Effects of Glutaraldehyde on Synovial Tissue

2019

Objective The aim of this animal study was to investigate the short and long-term local histomorphologic effects and the utility of intra-articular application of ibuprofen. Methods Forty-six Wistar Albino rats were used in the study. The rats were randomized into 5 groups of 8 and a sham group of 6. The 40 rats in the study groups were anaesthetised with 60 mg/kg of ketamine, then 0.25 ml ibuprofen (25 mg) was injected to the right knee joint of each rat (ibuprofen group) and 0.25 ml 0.9% saline to the left knee joint as the control group. To the 6 rats in the sham group, only puncture was applied to both knee joints. The rats in each of the 5 study groups were sacrificed on days 1, 2, 7, 14 and 21 respectively. The histomorphologic changes were graded on a 6-point scale regarding inflammation of the synovia, cartilage tissue, and subchondral bone. Inflammation scores were compared using the Mann Whitney U-test and comparisons of the sacrifice day and drug used were evaluated with ...

Arthritis and Rheumatism, 2005

ObjectiveTo examine the concentration of glucosamine in the synovial fluid and its pharmacokinetics in serum in a large animal model following dosing with glucosamine HCl at clinically relevant levels.To examine the concentration of glucosamine in the synovial fluid and its pharmacokinetics in serum in a large animal model following dosing with glucosamine HCl at clinically relevant levels.MethodsEight adult female horses were studied. After an overnight fast, glucosamine HCl (20 mg/kg of body weight) was administered by either nasogastric (NG) intubation or intravenous (IV) injection. Blood samples were collected before dosing and at 5, 15, 30, 60, 120, 180, 240, 360, 480, and 720 minutes after dosing. Synovial fluid samples were collected from the radiocarpal joints 48 hours before dosing and at 1 and 12 hours after dosing. Glucosamine was assayed by fluorophore-assisted carbohydrate electrophoresis.Eight adult female horses were studied. After an overnight fast, glucosamine HCl (20 mg/kg of body weight) was administered by either nasogastric (NG) intubation or intravenous (IV) injection. Blood samples were collected before dosing and at 5, 15, 30, 60, 120, 180, 240, 360, 480, and 720 minutes after dosing. Synovial fluid samples were collected from the radiocarpal joints 48 hours before dosing and at 1 and 12 hours after dosing. Glucosamine was assayed by fluorophore-assisted carbohydrate electrophoresis.ResultsThe maximum concentration of glucosamine in serum reached ∼300 μM (∼50 μg/ml) following IV dosing and ∼6 μM (∼1 μg/ml) following NG dosing. Synovial fluid concentrations reached 9–15 μM with IV dosing and 0.3–0.7 μM with NG dosing, and remained elevated (range 0.1–0.7 μM) in most animals even at 12 hours after dosing. Following NG dosing, the median serum maximal concentration of 6.1 μM (range 4.38–7.58) was attained between 30 minutes and 4 hours postdose. The mean apparent volume of distribution was 15.4 liters/kg, the mean bioavailability was 5.9%, and the mean elimination half-life was 2.82 hours.The maximum concentration of glucosamine in serum reached ∼300 μM (∼50 μg/ml) following IV dosing and ∼6 μM (∼1 μg/ml) following NG dosing. Synovial fluid concentrations reached 9–15 μM with IV dosing and 0.3–0.7 μM with NG dosing, and remained elevated (range 0.1–0.7 μM) in most animals even at 12 hours after dosing. Following NG dosing, the median serum maximal concentration of 6.1 μM (range 4.38–7.58) was attained between 30 minutes and 4 hours postdose. The mean apparent volume of distribution was 15.4 liters/kg, the mean bioavailability was 5.9%, and the mean elimination half-life was 2.82 hours.ConclusionClinically relevant dosing of glucosamine HCl in this large monogastric animal model results in serum and synovial fluid concentrations that are at least 500-fold lower than those reported to modify chondrocyte anabolic and catabolic activities in tissue and cell culture experiments. We conclude that the apparent therapeutic benefit of dietary glucosamine on pain and joint space width in humans and animals may be secondary to its effects on nonarticular tissues, such as the intestinal lining, liver, or kidney, since these may be exposed to much high levels of glucosamine following ingestion.Clinically relevant dosing of glucosamine HCl in this large monogastric animal model results in serum and synovial fluid concentrations that are at least 500-fold lower than those reported to modify chondrocyte anabolic and catabolic activities in tissue and cell culture experiments. We conclude that the apparent therapeutic benefit of dietary glucosamine on pain and joint space width in humans and animals may be secondary to its effects on nonarticular tissues, such as the intestinal lining, liver, or kidney, since these may be exposed to much high levels of glucosamine following ingestion.

Arthritis & Rheumatism, 2002

Objective. To determine if oral glucosamine (GlcN) improves joint biology after acute damage by a protease. Methods. The effect of 8 weeks of dietary GlcN (20 or 100 mg/kg/day) on knee joint cartilage was evaluated in 2.2-kg male NZW rabbits with and without damage introduced by intraarticular injection of chymopapain (CP). Cartilage was evaluated histologically and scored according to the Mankin scale. Analyses of total hydroxyproline and glycosaminoglycan (GAG) contents and reverse transcription-polymerase chain reaction (RT-PCR) analysis of selected genes were performed. Results. After 8 weeks, there was no effect of GlcN on the GAG content of normal cartilage. Both levels of GlcN treatment significantly increased the sulfated GAG content in the cartilage of the medial femoral condyle in damaged and contralateral knees, but did not change the collagen content. In CP-injected knees, there was still some loss of surface proteoglycan (PG) that was not completely corrected by dietary GlcN. Even after 8 weeks, levels of messenger RNA (mRNA) detected by RT-PCR showed changes indicative of damage and repair, such as elevated type II collagen mRNA, and these levels were not influenced by GlcN treatment. Meniscal GAG content was increased in the contralateral knee of rabbits receiving high-dose GlcN, but was decreased in those receiving no GlcN or low-dose GlcN. Neither diet nor treatment affected the meniscal collagen content. Conclusion. These results suggest that oral GlcN treatment might be useful in a situation where GlcN is limiting, such as where there is a rapid replacement of cartilage PG. Glucosamine (GlcN) is a dietary supplement that is proposed to be "disease-modifying," that is, capable of protecting or restoring cartilage structure and slowing the development of osteoarthritis (OA) (1). A number of human studies have been completed or are under way in Europe, Canada, and the US to evaluate GlcN alone or in combination with chondroitin sulfate. Recent metaanalyses of completed studies suggest that there is relief of pain in ϳ50% of patients, which is equivalent to the results with low-dose nonsteroidal antiinflammatory drugs and higher than the results with placebo (typically, 30% response) (1-3). A recent study demonstrating that oral GlcN preserves cartilage height in the knee, as assessed over 3 years by standardized radiography, is encouraging (4). Intraarticular, intramuscular, and oral dosing all appear to work, but the maximum pain relief and effect on symptoms is not reached for several weeks and persists for several weeks or months after stopping the drug, which is suggestive of a slow adaptive response (3). There are no studies that link pain or symptomatic relief to the preservation of cartilage structure. Additionally, there is no information on the duration of GlcN treatment needed to affect proteoglycan (PG) restoration, which might be expected to be much more rapid than relief of symptoms if it is a direct effect on the chondrocyte. Because of its availability as the drug GlcN sulfate (Dona 200S; Rotta Research Laboratorium, Monza, Italy) in Europe and its use in animals (5,6), an extensive toxicologic and pharmacologic database on GlcN has been compiled, and GlcN has an excellent safety record. The basic biologic and biochemical studies on possible mechanisms of action of GlcN in cartilage Supported by a Biomedical Science grant from the Arthritis Foundation.

Revista Brasileira de Ortopedia (English Edition), 2010

Objective: To evaluate the effects of intra-articular injections of corticosteroids, native hyaluronic acid and branched-chain hyaluronic acid in experimentally-induced osteoarthrosis. Methods: 44 rabbits underwent anterior cruciate ligament resection and were then divided into four groups of eleven. Group 1: one intra-articular injection of saline solution per week, for three weeks; Group 2: three injections (one per week) of native hyaluronic acid; Group 3: three injections (one per week) of branched-chain hyaluronic acid; Group 4: two injections of betamethasone with an interval of three weeks. The cartilage of the tibial plateaus was evaluated macroscopically twelve weeks after surgery. Changes to the joint surface were graded as follows: Grade 0: smooth joint surface without relief changes; Grade 1: rough surface without any depressions; Grade 2: similar to grade 1, but with depressions on the joint surface; and Grade 3: subchondral bone exposure. The statistical analysis consisted of the use of Student's t test, chi-square test and analysis of variance (ANOVA). The significance level used was 5%. Results: A statistical difference was found between the control group and the three study groups (2, 3 and 4) in relation to the development and severity of arthrosis. However, there was no difference between the groups regarding the drugs studied. Conclusion: A similar degree of attenuation of the osteoarthrosis process in the rabbits' knees was found with the use of intra-articular injections of low-molecular-weight and high-molecular-weight glycosaminoglycans, and the corticosteroid betamethasone, compared with placebo.

Experimental physiology, 1991

After the injection of [3H]acetyl-labelled hyaluronan into normal rabbit knee joints, about 90% of its isotope content was ultimately accounted for as 3H2O. The rate of elimination of hyaluronan from synovial fluid was therefore estimated from changes in the level of 3H2O in plasma. The half-life of plasma 3H2O was 6.2 days (S.D. 0.7). As estimated from its metabolism to 3H2O, the mean intrasynovial half-life of [3H]hyaluronan of high molecular weight (modal relative molecular mass (Mr) greater than 6.0 x 10(6) was 13.2 h (range 11-15.5 h; n = 4); an otherwise identical preparation of low molecular weight (modal Mr 0.09 x 10(6] exhibited a mean half-life of 10.2 h (range 7.8-13.5 h; n = 4). The difference between the two groups was significant (P = 0.029). Both estimates were nevertheless close to those determined by others in the same species for injected proteoglycans (Mr 2.5 x 10(6), t1/2 = 12 h) and for endogenous hyaluronan calculated from changes in concentration during intrav...

Annals of the Rheumatic Diseases, 2005

To examine the therapeutic efficacy of N-acetylglucosamine (GlcNAc) in rabbits with experimental osteoarthritis (OA). Methods: Experimental OA was induced in rabbits by anterior cruciate ligament transection (ACLT). In the first study, rabbits (six in each group) received intramuscular injections of GlcNAc or normal saline three times a week starting 1 week postoperatively. In the second study, rabbits (eight in each group) were injected intra-articularly with GlcNAc (either once or twice a week) or normal saline. In the third study, rabbits (seven in each group) were injected intra-articularly twice a week with either GlcNAc, hyaluronan, or normal saline. Animals were killed 8 weeks after ACLT for macroscopic and histological assessment of the knee joints. Results: Intramuscular administration of GlcNAc in rabbits with experimental knee OA did not show chondroprotective effects but showed mild anti-inflammatory activity. In contrast, intra-articular administration of GlcNAc twice a week reduced cartilage degradation. Additionally, intra-articular GlcNAc also suppressed synovitis. Once a week intra-articular injections of GlcNAc did not demonstrate therapeutic efficacy. The chondroprotective efficacy of GlcNAc was better than that of viscosupplementation treatment with hyaluronan. Conclusion: Intra-articular GlcNAc has chondroprotective and anti-inflammatory activity in experimental OA.

2017

An effect of antiseptics on the joints tissue growing organism requires further study, which is primarily due to the need of foresight and reducing the consequences of carried diseases. The aim. of the reserch is to determine the concentration of the octenidine dihydrochloride ("Octenisept"), antiseptics, whose effectiveness is proved concerning to a wide range of microorganisms, in which it can be used in septic diseases of the musculoskeletal system of the growing organism. The research of influence on the joints tissue the octenidine dihydrochloride in different partings studied in experiments on 40 immature 2-month-old white laboratory rats. Reactive and inflammatory changes, which expressed in different degrees, noted in the synovial layer of the animals‘ joint capsule, virtually in all animals in an experimental and control group. Significant differences observed in animals of the first control group (6 hours after washing the joint) where the thickness index of synovial layer, concerning the intact animals were by 16, 8 % higher. The thickness of the capsule was significantly higher than in the capsule of the intact animals and animals in the knee joint study group. Thus, in the group of animals where the joint was washed on octenidine dihydrochloride at 1:4 dilution, the thickness of the capsule was by 33.6 % more, in the group of animals with joint lavage octenidine dihydrochloride at a dilution of 1:3 through 6:00 capsule thickness values were (about intact animals) by 38.8 % higher, and after 12 hours - by 22.5 %. Based on the results obtained on the effect of octenidine dihydrochloride (taken at different dilutions) in the tissue of the knee joint, revealed that it has no toxic effect on articular cartilage and synovial membrane and other components of the joint. Using of the preparation at the 1:4 dilution does not cause inflammatory changes in the tissues of the joints, laboratory animals, allowing its using in this concentration in the treatment of inflammatory diseases of the musculoskeletal system in the growing organism.

Osteoarthritis and Cartilage, 2009

Objective: To compare synovial glucosamine levels in normal and inflamed equine joints following oral glucosamine administration and to determine whether single dose administration alters standard synovial parameters of inflammation.

Canadian Journal of Physiology and Pharmacology, 2004

Analgesics are commonly injected intra-articularly for analgesia after arthroscopic surgery, especially of knee joints. The aim of this study was to research the effects of ketorolac and morphine on articular cartilage and synovial membrane. This study used rabbit right and left hind knee joints. The treatments, saline, morphine, or ketorolac, were administered intra-articularly 24 h after injection, and 5 joints from animals in each drug group were chosen randomly to form Group I and subgroups of Group I. The same procedures were applied after 48 h and 10 days of injection to form Groups II and III, respectively, and subgroups of these groups. Knee joints were excised and a blinded observer evaluated the histopathology according to inflammation of the articular cartilage, inflammatory cell infiltration, hypertrophy, and hyperplasia of the synovial membrane. No histopathological changes were found in the control groups. In the ketorolac and morphine groups, there were varying degree...