Artritis Idiopática Juvenil: manifestaciones clínicas y tratamiento / Juvenile Idiopathic Arthritis: clinical manifestation and treatment

Resumen La Artritis Idiopática Juvenil es la enfermedad reumática más frecuente en niños. Es una enfermedad crónica, degenerativa y de etiología desconocida; que puede dejar múltiples secuelas en la población pediátrica. Consta de siete afecciones definidas por la International League of Associations for Rheumatology del 2001: Artritis Sistémica, Oligoartritis, Artritis con Factor Reumatoide positivo o Factor Reumatoide negativo, Artritis relacionada a entesitis, Artritis psoriasica y Artritis indiferenciada; distintas tanto en el aspecto clínico, patogénico como evolutivo. Esta enfermedad se caracteriza por una alteración de la regulación del sistema inmunitario innato con una falta de linfocitos T autorreactivos y autoanticuerpos. La inflamación continua estimula el cierre rápido y prematuro del cartílago de crecimiento provocando un acortamiento óseo. Para llegar a su diagnóstico no se requiere más que una buena historia clínica y examen físico, ya que no hay laboratorios o gabinete lo bastante sensible que nos puedan ayudar. Fármacos como el metrotexate y los inhibidores del factor de necrosis tumoral han venido a modificar la evolución de la enfermedad y mejorar la calidad de vida de estos pacientes.

Abstract Juvenile idiopathic arthritis is the most common rheumatic disease in children. It is a chronic and degenerative disease, with an unknown etiology; that can leave multiple sequels in the pediatric population. There are seven conditions defined by 2001 International League of Associations for Rheumatology: Systemic Arthritis, Oligoarthritis, Arthritis with positive rheumatoid factor or negative rheumatoid factor, enthesitis-related arthritis and undifferentiated arthritis; distinct in clinical, pathogenetic and evolutionary aspects. This disease is characterized by an alteration on the regulation of the innate immune system with a lack of autoreactive lymphocytes T and autoantibodies. Continuous inflammation stimulates the rapid and premature closure of the growth cartilage causing bone shortening. To arrive at the diagnosis, it is only necessary to have a good medical history and physical exam, since there are no laboratory test sensitive enough to help us. Drugs such as methotrexate and tumor necrosis factor inhibitors have come to modify the evolution of the disease and improve the quality of life of these patients.

Hyaluronic acid has chondroprotective and joint-preserving effects on LPS-induced synovitis in horses.

The intra-articular use of hyaluronic acid (HA) for the treatment of synovitis and osteoarthritis is still controversial. As a consequence, corticosteroids remain the most frequently employed therapeutic agents, despite their potential systemic and local deleterious effects. This study examined the anti-inflammatory, antioxidant, and chondroprotective activities of low and high molecular weight hyaluronic acid (LMW-HA and HMW-HA) on lipopolysaccharide (LPS)-induced synovitis in horses compared to triamcinolone acetonide (TA). LPS was injected in the metacarpophalangeal joints, which were treated intra-articularly with either TA (as control) or LMW-HA or HMW-HA. Joint clinical evaluation and synovial fluid (SF) analysis were performed at 0, 8, 24, and 48 h. The white blood cell counts (WBC), prostaglandin E2 (PGE2), interleukin (IL)-1, IL-6, IL-10, tumor necrosis factor-α, chondroitin sulfate (CS) and HA concentrations, oxidative burst, and HA molecular weights were measured. TA reduced the lameness, swelling, and PGE2 release but increased the SF CS concentrations enormously at 24h and 48h, and decreased the SF HA modal molecular weight. These results indicate the breakdown of articular cartilage aggrecan and SF HA. In contrast, LMW-HA and HMW-HA were less effective in reducing the inflammation symptoms, but preserved the joints because only a modest increase in CS occurred at 24 h, decreasing at 48 h, and the SF HA was maintained. The HA-treatment also had anti-inflammatory actions, and LMW-HA was the most effective in reducing the release of cytokine. In summary, the HA treatment inhibited efficiently the digestion of cartilage proteoglycans and SF HA breakdown.

Involvement of TLR4 in the protective effect of intra-articular administration of curcumin on rat experimental osteoarthritis

Purpose: In view of the principal role of Toll-like receptor 4 (TLR4) in mediating sterile inflammatory response contributing to osteoarthritis (OA) pathogenesis, we used lipopolysaccharide (LPS), a known TLR4 activator, to clarify whether modulation of TLR4 contributed to the protective actions of intra-articular administration of curcumin in a classical rat OA model surgically induced by anterior cruciate ligament transection (ACLT). Methods: The rats underwent ACLT and received 50μl of curcumin at the concentration of 1 mg mL-1and 10 μg LPS by intra-articular injection once a week for 8 weeks. Morphological changes of the cartilage and synovial tissues were observed. Apoptotic chondrocytes were detected using TUNEL assay. The concentrations of IL-1β and TNF-ɑ in synovial fluid were determined using ELISA kits. The mRNA and protein expression levels of TLR4 and NF-κB p65 were detected by real-time PCR and Western blotting, respectively. Results: Intra-articular administration of curcumin significantly improved articular cartilage injury, suppressed synovial inflammation and down-regulated the overexpression of TLR4 and its downstream NF-κB caused by LPS-induced TLR4 activation in rat osteoarthritic knees. Conclusion: The data suggested that the inhibition of TLR4 signal might be an important mechanism underlying a protective effect of local curcumin administration on OA.(AU)

Oral glucosamine and chondroitin sulfate on synovial fluid biomarkers from osteoarthritic equine joints / Efeitos da glucosamina e condroitim sulfato oral sobre biomarcadores do líquido sinovial de articulações osteoartríticas de equinos

Several studies, mainly in vitro, have shown that chondroitin sulfate (CS) and glucosamine (GlcN) do have chondro protective and anti-inflammatory actions. The aim of the present study was to investigate whether oral CS/GlcN supplementation has effects on the CS, hyaluronic acid (HA) and prostaglandin E2 (PGE2) concentrations on synovial fluid of equine osteoarthritic joints. Horses with mild osteoarthritis (OA) in tibiotarsal joint received daily PO doses of CS and GlcN (2.8/3.1 g) for 25 days. Synovial fluid (SF) and urine samples were collected before treatment (day 0), and every 7 days, until day 55 (30 days after the end of treatment). Urinary CS increased upon oral treatment, indicating that this compound was systemically distributed. Concerning the SF, CS concentration increased after the end of the treatment and returning to baseline afterwards, while HA and PGE2 concentrations did not change. Despite the systemic distribution, oral supplementation of CS/GlcNfor 25 days was insufficient as an anti-inflammatory support. However, it is possible to infer that there was an anabolic effect upon cartilage matrix.(AU)

Vários estudos, principalmente in vitro, têm mostrado que o condroitim sulfato (CS) e a glucosamina (GLcN) possuem ação condroprotetora e anti-inflamatória. O objetivo deste trabalho foi investigar se a administração oral de CS/GLcN possui efeito sobre as concentrações de CS, ácido hialurônico (AH) e prostaglandina E2 (PGE2) do liquido sinovial (LS) de articulações equinas com osteoartrite (OA). Cavalos diagnosticados com OA tibiotársica grau leve receberam por via oral doses diárias de CS e GlcN (2,8g/3,1g) por 25 dias. Amostras de LS e urina foram coletadas antes do tratamento (dia 0) e a cada 7 dias até o dia 55 (30 dias após o fim do tratamento). Houve aumento do CS urinário, indicando a distribuição sistêmica desse composto. No LS, a concentração de CS aumentou após o final do tratamento e retornou aos valores basais em seguida, enquanto as concentrações de HA e PGE2 não apresentaram alterações. Apesar da distribuição sistêmica, a suplementação oral de CS/GlcNpor 25 dias foi insuficiente como medida anti-inflamatória. Contudo, pode-se inferir que houve efeito anabólico sobre a matriz cartilagínea.(AU)

Effects of medical ozone upon healthy equine joints: Clinical and laboratorial aspects.

OBJECTIVE: The aim of this study was to verify whether transient inflammatory reactions induced by intra-articular medicinal ozone administration affect joint components, by in vivo evaluation of inflammatory (prostaglandin E2, Substance P, Interleukin-6, Interleukine-1, Tumor Necrosis Factor), anti-inflammatory (Interleukin-10) and oxidative (superoxide dismutase activity and oxidative burst) biomarkers and extracellular matrix degradation products (chondroitin sulphate and hyaluronic acid) in synovial fluid. METHODS: The effects of medicinal ozone were analyzed at two ozone concentrations (groups A and B, 20 and 40 µg/ml, respectively), using oxygen-injected joints as controls (group C); each group received ten treatments (15 ml gas per treatment). Physical evaluation, evaluation of lameness, ultrasonography, and synovial fluid analysis were performed. RESULTS: All joints presented mild and transient effusion throughout the study. Group B exhibited the highest lameness score on day 14 (P<0.05), detected by the lameness measurement system, probably because of the higher ozone concentration. All groups exhibited increased ultrasonography scores on day 14 (P < 0.05). Groups A and B exhibited increased proteins concentrations on day 21 (P<0.05). There was no change in hyaluronic acid concentration or the percentage of high-molecular weight hyaluronic acid throughout the experiment. Chondroitin sulfate concentrations decreased in group B, and did not change in group A and C, indicating that neither treatment provoked extracellular matrix catabolism. Cytokine and eicosanoid concentrations were not significantly changed. CONCLUSIONS: The ozonetherapy did not cause significant inflammation process or cartilage degradation, therefore, ozonetherapy is safe at both evaluated doses.

A promising novel formulation for articular cartilage regeneration: Preclinical evaluation of a treatment that produces SOX9 overexpression in human synovial fluid cells.

Osteoarthritis (OA) is a chronic disorder of synovial joints, in which there is progressive softening and disintegration of the articular cartilage. OA is the most common form of arthritis, and is the primary cause of disability and impaired quality of life in the elderly. Despite considerable medical necessity, no treatment has yet been proven to act as a disease­modifying agent that may halt or reverse the structural progression of OA. The replacement of the joint with a prosthesis appears to be the best option in the advanced stages of the disease. A formulation (BIOF2) for cartilage regeneration has been recently developed. The present study evaluated the effects of BIOF2 on gene expression in human cell cultures, followed by efficacy trials in three OA animal models. Human synovial fluid cells that were exposed to the formulation exhibited increased transcription factor SOX­9 (SOX9; chondrogenic factor) expression, and decreased mimecan (mineralization inducer) and macrophage­stimulating protein receptor (osteoclastogenic factor) expression. The intra­articular application of BIOF2 in the animal models significantly increased cartilage thickness from 12 to 31% at 28 days, compared with articular cartilage treated with saline solution. The articular area and number of chondrocytes additionally increased significantly, maintaining an unaltered chondrocyte/mm2 proportion. Evaluation of the histological architecture additionally displayed a decrease in the grade of articular damage in the groups treated with BIOF2. In conclusion, BIOF2 has proven to be effective for treating OA in animal models, most likely due to SOX9 overexpression in articular cells.

Macrophage migration inhibitory factor drives neutrophil accumulation by facilitating IL-1ß production in a murine model of acute gout.

This study evaluated the role of macrophage migration inhibitory factor in inflammation caused by monosodium urate crystals. The concentration of macrophage migration inhibitory factor was increased in synovial fluid of patients with acute gout, and there was a positive correlation between intra-articular macrophage migration inhibitory factor and IL-1ß concentrations. In mice, the injection of monosodium urate crystals into the knee joint increased the levels of macrophage migration inhibitory factor in macrophages and in inflamed tissue. The injection of recombinant macrophage migration inhibitory factor into the joint of mice reproduced the inflammatory response observed in acute gout, including histologic changes, the recruitment of neutrophils, and increased levels of IL-1ß and CXCL1. Importantly, the accumulation of neutrophils and the amount IL-1ß in the joints were reduced in macrophage migration inhibitory factor-deficient mice when injected with monosodium urate crystals. We observed a similar effect when we blocked macrophage migration inhibitory factor with (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid or anti-macrophage migration inhibitory factor. In addition, the blockade of IL-1R and CXCR2 reduced recombinant macrophage migration inhibitory factor-induced neutrophil recruitment. Mechanistically, recombinant macrophage migration inhibitory factor is important for the synthesis of il1ß mRNA in vivo and in isolated macrophages. Altogether, macrophage migration inhibitory factor promotes neutrophil accumulation and is important for IL-1ß production, which are 2 crucial events contributing to the pathogenesis of acute gout.

Chenopodium ambrosioides L. Reduces Synovial Inflammation and Pain in Experimental Osteoarthritis.

The chronicity of osteoarthritis (OA), characterized by pain and inflammation in the joints, is linked to a glutamate receptor, N-methyl-D-aspartate (NMDA). The use of plant species such as Chenopodium ambrosioides L. (Amaranthaceae) as NMDA antagonists offers a promising perspective. This work aims to analyze the antinociceptive and anti-inflammatory responses of the crude hydroalcoholic extract (HCE) of C. ambrosioides leaves in an experimental OA model. Wistar rats were separated into six groups (n = 24): clean (C), negative control (CTL-), positive control (CTL+), HCE0.5, HCE5 and HCE50. The first group received no intervention. The other groups received an intra-articular injection of sodium monoiodoacetate (MIA) (8 mg/kg) on day 0. After six hours, they were orally treated with saline, Maxicam plus (meloxicam + chondroitin sulfate) and HCE at doses of 0.5 mg/kg, 5 mg/kg and 50 mg/kg, respectively. After three, seven and ten days, clinical evaluations were performed (knee diameter, mechanical allodynia, mechanical hyperalgesia and motor activity). On the tenth day, after euthanasia, synovial fluid and draining lymph node were collected for cellular quantification, and cartilage was collected for histopathological analysis. Finally, molecular docking was performed to evaluate the compatibility of ascaridole, a monoterpene found in HCE, with the NMDA receptor. After the third day, HCE reduced knee edema. HCE5 showed less cellular infiltrate in the cartilage and synovium and lower intensities of allodynia from the third day and of hyperalgesia from the seventh day up to the last treatment day. The HCE5 and HCE50 groups improved in forced walking. In relation to molecular docking, ascaridole showed NMDA receptor binding affinity. C. ambrosioides HCE was effective in the treatment of OA because it reduced synovial inflammation and behavioral changes due to pain. This effect may be related to the antagonistic effect of ascaridole on the NMDA receptor.

Antinociceptive and anti-inflammatory effects of Caryocar coriaceum Wittm fruit pulp fixed ethyl acetate extract on zymosan-induced arthritis in rats.

The ethyl acetate extract from the fruit pulp of Caryocar coriaceum Wittm (Caryocaraceae), popularly known as pequi, has wide applications in popular medicine. Preclinical tests have demonstrated the therapeutic properties of the oil. We investigated the antinociceptive and anti-inflammatory effects of Pequi C. coriaceum Wittm ethyl acetate extract (PCCO) on zymosan-induced arthritis in rat knee joint. The animals were pretreated with PCCO for 7 consecutive days or with a single dose. Paw elevation time (PET), leukocyte infiltration, myeloperoxidase activity (MPO) and cytokine levels were assessed 4h after zymosan injection. Synovial tissue was harvested for immunohistochemical analysis, edema and vascular permeability. We observed a significant decrease in PET with PCCO pretreatment. PCCO showed a significant reduction of leukocyte migration and a decrease in MPO. Decreases were observed in cytokine release in the synovial fluid and TNF-α and cyclooxygenase-1 immunostaining in synovial tissue. Edema was inhibited by treatment with all doses of PCCO. The data suggest that PCCO exerts antinociceptive and anti-inflammatory effects on arthritis in rats.

Enhancement of the inhibitory effect of an IL-15 antagonist peptide by alanine scanning.

IL-15 is a proinflammatory cytokine that acts early in the inflammatory response and has been associated with several autoimmune diseases including rheumatoid arthritis, where it had been proposed as a therapeutic target. We recently reported an IL-15 antagonist peptide corresponding to sequence 36-45 of IL-15 (KVTAMKCFLL) named P8, which specifically binds to IL-15Rα and inhibits IL-15 biological activity with a half maximal inhibitory concentration (IC50) of 130 µ m in CTLL-2 proliferation assay. In order to improve binding of peptide P8 to the receptor IL-15Rα, we used an Ala scan strategy to study contribution of each individual amino acid to the peptide's antagonist effect. Here, we found that Phe and Cys are important for peptide binding to IL-15Rα. We also investigated other single site mutations and replaced the second Lys in the sequence by the polar non-charged amino acid threonine. The resulting peptide [K6T]P8 exhibited a higher activity than P8 with an IC50 of 24 µm. We also found that this peptide was more active than peptide P8 in the inhibition of TNFα secretion by synovial cells from rheumatoid arthritis patients. The peptide [K6T]P8 described in this work is a new type of IL-15 antagonist and constitutes a potential therapeutic agent for rheumatoid arthritis.

Evaluation of the pro-inflammatory potential of nanostructured drug carriers in knee-joints of rats: effect on nociception, edema, and cell migration.

Nanocarriers have been developed aiming at drug delivery; however, the irritating effects of these nanoparticles on naïve or inflamed articular tissues are not known. Poly(D,L-lactide) (N-PLA), methoxy poly(ethylene glycol)-b-poly(D,L-lactide) (N-PEG-PLA), and Dynasan 116 (SLN) were used to prepare the nanocarriers. The average diameter (nm) and zeta potential (mV) of these particles were, respectively, 251 and -33.2, 169 and -22.1, and 105 and -13.0. Naive or carrageenan-primed knee-joints received 100 microL of nanoparticle suspensions or control solution. Incapacitation and articular diameter were determined hourly. Synovial leukocytes were counted 6 h after nanoparticle injection. N-PLA increased the articular diameter and leukocytes, but did not cause incapacitation. In primed knee-joints, N-PLA caused incapacitation, and increased the articular diameter and leukocytes. SLN did not produce inflammatory signals either in naive or primed knees. In primed knee-joints, N-PEG-PLA presented an intermediate effect characterized by an increase in the articular diameter, and a slight increase of leukocytes, but not incapacitation. These results suggest that solid lipid nanoparticles may be safer than polymeric ones, which may be correlated to their chemical composition and superficial charge.

Stereoselective disposition of fenoprofen in plasma and synovial fluid of patients with rheumatoid arthritis.

The simultaneous disposition of fenoprofen enantiomers in synovial fluid and plasma was studied in 11 patients with arthritis and chronic knee effusions treated with a single oral dose of 600 mg rac-fenoprofen. A plasma sample and a synovial fluid sample were collected simultaneously from each patient up to 16 h after the administration of fenoprofen. A stereospecific assay for fenoprofen using LC-MS-MS was developed and applied successfully to the analysis of the enantiomers in plasma (LOQ = 10 ng of each enantiomer/ml) and synovial fluid (LOQ = 25 ng of each enantiomer/ml). The values of the area under the curve (AUC) for the S-(+)-fenoprofen eutomer were approximately 2.5 times higher in plasma than in synovial fluid (256 vs 104 microg h/ml), while the values for the R-(-)-fenoprofen distomer were about four times higher in plasma than in synovial fluid (42.5 vs 10.5 microg h/ml). These data demonstrate accumulation of the S-(+)-fenoprofen eutomer in plasma and in synovial fluid, with concentrations versus time AUC (+)/(-) ratios of 6.0 in plasma and 9.9 in synovial fluid, suggesting a greater accumulation of the eutomer at the active site represented by synovial fluid than in plasma. This result demonstrates the importance of enantioselective methods and of analysis of synovial fluid rather than plasma in studies of the pharmacokinetics-pharmacodynamics of fenoprofen.

Tumour necrosis factor-alpha mediates neutrophil migration to the knee synovial cavity during immune inflammation.

Tumour necrosis factor (TNF)-alpha, interleukin-1beta, interleukin-8 and leukotriene B4 have an important role on neutrophil recruitment during immune-inflammation. Here we evaluated the participation of several inflammatory mediators on ovalbumin-induced neutrophil recruitment in the knee articular space of immunized rats. Ovalbumin administration in immunized, but not in control, rats induced a dose- and time-dependent neutrophil accumulation, which was inhibited by dexamethasone, pentoxifylline or thalidomide, but not by selective inhibitors of nitric oxide (nitro-L-arginine), platelet-activating factor (BN50730 or UK74505), prostaglandins (indomethacin), histamine (meclisine) or leukotriene B4 (MK 886 and CP105,696). Anti-TNF-alpha antiserum, but not anti-interleukin-1beta or anti-CINC-1 (cytokine-induced neutrophil chemoattractant 1) antisera, impaired ovalbumin-induced neutrophil accumulation. High amounts of TNF-alpha were detected in the exudates, which was inhibited by dexamethasone, pentoxifylline and thalidomide. These results suggest a specific role for TNF-alpha in this model, and the ability of pentoxifylline and thalidomide to inhibit both neutrophil influx and TNF-alpha release may have therapeutic implications in arthritis.

Reactive nitrogen species scavenging, rather than nitric oxide inhibition, protects from articular cartilage damage in rat zymosan-induced arthritis.

1. The contribution of nitric oxide (NO) and peroxynitrite (PN) to inflammation in a zymosan-induced (1 mg, intra-articular, i.art.) rat model of arthritis was assessed by histopathology and by measuring the glycosaminoglycan (GAG) content of the articular cartilage. 2. Progression of the chronic synovitis in zymosan-induced arthritis (ZYA) was associated with increased nitrite and nitrotyrosine (3-NT) levels in the joint exudates that paralleled a progressive loss of the GAG content. An increase in 3-NT was also observed after i.art. PN. 3. The nonselective nitric oxide synthase (NOS) inhibitor l-N(G)-nitroarginine methyl ester (25-75 mg x kg(-1)day(-1)) or the selective inducible NOS inhibitor aminoguanidine (50-100 mg x kg(-1)day(-1)) given 1 h before (prophylactic) or 3 days after (therapeutic) injection of the zymosan ameliorated the synovitis, but worsened the GAG loss, as measured at the end of the experiment (day 7). 4. The PN scavenger uric acid (100-250 mg x kg(-1) i.p. four times daily) given prophylactically until the end of the experiment (day 14), in a dose compatible with its PN scavenging activity, significantly decreased both the synovitis and the GAG loss. 5. In conclusion, PN formation is associated with cartilage damage in addition to proinflammatory activity in ZYA. NOS inhibitors and a PN scavenger were able to reduce the cellular infiltration, while displaying opposite effects on cartilage homeostasis either by enhancing or ameliorating the damage, respectively.

Interrelationship of the kinin system, nitric oxide and eicosanoids in the antigen-induced arthritis in rabbits.

The aim of the present study was to investigate the interrelationship of the kinin system, nitric oxide and eicosanoids in the acute phase of antigen-induced arthritis (AIA) in rabbits. The arthritis was induced in immunized rabbits and the following parameters were evaluated 24 hours later: leukocyte influx (total and differential white cell count), vascular permeability (Evans's blue method), and synovial PMN cell infiltrate. PGE2 and LTB4 (radioimmunoassay) levels were quantified in the synovial fluid. The animals were pre-treated with 20mg/kg/day during 14 days with L-NAME or D-NAME and/or Enalapril (0.12 mg/kg/day-14 days), and/or the B2 antagonist of Bradykinin HOE 140 (0.9 mg/kg). Our results showed that L-NAME was effective in the prevention of AIA with reduction of all Inflammatory parameters analyzed. Enalapril partially reverted the L-NAME anti-inflammatory effects. The simultaneous treatment with HOE 140 abolished this reversion and returned the inflammatory parameters to the levels observed in L-NAME treated animals. Our results suggest that pressoric alterations induced by L-NAME could not account for all its anti-inflammatory action in this model of experimental arthritis. Additionally the contribution of the kinin system in AIA was characterized as well as its interaction with eicosanoids and nitric oxide.

Farmacodinamia clínica del ácido tiaprofénico / Clinical pharmacodynamics of the tiaprofenic acid

El ácido tiaprofénico [ácido alfa-benzoil-5-thienil- 2 propiónico ha demostrado ser un activo inhibidor reversible de la ciclooxigenasa. La evidencia de que ciertas prostaglandinas (PGs), enzimas lisozómicas y otros autacoides producían injuria articular y reacciones sinoviales, nos sugirió la investigación de la eficacia a corto plazo del ácido tiaprofénico, en el tratamiento de la artritis reumatoidea. El estudio fue realizado sobre 20 pacientes adultos, portadores de sinovitis con derrame, a los cuales fue suspendida toda otra medicación antiinflamatoria, 7 días antes de comenzar el estudio. En todos los pacientes se analizó la concentración de: PGE2 2, P6F2-alfa fosfatasa ácida, dehidrogenasa láctica y cantidad de células en el líquido sinovial, antes y después de 8 días de tratamiento con 600mg/día/vía oral, de ácido tiaprofénico. La detección de los niveles de las PGs se realizó por cromatografía sobre capa fina y ensayo biológico sobre fundus gástrico de rata, contra testigo. Luego del 5§ día se observó una disminución progresiva de la reacción inflamatoria. En corto tiempo el ácido tiaprofénico provocó una caída significativa en los valores de LDH (p<0,02), PGE2 (p<0,001), fosfatasa ácida (p<0,005)., PGF2-alfa (p<0,001) y en el número de células (p<0,02). Concluimos en que el ácido tiaprofénico es una droga anti-PGs y antiinflamatoria efectiva a corto período de tratamiento

Farmacodinamia clínica del ácido tiaprofénico / Clinical pharmacodynamics of the tiaprofenic acid

El ácido tiaprofénico [ácido alfa-benzoil-5-thienil- 2 propiónico ha demostrado ser un activo inhibidor reversible de la ciclooxigenasa. La evidencia de que ciertas prostaglandinas (PGs), enzimas lisozómicas y otros autacoides producían injuria articular y reacciones sinoviales, nos sugirió la investigación de la eficacia a corto plazo del ácido tiaprofénico, en el tratamiento de la artritis reumatoidea. El estudio fue realizado sobre 20 pacientes adultos, portadores de sinovitis con derrame, a los cuales fue suspendida toda otra medicación antiinflamatoria, 7 días antes de comenzar el estudio. En todos los pacientes se analizó la concentración de: PGE2 2, P6F2-alfa fosfatasa ácida, dehidrogenasa láctica y cantidad de células en el líquido sinovial, antes y después de 8 días de tratamiento con 600mg/día/vía oral, de ácido tiaprofénico. La detección de los niveles de las PGs se realizó por cromatografía sobre capa fina y ensayo biológico sobre fundus gástrico de rata, contra testigo. Luego del 5º día se observó una disminución progresiva de la reacción inflamatoria. En corto tiempo el ácido tiaprofénico provocó una caída significativa en los valores de LDH (p<0,02), PGE2 (p<0,001), fosfatasa ácida (p<0,005)., PGF2-alfa (p<0,001) y en el número de células (p<0,02). Concluimos en que el ácido tiaprofénico es una droga anti-PGs y antiinflamatoria efectiva a corto período de tratamiento (AU)