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ID PMID Title PublicationDate abstract
12483744 Peptide-induced suppression of collagen-induced arthritis in HLA-DR1 transgenic mice. 2002 Dec OBJECTIVE: To identify peptides capable of altering the immune response to type II collagen (CII) in the context of HLA-DR. METHODS: Immunizing mice transgenic for the human HLA-DRB1*0101 immune response gene with CII elicits an arthritis (collagen-induced arthritis [CIA]) that resembles rheumatoid arthritis. We have previously identified an immunodominant determinant of CII, CII (263-270), recognized by T cells in the context of DR1. To produce synthetic peptides with the potential of disrupting the DR1-restricted immune response, synthetic analog peptides were developed that contain site-directed substitutions in critical positions. These peptides were used to treat CIA in DR1 transgenic mice. RESULTS: An analog peptide, CII (256-276, N(263), D(266)), that inhibited T cell responses in vitro, was identified. When DR1 mice were coimmunized with CII and CII (256-276, N(263), D(266)), the incidence and severity of arthritis were greatly reduced, as was the antibody response to CII. Moreover, CII (256-276, N(263), D(266)) was effective in down-regulating the immune responses to CII and arthritis, even when administered 2 weeks following immunization with CII. Spleen and lymph node cells from CII-immunized mice cultured with CII (256-276, N(263), D(266)) in vitro produced increased amounts of interleukin-4 (IL-4) compared with cells cultured with the wild-type peptide, CII (256-276). Furthermore, CII (256-276, N(263), D(266)) was incapable of preventing arthritis in DR1 IL-4(-/-) mice (genetically deficient in IL-4). CONCLUSION: These data establish that CII (256-276, N(263), D(266)) is a potent suppressor of the DR-mediated immune response to CII. Its effect is mediated, at least in part, by IL-4. These experiments represent the first description of an analog peptide of CII recognized by T cells in the context of a human major histocompatibility complex molecule that can suppress autoimmune arthritis.
14752934 [A case of Sjögren's syndrome associated with chronic hepatitis C and sarcoidosis]. 2003 Dec A 68-year-old female had been treated for chronic type C hepatitis at our department since June, 1992. In August of the same year, swelling of the right eyelid developed and she was diagnosed as having sarcoidosis on the basis of uveitis, skin lesions, and bilateral hilar lymphadenopathy (BHL) on chest X-ray. With steroid therapy, the symptom improved and BHL disappeared. In July, 2001, dryness of the mouth and dry eyes developed, and she was diagnosed as having Sjögren's syndrome (SjS). This case may be precious in discussing the pathophysiology of sarcoidosis and SjS including the association with hepatitis C virus infection.
12860722 Parasympathetic nervous system dysfunction in primary Sjögren's syndrome. 2003 Aug In the past sicca syndromes were attributed to destruction of glandular tissue. It is now thought that cytokines, autoantibodies, and parasympathetic nervous system dysfunction all have an important role in the xerostomia and xerophthalmia in Sjögren's syndrome.
12043187 [Report of a patient of primary Sjögren syndrome, IgA nephropathy and chronic idiopathic 2002 Apr We describe the case of a 61-year-old woman diagnosed with primary Sjögren's syndrome (SS) after an 8-year history of IgA nephropathy and a 3-year history of recurrent purpuric rashes. Her two daughters had previously been diagnosed with other autoimmune diseases. One daughter had Graves' disease and the other had Hashimoto's disease and systemic lupus erythematosus. The diagnosis of SS was made based on dryness of mucous membranes, Shirmer test, and parotid sialography. Thrombocytopenia, high platelet-aggregated IgG (PA-IgG) level, and normal megakaryocytes count in bone marrow suggested that her recurrent purpuric rashes were due to idiopathic thrombocytopenic purpura (ITP). Patients with SS may develop other autoimmune diseases. This case aids understanding of the immune pathogenesis and genetic background of SS.
15485622 Id3 knockout mice as a new model for sjogren's syndrome: only a T cell defect or more? 2004 Oct Id3(-/-) mice were found to have autoantibodies, lymphocytic infiltrates in, and decreased secretion by exocrine glands. Similar symptoms are found in primary Sjogren's Syndrome. In this issue of Immunity, Li and colleagues suggest an important role for Id3 function in T cell development and Sjogren's Syndrome.
15479901 Late neonatal lupus erythematosus onset in a child born of a mother with primary Sjögren' 2004 Nov BACKGROUND: The neonatal lupus syndrome can be present as congenital heart block (CHB) or as neonatal lupus erythematosus (NLE), both seldom passively acquired autoimmune diseases. CHB starts around week 20 of pregnancy and is a lifelong event, whereas NLE is self limiting and usually starts at the 6th week of the child's age-the maximum recorded up to week 20. CASE REPORT: An asymptomatic mother with primary Sjogren's syndrome and anti-SSA/Ro52, anti-SSA/Ro60, and anti-SSB/La autoantibodies is described who, at gestational week 23 during her first pregnancy, was diagnosed as having a male fetus with CHB due to third degree atrioventricular block. The boy from the second pregnancy developed skin eruptions which clinically and by biopsy were compatible with NLE at week 20+1 post partum. CONCLUSIONS: Our case of NLE, starting at week 20+1 of age, seems to be the latest reported clinical case of NLE. Development of CHB and NLE in two consecutive boy pregnancies is unusual.
15453861 Neurosarcoidosis mimicking Sjögren's syndrome. 2004 Oct PURPOSE: To describe a patient with a long disease history who was finally diagnosed with neurosarcoidosis and to discuss the reasons behind the delayed diagnosis. CASE REPORT: A 58-year-old man with sick sinus syndrome and bradycardia, which was treated with a pacemaker, developed first right and then left facial palsy. Subsequently, multiple cranial nerve palsies developed and later spontaneously resolved. Neurosarcoidosis was suspected at that stage, but excluded because the patient had no typical sarcoid lung changes, his serum and cerebrospinal fluid angiotensin converting enzyme activity levels were normal and a computed tomography scan disclosed no central nervous system changes. During follow-up, the patient developed extremely dry eyes and mouth, suggesting Sjögren's syndrome. Rheumatology consultation did not reveal any autoimmune or visceral features typical of Sjögren's syndrome and autoantibodies were negative. However, both labial salivary gland and conjunctival biopsies revealed non-caseating granulomas, and neurosarcoidosis was diagnosed. CONCLUSIONS: Neurosarcoidosis is a relatively rare disease with a somewhat poor longterm prognosis in one-third of cases, although the neurological manifestations often diminish or disappear in response to glucocorticoid treatment. Diagnosis is often a clinical challenge, especially in the absence of pulmonary changes or other features typical of sarcoidosis. The labial salivary gland and conjunctiva provide helpful biopsy sites for histopathological confirmation of the diagnosis.
15358578 Nodular cystic fat necrosis with systemic sclerosis. 2004 Sep Nodular cystic fat necrosis is a distinct spectrum characterized clinically by mobile subcutaneous nodules and histologically by encapsulated fat necrosis. We describe herein a case of nodular cystic fat necrosis in a patient with systemic sclerosis in the atrophic stage. Several mobile, firm nodules were surgically removed from the flexural aspect of the forearm and lower leg. Histopathology showed features of nodular cystic fat necrosis with lipomembranous changes and calcification. Of interest, lipomembranous changes were seen also in the biopsied specimen from the extensor aspect of the forearm of scleroderma. We speculate that multiple, chronic, local or systemic events causing a compromise in the blood supply of the subcutaneous tissues may contribute to the induction of lipomembranous changes in the affected skin as well as nodular cystic fat necrosis in this case.
14534487 [Association of distal tubular acidosis, Hashimoto's thyroiditis and Gougerot-Sjögren's s 2003 Sep 20 INTRODUCTION: Distal tubular acidosis is associated with auto-immune diseases not specific to organ. The coexistence of distal tubular acidosis and auto-immune thyroid affection is very rare. OBSERVATION: A 36-year-old woman exhibiting primary hypothyroidism, Gougerot-Sjögren's syndrome and hypergammaglobulinemia, presented distal tubular acidosis revealed by severe hypokaliemia and complicated by quadriplegia and circulatory arrest. Correcting the thyroid defect did not appear to influence the progression of acidosis. COMMENTS: Based on this observation, one can discuss the pathogenesis of distal tubular acidosis during auto-immune diseases (hypothyroidism, Gougerot-Sjögren's syndrome and monoclonal hypergammaglobulinemia) and its impact on therapy.
12931669 [Sjören's syndrome with infiltrative lung disease showing upper lung field predominance]. 2003 Jul We report two cases of Sjören's syndrome (SjS) with infiltrative lung disease showing upper lung field predominance. Case 1 was seen in a 68-year-old woman, who was admitted with dyspnea on exercise. Chest CT scanning demonstrated a central predominance of irregularly shaped consolidation with tractionectasis, distributed along the broncho-vascular bundles in both upper lobes. Case 2 occurred in a 70-year-old woman, who was admitted with cough. Chest CT scan showed a central predominance of irregularly shaped opacities with multiple small cystic structures in both upper lobes. Both cases were shown to be nonspecific interstitial pneumonia (NSIP) by video-assisted thoracoscopic lung biopsy, in which lung involvements were distributed around the bronchovascular sheath with relative sparing of the subpleural region. Although neither case complained of sicca symptoms, decreased saliva production was detected using the Saxon test, and further examinations revealed the presence of primary SjS. Pulmonary involvement in SjS is variable, and distribution along the broncho-bronchioles in the majority of the upper central lung field is a characteristic appearance of SjS lung disease. In patients with such patterns in chest radiography, further diagnostic differentiation should be conducted to confirm or rule out SjS.
15297470 Nitric oxide (NO)-releasing naproxen (HCT-3012 [(S)-6-methoxy-alpha-methyl-2-naphthaleneac 2004 Dec Administration of selective and nonselective cyclooxygenase (COX)-2 inhibitors to rheumatoid arthritis patients taking low doses of acetylsalicylic acid (ASA) for cardiovascular prevention associates with increased risk of gastrointestinal bleeding. The present study was undertaken to investigate whether administration of HCT-3012 [(S)-6-methoxy-alpha-methyl-2-naphthaleneacetic acid 4-(nitrooxy)butyl ester], a nitric oxide (NO)-releasing derivative of naproxen, exacerbates gastric mucosal injury in arthritic rats administered low doses of ASA. Our results demonstrated that while treating arthritic rats with a dose of 30 mg/kg/day ASA causes detectable mucosal injury, but had no effect on arthritis score and interleukin-6 plasma levels, coadministration of naproxen (10 mg/kg/day) and celecoxib (30 mg/kg/day), in combination with ASA from day 7 to day 21, attenuates arthritis development (P <0.01 versus arthritis alone), but markedly enhanced gastric mucosal damage caused by ASA (P <0.01 versus ASA alone). In contrast, coadministration of HCT-3012 (15 mg/kg/day) significantly attenuated arthritis development, because HCT-3012 was equally or more effective than naproxen and celecoxib in attenuating local and systemic inflammation (P >0.001 versus arthritis) without exacerbating gastric mucosal injury caused by ASA. Arthritis development associates with gastric COX-2 induction, mRNA and protein, and enhanced gastric prostaglandin E2 (PGE2) synthesis (P <0.01 versus control rats). Although all treatments, including celecoxib, were effective in reducing gastric PGE2 synthesis, administering arthritic rats with ASA resulted in a significant increase in gastric content of aspirin-triggered lipoxin (ATL), a COX-2-derived lipid mediator that regulates proinflammatory responses at the neutrophils/endothelial interface. Administering arthritic rats with naproxen and celecoxib abrogates ATL formation induced by ASA although enhanced neutrophils accumulate into the gastric mucosa (P <0.01 versus ASA alone). In contrast, whereas HCT-3012 inhibited ATL formation, it did not increase neutrophil recruitment into the gastric microcirculation. Collectively, these data indicate that HCT-3012 derived from NO has the potential to compensate for inhibition of PGE2 and ATL and to protect the gastric mucosa by limiting the recruitment of neutrophils. These data suggest that HCT-3012 might be a safer alternative to nonsteroidal anti-inflammatory drugs and coxibs in rheumatic patients that take low doses of ASA.
15182735 Protective and anti-arthritic effects of deer antler aqua-acupuncture (DAA), inhibiting di 2004 Jul The effect of water extract of deer antler aqua-acupuncture (DAA; Cervi Pantotrichum Cornu) prepared from the pilose antler of Cervus korean TEMMINCK var. mantchuricus Swinhoe (Nokyong in Korean), a traditional immunosuppressive and immunoactivating Korean herbal acupuncture [Int. Immunopharm. 3 7 (2003) 1001] on rat chondrocyte apoptosis was studied. Terminally differentiated hypertrophic chondrocytes were isolated from rat costochondrial cartilage and cell death was measured in the presence of 3-5 mM phosphate ions (Pi). The effect of 10 microg/ml DAA was compared to that of phosphonoformic acid (PFA), a competitive inhibitor of the Na-Pi co-transport on Pi-induced apoptosis in chondrocytes. A total of 1 mM PFA blocked anion-induced cell death and prevented an increase in the cell Pi content. In a parallel study, we determined that the DAA also protected chondrocytes from death. On the other hand, the effect of DAA was also evaluated as an inhibitor of dihydroorotate dehydrogenase (DHO-DHase) and tested in the rat collagen-induced arthritis (CIA) model. Female 7-week-old Sprague-Dawley rats were used for the evaluation of DAA in the CIA model. Arthritis was evaluated by arthritis score, body weight loss, bone destruction score. DAA was administered by bilateral Shinsu (B23) acupuncture five times per week (10, 20, 30, and 100 microg/kg/day). DAA inhibited rat liver DHO-DHase in vitro with Ki = 843 +/- 43 microg/ml. The anti-proliferative effect of DAA was caused by cell cycle arrest at the S-phase. Treatment with 300 mg/kg/day of DAA completely prevented the development of CIA based on the reduction of the arthritis score. The 50% effective dose (ED50) of DAA on arthritis score was 64 mg/kg. DAA ameliorated body weight loss associated with disease onset. DAA suppressed the development of arthritis, even when it was administered after a booster immunization of collagen. DAA is a novel immunosuppressant which inhibits DHO-DHase and its effects in CIA suggest that it could be useful in the treatment of rheumatoid arthritis.
15626310 [Favourable effect of lacrimal plugs after 3 and 9 months in 20 patients with severe sicca 2004 Dec 4 OBJECTIVE: To describe the results of the insertion of lacrimal plugs in patients with severe symptoms of dry eyes. DESIGN: Prospective descriptive study. METHOD: 20 patients who had severe symptoms of dry eyes despite topical therapy were included. The diagnoses were: 'primary Sjögren's syndrome' (n = 10), 'probably a primary Sjögren's syndrome' (n = 5) and 'secondary Sjögren's syndrome' (n = 5). Following a favourable subjective reaction to resorbable plugs, a non-resorbable silicone plus was inserted bilaterally into the openings of the inferior lacrimal ducts. During follow-up, the effect of treatment was assessed by means of various measurements of function of the lacrimal glands. RESULTS: After 3 and 9 months there was a measurable favourable effect with regard to tear production (Schirmer-test), tear film stability ('tear film break-up time'), the damage to the cornea (Bengal-red-test) and the subjective symptoms of dry eye on a visual analogue scale (VAS). The difference in comparison with the initial values was significant except for the Bengal-red-test after 9 months. There were no complications. In the 5 patients with a basal Schirmer test value of o mm after 5 min, there was no improvement.
12043189 [Two cases of limited cutaneous nodular amyloidosis with primary Sjögren's syndrome]. 2002 Apr We described two female patients with primary Sjögren's syndrome associated with localized cutaneous nodular amyloidosis (LCNA), in which amyloid protein was derived from immunoglobulin light chain. Case 1; a 70-year-old female had complained with polyarthralgia, low-grade fever and parotid gland swelling. She was diagnosed as primary Sjögren's syndrome. Three years later she noticed brown color small tumor on the thigh and yellow to brown nodules on the bilateral calves of legs. Skin biopsy from the left thigh revealed amyloid L protein deposition, which was positive for anti-lambda light chain staining, in almost entire dermis. Infiltration of lymphocytes and plasma cells around the amyloid deposit were prominent. Case 2; a 51-year-old female had noticed increasing eruption on the hip. Skin biopsy revealed amyloid L protein deposition in the dermis, which was negative for anti-lambda nor kappa light chain staining. When she was refereed to our hospital, she complained of xerostomia and xerophthalmia. She was diagnosed as primary Sjögren's syndrome. In both cases, histological examination of a minor salivary gland biopsy revealed infiltration of lymphocytes and plasma cells but not amyloid deposit. Serum M protein and urine Bence-Jones protein were not detected. These cases represent localized amyloidosis without systemic involvement. It is widely recognized that Sjögren's syndrome is frequently accompanied by B cell lymphoproliferative disorders. In LCNA, infiltration of plasma cells around the amyloid deposits was frequently prominent. The relation between these two disorders is discussed.
15542046 TNF-alpha antibodies and osteoprotegerin decrease systemic bone loss associated with infla 2004 Nov INTRODUCTION: Rheumatoid arthritis (RA) is associated with focal and systemic bone loss involving cytokines such as RANKL and TNF-alpha. RANK-L promotes focal and systemic osteoporosis, whereas osteoprotegerin (OPG) inhibits bone resorption. Although anti-TNF-alpha antibodies (anti-TNF-alpha Ab) decrease joint inflammation and bone erosions, their effects on bone loss are unknown. The aim of this study was to evaluate the effects of OPG and anti-TNF-alpha Ab, separately or in combination, on inflammation and bone remodeling in collagen-induced arthritis (CIA), a model of RA. METHODS: DBA/1 mice (n=28) were immunized with bovine type II collagen and treated with OPG-Fc or anti-TNF-alpha Ab or both, or saline. One group of mice (n=7) was not immunized (naive group). Urinary deoxypyridinoline (D-pyr) and whole-body bone mineral density (BMD) were measured at baseline and at sacrifice. Histomorphometric parameters were evaluated at the femoral metaphysis. RESULTS: Anti-TNF-alpha Ab, but not OPG, decreased the clinical arthritis score (P<0.02 vs. saline) and the histological score of inflammation. The BMD change from baseline to sacrifice (DeltaBMD) was significantly smaller in CIA mice than naive mice. OPG and anti-TNF-alpha Ab significantly increased DeltaBMD versus saline, and the effect was greater with OPG (P<0.003). DeltaD-pyr decreased by 65% with OPG and 13% with anti-TNF-alpha Ab. Compared with saline, OPG increased trabecular bone volume (BV/TV) (P<0.02), decreased trabecular separation (P<0.02), and decreased the bone formation rate (BFR) (P<0.01). Anti-TNF-alpha Ab produced no significant changes in bone volume or trabecular separation but increased trabecular thickness (P<0.02 vs. saline) to a value close to that in naive mice, suggesting preservation of bone formation. No additive effects of OPG and anti-TNF-alpha Ab were found. CONCLUSIONS: Systemic OPG and anti-TNF-alpha Ab therapy prevented bone loss in CIA mice through distinct mechanisms involving decreased bone resorption and preserved bone formation. Combining these two agents might help to prevent bone loss in inflammatory diseases.
15500626 Pathogenesis of collagen-induced arthritis: modulation of disease by arthritogenic T-cell 2004 Nov Collagen-induced arthritis (CIA) is an animal model of human rheumatoid arthritis that can be induced in susceptible mice by immunization with type II collagen (CII) or with collagen fragments, including cyanogen bromide (CB) peptides. One susceptible mouse strain, B10.RIII (I-Ar), has previously been found to respond to two major T-cell determinants, namely CII 610-618 (GPAGTAGAR) within CB10 and CII 445-453 (GPAGPAGER) within CB8. Although CB10 contains the immunodominant determinant, it is not arthritogenic. Using recombinant techniques, the determinant within CB10 was mutated to rCB10(T614P,A617E), generating a recombinant CB10 that in effect contained the arthritogenic epitope. When used for immunization, rCB10(T614P,A617E) was arthritogenic. This suggested that the arthritogenic property was intrinsic to the epitope and unrelated to its position within the CII molecule. To test this hypothesis, additional mutants were generated. The wild-type T-cell epitope of CB10 was deleted from its natural position, and the 'arthritogenic' GPAGPAGER T-cell epitope was inserted into the C-terminal portion of the CB10 peptide. The resulting peptide induced arthritis in B10.RIII mice. Adding a second copy of the T-cell determinant to other sites within CB10, however, had varying results. A second T-cell epitope located at the C-terminus of rCB10 significantly increased the incidence and severity of arthritis, while determinants placed in other positions had little effect. These data indicate that the T-cell epitope has intrinsic arthritogenic properties, but there are positional and structural constraints that affect its arthritogenicity. Enhanced arthritis was associated with an increased T-cell proliferation to the peptides, an increase in the level of inflammatory cytokines, and higher levels of anti-CII immunoglobulin. These data suggest that the position and copy number of T-cell determinants also affect the overall immune T-cell responses.
12871194 Gene expression profiles in human autoimmune disease. 2003 To acquire a functional view of human autoimmunity, we compared differences in gene expression (>4000 genes) in the peripheral blood mononuclear cells of normal individuals following immunization to those in individuals with four different autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, insulin dependent diabetes mellitus, and multiple sclerosis). Each individual from all disease groups displayed a similar pattern of gene expression that was highly distinct from the gene expression pattern of the immunized group. These findings indicate that the expression pattern accompanying autoimmunity is not simply a recapitulation of the immune response to non-self. Of note, expression levels of genes that encode key proteins in several distinct apoptosis pathways were markedly reduced in all autoimmune disease groups. Taken together, these data indicate that the pattern of gene expression describes a molecular portrait of autoimmunity that is constant among individuals with autoimmune disease but is independent of the specific autoimmune disease and the clinical parameters associated with any individual autoimmune disease.
11824948 Evidence for synovitis in active polymyalgia rheumatica: sonographic study in a large seri 2002 Jan OBJECTIVE: To determine the frequency and localization of synovitis and enthesitis in patients with active, untreated polymyalgia rheumatica (PMR) by ultrasonography (US). METHODS: Polyarticular sonographic evaluation was carried out in 50 consecutive patients with PMR at disease onset. Results were compared with 50 consecutive patients with seronegative spondyloarthropathies (SpA) and 50 with seronegative and seropositive rheumatoid arthritis (RA) at disease onset. RESULTS: Synovitis and/or effusion was detected, in at least one joint, in 100% of patients with PMR. The most frequent alterations observed in patients with PMR were effusion in the subacromial-subdeltoid (SA-SD) bursa in 70% of patients, tenosynovitis of the long head of the biceps tendon (LHBT) in 68%, glenohumeral joint effusion in 66%, tenosynovitis of the flexor tendons in the carpal tunnel in 38%, radiocarpal effusion in 18%, wrist extensors tenosynovitis in 18%, coxofemoral joint effusion in 40%. knee effusion in 38%, and ankle effusion in 10%. Enthesitis and tendonitis of the anchoring tendons were relatively rare in all the articular sites. Comparison of the SpA and PMR patients showed that enthesitis (mostly in the elbow, knee, and heel) was significantly more frequent in SpA. There was a significant difference in glenohumeral and coxofemoral effusion between the PMR and SpA patients (66% vs 16% and 40% vs 14%, respectively). Comparison of PMR and RA patients showed no significant difference in the involvement of entheses, shoulder, hip, or wrist flexor tendons in the carpal tunnel. Synovitis of the elbow, knee, and wrist was significantly more frequent in the SpA and RA patients than in those with PMR. CONCLUSION: Synovitis was detected in at least one site in 100% of patients with PMR. SA-SD bursitis, LHBT tenosynovitis, carpal tunnel syndrome, and glenohumeral, knee and hip synovitis were the most frequent alterations in PMR. Enthesitis was relatively rare at any articular site.
12787304 Tumor suppressor protein p53 and anti-p53 autoantibodies in pediatric rheumatological dise 2003 Jun The tumor suppressor protein p53 plays an important role in cell cycle regulation. One of the major features in rheumatic diseases is the abnormal proliferation of lymphocytes. p53 expression in peripheral blood mononuclear cells (by flowcytometry) and serum anti-p53 antibodies (by ELISA) were therefore measured in 18 children and adolescents with juvenile rheumatoid arthritis (JRA) and 17 with systemic lupus erythematosus (SLE) in comparison to 20 healthy controls, to determine their role. p53 expression in patients was insignificantly higher than that of controls (2.28 +/- 2.71% vs. 1.08 +/- 1.02%, respectively, p > 0.05) with 29.4% of the patients showing values above a cut-off level of 2.55% (95th percentile of controls). SLE patients with active disease had significantly higher p53 expression compared to controls and to patients with quiescent disease although no significant correlation with ESR or complement 3 was detected. Seropositivity to anti-p53 antibodies was observed in none of controls but in 22.8% of patients, all of whom, except one, had active disease. Seropositivity to anti-p53 antibodies was more prominent in lupus nephritis than in other presentations of SLE (p < 0.05). The mean p53 expression in seropositive patients was insignificantly higher than in seronegatives. p53 expression and seropositivity to anti-p53 were slightly higher in SLE than in JRA and were not significantly affected by the mode of therapy. Thus, the overexpression of p53 in some patients with active SLE and JRA might explain the abnormal proliferation of autoreactive lymphocytes that perpetuates the inflammatory response. The presence of anti-p53 antibodies might cause malfunctioning of p53 protein interfering with its regulatory functions.
12126975 Pharmacological studies of diacerein in animal models of inflammation, arthritis and bone 2002 Jul 12 Diacerein has proved to be effective in the treatment of osteoarthritis. We investigated the effects of diacerein in animal models of carrageenin-, zymosan-, or dextran-induced paw edema and adjuvant-induced arthritis and in ovariectomized rats. In acute inflammatory models, unlike classical nonsteroidal anti-inflammatory drugs such as naproxen and ibuprofen, diacerein inhibited the rat paw edema induced by various agents. In the adjuvant-induced arthritic rats, diacerein at 100 mg/kg/day significantly suppressed the paw edema and the increase in serum mucoprotein. Addition of 3 mg/kg/day naproxen to each diacerein (3, 10, 30 mg/kg/day) dose resulted in significantly greater anti-inflammatory activity than with naproxen alone. In the ovariectomized rats, diacerein (10, 100 mg/kg/day) also significantly prevented bone loss and reduced the serum alkaline phosphatase and decreased the excretion of urinary hydroxyproline. In addition, rhein (10, 30 microM) inhibited calcium release from mouse calvaria induced by interleukin-1 beta, prostaglandin E(2) and parathyroid hormone 1-34 human fragment. These findings indicate that diacerein is a novel anti-inflammatory drug with pharmacological properties different from those of classical nonsteroidal anti-inflammatory drugs and support the clinical investigation of the use of combination therapy with diacerein and nonsteroidal anti-inflammatory drugs in patients with not only osteoarthritis but also rheumatoid arthritis.