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Transplantation Nov 1999Long-term cyclosporine (CsA) treatment leads to a decreased glomerular filtration rate, hyalinosis of afferent arterioles, and striped cortical tubulo-interstitial...
BACKGROUND
Long-term cyclosporine (CsA) treatment leads to a decreased glomerular filtration rate, hyalinosis of afferent arterioles, and striped cortical tubulo-interstitial fibrosis. We showed previously that pentosan polysulfate (SP54) prevented the development of microvascular and interstitial lesions in mouse models of progressive glomerulosclerosis. In this study, we examined the effect of pentosan polysulfate on the development of CsA nephropathy.
METHODS
Pair-fed Sprague-Dawley rats were fed a low-sodium (0.03%) diet and received CsA (15 mg/kg, subcutaneously, in olive oil)/5% glucose, pentosan polysulfate (10 mg/kg, subcutaneously in 5% glucose) plus CsA, olive oil/pentosan polysulfate, or olive oil/5% glucose for 30 days. Creatinine clearance (CrCl) was determined at three time points. Afferent arteriolar lesions, glomerular volume, and tubulo-interstitial lesions were quantitated. RNA was extracted from cortex.
RESULTS
Severe lesions were found in the CsA group. A reduction in the number of affected arterioles (32%) and the degree of chronic tubulo-interstitial lesions (44%) was found in pentosan polysulfate/CsA-treated rats. A 20% decrease in glomerular volume was found in CsA rats, but not in pentosan polysulfate/CsA-treated rats. Pentosan polysulfate treatment did not prevent the CsA-induced decrease in CrCl (approximately 30%) at 4 weeks. CsA did not affect cortical endothelial or neuronal nitric-oxide synthase or mRNA levels, but there was small increase in neuronal nitric-oxide synthase mRNA levels in the pentosan polysulfate/CsA-treated group.
CONCLUSIONS
Pentosan polysulfate reduced structural renal lesions in CsA-treated, salt-depleted Sprague-Dawley rats.
Topics: Animals; Arterioles; Creatinine; Cyclosporine; Diet, Sodium-Restricted; Kidney; Kidney Cortex; Kidney Glomerulus; Male; Mice; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Pentosan Sulfuric Polyester; RNA, Messenger; Rats; Rats, Sprague-Dawley; Renal Circulation; Transcription, Genetic
PubMed: 10589959
DOI: 10.1097/00007890-199911270-00025 -
American Journal of Clinical Oncology Jun 2015The optimal management of persistent hemorrhagic radiation cystitis is ill-defined. Various options are available and include oral agents (ie, sodium pentosan... (Review)
Review
The optimal management of persistent hemorrhagic radiation cystitis is ill-defined. Various options are available and include oral agents (ie, sodium pentosan polysulfate), intravenous drugs (ie, WF10), topical agents (ie, formalin), hyperbaric oxygen, and endoscopic procedures (ie, electrical cautery, argon plasma coagulation, laser coagulation). In general, it is best to manage patients conservatively and intervene only when necessary with the option least likely to exacerbate the cystitis. More aggressive measures should be employed only when more conservative approaches fail. Bladder biopsies should be avoided, unless findings suggest a bladder tumor, because they may precipitate a complication.
Topics: Administration, Intravenous; Administration, Intravesical; Administration, Oral; Anticoagulants; Chlorine; Cystitis; Formaldehyde; Hematuria; Humans; Hyaluronic Acid; Hyperbaric Oxygenation; Laser Coagulation; Oxides; Pentosan Sulfuric Polyester; Radiation Injuries; Radiation-Protective Agents; Radiotherapy; Urinary Bladder
PubMed: 24322335
DOI: 10.1097/COC.0000000000000016 -
Aktuelle Urologie Dec 2021It is currently assumed that interstitial cystitis/bladder pain syndrome is caused by damage to the glycosaminoglycane layer on the urothelium of the urinary bladder....
INTRODUCTION
It is currently assumed that interstitial cystitis/bladder pain syndrome is caused by damage to the glycosaminoglycane layer on the urothelium of the urinary bladder. This layer can be repaired by oral therapy with pentosan polysulfate sodium. The focus of this article is on the history of this drug, its efficacy, its valuation in guidelines and especially the possible correlation with maculopathy.
METHODS
Literature research in PubMed and Embase.
RESULTS
PPS has a US and European approval for the therapy of IC characterised by glomerulations or a Hunner lesion detected by endoscopy and bladder distension. Its efficacy was proven in randomised trials. This led to a recommendation as a basic pharmaceutical therapy (in addition to behavioural intervention, dietary therapy or other drug treatments such as pain therapy). After a treatment period of six months, efficacy should be re-evaluated. Side-effects include mild haemodilution, nausea and loss of hair. Two publications of a US eye clinic have recently postulated a correlation between prolonged high-dose therapy with PPS and a special kind of maculopathy. Although this correlation was rejected in a large-scale health service study in Germany, a "red-hand-letter" led to the recommendation to perform an ophthalmologic examination before and during the treatment with PPS. Due to a pending litigation between payers and the distributor, PPS is currently out of trade in Germany. However, PPS can still be prescribed but must be imported from adjacent European countries. Unfortunately, these modalities have led to a significant undersupply of patients with IC/BPS. It is feared that this undersupply will increase further as the litigation is ongoing.
CONCLUSION
Being the only causally acting compound in the therapy of IC/BPS, PPS has an exceptional status. Although an ongoing litigation is pending in Germany and the correlation with maculopathy is still unclear, PPS must remain part of the current and future therapy of IC/BPS.
Topics: Cystitis, Interstitial; Drug-Related Side Effects and Adverse Reactions; Germany; Humans; Pentosan Sulfuric Polyester; Urinary Bladder
PubMed: 34583396
DOI: 10.1055/a-1629-0199 -
JAMA Ophthalmology Mar 2021
Topics: Humans; Macular Degeneration; Pentosan Sulfuric Polyester; Pharmaceutical Preparations
PubMed: 33538763
DOI: 10.1001/jamaophthalmol.2020.6615 -
JAMA Ophthalmology Mar 2021
Topics: Humans; Macular Degeneration; Pentosan Sulfuric Polyester; Pharmaceutical Preparations
PubMed: 33538767
DOI: 10.1001/jamaophthalmol.2020.6618 -
Ophthalmic Surgery, Lasers & Imaging... Oct 2019A pigmentary maculopathy associated with chronic use of the drug pentosan polysulfate sodium (PPS) was recently described. The authors present a case of PPS-associated...
A pigmentary maculopathy associated with chronic use of the drug pentosan polysulfate sodium (PPS) was recently described. The authors present a case of PPS-associated maculopathy that continued to progress for 6 years after discontinuation of this medication. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:656-659.].
Topics: Anticoagulants; Disease Progression; Female; Humans; Macular Degeneration; Middle Aged; Pentosan Sulfuric Polyester
PubMed: 31671200
DOI: 10.3928/23258160-20191009-10 -
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 -
Medical Hypotheses Apr 2011Intervertebral disc degeneration (IDD) is a major health problem world-wide, and several spinal disorders are closely associated with it. Although people have invested a...
Intervertebral disc degeneration (IDD) is a major health problem world-wide, and several spinal disorders are closely associated with it. Although people have invested a great deal of time and effort, how to prevent and reverse the IDD for the researchers is still a difficult and hot issue. Intervertebral disc belongs to cartilage tissue, and IDD also is the cartilage degeneration disease. A large quantity of studies have shown that Calcium pentosan polysulfate (CaPPS) and sodium pentosan polysulfate (NaPPS) possess chondroprotective activities and play an important role in maintaining cartilage integrity. We reasonably hypothesize that NaPPS and CaPPS may be used to treat IDD. The possible mechanism may include that: (1) the significant effects of NaPPS and CaPPS in improving capillary blood flow could maintain nutritional supply to intervertebral disc, and preserve intervertebral disc tissue against degeneration; (2) CaPPS and NaPPS preserve cartilage integrity, proteoglycan synthesis, and improve cartilage biomechanical properties; (3) as the multifaceted exosite inhibitors of proteinases NaPPS and CaPPS strongly impede the activity and production of proteinases; (4) promotion of the balance between proteinases and TIMPs also may be involved in treating IDD; (5) NaPPS and CaPPS exhibit potent anti-inflammatory effects, and then reduce inflammation-induced IDD. If the hypothesis were conformed, the symptoms caused by IDD and its related diseases would be a corresponding alleviation or even disappearance, which could greatly alleviate the suffering of patients from disc degeneration diseases. Certainly, many roles of CaPPS and NaPPS, such as effectiveness, safety and side effects, need to be tested, and further works such as animal model and clinical trial, need to be done to prove this hypothesis.
Topics: Extracellular Matrix; Humans; Intervertebral Disc Degeneration; Pentosan Sulfuric Polyester; Peptide Hydrolases; Protease Inhibitors
PubMed: 21296506
DOI: 10.1016/j.mehy.2011.01.016 -
Seminars in Thrombosis and Hemostasis 1991
Comparative Study Review
Topics: Acquired Immunodeficiency Syndrome; Animals; Anticoagulants; Antiviral Agents; Blood Coagulation Tests; Endothelium, Vascular; Enzyme Inhibitors; Factor Xa Inhibitors; Fibrinolysis; Fibrinolytic Agents; HIV-1; Hemorrhage; Heparin; Heparin Cofactor II; Humans; Liver; Muscle, Smooth, Vascular; Pentosan Sulfuric Polyester; Platelet Aggregation; Thromboembolism; Thrombolytic Therapy; Virus Replication
PubMed: 1719639
DOI: No ID Found -
Investigative Ophthalmology & Visual... Feb 2024There are numerous reports of a distinctive maculopathy in adults exposed to pentosan polysulfate sodium (PPS), a drug prescribed to treat bladder discomfort associated...
PURPOSE
There are numerous reports of a distinctive maculopathy in adults exposed to pentosan polysulfate sodium (PPS), a drug prescribed to treat bladder discomfort associated with interstitial cystitis. We tested whether PPS treatment of mice injures RPE or retina to provide insight into the etiology of the human condition.
METHODS
Mice were fed PPS-supplemented chow over 14 months. RPE and retinal function was assessed by electroretinography (ERG) regularly. Following euthanasia, one eye was used for sagittal sectioning and histology, the contralateral for RPE flatmounting. ZO-1 positive RPE cell borders were imaged using confocal microscopy and cell morphology was analyzed using CellProfiler.
RESULTS
After 10 months of PPS treatment, we observed diminution of mean scotopic c-wave amplitudes. By 11 months, we additionally observed diminutions of mean scotopic a- and b-wave amplitudes. Analysis of flatmounts revealed altered RPE cell morphology and morphometrics in PPS-treated mice, including increased mean en face cell area and geometric eccentricity, decreased RPE cell solidity and extent, and cytosolic translocation of alpha-catenin, all markers of RPE cell stress. Sex and regional differences were seen in RPE flatmount measures. Shortened photoreceptor outer segments were also observed.
CONCLUSIONS
PPS treatment reduced RPE and later retina function as measured by ERG, consistent with a primary RPE injury. Post-mortem analysis revealed extensive RPE pleomorphism and polymegathism and modest photoreceptor changes. We conclude that PPS treatment of mice causes slowly progressing RPE and photoreceptor damage and thus may provide a useful model for some retinal pathologies.
Topics: Adult; Humans; Animals; Mice; Pentosan Sulfuric Polyester; Retina; Electroretinography; Causality; Retinal Diseases
PubMed: 38381414
DOI: 10.1167/iovs.65.2.28