Literature on Psoriatic Arthritis

Related ArticlesAntilipoxygenase activity of copper complexes of aminoalkanoate type.

Neuro Endocrinol Lett. 2006 Dec;27 Suppl 2:180-2

Authors: Ponist S, Valentova J, Bezakova L, Oblozinsky M

OBJECTIVES: Lipoxygenases (EC 1.13.11.12, LOX) catalyze the hydroperoxidation of polyunsaturated fatty acids (PUFA). This reaction leads to the production of conjugated hydro peroxide dienes of PUFA. In animals, LOX generate leukotriens (LT) and lipoxins, which belong to inflammatory mediators. It is believed that restricting LT synthesis by inhibition of LOX would have therapeutic utility for the treatment of a variety of inflammatory conditions (e.g. asthma, rheumatoid arthritis, psoriasis). METHODS & RESULTS: The process of production and elimination of radical intermediates in vitro can be monitored by determination of LOX activity. We assessed the concentration of PUFA hydroperoxides in our system with LOX-catalyzed enzyme reaction spectrophotometrically. The inhibition of LOX activity (LOX from cytosol fraction of rat lungs) with selected N-salicylideneaminoalkanoatocopper(II) complexes was tested. In our experiments, all compounds tested showed an inhibitory effect on LOX catalyzed hydroperoxidation of PUFA. Cu(II) (from CuSO(4).5H(2)O dilution) ions also inhibited this enzyme reaction, but all compounds studied had a 10 times higher anti-LOX activity. The most effective of these complexes was monohydrate aqua-(N-salicylidene-L-a-alaninato)copper(II) complex [Cu(sal-L-alpha-ala)(H(2)O)].H(2)O with IC(50) 1.86×10(-4) mol/l. CONCLUSIONS: These complexes are known for their anti-phlogistic and radioprotective properties and they can be classified as potential antiradical compounds. The structure of these complexes is similar to the active site of Cu,Zn-SOD (superoxide dismutase) and superoxide radical scavenger activity of these complexes is known. We found that these copper complexes were capable to inhibit LOX activity, which may be related with their anti-radical properties.

PMID: 17159810 [PubMed - in process]

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Related ArticlesDrug evaluation: the C5a receptor antagonist PMX-53.

Curr Opin Mol Ther. 2006 Dec;8(6):529-38

Authors: Köhl J

Peptech is developing PMX-53, a complement C5a inhibitor for the potential treatment of inflammatory disorders, including rheumatoid arthritis and psoriasis. Phase Ib/IIa clinical trials have been completed for both indications.

PMID: 17243489 [PubMed - indexed for MEDLINE]

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Related Articles[Genetics in patients with psoriatic arthritis]

Orv Hetil. 2006 Dec 17;147(50):2415-9

Authors: Katalin I, Koó E, Magdolna S, Vladimir B, Bitterova O

OBJECTIVES: HLA antigens were studied in 100 Hungarian patients suffered from psoriatic arthritis. Genetic markers for the development of different clinical pattern of the disease and skin disorder were identified. METHODS: Determination of class I and class II antigens was performed by using microlymphocytotoxicity assay. RESULTS: The frequency of HLA-Cw6, HLA-B16 (and its split B-39) and HLA-B27 antigens were significantly higher in psoriatic arthritis patients than in the Hungarian general population. No connection was found between HLA-DR4, DR7, B17 antigens and psoriatic arthritis. The patients were classified according to the subgroups proposed by Gladman. The comparisons between the clinical subgroups revealed a significant association of HLA-B27 with spondylitis (Gladman 4, 5, 6, 7). There was no association between HLA DR4 and polyarticular pattern of the disease (Gladman 3, 7). Psoriasis seemed to be significantly associated only with HLA-Cw6. There was a higher frequency of HLA-B38 in psoriatic arthritis patients with erythroderma.

PMID: 17274187 [PubMed - in process]

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Related ArticlesEfficacy of infliximab on MRI determined bone oedema in psoriatic arthritis.

Ann Rheum Dis. 2006 Dec 21;

Authors: Marzo-Ortega H, McGonagle D, Rhodes LA, Tan AL, Conaghan PG, O’connor P, Tanner SF, Fraser A, Veale D, Emery P

BACKGROUND: and aims: Psoriatic arthritis is commonly associated with bone pathology including entheseal new bone formation and osteolysis. On MRI, areas of active clinical involvement are represented by bone oedema and synovitis. The purpose of this study was to assess the impact of infliximab on bone oedema in PsA as shown by magnetic resonance imaging. METHODS: 18 patients with joint swelling, psoriasis and seronegativity for rheumatoid factor received 4 infusions of infliximab 3 mg/kg in combination with methotrexate. MRI of affected hand (12 patients) or knee joints (6 patients) was performed pre and post therapy. The primary outcome was the assessment of bone oedema and synovitis at 20 weeks as shown by MRI. Secondary outcomes included the ACR response criteria, psoriasis skin scores (PASI) and a quality of life measure (PsAQoL). RESULTS: At baseline, bone oedema was seen in 50% of the patients (7 hands and 2 knees) in 30% of scanned joints and this improved or resolved in all cases in the hand joints (p=0.018) and one knee joint at 20 weeks. MRI synovitis was reduced in 90% of cases. Likewise a statistically significant improvement in all clinical outcomes was seen at week 20 including PASI (p=0.003) and PsAQoL (p=0.006). 65% (n=11) of the patients achieved an ACR response, of which 45% had ACR70 or above and 54% ACR20 or ACR50. CONCLUSIONS: Infliximab therapy is associated with dramatic improvements in MRI determined bone oedema in PsA in the short term. It remains to be determined whether this translates into the prevention of radiographic new bone formation, bone fusion or osteolysis in PsA.

PMID: 17185324 [PubMed - as supplied by publisher]

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Related ArticlesMycophenolate mofetil treatment improves hypertension in patients with psoriasis and rheumatoid arthritis.

J Am Soc Nephrol. 2006 Dec;17(12 Suppl 3):S218-25

Authors: Herrera J, Ferrebuz A, Macgregor EG, Rodriguez-Iturbe B

Evidence that was obtained in several experimental models and in strains of hypertensive rats indicates that infiltration of inflammatory cells and oxidative stress in the kidney play a role in the induction and maintenance of hypertension. Similar evidence is lacking in human hypertension, at least in part, because immunosuppressive treatment is unjustified in patients with hypertension. For addressing this issue, patients who were prescribed by their private physicians mycophenolate mofetil (MMF) for the treatment of psoriasis or rheumatoid arthritis and had, in addition, grade I essential hypertension and normal renal function were studied. Eight patients were studied before MMF was started, during MMF treatment, and 1 mo after MMF treatment had been discontinued. Other treatments and diet were unchanged in the three phases of the study. MMF therapy was associated with a significant reduction in systolic, diastolic, and mean BP. Urinary excretion of TNF-alpha was reduced progressively by MMF treatment and increased after MMF was discontinued. Reduction of urinary malondialdehyde, TNF-alpha, and RANTES excretion during MMF administration did not reach statistical significance but had a direct positive correlation with the BP levels. These data are consistent with the hypothesis that renal immune cell infiltration and oxidative stress play a role in human hypertension.

PMID: 17130265 [PubMed - in process]

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Related ArticlesToll-like Receptor-2 Expression Is Upregulated in Antigen-Presenting Cells from Patients with Psoriatic Arthritis: A Pathogenic Role for Innate Immunity?

J Rheumatol. 2006 Dec 15;

Authors: Candia L, Marquez J, Hernandez C, Zea AH, Espinoza LR

OBJECTIVE: To study Toll-like receptor-2 (TLR-2) and TLR-4 expression in antigen-presenting cells from patients with psoriatic arthritis (PsA). METHODS: We measured expression of TLR-2 and TLR-4 in monocyte-derived dendritic cells from patients with PsA and with rheumatoid arthritis (RA), and in healthy controls. Dendritic cells were obtained from freshly isolated monocytes, stimulated with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin 4 (IL-4) after 6 days in culture. To obtain mature dendritic cells, lipopolysaccharide stimulation and 2 additional days in culture were necessary. The expression of TLR-2, TLR-4, HLA-DR, and CD86 was studied at baseline, at 6 days, and at 8 days by flow cytometry. To establish the functional properties of TLR expression we studied the following cytokines in cell supernatants: tumor necrosis factor-a (TNF-a), interferon-g (IFN-g), IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, and GM-CSF. TLR-2 expression was confirmed by Western blot analysis. RESULTS: Ten PsA patients with active disease and 8 healthy controls were studied, along with 4 patients with RA. TLR-2 expression was increased in immature dendritic cells from patients with PsA. Monocytes and mature dendritic cells did not show statistically significant differences. No difference was observed in the expression of TLR-4 in any cell type. The supernatant expression of cytokines showed a Th1 pattern, mostly with increased expression of TNF-a, IFN-g, and IL-2. Western blot analysis confirmed the increased expression of TLR-2. CONCLUSION: Upregulation of TLR-2 expression provides support for a role of the innate immune system in the pathogenesis of PsA.

PMID: 17183618 [PubMed - as supplied by publisher]

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Related Articles[Perspectives in clinical immunology]

Recenti Prog Med. 2006 Dec;97(12):787-96

Authors: Rolla G, Ferrero N, Bergia R, Guida G

Since the last years the better knowledge of immunologic mechanisms underlying autoimmune phenomena and rejection of allotransplants has been accompanied by an impressive production of new drugs: new inhibitors of purine and pyrimidine synthesis, as mycophenolate mofetil and leflunomide respectively, new inhibitors of calcineurin, such as tacrolimus, and target of rapamycine, such as sirolimus. Moreover, the tremendous advance in the methodology of producing monoclonal antibodies and the genetic engineering of proteins has led to a wide variety of biological agents, many of them have been approved as important new therapies for autoimmune diseases and against graft rejection. Monoclonal antibodies targeting IL-2 cytokine receptor have been shown to be useful in decrease the incidence of rejection. Moreover, monoclonal antibodies are available which target inflammatory cytokines, such as TNFalpha and IL-1, while other monoclonal antibodies may cause immune cell depletion, such as anti CD20 rituximab, or cause dysruption of costimuli, like CTLA4Ig abatacept in the treatment of rheumatoid arthritis and anti CD11 efalizumab in the treatment of psoriasis. The new biologic agents have induced salutary clinical effects and extended the therapeutic option of patients not responding to existing treatments. The future looks brighter than ever as the recorded success fuels efforts to optimize the use of the biologic agents and extend their use in other diseases.

PMID: 17252738 [PubMed - in process]

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Related ArticlesLack of genetic association of the interleukin-4 receptor single-nucleotide polymorphisms I50V and Q551R with erosive disease in psoriatic arthritis.

Arthritis Rheum. 2006 Dec;54(12):4023-4

Authors: Lascorz J, Hüffmeier U, Schulze-Koops H, Skapenko A, Reis A, Lohmann J, Wendler J, Traupe H, Küster W, Burkhardt H

PMID: 17133536 [PubMed - indexed for MEDLINE]

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Related ArticlesPolyarticular arthritis secondary to Mycobacterium bovis infection: An unusual clinical presentation.

Joint Bone Spine. 2006 Dec 4;

Authors: Cachafeiro-Vilar A, García-Padilla C, Reyes E, Hernández-Molina G

We describe a 37-year-old Mexican man with incapacitating polyarticular arthritis secondary to Mycobacterium bovis infection. A dermatologist diagnosed psoriasis two years before admission. One year later due to symmetric ankle and knee arthritis, he was treated with three doses of etanercept. The arthritis extended to the carpus and metacarpophalangeal joints. Multifocal dactylitis and a left ankle periarticular abscess were documented. Concomitantly he developed fever, cough, and adenopathies. Ankle MRI showed osteomyelitis of the calcaneous with a posterior abscess. A CT-body scan documented mild pleural effusion that corresponded to an exudate. An ankle aspiration yielded a caseous fluid with acid-fast bacilli. Knee and ankle synovial biopsies documented a granulomatous synovitis. A lymph node biopsy showed granulomas with caseous necrosis. After 1 month, Mycobacterium bovis was isolated from these tissues. Antituberculous regimen was started with satisfactory response. Although largely eradicated, bovine tuberculosis still occurs. Nevertheless, the clinical presentation as polyarthritis is very uncommon and represents a diagnostic challenge.

PMID: 17196422 [PubMed - as supplied by publisher]

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Related ArticlesRisk of new-onset uveitis in patients with juvenile idiopathic arthritis treated with anti-TNFalpha agents.

J Pediatr. 2006 Dec;149(6):833-6

Authors: Saurenmann RK, Levin AV, Feldman BM, Laxer RM, Schneider R, Silverman ED

OBJECTIVE: To determine whether treatment with tumor necrosis factor alpha (TNFalpha)-blocking agents alters the incidence of new-onset uveitis in patients with juvenile idiopathic arthritis (JIA). STUDY DESIGN: Cohort study based on retrospective chart review. The charts of all 1109 patients with a diagnosis of JIA seen between January 1, 1996, and June 30, 2003, at our clinic were reviewed for diagnosis of uveitis and treatment with TNFalpha inhibitors. Cox regression analysis was performed with anti-TNFalpha treatment as a time-dependent covariate for risk of development of uveitis. RESULTS: We identified 70 patients treated with anti-TNFalpha without a prior diagnosis of uveitis. Two of these 70 patients (2.9%), both treated with etanercept, had development of new-onset uveitis during anti-TNFalpha therapy. One had juvenile psoriatic arthritis diagnosed 4.1 years before onset of uveitis. The other had extended oligoarticular JIA diagnosed 6.4 years before onset of uveitis. We found no statistically significant difference in the risk for development of uveitis between patients with or without anti-TNFalpha treatment. CONCLUSIONS: In our patients with JIA, anti-TNFalpha treatment did not alter the risk for development of new-onset uveitis. However, anti-TNFalpha therapy with etanercept did not prevent the development of uveitis in 2 patients.

PMID: 17137902 [PubMed - in process]

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