RESUMEN
OBJECTIVE: To investigate polyamine metabolism in rheumatoid synovial adherent cells stimulated by interleukin- 1beta (IL-1beta). METHODS: Synovial adherent cells obtained from patients with rheumatoid arthritis (RA) were cultured and incubated in the presence or absence of human recombinant IL-1beta at a concentration of 10 ng/ml for 24 h. The cellular contents of polyamines as well as the activities of spermidine/spermine N1-acetyltransferase (SAT) and ornithine decarboxylase (ODC) were measured. RESULTS: Polyamines in synovial adherent cells decreased significantly after 24 h incubation in the absence of IL-1beta. However, in the presence of IL-Ibeta, putrescine and N'-acetylspermidine increased significantly. No significant difference was observed between the amount of spermidine in synovial adherent cells incubated with and without IL-1beta. Spermine and N8-acetylspermidine in synovial adherent cells incubated with IL-1beta decreased significantly more than in synovial adherent cells incubated without. SAT activity reached a peak 12 h after the addition of IL-1beta and then decreased, while the ODC activity did not increase. SAT activity was elevated by the addition of IL-1beta in a dose dependent manner. CONCLUSION: An increase in the putrescine level in rheumatoid synovial adherent cells as a result of the elevation of SAT activity induced by IL-1beta may play a role in RA.
Asunto(s)
Acetiltransferasas/metabolismo , Artritis Reumatoide/metabolismo , Interleucina-1/farmacología , Putrescina/metabolismo , Membrana Sinovial/enzimología , Artritis Reumatoide/inmunología , División Celular/efectos de los fármacos , División Celular/fisiología , Células Cultivadas , Colagenasas/metabolismo , Dinoprostona/metabolismo , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Expresión Génica/fisiología , Humanos , Metaloproteinasa 3 de la Matriz/genética , Espermidina/metabolismo , Espermina/metabolismo , Membrana Sinovial/citología , Membrana Sinovial/efectos de los fármacosRESUMEN
OBJECTIVE: To elucidate the major source of pyridinium crosslinks in rheumatoid arthritis (RA). METHODS: Serum samples were collected from 75 patients with RA and 41 healthy controls, and synovial fluid (SF) samples were collected from 20 patients with RA and 13 with osteoarthritis (OA). Paired samples of serum and SF were collected at the same time from 26 patients with RA. Levels of pyridinium crosslinks were determined by a recently developed high sensitivity assay method using high pressure liquid chromatography. RESULTS: The levels of serum pyridinoline (PYD) and serum deoxypyridinoline (DPD) were significantly higher in patients with RA than in healthy controls, and significantly correlated with laboratory variables indicating disease activity and severity. The levels of SF DPD, but not SF PYD, were significantly higher in patients with RA than in patients with OA. The levels of SF PYD and SF DPD both showed a significantly positive correlation with those of either SF interleukin 1beta or SF interleukin 6 in patients with RA. Finally, the levels of PYD, but not DPD, were higher in SF than in serum in all paired RA samples collected at the same time, with significant correlation between the members of each pair. CONCLUSION: These observations suggest than an increase of PYD in RA serum may originate mostly from affected joints and that an increase of DPD in RA serum may be influenced more by systemic bone resorption.
Asunto(s)
Aminoácidos/análisis , Artritis Reumatoide/metabolismo , Líquido Sinovial/química , Adulto , Anciano , Aminoácidos/sangre , Biomarcadores/análisis , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The present study determined the levels in synovial fluid (SF) of vitamin D metabolites (1,25-dihydroxyvitamin D (1,25(OH)2D), 24,25-dihydroxyvitamin D (24,25(OH)2D) and 25-hydroxyvitamin D (25-OH-D)), and of the cytokines. We evaluated SF from 21 patients with rheumatoid arthritis (RA) and 6 patients with osteoarthritis (OA). The levels of vitamin D metabolites in SF, as determined by two different extraction methods, were significantly correlated (p < 0.05, n=7). The levels of 3 vitamin D metabolites were significantly higher in the RA SF than in OA SF (p < 0.05). The ratio of 1,25(OH)2D/25-OH-D in RA SF, which is presumed to reflect the activity of 25-OH-D-1-hydroxylase (1-OH-ase), was positively correlated with the levels of interleukin-1alpha (IL-1alpha), IL-1beta, and IL-2 in such SF, and was significantly higher than that in sera from RA patients. This suggests an important role for these cytokines in the activation of 1-OH-ase in RA synovium. The ratio of 24,25(OH)2D/25-OH-D, which is presumed to reflect 25-OH-D-24-hydroxylase (24-OH-ase) activity, was significantly correlated with 1,25(OH)2D levels only in RA SF, but not in sera from RA patients, suggesting a local regulation of vitamin D metabolism that 1,25-(OH)2D induces 24-OH-ase as in other target cells. Our observations suggested that 1,25(OH)2D and 24,25(OH)2D are produced locally from 25-OH-D in RA synovium, and that the syntheses of 1,25(OH)2D and 24,25(OH)2D may be affected by IL-1/IL-2 and 1,25(OH)2D in RA SF, respectively.
Asunto(s)
Artritis Reumatoide/metabolismo , Interleucina-1/metabolismo , Interleucina-2/metabolismo , Líquido Sinovial/metabolismo , Vitamina D/análogos & derivados , Humanos , Vitamina D/metabolismoRESUMEN
OBJECTIVE: To determine the levels of hepatocyte growth factor (HGF) in synovial fluids (SF) and sera from patients with rheumatoid arthritis (RA); to examine how these correlate with several disease variables in patients with RA and with levels of interleukin-6 (IL-6) in SF of these patients; and to examine whether HGF is released from adherent synovial cells (ASC) and synovial fluid cells (SF cells). METHODS: An enzyme linked immunosorbent assay was used to measure levels of HGF and IL-6. SF samples were obtained from 22 patients with RA, 12 with osteoarthritis (OA), and one with septic arthritis. Serum samples were collected from 40 patients with RA. HGF levels in culture supernatants from ASC and SF cells were measured. RESULTS: The mean values of HGF in SF were 1.21 ng/ml for patients with RA, 0.19 ng/ml for those with OA and 0.18 ng/ml for the one with septic arthritis. HGF levels in SF of patients with RA were significantly higher than of those with OA (p < 0.01). The levels for patients with RA correlated with the serum C-reactive protein concentrations (r = 0.626, p < 0.01) and IL-6 levels in SF (r = 0.476, p < 0.05). The mean value of HGF in sera from patients with RA was 0.28 ng/ml. HGF levels in SF were higher than those in sera drawn simultaneously from the same patients with RA. In vitro, release of HGF from rheumatoid ASC was not detected. However, SF cells from patients with RA released HGF spontaneously. CONCLUSION: Our observations suggest that HGF in SF of patients with RA is produced by SF cells and is related to disease activity of RA, and thus that HGF may play a role in RA.
Asunto(s)
Artritis Reumatoide/metabolismo , Factor de Crecimiento de Hepatocito/metabolismo , Líquido Sinovial/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/patología , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Femenino , Factor de Crecimiento de Hepatocito/sangre , Humanos , Interleucina-6/metabolismo , Masculino , Persona de Mediana Edad , Líquido Sinovial/citologíaRESUMEN
OBJECTIVE: To compare urinary polyamine levels in patients with rheumatoid arthritis (RA), with osteoarthritis (OA), and in healthy controls and examine the relationship between urinary polyamine levels and several disease variables in patients with RA. METHODS: We determined the concentrations of urinary polyamines in 33 patients with RA, 24 with OA, and 20 healthy controls, using the enzymatic assay method. For patients with RA relevant clinical and laboratory variables were obtained and functional and radiologic scores determined for the joints. RESULTS: Urinary polyamine levels were significantly higher in patients with RA versus those with OA and healthy controls. In patients with RA the levels of urinary polyamines correlated significantly with the concentrations of serum C-reactive protein (CRP); there was also a statistically significant negative correlation between their urinary polyamine levels and average grip strength in either hand. Moreover, the levels of urinary polyamines in patients with RA showed an increase in proportion to the degree of joint functional damage and radiologic progression. CONCLUSION: Our results confirm our previous report of an increase in the amount of free putrescine in synovial fluids and a significant correlation between the putrescine contents of synovial tissues and the serum CRP concentrations in patients with RA; they also suggest that urinary polyamine levels may be related to the activity and progression of RA, indicating that polyamine may play an important role in RA.
Asunto(s)
Artritis Reumatoide/orina , Poliaminas/orina , Adulto , Anciano , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/fisiopatología , Artrografía , Proteína C-Reactiva/análisis , Femenino , Humanos , Articulaciones/fisiopatología , Masculino , Persona de Mediana Edad , Osteoartritis/orina , Valores de ReferenciaRESUMEN
We determined the polyamine contents of the synovial tissues from 11 patients with rheumatoid arthritis (RA), and the free putrescine levels in the synovial fluids (SF) from 10 patients with RA, 7 with osteoarthritis (OA), 5 with posttraumatic arthritis, and 3 with infectious arthritis. Putrescine levels in the synovial tissues correlated with serum C reactive protein concentration in patients with RA. Free putrescine levels in SF were significantly elevated in patients with infectious arthritis, compared with those found in RA, OA, and posttraumatic arthritis. Free putrescine levels in SF from patients with RA were significantly higher than in those with OA. Our findings suggest that polyamines may play an important role in RA.
Asunto(s)
Artritis Reumatoide/metabolismo , Poliaminas/análisis , Líquido Sinovial/química , Membrana Sinovial/química , Adulto , Anciano , Artritis Infecciosa/metabolismo , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis/metabolismo , Poliaminas/metabolismo , Putrescina/análisis , Putrescina/metabolismoRESUMEN
The changes in total fat mass (TFM) and lean body mass (LBM) under semistarvation treatment were measured by dual-photon absorptiometry (DPA) in this study. Three females with massive obesity were followed over two periods consuming a very-low-calorie diet (VLCD). Although LBM changes attributed to water shifts related to sodium balance were observed, DPA proved sensitive enough to measure LBM and TFM changes in semistarvation treatment. LBM measured by DPA did not change significantly following 4 weeks of VLCD. However, TFM decreased significantly (70.9 +/0 24.1 kg to 62.4 +/- 21.7 kg) and paralleled body weight.
Asunto(s)
Composición Corporal , Dieta Reductora , Obesidad/metabolismo , Inanición/metabolismo , Absorciometría de Fotón , Adulto , Agua Corporal , Ingestión de Energía , Femenino , Humanos , Monitoreo Fisiológico , Nitrógeno/metabolismo , Obesidad/dietoterapia , Proteínas/metabolismo , Triyodotironina/metabolismo , Pérdida de PesoRESUMEN
The intraperitoneal fibrin formation and its inhibition by intraperitoneal heparin and/or antithrombin III (AT III) were examined in 8 patients on continuous ambulatory peritoneal dialysis (CAPD). With 1,000 and 2,000 U/L of heparin added to inflow dialysate, the concentration of fibrinopeptide A (FPA) in plasma decreased from 39.43 +/- 5.30 (mean +/- SEM) to 8.00 +/- 2.20 and to 0.74 +/- 0.12 ng/ml, respectively. The FPA concentration in outflow dialysate decreased from 34.20 +/- 5.75 to 12.94 +/- 2.10 ng/ml (1,000 U/l of heparin) and to 4.54 +/- 0.79 ng/mg (2,000 U/l of heparin). The AT III concentration was 0.47 +/- 0.07 mg/dl in dialysate and that in plasma was 24.20 +/- 2.76 mg/dl. With 100 U/bag of AT III added to inflow dialysate, the AT III concentration increased from 0.47 +/- 0.07 to 3.36 +/- 0.17 mg/dl in outflow dialysate but did not increase in plasma. The inhibition of fibrin formation of intraperitoneal heparin was increased by addition of AT III without a systemic inhibitory effect on fibrin formation. These data suggest that intraperitoneal administration of heparin without AT III would be sufficient for the purpose of preventing fibrin formation in CAPD patients without any trouble, and additional AT III might increase inhibitory effect of heparin.