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ID PMID Title PublicationDate abstract
16751698 [Bone and bone related biochemical examinations. Bone and collagen related metabolites. Bi 2006 Jun Now, it is becoming known that the mechanisms of cartilage matrix destruction such as roles of degradative enzymes and cytokines. It is important to develop the reliable biomarkers to detect the early stage of cartilage destruction. The biomarker could be useful tool not only to understand the progression of joint destruction in osteoarthritis and rheumatoid arthritis but also to develop new treatment.
17029105 Production of interleukin-6 and interleukin-8 by nurse-like cells from rheumatoid arthriti 2005 It has been reported that nurse-like cells (NLCs) play a critical role in the pathogenesis of rheumatoid arthritis (RA). The interaction between NLCs established from RA patients (RA-NLCs), and freshly isolated blood monocytes was analyzed to further elucidate the pathogenesis of RA. RA-NLC lines were established from the synovium of RA patients. The RA-NLCs were cultured with monocytes freshly isolated from peripheral blood of healthy donors, and induction of interleukin (IL)-6 and IL-8 as well as the mRNA expression of these cytokines was examined. The levels of IL-6 were over 400 times higher in the supernatant from coculture of RA-NLCs and monocytes than in those from cultures of RA-NLCs alone. Anti-tumor necrosis factor (TNF)-alpha monoclonal antibody inhibited the induction of both cytokine in a dose-dependent fashion, although there was no detectable level of TNF-alpha in the supernatant from coculture. In addition, coculture of RA-NLCs and monocytes without direct cell contact did not induce cytokine production. To determine IL-6 producing cells, RA-NLCs and monocytes were separated into each fraction after coculture for 24 h. Cocultured RA-NLCs contained approximately 80 times higher IL-6 mRNA than the RA-NLCs cultured alone. The levels of IL-8 were also much higher (about 900 times) in the supernatant from coculture than in those from cultures of RA-NLCs alone. Cocultured RA-NLCs expressed IL-8 mRNA about 620 times higher than those cultured alone. These results indicate that NLCs produce high levels of IL-6 and IL-8 after cell-cell interaction with monocytes/macrophages via membrane-bound TNF-alpha, and that activation of NLCs by monocytes/macrophages may be involved in the pathogenesis of RA through maintenance of synovial inflammation.
16409728 [A study of antiendothelial cell antibodies in Behcet's disease]. 2005 Dec OBJECTIVE: To investigate the clinical significant of antiendothelial cell antibodies (AECA) in Behcet's disease. METHODS: With human umbilical vein endothelial cell as substrate cell, sera from 59 Behcet's disease patients were detected for the presence of AECA by using fixed cell-ELISA. The associations of AECA to clinical disease activity were analyzed. In addition, Sera from other 70 systemic vasculitis (including 28 Takayasu arteritis, 20 Wegener's granulomatosis, 8 polyarteritis nodosa, 9 microscopic polyangiitis, 5 Churg-Strauss syndrome), 57 systemic lupus erythematosus (SLE), 25 rheumatoid arthritis and 85 healthy donors were screened for AECA. The associations of AECA to clinical disease activity were analyzed. RESULTS: The prevalence of AECA by human umbilical vein endothelial cell cell-ELISA was 47.5% in Behcet's disease. Compared with patients with rheumatoid arthritis (4.0%) and normal group (1.2%), AECA were more frequently found in patients with Behcet's disease, other systemic vasculitis (68.6%) and SLE (45.7%) (P < 0.01). The positive result on pathergy testing was more frequently found in AECA-positive patient with Behcet's disease (P < 0.05). After the treatment, patients with active disease entering remission showed a decrease in both AECA titers and the mean level of ESR (P < 0.05). CONCLUSIONS: AECA could be found more frequently in patients with Behcet's disease, associated closely with disease activity, which suggest that AECA may be used as an index in monitoring disease activity and effect of therapy in Behcet's disease. But AECA could also be found in other systemic vasculitis and SLE.
16356194 THR0921, a novel peroxisome proliferator-activated receptor gamma agonist, reduces the sev 2006 THR0921 is a novel peroxisome proliferator-activated receptor gamma (PPARgamma) agonist with potent anti-diabetic properties. Because of the proposed role of PPARgamma in inflammation, we investigated the potential of orally active THR0921 to inhibit the pathogenesis of collagen-induced arthritis (CIA). CIA was induced in DBA/1J mice by the injection of bovine type II collagen in complete Freund's adjuvant on days 0 and 21. Mice were treated with THR0921 (50 mg/kg/day) starting on the day of the booster injection and throughout the remaining study period. Both clinical disease activity scores as well as histological scores of joint destruction were significantly reduced in mice treated with THR0921 compared to untreated mice. Proliferation of isolated spleen cells, as well as circulating levels of IgG antibody to type II collagen, was decreased by THR0921. Moreover, spleen cell production of IFN-gamma, tumor necrosis factor (TNF)-alpha and IL-1beta in response to exposure to lipopolysaccharide or type II collagen was reduced by in vivo treatment with THR0921. Steady state mRNA levels of TNF-alpha, IL-1beta, monocyte chemotactic protein-1 and receptor activator of nuclear factor kappaB ligand (RANKL) in isolated joints were all decreased in mice treated with THR0921. Finally, THR0921 inhibited osteoclast differentiation of bone marrow-derived cells stimulated with macrophage colony-stimulating factor and RANKL. In conclusion, THR0921 attenuates collagen-induced arthritis in part by reducing the immune response. As such, PPARgamma may be an important therapeutic target for rheumatoid arthritis.
16984225 Intraarticular interferon-beta gene therapy ameliorates adjuvant arthritis in rats. 2006 Oct Interferon (IFN)-beta has significant immunomodulatory properties and has received much interest as a potentially therapeutic agent for rheumatoid arthritis (RA). Systemic IFN-beta treatment of patients with RA was not effective, probably because of pharmacokinetic issues. Therefore, we studied the effect of local IFN-beta production by adenovirus-mediated gene transfer to the ankle joints of arthritic rats. Adjuvant arthritis (AA) in rats was used as a model to study intraarticular gene therapy with an adenoviral vector encoding the rat IFN-beta gene (Ad.IFN-beta). The effect on paw swelling was measured by water displacement plethysmometry. Synovial tissue of the hind paws was examined by immunohistochemistry. Bone destruction was analyzed on the basis of radiographs. In addition, quantitative real-time polymerase chain reaction was used to assess IFN-beta expression. Levels of IFN-beta mRNA and protein peaked 2 days after intraarticular injection and declined thereafter. Local delivery of Ad.IFN-beta after the onset of disease reduced paw swelling significantly. This was accompanied by a reduction in synovial inflammation. The clinical effects in rat AA lasted up to 9 days. Strikingly, Ad.IFN-beta treatment protected bone from erosion, reduced levels of c-Cbl and Cbl-b (both signaling molecules essential for osteoclast activity), and reduced the matrix metalloproteinase-3:tissue inhibitor of metalloproteinase-1 ratio in the joint. Immunohistochemical analysis of the synovial tissue revealed a clear shift toward a more antiinflammatory cytokine profile. Local overexpression of IFN-beta inhibits arthritis progression and protects against bone destruction in rat AA. These findings validate IFN-beta as a therapeutic molecule for intraarticular gene therapy of arthritis.
16142877 Roxithromycin specifically inhibits development of collagen induced arthritis and producti 2005 Sep OBJECTIVE: Roxithromycin (RXM) is a macrolide antibiotic that is effective in treatment of chronic lower respiratory tract diseases including diffuse panbronchiolitis and bronchial asthma. Its mechanism of action apart from its antibacterial action remains unclear. To determine the mechanism of action of RXM, we evaluated the effect of RXM on T cell functions and the inflammatory responses in mice with collagen induced arthritis (CIA). METHODS: T cell proliferation, cytokine production by T cells stimulated through CD28, CD26, or PMA with or without anti-CD3 Mab, cytokine production by macrophages stimulated with lipopolysaccharide, and transendothelial migration of T cells were analyzed in the presence or absence of various concentrations of RXM. We evaluated the effect of RXM treatment in collagen induced arthritis in mice. RESULTS: RXM did not affect the production of Th1-type and Th2-type cytokines, whereas it specifically inhibited production of proinflammatory cytokines such as tumor necrosis factor-a and interleukin 6 (IL-6) by T cells and macrophages. RXM inhibited T cell migration. We found that RXM treatment of mice with CIA reduced the severity of arthritis and serum level of IL-6, as well as leukocyte migration into the affected joints and destruction of bones and cartilage. CONCLUSION: Our findings strongly suggest that RXM may be useful for the therapy of rheumatoid arthritis as well as other inflammatory diseases such as Crohn's disease.
15934059 Effects of combination M40403 and dexamethasone therapy on joint disease in a rat model of 2005 Jun OBJECTIVE: To investigate the effects of combination therapy with M40403, a superoxide dismutase mimetic (SODm), and dexamethasone (DEX) on collagen-induced arthritis (CIA) in rats. METHODS: CIA was elicited in Lewis rats by an intradermal injection of 100 mul of an emulsion of bovine type II collagen (CII) in Freund's incomplete adjuvant (IFA) at the base of the tail. On day 21, a second injection of CII in IFA was administered at the base of the tail. RESULTS: Lewis rats developed erosive arthritis of the hind paw when immunized with an emulsion of CII in IFA. The histopathology of CIA included erosion of the articular cartilage at the joint margins and subchondral bone resorption. Immunohistochemical analysis for nitrotyrosine, poly(ADP-ribose) polymerase (PARP), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2) revealed positive staining in inflamed joints of collagen-treated rats. The combination therapy with M40403 2 mg/kg and DEX 0.01 mg/kg significantly reduced the development of the inflammatory process and reduced the degree of staining for iNOS, COX-2, nitrotyrosine, and PARP. No significant difference in the degree of staining between the combination therapy and the higher dose of DEX (0.1 mg/kg) was found. Furthermore, radiographic evidence of protection from bone resorption was apparent in the tibiotarsal joints of rats that received the combination therapy. CONCLUSION: This study shows that combination therapy with M40403 and DEX reduced the degree of chronic inflammation and tissue and bone damage associated with CIA in the rat. It supports the possible use of SODm in combination with steroids to reduce the dose necessary and the side effects related to the use of steroids in the management of chronic diseases such as rheumatoid arthritis.
21794264 [Cost analysis in a cohort of rheumatoid arthritis patients managed in rheumatology units 2005 Dec OBJECTIVE: To assess the annual costs of rheumatoid arthritis (RA) patients attended at rheumatology units in Spanish public hospitals. METHODS: A longitudinal, prospective, multicenter, observational, 1-year study was performed in the rheumatology units of randomly selected Spanish public hospitals. Randomly selected RA patients were included. The patients made four visits (at baseline and every 4 months). Resource use and costs were collected from patient diaries and structured questionnaires. RESULTS: A total of 301 patients were included and 190 (83% women) completed the study. The mean (± SD) age was 59±13 years and the mean disease duration was 10±10 years. The median annual cost per patient was 3,845 euros (318-36,783). The estimated total annual cost of the Spanish RA population managed in the rheumatology units of public hospitals was 590,110,000 euros. Of total costs, 74% were direct costs and 26% were indirect costs. Medical costs represented 81% of direct costs. The main components of medical costs were drugs (56%), medical visits (21%), complementary tests (12%), and hospitalizations (11%). Permanent work disability represented 66% of indirect costs. CONCLUSIONS: Direct costs were substantially higher than indirect costs. The main components of medical costs were drugs. There was high variability in resource use with a wide range of annual costs per patient.
15981980 [Pathophysiology of and clinical significance of polyunsaturated fatty acids n-3 family]. 2005 Polyunsaturated fatty acids of n-3 family play an important role in the prevention of ischemic heart disease, as was shown in many epidemiological as well as intervention studies. These fatty acids are essential and human organism is fully dependent on their dietary intake from chloroplast of green plants and fat of aquatic animals. Cardioprotective action of these acids results from their complex effect (antiarrhytmic, antithrombotic, antiinflammatory, hypolipidemic etc.). These acids can, with the exception of glucose homeostasis, favourably influence individual components of the metabolic syndrome. Beneficial effects of n-3 polyunsaturated fatty acids are supposed also in chronic inflammatory and autoimmune diseases, psychiatric-neurological diseases and malignant tumours. In the case of rheumatoid arthritis, antiinflammatory effects of polyunsaturated fatty acids were proven. In general, favourable effects of the optimal income of n-3 polyunsaturated fatty acids can be explained by the influencing of cellular metabolic functions, incorporation into membrane phospholipids, modulation of enzymes and signal molecules as well as by direct impact on gene expression. Polyunsaturated fatty acids of n-3 family have high therapeutic potential, which results from the combined action on different levels of cell functions. In some diseases, their effect is nearly pharmacological - prevention of the sudden death and fatal myocardial infarction, treatment of hyper- and dyslipoproteinemias, suppression of the inflammatory activity in rheumatoid arthritis. In another group of diseases, they have supporting effect (prevention of the arterial hypertension in metabolic syndrome) and, finally, in the last one (psychiatric-neurological diseases and tumours), more data of defined clinical groups are necessary for final evaluation.
16433522 A fluoroacetamidine-based inactivator of protein arginine deiminase 4: design, synthesis, 2006 Feb 1 Protein arginine deiminase 4 (PAD4) is a calcium-dependent transcriptional corepressor that has been implicated in the onset and progression of rheumatoid arthritis. Herein we describe the synthesis and in vitro evaluation of a fluoroacetamidine-containing compound, N-alpha-benzoyl-N5-(2-fluoro-1-iminoethyl)-l-ornithine amide, 1, hereafter referred to as F-amidine, that is the most potent PAD4 inhibitor ever described. Additional studies described herein indicate that F-amidine can also inhibit PAD4 activity in vivo. The bioavailability of this compound suggests that F-amidine will be a powerful chemical probe of PAD4 function that can be used to dissect the roles of this enzyme in both rheumatoid arthritis and transcriptional control. The fact that inhibition is of an irreversible nature suggests that, with appropriate functionalization, F-amidine analogues will be robust activity-based protein-profiling and proteomic capture reagents.
16276047 [The role of BAFF in autoimmune diseases]. 2005 Oct B cell activating factor belonging to the tumor necrosis factor family (BAFF) is a tumor necrosis factor (TNF) superfamily member best known for its role in the survival and maturation of B cells. BAFF is a ligand for three TNF receptor superfamily members: B-cell maturation antigen (BCMA), transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), and BAFF receptor (BAFF-R). Among them, BAFF-R plays the central role in the BAFF system, whereas TACI plays the inhibitory role. BAFF/BAFF receptors appear to span nearly all stages of B-lineage differentiation, ranging from the development, selection, and homeostasis of naive primary B cells to the maintenance of long-lived bone marrow plasma cells. Furthermore, excessive BAFF rescues self-reactive B cells from anergy, which may play a crucial role in the induction and development of autoimmunity. Mice overexpressing BAFF exhibit increased B cell numbers in spleen and lymph node and autoimmune phenotype similar to patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome. Furthermore, inhibition of BAFF by TACI-Ig and BAFFR-Ig has been successful in treating murine models of SLE and rheumatoid arthritis. In humans, previous reports have shown elevated serum BAFF levels in SLE, rheumatoid arthritis, Sjögren's syndrome, and systemic sclerosis patients. Thus, the dysregulation of BAFF/BAFF receptor system may contribute to induction and development of autoimmune diseases and become one of important therapeutic targets.
16697661 Role of PTPN22 in type 1 diabetes and other autoimmune diseases. 2006 Aug We recently discovered that a single-nucleotide polymorphism (SNP) in the lymphoid tyrosine phosphatase (LYP), encoded by the PTPN22 gene on chromosome 1p13, correlates strongly with the incidence of type 1 diabetes (T1D) in two independent populations. This findings has now been verified by numerous studies and it has been expanded to rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus, Graves' disease, generalized vitiligo and other autoimmune disease. Here we review the genetics of the SNP and its association with autoimmunity, discuss the function of the phosphatase in signaling, the biochemistry of the disease-predisposing allele, and the possible mechanisms by which PTPN22 contributes to the development of human disease.
16188400 Predisposing conditions and risk factors for development of symptomatic meningioma in adul 2005 BACKGROUND: Risk factors and predisposing factors for the development of symptomatic meningioma during adult life are not well known. METHODS: Data from 306 consecutive patients with primary meningioma were collected retrospectively in a hypothesis-generating study. Factors studied included localisation of tumours, blood group typing, and risk factors, such as diabetes mellitus, coronary arterial disease, hypertension, rheumatoid arthritis, bronchial asthma, smoking, obesity, and second primary tumour. Case-control analysis of putative risk factors was carried out using a control data set from the German East-West Health Survey (n=7466, age range 25-69 years). Patients and controls were matched for age, gender, geographic area, and time of data collection. RESULTS: Rh(D) positive cases were significantly less frequent in the patient group compared to controls (p=0.01). Pre-existing diabetes was associated with meningioma in middle-aged (40-69 years) patients (odds ratio, OR 13.94-4.30, p=0.001-0.05). In female patients, arterial hypertension was significantly associated with occurrence of meningioma in the age group 60-69 years (OR=2.23, p=0.041). Rheumatoid arthritis had a negative association with meningioma in both males and females in the age groups above 50 years (OR 0.19-0.27, p=0.02-0.034). Bronchial asthma, smoking, and obesity were not significantly associated with meningioma. A second primary tumour was present in 12 cases. The most frequent combination was meningioma and breast cancer (5/12). CONCLUSIONS: This study shows statistically significant association of some co-morbidities with symptomatic meningioma in adults. Areas of interest have been identified where further research would be necessary.
16849504 MAPKAP kinase 2-deficient mice are resistant to collagen-induced arthritis. 2006 Aug 1 TNF-alpha is a pleiotropic cytokine considered a primary mediator of immune regulation and inflammatory response and has been shown to play a central role in rheumatoid arthritis (RA). MAPKAP kinase 2 (MK2) is a serine/threonine kinase that is regulated through direct phosphorylation by p38 MAPK, and has been shown to be an essential component in the inflammatory response that regulates the biosynthesis of TNF-alpha at a posttranscriptional level. The murine model of collagen-induced arthritis (CIA) is an established disease model to study pathogenic mechanisms relevant to RA. In this study, we report that deletion of the MK2 gene in DBA/1LacJ mice confers protection against CIA. Interestingly, the MK2 heterozygous mutants display an intermediate level of protection when compared with homozygous mutant and wild-type littermates. We show that MK2(-/-) and MK2(+/-) mice exhibit decreased disease incidence and severity in the CIA disease model and reduced TNF-alpha and IL-6 serum levels following LPS/d-Gal treatment compared with wild-type mice. Additionally, we show that levels of IL-6 mRNA in paws of mice with CIA correlate with the disease status. These findings suggest that an MK2 inhibitor could be of great therapeutic value to treat inflammatory diseases like RA.
17276893 Induction of immune tolerance by oral IVIG. 2007 Mar In the last years evidence has been provided for the importance of B cells in the pathogenesis of rheumatoid arthritis (RA). Several studies have supported the concept that humoral immunity, manifested by the production of autoantibodies, such as rheumatoid factors (RFs), plays a significant role in the course of the disease. Specific targeting of autoantibody-producing B cells, such as RF-producing B cells, should therefore be a promising new approach in the treatment of RA. We used a mouse model to induce human RF responses and asked the question whether oral treatment with the antigen (human IgG) recognized by RFs could induce immune tolerance to RF responses. Balb/c mice were orally treated with polyvalent human IgG before and after immunization with insoluble immune complexes (ICs) that triggered the induction of RFs. Serum titers of RFs were significantly reduced after both primary and booster immunization when human IgG was given as a single oral dose or continuously in drinking water. Continuous treatment with human IgG even prevented booster effects on RFs when treatment started after primary immunization. Treatment with IgG fragments provided evidence that the observed effect of human IgG was mediated by the Fc part and not the Fab part of IgG. Furthermore, transfer of spleen cells obtained from mice after oral treatment with human IgG suppressed RF responses in recipient mice. These data give promising indications that oral human IgG might represent an alternative approach for immunosuppressive B-cell targeted therapies in RA.
17097389 Childhood acquired lipodystrophy: a retrospective study. 2006 Dec OBJECTIVE: We sought to describe the clinical characteristics and complications of children with acquired lipodystrophy (LD). METHODS: We conducted a retrospective chart review at a tertiary, academic children's hospital of children clinically given a diagnosis of acquired LD between January 1997 and December 2004. RESULTS: During the study period, 23 patients were identified. Their mean age at diagnosis was 9.74 +/- 3.98 years. Of patients, 61% were girls. The length of the follow-up was 4.8 +/- 3.5 years from the time of LD diagnosis. Of patients, 30% had evidence of localized disease (7 of 23), 26% (6 of 23) had localized partial disease, and 44% (10 of 23) had generalized LD. The most common underlying diagnosis was dermatomyositis (78%), alone or in association with other autoimmune diseases (juvenile rheumatoid arthritis 17%). Panniculitis with autoimmunity was noted in 17% of the patients. More than half of the patients had at least one complication attributable to LD such as acanthosis nigricans (22%), hyperpigmentation (22%), hepatomegaly (13%), hypertension (13%), protuberant abdomen (9%), and hyperlipidemia (4%). The only predictor for development of complications was the age of diagnosis of LD, with younger age being associated with increased risk (7 vs 12 years, P = .04). LIMITATIONS: Limitations were inherent to the retrospective design. CONCLUSIONS: Childhood acquired LD is seen more frequently in the context of autoimmunity. Affected children should be monitored for the development of complications, particularly if given a diagnosis of LD at a younger age.
17038468 Potential new targets in arthritis therapy: interleukin (IL)-17 and its relation to tumour 2006 Nov Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by chronic joint inflammation and destruction. Interleukin (IL)-17 is a T cell cytokine expressed in the synovium and synovial fluid of patients with RA. IL-17 is a potent inducer of various cytokines such as tumour necrosis factor (TNF) and IL-1. IL-17 has been shown to have additive or even synergistic effects with TNF and IL-1 during the induction of cytokine expression and joint damage in vitro and in vivo. TNFalpha and IL-1 are considered powerful targets in the treatment of RA because of their leading role in driving the enhanced production of cytokines, chemokines, and degradative enzymes. Besides anti-TNF and anti-IL-1 therapies, whose clinical efficacy is now established, new targets have been proposed for RA which is not responding to conventional treatments. This paper discusses the role of IL-17 in experimental arthritis and its interrelationship with TNF and IL-1, currently the most targeted cytokines in the treatment of RA. IL-17 is involved in both initiation and progression of murine experimental arthritis. Studies have shown that IL-17 not only synergises with TNF, but also enhances inflammation and destruction independent of IL-1 and TNF. On the basis of these studies, the authors propose IL-17 as an interesting additional target in the treatment of RA.
17032248 Anti-TNF effects on destructive fibroblasts depend on mechanical stress. 2006 Nov Joint destruction in rheumatoid arthritis (RA) starts typically at sites of mechanically stressed inserts of the synovial membrane near the cartilage/bone border. In the therapy of RA, tumour necrosis factor (TNF) antagonists have rapidly emerged as a valuable class of anti-rheumatic agents that reduce joint destruction. The aim of this study was to investigate and profile genes involved in the interaction between articular movement and anti-TNF therapy in an in vitro model. Murine LS48 cells, an established substitute for invasive RA synovial fibroblasts, were cultured, stretched and/or treated with anti-TNF-alpha antibody for 24 h. RNA was isolated and gene transcript levels were determined using U74Av2 Affymetrix GeneChips to identify transcriptional events. Positive findings were verified by polymerase chain reaction (PCR). We identified 170 differentially regulated genes, including 44 of particular interest. Gene expression fell into different functional groups that can be explained by RA pathogenesis and experimental conditions. For 21 genes of the 44 of particular interest, regulation could be confirmed by real-time PCR. Remarkably, we found structural as well as functional genes differently regulated between stretched cells, anti-TNF-treated cells, and stretched cells treated with anti-TNF antibody. Additionally, we also found a large number of genes that are apparently not related to the experimental conditions. Mechanical exertion modulates gene expression and subsequently cellular response to anti-TNF therapy. Results in exerted cells correspond to current knowledge regarding RA pathogenesis and underline the relevance of our experimental approach. Finally, the central function of the interleukin-18 system in joint destruction could be confirmed by our findings.
15798098 Noncalcemic actions of vitamin D receptor ligands. 2005 Aug 1alpha,25-Dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], the active metabolite of vitamin D(3), is known for the maintenance of mineral homeostasis and normal skeletal architecture. However, apart from these traditional calcium-related actions, 1,25-(OH)(2)D(3) and its synthetic analogs are being increasingly recognized for their potent antiproliferative, prodifferentiative, and immunomodulatory activities. These actions of 1,25-(OH)(2)D(3) are mediated through vitamin D receptor (VDR), which belongs to the superfamily of steroid/thyroid hormone nuclear receptors. Physiological and pharmacological actions of 1,25-(OH)(2)D(3) in various systems, along with the detection of VDR in target cells, have indicated potential therapeutic applications of VDR ligands in inflammation (rheumatoid arthritis, psoriatic arthritis), dermatological indications (psoriasis, actinic keratosis, seborrheic dermatitis, photoaging), osteoporosis (postmenopausal and steroid-induced osteoporosis), cancers (prostate, colon, breast, myelodysplasia, leukemia, head and neck squamous cell carcinoma, and basal cell carcinoma), secondary hyperparathyroidism, and autoimmune diseases (systemic lupus erythematosus, type I diabetes, multiple sclerosis, and organ transplantation). As a result, VDR ligands have been developed for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism. Furthermore, encouraging results have been obtained with VDR ligands in clinical trials of prostate cancer and hepatocellular carcinoma. This review deals with the molecular aspects of noncalcemic actions of vitamin D analogs that account for the efficacy of VDR ligands in the above-mentioned indications.
16927760 [Ophthalmological involvement in rheumatic disease]. 2006 PURPOSE: The main objective of this study was to identify the prevalence of ocular manifestations in rheumatic patients admitted in a specialized clinic. METHODS: Information regarding rheumatic and ocular diseases was extracted from medical records system available in "Dr. I. Cantacuzino" Clinical Hospital from Bucharest. The prevalence of ocular involvement reported passively by rheumatologists (retrospective descriptive study of 375 different cases of rheumatic patients) was compared with the literature data. RESULTS: There were 45 cases of ocular manifestations. Keratoconjunctivitis sicca was noted in 16 patients with rheumatoid arthritis, two patients with systemic lupus erythematosus and one patient with scleroderma. Anterior uveitis was found in seven patients with ankylosing spondylitis, one patient with reactive arthritis, two patients with psoriatic arthritis and one patient with LES. Conjunctivitis was present in two patients with reactive arthritis. In LES ocular involvement also included four cases of retinal vasculitis. Complications clearly related to steroid therapy were nine cases of cataracts. One case with typical "bull's eye" maculopathy due to Hydroxychloroquine treatment was detected. CONCLUSIONS: The main conclusion of our study is that the rheumatic patients need to be referred to an ophthalmologist for the diagnosis and the optimal treatment of ocular involvement.