Boiogito, a Kampo medicine, improves hydrarthrosis in a rat model of knee osteoarthritis.

BACKGROUND: Hydrarthrosis, which is associated with knee pain and limited range of motion, decreases the quality of life (QOL) of patients with osteoarthritis (OA). The Kampo medicine boiogito is prescribed for the treatment of knee OA with hydrarthrosis; however, its precise mechanisms of action remain unknown. The purposes of this study were to assess the pharmacological effects of boiogito and its mechanisms of action on joint effusion in rats with surgically induced OA. METHODS: A rat OA model was produced by transecting the anterior (cranial) cruciate ligament, medial collateral ligament, and medial meniscus in the right knee joints of 7-week-old female Wistar rats. The rats were given chow containing boiogito (1 or 2%) or indomethacin (0.002 %) for 4 weeks after surgical transection. Levels of interleukin-1ß (IL-1ß) and hyaluronic acid (HA) were measured by enzyme-linked immunosorbent assay. Knee joint pain was assessed using an incapacitance tester. Osmotic water permeability in cultured rabbit synovial cells was assessed using stopped-flow analysis. RESULTS: Increased synovial fluid volume and knee joint pain were observed in rats with surgically induced OA. In rats with OA, levels of IL-1ß and HA in the articular cavity were higher but concentration of HA in synovial fluid was lower than in sham-operated rats, suggesting excessive synovial fluid secretion. Administration of boiogito improved hydrarthrosis, IL-1ß, and HA concentrations and alleviated knee joint pain in rats with OA. Indomethacin reduced IL-1ß and knee joint pain but failed to improve hydrarthrosis or HA concentration in rats with OA. Osmotic water permeability in synovial cells, which is related to the function of the water channel aquaporin, was decreased by treatment with boiogito. CONCLUSION: Boiogito ameliorates the increased knee joint effusion in rats with OA by suppressing pro-inflammatory cytokine IL-1ß production in the articular cavity and regulating function of water transport in the synovium. The improvement of hydrarthrosis by boiogito results in the increased HA concentration in synovial fluid, thus reducing joint pain. Boiogito may be a clinically useful treatment of QOL in patients with OA with hydrarthrosis.

TNF-alpha-induced aquaporin 9 in synoviocytes from patients with OA and RA.

OBJECTIVES: To determine whether aquaporins (AQPs) are expressed in the synovial tissues of patients with OA and RA, and to examine the patterns of expression in patients with and without hydrarthrosis. METHODS: AQPs were detected in synovial tissue samples from patients with OA and RA using RT-PCR and immunohistochemistry. Fibroblast-like synoviocytes (FLSs) from patients with OA and RA were cultured and stimulated with TNF-alpha. The expression of AQPs in FLSs was examined using RT-PCR and western blot analyses and the function of aquaglyceroporins was examined by a glycerol uptake assay. RESULTS: AQP1, -3 and -9 mRNAs were expressed in synovial tissues from patients with OA and RA. AQP1, -3 and -9 proteins were also detected by immunohistochemistry. AQP9 mRNA was expressed more strongly in the synovial tissues of OA patients with hydrarthrosis than those without. AQP9 mRNA and protein expression were strongly induced with TNF-alpha treatment in FLSs, whereas the expression of AQP1 and -3 mRNAs was not induced with TNF-alpha treatment. AQP9 as an aquaglyceroporin was induced by TNF-alpha. CONCLUSIONS: AQP9 mRNA was detected in synovial tissues from OA and RA patients with hydrarthrosis. AQP9 expression was strongly induced in FLSs with TNF-alpha. Although the functions of AQP1, -3 and -9 in synovial tissues remain to be elucidated, it suggested that AQP9 might be related to the pathogenesis of hydrarthrosis and inflammatory synovitis.

Calcium pyrophosphate crystals in intermittent hydrarthrosis.

A 49-year-old female presented with intermittent hydrarthrosis affecting the right knee. Numerous calcium pyrophosphate crystals were demonstrated in synovial fluid aspirated from the knee.

The distribution of proquazone and three of its metabolites in serum and synovial fluid.

In 13 patients with hydrarthrosis of the knee, samples of synovial fluid and blood were drawn at regular intervals, following a single oral dose of 600 mg proquazone. The concentrations of the unchanged drug were measured fluorimetrically and those of its three principal, active metabolites by high pressure liquid chromatography. The absorption and distribution of proquazone and its metabolites were rapid. Measurable--in some cases considerable--concentrations were to be found in both the synovial fluid and serum as early as 30 minutes after intake. High concentrations were still present up to 7 hours after intake. Considerable variations were observed, both between patients and over time for each patient, so that only qualitative rather than quantitative kinetic conclusions could be drawn from the results. The concentrations were generally lower in the synovial fluid than in the serum, which may be ascribed to the drug's high protein binding.

[Plasma concentration and systemic effect of betamethasone after intra-articular injection (author's transl)]. / Plasmakonzentration und systemische Wirkung von Betamethason nach intraartikulärer Injektion.

Plasma concentrations of betamethasone, cortisol and corticosterone were measured before and after intraarticular injection of a betamethasone-depot preparation (Celestan-Depot) by radioimmuno-assay in 31 patients. Plasma concentration of betamethasone reached its maximum of between of 10 and 17 microgram/dl 30 min after injection. It had fallen to half after 2 hours, and practically to nil from the eighth day onwards. Lowest plasma levels of cortisol and corticosterone occurred after 6--24 hours, returning to the normal range after four days. In nine patients with knee-joint effusion and synovitis the plasma concentration of betamethasone was significantly higher after 24 hours, and cortisol and corticosterone values after 48 hours significantly more suppressed, than in patients without joint effusions and signs of inflammation. The results indicate that plasma concentration of betamethasone and the suppressant effect on the adrenal cortex after intra-articular injection is similar to that after intramuscular applications. Correspondingly, systemic application of the cortisol derivatives can cause significant side effects and be contra-indicated also after intra-articular injection.

Hyaluronan, cartilage destruction and hydrarthrosis in traumatic arthritis.

The concentrations of hyaluronan (HA) and chondroitin sulfate (CS) in synovial fluids from patients with traumatic arthritis (TA) with and without hydrarthrosis were measured. The CS in synovial fluids was determined as a marker of cartilage destruction by high performance liquid chromotography. The concentration of HA in synovial fluids was lower in patients with hydrarthrosis than in healthy volunteers and patients with TA without hydrarthrosis, whereas the total amounts of HA and CS and the concentration of CS were higher in patients with hydrarthrosis. To investigate the relation between hydrarthrosis and production of HA in synovial tissues, TA synovial tissue biopsies were stained for HA with biotinylated HA binding region. The intensity of HA staining was higher in specimens from patients with hydrarthrosis than in normal and TA without hydrarthrosis specimens. Thus, there may be a correlation between hyperproduction of HA, cartilage destruction and increase in fluid volume in TA.

Transport time for salicylates from blood to joint fluid-- a test of histopathology of the synovial membrane.

Samples of blood and joint fluid, from sixty patients who had taken Bufferin, were examined for salicylates. The earliest appreance of salicylates occurred in blood between 3 and 13 minutes after intake, and in joint fluid between 11 and 36 minutes. The individual time lapse from the first appearance of salicylates in blood to that in joint fluid, designated the transport time, varied presumably with the changes of the synovial membrane caused by diseases; it was small in synovitis following trauma or focal infection and in osteoarthritis of short duration; it was greater in osteoarthritis, psoriatic arthritis, and rheumatoid arthritis of longer duration, and it showed great variations in immediate traumatic synovitis. Salicylates attained maximum concentration in joint fluid 100 to 155 minutes after intake. Similar factors as above probably accounted for the differences in these time intervals.

Hydroxyproline levels and collagenolytic activity in synovial fluids of patients with rheumatic diseases.

Free, total, and peptide hydroxyproline levels were determined in synovial fluid obtained from the knee joints of 60 patients with theumatoid arthritis (RA), and 26 patients with degenerative joint disease. In addition, in 160 synovial fluid samples obtained from 121 patients including 50 with degenerative joint disease, 60 with RA, 3 with Reiter's syndrome, 3 with hydarthrosis intermittens and 5 with ankylosing spondylitis, the collagenolytic activity was determined. The mean values of free and peptide hydroxyproline in the inflammatory and degenerative fluids were the same, but slight differences were found in the mean values of total hydroxyproline. No effect on the level of free and bound hydroxyproline was observed after treatment with intra-articular hydrocortisone and gold salts. The collagenolytic activity of synovial fluid was registered in 38% of cases of RA and in some cases of Reiter's syndrome and hydrarthrosis intermittens, but it was not found in 50 cases of degenerative joint disease or in cases of ankylosing spondylitis. During a longer observation of patients with inflammatory forms of RA a variability in the collagenolytic activity was observed in repeated examinations of the fluid obtained from the same patient; this activity appeared and disappeared. The incidence of collagenolytic activity and its values were higher in patients with active rheumatoid process and this activity was present more frequently in patients with a short history of the disease (up to 3 years). The collagenolytic activity of rheumatoid fluids was, to a high degree, inhibited by normal human serum. The problem of presence or lack of collagenolytic activity in rheumatoid fluids is discussed.