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Semergen Mar 2024Skin ulcers are a serious health problem with significant socioeconomic and labour repercussions and a high tendency to chronicity and recurrence; approximately, up to...
UNLABELLED
Skin ulcers are a serious health problem with significant socioeconomic and labour repercussions and a high tendency to chronicity and recurrence; approximately, up to 50% remain active between six months to one year.
AIM
To study the role of drugs in the aetiology of skin ulcers.
MATERIAL AND METHOD
A comprehensive study of all spontaneous reports related to skin ulcers that appear in the Spanish Pharmacovigilance System of Medicines for Human Use database.
RESULTS
A total of 292 reports were identified containing suspected adverse drug reactions (ADRs) of ulcer lesion type. Three hundred sixty-nine medications with 427 active ingredients were identified. The ulcers appeared mainly in women with a mean age of 56.6 years. The most frequently reported suspected drugs were SGLT-2, vaccines against COVID-19, methotrexate, hydroxycarbamide, trimethoprim-sulfamethoxazole, foscarnet trisodium hexahydrate, ribavirin, docetaxel, acenocumarol and imiquimod, and the combination of lidocaine Hcl-pentosan polysulfate sodium-triamcinolone acetonide.
DISCUSSION
Numerous medications may cause ulcers as an adverse reaction. This possibility should not be ruled out when a new skin lesion appears after the administration of new drugs since 25% of the ADRs were unknown at the time of their notification, as were the cases of ulcers associated with i-SGLT2 and vaccines against COVID at the beginning of their commercialization. However, informative health alerts can be generated by continuously notifying suspected ADRs, so we strongly advise reporting any suspected ADRs to the regional pharmacovigilance system.
Topics: Female; Humans; Middle Aged; Ulcer; Spain; COVID-19 Vaccines; Skin Ulcer; Drug-Related Side Effects and Adverse Reactions
PubMed: 37832472
DOI: 10.1016/j.semerg.2023.102121 -
Journal of Vitreoretinal Diseases 2023We investigated the potential for indication bias to be present in previous studies of pentosan polysulfate sodium (PPS) pigmentary retinopathy by comparing the...
We investigated the potential for indication bias to be present in previous studies of pentosan polysulfate sodium (PPS) pigmentary retinopathy by comparing the incidence and risk of retinopathy in patients with interstitial cystitis (IC) to matched controls. Adult women with IC from a multicenter database of electronic medical record data were matched to non-IC controls at a 1:4 ratio. The IC cohort was subdivided according to duration of PPS use: never, <5 years, and ≥5 years. Incidence and risk (estimated by Cox proportional hazards models) of retinopathy (defined by 6 , Ninth and Tenth Revision codes) were compared between groups. There were 22 060 women with IC and 88 240 women without IC. Average age was 53.92 years (SD, 16.22 years), and 96 110 (87.14%) patients were non-Hispanic White. Incidence of retinopathy per 100 000 person-years was 173.88 (95% CI, 162.78-185.53) for patients without IC, 226.63 (95% CI, 197.73-258.56) for IC without PPS use, 293.02 (95% CI 230.86-366.75) for IC with <5 years of PPS use, and 558.91 (95% CI, 399.29-761.07) for IC with ≥5 years of PPS use. Adjusted hazard ratios were 1.31 (95% CI, 1.13-1.51, < .001) for IC without PPS use, 1.70 (95% CI, 1.35-2.15, < .001) for IC with <5 years of PPS use, and 3.10 (95% CI, 2.26-4.27, < .001) for IC with ≥5 years of PPS use. Patients with IC had greater incidence and risk of retinopathy. PPS use further increased the incidence and risk of retinopathy.
PubMed: 37706083
DOI: 10.1177/24741264231190978 -
American Journal of Ophthalmology Case... Dec 2023To report the structural and functional changes in a 67-year-old male with pentosan polysulfate sodium (PPS) maculopathy with a progressive resolution of bilateral...
PURPOSE
To report the structural and functional changes in a 67-year-old male with pentosan polysulfate sodium (PPS) maculopathy with a progressive resolution of bilateral vitelliform lesions after PPS cessation.
OBSERVATIONS
The patient was initially seen after taking daily PPS for over 26 years. Three months after discontinuing PPS, the bilateral vitelliform lesions identified on spectral-domain optical coherence tomography (SD-OCT) at initial consultation had completely resolved. Bilateral resolution of vitelliform lesions was associated with a decline in best-corrected visual acuity, and ellipsoid zone disruption on SD-OCT.
CONCLUSIONS AND IMPORTANCE
Several PPS maculopathy phenotypes have been previously described including vitelliform lesions. Our case highlights that discontinuing PPS may lead to rapid resolution of vitelliform lesions in PPS maculopathy and may be associated with a rapid reduction in vision.
PubMed: 37645698
DOI: 10.1016/j.ajoc.2023.101875 -
Retinal Cases & Brief Reports Sep 2023The purpose of this study was to describe a case of development of pentosan polysulfate sodium (PPS)-related maculopathy that exhibited potential improvement in imaging...
PURPOSE
The purpose of this study was to describe a case of development of pentosan polysulfate sodium (PPS)-related maculopathy that exhibited potential improvement in imaging findings after drug cessation.
METHODS
This study is a case report.
RESULTS
A 66-year-old woman presented with progressive pigmentary maculopathy associated with long-term PPS usage, including development of a choroidal neovascular membrane in her right eye. After discontinuation of PPS, her clinical course was notable for partial subjective and objective improvement in visual acuity, as well as partial improvement in outer retinal architecture on ocular coherence tomography, but persistence of retinal pigment epithelium atrophy and autofluorescence changes.
CONCLUSION
The course of retinopathy after discontinuation of PPS has yet to be fully determined and has so far been suggested to be progressive. Anatomical improvements seen in our case suggest that further investigations are warranted to determine whether there is potential for partial reversal of some changes in PPS maculopathy.
Topics: Female; Humans; Aged; Pentosan Sulfuric Polyester; Retinal Diseases; Macular Degeneration; Retina; Choroidal Neovascularization
PubMed: 37643033
DOI: 10.1097/ICB.0000000000001242 -
Ophthalmology. Retina Nov 2023
Topics: Humans; Pentosan Sulfuric Polyester; Visual Field Tests; Macular Degeneration; Retinal Diseases
PubMed: 37619623
DOI: 10.1016/j.oret.2023.08.009 -
Journal of Pharmaceutical and... Oct 2023Several publications have recently proposed NMR spectroscopy to evaluate the critical quality attributes (CQA) of pentosan polysulfate sodium (PPS), the active...
Several publications have recently proposed NMR spectroscopy to evaluate the critical quality attributes (CQA) of pentosan polysulfate sodium (PPS), the active ingredient of Elmiron™ approved to treat interstitial cystitis. PPS is a polymer of sulfated β(1-4)-d-xylopyranose residues randomly substituted by 4-O-methyl-glucopyranosyluronic acid, containing, beyond the main xylose-2,3-O-disulfate repetitive unit, some minor residues that can be marker of both the starting material and preparation process. In the present study we assigned some previously unknown cross-peaks in H-C HSQC NMR of PPS related to its minor sequences adding additional details to its CQA. Four anomeric cross-peaks related to glucuronate-branched xylose and different sulfation pattern as well as the preceding xyloses were identified. Two minor process-related signals of monosulfated xyloses (unsubstituted in position 2 or 3) were also assigned. The isolation of a disaccharide fraction allowed the assignment of the reducing end xylose-α/β as well as the preceding xylose residues to be corrected. Additionally, the oversulfation of PPS allowed detection of the reducing end xylose-tri-1,2,3-O-sulfate. The newly identified cross-peaks were integrated into an updated quantitative NMR method. Finally, we demonstrated that an in-depth PPS analysis can be obtained using NMR instruments at medium magnetic fields (500 MHz/600 MHz), commonly available in pharmaceutical industries.
Topics: Pentosan Sulfuric Polyester; Monosaccharides; Xylose; Magnetic Resonance Imaging; Sulfates; Magnetic Resonance Spectroscopy
PubMed: 37619291
DOI: 10.1016/j.jpba.2023.115672 -
Carbohydrate Polymers Nov 2023Pentosan polysulfate sodium (PPS) is a semi-synthetic, heparin-like polysaccharide with manifold therapeutic actions. It is approved for treatment of bladder pain...
Pentosan polysulfate sodium (PPS) is a semi-synthetic, heparin-like polysaccharide with manifold therapeutic actions. It is approved for treatment of bladder pain syndrome / interstitial cystitis in humans and treatment of musculoskeletal diseases in animals. PPS is produced by a complex procedure using beech wood as starting material. It consists of a mixture of sulfated glucuronoxylans, whose structural composition cannot be fully characterized by physicochemical analysis. The question arises whether PPS follow-on products are identical with the original and thus meet the requirement for generic drug application. The aim of this study was to investigate whether commercially available PPS products differ in physicochemical characteristics and biological effects from the original. Ten PPS preparations from different manufactures were analyzed using orthogonal analytical techniques including, inter alia, size exclusion chromatography with triple detection, nuclear magnetic resonance spectroscopy, and high-resolution mid-infrared spectroscopy in aqueous solution with chemometric evaluation. For functional analysis, we measured the plasma kallikrein generation in human plasma and FXII activation. The study revealed significant structural and biological differences between PPS from different sources. Therefore, follow-on products cannot be considered identical but at best similar to original PPS. However, their similar efficacy and safety have still to be proven by comprehensive studies.
PubMed: 37567725
DOI: 10.1016/j.carbpol.2023.121201 -
Brain Pathology (Zurich, Switzerland) Sep 2023Genetic Creutzfeldt-Jakob disease (gCJD) with V180I prion protein gene (PRNP) mutation shows weaker prion protein (PrP) deposition histologically compared with sporadic...
Genetic Creutzfeldt-Jakob disease (gCJD) with V180I prion protein gene (PRNP) mutation shows weaker prion protein (PrP) deposition histologically compared with sporadic CJD, and it is more difficult to detect protease-resistant prion protein in immunoblotting. However, we previously reported the autopsy case of a patient with V180I gCJD who was treated with pentosan polysulfate sodium (PPS); this case had increased protease-resistant PrP deposition. It has been suggested that PPS might reduce protease-resistant PrP; however, the detailed pharmacological and histopathological effects of PPS in humans remain unknown. We examined autopsied human brain tissue from four cases with V180I gCJD that were added to our archives between 2011 and 2021: two cases treated with PPS and two cases without PPS. We conducted a neuropathological assessment, including immunohistochemistry for PrP. We also performed immunoblotting for PrP on homogenate samples from each brain to detect protease-resistant PrP using both a conventional procedure and size-exclusion gel chromatography for the purification of oligomeric PrP. Both PPS-treated cases showed long survival time over 5 years from onset and increased PrP deposition with a characteristic pattern of coarse granular depositions and congophilic PrP microspheres, whereas the cases without PPS showed around 1-year survival from onset and relatively mild neuronal loss and synaptic PrP deposition. Although cortical gliosis seemed similar among all cases, aquaporin 4-expression as a hallmark of astrocytic function was increased predominantly in PPS cases. Immunoblotting of non-PPS cases revealed protease-resistant PrP in the oligomeric fraction only, whereas the PPS-treated cases showed clear signals using conventional procedures and in the oligomeric fraction. These unique biochemical and histopathological changes may reflect the progression of V180I gCJD and its modification by PPS, suggesting the possible existence of toxic PrP-oligomer in the pathophysiology of V180I gCJD and beneficial effects of PPS toward the aggregation and detoxication of toxic PrP-oligomer.
Topics: Humans; Creutzfeldt-Jakob Syndrome; Prions; Prion Proteins; Pentosan Sulfuric Polyester; Peptide Hydrolases; Mutation
PubMed: 37525413
DOI: 10.1111/bpa.13197 -
Biochemistry Jul 2023Heparanase (HPSE) is the only mammalian -β-glucuronidase known to catalyze the degradation of heparan sulfate. Dysfunction of HPSE activity has been linked to several...
Heparanase (HPSE) is the only mammalian -β-glucuronidase known to catalyze the degradation of heparan sulfate. Dysfunction of HPSE activity has been linked to several disease states, resulting in HPSE becoming the target of numerous therapeutic programs, yet no drug has passed clinical trials to date. Pentosan polysulfate sodium (PPS) is a heterogeneous, FDA-approved drug for the treatment of interstitial cystitis and a known HPSE inhibitor. However, due to its heterogeneity, characterization of its mechanism of HPSE inhibition is challenging. Here, we show that inhibition of HPSE by PPS is complex, involving multiple overlapping binding events, each influenced by factors such as oligosaccharide length and inhibitor-induced changes in the protein secondary structure. The present work advances our molecular understanding of the inhibition of HPSE and will aid in the development of therapeutics for the treatment of a broad range of pathologies associated with enzyme dysfunction, including cancer, inflammatory disease, and viral infections.
Topics: Animals; Heparitin Sulfate; Glucuronidase; Mammals
PubMed: 37368361
DOI: 10.1021/acs.biochem.3c00038 -
American Journal of Ophthalmology Nov 2023To describe the progression of pentosan polysulfate sodium (PPS) maculopathy after drug discontinuation qualitatively and quantitatively using multimodal imaging...
PURPOSE
To describe the progression of pentosan polysulfate sodium (PPS) maculopathy after drug discontinuation qualitatively and quantitatively using multimodal imaging assessmen.
DESIGN
Prospective case series.
METHODS
Patients with PPS maculopathy were evaluated after discontinuation of PPS. Near-infrared reflectance (NIR), fundus autofluorescence (FAF), and optical coherence tomography (OCT) were evaluated in all patients at baseline and at the final follow-up visit at least 12 months later. A qualitative and quantitative analysis of the retinal imaging findings was performed. Patterns of disease progression were evaluated. Area of disease involvement on FAF, retinal pigment epithelium (RPE) atrophy on FAF and NIR, and retinal layer thicknesses on OCT were measured at baseline and at the follow-up visit.
RESULTS
A total of 26 eyes were included, with a follow-up period ranging from 13 to 30 months. The diseased area measured on FAF showed significant expansion in all eyes from baseline to follow-up despite drug cessation (P = .03) with a median linearized rate of change of 0.42 mm/y. There was significant reduction in the central macular thickness (P = .04), inner nuclear layer thickness (P = .003), outer nuclear layer thickness (P = .02), and subfoveal choroidal thickness (P = .003) at follow-up vs baseline. New areas of RPE atrophy on FAF in the macula developed in 4 eyes while preexisting atrophic lesions increased in size in 5 eyes.
CONCLUSION
Eyes with baseline PPS maculopathy all exhibited remarkable progression with qualitative and quantitative multimodal imaging analysis despite drug discontinuation. Disease progression may be attributed to underlying inner choroidal ischemia or RPE impairment.
Topics: Humans; Pentosan Sulfuric Polyester; Fluorescein Angiography; Macular Degeneration; Retinal Diseases; Tomography, Optical Coherence; Disease Progression; Atrophy; Retinal Pigment Epithelium
PubMed: 37327961
DOI: 10.1016/j.ajo.2023.05.021