Intra-articular Route Research Articles

Multimodal approach to intraarticular drug delivery in knee osteoarthritis.

The expectations from any future disease-modifying treatment for knee osteoarthritis (KOA) are extremely high as it has to impact the joint as a whole leading to favorable alterations of diverse tissues and functions. In this light, targeting the knee only from the inside may not be biologically justified for the management of a whole joint disease such as KOA. Our hypothesis to test is whether any injectable therapeutic intervention alone can lead to disease modification of KOA which is viewed in the complexity of the modern concept of osteoarthritis (OA) as a whole joint disease. Therefore, we aimed at analyzing the intraarticular route to the KOA patient in an attempt to unveil its "biological" constraints. A comprehensive search through databases was carried out using specific keywords to add objectivity to the main messages. The literature analysis has shown that "cutting-edge" intraarticular therapies may offer a key to non-invasive symptomatic relief. Changing the course of KOA, however, may necessitate a multimodal approach towards the knee joint including a combination of intraarticular injections with interventions on multiple levels. Importantly, our understanding of OA has evolved redefining the concept of the disease, being in interaction with the human body as a whole. Any future conservative disease-modifying treatment of KOA should aim at a multimodal, holistic approach towards the knee joint including but not limited only to intraarticular injections. A combination with other interventions should be further researched.

Intra-Articular Route for the System of Molecules 14G1862 from Centella Asiatica: Pain Relieving and Protective Effects in a Rat Model of Osteoarthritis.

Current pharmacological therapies for the management of chronic articular diseases are far from being satisfactory, so new strategies need to be investigated. We tested the intra-articular pain relieving properties of a system of molecules from a characterized Centella asiatica extract (14G1862) in a rat model of osteoarthritis induced by monoiodoacetate (MIA). 14G1862 (0.2–2 mg mL−1) was intra-articularly (i.a.) injected 7 days after MIA, behavioural and histological evaluations were performed 14, 30 and 60 days after treatments. Moreover, the effect of 14G1862 on nitrate production and iNOS expression in RAW 264.7 macrophages stimulated with LPS was assessed. In vitro, 14G1862 treatment attenuated LPS-induced NO production and iNOS expression in a comparable manner to celecoxib. In vivo, 14G1862 significantly reduced mechanical allodynia and hyperalgesia, spontaneous pain and motor alterations starting on day 14 up to day 60. The efficacy was higher or comparable to that evoked by triamcinolone acetonide (100 μg i.a.) used as reference drug. Histological evaluation highlighted the improvement of several morphological parameters in MIA + 14G1862-treated animals with particularly benefic effects on joint space and fibrin deposition. In conclusion, i.a. treatment with Centella asiatica is a candidate to be a novel effective approach for osteoarthritis therapy.

A Systematic Review of Intra-Articular Ketamine for Postoperative Analgesia.

This systematic review appraises the evidence from human clinical trials comparing postoperative pain scores and opioid consumption in patients receiving intra-articular ketamine versus other modalities of analgesia after orthopedic joint procedures. Studies were identified from Embase, Scopus, and OVID Medline databases. Included studies compared patients receiving intra-articular ketamine versus other modalities of analgesia. The primary outcome of interest was postprocedural pain score and total opioid consumption, whereas secondary outcomes included time to rescue analgesic medication request, active range of motion, time to mobilization, and adverse effects. Seventeen studies were included. Dosage of ketamine varied widely from 0.25 to 2 mg/kg. Fifteen of 17 demonstrated decreased overall pain scores and decreased total postoperative opioid consumption in patients receiving intra-articular ketamine versus control groups. Included studies generally demonstrated reduced time to mobilization and increased latency until rescue analgesic medication in the intra-articular ketamine group. Patients who received intra-articular ketamine generally reported lower pain scores and had lower postoperative opioid consumption after orthopedic joint procedures. This suggests that the intra-articular route of ketamine delivery may be a useful analgesic modality, although future larger-scale trials should explore its pharmacokinetics, optimal dosing, safety, and cost-effectiveness.

Effect of Simvastatin on Iodoacetate-induced Temporomandibular Joint Osteoarthritis in Rats

Objectives: osteoarthritis (OA) is one of the harmful disorders affecting the body joint including the temporomandibular joint (TMJ). Although OA is believed to be non-inflammatory disorder, antiinflammatory agents, as simvastatin, have been used for OA treatment. Simvastatin is presumed to possess antiosteoarthritic effect beside its antilipidemic influences. The present study tried to estimate the effect of simvastatin on the monoiodoacetate (MIA)-induced TMJ osteoarthritis. Materials and methods: thirty young adult female Sprague-Dawley rats were randomly categorized into; control, osteoarthritis and osteoarthritis with simvastatin groups. Both MIA for osteoarthritis induction and simvastatin for therapy were delivered unilaterally via the intra-articular route at the right side as a single dose for each. Results: the simvastatin administration has relatively reduced the MIA-induced osteoarthritic manifestations, and/or inhibited the progress of some osteoarthritic degenerative features but it failed to control others. The most striking findings with simvastatin administration were the prominent thickening of the condylar proliferative layer, as well as the development of osteophytes at the anterior pole of mandibular condyle. The condylar cartilage matrix showed enhancement of the extracellular matrix production with simvastatin administration. Discussion: the present study has clarified the relative antiosteoarthritic effect of simvastatin intraarticular injection. Though simvastatin has valuable palliative effect, it failed to prevent the advancement of some osteoarthritic manifestations. Conclusion: temporomandibular joint osteoarthritis (TMJOA) treated by simvastatin relieve some osteoarthritic features and modulate the structure of some joint components to compensate the damaged induced structures with MIA.

BUTTER PAPER AS A COST EFFECTIVE DRESSING FOR SUPERFICIAL INTERMEDIATE THICKNESS BURN

Introduction Post-operative pain is very common distressing symptom after any surgical procedure.Different drugs in different routes have been used for controlling post-arthroscopic pain.We have compared the efficacy of analgesic effect of plain ropivacaine versus ropivacaine with dexmedetomidine as an adjuvant when administered through the intra-articular route in arthroscopic knee surgery. Materials and Methods From June 2017 to June 2019 sixty patients undergoing elective knee arthroscopy were randomly assigned to two groups (n=30). Group R received 19 ml of 0.50% ropivacaine and 1 ml of isotonic saline (total volume 20 ml) intraarticularly. Group RD received 100 μg (1 ml) of dexmedetomidine added to 19 ml of 0.50% ropivacaine intra-articularly(total 20ml).Pain was assessed using visual analogue scale(VAS) and diclofenac sodium given as rescue analgesia when VAS>4.Time of first analgesia request and total dose of rescue analgesics used in 24 hours were calculated. Results VAS score were significantly lower in Group RD, time to first analgesic requirement was significantly greater in Group RD than in Group R and total dose of analgesics used in Group RD patients was significantly less compared to patients in Group R. Conclusion Dexmedetomidine, added as adjunct to ropivacaine in patients undergoing arthroscopic knee surgery, improves the quality and duration of postoperative analgesia.

Promotion of G1/S Transition and Inhibition of Inflammatory Cytokine Production by Hydroxypyridinone-Coumarin in Osteoarthritis Rats.

BackgroundOsteoarthritis is a joint disorder characterized by articular cartilage degradation leading to joint stiffness and pain. The present study investigated the effect of hydroxypyridinone-coumarin on proliferation of chondrocytes.Material/MethodsChondrocyte proliferation was assessed by MTT assay, and distribution of cells in various phases of the cell cycle was determined using flow cytometry. RT-PCR and Western blot assays were used for assessment of mRNA and protein levels, respectively. Osteoarthritis was induced in the rats by injecting monosodium iodoacetate (5 mg/kg) by the intra-articular route. The rats in the treatment groups were intraperitoneally injected with 5, 10, or 15 mg/kg doses of hydroxypyridinone-coumarin alternately for 1 month.ResultsThe proliferation of chondrocytes was increased significantly (P<0.05) by treatment with hydroxypyridinone-coumarin in a concentration-based manner. The increase in chondrocyte proliferation by hydroxypyridinone-coumarin was maximum at 50 μM. Treatment with hydroxypyridinone-coumarin markedly increased chondrocyte population in S and G2/M phases, with subsequent reduction in G0/G1 phase. The cyclin D1, CDK4, and CDK6 levels in the chondrocytes were increased by treatment with hydroxypyridinone-coumarin. The production of IL-6, TNF-α, and IL-1β in the osteoarthritis rats was markedly suppressed by hydroxypyridinone-coumarin. Treatment of the OA rats with hydroxypyridinone-coumarin markedly reduced the expression of IκB-α and NF-κB p65.ConclusionsThe present study revealed that the proliferative potential of chondrocytes is increased by hydroxypyridinone-coumarin through acceleration of G1/S transition. Moreover, hydroxypyridinone-coumarin treatment reduced inflammatory cytokine production in the osteoarthritis rats. Therefore, hydroxypyridinone-coumarin should be evaluated further for possible use in the treatment of osteoarthritis.

Efficacy of Intra-Articular Dexmedetomidine for Postoperative Analgesia in Arthroscopic Knee Surgery

Introduction Post-operative pain is very common distressing symptom after any surgical procedure.Different drugs in different routes have been used for controlling post-arthroscopic pain.We have compared the efficacy of analgesic effect of plain ropivacaine versus ropivacaine with dexmedetomidine as an adjuvant when administered through the intra-articular route in arthroscopic knee surgery. Materials and Methods From June 2017 to June 2019 sixty patients undergoing elective knee arthroscopy were randomly assigned to two groups (n=30). Group R received 19 ml of 0.50% ropivacaine and 1 ml of isotonic saline (total volume 20 ml) intraarticularly. Group RD received 100 μg (1 ml) of dexmedetomidine added to 19 ml of 0.50% ropivacaine intra-articularly(total 20ml).Pain was assessed using visual analogue scale(VAS) and diclofenac sodium given as rescue analgesia when VAS>4.Time of first analgesia request and total dose of rescue analgesics used in 24 hours were calculated. Results VAS score were significantly lower in Group RD, time to first analgesic requirement was significantly greater in Group RD than in Group R and total dose of analgesics used in Group RD patients was significantly less compared to patients in Group R. Conclusion Dexmedetomidine, added as adjunct to ropivacaine in patients undergoing arthroscopic knee surgery, improves the quality and duration of postoperative analgesia.

Disposition and effect of intra-articularly administered dexamethasone on lipopolysaccharide induced equine synovitis

BackgroundDexamethasone is used for the intra-articular route of administration in management of aseptic arthritis in horses. Despite its widespread use there is very little quantitative data of the disposition and response to dexamethasone. The aim of this study was to investigate and describe the synovial fluid and plasma dexamethasone concentration over time and to explore the relation between synovial fluid concentration and response using clinical endpoints as response biomarkers after IA injection of dexamethasone disodium salt solution in an equine model of synovitis.ResultsInflammation was induced in the radiocarpal joint of six horses by injection of 2 ng lipopolysaccharide (LPS). Two hours later either saline or dexamethasone was injected in the same joint in a two treatment cross over design. Each horse was treated once with one of the six doses dexamethasone used (0.01, 0.03, 0.1, 0.3, 1 or 3 mg) and once with saline. Dexamethasone was quantified by means of UHPLC–MS/MS. Dexamethasone disposition was characterised by means of a non-linear mixed effects model. Lameness was evaluated both objectively with an inertial sensor based system and subjectively scored using a numerical scale (0–5). Joint circumference, skin temperature over the joint and rectal temperature were also recorded. The LPS-challenge induced lameness in all horses with high inter-individual variability. Dexamethasone significantly decreased lameness compared with saline. Other variables were not statistically significant different between treatments. Objective lameness scoring was the most sensitive method used in this study to evaluate the lameness response. A pharmacokinetic/pharmacodynamic model was successfully fitted to experimental dexamethasone and lameness data. The model allowed characterization of the dexamethasone synovial fluid concentration–time course, the systemic exposure to dexamethasone after intra-articular administration and the concentration–response relation in an experimental model of synovitis.ConclusionsThe quantitative data improve the understanding of the pharmacology of dexamethasone and might serve as input for future experiments and possibly contribute to maintain integrity of equine sports.

Pain relief following arthroscopy: A comparative study of intra-articular bupivacaine, neostigmine, and clonidine

Background and Aims: Quality pain relief after arthroscopic knee surgery is not only a challenge but also a necessity for adequate postoperative rehabilitation after anterior cruciate ligament (ACL) repair. In the past, different agents were tried for pain relief by parenteral and intra-articular routes with varying results. The aim of the present study is to compare the analgesic effects of intra-articularly instilled bupivacaine, clonidine, and neostigmine in the postoperative period after ACL repair. Methods: This was a double-blind study on three groups of patients, wherein bupivacaine, clonidine, or neostigmine was instilled intra-articularly at the end of knee arthroscopic ACL repair and the postprocedure pain relief was assessed. All patients received subarachnoid block with the same volume (17.5 mg) of 0.5% bupivacaine heavy. Postoperative pain was assessed with the visual analog scale (VAS), and rescue analgesics were prescribed for a more than tolerable pain. Pain score was observed at definite intervals and rescue doses were charted in crosstabs. Efficiency of the three drugs in question was tested with Bonferroni technique. Results: VAS scores at 2 h, 6 h, and 12 h were lowest with bupivacaine followed by clonidine and neostigmine. The requirement of rescue analgesics was also in the same order. Conclusion: On the basis of this study, we conclude that intra-articularly instilled bupivacaine provides superior and long-lasting analgesia than clonidine and neostigmine.

A prospective comparative study between intravenous and intraarticular tranexamic acid administration in decreasing the perioperative blood loss in total knee arthroplasty

PurposeTotal knee arthroplasty (TKA) is a common and safe surgical procedure, but the high perioperative blood loss is a cause of concern. Use of tranexamic acid to address this issue has gained popularity recently but no clear consensus is available regarding its ideal mode of administration. We conducted this study to evaluate and compare the efficacy of intravenous as well as intraarticular routes of administration of tranexamic acid. Methods300 patients planned for B/L Total Knee Arthroplasty were randomized into 3 groups; group IV (Intravenous, n = 100), group IA (Intraarticular, n = 100) and a control group (n = 100). In group IV, patients received 1 g tranexamic acid intravenously; in group IA 2.5 g tranexamic acid was given intraarticular in both knees and a control group which did not receive tranexamic acid. The primary outcomes measures were total blood loss (intraoperative blood loss + drain amount), pre and post surgery haemoglobin levels and the transfusion rate and quantity. The secondary outcome measures were complications. ResultsAdministration of tranexamic acid through either of the two routes resulted in statistically significant decrease in the total perioperative blood loss and transfusion requirement. There was no statistically significant difference in the results between the two test groups. ConclusionsBoth intravenous as well as intraarticular administration of tranexamic acid provided excellent results no known adverse effects. However neither of the two modalities should be considered superior to the other.

Mycoplasma leachii causes polyarthritis in calves via the blood route but is not associated with pneumonia

Mycoplasma leachii was initially isolated from arthritic calves in South Queensland, Australia, and its ability to cause clinical polyarthritis in calves was demonstrated by experimental infection. However, the source of M. leachii infection in calves and its means of spreading are not well known. In this study, one-month-old calves were inoculated with cultures of M. leachii or joint fluid (collected from M. leachii-infected calves) through the intraarticular, intravenous, intratracheal, intranasal or oral routes. Multidisciplinary procedures, including clinical assessment, etiology assessment, pathology and immunohistochemistry (IHC), were used to evaluate the pathogenicity of M. leachii in calves and to elucidate the transmission route of M. leachii infection in calves. The results showed that all calves inoculated intraarticularly with cultured GN407 or joint fluid and two-thirds of the calves inoculated intravenously with joint fluid developed severe polyarthritis, and the M. leachii antigen was detected in the joints of all infected calves by IHC and PCR. In contrast, calves inoculated with cultured M. leachii or joint fluid through the intratracheal, intranasal or oral routes did not show any M. leachii infection in the clinical assessment, etiology assessment, or pathology and IHC results. These results indicated that polyarthritis caused by M. leachii in calves is transmitted via the blood route; however, this disease is not transmitted through the respiratory or digestive routes. In addition, the M. leachii antigen was not detected in the lungs of all the inoculated calves using IHC and PCR, indicating that M. leachii is not associated with pneumonia, even in the calves inoculated through the respiratory duct. These findings are important information for the prevention and control of calf polyarthritis caused by M. leachii.

Drug-fortified liposomes as carriers for sustained release of NSAIDs: The concept and its validation in the animal model for the treatment of arthritis

Drug-fortified cationic liposomes of 6‑methoxy‑2‑naphthylacetic acid (6‑MNA) were prepared and characterized by various techniques. The residence time of drug-fortified liposomes in joint cavity was evaluated by intra-articular (IA) administration of the radio-labeled (99mTc) liposomal formulation in the inflamed joints in rats. The cationic liposomal formulation composed of 6‑MNA (3) as an active agent, its double salt (4) with the lipid 1,2‑distearoyl‑sn‑glycero‑3‑phosphoethanolamine (DSPE), and pharmaceutically acceptable excipients such as hydrogenated soyabean phospatidylcholine (HSPC) and 1,2‑dioleyloxy‑3‑trimethylammoniumpropane chloride (DOTAP) were developed using thin film hydration technique. The cryo-TEM analysis confirmed that the prepared optimized liposomal formulation (DFL-2) was a mixture of small unilamellar vesicles (SUVs), large unilamellar vesicles (LUVs) and multilamellar vesicles (MLVs). In addition, the TEM analysis confirmed that the prepared liposomes were of spherical in shape having liposome size in the range of 500–900 nm and zeta potential of about +30 mV. The developed cationic liposomes exhibited sustained release profile of payload of 6‑MNA for over >12 h and about five times higher retention in the inflamed animal joints after 24 h (by scintigraphy of the joints) as compared to the plain 6‑MNA solution when administered by IA route. The anti-inflammatory activity of prepared liposomal composition is evaluated by Freund's adjuvant induced arthritic model in rats. The liposomal formulation was well tolerated by all animals indicating good biocompatibility. Further, the cationic liposomal formulation treated group showed decreased erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level in comparison to the control and the standard groups in the in vivo study. The improved efficacy of the drug-fortified liposomal formulation was due to the coupled effect of longer retention and sustained release of the active drug 6‑MNA in the joints. From the obtained results it could be concluded that the combined effect of the cationic charge on the drug-fortified liposomes and the inherent affinity of the active agent towards the synovial joint tissues, coupled with slow release of the active drug due to double salt approach at the site of administration could potentially decrease the frequency of IA drug administration. Hence such a formulation could prove to be a therapeutic boon for the management of late stage arthritis.

Intra-articular delivery of a nanocomplex comprising salmon calcitonin, hyaluronic acid, and chitosan using an equine model of joint inflammation.

Polyelectrolyte nanoparticle constructs (NPs) comprising salmon calcitonin (sCT), chitosan (CS), and hyaluronic acid (HA) were previously established as having anti-inflammatory potential when injected via the intra-articular (i.a.) route to a mouse model. We attempted to translate the formulation to a large animal model, the lipopolysaccharide (LPS)-stimulated equine model of joint inflammation. The aim was to manufacture under aseptic conditions to produce sterile pyrogen-free NPs, to confirm physicochemical characteristics, and to test toxicity and efficacy in a pilot study. NP dispersions were successfully formulated using pharmaceutical-grade source materials and were aseptically manufactured under GMP-simulated conditions in a grade A modular aseptic processing workstation. The NP formulation had no detectable pathogen or endotoxin contamination. NPs were then tested versus a lactated Ringer's solution control following single i.a. injections to the radiocarpal joints of two groups of four horses pre-treated with LPS, followed by arthrocentesis at set intervals over 1week. There was no evidence of treatment-related toxicity over the period. While there were no differences between clinical read-outs of the NP and the control, two synovial fluid-derived biomarkers associated with cartilage turnover revealed a beneficial effect of NPs. In conclusion, NPs comprising well-known materials were manufactured for an equine i.a.-injectable pilot study and yielded no NP-attributable toxicity. Evidence of NP-associated benefit at the level of secondary endpoints was detected as a result of decreases in synovial fluid inflammatory biomarkers.

Effect of Boron on the Repair of Osteochondral Defect and Oxidative Stress in Rats: an Experimental Study.

The aim of this study was to investigate the effect of boron on the repair of osteochondral defect and also on some antioxidant and oxidant parameters of both cartilage tissue and blood. A total of 24 adult male Wistar rats weighing between 350 and 400g were used in the study. Animals were randomly divided into control (n = 8), boron (n = 8) and hyaluronic acid (HA) groups (n = 8). Under general anesthesia, a cylindrical full-thickness osteochondral defect 1.5mm in diameter and 2mm in depth was formed using a drill on the anterior side of the articular surface of the femur condyle. Boron group received 0.1ml (10mg/kg) of boron and HA group received 0.1ml of HA, whereas control group received 0.1ml of physiological saline solution. All agents administered intraarticular route and once a week for four times. At the end of the third month, the animals were euthanized and blood and joint tissue malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase levels were measured. Defected femoral condyles of the rats were removed for a histopathological examination. Histopathology revealed that the total cartilage repair score of the HA group was better than those detected in boron and control groups. Blood and articular cartilage GSH, SOD, and catalase levels were higher in the boron and HA groups as compared to the control group, while MDA level was lower compared to the control group. In conclusion, it was suggested that boron was not as effective as HA in the repair of osteochondral defect, but its antioxidant property was superior to HA.

Benzoxime inhibits matrix metalloproteinase-13 activation and cartilage damage in osteoarthritis rats via inhibition of NF-κB pathway

Purpose: To investigate the effect of benzoxime on degradation of articular cartilage in a rat model of osteoarthritis (OA), and the mechanism involved.Methods: The OA rat model was prepared by injecting monosodium iodoacetate (MIA) intra-articularly to Wistar rats. Rats in the treatment group were given benzoxime (5 mg/kg) daily for 21 days through the intra-articular route. The animals were then examined for behavioral changes by assessment of asymmetry in bearing weight and paw withdrawal threshold of the hind limb. Western blot assay was used for the analysis of inflammatory cytokine expressions.Results: The expression of P2X purinoceptor 7 receptor (P2X7R) mRNA was significantly elevated in the OA rats (p &lt; 0.02). However, benzoxime treatment caused a marked decrease in the level of P2X1-8R mRNA. Benzoxime treatment also prevented asymmetry in bearing weight, decreased paw withdrawal threshold, and inhibited the expressions of interleukin-1β, interleukin-6 and tumor necrosis factor-α in plasma and cartilage. Moreover, benzoxime exhibited significant inhibitory effects on the expressions of P2X7R, matrix metalloproteinase (MMP)-13 and prostaglandin E2 (PGE2) in cartilage tissue. It also significantly suppressed OA-induced increases in the levels of inhibitor of nuclear factor-κB (NF-κB) kinase (IKK)α, IKKβ, IκBα and NF-κB p65, and blocked OA-induced increases in the expressions of P2X7R, MMP-13 and PGE2.Conclusion: These results demonstrate that benzoxime prevents cartilage degradation in OA rats by targeting NF-κB signaling pathway. Thus, benzoxime possesses clinical and therapeutic potentials for the prevention of cartilage degradation in OA.Keywords: Interleukin-1β, Purinoceptor-7, Benzoxime, Osteoarthritis, Prostaglandin, Matrix metalloproteinases

LOX-1-deficient mice are resistant to zymosan-induced arthritis: A mini review

Background: Some reports have shown that metabolic syndrome, including hypertension, hyperlipidemia, and diabetes mellitus, contributes to osteoarthritis (OA) development. Further, lectin-like oxidized low-density lipoprotein (ox-LDL) and ox-LDL receptor-1 (LOX-1), which contributes to atherosclerosis, have also been considered factors contributing to OA development. Several studies have suggested that the LOX-1/ox-LDL system is involved in OA development in vitro. We have suggested the same and conducted in vitro and in vivo studies to validate this concept. However, the role of the LOX-1/ox-LDL system in OA development has not been clarified. This study aimed to identify the mechanism of the LOX-1/ox-LDL system to clarify OA development. Methods: A zymosan-induced arthritis model was used to identify the mechanism of the LOX-1/ox-LDL system using LOX-1-knockout (KO) mice. Zymosan was administered via the intra-articular route to induce arthritis. Results: From our experiment, we found that the LOX-1/ox-LDL system contributes to OA development through matrix metalloproteinase-3. Conclusion: Our findings suggest that the treatment of abnormal lipid metabolism may contribute to the prevention and suppression of arthritis.

The comparative efficacy and safety of topical and intravenous tranexamic acid for reducing perioperative blood loss in Total knee arthroplasty- A randomized controlled non-inferiority trial

BackgroundTotal Knee Arthroplasty (TKA) can be associated with significant perioperative blood loss and blood transfusions. This is a prospective randomised non-inferiority trial comparing intraarticular (IA) and intravenous (IV) routes of administering Tranexamic acid (TXA) with regard to efficacy and safety. MethodsA total of 113 patients who underwent primary unilateral TKA from January to June 2017 randomly received either 1.5g TXA in 100mL normal saline solution (IA group, n=58) or 10mg/kg TXA (IV group, n=55) at 10min before the tourniquet inflation and at tourniquet release. Haemoglobin (Hb) drop on third day (primary outcome), visible blood loss (VBL), hidden blood loss (HBL), total blood loss (TBL), transfusion requirement, incidence of deep vein thrombosis (DVT), wound complications and renal function derangement (secondary outcomes) were recorded. ResultsThe mean difference in haemoglobin drop between both groups was 0.25g/dL with 90% CI of −0.07 to 0.58. Since the lower bound of 90% CI was above equivalence margin of −0.35, IA group was found to be non-inferior to IV group in terms of Hb drop. The mean difference between both groups of VBL, HBL and TBL were 0.85mL (p value 0.90), −7.9mL (p value 0.90) and −6.2mL (p value 0.93) respectively. Transfusions and wound complications were statistically insignificant. None of the patients had DVT or renal function derangement. ConclusionIA TXA is not inferior to IV TXA with regard to efficacy and safety and may be preferred considering ease of administration and lack of systemic absorption.

Intra-articular dexmedetomidine and clonidine for postoperative analgesia in arthroscopic knee surgery

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Many drugs have been used for postoperative pain management which is a common and distressing symptom after knee arthroscopy. But no single ideal intra-articular drug has been found. This study was done to assess the efficacy of intra-articular dexmedetomidine and clonidine for postoperative pain relief in patients undergoing arthroscopic knee surgeries&lt;span lang="EN-IN"&gt;.&lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; Fifty patients of American Society of Anaesthesiologists of grade I/II, aged 20-70 years posted for arthroscopic knee surgery were randomly divided into groups I (clonidine group) and group II (dexmedetomidine group). 25 patients in group I received 1 µg/ kg of clonidine diluted to 20 ml in normal saline and group II patients received 1 µg/kg of dexmedetomidine diluted to 20 ml in normal saline via intra-articular route at the end of the surgery. Visual analogue score (VAS), time to give the first dose of analgesia and total dose of analgesic required in first 24 hours was evaluated in each group.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; VAS score was lower and time to first analgesic requirement was greater in Group II in comparison to Group I which was statistically significant. Total dose of analgesic used in Group II patients was significantly less compared to patients in Group I which was statistically significant&lt;span lang="EN-IN"&gt;. &lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Intra-articular dexmedetomidine is more effective in providing prolonged postoperative analgesia after arthroscopic knee procedures and reduces the total dose of analgesic required postoperatively compared to clonidine&lt;span lang="EN-IN"&gt;.&lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt; &lt;/p&gt;

The establishment of a porcine rheumatoid arthritis model: Collagen induced arthritis minipig model

Rheumatoid arthritis (RA) research has been largely dependent on collagen induced arthritis (CIA) rodent models, however, they may not translate well to humans due to innate differences in the size, physiology and lifespan. The present study aimed to establish a CIA porcine model with the physical, hematological, histopathological and etiological properties closer to their human equivalent in an attempt to better meet the needs of RA research.Three month old minipigs were administered of bovine type II collagen (CII) emulsified with complete Freund's adjuvants on Day 1 and incomplete Freund's adjuvants on Day 22, via an intradermal or intra-articular route. The clinical, radiological and hematological assessments of immunized animals were made periodically until Day 43, during which period the onset and progression of arthritis was recorded and characterized. In addition, the histopathological and micro-tomographic assessments of the cartilage degradation with regard to mononuclear cell infiltration, and joint deformity indicated a higher severity in the intradermal injection group over the intra-articular group.With confirmation of the susceptibility to heterogeneous CII for arthritis induction in minipig, the potential suitability of this test system as a large animal model for RA has been demonstrated.

Particles for Local Delivery of Proteins Using Intra-Articular Route.

Designing a vehicle for local delivery of proteins using intra-articular route is an attractive option to minimize the adverse effects associated with systemic exposure and to maximize the efficacy. Slowly dissolving silylated microparticles are designed with specific size and shape that are capable of extending the retention time of a model protein (bovine serum albumin) in the murine knee joint. No cytotoxicity is observed for the reconstituted formulation when tested against synovial fibroblasts and RAW 264.7 macrophages.