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ID PMID Title PublicationDate abstract
22157716 Sjögren's syndrome autoantibodies provoke changes in gene expression profiles of inflamma 2012 Apr We explore the association of the inflammatory gene expression profile observed in the chronic inflammatory autoimmune disorder Sjögren's syndrome (SS) with changes in TNF-α converting enzyme (TACE), tumor necrosis factor (TNF)-α and nuclear factor (NF)-κB levels showing that pathways that include TNF-α signaling converge on NF-κB contributing to exacerbate the diseases. The treatment of human salivary gland epithelial cells (SGECs) with SS anti-Ro/SSA autoantibodies (Abs) result in a progressive increase in NF-κB-DNA binding, that includes a marked enhancement in NF-κB subunit p65 protein-DNA binding. A human cytokine multi-analyte array demonstrated that the NF-κB proinflammatory target genes, increased by anti-Ro/SSA Abs treatment, includes CXC chemokines (CXCL1, CXCL6 and CXCL9), CC chemokines (CCL2, CCL13 and CCL20), interleukins (IL-1α, IL-1β, IL-1F8, IL-6, IL-8, IL-9, IL-13, IL-17 and IL-22) and their receptors (IL-1RN, IL-10Rα, IL-13Rα, CCR1, CCR2, CCR3, CCR4 and CXCR1). Blockade of TACE through the use of the specific inhibitor TAPI-1 regulates proinflammatory cytokines production in SGEC treated with anti-Ro/SSA Abs inhibiting NF-κB nuclear translocation and activation. To further investigate the role of NF-κB on anti-Ro/SSA Abs-determined proinflammatory gene expression, we used the inhibitory protein IκB-α dominant negative super-repressor as inhibitor of NF-κB-DNA binding, demonstrating that transfection with dominant-negative IκB-α in anti-Ro/SSA-treated SGEC determined a marked reduction of proinflammatory cytokines gene expression. Although further studies are needed to clarify the mechanisms underlying SS, our results demonstrate that SS Abs exert their pathogenic effects via triggering the TACE/TNF-α/NF-κB axis.
21702009 Changes in Rab3D expression and distribution in the acini of Sjögren's syndrome patients 2011 Oct OBJECTIVE: Oral and ocular dryness are frequent and serious symptoms of Sjögren's syndrome (SS) that reflect problems in secretion due to glandular dysfunction. Exocytosis, an important process in the secretory pathway, requires the participation of Rab family GTPases. This study was undertaken to analyze the expression and localization of Rab3D and Rab8A and to examine their correlation with acinar cell polarity and glandular secretory function. METHODS: Nineteen patients with SS and 17 controls were evaluated. Levels of Rab3D and Rab8A messenger RNA (mRNA) and protein were determined by real-time polymerase chain reaction and Western blotting. Subcellular localization of proteins was determined by indirect immunofluorescence analysis. RESULTS: In patients with SS, total Rab3D protein levels decreased significantly, while mRNA levels remained unchanged. For Rab8A, no changes in either mRNA or protein levels were detected. In serous acini of labial salivary glands from patients with SS, the following 4 patterns of Rab3D staining were distinguishable: severely decreased, distribution throughout the cytoplasm, distribution throughout the cytoplasm combined with loss of nuclear polarity, and normal apical localization. Basal localization of Rab8A was not modified. Rab3D changes were accompanied by apicobasolateral redistribution of ezrin, loss of nuclear polarity, thicker Golgi stacks, and mucin 7 accumulation in the cytoplasm. Finally, low Rab3D protein levels correlated with alterations in scintigraphy measurements. CONCLUSION: Our findings indicate that Rab3D regulates the exocytosis of many components critical for the maintenance of oral physiology. Hence, the changes observed in Rab3D expression and distribution are likely to contribute to the decrease in or loss of saliva components (i.e., mucins), which may explain the variety of oral and ocular symptoms associated with SS.
21557916 [The effect of secondary lymphoid tissue chemokine and its receptor on chemotaxis of perip 2011 May AIM: To investigate the effect of secondary lymphoid tissue chemokine (SLTC) and its receptor CCL21/CCR7 on chemotaxis of peripheral blood lymphocytes in the patients with Sjögren's syndrome (SS) and explore their roles in the SS pathogenesis. METHODS: Thirty-one SS patients were selected, including 18 primary SS patients (pSS) and 13 secondary SS (sSS) patients. In addition, 20 healthy persons were selected as normal controls. Peripheral blood lymphocytes were isolated from all the SS patients and normal controls. The cell trans-membrane test with 24-well transwells was used to detect the effect of CCL21/CCR7 on the lymphocyte migration. RESULTS: In the presence of CCL21, the chemotactic indexes (CIs) of lymphocytes from pSS and sSS patients were 2.92±0.12 and 2.80±0.28, respectively. Both of them were significantly higher than that of normal controls (CI=1.32±0.11, P<0.01), while there was no difference between pSS and sSS patients. After anti-CCR7 mAb pretreatment, the lymphocyte CIs of pSS and sSS patients respectively, decreased significantly to 1.04±0.05 and 1.03±0.08 as compared with untreated controls. CONCLUSION: CCR7 is the one of the important factors resulting in lymphocyte migration. CCL21/CCR7 interaction mediates the migration of peripheral lymphocytes in SS patients and may be involved in the gland damage due to the infiltration of massive lymphocytes in exocrine glands in SS patients.
20946951 Degree of modification of Ro60 by the lipid peroxidation by-product 4-hydroxy-2-nonenal ma 2011 May 15 Our previous work showed that immunization of rabbits with 4-hydroxy-2-nonenal-modified Ro60 (HNE-Ro60) accelerates autoimmunity. We extended this model into mice, hypothesizing that the severity of autoimmunity would be dependent on the degree of HNE modification of Ro60. Five groups of BALB/c mice (10/group) were used. Group I was immunized with Ro60. Groups II to IV were immunized with Ro60 modified with 0.4 mM (low), 2 mM (medium), and 10 mM (high) HNE, respectively. Group V controls received Freund's adjuvant. A rapid abrogation of tolerance to Ro60/La antigens occurred in mice immunized with HNE-modified Ro60, especially in the low and medium HNE-Ro60 groups. Lymphocytic infiltration and significantly high decrement in salivary flow (37%) compared to controls was observed only in the high HNE-Ro60 group, suggesting induction of a Sjögren syndrome-like condition in this group. Anti-dsDNA occurred only in mice immunized with medium HNE-Ro60. This group did not have a significant decrement in salivary flow, suggesting induction of a systemic lupus erythematosus-like manifestation in this group. Significantly high antibodies to Ro60 were found in saliva of mice in the low and medium HNE-Ro60 and the Ro60 groups, as well as anti-HNE Ro60 in the low and medium HNE-Ro60 groups. Understanding the mechanism of this differential induction may help discriminate between these two autoimmune diseases.
23285844 [A case of neuromyelitis optica presenting ileus as a neurologic finding]. 2012 Oct PURPOSE: To report an atypical case of neuromyelitis optica (NMO) with Sjögren syndrome that presented only ileus as a neurologic finding. CASE: A thirty two-year-old woman was hospitalized for abnormal abdominal symptoms, and was diagnosed as having paralytic ileus. Dry eye symptoms due to Sjogren syndrome were also observed, and visual acuity OU decreased suddenly 10 days after hospitalization. The best corrected visual acuity was 0.04 OD and 0.6 OS, and the optic discs OU were swollen and red. Although no neurologic signs were found, pleocytosis and abnormal MRI findings suggested NMO. Steroid pulse therapy was performed, and after three cycles, the ileus symptoms disappeared, and the disturbed visual acuity OU returned to normal. Because the anti-aquaporin 4 antibody was positive and no abnormal abdominal findings that might have caused ileus were found, we diagnosed NMO presenting only paralytic ileus as a neurologic finding. CONCLUSIONS: Differential diagnosis is important for NMO initiated by ileus as the only neurologic sign.
22819441 Platelet serotonin in primary Sjögren's syndrome: level and relation with disease activit 2012 Oct 15 Primary Sjögren's syndrome (pSS) is chronic autoimmune disorder of unknown ethiopathogenesis. In line with the concept of neuroimmunohormonal dysregulation in inflammatory rheumatic diseases, the aim of this study was to investigate platelet serotonin level (PSL) in patients with pSS and its relation with the activity and duration of the disease. Significantly lower PSL in pSS patients (N=61) was shown as compared to healthy controls (N=103). No correlation was found between PSL and the actual disease activity assessed by the recently developed EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). Results suggest involvement of the serotonin system in the pathogenesis of pSS.
22526830 Thrombotic thrombocytopenic purpura with an autoantibody to ADAMTS13 complicating Sjögren 2013 Mar An association between thrombotic thrombocytopenic purpura (TTP) and Sjögren's syndrome (SS) is rare. This is the first report of two patients with TTP who had inhibitory autoantibodies to ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 repeats) complicating primary SS. A rapid diagnosis of TTP, which is a potentially lethal condition, made it possible to treat the two cases successfully. Only eight similar cases with TTP complicating SS have been reported in the literature. The possible presentation of primary SS without classic sicca symptoms, but with haematological abnormalities including TTP, should be recognised. Furthermore, it is important to measure ADAMTS13 activity and anti-ADAMTS13 antibodies, because TTP with SS seems to be a concurrent overlapping autoimmune disorder. We suggest that plasma exchanges in combination with corticosteroids should be administered as early as possible, since they appeared to be effective in treating TTP with SS, including in our cases.
22341852 Immune regulation and B-cell depletion therapy in patients with primary Sjögren's syndrom 2012 Aug Primary Sjögren's syndrome (pSS) is an autoimmune exocrinopathy characterized by chronic inflammation and destruction of the salivary and lacrimal glands. B- and T- lymphocyte infiltrations in the salivary glands with development of germinal center-like structures are characteristic for pSS. Overexpression of soluble factors, such as interferon α (IFNα) and B-cell activating factor (BAFF), are supposed to be important factors in the initiation and continuation of this disorder. The efficacy and success of B-cell depleting therapy in reducing disease activity in pSS patients for about six to nine months supports the notion that B-cells are major key players in disease manifestation of pSS. In addition to B-cells, also Th-cells (mainly Th17) seem to be involved in the pathogenetic process. In this review, we will discuss recent research findings regarding the cytokines IFNα and BAFF as wells as the role of B- and T-cells in pSS. Emphasis will be put on the impact of B-cell depletion therapy as well as on the presumed impact of therapies aimed for targeting BAFF, either as a sole modality or as a combined treatment with B-cell depletion.
22955477 Relation of sensory peripheral neuropathy in Sjögren syndrome to anti-Ro/SSA. 2012 Sep BACKGROUND: Sjögren syndrome is a common, chronic autoimmune disease that typically produces inflammation and poor function of the salivary and lacrimal glands. Other organs can be affected, including the nervous system. Sensory peripheral neuropathy is a common manifestation of the disease. METHODS: Eight-eight patients attending a dry eyes-dry mouth clinic were diagnosed to have primary Sjögren syndrome and underwent a neurological examination. Anti-Ro (or SSA) and anti-La (or SSB) were determined using immunodiffusion as well as Inno-Lia and BioPlex ANA screen. Serum vitamin B(12) levels were determined using an enzyme-linked microtiter plate assay. RESULTS: Twenty-seven (31%) of the 88 patients had peripheral neuropathy as defined by loss of light touch, proprioception, or vibratory sensation. Anti-Ro and anti-La were found by immunodiffusion in 12 patients, and 8 of these 12 had neuropathy (χ(2) = 8.46, P = 0.0036, odds ratio = 6.0 compared to those without precipitating anti-Ro and anti-La). Of the 27 patients with only anti-Ro by immunodiffusion, 13 (48.1%) had neuropathy (χ(2) = 5.587, P = 0.018, compared to those without anti-Ro). There was no relationship of the other, more sensitive measures of anti-Ro and anti-La to neuropathy. In addition, we found no association of serum vitamin B(12) levels to neuropathy among these patients with Sjögren syndrome. CONCLUSIONS: Sensory peripheral neuropathy is common among patients with Sjögren syndrome and is associated with the presence of anti-Ro and anti-La when determined by immunodiffusion.
22510428 Adult-onset Still's disease: still a diagnosis of exclusion. A nested case-control study i 2012 Jul OBJECTIVES: Several sets of criteria have been proposed to classify adult-onset Still's disease (AOSD), those of Yamaguchi being the most commonly used. The Yamaguchi criteria demand the exclusion of other conditions. A clinical scale, recently proposed by Crispin et al., but not yet validated, would allow a positive diagnosis of AOSD in a majority of patients, without the need of thorough diagnostic procedures. METHODS: From a database of 447 patients with classical fever of unknown origin (FUO), collected over a 10-year period (2000-2009) at a general internal medicine department of a university hospital, 22 patients with AOSD according to the Yamaguchi criteria were extracted and compared with 44 controls, matched to index year. Clinical and laboratory parameters were recorded. Sensitivity, specificity and accuracy of the Yamaguchi criteria and of the clinical score were assessed. RESULTS: Lower age, joint symptoms, rash, throat ache, neutrophilic leukocytosis, and elevated erythrocyte sedimentation rate were the principal characteristics supporting a diagnosis of AOSD in patients with FUO. Sensitivity, specificity, and accuracy of the Yamaguchi criteria were 95% or more. The clinical scale, while being specific (98%), lacked sensitivity (55%) and had lower accuracy (83%). CONCLUSIONS: In patients with FUO, the Yamaguchi criteria are a time honored and reliable guide to a diagnosis of AOSD. The clinical scale may serve to rule in, rather than to rule out, AOSD. In many patients, Still's disease is still a diagnosis of exclusion.
22338619 Mortality and long term survival prognostic factors of patients with systemic autoimmune d 2012 May OBJECTIVES: To determine mortality and long-term survival factors in patients with systemic autoimmune diseases (SAD) admitted to the intensive care unit (ICU). METHODS: Retrospective observational study including all consecutive patients with a diagnosis of any systemic autoimmune disease admitted to the medical ICU in a tertiary hospital between 1999 and 2007. Factors associated with reduced survival were identified by means of log rank test and backward stepwise Cox regression. RESULTS: Thirty-seven patients (26 females) were included with median age being 44.3 years (interquartilic range [IQR]: 31.3). Sixteen (43.2%) patients had systemic lupus erythematosus, 9 (24.3%) had systemic vasculitis, 4 (10.8%) had systemic sclerosis and 4 (10.8%) had primary antiphospholipid syndrome. The main reason for ICU admission was autoimmune disease flare-up in 20 (54.0%) patients, followed by infections in 12 (32.4%). Median APACHE II at admission was 17 (IQR 7). At the end of follow-up, 15 (40.5%) patients died, 10 (27%) during hospitalisation (7 in the ICU) and 5 after hospital discharge. Factors associated with reduced long-term survival were: APACHE II score ≥18 (HR 6.02, 95% CI 1.76-20.62), age <45 years (HR 6.54, 95% CI 1.84-23.29), presence of any previous chronic disease (HR 18.20, 95% CI 3.72-88.96), and increase of corticosteroid therapy during ICU stay (HR 22.87, 95% CI 4.31-121.30). CONCLUSIONS: The long-term survival of patients with systemic autoimmune diseases admitted to the ICU was related with age, higher APACHE II score, previous chronic diseases, and an increase in corticosteroids dose when comparing with previous ICU admissions.
22309821 The salivary gland epithelial cells of patients with primary Sjögren's syndrome manifest 2012 Aug Several lines of evidence indicate that salivary gland epithelial cells (SGEC) play an important role in the pathogenesis of primary Sjogren's syndrome (SS). Normal SGEC have been shown to possess functional estrogen receptors, however, the estrogenic response of SGEC in patients with SS has not been previously assessed. To address this issue, we comparatively tested cultured non-neoplastic SGEC lines from SS patients (SS-SGEC, n = 8) and from disease controls (control-SGEC, n = 12) in a standard estrogenic inhibition assay of cytokine-induced adhesion molecule expression, where the modulation of the expression of constitutive and interferon-gamma (IFNγ)-induced CD54/ICAM.1 molecules following treatment with 17β-estradiol (E2) was evaluated by flow cytometry. Similarly high ICAM.1 expression was induced by IFNγ in control-SGEC and SS-SGEC lines. E2-treatment did not modify the constitutive ICAM.1 expression in either control-SGEC or SS-SGEC lines. In line with previous results, E2-pretreatment of control-SGEC was found to impede significantly the IFNγ-induced upregulation of ICAM.1 (p = 0.003). However, such inhibition was not observed in the SS-SGEC lines (p = 0.55). Such aberrant response of SS-SGEC to estrogens did not appear to associate with altered expression of estrogen receptor (ER) proteins, as no discernible differences could be revealed by immunoblotting and immunohistochemistry in the patterns or the intensity of ERα and ERβ (ERβ1- and ERβ2-isoforms) protein expression in SGEC lines or minor salivary gland tissues between SS patients and disease controls. The deficient estrogenic responsiveness of SS-SGEC likely represents a manifestation of the intrinsic epithelial activation that characterizes SS and possibly indicates the perturbation of the immunoregulatory potential of estrogens in SS-epithelia.
23291020 [The clinical observation of different therapeutic strategies in combined primary biliary 2012 Nov OBJECTIVE: To investigate the role of different therapeutic regimens in primary biliary cirrhosis (PBC)complicating Sjögren syndrome (SS). METHODS: A total of 79 patients diagnosed as PBC complicating SS were enrolled and randomly divided into three groups: Group U (29 patients) received ursodeoxycholic acid (UDCA) alone, Group UP (37 patients) received UDCA and prednisolone, Group UA (13 patients) received UDCA and azathioprine. The clinical and laboratory data were collected at 0, 3, 6 and 12 months after treatment. RESULTS: Fatigue and pruritus were improved in each group with no difference among them (P > 0.05). The levels of ALT, AST, alkaline phophatase (ALP), gamma-glutamyl transferase (GGT), TBil, DBil, IgG, and IgM in the three groups were all decreased after treatment (P < 0.05), while there were no statistical differences among the three groups (P > 0.05). CONCLUSIONS: The combination therapy of UDCA with prednisolone or azathioprine was not better than UDCA alone. The therapeutic policy of PBC complicating SS involved in the liver should settle PBC mainly.
23123433 Polymicrobial and microsporidial keratitis in a patient using Boston scleral contact lens 2013 Apr AIM: To report a rare case of microsporidial and polymicrobial keratitis in a patient with Sjogren's syndrome and ocular cicatricial pemphigoid. METHOD: This is a descriptive case report. A 66-year-old lady diagnosed with Sjogren's syndrome (SS) and ocular cicatricial pemphigoid (OCP) presented to us with microbial keratitis after using a Boston sclera contact lens for a painful epithelial defect. After 9 days of medical treatment, she underwent therapeutic penetrating keratoplasty. RESULTS: 10% potassium hydroxide and calcofluor white wet mount revealed microsporidial spores. Gram positive cocci and Gram variable bacilli on Gram stain were identified as Staphylococcus epidermidis and Corynebacterium accolens in culture. Histopathological examination of the corneal tissue confirmed the presence of microsporidial spores. CONCLUSION: Microsporidal keratitis can occur in patients with severe ocular surface disease due to SS and OCP. Predisposing factors include dry eye, local and systemic immunosuppression and Boston scleral contact lens. Early surgical intervention may be needed to eradicate the infection.
22555904 Movement disorders in autoimmune diseases. 2012 Jul Movement disorders have been known to be associated with a variety of autoimmune diseases, including Sydenham's chorea, pediatric autoimmune neuropsychiatric disorders associated with streptococcus, systemic lupus erythematosus, antiphospholipid syndrome, gluten sensitivity, paraneoplastic and autoimmune encephalopathies. Tremors, dystonia, chorea, ballism, myoclonus, parkinsonism, and ataxia may be the initial and even the only presentation of these autoimmune diseases. Although antibodies directed against various cellular components of the central nervous system have been implicated, the pathogenic mechanisms of these autoimmune movement disorders have not yet been fully elucidated. Clinical recognition of these autoimmune movement disorders is critically important as many improve with immunotherapy or dietary modifications, particularly when diagnosed early. We discuss here the clinical features, pathogenic mechanisms, and treatments of movement disorders associated with autoimmune diseases, based on our own experience and on a systematic review of the literature.
21880794 Type 1 hyperlipoproteinemia and recurrent acute pancreatitis due to lipoprotein lipase ant 2011 Nov CONTEXT: Type 1 hyperlipoproteinemia (T1HLP) in childhood is most often due to genetic deficiency of lipoprotein lipase (LPL) or other related proteins. OBJECTIVE: The aim was to report a case of marked hypertriglyceridemia and recurrent acute pancreatitis due to the presence of LPL autoantibody in a young girl who was subsequently diagnosed with Sjögren's syndrome. SUBJECT AND METHODS: A 9-yr-old African-American girl presented with acute pancreatitis and serum triglycerides of 4784 mg/dl. Strict restriction of dietary fat reduced serum triglycerides, but she continued to experience recurrent pancreatitis. Approximately 18 months thereafter, she developed transient pauciarticular arthritis with elevated serum antinuclear antibody (>1:1280). Minor salivary gland biopsy revealed chronic sialadenitis with a dense periductal lymphocytic aggregate suggestive of Sjögren's syndrome. Genomic DNA was analyzed for LPL, GPIHBP1, APOA5, APOC2, and LMF1. Immunoblotting was performed to detect serum LPL autoantibody. RESULTS: The patient had no disease-causing variants in LPL, GPIHBP1, APOA5, APOC2, or LMF1. Immunoblotting revealed serum LPL antibody. The patient responded to immunosuppressive therapy for Sjögren's syndrome with resolution of hypertriglyceridemia. CONCLUSIONS: Unexplained T1HLP in childhood could be secondary to LPL deficiency induced by autoantibodies. Therefore, diagnosis of autoimmune T1HLP should be entertained if clinical features are suggestive of an autoimmune process.
21303487 Importance of serine727 phosphorylated STAT1 in IFNγ-induced signaling and apoptosis of h 2011 Feb AIM: It is reported that in salivary glands of Sjögren's syndrome (SS), interferon gamma (IFNγ) and IFNγ-inducible genes containing signal transducers and activators of transcription 1 (STAT1) are upregulated and play a crucial role in the pathogenesis of SS. The aim of this study is to clarify which phosphorylation of STAT1, serine727 (Ser(727)) or tyrosine701 (Tyr(701)) of STAT1, is important for IFNγ signaling and IFNγ-induced apoptosis in salivary gland cells. METHODS: We established STAT1 Tyr(701) variant (tyrosine to phenylalanine; Y701F) and STAT1 Ser(727) variant (serine to alanine; S727A), which were transfected into human salivary gland (HSG) cells. HSG cells transfected with these mutant-STAT1 were analyzed on the expression of IFNγ-inducible genes and apoptosis after stimulation with IFNγ. RESULTS: In Y701F mutant-STAT1 transfected HSG cells (Ser(727)-dominant HSG cells), IFNγ-inducible genes such as IP10, IRF1, and Fas expression were increased after stimulation with IFNγ. In Ser(727)-dominant HSG cells, the induction of apoptosis after stimulation with IFNγ was also increased compared with S727A mutant-STAT1 transfected HSG cells (Tyr(701)-dominant HSG cells). CONCLUSION: Phosphorylation of Ser(727) in STAT1 might be more important in IFNγ signaling and the induction of apoptosis in HSG cells than phosphorylation of Tyr(701). Accordingly, we propose that phosphorylation of Ser(727) in STAT1 could be a potentially suitable new therapeutic target for SS patients to prevent the destruction of salivary glands.
21175575 The novel phospho-non-steroidal anti-inflammatory drugs, OXT-328, MDC-22 and MDC-917, inhi 2011 Apr BACKGROUND AND PURPOSE: The use of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of rheumatoid arthritis (RA) is limited by their toxicity. We evaluated the anti-inflammatory efficacy and safety of three novel modified NSAIDs, phospho-aspirin, phospho-ibuprofen and phospho-sulindac. EXPERIMENTAL APPROACH: We determined the anti-inflammatory effects and gastrointestinal safety of the phospho-NSAIDs in the rat adjuvant arthritis model and studied their mechanism of action in cultured cells, Cytokines were measured with elisa and activation of nuclear factor-κB (NF-κB) by immunohistochemistry. KEY RESULTS: All three phospho-NSAIDs showed less gastrointestinal toxicity than their parent compounds and demonstrated strong anti-inflammatory effects, essentially reversing joint inflammation and oedema. They have a broad but not uniform effect on the expression of relevant cytokines, in general decreasing IL-6 and IL-1β and increasing IL-10 levels in rat plasma and cultured cells. Phospho-sulindac and phospho-ibuprofen but not phospho-aspirin suppressed PGE(2) production in vitro, whereas phospho-aspirin (in contrast to aspirin) showed the same effect in vivo. In joint tissues, phospho-aspirin inhibited NF-κB activation, and suppressed inflammation and bone resorption. Phospho-aspirin also inhibited Jurkat T cell proliferation. In general, phospho-aspirin had greater efficacy but different effects upon inflammatory mediators compared with aspirin. The chemical modification of the parent NSAIDs seems crucial for their safety and efficacy. CONCLUSIONS AND IMPLICATIONS: Phospho-aspirin, phospho-ibuprofen and phospho-sulindac were safer than their parent NSAIDs, were highly effective in rat adjuvant arthritis and inhibited many key mediators in the pathophysiology of RA. These novel compounds are promising candidate drugs for the treatment of RA and merit further evaluation.
22232951 [The role of magnetic resonance imaging in seronegative spondyloarthritides]. 2011 Seronegative spondyloarthritides (SpA) is a group of inflammatory rheumatic diseases characterized by inflammation of the sacroiliac joints and/or the spine, enthesitis and peripheral arthritis. MRI is the imaging method of choice for visualization of the sacroiliac joint and spine according to the new ASAS classification criteria for axial SpA. It can visualize both active inflammation and structural damage and is not associated with radiation exposure. MRI findings characteristic for active disease include bone marrow edema and contrast enhancement of the bone marrow and the joint space, while chronic changes include bone erosions, sclerosis, periarticular fatty tissue accumulation, bone spurs and ankylosis. MRI has higher sensitivity comparing to other radiological modalities. MRI.is the most important diagnostic imaging method in early SpA. It is sensitive and reliable for objective monitoring of the disease process and it is essential in the management of patients with SpA.
21397001 Comparison of toxic reaction of Tripterygium wilfordii multiglycoside in normal and adjuva 2011 May 17 AIM OF THE STUDY: Tripterygium wilfordii multiglycoside (GTW), an authorized Chinese patent drug, is used for treatment of rheumatoid arthritis and other immune disease. This study was to determine whether GTW induced different toxic reactions in adjuvant arthritis rats (AA rats) compared to those in normal rats. MATERIALS AND METHODS: To prepare arthritic rat model, male Sprague-Dawley (SD) rats were immunized by injecting complete Freund's Adjuvant into right hind footpad. And then, GTW was given to rats intragastrically at dosage of 7 or 105 mg kg(-1)day(-1) from day 15 to day 28 after immunization. Routine clinical parameters and histopathologic changes of liver, kidney and testis were examined. Metabolic profiling in serum of groups was analyzed by LC-MS. A principal component analysis (PCA) and partial-least-squares discriminate analysis (PLS-DA) were carried out combined with mass spectrometry (MS) data set. All the quantitative data were performed by two-way ANOVA analysis following Student's t-test. RESULTS AND CONCLUSIONS: Treatment with GTW at both doses could diminish the right and left hind paws swelling. There was slight lipoid degeneration in hepatic tissue of normal rats treated by high dose of GTW, but there were not distinctly pathological changes in hepatic tissue of AA rats treated by GTW. Compared normal rats administered with GTW, no statistically significant difference in the serum alanine aminotransferase (ALT), creatinine (CRE), and blood urea nitrogen (BUN) levels were observed. However, the serum aspartate aminotransferase (AST) level was significant decreased in AA rats under exposure GTW compared with normal rats in the same conditions (p<0.05), which indicated that GTW could offer a different liver toxic reaction in normal and AA rats. The metabolic analysis showed that a clear separation of PCA and PLS-DA score spot in normal rats, but not separation was seen in AA rats perturbed with low dosage GTW. The result indicated low dosage GTW might arouse a general toxic in normal rats but not in AA rats. The biomarker analysis showed that the level of lysophosphatidylcholines (LPCs) was down-regulated, but the level of ursodeoxycholic acid (UDCA) and chenodexycholic acid (CDCA) was up-regulated in AA rats compared with normal rats under exposure GTW. According to pathway analysis of metabolic markers, we conceived that LPC, UDCA and CDCA were the critical intermediates of choline and fatty acid metabolism. And the lipid metabolism was a correlative outcome of GTW induced toxicity in the liver in physiological condition animals. Taken together, GTW could induce different toxic reactions between normal and AA rats, and the lipid metabolism might be part of the mechanism for the hepatic lipidosis or the other liver injury.