Can treatment with chondroitin and glucosamine sulphate prevent changes in the articular disc caused by temporomandibular joint osteoarthritis?

BACKGROUND: Chondroitin and glucosamine sulphates (CGS) are considered structure-modifying drugs and have been studied in the prevention, delay or reversal of structural morphological changes in joints caused by osteoarthritis. OBJECTIVE: The aim of the present study was to investigate the action of CGS on the progression of chemically induced osteoarthritis in the temporomandibular joint (TMJ) of rabbits by evaluating the serum levels of tumour necrosis factor (TNF-α) and collagen in the articular discs. MATERIALS AND METHODS: A sample of 36 male rabbits was divided into three groups: control (CG), osteoarthritis (OG) and treatment (TG). The disease was induced by intra-articular injection of sodium monoiodoacetate (10 mg/mL) in the OG and TG groups bilaterally. After 10 days, the TG animals received subcutaneous injection of chondroitin sulphates and glucosamine (7.5 mg/kg) and the OG and CG received saline solution (50 µL). Euthanasia times were subdivided into 40 and 100 days. Collagen quantification was performed by biochemical and histological analysis and for the quantification of serum levels of TNF-α, an enzyme immunoassay was used. RESULTS: The TG showed an increase in the collagen area of the articular disc when compared to the CG and the OG. The increase collagen concentration in the discs did not show a statistically significant difference between the groups. Post-treatment TNF-α levels were significantly lower in TG compared to OG. CONCLUSIONS: The results indicate that CGS treatment delayed the degeneration of the collagen in the TMJ articular disc and reduced serum TNF-α levels, indicating a preventive effect on OA progression.

Tanshinone IIA alleviates IL-1ß-induced chondrocyte apoptosis and inflammation by regulating FBXO11 expression.

OBJECTIVE: This study explored the pharmacological mechanism of Tanshinone IIA (TAN IIA) in the treatment of Osteoarthritis (OA), which provided a certain reference for further research and clinical application of Tan IIA in OA. METHODS: CHON-001 cells were stimulated with 10 µg/mL IL-1ß for 48 h and treated with 10 µM TAN IIA for 48 h. Cellular viability and apoptosis were evaluated by CCK-8 assay and flow cytometry, and Cleaved caspase-3 was measured by Immunoblot assay and RT-qPCR. TNF-α, IL-6, and iNOS in CHON-001 cells were determined by RT-qPCR and ELISA. To further verify the effect of TAN IIA on OA, a rat model of OA in vivo was established by right anterior cruciate ligament transection. TAN IIA was administered at 50 mg/kg or 150 mg/kg for 7 weeks. The degree of cartilage destruction in OA rats was observed by TUNEL and HE staining. Cleaved caspase-3 and FBXO11 were measured by immunohistochemical staining, RT-qPCR, and Immunoblot. TNF-α, IL-6, and iNOS in chondrocytes of OA rats were detected by ELISA. RESULTS: IL-1ß stimulated CHON-001 cell apoptosis and inflammation, and TAN IIA had anti-apoptosis and anti-inflammatory effects on IL-1ß-regulated CHON-001 cells. TAN IIA down-regulated FBXO11 and inhibited PI3K/AKT and NF-κB pathways, thereby alleviating apoptotic and inflammatory reactions in CHON-001 cells under IL-1ß treatment. Moreover, TAN IIA treatment improved chondrocyte apoptosis and inflammations in OA rats. CONCLUSION: TAN IIA inhibits PI3K/Akt and NF-κB pathways by down-regulating FBXO11 expression, alleviates chondrocyte apoptosis and inflammation, and delays the progression of OA.

The effect of low dose intra-articular S(+) ketamine on osteoarthritis in rats: an experimental study.

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 7th day post OA induction, animals received either saline or S(+)-ketamine (0.5 mg.kg-1). 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.

Ethanolic Extract of Propolis Modulates Autophagy-Related microRNAs in Osteoarthritic Chondrocytes.

Osteoarthritis is a multifactorial joint disease characterized by degeneration, and aging stands as a significant risk factor. Autophagy, a crucial cellular homeostasis mechanism, is influenced by aging and closely linked to cartilage health. This correlation between autophagy, cell death, and OA underscores its relevance in disease progression. MicroRNAs have emerged as autophagy regulators, with miRNA-based interventions showing promise in preclinical models. Remarkably, the ethanolic extract of propolis exhibits positive effects on autophagy-related proteins and healthy cartilage markers in an in vitro osteoarthritis model. The aim of this brief report was to evaluate through in silico analysis and postulate five microRNAs that could regulate autophagy proteins (AKT1, ATG5, and LC3) and assess whether the ethanolic extract of propolis could regulate the expression of these microRNAs. Among the examined miRNAs (miR-19a, miR-125b, miR-181a, miR-185, and miR-335), the ethanolic extract of propolis induced significant changes in four of them. Specifically, miR-125b responded to EEP by counteracting IL-1ß-induced effects, while miR-181a, miR-185, and miR-335 exhibited distinct patterns of expression under EEP treatment. These findings unveil a potential link between miRNAs, EEP, and autophagy modulation in OA, offering promising therapeutic insights. Nevertheless, further validation and clinical translation are warranted to substantiate these promising observations.

Comparison of Four Treatment Protocols with Intra-Articular Medium Molecular Weight Hyaluronic Acid in Induced Temporomandibular Osteoarthritis: An Experimental Study.

The aim was to compare the effect between a single intra-articular infiltration (1i) and two infiltrations (2i) of medium molecular weight hyaluronic acid (MMW-HA) of high viscosity (HV) and low viscosity (LV) on the histopathological characteristics of temporomandibular joint (TMJ) osteoarthritis (OA) induced in rabbits. An experimental study was conducted on Oryctolagus cuniculus rabbits, including 42 TMJs, distributed between (1) TMJ-C, control group; (2) TMJ-OA, group with OA; (3) TMJ-OA-wt, group with untreated OA; (4) group treated with HA-HV-1i; (5) group treated with HA-HV-2i; (6) group treated with HA-LV-1i; and (7) group treated with HA-LV-2i. The results were evaluated using the Osteoarthritis Research Society International (OARSI) scale and descriptive histology considering the mandibular condyle (MC), the articular disc (AD), and the mandibular fossa (MF). The Kruskal-Wallis test was used for the statistical analysis, considering p < 0.05 significant. All treated groups significantly decreased the severity of OA compared to the TMJ-OA-wt group. The HA-HV-2i group showed significant differences in the degree of OA from the TMJ-OA group. The degree of OA in the HA-HV-2i group was significantly lower than in the HA-LV-1i, HA-LV-2i, and HA-HV-1i groups. The protocol that showed better results in repairing the joint was HA-HV-2i. There are histological differences depending on the protocol of the preparation used: two infiltrations seem to be better than one, and when applying two doses, high viscosity shows better results.

Propolis as a Potential Therapeutic Agent to Counteract Age-Related Changes in Cartilage: An In Vivo Study.

Aging is intricately linked to chronic low-grade systemic inflammation, which plays a significant role in various age-related conditions, including osteoarthritis (OA). The aging process significantly influences the development of OA due to alterations in cartilage composition, reduced proteoglycan content, dysregulation of growth factor signaling, and heightened oxidative stress. Propolis, a natural product renowned for its potent antioxidant and anti-inflammatory properties, has the potential to mitigate age-induced changes in cartilage. The primary objective of this study was to rigorously assess the impact of in vivo propolis treatment on the histopathological characteristics of knee articular cartilage in senescent rats. This study involved a cohort of twenty male Sprague-Dawley rats, randomly allocated into four distinct groups for comparative analysis: YR (control group consisting of young rats), SR (senescent rats), SR-EEP (senescent rats treated with an ethanolic extract of propolis, EEP), and SR-V (senescent rats administered with a control vehicle). This study employed comprehensive histological and stereological analyses of knee articular cartilage. Propolis treatment exhibited a significant capacity to alleviate the severity of osteoarthritis, enhance the structural integrity of cartilage, and augment chondrocyte density. These promising findings underscore the potential of propolis as a compelling therapeutic agent to counteract age-related alterations in cartilage and, importantly, to potentially forestall the onset of osteoarthritis.

The management of osteoarthritis symptomatology through nanotechnology: a patent review.

Osteoarthritis is considered a degenerative joint disease that is characterised by inflammation, chronic pain, and functional limitation. The increasing development of nanotechnology in drug delivery systems has provided new ideas and methods for osteoarthritis therapy. This review aimed to evaluate patents that have developed innovations, therapeutic strategies, and alternatives using nanotechnology in osteoarthritis treatment. The results show patents deposited from 2015 to November 2021 in the online databases European Patent Office and World Intellectual Property Organisation. A total of 651 patents were identified for preliminary assessment and 16 were selected for full reading and discussion. The evaluated patents are focused on the intraarticular route, oral route, and topical route for osteoarthritis treatment. The intraarticular route presented a higher patent number, followed by the oral and topical routes, respectively. The development of new technologies allows us to envision a promising and positive future in osteoarthritis treatment.

Chelidonine reduces IL-1ß-induced inflammation and matrix catabolism in chondrocytes and attenuates cartilage degeneration and synovial inflammation in rats.

Chondrocyte inflammation and catabolism are two major features in the progression of osteoarthritis (OA). Chelidonine, a principal alkaloid extracted from Chelidonium majus, is suggested to show anti-inflammation, anti-apoptosis, and anti-oxidation activities in various diseases. However, its potential effects on OA cartilage degeneration remains unclear. To evaluate the effect of chelidonine on OA and its underlying mechanism, we incubated chondrocytes with interleukin (IL)-1ß and chelidonine at varying concentrations. Then, we performed the CCK-8 assay, fluorescence immunostaining, reverse transcription PCR, ELISA, and western blotting to evaluate cell viability, catabolic/inflammatory factors, levels of extracellular matrix (ECM)-related proteins, and the involved pathways. H&E and Safranin-O staining and ELISA were performed to measure cartilage degradation and synovial inflammation. Chelidonine suppressed the IL-1ß-mediated catabolism and inflammation of chondrocytes. Chelidonine suppressed the NF-κB pathway activation. Similarly, our in vivo experiment showed that chelidonine partially attenuated cartilage degradation while inhibiting synovial inflammation. Chelidonine inhibited inflammation and catabolism through modulation of NF-κB pathways in vitro, thereby avoiding rat cartilage degeneration and synovial inflammation within OA.

Antiangiogenic Effect of Dopamine and Dopaminergic Agonists as an Adjuvant Therapeutic Option in the Treatment of Cancer, Endometriosis, and Osteoarthritis.

Dopamine (DA) and dopamine agonists (DA-Ag) have shown antiangiogenic potential through the vascular endothelial growth factor (VEGF) pathway. They inhibit VEGF and VEGF receptor 2 (VEGFR 2) functions through the dopamine receptor D2 (D2R), preventing important angiogenesis-related processes such as proliferation, migration, and vascular permeability. However, few studies have demonstrated the antiangiogenic mechanism and efficacy of DA and DA-Ag in diseases such as cancer, endometriosis, and osteoarthritis (OA). Therefore, the objective of this review was to describe the mechanisms of the antiangiogenic action of the DA-D2R/VEGF-VEGFR 2 system and to compile related findings from experimental studies and clinical trials on cancer, endometriosis, and OA. Advanced searches were performed in PubMed, Web of Science, SciFinder, ProQuest, EBSCO, Scopus, Science Direct, Google Scholar, PubChem, NCBI Bookshelf, DrugBank, livertox, and Clinical Trials. Articles explaining the antiangiogenic effect of DA and DA-Ag in research articles, meta-analyses, books, reviews, databases, and clinical trials were considered. DA and DA-Ag have an antiangiogenic effect that could reinforce the treatment of diseases that do not yet have a fully curative treatment, such as cancer, endometriosis, and OA. In addition, DA and DA-Ag could present advantages over other angiogenic inhibitors, such as monoclonal antibodies.

Differences According to the Type of Exogenous Hyaluronic Acid and its Frequency of Infiltration in the Treatment of Temporomandibular Osteoarthritis / Diferencias Según el Tipo de Ácido Hiaurónico Exógeno y su Frecuencia de Infiltración en el Tratamiento de la Osteoartritis Temporomandibular

SUMMARY: One of the most important minimally invasive treatments today in temporomandibular joint osteoarthritis (TMJ- OA) is the intra-articular exogenous hyaluronic acid (HA) injection, which has yielded good results in pain relief and improves mandibular function with few side effects. However, the effectiveness of HA continues to be controversial, partly due to the heterogeneity in the injection protocols in their molecular weight, viscosity and frequency of infiltration, among other properties. The aim of this review is to identify the differences in the histological and clinical effects of the different types of HA and the frequency of infiltration on TMJ-OA treatment. Materials and methods: A bibliographic search was performed in the PubMed, Web of Science and Scopus databases. The search was limited up to September 2022. Search terms included "osteoarthritis", "hyaluronic acid, "molecular weight", "concentration", "viscosity", "dose" and "temporomandibular", using AND/OR as Boolean terms. Results: Exogenous HA in its different molecular weights offers an improvement in histological and clinical characteristics. Apparently, low and medium molecular weight HA presents better results. No clinical studies related to the degree of HA viscosity were found. Respect to the frequency of infiltration, single injection, weekly injections for 3 weeks, weekly injections for 5 weeks and other protocols are used. However, their comparison is complex. There seems to be differences in the effects of the different HA preparations for the treatment of TMJ-OA, mainly in their molecular weight. However, the evidence remains scant.

Uno de los tratamientos mínimamente invasivos más importantes en la actualidad en la artrosis de la articulación temporomandibular (OATM) es la inyección intraarticular de ácido hialurónico (AH) exógeno, que ha dado buenos resultados en el alivio del dolor y mejora la función mandibular con pocos efectos secundarios. Sin embargo, la efectividad del AH continúa siendo controversial, en parte debido a la heterogeneidad en los protocolos de inyección en cuanto a su peso molecular, viscosidad y frecuencia de infiltración, entre otras propiedades. El objetivo de esta revisión fue identificar las diferencias en los efectos histológicos y clínicos de los diferentes tipos de HA y la frecuencia de infiltración en el tratamiento de TMJ-OA. Se realizó una búsqueda bibliográfica en las bases de datos PubMed, Web of Science y Scopus. La búsqueda se limitó hasta septiembre de 2022. Los términos de búsqueda incluyeron "osteoartritis", "ácido hialurónico", "peso molecular", "concentración", "viscosidad", "dosis" y "temporomandibular", utilizando AND/OR como términos booleanos. El HA exógeno en sus diferentes pesos moleculares ofrece una mejora en las características histológicas y clínicas. Aparentemente, el AH de bajo y medio peso molecular presenta mejores resultados. No se encontraron estudios clínicos relacionados con el grado de viscosidad del HA. Respecto a la frecuencia de infiltración, se utilizan inyecciones únicas, inyecciones semanales durante 3 semanas, inyecciones semanales durante 5 semanas y otros protocolos. Sin embargo, su comparación es compleja. Parece haber diferencias en los efectos de las diferentes preparaciones de HA para el tratamiento de la OA-TMJ, principalmente en su peso molecular. Sin embargo, la evidencia sigue siendo escasa.

Postoperative efficacy of chondroprotectors and diacerein in dogs with osteoarthritis secondary to cranial cruciate ligament disease.

Background: Cranial cruciate ligament disease is one of the leading causes of pelvic limb claudication in canines and osteoarthritis in the stifle joint. Historically, studies have focused on surgical options to improve the stability of the stifle joint, although none of the techniques described in the literature prevents the development of osteoarthritis. Aim: This study aimed at proving the presence of osteoarthritis at the time of diagnosis of cranial cruciate ligament rupture, as well as evaluating the benefits of administering diacerein (DAR) or chondroprotective coadjuvants to the extracapsular fabelo-tibial technique. Methods: Seventeen dogs aged between 2 and 8, weighing more than 25 kg, with no predilection for breed or sex, were operated on using this technique. These were divided into three groups: DAR, Chondroprotector (CP), and Control. The animals were treated for 90 days and controlled clinically, radiologically, and using multidimensional scales for pain and quality of life. The statistical analysis used was descriptive and through non-parametric tests. Results: All patients had some degree of osteoarthritis at the beginning of the study associated with the presence of pain. The treated groups improved the claudication scores; however, the changes were significant for the DAR group. The pain score improved in all animals, including those in the Control group; however, the differences were significant only in the treated groups. On the other hand, no significant differences were detected in the radiological studies, so it would be convenient to perform this study over more than 90 days. Conclusion: The surgical treatment accompanied by drugs that act on the degradation of articular cartilage has better clinical results.

Nuevas estrategias tecnológicas para la administración de fármacos en el tratamiento de patologías articulares / New technological strategies for drug administration in the treatment of joint pathologies

Despite the availability of drugs and pharmaceutical forms for the treatment of rheumatoid arthritis and osteoarthritis symptoms, their adverse effects and lack of response to therapy reinforces the need to search for new technological formulation strategies capable of delaying the progress of the disease, with better therapeutic results and prolonged control of arthropathy. The aim of this bibliographic review was to identify new reported therapeutic approaches for these diseases. The treatment of rheumatoid arthritis and osteoarthritis is an unresolved challenge, due to the complexity of these diseases. Thus, the new therapies aim to suppress inflammatory mediators and to reduce the degradation of the extracellular matrix. In addition, the use of nano and microtechnology takes advantage of the properties of polymers, lipids, peptides, and nucleic acids to develop controlled drug release systems, aiming to obtain highly effective precision therapies, whose usefulness should be evaluated in future clinical trials.

Utilização da cannabis sativa para tratamento de dor crônica em cães / Use of cannabis sativa for the treatment of chronic pain in dogs / Uso de cannabis sativa para el tratamiento del dolor crónico en perros

A Cannabis sativa é uma planta que apresenta vários benefícios terapêuticos para animais, como tratamento da dor neuropática, inflamatória e osteoartrose. A dor é bastante recorrente na rotina clínica, sendo importante seu manejo para que seja ofertada uma melhor qualidade e conforto de vida para o paciente. O estudo objetivou identificar, a partir de evidências científicas, as características da utilização medicinal do uso de Cannabis Sativa no tratamento da dor crônica no cão, utilizando um dos seus princípios ativos, canabidiol (CBD). Foi feito uma revisão bibliográfica onde foi realizada a busca de estudos experimentais e relatos de caso em bases de dados eletrônicos, sendo incluídas fontes contendo a utilização do CBD em animais, que abordaram controle da dor, assim como escore avaliativo da dor antes, durante e após o tratamento proposto. Após eleger e analisar 54 estudos percebe-se que na medicina veterinária o uso do canabidio é insuficiente, uma vez que o foco da maior parte dos estudos clínicos é voltado para medicina humana. Ainda assim, a utilização de CBD mostrou-se eficaz, confirmando uma nova alternativa para o controle da dor em animais.(AU)

Cannabis sativa is a plant that has several therapeutic benefits for animals, such as the treatment of neuropathic and inflammatory pain and osteoarthritis. Pain is quite recurrent in the clinical routine, and its management is important to offer a better quality and comfort of life for the patient. The study aimed to identify, based on scientific evidence, the characteristics of the medicinal use of Cannabis Sativa in the treatment of chronic pain in dogs, using one of its active principles, cannabidiol (CBD). A bibliographical review was carried out in which experimental studies and case reports were searched in electronic databases, including sources containing the use of CBD in animals, which addressed pain control, as well as pain assessment score before, during and after the proposed treatment. After choosing and analyzing 54 studies, it is clear that in veterinary medicine the use of CBD is few, and the focus of clinical studies is on human medicine. The use of CBD proved to be effective, thus confirming a new alternative for pain control in animals.(AU)

El cannabis sativa es una planta que tiene varios beneficios terapéuticos para los animales, como el tratamiento del dolor neuropático e inflamatorio y la osteoartritis. El dolor es bastante recurrente en la rutina clínica, y su manejo es importante para ofrecer una mejor calidad y comodidad de vida al paciente. El estudio tuvo como objetivo identificar, con base en la evidencia científica, las características del uso medicinal de Cannabis Sativa en el tratamiento del dolor crónico en perros, utilizando uno de sus principios activos, el cannabidiol (CBD). Se realizó una revisión bibliográfica en la que se buscaron estudios experimentales y reportes de casos en bases de datos electrónicas, incluyendo fuentes que contengan el uso de CBD en animales, que abordaran el control del dolor, así como la puntuación de evaluación del dolor antes, durante y después del tratamiento propuesto. Después de elegir y analizar 54 estudios, queda claro que en medicina veterinaria el uso de cannabidio es insuficiente, ya que el foco de la mayoría de los estudios clínicos está en la medicina humana. Aun así, el uso de CBD demostró ser efectivo, confirmando una nueva alternativa para el control del dolor en animales.(AU)

Evaluation of the Effects of Gamma Radiation Sterilization on Rhein-Loaded Biodegradable Microparticles for the Treatment of Osteoarthritis.

In previous work, we reported on the design of biodegradable rhein-loaded PLGA microparticles for the treatment of osteoarthritis. Considering that a formulation designed for intra-articular administration must meet sterility requirements to guarantee its safety, in this study the effect of gamma radiation sterilization on these microparticles was evaluated. The size, morphology, and surface characteristics of the microparticles and the encapsulation efficiency of rhein were not affected by the sterilization process. Although DSC and PXRD analyses suggested otherwise, rhein release profiles were not altered by gamma radiation. The release of rhein from the microparticles was fitted to a Gompertz model. In conclusion, the results of this study suggest that gamma radiation is a suitable method for the sterilization of rhein-loaded PLGA microparticles to enable their intra-articular administration in order to provide a therapeutic solution to patients suffering from chronic joint diseases.

Eficácia e segurança da combinação Glicosamina e Condroitina comparada a medicamentos disponíveis no SUS para o tratamento de osteoartrite: revisão rápida / Effectiveness and safety of Glucosamine and Chondroitin combination compared to drugs available in Brazilian Public Health System for the treatment of Osteoarthritis: rapid review

Tecnologia: Combinação de glicosamina e condroitina. Indicação: Tratamento de osteoartrite em adultos. Pergunta: O tratamento com a combinação de glicosamina e condroitina é mais eficaz e seguro que os demais tratamentos para osteoartrite disponíveis no SUS? Métodos: Uma revisão rápida de evidências, uma revisão de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2. Resultados: Foi selecionada uma revisão sistemática, que atendiam aos critérios de inclusão. Conclusão: A combinação de glicosamina com condroitina, comparados ao placebo, mostrou ser mais eficaz para tratamento da dor e função e alcançou o segundo lugar nas alternativas terapêuticas para tratamento da dor e função

Technology: Combination of glucosamine and chondroitin. Indication: Treatment of osteoarthritis in adults. Question: Is the treatment with the combination of glucosamine and chondroitin more effective and safer than the other treatments for osteoarthritis available in the Brazilian Public Health System? Methods: A rapid review of evidence, a overview of systematic reviews, with bibliographic search done in PUBMED database, using a structured search strategy. The methodological quality of systematic reviews was assessed using AMSTAR-2. Results: A systematic review was selected, which met the inclusion criteria. Conclusion: The combination of glucosamine and chondroitin, compared to placebo, proved to be more effective for the treatment of pain and function and reached second place in therapeutic alternatives for the treatment of pain and function

[New technological strategies for drug administration in the treatment of joint pathologies]. / Nuevas estrategias tecnológicas para la administración de fármacos en el tratamiento de patologías articulares.

Despite the availability of drugs and pharmaceutical forms for the treatment of rheumatoid arthritis and osteoarthritis symptoms, their adverse effects and lack of response to therapy reinforces the need to search for new technological formulation strategies capable of delaying the progress of the disease, with better therapeutic results and prolonged control of arthropathy. The aim of this bibliographic review was to identify new reported therapeutic approaches for these diseases. The treatment of rheumatoid arthritis and osteoarthritis is an unresolved challenge, due to the complexity of these diseases. Thus, the new therapies aim to suppress inflammatory mediators and to reduce the degradation of the extracellular matrix. In addition, the use of nano and microtechnology takes advantage of the properties of polymers, lipids, peptides, and nucleic acids to develop controlled drug release systems, aiming to obtain highly effective precision therapies, whose usefulness should be evaluated in future clinical trials.

Effects of oral treatment with chondroitin sulfate and glucosamine in an experimental model of metacarpophalangeal osteoarthritis in horses.

BACKGROUND: Combined chondroitin sulfate (CS) and glucosamine (GlcN) has been widely used in oral formulations to prevent and treat osteoarthritis. CS is effective for controlling pain in osteoarthritic patients, whereas GlcN can stimulate glycosaminoglycan synthesis, thus reducing extracellular matrix degradation. Although several studies have been published on this topic, the effectiveness of treatment with oral CS and GlcN remains uncertain. The objective of this study was to analyze the progression of experimentally induced osteoarthritis in horses and verify the effectiveness of an oral compound based on CS and GlcN to treat and/or modulate this disease. The study analyzed the metacarpophalangeal joint of the left thoracic limb of 16 horses divided into two groups, with eight horses treated with CS and GlcN in the treated group (GT) and eight untreated horses in the control group (GC). Chondral lesions were induced through arthroscopy, which was defined as time-point zero (T0). Physical, ultrasonographic, and radiographic examinations and synovial fluid biomarkers measurements were performed on days 0, 30, 60, 90, and 120. At the end of the experiment (T4), arthroscopy was performed again to macroscopically evaluate the joints and collect material for microscopic analysis. RESULTS: Significant differences were observed between groups in some evaluated parameters, such as visual lameness assessment, synovial concentrations of prostaglandin E2, and ultrasound examination. However, the GT still presented slightly improved results for joint flexion angle, analysis of lameness using sensors, and histopathological analysis of chondral repair tissue, however, without the statistical significance (p>0.05). CONCLUSIONS: The treatment was considered effective in the clinical modulation of experimental osteoarthritis, with improvement of some parameters in the GT. However, this type of treatment may not be entirely effective to change the catabolic process in articular cartilage and the progressive induced chondral damage.

Use of cannabis in the treatment of animals: a systematic review of randomized clinical trials.

Cannabis is used in the treatment of several human conditions; however, its use is still less explored in veterinary medicine. This systematic review aims to summarize the evidence of efficacy and safety of the use of cannabis for the treatment of animal disease. A literature search was performed for studies published until 16 March 2021 in five databases. Randomized clinical trials (RCTs) that reported the efficacy or safety of cannabis in the treatment of animal disease were included. The RoB 2 Tool was used to assess the risk of bias. A total of 2427 records were identified, of which six studies fully met the eligibility criteria. RCTs were conducted in dogs with osteoarthritis (n = 4), with epilepsy (n = 1), and with behavioral disorders (n = 1). All studies used cannabidiol (CBD) oil in monotherapy or in combination with other drugs. Studies used CBD at 2 or 2.5 mg kg-1 twice daily (n = 4), orally (n = 5), during 4 or 6 weeks (n = 3), and compared CBD with placebo (n = 5). CBD significantly reduced pain and increased activity in dogs with osteoarthritis (n = 3). Moreover, CBD significantly reduced the frequency of seizures in dogs with epilepsy (n = 1) and the aggressive behavior of dogs (n = 1). Although promising results were identified, studies were heterogeneous and presented risks of bias that required caution in the interpretation of findings. Therefore, there was some evidence to support the use of CBD in dogs with osteoarthritis to reduce pain and increased activity, but limited evidence against epilepsy and behavioral problems. In addition, CBD was well tolerated with mild adverse effects. More RCTs with high quality of evidence are needed, including greater numbers of animal subjects, additional species, and clear readout measures to confirm these findings.

Plasma rico en plaquetas en patología ortopédica seleccionada / Platelet-Rich Plasma in Certain Orthopedic Conditions

CONTEXTO CLÍNICO: Los trastornos musculoesqueléticos comprenden más de 150 trastornos que afectan el sistema locomotor, los mismos pueden ser repentinos y de corta duración (como fracturas, esguinces y distensiones), hasta enfermedades crónicas que pueden causar limitaciones en las capacidades funcionales e incapacidad permanentes. Abarcan articulaciones (artrosis, artritis), huesos (osteoporosis, osteopenia y fracturas debidas a la fragilidad ósea, fracturas traumáticas), músculos y tendones. Los trastornos musculoesqueléticos son el factor que más contribuye a la necesidad de servicios de rehabilitación entre los niños y representan aproximadamente dos tercios de las necesidades de rehabilitación en adultos. Los trastornos musculoesqueléticos cursan con dolor (el cual puede ser persistente) y limitación de la movilidad, destreza y el nivel general de funcionamiento, lo que puede llevar a la reducción de la capacidad de las personas para trabajar.1 Datos de la Universidad de Washington relativos a la carga mundial de morbilidad, aproximadamente 1,710 millones de personas en todo el mundo sufren de algún trastorno musculoesqueléticos. Aunque la prevalencia de trastornos musculoesqueléticos varía según la edad y el diagnóstico, estos afectan a personas de todas las edades en todo el mundo. Con respecto a las lesiones de los tendones, estas afecciones son comunes no solo en población físicamente activa, sino que también aparecen en la población sedentaria. Por lo que cabe señalar, que además de los deportes, los factores intrínsecos como la nutrición, el peso y la edad, pueden influir en la ocurrencia de las lesiones de los tendones. Se debe destacar que el termino tendinitis y tendinosis no son sinónimos, aunque ambas afectan a los tendones, el término tendinitis hace referencia al proceso inflamatorio agudo y tendinosis o tendinopatía se refiere a la degeneración crónica de un tendón. Por lo tanto, las lesiones tendinosas crónicas son propensos recurrentes, que llevan a los pacientes a tener dolor, deterioro del movimiento y funcionalidad, con requerimientos de un largo periodo de recuperación. Estas lesiones agudas o crónicas, pueden afectar cualquiera de las unidades músculo tendinosas, sin embargo, se presentan con mayor frecuencia en los tendones de Aquiles, patelar, lateral del codo, manguito rotador y cadera. TECNOLOGÍA: El PRP es un preparado de pequeño volumen de plasma con una concentración de plaquetas cuatro veces superior a los niveles sanguíneos. 5 Su mecanismo de acción se basa en la activación de las plaquetas con la consiguiente liberación por parte de las mismas de factores de crecimiento implicados en los procesos de regeneración tisular, entre ellos: factor de crecimiento derivado de plaquetas, factor de crecimiento transformante beta, factor de crecimiento insulínico tipo 1, factor de crecimiento endotelial vascular, y factor de crecimiento de tejido conectivo.6 Los concentrados de PRP pueden estimular la liberación supra fisiológica de factores de crecimiento para activar la curación de lesiones crónicas y acelerar el proceso de reparación de lesiones agudas.6 Las principales ventajas del uso de PRP incluyen su seguridad ya que es un producto autólogo sin efectos adversos conocidos. Se obtiene de la sangre del propio paciente mediante un proceso de doble centrifugación que puede realizarse en laboratorios de medicina transfusional, en el quirófano o sala de procedimientos utilizando centrífugas diseñadas para tal fin. La obtención del PRP se realiza en forma ambulatoria. La vía de aplicación dependerá de cada indicación. En el tratamiento de la patología ortopédica, se utiliza en forma líquida mediante su inyección, combinado o no con anestésico local en el sitio de dolor, inserción tendinosa o en el área cruenta de la reparación tendinosa o ligamentaria. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de plasma rico en plaquetas para el tratamiento de patologías ortopédicas (tendinopatías, lesiones de ligamento y artrosis) seleccionadas. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y políticas de cobertura de diferentes sistemas de salud. RESULTADOS: Se incluyeron, diez RS, cinco GPC y nueve informes de políticas de cobertura de tecnología para indicación. CONCLUSIONES : Evidencia de baja calidad sugiere que el uso de plasma rico en plaquetas para el tratamiento de la osteoartritis de rodilla, epicondilitis lateral y reconstruccion de ligamentos cruzados anterior y de tendon aquiliano puede producir un beneficio neto marginal dado que mostró mejoría leve en la función de las articulaciones y del dolor en comparación al tratamiento habitual. Evidencia de baja calidad sugiere que el uso de plasma rico en plaquetas para el tratamiento de las tendinopatías (aquiliana, rotuliana, manguito rotador) y osteoartritis de cadera no produciría un beneficio neto dado que no se observaron mejorías en la funcionalidad de la articulación o disminución del dolor. Evidencia de moderada calidad muestra que la adición de plasma rico en plaquetas en la reparación artroscópica de la rotura del manguito rotador, probablemente produce un beneficio neto mayor dado que reduce casi en 44% el riesgo de re-roturas, además de mejorar la funcionalidad de la articulación en comparación a realizar solamente la reparación artroscopica. Las guías de práctica clínica relevadas no recomiendan el uso del plasma rico en plaquetas para el tratamiento de las osteoartritis, ni las tendinopatías. Las aseguradoras privadas de Estados Unidos no dan cobertura para el uso de plasma rico en plaquetas en estas patologías ya que lo consideran experimental. No se han encontrado evaluaciones económicas locales, por lo que se desconoce la costo efectividad del uso del plasma rico en plaquetas para estas indicaciones.

Intra-articular ozone slows down the process of degeneration of articular cartilage in the knees of rats with osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a joint disease of multifactorial etiology, affecting mainly the knees. We aimed to evaluate the effects of two different doses of gaseous ozone intra-articularly on the knee cartilage morphology of rats with osteoarthritis (OA). METHODS: The articular lesion was induced by sodium monoiodoacetate (MIA). 40 Wistar rats were divided into 4 groups: G1 control (without lesion and without treatment), G2 articular lesion (AL) (only lesion MIA-induced), G3 AL + treatment with 5 µg/mL of ozone intra-articular, and G4 AL + treatment with 10 µg/mL of ozone intra-articular. The experiment was carried out for 60 days. RESULTS: Both doses of ozone intra-articular demonstrated less reduction in joint space (G3 and G4) compared to the G2, formation of osteophytes, but without subchondral sclerosis. Ozone decreased the volumetric density of the articular lesion (VV(AL)) of tibial. The treatments recovered VV(AL) of the femur similar to G1. Ozone lower dose (G3) showed lower tibia and femur macroscopic scores. CONCLUSION: Intra-articular gaseous ozone can delay the degeneration of articular cartilage and can represents an integrative therapy in the OA treatment of knee after 60 days of treatment. For the first time the role of ozone in articular cartilage degeneration was evaluated helping to understand this therapy.