RESUMEN
The review article is devoted to the possibilities of using targeted therapy for urothelial diseases, namely painful bladder syndrome (BPS). The protective structural components of the bladder mucosa, as well as their chemical features, are described in detail. Pentosanpolysulfate (PPS), being an oral heparinoid, can be used as part of pathogenetic therapy to restore the mucous membrane of the bladder. The efficacy and safety of this drug has been proven by us in a multicenter, randomized, double-blind, placebo-controlled trial. An additional assessment of the effectiveness and safety of the use of PPS in BPS was confirmed as part of our systematic review and meta-analysis. Thus, PPS is a pathogenetically sound tool in the treatment of patients with painful bladder syndrome.
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Dolor Crónico , Cistitis Intersticial , Cistitis Intersticial/tratamiento farmacológico , Humanos , Estudios Multicéntricos como Asunto , Dolor Pélvico/tratamiento farmacológico , Poliéster Pentosan Sulfúrico/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Sodio/uso terapéutico , UrotelioRESUMEN
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.
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Neoplasias de la Vejiga Urinaria , Antibacterianos/uso terapéutico , Vacuna BCG/efectos adversos , Humanos , Poliéster Pentosan Sulfúrico/uso terapéutico , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
INTRODUCTION: Hemorrhagic cystitis can commonly occur following an allogeneic hematopoietic cell transplant and treatment options are currently limited. Pentosan polysulfate, a heparin-like, sulfated polysaccharide, is used to relieve bladder pain and discomfort associated with interstitial cystitis. Initial reports in patients with hemorrhagic cystitis demonstrate that pentosan polysulfate may hasten hemorrhagic cystitis resolution and control symptoms. METHODS AND RESULTS: This report includes a retrospective case series of six patients who received pentosan polysulfate for the treatment of hemorrhagic cystitis following an allogeneic hematopoietic cell transplant. Pentosan polysulfate was initiated at a median of 4.5 days (range: 3-18) following hemorrhagic cystitis onset and continued for a median duration of 17.5 days (range: 7-64). Four patients were tested for BK virus and all were found to have BK viremia and viruria around the time of pentosan polysulfate initiation. The median number of red blood cell transfusions seemed to decrease in the patients initiated on pentosan polysulfate. All patients received a multi-agent treatment regimen, which included pentosan polysulfate, and half the patients had symptom resolution. The median time to symptom resolution from pentosan polysulfate initiation was 9 days (range: 7-10). CONCLUSION: Pentosan polysulfate was well-tolerated and seemed to assist with symptom resolution. Future studies are needed to confirm the impact of pentosan polysulfate on the treatment of hemorrhagic cystitis.
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Cistitis Intersticial , Cistitis , Trasplante de Células Madre Hematopoyéticas , Cistitis/tratamiento farmacológico , Cistitis/etiología , Cistitis Intersticial/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológico , Humanos , Poliéster Pentosan Sulfúrico/uso terapéutico , Estudios RetrospectivosRESUMEN
Ulcerative colitis (UC) primarily affects the mucosa of the distal colon. Dysregulated immune response in genetically-prone persons is claimed to be responsible for chronic intestinal inflammation. This study aimed to explore the efficacy and the hematological effects of pentosan polysulfate sodium (PPS) in a dextran sulfate sodium (DSS)-induced colitis model. Forty C57BL/6 female mice were equally divided into five groups: control group, DSS-colitis group, DSS-colitis treated with 5-aminosalicylic acid, DSS-colitis treated with PPS, and DSS-colitis treated with both drugs. Disease activity index (DAI) and colon length were calculated. Colonic IL-6 and IL-35 levels were assayed by ELISA. IL-35 gene expression was evaluated by qRT-PCR. Colon tissue samples were examined by H&E stain and immunohistochemistry (IHC) of Ki67. The colitis group subjected to combined treatment showed the best outcome with significant improvement of DAI and increased colon length. Colonic IL-6 was significantly lower in both PPS- and combination-treated groups accompanied by a significantly higher IL-35 level and its EBI3 subunit mRNA expression. However, the PPS-treated colitis group showed higher gene expression of IL-35 EBI3 subunit by 1.5-fold compared with the combined group. The colon mucosa and crypts were significantly preserved in mice treated with both drugs with the best Ki67 positive cell density. PPS is a safe and promising drug in the treatment of UC as it exerted the best positive effect on the anti-inflammatory IL-35 level and gene expression. However, superior improvement of DAI was seen when PPS was added to ASA with a greater mucosal proliferation and repair.
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Colitis Ulcerosa , Colitis , Animales , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Colitis Ulcerosa/tratamiento farmacológico , Colon , Sulfato de Dextran/farmacología , Modelos Animales de Enfermedad , Femenino , Interleucinas/metabolismo , Mesalamina/uso terapéutico , Ratones , Ratones Endogámicos C57BL , Poliéster Pentosan Sulfúrico/farmacología , Poliéster Pentosan Sulfúrico/uso terapéutico , Transducción de SeñalRESUMEN
BACKGROUND: Bladder pain syndrome (BPS), which includes the condition of interstitial cystitis, is a poorly understood clinical condition for which patients present with varying symptoms. Management of BPS is challenging for both patients and practitioners. At present, there is no universally accepted diagnosis and diverse causes have been proposed. This is reflected in wide-ranging treatment options, used alone or in combination, with limited evidence. A network meta-analysis (NMA) simultaneously comparing multiple treatments may help to determine the best treatment options for patients with BPS. OBJECTIVES: To conduct a network meta-analysis to assess the effects of interventions for treating people with symptoms of bladder pain syndrome (BPS). SEARCH METHODS: We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL, in the Cochrane Library), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and handsearched journals and conference proceedings (searched 11 May 2018) and the reference lists of relevant articles. We conducted a further search on 5 June 2019, which yielded four small studies that were screened for eligibility but were not incorporated into the review. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs of interventions for treating adults with BPS. All types of interventions (including conservative, pharmacological and surgical) were eligible. DATA COLLECTION AND ANALYSIS: We assessed the risk of bias of included studies using Cochrane's 'Risk of bias' tool. Primary outcomes were the number of people cured or improved, pain, frequency and nocturia. For each outcome, random-effects NMA models were fitted using WinBUGS 1.4. We monitored median odds ratios (ORs) for binary outcomes and mean differences (MDs) for continuous outcomes with 95% credible intervals (Crls). We compared results of the NMA with direct evidence from pairwise meta-analysis of head-to-head trials. We used the CINeMA tool to assess the certainty of evidence for selected treatment categories. MAIN RESULTS: We included 81 RCTs involving 4674 people with a median of 38 participants (range 10 to 369) per RCT. Most trials compared treatment against control; few trials compared two active treatments. There were 65 different active treatments, and some comparisons were informed by direct evidence from only one trial. To simplify, treatments were grouped into 31 treatment categories by mode of action. Most studies were judged to have unclear or high risk of bias for most domains, particularly for selection and detection bias. Overall, the NMA suggested that six (proportion cured/improved), one (pain), one (frequency) and zero (nocturia) treatment categories were effective compared with control, but there was great uncertainty around estimates of effect. Due to the large number of intervention comparisons in this review, we focus on three interventions: antidepressants, pentosan polysulfate (PPS) and neuromuscular blockade. We selected these interventions on the basis that they are given 'strong recommendations' in the EAU Guidelines for management of BPS (EAU Guidelines 2019). We found very low-certainty evidence suggesting that antidepressants were associated with greater likelihood of cure or improvement compared with control (OR 5.91, 95% CrI 1.12 to 37.56), but it was uncertain whether they reduced pain (MD -1.27, 95% CrI -3.25 to 0.71; low-certainty evidence), daytime frequency (MD -2.41, 95% CrI -6.85 to 2.05; very low-certainty evidence) or nocturia (MD 0.01, 95% CrI -2.53 to 2.50; very low-certainty evidence). There was no evidence that PPS had improved cure/improvement rates (OR 0.14, 95% CrI 0.40 to 3.35; very low-certainty evidence) or reduced pain (MD 0.42, 95% CrI -1.04 to 1.91; low-certainty evidence), frequency (MD -0.37, 95% CrI -5.00 to 3.44; very low-certainty evidence) or nocturia (MD -1.20, 95% CrI -3.62 to 1.28; very low-certainty evidence). There was evidence that neuromuscular blockade resulted in greater cure or improvement (OR 5.80, 95% CrI 2.08 to 18.30) but no evidence that it improved pain (MD -0.33, 95% CrI -1.71 to 1.03), frequency (MD -0.91, 95% CrI -3.24, 1.29) or nocturia (MD -0.04, 95% CrI -1.35 to 1.27). The certainty of this evidence was always very low. AUTHORS' CONCLUSIONS: We are uncertain whether some treatments may be effective in treating patients with BPS because the certainty of evidence was generally low or very low. Data were available for a relatively large number of trials, but most had small sample sizes and effects of treatments often could not be estimated with precision. An NMA was successfully conducted, but limited numbers of small trials for each treatment category hampered our ability to fully exploit the advantages of this analysis. Larger, more focused trials are needed to improve the current evidence base.
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Cistitis Intersticial/terapia , Metaanálisis en Red , Antidepresivos/uso terapéutico , Sesgo , Femenino , Humanos , Masculino , Bloqueantes Neuromusculares/uso terapéutico , Nocturia/terapia , Poliéster Pentosan Sulfúrico/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
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.
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Cistitis Intersticial , Células Madre Mesenquimatosas , Tejido Adiposo , Animales , Cistitis Intersticial/tratamiento farmacológico , Inflamación , Poliéster Pentosan Sulfúrico/farmacología , Poliéster Pentosan Sulfúrico/uso terapéutico , RatasRESUMEN
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.
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Cistitis Intersticial/tratamiento farmacológico , Administración Intravesical , Toxinas Botulínicas Tipo A/uso terapéutico , Brasil , Sulfatos de Condroitina/uso terapéutico , Toma de Decisiones Clínicas , Dimetilsulfóxido/uso terapéutico , Diterpenos/uso terapéutico , Humanos , Ácido Hialurónico/uso terapéutico , Lidocaína/uso terapéutico , Mycobacterium bovis , Poliéster Pentosan Sulfúrico/uso terapéutico , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Humanos , Cistitis Intersticial/tratamiento farmacológico , Poliéster Pentosan Sulfúrico/uso terapéutico , Administración Intravesical , Brasil , Dimetilsulfóxido/uso terapéutico , Sulfatos de Condroitina/uso terapéutico , Resultado del Tratamiento , Toxinas Botulínicas Tipo A/uso terapéutico , Diterpenos/uso terapéutico , Toma de Decisiones Clínicas , Ácido Hialurónico/uso terapéutico , Lidocaína/uso terapéutico , Mycobacterium bovisRESUMEN
Background: Among the numerous therapeutic approaches used in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) few have been assessed with a sufficient level of evidence. The safety and efficacy of pentosan polysulfate sodium (PPS) has been shown in several open-label and comparative clinical trials with different populations including two meta-analyses. In the context of the approval procedure of PPS for the treatment of IC/BPS by the European Medicines Agency we updated the findings of the previous analyses by incorporating the results of the latest studies.Method: Relevant studies based on a systematic review of PubMed/Medline and the Cochrane Library in June 2018 were identified. For completeness control, clinical trial registries were also searched. Only randomized, placebo-controlled clinical trials providing sufficient information to estimate at least one relevant effect size measure to compare the efficacy of PPS versus placebo were included in the analysis.Results: Of the studies identified in the literature search, six randomized placebo-controlled studies met the pre-defined eligibility criteria. Analyses showed no indication of heterogeneity or publication bias. Treatment with PPS led to a statistically significant improvement in the patient's overall response assessment (p < .001), pain (p = .009) and urgency (p = .005).Conclusions: Our meta-analyses confirmed the results of preceding meta-analyses showing that PPS is efficacious compared to placebo in the treatment of bladder pain, urinary urgency and frequency of micturition and thus an evident option for the treatment of IC/BPS symptoms.
Asunto(s)
Cistitis Intersticial/tratamiento farmacológico , Poliéster Pentosan Sulfúrico/uso terapéutico , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
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⯵g/g) and arthritic rats treated with meloxicam (2⯵g/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-1ß, 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.
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Artritis Experimental/tratamiento farmacológico , Colágeno Tipo II/toxicidad , Poliéster Pentosan Sulfúrico/uso terapéutico , Animales , Antiinflamatorios/farmacología , Bovinos , Colágeno Tipo II/química , Citocinas/genética , Citocinas/metabolismo , Adyuvante de Freund , Regulación de la Expresión Génica/efectos de los fármacos , Lípidos , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/uso terapéuticoRESUMEN
INTRODUCTION: Interstitial cystitis (IC) and bladder pain syndrome (BPS) are chronic conditions that can be debilitating for patients. There is no consensus as to their etiology, and there are many proposed treatment algorithms. Oftentimes multimodal therapy, such as combining behavioral modification and physical therapy alongside pharmacotherapies, will be utilized. With the various treatment options available to patients and providers, there is an ever-growing need to implement evidence-based therapies. AREAS COVERED: The authors explore the different pharmacotherapies as commonly recommended in the American Urological Association (AUA) and European Association of Urology (EAU) multitiered guidelines for IC/BPS treatment as well as other investigational therapies. Pharmacotherapies targeting bladder, pelvic, and/or systemic factors in the overall treatment of IC/BPS are discussed with a particular focus on evidence-based guideline therapies. This article also looks at emerging therapies of interest. EXPERT OPINION: IC/BPS is a syndrome that requires a multimodal approach, including clinical phenotyping and directed therapy based on the patient's symptoms. The AUA and EAU provide guidelines for practitioners to follow, but adequate treatment requires the therapy to be targeted toward the patient's phenotypic domain.
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Antidepresivos Tricíclicos/uso terapéutico , Cistitis Intersticial/tratamiento farmacológico , Amitriptilina/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Cimetidina/uso terapéutico , Cistitis Intersticial/diagnóstico , Cistitis Intersticial/patología , Antagonistas de los Receptores Histamínicos/uso terapéutico , Humanos , Hidroxizina/uso terapéutico , Inmunosupresores/uso terapéutico , Poliéster Pentosan Sulfúrico/uso terapéuticoRESUMEN
Although an effective therapy for prion disease has not yet been established, many advances have been made toward understanding its pathogenesis, which has facilitated research into therapeutics for the disease. Several compounds, including flupirtine, quinacrine, pentosan polysulfate, and doxycycline, have recently been used on a trial basis for patients with prion disease. Concomitantly, several lead antiprion compounds, including compound B (compB), IND series, and anle138b, have been discovered. However, clinical trials are still far from yielding significantly beneficial results, and the findings of lead compound studies in animals have highlighted new challenges. These efforts have highlighted areas that need improvement or further exploration to achieve more effective therapies. In this work, we review recent advances in prion-related therapeutic research and discuss basic scientific issues to be resolved for meaningful medical intervention of prion disease.
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Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/tratamiento farmacológico , Síndrome de Creutzfeldt-Jakob/historia , Aminopiridinas/uso terapéutico , Animales , Modelos Animales de Enfermedad , Doxiciclina/uso terapéutico , Descubrimiento de Drogas , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Poliéster Pentosan Sulfúrico/uso terapéutico , Quinacrina/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Investigación Biomédica TraslacionalRESUMEN
Current treatment options for MPS I have limited effects on some organs, including the skeletal system. In MPS animal models pentosan polysulphate (PPS) reduces the concentrations of glycosaminoglycans (GAGs) in tissues and body fluids and improves cartilaginous and osseous pathologies. The goals of this study were to investigate primarily the safety and secondary the clinical effects, concerning mobility and pain, of PPS treatment in MPS I patients. Four MPS I-Hurler-Scheie/-Scheie patients aged 35.6 ± 6.4 years with one male were included in the study. All patients were on enzyme replacement therapy since 9.45 ± 3.75 years. PPS was applied subcutaneously in two patients with 1 mg/kg and in two patients with 2 mg/kg, weekly for 12 weeks and then biweekly for 12 weeks. The 24-week treatment with PPS was well tolerated by all patients. Urinary GAG concentrations were reduced from 4.13 ± 1.17 at baseline to 2.69 ± 0.36 mg/mmol creatinine after 24-week treatment with 1 mg/kg PPS, and from 6.71 ± 0.62 to 2.65 ± 0.09 mg/mmol creatinine with 2 mg/kg PPS. An improvement in range of motion was noted in three out of four patients. The pain intensity score was reduced from 4.5 ± 1.77 at baseline to 1.8 ± 0.47 after 24-week treatment with 1 mg/kg PPS; patients with 2 mg/kg PPS already had minimal pain at the start of the study. In conclusion, PPS treatment in a small number of adult MPS I patients was well tolerated and resulted in a significant reduction of urinary GAG excretion and in an improvement of joint mobility and pain.
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Mucopolisacaridosis I/tratamiento farmacológico , Poliéster Pentosan Sulfúrico/uso terapéutico , Adulto , Animales , Cartílago/efectos de los fármacos , Cartílago/metabolismo , Terapia de Reemplazo Enzimático/métodos , Femenino , Glicosaminoglicanos/metabolismo , Humanos , Masculino , Mucopolisacaridosis I/metabolismo , Rango del Movimiento Articular/efectos de los fármacosRESUMEN
Painful bladder syndrome/interstitial cystitis is a debilitating chronic bladder disease that primarily affects women. The disease is due to a damage of urothelial cell lining. As a result, potassium particles and other toxic substances in urine can leak into bladder mucosa, causing the symptoms of lower abdominal/pelvic discomfort, pain, increased urination frequency, urgency, nocturia, and so on, all of which can substantially reduce the quality of daily life. There are multiple symptom reliving therapies. Among them, only pentosan polysulfate sodium, sold under the brand name of Elmiron, has been approved for oral use by US Food and Drug Administration. It provides the relief after several months of use. Based on the scientific leads presented in this article, we propose that human chorionic gonadotropin has a therapeutic potential that is worth investigating for the treatment of this disease.
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Gonadotropina Coriónica/uso terapéutico , Cistitis Intersticial/terapia , Animales , Femenino , Humanos , Masculino , Poliéster Pentosan Sulfúrico/uso terapéutico , Vejiga Urinaria/fisiopatologíaRESUMEN
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.
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Enfermedades de los Gatos/tratamiento farmacológico , Cistitis/veterinaria , Glicosaminoglicanos/uso terapéutico , Poliéster Pentosan Sulfúrico/uso terapéutico , Obstrucción Uretral/veterinaria , Administración Intravesical , Animales , Gatos , Cistitis/tratamiento farmacológico , Método Doble Ciego , Glicosaminoglicanos/administración & dosificación , Masculino , Poliéster Pentosan Sulfúrico/administración & dosificación , Examen Físico/veterinaria , Resultado del Tratamiento , Obstrucción Uretral/tratamiento farmacológico , Cateterismo Urinario/veterinariaRESUMEN
Inflammation contributes to ANG II-associated impairment of renal autoregulation and microvascular P2X1 receptor signaling, but its role in renal autoregulation in mineralocorticoid-induced hypertension is unknown. Autoregulatory behavior was assessed using the blood-perfused juxtamedullary nephron preparation. Hypertension was induced in uninephrectomized control rats (UNx) by subcutaneous implantation of a DOCA pellet plus administration of 1% NaCl in the drinking water (DOCA-salt) for 3 wk. DOCA-salt rats developed hypertension that was unaltered by anti-inflammatory treatment with pentosan polysulfate (DOCA-salt+PPS) but was suppressed with "triple therapy" (hydrochlorothiazide, hydralazine, and reserpine; DOCA-salt+TTx). Baseline arteriolar diameters were similar across all groups. UNx rats exhibited pressure-dependent vasoconstriction with diameters declining to 69 ± 2% of control at 170 mmHg, indicating intact autoregulation. DOCA-salt treatment significantly blunted this pressure-mediated vasoconstriction. Diameters remained between 91 ± 4 and 98 ± 3% of control over 65-170 mmHg, indicating impaired autoregulation. In contrast, pressure-mediated vasoconstriction was preserved in DOCA-salt+PPS and DOCA-salt+TTx rats, reaching 77 ± 7 and 75 ± 3% of control at 170 mmHg, respectively. ATP is required for autoregulation via P2X1 receptor activation. ATP- and ß,γ-methylene ATP (P2X1 receptor agonist)-mediated vasoconstriction were markedly attenuated in DOCA-salt rats compared with UNx (P < 0.05), but significantly improved by PPS or TTx (P < 0.05 vs. DOCA-salt) treatment. Arteriolar responses to adenosine and UTP (P2Y2 receptor agonist) were unaffected by DOCA-salt treatment. PPS and TTx significantly reduced MCP-1 and protein excretion in DOCA-salt rats. These results support the hypothesis that hypertension triggers inflammatory cascades but anti-inflammatory treatment preserves renal autoregulation in DOCA-salt rats, most likely by normalizing renal microvascular reactivity to P2X1 receptor activation.
Asunto(s)
Antihipertensivos/uso terapéutico , Arteriolas/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Poliéster Pentosan Sulfúrico/uso terapéutico , Receptores Purinérgicos P2X1/metabolismo , Adenosina Trifosfato/análogos & derivados , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antihipertensivos/farmacología , Arteriolas/metabolismo , Presión Sanguínea , Quimiocina CCL2/orina , Modelos Animales de Enfermedad , Homeostasis/efectos de los fármacos , Hidralazina/farmacología , Hidralazina/uso terapéutico , Hidroclorotiazida/farmacología , Hidroclorotiazida/uso terapéutico , Hipertensión/etiología , Hipertensión/metabolismo , Hipertensión/fisiopatología , Técnicas In Vitro , Riñón/irrigación sanguínea , Riñón/efectos de los fármacos , Riñón/metabolismo , Masculino , Poliéster Pentosan Sulfúrico/farmacología , Proteinuria/tratamiento farmacológico , Ratas Sprague-Dawley , Reserpina/farmacología , Reserpina/uso terapéutico , VasoconstricciónRESUMEN
OBJECTIVE: To survey veterinary practitioners in Australia on how they administer pentosan polysulfate (PPS) to horses and their perceptions of the efficacy of PPS for: the prevention and treatment of osteoarthritis (OA), the treatment of OA when PPS is combined with other drugs, and the efficacy of PPS compared with other disease-modifying osteoarthritic drugs. DESIGN: Practitioners were contacted by email, which contained a link to an online survey. RESULTS: A total of 76 responses (34.5%) to the survey were received. Respondents most commonly used PPS as prophylactic therapy prior to competition (80.3%). As a prophylactic agent, PPS was considered by 48.2% of respondents to have high efficacy. The most common dose regimen for prevention and treatment of OA was 3 mg/kg, intramuscularly, once weekly for 4 weeks followed by monthly injections. Most respondents (78%) combined PPS with other drugs for treatment of OA. Intra-articular corticosteroids and hyaluronate (HA) was the most common drug combination used with PPS. PPS was preferred as a prophylactic agent when compared with HA (88.7% vs 11.3%). For treating OA, 83% of respondents considered a combination of PPS, HA and glucosamine to be more efficacious than PPS alone. However, the most common reason not to use this combination was cost (79.1%). CONCLUSION: All respondents used PPS for prophylaxis and/or treatment of OA despite limited published scientific evidence proving its efficacy in horses. Further research is necessary to provide evidence of the clinical efficacy of PPS for the prevention and treatment of OA in horses.
Asunto(s)
Anticoagulantes/uso terapéutico , Enfermedades de los Caballos/tratamiento farmacológico , Osteoartritis/veterinaria , Poliéster Pentosan Sulfúrico/uso terapéutico , Animales , Australia , Glicosaminoglicanos/uso terapéutico , Encuestas Epidemiológicas , Enfermedades de los Caballos/prevención & control , Caballos , Humanos , Osteoartritis/tratamiento farmacológico , Osteoartritis/prevención & control , Resultado del Tratamiento , Veterinarios , Medicina VeterinariaRESUMEN
BACKGROUND: We previously demonstrated the benefits of daily, oral pentosan polysulfate (PPS) treatment in a rat model of mucopolysaccharidosis (MPS) type VI. Herein we compare these effects to once weekly, subcutaneous (s.c.) injection. The bioavailability of injected PPS is greater than oral, suggesting better delivery to difficult tissues such as bone and cartilage. Injected PPS also effectively treats osteoarthritis in animals, and has shown success in osteoarthritis patients. METHODOLOGY/PRINCIPAL FINDINGS: One-month-old MPS VI rats were given once weekly s.c. injections of PPS (1, 2 and 4 mg/kg, human equivalent dose (HED)), or daily oral PPS (4 mg/kg HED) for 6 months. Serum inflammatory markers and total glycosaminoglycans (GAGs) were measured, as were several histological, morphological and functional endpoints. Overall, weekly s.c. PPS injections led to similar or greater therapeutic effects as daily oral administration. Common findings between the two treatment approaches included reduced serum inflammatory markers, improved dentition and skull lengths, reduced tracheal deformities, and improved mobility. Enhanced effects of s.c. treatment included GAG reduction in urine and tissues, greater endurance on a rotarod, and better improvements in articular cartilage and bone in some dose groups. Optimal therapeutic effects were observed at 2 mg/kg, s.c.. No drug-related increases in liver enzymes, coagulation factor abnormalities or other adverse effects were identified following 6 months of s.c. PPS administration. CONCLUSIONS: Once weekly s.c. administration of PPS in MPS VI rats led to equal or better therapeutic effects than daily oral administration, including a surprising reduction in urine and tissue GAGs. No adverse effects from s.c. PPS administration were observed over the 6-month study period.
Asunto(s)
Mucopolisacaridosis VI/tratamiento farmacológico , Poliéster Pentosan Sulfúrico/administración & dosificación , Poliéster Pentosan Sulfúrico/farmacología , Administración Oral , Animales , Disponibilidad Biológica , Fenómenos Biomecánicos , Cartílago Articular/efectos de los fármacos , Cartílago Articular/patología , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Fémur/diagnóstico por imagen , Fémur/efectos de los fármacos , Glicosaminoglicanos/metabolismo , Placa de Crecimiento/efectos de los fármacos , Placa de Crecimiento/patología , Inyecciones Subcutáneas , Masculino , Movimiento/efectos de los fármacos , Mucopolisacaridosis VI/metabolismo , Mucopolisacaridosis VI/patología , Mucopolisacaridosis VI/fisiopatología , Poliéster Pentosan Sulfúrico/farmacocinética , Poliéster Pentosan Sulfúrico/uso terapéutico , Ratas , Columna Vertebral/diagnóstico por imagen , Columna Vertebral/efectos de los fármacos , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: A small number of patients with variant Creutzfeldt-Jakob disease (vCJD) have been treated with intraventicular pentosan polysulfate (iPPS) and extended survival has been reported in some cases. To date, there have been no reports on the findings of postmortem examination of the brain in treated patients and the reasons for the extended survival are uncertain. We report on the neuropathological findings in a case of vCJD treated with PPS. METHODS: Data on survival in vCJD is available from information held at the National CJD Research and Surveillance Unit and includes the duration of illness in 176 cases of vCJD, five of which were treated with iPPS. One of these individuals, who received iPPS for 8â years and lived for 105â months, underwent postmortem examination, including neuropathological examination of the brain. RESULTS: The mean survival in vCJD is 17â months, with 40â months the maximum survival in patients not treated with PPS. In the 5 patients treated with PPS survival was 16 months, 45 months, 84 months, 105 months and 114â months. The patient who survived 105â months underwent postmortem examination which confirmed the diagnosis of vCJD and showed severe, but typical, changes, including neuronal loss, astrocytic gliosis and extensive prion protein (PrP) deposition in the brain. The patient was also given PPS for a short period by peripheral infusion and there was limited PrP immunostaining in lymphoreticular tissues such as spleen and appendix. CONCLUSIONS: Treatment with iPPS did not reduce the overall neuropathological changes in the brain. The reduced peripheral immunostaining for PrP may reflect atrophy of these tissues in relation to chronic illness rather than a treatment effect. The reason for the long survival in patients treated with iPPS is unclear, but a treatment effect on the disease process cannot be excluded.