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1.
Asia Pac J Ophthalmol (Phila) ; 11(2): 100-110, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35533330

RESUMO

ABSTRACT: Pentosan polysulfate (PPS) sodium (Elmiron) is the only Food and Drug Administration (FDA)-approved oral medication to treat interstitial cystitis, also known as bladder pain syndrome. A symptomatic pigmentary maculopathy associated with PPS was reported in 2018. Since then, recognition of this unique drug toxicity has increased rapidly. This potentially sight-threatening side effect prompted the FDA in June 2020 to update the label for PPS to warn about "retinal pigmentary changes." A challenging feature of pentosan maculopathy is its ability to mimic many other retinal conditions, including inherited retinal dystrophies such as pattern dystrophy, mitochondrially inherited diabetes and deafness, and Stargardt disease, and age-related macular degeneration. In this review, we discuss the history of PPS maculopathy and its implications for thousands of at-risk interstitial cystitis patients. We use published literature and an illustrative case from our institution to highlight the importance of diagnosing PPS maculopathy. We also compare PPS maculopathy to age-related macular degeneration, explain why differentiating between the 2 is clinically important, and highlight avenues for further research. Finally, we highlight the paucity of data on patients of color and why this lack of understanding may impact patient care.


Assuntos
Cistite Intersticial , Degeneração Macular , Distrofias Retinianas , Anticoagulantes/efeitos adversos , Cistite Intersticial/induzido quimicamente , Cistite Intersticial/diagnóstico , Cistite Intersticial/tratamento farmacológico , Feminino , Humanos , Degeneração Macular/induzido quimicamente , Degeneração Macular/diagnóstico , Degeneração Macular/tratamento farmacológico , Masculino , Poliéster Sulfúrico de Pentosana/efeitos adversos
2.
Sci Rep ; 12(1): 7923, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562591

RESUMO

Each prion strain has its own characteristics and the efficacy of anti-prion drugs varies. Screening of prion disease therapeutics is typically evaluated by measuring amounts of protease-resistant prion protein (PrP-res). However, it remains unclear whether such measurements correlate with seeding activity, which is evaluated by real-time quaking-induced conversion (RT-QuIC). In this study, the effects of anti-prion compounds pentosan polysulfate (PPS), Congo red, and alprenolol were measured in N2a58 cells infected with Fukuoka-1 (FK1) or 22L strain. The compounds abolished PrP-res and seeding activity, except for N2a58/FK1 treated with PPS. Interestingly, the seeding activity of N2a58/FK1, which was reduced in the presence of PPS, was not lost and remained at low levels. However, upon removal of PPS, both were gradually restored to their original levels. These results indicate that low-level persistent prion infection keeping measurable seeding activity is induced by PPS in a strain-dependent manner. Furthermore, for protein misfolding cyclic amplification (PMCA), the anti-prion effect of PPS decreased in FK1 compared to 22L, suggesting that the differences occur at the level of the direct conversion. Our findings demonstrate that the advantages of RT-QuIC and PMCA can be exploited for more accurate assessment of therapeutic drug screening, reflecting strain differences.


Assuntos
Doenças Priônicas , Príons , Animais , Camundongos , Poliéster Sulfúrico de Pentosana/farmacologia , Poliéster Sulfúrico de Pentosana/uso terapêutico , Proteínas PrPSc/metabolismo , Doenças Priônicas/tratamento farmacológico , Doenças Priônicas/metabolismo , Proteínas Priônicas/metabolismo , Príons/metabolismo
3.
Neurourol Urodyn ; 41(5): 1121-1126, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35391498

RESUMO

OBJECTIVE: To describe prescription prevalence of oral bladder pain medications among women with interstitial cystitis/bladder pain syndrome (IC/BPS) and to compare with current treatment guidelines. METHODS: We sampled female patients with an ICD-9/10 diagnosis of IC/BPS (595.1/N30.10) by querying active users of the Veterans Health Administration. Medical records were reviewed to determine whether patients met IC/BPS diagnostic criteria. A cohort of women with other pelvic pain disorders was identified. Prescription prevalence of typical non-narcotic oral bladder pain medications was compared between the two groups and healthy controls. Prescription prevalence was also compared before and after the diagnosis of IC/BPS was made using Poisson regression. RESULTS: There were 641 women who met criteria for IC/BPS and 197 women with "Other pelvic pain" disorders. Women with IC/BPS were prescribed a pain medication more often than those with "Other pelvic pain" (77% vs. 59%, p < 0.0001). Of the women with IC/BPS, 44% tried three or more pain medications. Of women with a diagnosis of IC/BPS, only 67% were prescribed an American Urological Association-recommended medication. Prescription prevalence increased after diagnosis for both pentosan polysulfate (10%-29%, p < 0.0001) and hydroxyzine (17%-40%, p < 0.0001), but not for amitriptyline or cimetidine. Amitriptyline was prescribed to 223 women with IC/BPS, only 125 of which (56%) had a documented history of depression. CONCLUSIONS: Many women with IC/BPS required multiple bladder prescriptions, highlighting the difficulty in finding an effective treatment for IC/BPS. Pentosan polysulfate and hydroxyzine were preferred IC/BPS medications. Our next step will be to analyze treatment patterns in those patients who did not receive medications.


Assuntos
Dor Crônica , Cistite Intersticial , Amitriptilina/uso terapêutico , Dor Crônica/tratamento farmacológico , Cistite Intersticial/diagnóstico , Cistite Intersticial/tratamento farmacológico , Cistite Intersticial/epidemiologia , Prescrições de Medicamentos , Feminino , Humanos , Hidroxizina/uso terapêutico , Dor Pélvica/diagnóstico , Dor Pélvica/tratamento farmacológico , Dor Pélvica/epidemiologia , Poliéster Sulfúrico de Pentosana/uso terapêutico
4.
Urol Clin North Am ; 49(2): 273-282, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35428433

RESUMO

Interstitial cystitis/bladder pain syndrome (IC/BPS) is defined as persistent or chronic discomfort perceived to be related to the urinary bladder accompanied by urinary urgency or frequency. Pharmacotherapies used to treat IC/BPS include oral and intravesical agents. Oral therapies include amitriptyline, hydroxyzine, cyclosporine A, and pentosan polysulfate sodium (PPS), although the recent finding of pigmented maculopathy with chronic PPS is very concerning and must be discussed with patients, many of whom will choose to either come off this medicine or not even start it. Certolizumab pegol is a pharmacologic therapy that is currently in clinical development for treatment of IC/BPS symptoms.


Assuntos
Cistite Intersticial , Cistite Intersticial/tratamento farmacológico , Feminino , Humanos , Masculino , Poliéster Sulfúrico de Pentosana/uso terapêutico , Bexiga Urinária
5.
Br J Clin Pharmacol ; 88(7): 3428-3433, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35277990

RESUMO

AIMS: Recent epidemiologic studies have examined the risk of maculopathy with pentosan polysulfate sodium (PPS), a drug indicated for the treatment of interstitial cystitis. However, results have been contradictory. Thus, we quantified the risk of maculopathy with PPS with a focus on risk with duration of use. METHODS: We used a new user, retrospective cohort study with an active comparator. We created a cohort of mutually exclusive 6221 PPS users and 89 744 amitriptyline users, a tricyclic antidepressant also used for the treatment of pain secondary to interstitial cystitis. Subjects were selected from the PharMetrics Plus database (IQVIA, Durham, NC) from 2006 to 2020. Cohort members were followed to the first event of the study outcome (maculopathy) or end of enrolment. A Cox regression model was constructed to adjust for potential confounders. RESULTS: The mean follow-up was 3.0 years for PPS users and amitriptyline users. The adjusted hazard ratio (HR) for maculopathy in PPS users was 2.64 (95% confidence interval [CI]: 1.90-3.68). The HR for the sensitivity analysis that combined maculopathy and age-related macular degeneration (AMD) was 1.38 (95% CI: 1.16-1.65). A cumulative duration-response pattern was observed, with use greater than 3 years having a 9.5-fold risk of maculopathy (HR = 9.56, 95% CI: 3.60-25.37) compared to a 2.3-fold risk of maculopathy with use for 1 year or less (HR = 2.27, 95% CI: 1.50-3.43). The number needed to harm for the first 4 years of use was 250. CONCLUSIONS: The results of this study suggest an increased risk of maculopathy with PPS use, particularly with longer duration of use.


Assuntos
Cistite Intersticial , Degeneração Macular , Amitriptilina/efeitos adversos , Cistite Intersticial/induzido quimicamente , Cistite Intersticial/tratamento farmacológico , Cistite Intersticial/epidemiologia , Humanos , Degeneração Macular/induzido quimicamente , Degeneração Macular/tratamento farmacológico , Degeneração Macular/epidemiologia , Poliéster Sulfúrico de Pentosana/efeitos adversos , Estudos Retrospectivos
6.
PLoS One ; 17(3): e0265596, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35299233

RESUMO

Hepcidin which is the crucial regulator of iron homeostasis, produced in the liver in response to anemia, hypoxia, or inflammation. Recent studies have suggested that hepcidin and iron metabolism are involved in osteoporosis by inhibiting osteoblast function and promoting osteoclastogenesis. Pentosan polysulfate (PPS) is a heparin analogue and promising novel therapeutic for osteoarthritis (OA). This study was undertaken to determine whether PPS inhibits hepcidin-facilitated osteoclast (OC) differentiation and iron overload. Canine (n = 3) bone marrow mononuclear cells were differentiated to OC by macrophage colony-stimulating factor and receptor-activator of nuclear factor kappaB ligand with the treatment of hepcidin1 (200, 400, 800, 1200 nmol/L) and PPS (1, 5, 10, 20, 40 µg/mL). Differentiation and function of OC were accessed using tartrate-resistant acid phosphate staining and bone resorption assay while monitoring ferroportin1 (FPN1) and iron concentration by immunocytochemistry. Gene expression of OC for cathepsin K (CTK), matrix metallopeptidase-9, nuclear factor of activated-T-cells cytoplasmic 1 and FPN1 was examined. Hepcidin1 showed significant enhancement of OC number at 800 nmol/L (p<0.01). PPS impeded hepcidin-facilitated OC at 1, 5 and 10 µg/mL and reduction of resorption pits at 5 and 10 µg/mL (p< 0.01). All OC specific genes were downregulated with PPS, specifically in significant manner with CTK at higher concentrations. However, heparin induced FPN1 internalization and degradation was inhibited at higher concentrations of PPS while restoring iron-releasing capability of OC. We demonstrate for the first time that PPS is a novel-inhibitor of hepcidin-facilitated OC formation/function which might be beneficial for treatment of OA and osteoporosis.


Assuntos
Reabsorção Óssea , Osteoartrite , Osteoporose , Animais , Medula Óssea/metabolismo , Reabsorção Óssea/metabolismo , Diferenciação Celular , Cães , Heparina/metabolismo , Hepcidinas/genética , Hepcidinas/metabolismo , Ferro/metabolismo , Osteoartrite/metabolismo , Osteoclastos/metabolismo , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Poliéster Sulfúrico de Pentosana/farmacologia , Ligante RANK/metabolismo , Ligante RANK/farmacologia
7.
Int Immunopharmacol ; 106: 108620, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35247859

RESUMO

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.


Assuntos
Colite Ulcerativa , Colite , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite Ulcerativa/tratamento farmacológico , Colo , Sulfato de Dextrana/farmacologia , Modelos Animais de Doenças , Feminino , Interleucinas/metabolismo , Mesalamina/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Poliéster Sulfúrico de Pentosana/farmacologia , Poliéster Sulfúrico de Pentosana/uso terapêutico , Transdução de Sinais
8.
BMC Nephrol ; 23(1): 105, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35291969

RESUMO

BACKGROUND: Renal fibrosis is a common outcome of various renal damage, including diabetic nephropathy (DN), the leading cause of end-stage renal disease. Currently, there are no effective therapies for renal fibrosis. The present study aimed to determine whether pentosan polysulphate sodium (PPS), a FDA approved medication for interstitial cystitis, protects diabetic renal fibrosis. METHODS: Cell viability and apoptosis were evaluated in mouse mesangial cells (SV40-MES13) after incubating with the advanced glycation end products (AGEs), which play important roles in the pathogenesis of DN. Western blot and ELISA were performed to determine the expression of transforming growth factor-beta1 (TGF-ß1) and fibronectin (FN), two biomarkers of renal fibrosis, as well as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα), two biomarkers of inflammation. The miRNA-mRNA regulatory network involved in the phosphatidylinositol 3-kinase (PI3K)/Ser and Thr Kinase (AKT) signalling was investigated by miRNA deep sequencing and validated by RT-PCR and miRNA transfection. RESULTS: AGEs significantly inhibited cell proliferation and promoted cell apoptosis, which was associated with the overexpression of TGF-ß1, FN, IL-6, and TNFα. PPS almost completely reversed AGEs-induced biomarkers of fibrosis and inflammation, and significantly altered the miRNA expression profile in AGEs-treated cells. Notably, the PI3K/AKT signalling was one of the most significantly enriched pathways targeted by PPS-related differentially expressed miRNAs. PPS significantly up-regulated miR-466a-3p, which was shown to target PIK3CA, and mediated the inhibitory effect of PPS on AGEs-induced activation of PI3K/AKT pathway. CONCLUSIONS: The treatment of PPS protected against AGEs-induced toxicity in SV40 MES13 cells via miR-466a-3p-mediated inhibition of PI3K/AKT pathway.


Assuntos
Nefropatias Diabéticas , MicroRNAs , Animais , Biomarcadores , Nefropatias Diabéticas/patologia , Fibrose , Inflamação/complicações , Inflamação/tratamento farmacológico , Interleucina-6 , Camundongos , MicroRNAs/genética , Poliéster Sulfúrico de Pentosana/farmacologia , Fosfatidilinositol 3-Quinase , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
9.
J Pharm Biomed Anal ; 211: 114589, 2022 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-35038672

RESUMO

Pentosan Polysulfate Sodium (PPS) is a semi-synthetic polysulfated xylan sourced from beechwood tree barks. PPS, which is mainly composed of a xylose chain with branched O-methyl-glucuronate (MGA), can have heterogeneity in monosaccharide species, sequence and chemical modifications including sulfation and acetylation. The monosaccharide composition in polysaccharide therapeutics is a frequently quoted quality attribute (QA), which has been assessed using two-dimensional (2D) 1H-13C HSQC NMR. However, the sensitivity of 2D NMR for the assessment of PPS inter-lot variability from the same manufacturer was unclear and questions remained whether 2D NMR had sufficient sensitivity to distinguish normal batch to batch variations in this QA. Here, a 2D peak profile method was applied to compare high-resolution semi-quantitative (semi-q) HSQC spectra with the inclusion of intermediate precision spectra collected on two PPS drug lots released 29 months apart (where one of the lots was expired). The semi-q HSQC NMR confirmed the mass equivalence of total polysaccharides, O-Methyl and acetyl groups between the two lots. The 2D spectral peak profile results readily identified significant lot-to-lot differences (p < 0.05) in relative distribution among most monosaccharide species, in addition to heterogeneity in MGA distribution and acetyl transfer from PPS to free acetate in the expired lot. Precisely measured chemical QAs are prerequisites to establish normal batch variation in the innovator product, providing important reference ranges for complex generic drug developers. Overall, high-resolution semi-q HSQC NMR may provide a sensitive tool to measure fine chemical differences in polysaccharide therapeutics needed to establish chemical QAs and compare batches without concerns of intrinsic NMR method variation.


Assuntos
Imageamento por Ressonância Magnética , Poliéster Sulfúrico de Pentosana , Espectroscopia de Ressonância Magnética/métodos
11.
JAMA Ophthalmol ; 140(1): 37-42, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34792558

RESUMO

IMPORTANCE: Case series have identified a macular condition hypothesized to be associated with the use of pentosan polysulfate sodium (PPS). Observational studies seeking to quantify this association have yielded equivocal results. OBJECTIVE: To estimate the association between PPS exposure and maculopathy. DESIGN, SETTING, AND PARTICIPANTS: This disproportionality analysis was conducted using the US Food and Drug Administration Adverse Event Reporting System from January 2013 through June 2020. EXPOSURE: Adverse event reports for pentosan polysulfate were selected and compared with adverse event reports associated with drugs taken for the following indications: interstitial cystitis, cystitis, bladder disorder, or bladder pain. MAIN OUTCOME MEASURES: Retinal adverse events were identified using the retinal disorders Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query, which includes conditions associated with retinal damage attributable to blockage of its blood supply, nutritional deficiencies, toxins, and diseases affecting the retina. RESULTS: There were 2775 reports available for analysis in the PPS group (of which 1966 were for women [70.9%]) and 6833 reports in the other drugs group (of which 4036 [59.1%] were for women). The proportion of adverse events for any macular event relative to all other events was elevated for the users of PPS compared with those using other interstitial cystitis and bladder pain drugs (proportionate reporting ratio [PRR], 1.21 [95% CI, 1.01-1.44]). With respect to specific retinal conditions, macular degeneration (20 [0.8%] vs 15 [0.2%]), maculopathy (83 [3.4%] vs 2 [0.03%]), retinal dystrophy (3 [0.1%] vs 0), retinal injury (5 [0.2%] vs 0), and retinal toxicity (3 [0.1%] vs 0) were proportionately more common among users of PPS compared with those using other interstitial cystitis and bladder pain drugs, respectively. CONCLUSIONS AND RELEVANCE: The results of the current study add to the growing evidence that PPS use is associated with an increased risk of maculopathy. Studies that rule out prevalent retinal abnormalities prior to the initiation of PPS would strengthen the current body of literature.


Assuntos
Cistite Intersticial , Degeneração Macular , Distrofias Retinianas , Anticoagulantes/efeitos adversos , Cistite Intersticial/induzido quimicamente , Cistite Intersticial/tratamento farmacológico , Feminino , Humanos , Degeneração Macular/induzido quimicamente , Masculino , Dor/induzido quimicamente , Poliéster Sulfúrico de Pentosana/efeitos adversos
12.
Surv Ophthalmol ; 67(1): 83-96, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34000253

RESUMO

Pentosan polysulfate sodium (PPS), a semisynthetic sulfated polysaccharide, is the only FDA-approved oral therapy for interstitial cystitis. Recent studies have described a progressive, vision-threatening macular condition associated with long-term PPS use. We reviewed all publications concerning PPS maculopathy to consolidate known clinical features and to evaluate the strength of this association. Current literature supports a strong dose-dependent association between PPS exposure and a progressive maculopathy impacting the retinal pigment epithelium (RPE) and RPE-photoreceptor interface that may worsen even after drug cessation. Initial symptoms may include prolonged dark adaptation and difficulty reading with relative visual acuity preservation. Fundus examination often shows macular pigment clumps corresponding to lesions of focal RPE thickening. Fundus autofluorescence most clearly depicts the condition, with a distinctive pattern of hypo- and hyperautofluorescent spots in the posterior pole that sometimes extends to the retinal periphery. Many cases also show a characteristic peripapillary hypoautofluorescent halo. Near infrared reflectance may aid in early detection. RPE atrophy, cystoid macular edema, and macular neovascularization may also occur, potentially resulting in loss of central acuity. This newly described association implies significant public health risk. Ophthalmologists should screen PPS users with multimodal retinal imaging, and prescribers should minimize dose and duration of PPS use.


Assuntos
Degeneração Macular , Doenças Retinianas , Anticoagulantes , Humanos , Degeneração Macular/induzido quimicamente , Degeneração Macular/diagnóstico , Degeneração Macular/tratamento farmacológico , Poliéster Sulfúrico de Pentosana/efeitos adversos , Doenças Retinianas/diagnóstico , Epitélio Pigmentado da Retina/patologia
13.
Med Hypotheses ; 157: 110713, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34710749

RESUMO

Osteoarthritis is still a disease burden for pharmaceutical scientists and strategy makers. It is associated with the chronic inflammation of joints especially weight-bearing joints like knee, hip, backbone, and phalanges. NSAIDs that are used for the management of inflammation associated with osteoarthritis have high side effects related to gastric upset, gastric ulcer, and long term treatment associated with liver and kidney damage. Nanotechnology has gained a huge scope for the management of arthritis as it can reach out to the deep inside the cell and alter cellular physiology as desired. The present study hypothesizes the use of polyion complex nanoparticles of hyaluronic acid linked Pentosan polysulfate sodium, a disease-modifying agent for the treatment of osteoarthritis administered through transdermal route. The hypothesis involves the use of drug repurposing as the drug was initially approved for interstitial cystitis, a condition of the urinary bladder associated with pain and swelling. Being very low oral bioavailability and gastric irritation profile, the transdermal route would be beneficial. To overcome the problem associated with the oral route, there is a need for the targeted approach that will particularly reach at inflammatory sites. Thereby transdermal delivery of hyaluronic acid linked Pentosan polysulfate sodium through polyion complex nanoparticle therapy will be a novel therapeutic approach to combat osteoarthritis.


Assuntos
Cistite Intersticial , Nanopartículas , Osteoartrite , Reposicionamento de Medicamentos , Humanos , Ácido Hialurônico , Osteoartrite/tratamento farmacológico , Poliéster Sulfúrico de Pentosana
14.
Int Urogynecol J ; 32(11): 2891-2897, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34505923

RESUMO

INTRODUCTION AND HYPOTHESIS: Recent publications describe pigmentary changes in the retina associated with the use of pentosan polysulfate sodium, the only FDA-approved oral agent for relief of bladder pain or discomfort associated with interstitial cystitis. METHODS: To evaluate this association, we reviewed data from the FDA Adverse Event Reporting System and published case reports and observational studies. RESULTS: The totality of clinical and epidemiology evidence does not resolve the question of causation between pentosan use and retinal pigmentary changes; however, several elements support a potential association. CONCLUSION: Here, we provide our perspective on the available evidence the agency weighed when retinal pigmentary changes were added to pentosan labeling. It is important for urogynecologists prescribing pentosan to be aware of this potential association and be vigilant about assessing eye health in pentosan users.


Assuntos
Cistite Intersticial , Poliéster Sulfúrico de Pentosana , Humanos , Dor Pélvica , Estados Unidos , United States Food and Drug Administration
15.
PLoS One ; 16(9): e0255125, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34492036

RESUMO

Chikungunya virus (CHIKV) is an arthropod-borne virus that causes large outbreaks world-wide leaving millions of people with severe and debilitating arthritis. Interestingly, clinical presentation of CHIKV arthritides have many overlapping features with rheumatoid arthritis including cellular and cytokine pathways that lead to disease development and progression. Currently, there are no specific treatments or vaccines available to treat CHIKV infections therefore advocating the need for the development of novel therapeutic strategies to treat CHIKV rheumatic disease. Herein, we provide an in-depth analysis of an efficacious new treatment for CHIKV arthritis with a semi-synthetic sulphated polysaccharide, Pentosan Polysulfate Sodium (PPS). Mice treated with PPS showed significant functional improvement as measured by grip strength and a reduction in hind limb foot swelling. Histological analysis of the affected joint showed local inflammation was reduced as seen by a decreased number of infiltrating immune cells. Additionally, joint cartilage was protected as demonstrated by increased proteoglycan staining. Using a multiplex-immunoassay system, we also showed that at peak disease, PPS treatment led to a systemic reduction of the chemokines CXCL1, CCL2 (MCP-1), CCL7 (MCP-3) and CCL12 (MCP-5) which may be associated with the reduction in cellular infiltrates. Further characterisation of the local effect of PPS in its action to reduce joint and muscle inflammation was performed using NanoString™ technology. Results showed that PPS altered the local expression of key functional genes characterised for their involvement in growth factor signalling and lymphocyte activation. Overall, this study shows that PPS is a promising treatment for alphaviral arthritis by reducing inflammation and protecting joint integrity.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Febre de Chikungunya/tratamento farmacológico , Vírus Chikungunya/efeitos dos fármacos , Citocinas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Poliéster Sulfúrico de Pentosana/farmacologia , Animais , Anticoagulantes/farmacologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Artrite Reumatoide/virologia , Febre de Chikungunya/imunologia , Febre de Chikungunya/patologia , Febre de Chikungunya/virologia , Vírus Chikungunya/imunologia , Vírus Chikungunya/isolamento & purificação , Modelos Animais de Doenças , Feminino , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia , Inflamação/virologia , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL
16.
Aktuelle Urol ; 52(6): 556-560, 2021 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-34583396

RESUMO

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.


Assuntos
Cistite Intersticial , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Cistite Intersticial/tratamento farmacológico , Alemanha , Humanos , Poliéster Sulfúrico de Pentosana/efeitos adversos , Bexiga Urinária
19.
Optom Vis Sci ; 98(6): 552-556, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34039907

RESUMO

SIGNIFICANCE: Pentosan polysulfate sodium (PPS) maculopathy is a clinical entity characterized by a pigmentary maculopathy in the setting of chronic exposure to PPS. Pentosan polysulfate sodium is indicated for discomfort related to interstitial cystitis/painful bladder syndrome. Given a reported interstitial cystitis/painful bladder syndrome prevalence up to 2%, recognition is critical to mitigate visual sequelae. PURPOSE: We present an observational case report demonstrating typical findings of PPS maculopathy in a patient originally diagnosed with a pattern macular dystrophy. We demonstrate the importance of medical history, medication profile review, and multimodal imaging in the diagnosis and management. The patient provided written informed consent for medical information and images to be published. CASE REPORT: A 55-year-old White woman presented with a painless, bilateral loss of vision and bilateral pigmentary maculopathy that was initially diagnosed as pattern macular dystrophy. Detailed review of medical history, medication profile, and subsequent studies, including optical coherence tomography, near-infrared reflectance imaging, fundus autofluorescence, fluorescein angiography, and genetic studies, ultimately led to the diagnosis of PPS maculopathy. Pentosan polysulfate sodium was discontinued, and ongoing surveillance with multimodal imaging was encouraged. CONCLUSIONS: Because toxic maculopathies are an uncommon diagnosis, screening and recognition of PPS maculopathy are critical in the primary eye care setting. Discontinuation of the insulting agent may be necessary to prevent potentially severe and irreversible vision loss in the at-risk population.


Assuntos
Degeneração Macular , Distrofias Retinianas , Anticoagulantes , Feminino , Angiofluoresceinografia , Humanos , Pessoa de Meia-Idade , Poliéster Sulfúrico de Pentosana/efeitos adversos
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