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Veterinary Sciences Apr 2024Musculoskeletal injuries such as equine osteoarthritis, osteoarticular defects, tendonitis/desmitis, and muscular disorders are prevalent among sport horses, with a fair... (Review)
Review
Musculoskeletal injuries such as equine osteoarthritis, osteoarticular defects, tendonitis/desmitis, and muscular disorders are prevalent among sport horses, with a fair prognosis for returning to exercise or previous performance levels. The field of equine medicine has witnessed rapid and fruitful development, resulting in a diverse range of therapeutic options for musculoskeletal problems. Staying abreast of these advancements can be challenging, prompting the need for a comprehensive review of commonly used and recent treatments. The aim is to compile current therapeutic options for managing these injuries, spanning from simple to complex physiotherapy techniques, conservative treatments including steroidal and non-steroidal anti-inflammatory drugs, hyaluronic acid, polysulfated glycosaminoglycans, pentosan polysulfate, and polyacrylamides, to promising regenerative therapies such as hemoderivatives and stem cell-based therapies. Each therapeutic modality is scrutinized for its benefits, limitations, and potential synergistic actions to facilitate their most effective application for the intended healing/regeneration of the injured tissue/organ and subsequent patient recovery. While stem cell-based therapies have emerged as particularly promising for equine musculoskeletal injuries, a multidisciplinary approach is underscored throughout the discussion, emphasizing the importance of considering various therapeutic modalities in tandem.
PubMed: 38787162
DOI: 10.3390/vetsci11050190 -
BMJ Open May 2024Knee osteoarthritis (OA) is the most prevalent arthritis type and a leading cause of chronic mobility disability. While pain medications provide only symptomatic pain...
INTRODUCTION
Knee osteoarthritis (OA) is the most prevalent arthritis type and a leading cause of chronic mobility disability. While pain medications provide only symptomatic pain relief; growing evidence suggests pentosan polysulfate sodium (PPS) is chondroprotective and could have anti-inflammatory effects in knee OA. This study aims to explore the efficacy and safety of oral PPS in symptomatic knee OA with dyslipidaemia.
METHODS AND ANALYSIS
MaRVeL is a phase II, single-centre, parallel, superiority trial which will be conducted at Royal North Shore Hospital, Sydney, Australia. 92 participants (46 per arm) aged 40 and over with painful knee OA and mild to moderate structural change on X-ray (Kellgren and Lawrence grade 2 or 3) will be recruited from the community and randomly allocated to receive two cycles of either oral PPS or placebo for 5 weeks starting at baseline and week 11. Primary outcome will be the 16-week change in overall average knee pain severity measured using an 11-point Numeric Rating Scale. Main secondary outcomes include change in knee pain, patient global assessment, physical function, quality of life and other structural changes. A biostatistician blinded to allocation groups will perform the statistical analysis according to the intention-to-treat principle.
ETHICS AND DISSEMINATION
The protocol has been approved by the NSLHD Human Research Ethics Committee (HREC) (2021/ETH00315). All participants will provide written informed consent online. Study results will be disseminated through conferences, social media and academic publications.
TRIAL REGISTRATION NUMBERS
Australian New Zealand Clinical Trial Registry (ACTRN12621000654853); U1111-1265-3750.
Topics: Humans; Osteoarthritis, Knee; Pentosan Sulfuric Polyester; Dyslipidemias; Quality of Life; Male; Treatment Outcome; Female; Middle Aged; Clinical Trials, Phase II as Topic; Australia; Pain Measurement; Adult
PubMed: 38777590
DOI: 10.1136/bmjopen-2023-083046 -
Journal of Vitreoretinal Diseases 2024To describe a case of pentosan polysulfate maculopathy progression with 13 years of follow-up imaging. A case was analyzed and a literature review performed. A...
To describe a case of pentosan polysulfate maculopathy progression with 13 years of follow-up imaging. A case was analyzed and a literature review performed. A 65-year-old woman was referred to the retina service for a second opinion of a bilateral progressive pigmentary maculopathy. Her medical history was significant for interstitial cystitis that was actively treated with daily pentosan polysulfate since 2003. Multimodal imaging and fundus examination were consistent with pentosan polysulfate maculopathy. A review of records showed previous fundus imaging dating back 13 years that permitted longitudinal assessment of the disease course. Imaging findings were more prominent than the fundus examination findings. There was a 5-year period from the onset of parafoveal atrophy to foveal involvement. A pseudopodial pattern of disease expansion was seen on fundus autofluorescence. To our knowledge, this case represents the longest documented follow-up imaging of the progression of pentosan polysulfate maculopathy in the literature.
PubMed: 38770071
DOI: 10.1177/24741264241228375 -
Scientific Reports May 2024In this population-based cohort study, we investigated screening practices for maculopathy and incidences of specific macular/retinal conditions in pentosan polysulfate...
In this population-based cohort study, we investigated screening practices for maculopathy and incidences of specific macular/retinal conditions in pentosan polysulfate (PPS) users and assessed the relationship between these outcomes and drug exposure levels. Using a health claims database that covers approximately 50 million Koreans, we identified 138,593 individuals who were prescribed PPS between 2010 and 2021. For the 133,762 PPS users who initiated therapy between 2012 and 2021, the cumulative PPS dose for each participant was evaluated, and based on their cumulative PPS dose, patients were categorized into the high-risk (≥ 500 g), low-risk (50-500 g), and minimal exposure (< 50 g) groups. We analyzed the performance and methods of these examination methods used between 2018 and 2021 and compared them among cumulative dose groups to determine whether high-risk users underwent maculopathy screening more frequently or appropriately. We assessed the cumulative incidence of overall macular degeneration and maculopathy excluding common macular diseases following PPS therapy initiation. Most PPS users (99.7%) received a cumulative PPS dose < 500 g and the high- and low-risk groups comprised 445 (0.3%) and 22,185 (16.6%) patients, respectively. During the study period, monitoring examinations were conducted in 52.6% and 49.4% of high- and low-risk patients, respectively, revealing no significant difference between the two groups (P = 0.156). No significant differences were observed in the annual percentages of patients receiving ophthalmic examinations between the high- and low-risk groups (all P > 0.05). The cumulative incidences of overall macular degeneration and maculopathy excluding common macular diseases in high-risk users were 19.3% and 9.0%, respectively, which were significantly different from those of low-risk users (both P < 0.001). Multivariate Cox regression analysis revealed significantly higher risks of maculopathy excluding common macular diseases in the low- (Hazard ratio [HR] of 1.55 [95% CI 1.13-2.12]) and high-risk groups (HR of 1.66 [95% CI 1.22-2.27]) compared to the minimal exposure group. Our findings suggest a need for increased emphasis on PPS maculopathy screening in high-risk patients, highlighting raising awareness regarding exposure-dependent risks and the establishment of screening guidelines.
Topics: Humans; Pentosan Sulfuric Polyester; Male; Female; Middle Aged; Macular Degeneration; Risk Assessment; Aged; Adult; Incidence; Republic of Korea; Mass Screening; Cohort Studies
PubMed: 38760453
DOI: 10.1038/s41598-024-62041-y -
Investigative Ophthalmology & Visual... Apr 2024
PubMed: 38687494
DOI: 10.1167/iovs.65.4.47 -
Joint Bone Spine Apr 2024Osteoarthritis (OA) is the most prevalent arthritis-type and is a major contributor to chronic joint pain, impaired physical function, and limited mobility. By the end...
Osteoarthritis (OA) is the most prevalent arthritis-type and is a major contributor to chronic joint pain, impaired physical function, and limited mobility. By the end of 2020, a total of 595 million, equal to 7·6% of the global population, had OA; this figure is expected to rise exponentially by 2050. Even while the disorder's intricate pathophysiology is starting to appear intelligible, we are yet to have a cure for the disorder. OA is typically managed with traditional palliative measures, such as topical and systemic analgesics, including non-steroidal anti-inflammatory drugs, therapeutic exercise, and braces. Sometimes, intra-articular glucocorticoids, viscosupplementation, or regenerative interventions provide short-term pain relief and functional improvement; some may require arthroplasty. Researchers continue their efforts to unveil a new therapeutic target to be effective in OA that modifies symptoms and arrests disease progression as well. In the present literature review, insights into new therapeutic strategies in OA, for example, liposome-based dexamethasone, microspore-based triamcinolone, nerve growth factor antagonist, anti-ADAMTS-5 (A Disintegrin And Metalloproteinase Thrombospoidin Motifs - 5), pentosan polysulfate sodium, allogeneic stem cells, C-C chemokine receptor type-4 (CCR4) ligand 17 inhibitor, Wnt-signaling inhibitor, and anti-obesity medications are provided.
PubMed: 38685527
DOI: 10.1016/j.jbspin.2024.105739 -
Investigative Ophthalmology & Visual... Apr 2024Fluorescence lifetime ophthalmoscopy (FLIO) is an emerging clinical modality that could provide biomarkers of retinal health beyond fluorescence intensity. Adaptive...
PURPOSE
Fluorescence lifetime ophthalmoscopy (FLIO) is an emerging clinical modality that could provide biomarkers of retinal health beyond fluorescence intensity. Adaptive optics (AO) ophthalmoscopy provides the confocality to measure fluorescence lifetime (FL) primarily from the retinal pigment epithelium (RPE) whereas clinical FLIO has greater influence from fluorophores in the inner retina and lens. Adaptive optics fluorescence lifetime ophthalmoscopy (AOFLIO) measures of FL in vivo could provide insight into RPE health at different stages of disease. In this study, we assess changes in pentosan polysulfate sodium (PPS) toxicity, a recently described toxicity that has clinical findings similar to advanced age-related macular degeneration.
METHODS
AOFLIO was performed on three subjects with PPS toxicity (57-67 years old) and six age-matched controls (50-64 years old). FL was analyzed with a double exponential decay curve fit and with phasor analysis. Regions of interest (ROIs) were subcategorized based on retinal features on optical coherence tomography (OCT) and compared to age-matched controls.
RESULTS
Twelve ROIs from PPS toxicity subjects met the threshold for analysis by curve fitting and 15 ROIs met the threshold for phasor analysis. Subjects with PPS toxicity had prolonged FL compared to age-matched controls. ROIs of RPE degeneration had the longest FLs, with individual pixels extending longer than 900 ps.
CONCLUSIONS
Our study shows evidence that AOFLIO can provide meaningful information in outer retinal disease beyond what is obtainable from fluorescence intensity alone. More studies are needed to determine the prognostic value of AOFLIO.
Topics: Humans; Middle Aged; Aged; Retinal Pigment Epithelium; Pentosan Sulfuric Polyester; Retina; Ophthalmoscopy; Retinal Degeneration; Tomography, Optical Coherence; Fluorescein Angiography
PubMed: 38630675
DOI: 10.1167/iovs.65.4.27 -
Viruses Feb 2024Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus with high contagion and mortality rates. Heparan sulfate proteoglycans (HSPGs) are...
Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus with high contagion and mortality rates. Heparan sulfate proteoglycans (HSPGs) are ubiquitously expressed on the surface of mammalian cells. Owing to its high negatively charged property, heparan sulfate (HS) on the surface of host cells is used by many viruses as cofactor to facilitate viral attachment and initiate cellular entry. Therefore, inhibition of the interaction between viruses and HS could be a promising target to inhibit viral infection. In the current study, the interaction between the receptor-binding domain (RBD) of MERS-CoV and heparin was exploited to assess the inhibitory activity of various sulfated glycans such as glycosaminoglycans, marine-sourced glycans (sulfated fucans, fucosylated chondroitin sulfates, fucoidans, and rhamnan sulfate), pentosan polysulfate, and mucopolysaccharide using Surface Plasmon Resonance. We believe this study provides valuable insights for the development of sulfated glycan-based inhibitors as potential antiviral agents.
Topics: Animals; Heparin; Middle East Respiratory Syndrome Coronavirus; Sulfates; Glycosaminoglycans; Heparitin Sulfate; Mammals
PubMed: 38400013
DOI: 10.3390/v16020237 -
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