6-ketoprostaglandin-f1-alpha and Arthritis

This prospective randomised study was designed to assess the effect of an intra-articular injection of sodium hyarulonate on internal derangement in disorders of the temporomandibular joint. Fifteen patients (4 men, 11 women, mean (SEM) age 33(3) years) with unilateral internal derangement of the temporomandibular joint without radiographic evidence of the condylar degeneration who were randomly allocated to have arachidonic acid metabolites (n = 9) or cytokines (n = 6) measured in synovial fluid. The preauricular area was disinfected and anaesthetised locally with 1% lignocaine hydrochloride. Synovial fluid was collected by rinsing the joint with saline 5 ml. Sodium hyaluronate 1 ml (10 mg) was then injected into the superior compartment of the temporomandibular joint. The treatment was repeated after two weeks. The effects of sodium hyaluronate on total amounts of arachidonic acid metabolites and cytokines and on symptoms was measured. Injection of sodium hyaluronate caused significant reductions in the mean (SEM) of total amounts of leukotriene C4 (4.68 (2.27) to 0.48 (0.24) ng/joint), 6-keto-prostaglandin F1alpha (12.12 (2.78) to 5.19 (1.90) ng/joint), prostaglandin F2alpha (12.63 (5.51) to 4.21 (2.20) ng/joint), and interleukin-1beta (100.5 (14.2) to 50.8 (13.9) pg/joint), respectively (P<0.05 in each case). The mean (SEM) pain score was significantly reduced from 2.56 (0.18) to 0.89 (0.26) (P<0.01), the noise score from 2.18 (0.23) to 1.18 (0.18) (P<0.05), and degree of mouth opening from 28.2 (2.5) to 34.9 (2.0) mm (P<0.01). However, no improvement in symptoms was recorded in 1/9, 5/11, and 1/9 patients, respectively. These findings suggest that inflammation plays a part in internal derangement of the temporomandibular joint, and injection of an anti-inflammatory substance may be beneficial to such patients.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Anesthetics, Local; Anti-Inflammatory Agents; Arthritis; Dinoprost; Female; Humans; Hyaluronic Acid; Injections, Intra-Articular; Interleukin-1; Leukotriene C4; Lidocaine; Male; Middle Aged; Pain Measurement; Prospective Studies; Range of Motion, Articular; Synovial Fluid; Temporomandibular Joint Disorders; Therapeutic Irrigation

Our aim was to determine the amounts of eicosanoids in blood and synovial tissue of patients with knee arthrosis and to examine the effects of 2 doses of tepoxalin (50 mg twice, 200 mg twice), administered p.o. for 3.5 days. Concentrations of leukotriene B4 (LTB4, LTC4, and thromboxane B2 (TXB2) were measured in blood before and after oral administration of tepoxalin and release of prostaglandin E2 (PGE2), 6-keto-PGF1alpha, and LTC4 was measured in incubation media of synovial tissue, taken at surgery from patients treated with tepoxalin. Radioimmunoassay (RIA) was used to determine the levels of the eicosanoids. LT and TXB2 release was reduced by tepoxalin in both doses used. Under these conditions, PGE2, 6-keto-PGF1alpha, and LTC4 release from synovial tissue was detectable only after stimulation with calcium ionophore A23187. Washed synovial tissue, in which tepoxalin concentrations should be reduced, released higher amounts of all eicosanoids measured than directly incubated synovial tissue did. Pain after tepoxalin administration was significantly reduced. Relevant drug concentrations were detected in plasma and synovial fluid. Tepoxalin was well tolerated and had no marked adverse effects. At 400 mg, tepoxalin is a dual inhibitor of cyclooxygenase (CO) and 5-lipoxygenase (5-LO) in blood and synovial tissue.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Arthroplasty, Replacement, Knee; Dinoprostone; Double-Blind Method; Drug Administration Schedule; Female; Humans; Knee Joint; Leukotriene Antagonists; Leukotriene B4; Leukotriene C4; Male; Middle Aged; Pain; Pain Measurement; Premedication; Pyrazoles; Radioimmunoassay; Synovial Membrane; Thromboxane B2

The effects of a 7 day-treatment with isoxicam (200 mg/24 h) on the urinary excretion of prostaglandins (PG) were compared to those of indomethacin (150 mg/24 h) in a double-blind randomized study conducted in 18 patients with degenerative arthritic disease and normal renal function. Indomethacin decreased the urinary excretion of PGF2 alpha by about 70% and 6-keto-PGF1 alpha and thromboxane (Tx)B2, the stable break-down products of prostacyclin and TxA2 respectively, by about 40%. Isoxicam effects on urinary PG did not significantly differ from those of indomethacin. During both treatments, urinary gamma-glutamyl transferase and N- acetyl-glucosaminidase remained stable and none of the changes in the urinary excretion of PGs could be related to either plasma or urinary drug concentrations. In conclusion, chronic administration of isoxicam inhibited the renal PG biosynthesis to a similar extent than indomethacin which suggests that non steroidal anti-inflammatory drugs of the oxicam group ought also be used cautiously in patients with renal impairment.

Topics: 6-Ketoprostaglandin F1 alpha; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Dinoprost; Double-Blind Method; Female; Humans; Indomethacin; Kidney Diseases; Male; Middle Aged; Piroxicam; Prostaglandins; Thromboxane B2

Intraperitoneal and intra-articular (knee joint) injection of zymosan in the rat caused two phases of increased vascular permeability, a rapid increase (0.25-0.5 h) and a secondary increase (2-3 h) which was temporally associated with the onset of leukocyte infiltration. Intraperitoneal injection of zymosan led to a single peak of eicosanoid production (LTB4, C4, D4, E4 and 6-oxo-PGF1 alpha) which was maximal at 0.125-0.25 h. Intra-articular injection led to an initial peak of LTB4 production (maximal at 0.25 h) and a secondary peak of LTB4 and PGE2 production (maximal at 3 h). Oral administration of the 5-lipoxygenase (5-LO) inhibitors phenidone, BW A4C (N-hydroxy-N-[3-(3-phenoxyphenyl)-2-propenyl] acetamide), A63162 (N-hydroxy-N-[1-(4-(phenylmethoxy) phenyl)ethyl] acetamide and ICI 207 968 (2-[3-pyridylmethyl]-indazolinone inhibited LTB4 production in A23187 stimulation blood ex vivo. The glucocorticosteroid dexamethasone had no effect in this model. The initial phase of increased vascular permeability in the peritoneal cavity and LTB4 production was dose dependently inhibited by the 5-LO inhibitors phenidone, BW A4C, A63162, and ICI 207 968 but not by dexamethasone or colchicine. The initial phase of increased permeability in the joint was unaffected by phenidone, BW A4C, dexamethasone or colchicine. However the latter two drugs inhibited the later phase of increased permeability and leukocyte infiltration in the joint and peritoneal cavity. These results demonstrate that zymosan induces eicosanoid production in vivo but the relative importance of these mediators varies depending on the inflammatory site.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arthritis; Benzeneacetamides; Calcimycin; Colchicine; Dexamethasone; Dinoprostone; Disease Models, Animal; Hydroxamic Acids; Inflammation; Kinetics; Knee Joint; Leukocytes; Leukotriene B4; Leukotrienes; Lipoxygenase Inhibitors; Male; Peritonitis; Pyrazoles; Rats; Zymosan