来氟米特的合成研究

以乙酰乙酸乙酯为起始原料,经五步反应制得来氟米特,总收率为４３．６％,反应原料易得,反应条件温和,后处理方便,适合工业化生产。     

Serological markers of rheumatoid arthritis in patients with primary biliary cholangitis and the vice versa: A Tunisian study

BackgroundPrimary biliary cholangitis (PBC) is an autoimmune disease of the liver characterized by destructive lymphocytic cholangitis and anti-mitochondrial antibodies (AMA). Anti-gp210 and anti-Sp100, are used for the diagnosis of PBC in AMA-negative PBC patients. Patients with PBC have a propensity to have an extrahepatic manifestation which is especially autoimmune.ObjectiveWe aimed to determine the frequency of serological markers of rheumatoid arthritis (RA) (CCP-Ab or RF) in PBC patients and to do the vice versa.MethodsOur PBC study included 70 patients with PBC and 80 healthy blood donors (HBD) and our RA study included 75 patients with RA and 75 HBD. Anti-cyclic citrullinated peptide antibodies (CCP-Ab) and rheumatoid factor (RF) were performed by indirect ELISA. AMA, anti-Sp100 and anti-gp210 were determined by indirect immunofluorescence.ResultsRA autoantibodies (CCP-Ab or RF) were more frequent in PBC patients than in HBD (65.7% vs. 8.7% p 〈1 0 ⁻⁶). CCP-Ab were significantly more frequent in patients than in controls (15.7% vs. 2.5%; p = 0.004). Nine patients had both CCP-Ab and RF vs. none of controls (12.8% vs. 0%; p = 0.001). RF were detected in 45 patients with PBC and in 5 HBD (64.3% vs. 6.2%; p 〈1 0 ⁻⁶). In PBC patients, RF were more frequent than CCP-Ab (64.3% vs. 15.7%; p 〈1 0 ⁻⁶). RF-IgG were present in 18.5% of patients; RF-immunoglobulin (Ig) A in 34.3% and RF-IgM in 54.3%. These frequencies were significantly higher than those found in control group (1.2% for RF-IgG (p 〈1 0 ⁻³); 0% for RF-IgA (p 〈1 0 ⁻⁶); and 6.2% for RF-IgM (p 〈1 0 ⁻⁶)). In our PBC patients, RF-IgA were more frequent than RF-IgG (34.3% vs. 18.5%; p = 0.03) and than CCP-Ab (34.3% vs. 15.7%; p = 0.01). Six patients had only RF-IgA versus none of the control group (8.6% vs. 0%; p = 0.01). AMA, anti-Sp100 and anti-gp 210 were absent in all RA patients.ConclusionsSerological markers of RA were more frequent in PBC patients than in HBD and the vice versa was not true.     

Inhibition of neovascularization in vivo by gold compounds

As mononuclear cell infiltration and growth of pannus critically depend on synovial neovascularization in rheumatoid arthritis (RA), inhibition of the synovial blood vessels would have the potential to reduce rheumatoid inflammation. In this investigation, we studied the effect of gold sodium thiomalate (GST) and auranofin (AUR) on neovascularization in vivo by using a micropocket technique. Both GST and AUR suppressed rabbit corneal neovascularization in a dose-dependent fashion. Significant inhibition was observed by 3 mg/kg GST and 1 mg/kg AUR injected intravenously every other day. These injections maintained serum gold concentrations at the level of 2–5 g/ml and less than 2 g/ml in GST-and AUR-injected rabbits, respectively. These are concentrations attained in the serum or synovium of rheumatoid patients treated by gold compounds. Similar inhibition was observed by both intramuscular administration of GST and oral administration of AUR. In contrast, no inhibition was observed when non-steroidal anti-inflammatory drugs (NSAIDs; 20 mg/kg acetylsalicylic acid, 10 mg/kg ibuprofen and 10 mg/kg indomethacin) were injected intravenously on a daily basis. These results suggested that gold compounds have an antiangiogenic effect in vivo. The inhibition of neovascularization by gold compounds suggested that they may suppress rheumatoid synovitis by reducing the number of small blood vessels required for mononuclear cell infiltration and synovial tissue proliferation.     

An immunohistochemical and immunoelectron microscopic study of adhesion molecules in synovial pannus formation in rheumatoid arthritis

To investigate the mechanism of synovial pannus formation in rheumatoid arthritis, immunohistochemical and immunoelectron microscopic studies with monoclonal antibodies against the adhesion molecules, CD54 (ICAM-1), CD 11a (LFA-1), CDw49a (VLA-1), CDw49b (VLA-2), CDw49c (VLA-3), Cdw49d (VLA-4) and CDw49e (VLA-5), were carried out to determine the pattern of distribution of these molecules at the rheumatoid synovial cartilage junction. Treatment with anti-ICAM-1 resulted in membrane staining of most of the macrophages and fibroblasts infiltrating the synovial tissue and bordering the pannus-cartilage junction, suggesting the possibility that ICAM-1 may function to facilitate the adhesion of synovial type A cells bearing ICAM-1 to type B cells of the pannus. ICAM-1-positive macrophages and fibroblasts were often found to be in contact with lymphoid cells, suggesting also that a cellular immune reaction occurs in the formation of the pannus. In addition, VLA-3, VLA-4 and, particularly, VLA-5 were the predominant1 integrins expressed by rheumatoid synovial pannus. Since these three integrins all function as fibronectin receptors, it is possible that the fibronectin-rich environment of the rheumatoid cartilage surface effectively traps pannus cells expressing high levels of these molecules. The VLA-5 molecule was found in a pericellular and interterritorial matrix distribution in the present study, strongly suggesting that a recepfor-ligand interaction between VLA-5 and cartilage matrix may occur at the early stage of pannus formation. Furthermore, an increase in1 integrin may be necessary for the growth of the pannus and also for the upregulation of the VLA molecules, leading secondarily to increased attachment.     

Correlation of interleukin-2 receptor and neopterin secretion in rheumatoid arthritis

Summary In rheumatoid arthritis (RA) an immuno dysregulation alters the release of neopterin from human monocytes/macrophages, probably by activation of a feed-back regulation mechanism in pterin metabolism. With the overactivation of T-lymphocytes, the secretion of interleukin-2 and its receptor (IL-2R) is influenced. Investigation on 84 RA patients has shown that this immunoactivation is accompanied by an increased secretion of neopterin and soluble IL-2R in the serum, and that both parameters are very suitable for detection of inflammatory disease activity. The significant correlation between neopterin and IL-2R (r=0.65; p0.001) in RA points out a possible connection in pathomechanisms of the immune system.     

Prevalence of cardiac and aortic enlargement in rheumatoid arthritis and its relationship to some characteristics of the patients

Summary The chest radiographs of 309 patients with rheumatoid arthritis (RA) were compared with those of 309 controls matched for sex and age. Cardiac enlargement was more frequent in RA females than in controls (P<0.05) and the frequency of aortic shadow enlargement was higher in RA patients aged 60 years than in controls (P<0.05). Both cardiac and aortic enlargement was significantly related to several parameters of the severity and the activity of RA, corticosteroid therapy, and elevated blood pressure. A high mortality was present in patients with aortic enlargement and in patients with ECG signs of myocardial ischaemia.     

The geographical distribution of multiple sclerosis,rheumatoid arthritis,rheumatic heart disease and poststreptococcal nephritis in Sardinia: Climatic and socioeconomic factors

Summary The comparative geography of multiple sclerosis (MS) and non-neurological diseases considered to be autoimmune is of great interest. But there are few appropriate investigations. Some have found an increase in the frequency of MS, rheumatoid arthritis and rheumatic heart disease depending on the geographic latitude. Nevertheless, the significance of the latitude effect as an indicator of a possible etiological relationship between MS and these conditions has been questioned. In this paper, the frequency of MS, rheumatoid arthritis, rheumatic heart disease and poststreptococcal nephritis is reported from Sardinia where appreciable differences in climatic and socioeconomic conditions exist. There was a positive correlation of the distribution of MS with the distribution of rheumatic heart disease and poststreptococcal nephritis. On the other hand, no correlation was found with the distribution of rheumatoid arthritis.

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Zusammenfassung Die Ähnlichkeit zwischen Multipler Sklerose (MS) und nicht neurologischen autoimmunen Erkrankungen veranlassen zur Annahme, daß einige gemeinsame ätiologische Mechanismen im Spiele sein könnten. Das Problem der vergleichenden geographischen Verteilung von Multipler Sklerose und autoimmuner Krankheit ist wenig untersucht. Einige Forscher fanden eine ähnliche Zunahme der Häufigkeit der MS, rheumatoider Arthritis und rheumatischer Herzkrankheiten bei zunehmenden Breitengraden. Es besteht allerdings Zweifel, ob tatsächlich dieser latitude effect als ein wirklicher Indikator von ätiologischen Gemeinsamkeiten zwischen den genannten Krankheiten anzusehen ist. Wir berichten in der vorliegenden Arbeit über die Häufigkeit von MS, rheumatoider Arthritis und rheumatischen Herzkrankheiten sowie Nephritis nach Streptokokkeninfektionen in Sardinien, wo nennenswerte Unterschiede in Bezug auf klimatische und sozioökonomische Gegebenheiten bestehen. Die Verteilung der MS zeigte eine positive Korrelation mit der Verteilung rheumatischer Herzkrankheiten und von Nephritis nach Streptokokkeninfektion. Andererseits wurde keine Korrelation mit der Verteilung der Polyarthritis rheumatica festgestellt.

     

No interference of rheumatoid factor(s) with toxoplasmosis IgM determination in infancy

Sera from 263 newborns and infants suspected of congenital toxoplasmosis were tested for the presence of rheumatoid factor (RF) by the latex agglutination test, of which 40 were also tested by the enzyme-linked immunosorbent assay (ELISA). RF was detected in only one serum sample (0.38%), suggesting that false-positive results of the IgM-indirect fluorescent antibody test and the IgM-ELISA due to RF is most unusual in infancy.     

Cytokine enhancement of monocyte/synovial cell attachment to the surface of cartilage: a possible trigger of pannus formation in arthritis

Summary When rheumatoid articular cartilage samples were incubated with normal peripheral blood monocytes and cultured synovial cells in the presence of recombinant human interleukin-1 (IL-1) in vitro, large numbers of monocytes were seen to be attached to the articular surface. Significant numbers of monocytes invaded the cartilage tissue when the rheumatoid cartilage samples were pre-incubated with 10 U/ml of IL-1. Considerable numbers of monocytes were also attached to normal cartilage when these were pre-incubated with IL-1. It is of interest that recombinant human gamma interferon (-IFN) did not enhance monocyte attachment. However, there was a significantly greater attachment of monocytes to rheumatoid than to normal cartilage. When normal cartilage was exposed to collagenase and then incubated with monocytes or synovial cells in the presence of 10 U/ml of IL-1, large numbers of cells were attached to the natural cartilage surface but not to the cut surface. These phenomena were much more intense when the rheumatoid cartilage was pre-incubated with collagenase. These results indicate that increased levels of IL-1 in the rheumatoid joint may play an important role in joint destruction by stimulation of pannus formation by inducing synovial cell attachment to the articular surface.     

Altered thiol status in patients with rheumatoid arthritis

Summary The thiol status of patients with rheumatoid arthritis is significantly different from that of controls. Plasma thiol levels are lower, albumin thiol reactivity is altered and intracellular thiol levels measured after hemoglobin precipitation are increased. These variations correlate with other indices of disease severity and are one measure of a disturbance in the degree of oxidation of the blood. Penicillamine, in common with other effective therapeutic agents, produces an increase in serum thiol concentration. It causes a greater effect on serum thiol reactivity than other drugs and in particular it increases fast reacting thiol levels without significantly altering the slow reacting thiol level.