-
Brazilian Journal of Anesthesiology... 2024This study aimed to investigate the analgesic impact of S(+)-ketamine on pain behavior and synovial inflammation in an osteoarthritis (OA) model.
BACKGROUND
This study aimed to investigate the analgesic impact of S(+)-ketamine on pain behavior and synovial inflammation in an osteoarthritis (OA) model.
METHODS
Animals were grouped as follows: OA-Saline (n = 24) and OA-Ketamine (n = 24), OA induced via intra-articular sodium monoiodoacetate (MIA); a Non-OA group (n = 24) served as the control. On the 7 day post OA induction, animals received either saline or S(+)-ketamine (0.5 mg.kg). Behavioral and histopathological assessments were conducted up to day 28.
RESULTS
S(+)-ketamine reduced allodynia from day 7 to 28 and hyperalgesia from day 10 to 28. It notably alleviated weight distribution deficits from day 10 until the end of the study. Significant walking improvement was observed on day 14 in S(+)-ketamine-treated rats. Starting on day 14, OA groups showed grip force decline, which was countered by S(+)-ketamine on day 21. However, S(+)-ketamine did not diminish synovial inflammation.
CONCLUSION
Low Intra-articular (IA) doses of S(+)-ketamine reduced MIA-induced OA pain but did not reverse synovial histopathological changes.
IRB APPROVAL NUMBER
23115 012030/2009-05.
Topics: Ketamine; Animals; Osteoarthritis; Rats; Injections, Intra-Articular; Male; Analgesics; Rats, Wistar; Pain; Disease Models, Animal; Dose-Response Relationship, Drug; Hyperalgesia
PubMed: 38604407
DOI: 10.1016/j.bjane.2024.844502 -
Frontiers in Veterinary Science 2024Osteoarthritis (OA) remains a major cause of lameness in horses, which leads to lost days of training and early retirement. Still, the underlying pathological processes...
Osteoarthritis (OA) remains a major cause of lameness in horses, which leads to lost days of training and early retirement. Still, the underlying pathological processes are poorly understood. MicroRNAs (miRNAs) are small non-coding RNAs that serve as regulators of many biological processes including OA. Analysis of miRNA expression in diseased joint tissues such as cartilage and synovial membrane may help to elucidate OA pathology. Since integrin α10β1-selected mesenchymal stem cell (integrin α10-MSC) have shown mitigating effect on equine OA we here investigated the effect of integrin α10-MSCs on miRNA expression. Cartilage and synovial membrane was harvested from the middle carpal joint of horses with experimentally induced, untreated OA, horses with experimentally induced OA treated with allogeneic adipose-derived MSCs selected for the marker integrin α10-MSCs, and from healthy control joints. miRNA expression in cartilage and synovial membrane was established by quantifying 70 pre-determined miRNAs by qPCR. Differential expression of the miRNAs was evaluated by comparing untreated OA and control, untreated OA and MSC-treated OA, and joints with high and low pathology score. A total of 60 miRNAs were successfully quantified in the cartilage samples and 55 miRNAs were quantified in the synovial membrane samples. In cartilage, miR-146a, miR-150 and miR-409 had significantly higher expression in untreated OA joints than in control joints. Expression of miR-125a-3p, miR-150, miR-200c, and miR-499-5p was significantly reduced in cartilage from MSC-treated OA joints compared to the untreated OA joints. Expression of miR-139-5p, miR-150, miR-182-5p, miR-200a, miR-378, miR-409-3p, and miR-7177b in articular cartilage reflected pathology score. Several of these miRNAs are known from research in human patients with OA and from murine OA models. Our study shows that these miRNAs are also differentially expressed in experimental equine OA, and that expression depends on OA severity. Moreover, MSC treatment, which resulted in less severe OA, also affected miRNA expression in cartilage.
PubMed: 38596460
DOI: 10.3389/fvets.2024.1374681 -
Molecular Medicine (Cambridge, Mass.) Apr 2024Immune-mediated arthritis is a group of autoinflammatory diseases, where the patient's own immune system attacks and destroys synovial joints. Sustained remission is not...
BACKGROUND
Immune-mediated arthritis is a group of autoinflammatory diseases, where the patient's own immune system attacks and destroys synovial joints. Sustained remission is not always achieved with available immunosuppressive treatments, warranting more detailed studies of T cell responses that perpetuate synovial inflammation in treatment-refractory patients.
METHODS
In this study, we investigated CD4 + and CD8 + T lymphocytes from the synovial tissue and peripheral blood of patients with treatment-resistant immune-mediated arthritis using paired single-cell RNA and TCR-sequencing. To gain insights into the trafficking of clonal families, we compared the phenotypes of clones with the exact same TCRß amino acid sequence between the two tissues.
RESULTS
Our results show that both CD4 + and CD8 + T cells display a more activated and inflamed phenotype in the synovial tissue compared to peripheral blood both at the population level and within individual T cell families. Furthermore, we found that both cell subtypes exhibited clonal expansion in the synovial tissue.
CONCLUSIONS
Our findings suggest that the local environment in the synovium drives the proliferation of activated cytotoxic T cells, and both CD4 + and CD8 + T cells may contribute to tissue destruction and disease pathogenesis.
Topics: Humans; CD8-Positive T-Lymphocytes; Arthritis; Synovial Membrane; Clone Cells; Amino Acid Sequence; CD4-Positive T-Lymphocytes
PubMed: 38594612
DOI: 10.1186/s10020-024-00802-1 -
Journal of the American Veterinary... Jun 2024The objective of this study was to characterize extracellular vesicles (EVs) in plasma and synovial fluid obtained from horses with and without naturally occurring...
OBJECTIVE
The objective of this study was to characterize extracellular vesicles (EVs) in plasma and synovial fluid obtained from horses with and without naturally occurring post-traumatic osteoarthritis (PTOA).
ANIMALS
EVs were isolated from plasma and synovial fluid from horses with (n = 6) and without (n = 6) PTOA.
METHODS
Plasma and synovial fluid EVs were characterized with respect to quantity, size, and surface markers. Small RNA sequencing was performed, and differentially expressed microRNAs (miRNAs) underwent bioinformatic analysis to identify putative targets and to explore potential associations with specific biological processes.
RESULTS
Plasma and synovial fluid samples from horses with PTOA had a significantly higher proportion of exosomes and a lower proportion of microvesicles compared to horses without PTOA. Small RNA sequencing revealed several differentially expressed miRNAs, including miR-144, miR-219-3p, and miR-199a-3l in plasma and miR-199a-3p, miR-214, and miR-9094 in synovial fluid EVs. Bioinformatics analysis of the differentially expressed miRNAs highlighted their potential role in fibrosis, differentiation of chondrocytes, apoptosis, and inflammation pathways in PTOA.
CLINICAL RELEVANCE
We have identified dynamic molecular changes in the small noncoding signatures of plasma and synovial fluid EVs in horses with naturally occurring PTOA. These findings could serve to identify promising biomarkers in the pathogenesis of PTOA, to facilitate the development of targeted therapies, and to aid in establishing appropriate translational models of PTOA.
Topics: Animals; Horses; Synovial Fluid; Osteoarthritis; MicroRNAs; Horse Diseases; Extracellular Vesicles; Male; Female; Wounds and Injuries
PubMed: 38593834
DOI: 10.2460/javma.24.02.0102 -
American Journal of Veterinary Research Jun 2024To evaluate if a difference in synovial amikacin concentrations exists in the radiocarpal joint (RCJ) following different durations of instillation of an IV regional...
OBJECTIVE
To evaluate if a difference in synovial amikacin concentrations exists in the radiocarpal joint (RCJ) following different durations of instillation of an IV regional limb perfusion (IVRLP) perfusate.
ANIMALS
7 healthy horses.
METHODS
Horses received 2 IVRLPs with 2 g amikacin diluted to 60 mL with 0.9% NaCl via the cephalic vein in a crossover study design with a wash-out period between procedures. Instillation of the perfusate was administered over a 1-minute (technique 1) and 5-minute (technique 5) period. Concentrations of amikacin within the RCJ were measured at time (T) 5, 10, 15, 20, 25, and 30 minutes after instillation of the perfusate. Systemic concentrations of amikacin were measured at T0, 5, 10, 15, 20, 25, 29 minutes, and 1 minute after tourniquet removal (T31). Amikacin concentrations were determined by fluorescence polarization immunoassay.
RESULTS
The median maximum concentration (CMAX) of amikacin within the RCJ for technique 1 was 338.4 µg/mL (range, 60 to 4,925 µg/mL), while the median CMAX for technique 5 was higher at 694.8 µg/mL (range, 169.2 to 3,410 µg/mL; P = .398). There was a higher amikacin blood concentration over time for technique 1 compared to technique 5 (P = .004).
CLINICAL RELEVANCE
Administration of perfusate at different rates did not significantly affect synovial concentration of amikacin within the RCJ when performing IVRLP. However, increased systemic leakage was noted when the perfusate was administered over 1 minute, which might affect synovial concentrations in a larger group of horses.
Topics: Animals; Amikacin; Horses; Anti-Bacterial Agents; Cross-Over Studies; Male; Female; Synovial Fluid; Perfusion; Time Factors; Forelimb
PubMed: 38593824
DOI: 10.2460/ajvr.24.02.0029 -
Annals of Medicine and Surgery (2012) Apr 2024Lipoma arborescens is a rare synovial disorder, typically affecting the knee joint, with limited reports of atypical presentations. The study emphasizes the need for a...
INTRODUCTION AND IMPORTANCE
Lipoma arborescens is a rare synovial disorder, typically affecting the knee joint, with limited reports of atypical presentations. The study emphasizes the need for a multidisciplinary diagnostic approach and discusses the genetic and signalling factors associated with its pathogenesis.
CASE PRESENTATION
A 50-year-old male presented with a painless swelling in the dorsum of the right hand, a rare extra-articular manifestation of Lipoma arborescens. Comprehensive clinical, imaging, and histopathological evaluations confirmed the diagnosis, revealing unique features on MRI and frond-like fatty tissue infiltration on excisional biopsy.
CLINICAL DISCUSSION
The case underscores the distinct clinical characteristics, diagnostic challenges, and differential considerations associated with atypical Lipoma arborescens presentations. Extra-articular manifestation of Lipoma arborescens involving the dorsum (extensor aspect) of the hand is rare. Imaging techniques, including MRI and ultrasound, play a crucial role in accurate diagnosis, differentiating it from other joint pathologies. The MRI findings include intra-articular fat deposits and villous proliferation of the synovial membrane. At the same time, the histopathological analysis includes frond-like infiltration of sub-synovial tissue with mature adipocytes which helps in confirming the diagnosis.
CONCLUSION
Successful surgical excision of the extra-articular lesion highlights the importance of a comprehensive diagnostic strategy for managing this uncommon condition. The study contributes valuable insights into understanding, diagnosing, and treating atypical presentations of lipoma arborescens.
PubMed: 38576963
DOI: 10.1097/MS9.0000000000001884 -
Prilozi (Makedonska Akademija Na... Mar 2024Gonarthrosis is arthrosis of the knee joint, a chronic non-inflammatory disease manifested by progressive destruction of the intra-articular cartilage, accompanied by...
INTRODUCTION
Gonarthrosis is arthrosis of the knee joint, a chronic non-inflammatory disease manifested by progressive destruction of the intra-articular cartilage, accompanied by abnormal formation of the bones form the joint, changes in the synovial membrane and synovial fluid. Gonarthrosis is the most common type of arthrosis. Gonarthrosis can be treated conservatively and operatively. Among well-established surgical options for the treatment of medial gonarthrosis are high tibial osteotomy (HTO), unicompart-mental knee arthroplasty (UKA), and total knee arthroplasty (TKA). Proximal fibular osteotomy (PFO) or superior partial fibulectomy is a relatively recent procedure proposed to reduce knee pain in patients with medial compartment.
AIM
Our study aims to demonstrate an alternative treatment for gonarthrosis with proximal fibular osteotomy and reduced knee pain in patients with medial compartment osteoarthritis of the knee.
MATERIALS AND METHODS
At the Department of Orthopedics and Traumatology at J.Z.U "Borka Taleski" Prilep in the period from 2018 to 2021, 14 cases were treated, of which 11 were female and 3 were male. All patients were aged between 62 and 82 years with a mean age of 71.3 years. Patients had a severe degree of gonarthrosis (III/IV) according to Kellgren-Lawrence classification. Arthroscopy was performed in 2 patients. The fibula osteotomy was 7 cm away from the fibular head, with 1 cm resected bone fragment from the fibula.
RESULTS
The average duration of the surgery was 30 minutes. Patients were followed up on the 7th day, first month, 3 months and 6 months after surgery. The final evaluation of function was done after 6 months by examining the active and passive movements of the knee joint. In all 14 patients we have excellent results with pain reduction, improvement of movement and quality of life.
CONCLUSION
Proximal fibular osteotomy is an option for medial compartment osteoarthritis of the knee. Current literature is limited to small case series which report good outcomes in pain reduction, including the correction of varus deformity in medial gonarthrosis. Further studies are needed to determine the place of the PFO in the medial gonarthrosis management algorithm before it can be recommended for routine clinical use.
Topics: Humans; Male; Female; Middle Aged; Aged; Aged, 80 and over; Osteoarthritis, Knee; Fibula; Quality of Life; Pain; Osteotomy; Treatment Outcome
PubMed: 38575383
DOI: 10.2478/prilozi-2024-0002 -
European Journal of Pharmacology Jun 2024Fibroblast-like synoviocytes (FLS) play an important role in rheumatoid arthritis (RA)-related swelling and bone damage. Therefore, novel targets for RA therapy in FLS...
Fibroblast-like synoviocytes (FLS) play an important role in rheumatoid arthritis (RA)-related swelling and bone damage. Therefore, novel targets for RA therapy in FLS are urgently discovered for improving pathologic phenomenon, especially joint damage and dyskinesia. Here, we suggested that pyruvate kinase M2 (PKM2) in FLS represented a pharmacological target for RA treatment by antimalarial drug artemisinin (ART). We demonstrated that ART selectively inhibited human RA-FLS and rat collagen-induced arthritis (CIA)-FLS proliferation and migration without observed toxic effects. In particular, the identification of targets revealed that PKM2 played a crucial role as a primary regulator of the cell cycle, leading to the heightened proliferation of RA-FLS. ART exhibited a direct interaction with PKM2, resulting in an allosteric modulation that enhances the lactylation modification of PKM2. This interaction further promoted the binding of p300, ultimately preventing the nuclear translocation of PKM2 and inducing cell cycle arrest at the S phase. In vivo, ART obviously suppressed RA-mediated synovial hyperplasia, bone damage and inflammatory response to further improve motor behavior in CIA-rats. Taken together, these findings indicate that directing interventions towards PKM2 in FLS could offer a hopeful avenue for pharmaceutical treatments of RA through the regulation of cell cycle via PKM2 lactylation.
Topics: Synoviocytes; Arthritis, Rheumatoid; Animals; Cell Proliferation; Humans; Rats; Fibroblasts; Pyruvate Kinase; Thyroid Hormone-Binding Proteins; Male; Thyroid Hormones; Arthritis, Experimental; Cell Movement; Molecular Targeted Therapy; Membrane Proteins; Carrier Proteins; Small Molecule Libraries
PubMed: 38570082
DOI: 10.1016/j.ejphar.2024.176551 -
Journal of Orthopaedic Case Reports Mar 2024?Introduction: Periosteal chondromas are rare, slow-growing, benign cartilaginous tumors arising from the cortical surface of the bone, beneath the periosteal membrane....
INTRODUCTION
?Introduction: Periosteal chondromas are rare, slow-growing, benign cartilaginous tumors arising from the cortical surface of the bone, beneath the periosteal membrane. Typically affect young males, the most common site being the proximal humerus. There have been no reported cases of periosteal chondroma of the talus in the literature.
CASE REPORT
A 9-year-old Indian boy presented with a 1.5-year history of atraumatic right ankle pain and swelling, exacerbated by walking, with limited dorsiflexion. Physical examination revealed a firm, painless swelling on the anterior ankle's talar region, accompanied by equinus deformity. Radiography displayed osseous masses on the anterior talus. Magnetic resonance imaging indicated well-defined osseous growths originating from the talus's anterior aspect, likely osteochondromas, with adjacent osseous fragments in the tibiotalar joint, suggestive of loose bodies, supporting a clinical diagnosis of synovial chondromatosis. Surgical excision revealed whitish, hard, irregular tissue, confirmed as periosteal chondroma on histopathology. After 6 months, the patient is pain-free with unrestricted movement and no clinical or radiological signs of recurrence.
CONCLUSION
This case report presents a unique instance of previously unreported talus periosteal chondroma, adding novelty to medical literature. It details the diagnostic challenges and its intricacies. It provides a comprehensive overview of clinical presentation, imaging and histopathological findings, differentials and provisional diagnosis, surgical approach, and post-operative outcomes. The successful surgical management, along with the specific details of the surgical procedure (anteromedial approach, excision, and curettage), adds practical insights for orthopedic surgeons and contributes to the existing knowledge on treatment strategies for talus periosteal chondroma. This report will serve as an excellent educational resource.
PubMed: 38560317
DOI: 10.13107/jocr.2024.v14.i03.4292 -
Radiology Case Reports Jun 2024Lipoma arborescens is a rare and benign intra-articular lesion characterized by a lipomatous proliferation of the synovial membrane, usually affects the knee joint. It...
Lipoma arborescens is a rare and benign intra-articular lesion characterized by a lipomatous proliferation of the synovial membrane, usually affects the knee joint. It presents as an unusual cause of intermittent knee pain and joint effusion. We report a case of lipoma arborescens of the knee in a 23-year-old man that initially resembled inflammatory arthropathy. The diagnosis of Lipoma arborescens was made by magnetic resonance imaging of the knee and confirmed histologically by synovectomy. The purpose of our case is to show the imaging features enabling early diagnosis and appropriate treatment.
PubMed: 38559650
DOI: 10.1016/j.radcr.2024.02.106