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ID PMID Title PublicationDate abstract
17414952 New therapeutic approaches for spondyloarthritis. 2007 May PURPOSE OF REVIEW: Tumor necrosis factor alpha antagonists are effective for signs and symptoms of ankylosing spondylitis. Recent studies have evaluated the efficacy of these agents for structural disease modification. We critically review recent radiographic data suggesting that tumor necrosis factor alpha inhibition may have structure-modifying effects in ankylosing spondylitis, and may thereby alter the disease course. RECENT FINDINGS: Recent studies employing MRI suggest that therapy with tumor necrosis factor alpha antagonists significantly reduces spinal inflammation in active ankylosing spondylitis when compared to placebo; there was no comparable improvement in the severity of chronic stigmata, such as syndesmyophytes and vertebral bridging. These studies were of relatively short duration and small size. SUMMARY: Despite insufficient evidence to conclude definitively that tumor necrosis factor alpha-antagonist therapy provides durable and effective structure modification in ankylosing spondylitis, the data strongly suggest a benefit, at least in the short term. In the future, MRI data coupled with clinical outcomes in larger cohorts followed for longer durations may result in a paradigm shift for ankylosing spondylitis treatment similar to that undergone for rheumatoid arthritis, where patients with ankylosing spondylitis are offered therapy early in the disease course to arrest and prevent structural disease progression.
17188670 Beneficial effects of Murraya koenigii leaves on antioxidant defense system and ultra stru 2007 Jan 30 Oxidative stress and oxidative damage to tissues are common end points of chronic diseases such as atherosclerosis, diabetes, and rheumatoid arthritis. Oxidative stress in diabetes coexists with a reduction in the antioxidant status, which can further increase the deleterious effects of free radicals. The aim of the present study was to evaluate the possible protective effects of Murraya koenigii leaves extract against beta-cell damage and antioxidant defense systems of plasma and pancreas in streptozotocin induced diabetes in rats. The levels of glucose and glycosylated hemoglobin in blood and insulin, Vitamin C, Vitamin E, ceruloplasmin, reduced glutathione and TBARS were estimated in plasma of control and experimental groups of rats. To assess the changes in the cellular antioxidant defense system such as the level of reduced glutathione and activities of superoxide dismutase, catalase and glutathione peroxidase were assayed in pancreatic tissue homogenate. The levels of glucose, glycosylated hemoglobin, insulin, TBARS, enzymatic and non-enzymatic antioxidants were altered in diabetic rats. These alterations were reverted back to near control levels after the treatment of M. koenigii leaves extract. Transmission electron microscopic studies also revealed the protective nature of M. koenigii leaves on pancreatic beta-cells. These findings suggest that M. koenigii treatment exerts a therapeutic protective nature in diabetes by decreasing oxidative stress and pancreatic beta-cell damage. The antioxidant effect of the M. koenigii extract was compared with glibenclamide, a well-known hypoglycemic drug.
17109473 Expression and function of NKG2D in CD4+ T cells specific for human cytomegalovirus. 2006 Dec The human NKG2D killer lectin-like receptor (KLR) is coupled by the DAP10 adapter to phosphoinositide 3-kinase (PI3 K) and specifically interacts with different stress-inducible molecules (i.e. MICA, MICB, ULBP) displayed by some tumour and virus-infected cells. This KLR is commonly expressed by human NK cells as well as TCRgammadelta(+) and TCRalphabeta(+)CD8(+) T lymphocytes, but it has been also detected in CD4(+) T cells from rheumatoid arthritis and cancer patients. In the present study, we analysed NKG2D expression in human cytomegalovirus (HCMV)-specific CD4(+) T lymphocytes. In vitro stimulation of peripheral blood mononuclear cells (PBMC) from healthy seropositive individuals with HCMV promoted variable expansion of CD4(+)NKG2D(+) T lymphocytes that coexpressed perforin. NKG2D was detected in CD28(-) and CD28(dull )subsets and was not systematically associated with the expression of other NK cell receptors (i.e. KIR, CD94/NKG2 and ILT2). Engagement of NKG2D with specific mAb synergized with TCR-dependent activation of CD4(+) T cells, triggering proliferation and cytokine production (i.e. IFN-gamma and TNF-alpha). Altogether, the data support the notion that NKG2D functions as a prototypic costimulatory receptor in a subset of HCMV-specific CD4(+) T lymphocytes and thus may have a role in the response against infected HLA class II(+) cells displaying NKG2D ligands.
17094021 DA-9601 inhibits activation of the human mast cell line HMC-1 through inhibition of NF-kap 2007 Mar Mast cell-mediated allergic inflammation is involved in many diseases such as asthma, sinusitis, and rheumatoid arthritis. Mast cells induce synthesis and production of pro-inflammatory cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 with immune regulatory properties. The formulated ethanol extract of Artemisia asiatica Nakai (DA-9601) has been reported to have antioxidative and anti-inflammatory activities. In this report, we investigated the effect of DA-9601 on the expression of pro-inflammatory cytokines by the activated human mast cell line HMC-1 and studied its possible mechanisms of action. DA-9601 dose-dependently decreased the gene expression and production of TNF-alpha, IL-1beta, and IL-6 on phorbol 12-myristate 13-acetate (PMA)- and calcium ionophore A23187-stimulated HMC-1 cells. In addition, DA-9601 attenuated PMA- and A23187-induced activation of NF-kappaB as indicated by inhibition of degradation of IkappaBalpha, nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay. Our in vitro studies provide evidence that DA-9601 might contribute to the treatment of mast cell-derived allergic inflammatory diseases.
17078593 [How to evaluate the cardiovascular and renal risk at the individual level?]. 2006 Sep The cardiovascular impact of the non-steroidal anti-inflammatory drugs and the higher cardiovascular mortality during treatment of inflammatory rheumatism impose a rigorous evaluation of the cardiovascular risk of rheumatic patients. Large epidemiological studies have identified risk factors for cardiovascular diseases such as the age, male gender, family history (infarct, stroke), tobacco consumption, systolic arterial pressure, renal insufficiency, hypercholesterolemia, diabetes mellitis, sedentariness, obesity and "electric" ventricular hypertrophy. Some equations make it possible to evaluate the absolute cardiovascular risk at the individual level, which corresponds to the onset risk of a stroke in the 10 years to come in a subject according to the number and importance of each of his risk factors. It has been demonstrated that the correction of one or more risk factors reduce the overall cardiovascular risk justifying the strategies for evaluating this risk to define therapeutic intervention thresholds. The impact of a long-term anti-inflammatory treatment or an inflammatory disease such as rheumatoid arthritis has not been the subject of specific epidemiological study allowing these elements to be included in an equation of the estimation of the cardiovascular risk. However, the introduction of on anti-inflammatory treatment, likely to increase the cardiovascular risk of a patient, certainly justifies an evaluation of the absolute cardiovascular risk.
17047890 Improving management of musculoskeletal disorders in primary care: the Joint Adventures Pr 2007 Jul Musculoskeletal disorders represent a large and growing clinical challenge to primary care clinicians. Unfortunately, there appears to be a gap in current training and continuing education to meet this challenge. We used script concordance within a continuing medical education program entitled "Joint Adventures" to assist family physicians to acquire the knowledge, skills, and tools they need to improve their management of musculoskeletal disorders. Program workshops were coordinated through a national continuing education program of the College of Family Physicians of Canada. A group of 54 experts in musculoskeletal disorders including family physicians, rheumatologists, and orthopedists developed cases for six areas of management that were identified by family physicians during a needs survey delivered at a national scientific congress in primary care. Script concordance methodology was used in the Joint Adventures workshop to address knowledge gaps or lack of group consensus in the six areas including (1) diagnosis of osteoarthritis, (2) treatment and management of osteoarthritis, (3) treatment and management of rheumatoid arthritis, (4) diagnosis and treatment of back pain, (5) diagnosis and treatment of fibromyalgia and diagnosis, and (6) treatment of shoulder pain. Each workshop session included 5-30 family physicians, a specialist expert, and a family physician facilitator. Before each session, a group needs assessment was conducted to identify which one or two of the six cases would be used. Perceived knowledge and skill acquisition, self-assessed change in practice, and satisfaction with the program were measured at the conclusion of each session and again at 3 months post program. All programs were delivered from March 2003 to September 2005. Six hundred and fifty family physicians from across Canada completed the program. In general, participants reached concordance with each case. Measures of knowledge and skill acquisition and self-assessed change in practice were significantly improved with high rates of program satisfaction. The Joint Adventures program provided family physicians with knowledge and skills that changed their care of musculoskeletal disorders. This was achieved using consensus that was sensitive to local needs. Further use should be evaluated in other areas of medical practice as well.
16890260 Mosla dianthera inhibits mast cell-mediated allergic reactions through the inhibition of h 2006 Nov 1 In this study, we investigated the effect of the aqueous extract of Mosla dianthera (Maxim.) (AEMD) on the mast cell-mediated allergy model and studied the possible mechanism of action. Mast cell-mediated allergic disease is involved in many diseases such as asthma, sinusitis and rheumatoid arthritis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. AEMD inhibited compound 48/80-induced systemic reactions in mice. AEMD decreased immunoglobulin E-mediated local allergic reactions, passive cutaneous anaphylaxis. AEMD attenuated intracellular calcium level and release of histamine from rat peritoneal mast cells activated by compound 48/80. Furthermore, AEMD attenuated the phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-stimulated TNF-alpha, IL-8 and IL-6 secretion in human mast cells. The inhibitory effect of AEMD on the pro-inflammatory cytokines was nuclear factor-kappaB (NF-kappaB) dependent. AEMD decreased PMA and A23187-induced degradation of IkappaBalpha and nuclear translocation of NF-kappaB. Our findings provide evidence that AEMD inhibits mast cell-derived immediate-type allergic reactions and involvement of pro-inflammatory cytokines and NF-kappaB in these effects.
16720634 Etanercept treatment for three months is safe in patients with rheumatological manifestati 2007 Jan OBJECTIVE: The treatment of the rheumatological manifestations associated with hepatitis C virus (HCV) remains difficult. To examine the safety of anti-tumour necrosis factor-alpha treatment, nine patients having rheumatological manifestations associated with HCV were treated with etanercept 25 mg twice a week for 3 months. METHODS: Five patients had a positive viral load at study entry (Group I), four were negative (Group II). Clinical data recorded were: disease duration, painful and swollen joint count, patient global and physician global assessment, the number of 18 specified fibromyalgia tender points and the Health Assessment Questionnaire score. Laboratory studies included checking for the presence of cryoglobulinaemia and transaminase levels. Quantitative HCV viral RNA was performed by real-time polymerase chain reaction (PCR). RESULTS: At 3 months, no patient was found to have evidence of increased hepatic inflammation based on serial serum transaminase levels. In the five patients from Group I with detectable HCV RNA, no significant viral load increase was observed. No reactivation was observed in the four patients from Group II with undetectable HCV RNA. The effect on the clinical rheumatological manifestations was more heterogeneous but appears to be lower than that observed in rheumatoid arthritis. CONCLUSION: In this phase II open short-term study, etanercept appeared to be safe in patients with articular manifestations associated with HCV.
16714221 Fraxetin inhibits the induction of anti-Fas IgM, tumor necrosis factor-alpha and interleuk 2006 Jul The survival of osteoblast cells is one of the determinants of the development of osteoporosis in patients with inflamed synovium, such as in rheumatoid arthritis (RA). By means of alkaline phosphatase (ALP) activity and osteocalcin ELISA assay, we have shown that fraxetin exhibits a significant induction of differentiation in the human osteoblast-like cell line MG-63. In addition, we also assessed whether fraxetin affects inflammatory cytokine-mediated apoptosis in osteoblast cells. TNF-alpha or IL-1beta enhance apoptotic DNA fragmentation in anti-Fas IgM-treated MG-63 cells by increasing Fas receptor expression. However, TNF-alpha or IL-1beta treatment alone does not induce apoptosis. Treatment of MG-63 cells with fraxetin not only inhibited anti-Fas IgM-induced apoptosis, but also blocked the synergetic effect of anti-Fas IgM with TNF-alpha or IL-1beta on cell death. The apoptotic inhibition of fraxetin is associated with inhibition of TNF-alpha and IL-1beta-mediated Fas expression and enhancement of FLIP expression, resulting in a decrease of caspase-8 and caspase-3 activation. These results indicate a potential use of fraxetin in preventing osteoporosis by inhibiting inflammatory cytokine-mediated apoptosis in osteoblast cells.
16806730 Sympathetic nervous system plays an important role in the relationship between immune medi 2006 T helper (Th) lymphocytes have been classified into distinct subsets, Th1 and Th2 on the basis of the cytokines they produce. According to the cross-regulatory properties of Th1 and Th2 cells, one would assume that to be affected by a Th1 type disease increases susceptibility to a Th1 type disease and inhibits a Th2 type disease and vice versa about being affected by a Th2 type disease. However, the pattern of related diseases does not necessarily follow the conventional pattern of inhibitory effects of Th1 and Th2 immune responses on each other. For example, Mycobacteria including BCG, that induce Th1 immune responses; can modulate some Th1 type autoimmune diseases including MS, experimental autoimmune encephalomyelitis (EAE; an animal model for Multiple Sclerosis) and insulin-dependent diabetes mellitus (IDDM) thereby leading to an alleviation of their symptoms. Also BCG precipitates a syndrome similar to systemic lupus erythematosus (SLE), a Th2 type disease; in NOD mice. The coexistence of the major Th2-mediated atopic diseases such as asthma, eczema and allergic rhinitis with the Th1-mediated autoimmune conditions including; coeliac disease (CD), IDDM, rheumatoid arthritis (RA) and psoriasis is another example that is in apparent disagreement with counter-regulatory effects of Th1/Th2 phenotypes. HYPOTHESIS: SNS can be stimulated by pro-inflammatory cytokines, production of which is induced by mycobacteria including BCG. Although these cytokines can inhibit SNS activity in the site of inflammation and secondary lymphoid organs, they increase sympathetic tone in other places. Increased sympathetic tone can induce an anti-inflammatory and Th2 type milieu. This milieu can inhibit MS and IDDM and provide a susceptible environment for starting of SLE. Atopic diseases are Th2 type immune mediated diseases; therefore, they increase the production of Th2 type cytokine and decrease production of pro-inflammatory cytokines in the site of allergic reaction and also in secondary lymphoid organs. Therefore, atopic diseases decrease sympathetic tone in all tissues except in the sites of allergic reaction and secondary lymphoid organs. Decreased sympathetic tone results in a pro-inflammatory milieu and in such an environment, Th1 type autoimmune diseases can affect tissues.
16513876 Association of schizophrenia and autoimmune diseases: linkage of Danish national registers 2006 Mar OBJECTIVE: Individuals with schizophrenia and their relatives tend to have either higher or lower than expected prevalences of autoimmune disorders, especially rheumatoid arthritis, celiac disease, autoimmune thyroid diseases, and type 1 diabetes. The purpose of the study was to estimate the association of schizophrenia with these disorders as well as a range of other autoimmune diseases in a single large epidemiologic study. METHOD: The Danish Psychiatric Register, the National Patient Register, and a register with socioeconomic information were linked to form a data file that included all 7,704 persons in Denmark diagnosed with schizophrenia from 1981 to 1998 and their parents along with a sample of matched comparison subjects and their parents. The data linkage required that the autoimmune disease occur before the diagnosis of schizophrenia. RESULTS: A history of any autoimmune disease was associated with a 45% increase in risk for schizophrenia. Nine autoimmune disorders had higher prevalence rates among patients with schizophrenia than among comparison subjects (crude incidence rate ratios ranging from 1.9 to 12.5), and 12 autoimmune diseases had higher prevalence rates among parents of schizophrenia patients than among parents of comparison subjects (adjusted incidence rate ratios ranging from 1.3 to 3.8). Thyrotoxicosis, celiac disease, acquired hemolytic anemia, interstitial cystitis, and Sjögren's syndrome had higher prevalence rates among patients with schizophrenia than among comparison subjects and also among family members of schizophrenia patients than among family members of comparison subjects. CONCLUSIONS: Schizophrenia is associated with a larger range of autoimmune diseases than heretofore suspected. Future research on comorbidity has the potential to advance understanding of pathogenesis of both psychiatric and autoimmune disorders.
16474428 Regulation of cytokine production during phagocytosis of apoptotic cells. 2006 Feb Loss of self-tolerance and expansion of auto-reactive lymphocytes are the basis for autoimmunity. Apoptosis and the rapid clearance of apoptotic cells by phagocytes usually occur as coordinated processes that ensure regulated cellularity and stress response with non-pathological outcomes. Defects in clearance of apoptotic cells would contribute to the generation of self-reactive lymphocytes, which drive autoimmune disorders such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The IL-12 family of cytokines (IL-12, IL-23, and IL-27) and IL-10 are produced by phagocytic macrophages and play critical roles in the regulation of antigen-presenting cells (APCs) and effector lymphocytes during an immune response to pathogens. Inappropriate expression of these cytokines and their dysregulated activities have been strongly implicated in the pathogenesis of several autoimmune diseases. The production of pro- and anti-inflammatory cytokines by phagocytic APCs is delicately regulated during the ingestion of apoptotic cells as part of an intrinsic mechanism to prevent inflammatory autoimmune reactions. How apoptotic cell-derived signals regulate cytokine production is poorly understood. A recent study by our group demonstrated that phagocytosis of apoptotic cells by activated macrophages results in strong inhibition of IL-12 p35 gene expression by activating a novel transcription repressor, which we named GC-binding protein (GC-BP), through tyrosine dephosphorylation. We are also beginning to understand the molecular mechanisms underlying apoptotic cell-triggered production of IL-10 by phagocytes. These studies will help to elucidate some novel immune regulatory mechanisms and explore the regulation of immune responses to autoantigens with potentials to discover new therapeutic targets for the treatment of autoimmune disorders.
16310808 Effect of thalidomide affecting VEGF secretion, cell migration, adhesion and capillary tub 2006 Apr 25 Angiogenesis, new blood vessel formation, is a multistep process, precisely regulated by pro-angiogenic cytokines, which stimulate endothelial cells to migrate, proliferate and differentiate to form new capillary microvessels. Excessive vascular development and blood vessel remodeling appears in psoriasis, rheumatoid arthritis, diabetic retinopathy and solid tumors formation. Thalidomide [alpha-(N-phthalimido)-glutarimide] is known to be a potent inhibitor of angiogenesis, but the mechanism of its inhibitory action remains unclear. The aim of the study was to investigate the potential influence of thalidomide on the several steps of angiogenesis, using in vitro models. We have evaluated the effect of thalidomide on VEGF secretion, cell migration, adhesion as well as in capillary formation of human endothelial cell line EA.hy 926. Thalidomide at the concentrations of 0.01 microM and 10 microM inhibited VEGF secretion into supernatants, decreased the number of formed capillary tubes and increased cell adhesion to collagen. Administration of thalidomide at the concentration of 0.01 microM increased cell migration, while at 10 microM, it decreased cell migration. Thalidomide in concentrations from 0.1 microM to 10 microM did not change cell proliferation of 72-h cell cultures. We conclude that anti-angiogenic action of thalidomide is due to direct inhibitory action on VEGF secretion and capillary microvessel formation as well as immunomodulatory influence on EA.hy 926 cells migration and adhesion.
18625618 Development of an ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing 2009 Jan OBJECTIVES: To develop a new index for disease activity in ankylosing spondylitis (ASDAS) that is truthful, discriminative and feasible, and includes domains/items that are considered relevant by patients and doctors. METHODS: Eleven candidate variables covering six domains of disease activity, selected by ASAS experts in a Delphi exercise, were tested in a three-step approach, similar to the methodology used for the disease activity score in rheumatoid arthritis. Data on 708 patients included in ISSAS (International Study on Starting tumour necrosis factor blocking agents in Ankylosing Spondylitis) were used. Cross validation was carried out in the OASIS cohort (Outcome in Ankylosing Spondylitis International Study). RESULTS: Principal component analysis disclosed three factors with eigenvalues >0.75: patient assessments, peripheral joint assessments and acute phase reactants. Discriminant function analysis resulted in a correct classification in approximately 72% of the cases (prior probability approximately 50%). Regression analysis resulted in an index with five variables (total back pain, patient global assessment, duration of morning stiffness, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)). Three additional candidate indices were designed using similar methodology while omitting either ESR or CRP or patient global assessment. All four scores correlated with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; r = 0.67-0.80), patient (0.58-0.75) and physician's global assessment (0.41-0.48) of disease activity. All four candidate ASDAS indices performed better than BASDAI or single-item variables in discriminating between high and low disease activity state, according to doctors as well as patients in the OASIS cohort. CONCLUSION: The first steps in the development of a new assessment tool of disease activity in AS derived four candidate indices with good face and construct validity, and high discriminant capacity.
18613831 Th17 cells in human disease. 2008 Jun Our understanding of the role of T cells in human disease is undergoing revision as a result of the discovery of T-helper 17 (Th17) cells, a unique CD4(+) T-cell subset characterized by production of interleukin-17 (IL-17). IL-17 is a highly inflammatory cytokine with robust effects on stromal cells in many tissues. Recent data in humans and mice suggest that Th17 cells play an important role in the pathogenesis of a diverse group of immune-mediated diseases, including psoriasis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and asthma. Initial reports also propose a role for Th17 cells in tumorigenesis and transplant rejection. Important differences, as well as many similarities, are emerging when the biology of Th17 cells in the mouse is compared with corresponding phenomena in humans. As our understanding of human Th17 biology grows, the mechanisms underlying many diseases are becoming more apparent, resulting in a new appreciation for both previously known and more recently discovered cytokines, chemokines, and feedback mechanisms. Given the strong association between excessive Th17 activity and human disease, new therapeutic approaches targeting Th17 cells are highly promising, but the potential safety of such treatments may be limited by the role of these cells in normal host defenses against infection.
18568423 Progress in the discovery of selective, high affinity A(2B) adenosine receptor antagonists 2009 Mar The selective, high affinity A(2B) adenosine receptor (AdoR) antagonists that were synthesized by several research groups should aid in determining the role of the A(2B) AdoR in inflammatory diseases like asthma or rheumatoid arthritis (RA) and angiogenic diseases like diabetic retinopathy or cancer. CV Therapeutics scientists discovered the selective, high affinity A(2B) AdoR antagonist 10, a 8-(4-pyrazolyl)-xanthine derivative [CVT-6883, K(i)(hA(2B)) = 22 nM; K(i)(hA(1)) = 1,940 nM; K(i)(hA(2A)) = 3,280; and K(i)(hA(3)) = 1,070 nM] that has favorable pharmacokinetic (PK) properties (t (1/2) = 4 h and F > 35% rat). Compound 10 demonstrated functional antagonism at the A(2B) AdoR (K(B) = 6 nM) and efficacy in a mouse model of asthma. In two phase 1 clinical trials, CVT-6883 was found to be safe, well tolerated, and suitable for once daily dosing. A second compound 20, 8-(5-pyrazolyl)-xanthine, has been nominated for development from Baraldi's group in conjunction with King Pharmaceuticals that has favorable A(2B) AdoR affinity and selectivity [K(i)(hA(2B)) = 5.5 nM; K(i)(hA(1)) > 1,000 nM; K(i)(hA(2A)) > 1,000; and K(i)(hA(3)) > 1,000 nM], and it has been demonstrated to be a functional antagonist. A third compound 32, a 2-aminopyrimidine, from the Almirall group has high A(2B) AdoR affinity and selectivity [K(i)(hA(2B)) = 17 nM; K(i)(hA(1)) > 1,000 nM; K(i)(hA(2A)) > 2,500; and K(i)(hA(3)) > 1,000 nM], and 32 has been moved into preclinical safety testing. Since three highly selective, high affinity A(2B) AdoR antagonists have been nominated for development with 10 (CVT-6883) being the furthest along in the development process, the role of the A(2B) AdoR in various disease states will soon be established.
18525434 Prevention, diagnosis, and treatment of glucocorticoid induced osteoporosis by rheumatolog 2008 Jun OBJECTIVES: To examine current practices for the diagnosis and therapy for glucocorticoid-induced osteoporosis (GIOP) in patients under treatment with corticosteroids at outpatient clinics of rheumatologists in a Colombian Caribbean city. METHODS: All patients noted to be using of glucocorticoids (GC) on an index consult from February to May 2004 were included in a descriptive cross sectional study. Criteria for inclusion of patients were to have had, at least, one previous visit to the service. We evaluated the study population for osteoporosis diagnosis, procedures, and treatment. RESULTS: Of the 121 patients included, 103 (85.1%) were female and 18 (14.9%) were male; 76 patients (62.8%) were under 50 years, and 45 (37.2%) were over 50 years. Main reasons for corticosteroid use were rheumatoid arthritis in 68 patients (56.2%) and systemic lupus erythematous (SLE) in 31 patients (25.6%). Diagnostic testing for osteoporosis was reported on 50.1% of patients. Peripheral dual energy x-ray absorptiometry was the most frequently used method (52.6%). Therapeutic agents for GIOP were used in 96 patients (79.3%), with Calcium plus Vitamin D (55.2%) the principal treatments prescribed. CONCLUSIONS: We found similar rates of diagnosis and treatment for GIOP to those reported in North America and Europe, although in this study treatment was mainly with calcium and vitamin D. There was a statistically significant relationship between being studied with any diagnostic method and being treated for GIOP. There may be undertreatment for GIOP in Latin America. Local interventions to improve care for patients in chronic use of steroids are needed.
18509092 CNS aquaporin-4 autoimmunity in children. 2008 Jul 8 BACKGROUND: In adult patients, autoantibodies targeting the water channel aquaporin-4 (AQP4) are a biomarker for a spectrum of CNS inflammatory demyelinating disorders with predilection for optic nerves and spinal cord (neuromyelitis optica [NMO]). Here we describe the neurologic, serologic, and radiographic findings associated with CNS AQP4 autoimmunity in childhood. METHODS: A total of 88 consecutive seropositive children were identified through service evaluation for NMO-IgG. Sera of 75 were tested for coexisting autoantibodies. Clinical information was available for 58. RESULTS: Forty-two patients (73%) were non-Caucasian, and 20 (34%) had African ethnicity. Median age at symptom onset was 12 years (range 4-18). Fifty-seven (98%) had attacks of either optic neuritis (n = 48; 83%) or transverse myelitis (n = 45; 78%), or both. Twenty-six (45%) had episodic cerebral symptoms (encephalopathy, ophthalmoparesis, ataxia, seizures, intractable vomiting, or hiccups). Thirty-eight (68%) had brain MRI abnormalities, predominantly involving periventricular areas (in descending order of frequency): the medulla, supratentorial and infratentorial white matter, midbrain, cerebellum, thalamus, and hypothalamus. Additional autoantibodies were detected in 57 of 75 patients (76%), and 16 of 38 (42%) had a coexisting autoimmune disorder recorded (systemic lupus erythematosus, Sjögren syndrome, juvenile rheumatoid arthritis, Graves disease). Attacks were recurrent in 54 patients (93%; median follow-up, 12 months). Forty-three of 48 patients (90%) had residual disability: 26 (54%) visual impairment and 21 (44%) motor deficits (median Expanded Disability Status Scale 4.0 at 12 months). CONCLUSIONS: Aquaporin-4 autoimmunity is a distinctive recurrent and widespread inflammatory CNS disease in children.
18508495 Effects of n-3 fatty acids on autoimmunity and osteoporosis. 2008 May 1 Decreased consumption of n-3 fatty acids (FA) and diets rich in animal proteins, saturated fats and n-6 vegetable oils are associated with a higher incidence of cardiovascular disease (CVD), certain malignancies and autoimmune disorders such as rheumatoid arthritis and Systemic Lupus Erythematosus (SLE), and renal disease. Recent studies show that reduced calorie intake and supplementation of diet with n-3 FA delays the onset of autoimmune renal disease, primarily, due to increased antioxidant enzyme activities, decreased NF-kappaB activation and decreased IL-1, IL-6 and TNF-alpha mRNA expression in the kidney tissue. Studies in rodents show that addition of n-3 FA and soy protein to diet affords protection against bone loss induced by ovariectomy in mice due to NF-kappaB expression and decreased activation of osteoclasts. Together, the available evidence show that increased daily intake of dietary n-3 FA decreases the severity of autoimmune disorders, lessens the chance of developing CVD, and protects against bone loss during post-menopause.
18495733 B cell epitopes of the heterogeneous nuclear ribonucleoprotein A2: identification of a new 2009 May OBJECTIVES: Autoantibody formation and T cell reactivity against the heterogeneous nuclear ribonucleoprotein A2 (hnRNP-A2) has been observed in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Since no differences in epitope recognition were reported and the usefulness of anti-hnRNP-A2 antibodies as diagnostic markers of SLE is unknown, it was our objective to characterise linear B cell epitopes of hnRNP-A2 and to relate the anti-hnRNP-A2 antibody responses to disease activity and clinical features of SLE. METHODS: Sequential serum samples from 15 patients with SLE and sera from patients with other rheumatic diseases and healthy subjects were investigated by ELISA for autoantibody reactivities against a set of 13 overlapping peptides spanning the RNA-binding region of hnRNP-A2. Antibody reactivity against the complete protein was determined by western immunoblotting and ELISA. SLE disease activity was assessed by European Consensus Lupus Activity Measure scores, by SLE Index scores and the British Isles Lupus Assessment index. RESULTS: Anti-peptide antibody reactivities were found in 60% of SLE sera but in only 5% of control samples, and were mainly directed to four peptides, one of which (p155-175) appeared to be immunodominant. Antibodies to p155-175 were exclusively seen in patients with SLE and correlated with clinical disease activity as well as kidney and skin involvement. No correlations were found for the other anti-peptide antibody responses. CONCLUSION: Peptide p155-175 encompasses a disease-specific immunodominant epitope of hnRNP-A2. Since antibodies to p155-175 correlate with disease activity and nephritis, they may be useful as markers for active SLE.