CONCLUSION
There remains no clear specific treatment for BKV-HC. An effective multi-disciplinary approach leading to early recognition and initiation of treatment is encouraged. The development of novel therapies followed by well-designed clinical studies are urgently needed.
Topics: Adult; BK Virus; Child; Cystitis; Hemorrhage; Humans; Polyomavirus Infections; Tumor Virus Infections
PubMed: 30711618
DOI: 10.1016/j.ijsu.2019.01.019 -
Research in Veterinary Science Feb 2019Pentosan polysulfate (PPS) is currently under investigation as a potential disease-modifying antiarthritic agent. In the present study the effects of PPS on arthritic...
Pentosan polysulfate (PPS) is currently under investigation as a potential disease-modifying antiarthritic agent. In the present study the effects of PPS on arthritic profiles based on clinical score, ankle size, histological changes, and activity of inflammatory mediators using collagen-induced arthritic rat are reported. Model of arthritis was developed in Sprague Dawley rats by intradermal injection of bovine type II collagen emulsified with incomplete Freund's adjuvant. The rats were randomly divided into four groups: normal control, arthritic control, arthritic rats treated with PPS (at dose level 20 μg/g) and arthritic rats treated with meloxicam (2 μg/g). The treatment was continued daily until the day 30. Arthritic biomarkers (cartilage oligomeric matrix protein and tartrate-resistant acid phosphatase 5b) in synovial fluid, expression of inflammatory mediators (interleukin-1β, and tumor necrosis factor-α) and osteoclast marker genes (cathepsin K, tartrate-resistant acid phosphatase) in synovial membrane were measured. Daily administration of PPS to the arthritic rats significantly decreased the severity of arthritis by effectively suppressing the symptoms of arthritis and improving the functional recovery based on clinical score and histopathological evidence. Intriguingly, identical downregulation pattern of arthritis profiles, biological markers as well as relative mRNA levels of osteoclast markers and cytokines were monitored in arthritic rats treated with PPS. In conclusion, PPS exerted protective effects against collagen-induced arthritis in rats. The results suggest that PPS acts as an anti-inflammatory and anti-arthritic agent in decreasing the arthritic effects in collagen-induced arthritic rats.
Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Cattle; Collagen Type II; Cytokines; Freund's Adjuvant; Gene Expression Regulation; Lipids; Pentosan Sulfuric Polyester; Random Allocation; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha
PubMed: 30529273
DOI: 10.1016/j.rvsc.2018.11.028 -
PloS One 2018Diabetic kidney disease (DKD) is characterized by progressive glomerulosclerosis (GS). ROP mice have a sclerosis-prone phenotype. However, they develop severe, rapidly...
Diabetic kidney disease (DKD) is characterized by progressive glomerulosclerosis (GS). ROP mice have a sclerosis-prone phenotype. However, they develop severe, rapidly progressive GS when rendered diabetic. Since GS also develops in aged C57Bl6 mice, and can be reversed using bone marrow from young mice which have lower oxidative stress and inflammation (OS/Infl), we postulated that this might also apply to DKD. Therefore, this pilot study asked whether reducing OS/Infl in young adult sclerosis-prone (ROP) diabetic mice leads to resolution of existing GS in early DKD using safe, FDA-approved drugs.After 4 weeks of stable streptozotocin-induced hyperglycemia 8-12 week-old female mice were randomized and treated for 22 weeks as follows: 1) enalapril (EN) (n = 8); 2) pyridoxamine (PYR)+EN (n = 8); 3) pentosan polysulfate (PPS)+EN (n = 7) and 4) PPS+PYR+EN (n = 7). Controls were untreated (non-DB, n = 7) and hyperglycemic (DB, n = 8) littermates. PPS+PYR+EN reduced albuminuria and reversed GS in DB. Treatment effects: 1) Anti-OS/Infl defenses: a) PPS+PYR+EN increased the levels of SIRT1, Nrf2, estrogen receptor α (ERα) and advanced glycation endproduct-receptor1 (AGER1) levels; and b) PYR+EN increased ERα and AGER1 levels. 2) Pro-OS/Infl factors: a) PPS+PYR+EN reduced sTNFR1, b) all except EN reduced MCP1, c) RAGE was reduced by all treatments. In summary, PYR+PPS+EN modulated GS in sclerosis-prone hyperglycemic mice. PYR+PPS+EN also decreased albuminuria, OS/Infl and the sclerosis-prone phenotype. Thus, reducing OS/Infl may reverse GS in early diabetes in patients, and albuminuria may allow early detection of the sclerosis-prone phenotype.
Topics: Albumins; Animals; Creatinine; Diabetic Nephropathies; Disease Progression; Disease Susceptibility; Female; Gene Expression Regulation; Mice; Mice, Inbred C57BL; Oxidative Stress; Pilot Projects
PubMed: 30252878
DOI: 10.1371/journal.pone.0204366