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ID PMID Title PublicationDate abstract
11721675 Identification of the pharmaceutical care issues of rheumatoid arthritis patients in secon 2001 Oct OBJECTIVE: To explore the perceptions of multidisciplinary health care professionals (HCPs) and patients of the pharmaceutical care issues (PCIs) relating to rheumatoid arthritis (RA). DESIGN: Qualitative study using semi-structured one to one interviews and focus groups to explore patient perceptions. Interviews and focus groups were taped and transcribed verbatim, then described and coded for meaning to produce 'in-vivo' codes, which were then grouped to form themes. Nominal group methodology was used to generate and rank a list of HCP perceptions of the key PCIs of RA patients. The PCIs were ranked according to clinical importance and order of occurrence from admission as perceived by the HCP group. SETTING: Rheumatology ward and outpatient clinic in a teaching hospital. MAIN OUTCOME MEASURES: Generation and ranking of PCIs, generation of themes from patient interviews. RESULTS: Optimisation of pain control was identified by the nominal group as being the primary aim for patients on admission and was also the most commonly described symptom by patients. Two PCIs not predicted by the HCPs' nominal group was the frequency of infections and the associated discharge and patients described experiencing 'over-education' by HCPs, which could lead to anxiety. Complementary medicine in conjunction with traditional therapy was raised as a significant health benefit by patients. CONCLUSION: Many patients' views mirrored the PCIs identified by HCPs, but some were not anticipated; the value of patient interviews to ensure appropriate service development was demonstrated. Several PCIs emerged for future incorporation by the multi-disciplinary team into standardised models of pharmaceutical care for use in secondary care and at the secondary/primary care interface for improvement of seamless care. There is a need to target educational interventions and to identify those who will benefit from advice on complementary medicine. Further work is required to develop a tool to identify the educational needs of RA patients and targeting of the information provided. This will help ensure the delivery of pharmaceutical care is designed to match the needs of individual patients.
10394868 Wrist and finger joint MR imaging in rheumatoid arthritis. 1999 Jul PURPOSE: To elaborate the best MR imaging protocol for studies in rheumatoid arthritis (RA) and to evaluate the sensitivity and interobserver agreement with respect to detection of bone erosions (MR and radiography) and grading of synovial membrane hypertrophy (MR imaging only). MATERIAL AND METHODS: MR imaging and conventional radiography of wrist and metacarpophalangeal (MCP) joints were performed in 41 RA patients and 3 healthy controls. The following pulse sequences were applied: T1-weighted spin-echo (T1-SE) with and without contrast enhancement, T2-SE, T2-turbo-SE, T1-2D-FLASH, T1-3D-FLASH, fat-saturated-T1-SE, STIR and 3D-DESS. RESULTS: Bone erosions were found by MR compared to radiography in 261 versus 85 bones of the wrist (ratio 3.1) and 59 versus 21 MCP joint quadrants (ratio 2.81). MR and radiography interobserver agreements were both approximately 90%. Likewise, MR scored synovial membrane hypertrophy in wrist and MCP joints with a high interobserver agreement. The most informative MR sequence appeared to be contrast-enhanced T1-SE MR, preferably with fat saturation. A STIR sequence or T2-weighted fat saturation sequence was useful in screening for joint disease. CONCLUSION: The sensitivity of MR is superior to conventional radiography with respect to detection of bone erosions in wrist and MCP joints. The interobserver agreement for MR and radiography was similar. Thus, MR of wrist and finger joints may become a useful supplement to conventional radiography in the evaluation of RA patients in clinical trials and clinical practice.
11489536 A comparison of rheumatoid arthritis and fibromyalgia patients and healthy controls expose 2001 Aug 17 Specific weak time varying pulsed magnetic fields (MF) have been shown to alter animal and human behaviors, including pain perception and postural sway. Here we demonstrate an objective assessment of exposure to pulsed MF's on Rheumatoid Arthritis (RA) and Fibromyalgia (FM) patients and healthy controls using standing balance. 15 RA and 15 FM patients were recruited from a university hospital outpatient Rheumatology Clinic and 15 healthy controls from university students and personnel. Each subject stood on the center of a 3-D forceplate to record postural sway within three square orthogonal coil pairs (2 m, 1.75 m, 1.5 m) which generated a spatially uniform MF centered at head level. Four 2-min exposure conditions (eyes open/eyes closed, sham/MF) were applied in a random order. With eyes open and during sham exposure, FM patients and controls appeared to have similar standing balance, with RA patients worse. With eyes closed, postural sway worsened for all three groups, but more for RA and FM patients than controls. The Romberg Quotient (eyes closed/eyes open) was highest among FM patients. Mixed design analysis of variance on the center of pressure (COP) movements showed a significant interaction of eyes open/closed and sham/MF conditions [F=8.78(1,42), P<0.006]. Romberg Quotients of COP movements improved significantly with MF exposure [F=9.5(1,42), P<0.005] and COP path length showed an interaction approaching significance with clinical diagnosis [F=3.2(1,28), P<0.09]. Therefore RA and FM patients, and healthy controls, have significantly different postural sway in response to a specific pulsed MF.
11174466 Measurement of tumor necrosis factor-alpha messenger RNA in synovial fibroblasts by real-t 2001 Feb We applied a real-time quantitative assay to determine the expression of tumor necrosis factor-alpha (TNF-alpha) messenger RNA (mRNA) in tissue samples. This method is based on the real-time monitoring of reverse transcriptase-polymerase chain reaction (RT-PCR) with a dual-fluorescence-labeled probe and a sequence detector. A linear correlation existed between assay measurements and input target (r = 0.999). TNF-alpha mRNA was detected in the synovial cells of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and also in the U937, THP1, and HL60 cell lines. Stimulation with interleukin-1alpha (IL-1alpha) caused an immediate increase in the intracellular level of TNF-alpha mRNA. In particular, the relative copy number of TNF-alpha mRNA increased dramatically from 15 to 3554 in synovial cells from RA patients. This method is simple, accurate, and sensitive for the quantitative detection of TNF-alpha mRNA. The real-time quantitative RT-PCR assay may be valuable for measuring TNF-alpha mRNA expression in clinical samples.
11148180 Tartrate-resistant acid phosphatase isoform 5b as serum marker for osteoclastic activity. 2001 Jan BACKGROUND: Tartrate-resistant acid phosphatase (AcP) 5b is a marker of osteoclastic activity and bone resorption. Immunoassays for serum TRAcP may lack sensitivity and specificity because of the presence of non-bone isoform 5a. The purpose of this study was to isolate the serum isoforms, quantify their disease-related expressions, and test an improved immunoassay for TRAcP 5b. METHODS: We separated TRAcP isoforms chromatographically from pooled sera of healthy, rheumatoid arthritis (RA) and endstage renal disease (ESRD) subjects. TRAcP isoforms were identified by electrophoresis and quantified by biochemical and immunochemical assays. Serum TRAcP activity in healthy, RA, and ESRD cohorts was assessed at pH 5.5 and 6.1, and compared with bone alkaline phosphatase (BAP) and N-telopeptides of type I collagen (NTx). RESULTS: TRAcP isoforms 5a and 5b were present in all sera; 5b was identical to osteoclastic TRAcP. In serum from healthy subjects, 5a accounted for 87% of the enzyme protein but only 55% of the activity. In RA, both isoforms were increased two- to threefold in protein, but their specific activities were subnormal. In ESRD, only 5b was abnormal, being increased fivefold in protein and threefold in activity. In RA sera, TRAcP activity did not correlate with either BAP or NTx. In ESRD sera, TRAcP activity correlated with BAP and NTx only when measured at pH 6.1. CONCLUSIONS: All sera contained both TRAcP isoforms 5a and 5b, but only 5b was present in bone. TRAcP isoform expression was variable in different diseases. Measurement of TRAcP activity at pH 6.1 improves the specificity of immunoassay for isoform 5b.
9754677 Pharmacological effects of SA96 (bucillamine) and its metabolites as immunomodulating drug 1998 Jun SA96 (generic name, bucillamine) is a disease-modifying anti-rheumatoid arthritis (RA) drug with immunological effects. This compounds has two sulfhydryl groups in its molecule, and the differences and similarities between this drug and D-penicillamine, which is also a sulfhydryl group-containing anti-rheumatic drug, have frequently been discussed. To clarify the pharmacological differences between these two drugs, we examined the concentrations of the compounds and its metabolites in serum and synovial fluid, paying special attention to the metabolites of SA96 produced in vivo. SA96 was metabolized in a very short time to SA981 which is a disulfide compound formed by intramolecular binding of two sulfhydryl groups, and transferred to synovial fluid. In addition SA981 had significant suppressive effects on IL-6 and IL-8 production by synovial cells in vitro. These results demonstrate that SA96, which has two sulfhydryl groups, exhibits anti-rheumatic effects via a pharmacological action clearly different from that of D-penicillamine.
11163097 Noninherited maternal HLA antigens: a proposal to elucidate their role in the immune respo 2000 Dec In the last 10 years there has been renewed interest in the possible impact of the noninherited maternal HLA antigens (NIMA) on the immune response. This interest is only surpassed by an even stronger scepticism that the effect really exists and is clinically relevant. In this presentation we will summarize the published and some unpublished data supporting the existence of the NIMA effect and formulate the questions, which are relevant for understanding the mechanisms by which NIMA could influence the immune response. Three different approaches that could give us an insight of the cellular and molecular basis of the NIMA effect (if it exist) will be proposed.
10782806 Bucillamine suppresses human Th1 cell development by a hydrogen peroxide-independent mecha 2000 Apr OBJECTIVE: To clarify the effect of bucillamine, an antirheumatic drug related to D-penicillamine, on the development of human Th1 and Th2 cells in vitro. METHODS: Peripheral blood mononuclear cells (PBMC) or purified CD4+ T cells were subjected to the priming culture in which cells were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies for 3 days and expanded for 4 days in the presence of interleukin-2. Cytokine production by the generated cells was determined on a flow cytometer using intracellular cytokine staining. The effects of bucillamine were determined by adding it for the first 3 days of the priming culture. RESULTS: Bucillamine decreased the frequency of interferon-gamma (IFN-gamma) producing CD4+ T cells among generated CD4+ T cells after the priming culture of PBMC, although D-penicillamine did not. This effect of bucillamine was independent of hydrogen peroxide since it was not reversed by a catalase treatment. One of the bucillamine metabolites, SA981, which exerts its effects by a hydrogen peroxide-independent mechanism, decreased the frequency of IFN-gamma producing CD4+ T cells more potently than bucillamine. Bucillamine reduced the frequency of Th1 cells after the priming culture of purified CD4+CD45RO- T cells, indicating that bucillamine exerts the effect in the absence of monocytes or B cells. CONCLUSION: Bucillamine directly acts on CD4+CD45RO- T cells to suppress Th1 cell development by a hydrogen peroxide-independent mechanism. This previously unknown action may explain the in vivo effect of bucillamine in the treatment of rheumatoid arthritis.
9794428 Soluble VCAM-1 induces chemotaxis of Jurkat and synovial fluid T cells bearing high affini 1998 Nov 1 It has been shown that cells with high affinity very late Ag (VLA)-integrins have up-regulated expression of a beta1-subunit epitope, which is detected by 15/7 mAb. In this study, we demonstrate that soluble VCAM-1 (sVCAM-1) exhibits chemotactic activity of T cells with high affinity VLA-4 against VCAM-1, such as Jurkat T cells and IL-2-dependent T cells. Moreover, we found that T cells in the synovial fluid show high basal migration in the absence of sVCAM-1, compared with peripheral blood T cells in patients with rheumatoid arthritis. Among T cells in the synovial fluid, CD45RO+ memory T cells, in response to sVCAM-1, showed a much higher than basal migratory response when compared with CD45RA+ naive cells, while no significant difference was observed between CD4+ and CD8+ T cells. The chemotactic activity of sVCAM-1 is inhibited in the presence of anti-VCAM-1 and anti-VLA-4, which interfered with the binding between VCAM-1 and VLA-4. Inhibition studies using various kinase inhibitors (C3 exoenzyme, KN62, and H7) show that Rho, Ca2+/calmodulin-dependent kinase II, and protein kinase C are involved in signal transduction in sVCAM-1-induced chemotaxis, respectively, whereas tyrosine kinase seems to play a lesser role, since genistein showed only partial inhibition of T cell chemotaxis. Western blot analysis using an anti-phospho-serine mAb (MO82) reveals that Ser82 in the vimentin is phosphorylated specifically by Ca2+/calmodulin-dependent kinase II through sVCAM-1 activation in the IL-2 dependent T cells. Collectively, by inducing migration and recruitment of T cells through several kinase activations, sVCAM-1 contributes to the development of the inflammation of synovial lesion.
11114278 Release of cartilage and bone macromolecules into synovial fluid: differences between psor 2001 Jan OBJECTIVE: To elucidate whether differences in the destructive tissue process in cartilage and bone in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) can be recognised by different release patterns of molecular fragments derived from joint tissue. METHODS: Aggrecan, cartilage oligomeric matrix protein (COMP), and bone sialoprotein (BSP) were quantified by immunoassays in knee joint synovial fluid samples. These were obtained early in the disease course of patients with PsA and RA. At the time of arthrocentesis radiographs of their knee and hip joints were normal. RESULTS: At follow up no destruction had developed in the knees and hips of most patients with PsA (n=18), whereas the patients with RA could be separated into one "destructive" group (n=18) and one "non-destructive" group (n=25). Patients with PsA had low synovial fluid aggrecan concentrations (p<0.001 v the RA destructive group) but high COMP concentrations (p<0.01 and p<0.05 v destructive and non-destructive RA groups, respectively). Consequently, the aggrecan/COMP ratio was lowest in the PsA group (p<0.001 and p<0.01 v the destructive and non-destructive RA group, respectively). The synovial fluid concentrations of BSP did not differ between the three patient groups. CONCLUSIONS: The release pattern of aggrecan and COMP, reflecting cartilage turnover, differed between the PsA group and, particularly, the destructive RA group. This suggests that different pathophysiological mechanisms for cartilage involvement operate in these conditions, with different destructive potential. The BSP concentrations did not differ between the patients groups, which indicates similar levels of bone involvement.
9821596 A prospective randomized comparison of Sutter and Swanson silastic spacers. 1998 Oct This study compares two currently available prostheses for the reconstruction of rheumatoid joints. A single operator performed 72 resection arthroplasties with Swanson or Sutter prostheses being randomly allocated. Assessment of each patient was carried out preoperatively, and at 6 months and 12 months postoperatively by a single investigator. In the Swanson group an improvement of the flexion arc was seen, from 29 degrees to 44 degrees at 6 months but this reduced to 36 degrees at 12 months. In the Sutter group there was no significant difference between flexion arcs pre- and postoperatively. Grip strength improved in the Swanson group, but not in the Sutter group. Extensor lag was improved in both groups. Patient satisfaction measured by linear analogue scales for pain, function and deformity was high in both groups.
10596840 Plasma and tissue kallikrein in arthritis and inflammatory bowel disease. 1999 Sep To ascertain the participation of the plasma kallikrein-kinin system (KKS) in arthritis and inflammatory bowel disease, we used two rat models resembling rheumatoid arthritis and Crohn's disease. Proteoglycan-polysaccharide from group A streptococcus (PG-APS) produced chronic destructive inflammation and systemic response in the genetically susceptible Lewis rat, in the joints when injected intraperitoneally and in the bowel when injected into the gut wall. In both models, the KKS is activated, as evidenced by decreased prekallikrein, factor XI and high molecular weight kininogen. A specific plasma kallikrein inhibitor, Bz-Pro-Phe-boroarginine, reverses the plasma changes as well as the clinical gross and microscopic pathology of both the experimental arthritis and the inflammatory bowel disease in the genetically susceptible rats. We have also shown that the tissue kallikrein system is involved in the intestinal inflammatory changes. Intestinal tissue kalikrein (ITK) is localized in goblet cells in both normal and inflamed tissue. In chronic granulomatous inflammation, ITK is localized in macrophages. ITK decreases in chronic inflammation, probably due to secretion, since the mRNA is unchanged. Kallikrein binding protein, the ITK inhibitor, decreases due to enzyme-inhibitor complexes. Both plasma and tissue kallikrein are appealing targets for drug therapy of rheumatoid arthritis and Crohn's disease.
10225809 Rheumatic disease and the Australian aborigine. 1999 May OBJECTIVE: To document the frequency and disease phenotype of various rheumatic diseases in the Australian Aborigine. METHODS: A comprehensive review was performed of the archaeological, ethnohistorical, and contemporary literature relating to rheumatic diseases in these indigenous people. RESULTS: No evidence was found to suggest that rheumatoid arthritis (RA), ankylosing spondylitis (AS), or gout occurred in Aborigines before or during the early stages of white settlement of Australia. Part of the explanation for the absence of these disorders in this indigenous group may relate to the scarcity of predisposing genetic elements, for example, shared rheumatoid epitope for RA, B27 antigen for AS. In contrast, osteoarthritis appeared to be common particularly involving the temporomandibular joint, right elbow and knees and, most probably, was related to excessive joint loading in their hunter gatherer lifestyle. Since white settlement, high frequency rates for rheumatic fever, systemic lupus erythematosus, and pyogenic arthritis have been observed and there are now scanty reports of the emergence of RA and gout in these original Australians. CONCLUSION: The occurrence and phenotype of various rheumatic disorders in Australian Aborigines is distinctive but with recent changes in diet, lifestyle, and continuing genetic admixture may be undergoing change. An examination of rheumatic diseases in Australian Aborigines and its changing phenotype may lead to a greater understanding of the aetiopathogenesis of these disorders.
11698482 Enhancing effect of IL-1, IL-17, and TNF-alpha on macrophage inflammatory protein-3alpha p 2001 Nov 15 Macrophage inflammatory protein (MIP)-3alpha is a chemokine involved in the migration of T cells and immature dendritic cells. To study the contribution of proinflammatory cytokines and chemokines to the recruitment of these cells in rheumatoid arthritis (RA) synovium, we looked at the effects of the monocyte-derived cytokines IL-1beta and TNF-alpha and the T cell-derived cytokine IL-17 on MIP-3alpha production by RA synoviocytes. Addition of IL-1beta, IL-17, and TNF-alpha induced MIP-3alpha production in a dose-dependent manner. At optimal concentrations, IL-1beta (100 pg/ml) was much more potent than IL-17 (100 ng/ml) and TNF-alpha (100 ng/ml). When combined at lower concentrations, a synergistic effect was observed. Conversely, the anti-inflammatory cytokines IL-4 and IL-13 inhibited MIP-3alpha production by activated synoviocytes, but IL-10 had no effect. Synovium explants produced higher levels of MIP-3alpha in RA than osteoarthritis synovium. MIP-3alpha-producing cells were located in the lining layer and perivascular infiltrates in close association with CD1a immature dendritic cells. Addition of exogenous IL-17 or IL-1beta to synovium explants increased MIP-3alpha production. Conversely, specific soluble receptors for IL-1beta, IL-17, and TNF-alpha inhibited MIP-3alpha production to various degrees, but 95% inhibition was obtained only when the three receptors were combined. Similar optimal inhibition was also obtained with IL-4, but IL-13 and IL-10 were less active. These findings indicate that interactions between monocyte and Th1 cell-derived cytokines contribute to the recruitment of T cells and dendritic cells by enhancing the production of MIP-3alpha by synoviocytes. The inhibitory effect observed with cytokine-specific inhibitors and Th2 cytokines may have therapeutic applications.
9177925 Autoantibodies to collagens in Japanese patients with ankylosing spondylitis. 1997 May OBJECTIVE: We measured antibody levels against human type I, II, III and IV collagens in Japanese patients with ankylosing spondylitis (AS) by enzyme linked immunosorbent assay (ELISA). RESULTS: Significant elevations of antibodies against type II (IgG and IgA classes) and type IV (IgA class) collagens were observed in AS patients, whilst there was no significant elevation of any antibody class against type I or III collagen when compared to controls. CONCLUSION: These findings indicate that AS patients have immune responses to type II and IV collagens, which may be responsible for sustaining the characteristic local inflammations in AS.
9184269 Methotrexate-induced pneumonitis in patients with rheumatoid arthritis and psoriatic arthr 1997 May Pneumonitis is emerging as one of the most unpredictable and potentially serious, adverse effects of treatment with MTX. Its prevalence in rheumatoid arthritis (RA) has been estimated from several retrospective and prospective studies to range from 0.3% to 18%. On the other hand, MTX-induced pneumonitis seems to be very rare in psoriatic arthritis (PsA). Our review of 194 RA patients and 38 PsA patients receiving MTX has identified four RA patients and one PsA patient with MTX-induced pneumonitis, giving a prevalence of 2.1% and 0.03%, respectively. Diagnosis was suggested by clinical history and radiographic findings, but the bronchoalveolar lavage plays an important role both in excluding infectious agents and in providing information for understanding the pathogenesis of lung injury. The presence of a lymphocyte alveolitis with a predominance of CD4+ T cells in 3 RA patients and CD8+ T cells with a concomitant increase in neutrophils in another case suggests that immunologically mediated reactions may be one damage mechanism in MTX-induced pneumonitis. Although risk factors for MTX-induced pulmonary toxicity are poorly understood, the presence in 3 out of 5 of our patients of pre-existing lung disease, represented by diffuse interstitial changes on chest X-ray, and mild bronchial asthma in two RA patients and by pulmonary silicosis in the patient with PsA may account for a predisposition to the development of MTX pneumonitis.
10908695 Major histocompatibility complex phenotypes influence serum testosterone concentration. 2000 Jul OBJECTIVES: (a) To confirm our earlier observation that the phenotype HLA-DR4,7 occurs with higher frequency in male patients with rheumatoid arthritis (RA) than in female patients. (b) To test the hypothesis that DR7 is associated with low normal serum testosterone (Te) levels in healthy males; this might explain the increased frequency of DR4,7 in male patients since there appears to be a relationship between low serum Te and RA. (c) To characterize the association between HLA alleles and serum Te concentration in healthy males. METHODS: An additional 82 Newfoundland (NF) RA patients were HLA-DR typed and, combined with our earlier data and data from the 11th International Histocompatibility Workshop, gave HLA-DR and sex information on 373 RA patients. Ninety-four healthy NF males were typed for HLA, the microsatellite marker TNFa (located close to the tumour necrosis factor alpha gene) and complement factor B (BF). An additional 38 males were included, selected partly based on their HLA-B type. RESULTS: We confirmed our earlier finding of a higher frequency of HLA-DR4,7 in male RA patients compared with female RA patients (P<0.01). Contrary to our expectations we found that DR7 was associated with higher than mean values of Te as were B5, B27, DR1, TNFa7 and BF F positivity. Conversely, low Te concentrations were found in men with B15, DR2, DR5, TNFa5 and who were BF F negative. In 28 male 'early-onset' RA patients we did not find an increased frequency of HLA alleles associated with low Te levels as compared with the frequency in 41 'late-onset' patients, suggesting that if low Te level is a risk factor and is present before onset of RA then the level cannot be explained by an association between Te level and major histocompatibility complex (MHC) phenotype. CONCLUSION: This study indicates that a man's MHC phenotype may influence his serum Te concentration, but the relationship of this, if any, to the pathogenesis of RA remains an area of speculation.
9550483 Evaluative laboratory testing practices of United States rheumatologists. 1998 Apr OBJECTIVE: Several laboratory tests can be used to monitor disease activity in patients with rheumatic diseases. We sought to learn how rheumatologists use evaluative laboratory tests in the care of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. METHODS: We surveyed United States rheumatologists by mailed questionnaire. Of the 976 rheumatologists who received the questionnaire, 575 responded, for a response rate of 59%. RESULTS: Eighty-six percent of the respondents reported using either the erythrocyte sedimentation rate (ESR) or C-reactive protein level to monitor patients with RA, 92% used either the anti-DNA antibody level or complement C3 level to monitor patients with SLE, and 95% used either the ESR or ANCA levels to monitor patients with ANCA-associated vasculitis. The frequency of testing was distributed over a broad range, but testing was common. Testing on 50% of the visits or more was reported by 52% of respondents for RA, 59% of respondents for SLE, and 64% of respondents for ANCA-associated vasculitis. Between 7% and 11% of respondents reported testing patients on every visit, regardless of clinical disease activity. The majority of respondents reported not altering the treatment of clinically stable patients based on these test results. CONCLUSION: Evaluative laboratory testing is common, and is rarely used as an independent guide for treatment.
9236672 Relationship between pentosidine levels in serum and urine and activity in rheumatoid arth 1997 Jun Pentosidine is one of the advanced glycation end-products and is formed by glycosylation and oxidation. The aim of this study is to investigate the relationship between serum and urinary pentosidine levels and the activity of rheumatoid arthritis (RA). Using HPLC with column switching, we measured pentosidine in serum and urine from 77 patients with RA and 62 normal control subjects. The clinical features, blood biochemistry and activity of inflammation were examined in RA patients. Serum and urinary pentosidine in RA were significantly higher than in controls. Pentosidine significantly correlated with age, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor, joint score and Lansbury Index in RA. The levels of pentosidine were higher in patients with active RA than in those with inactive RA. Serum and urine levels of pentosidine correlated with the activity of RA, and serum and urinary pentosidine may be a significant and novel marker for evaluating the disease status and the activity of RA.
9794498 Effects of interleukin-1 receptor antagonist in a slow-release hylan vehicle on rat type I 1998 Oct PURPOSE: To determine the effect of hylan fluid (HA), a model slow release vehicle on the pharmacokinetic profile and efficacy of interleukin-1 receptor antagonist (IL-1ra) in rats with established type II collagen arthritis. METHODS: Female Lewis rats with type II collagen arthritis were treated daily, every other day or every third day with single subcutaneous (sc) injections of IL-1ra formulated in HA and the effects on arthritis determined. Results were compared to those obtained with IL-1ra in citrate buffered saline with EDTA and polysorbate (CSEP). Sequential blood levels were determined in rats injected sc with IL-1ra in CSEP or HA. RESULTS: Incorporation into HA led to slower release of IL-1ra into the bloodstream and maintained therapeutic blood levels of IL-1ra for a longer time compared to the IL-1ra/CSEP formulation. Single daily sc doses of 100 mg/kg IL-1ra in CSEP were ineffective in type II collagen arthritis. By contrast, once per day dosing of 100 mg/kg IL-1ra in HA provided 78% inhibition of paw swelling. Every other day dosing with 100 mg/kg IL-1ra in HA resulted in 62% inhibition. IL-1ra (100 mg/ kg in HA) given every third day provided 19% inhibition of arthritis. Improved efficacy correlated with improved pharmacokinetics. CONCLUSIONS: Administration of IL-1ra in the slow release vehicle HA improves pharmacokinetics and efficacy in rat type II collagen arthritis.