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ID PMID Title PublicationDate abstract
20018090 Comparative analysis of different approaches for dealing with candidate regions in the con 2009 Dec 15 Genome-wide association studies (GWAS) test hundreds of thousands of single-nucleotide polymorphisms (SNPs) for association to a trait, treating each marker equally and ignoring prior evidence of association to specific regions. Typically, promising regions are selected for further investigation based on p-values obtained from simple tests of association. However, loci that exert only a weak, low-penetrant role on the trait, producing modest evidence of association, are not detectable in the context of a GWAS. Implementing prior knowledge of association in GWAS could increase power, help distinguish between false and true positives, and identify better sets of SNPs for follow-up studies.Here we performed a GWAS on rheumatoid arthritis (RA) patients and controls (Problem 1, Genetic Analysis Workshop 16). In order to include prior information in the analysis, we applied four methods that distinctively deal with markers in candidate genes in the context of GWAS. SNPs were divided into a random and a candidate subset, then we applied empirical correction by permutation, false-discovery rate, false-positive report probability, and posterior odds of association using different prior probabilities. We repeated the same analyses on two different sets of candidate markers defined on the basis of previously reported association to RA following two different approaches. The four methods showed similar relative behavior when applied to the two sets, with the proportion of candidate SNPs ranked among the top 2,000 varying from 0 to 100%. The use of different prior probabilities changed the stringency of the methods, but not their relative performance.
19958649 [The clinical characteristics of primary biliary cirrhosis in China: a systematic review]. 2009 Nov OBJECTIVE: To summarize the clinical features, diagnosis and treatment of patients with primary biliary cirrhosis (PBC) in China. METHODS: Systematic analysis of clinical characteristics by searching the Chinese literatures. RESULTS: From 1955 to 2007, 2740 PBC patients were reported in 103 papers (duplicated reports were deleted). The detailed information of 985 patients from 16 papers were collected. Female : male was 6.82:1. The age range was 42 to 56.2-year-old. The time from onset to diagnosis was 12 to 98.4 months. The most common symptoms were fatigue (72.40%), jaundice (67.41%), anorexia (68.58%) and pruritus (45.60%). 20% patients were asymptomatic at onset. The most frequent physical signs were splenomegaly (57.53%), hepatomegaly (43.56%) and ascites (18.45%). Serum alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) levels were markedly elevated in most of these patients. The immunological marks of AMA and M2 were positive in 88.98% and 82.65% patients, respectively. The most common comorbidity were Sjögren syndrome (9.14%), rheumatoid arthritis (3.95%) and diabetes type II (2.54%). Of the 507 patients treated with ursodeoxycholic acid (UDCA), 345 patients got complete or partial clinical biochemical response. The common complications were gastrointestinal bleeding (41.67%) and liver failure (41.67%). Liver transplantation was the only effective way for the treatment of the end-stage liver disease. CONCLUSION: The clinical feature of primary biliary cirrhosis in China was similar to the overseas literatures. Further research should focus on epidemic investigation, early diagnosis, long term follow up of asymptomatic patients, immunological mechanism and the efficacy of liver transplantation.
19864560 A key role for gp130 expressed on peripheral sensory nerves in pathological pain. 2009 Oct 28 Interleukin-6 (IL-6) is a key mediator of inflammation. Inhibitors of IL-6 or of its signal transducing receptor gp130 constitute a novel class of anti-inflammatory drugs, which raise great hopes for improved treatments of painful inflammatory diseases such as rheumatoid arthritis. IL-6 and gp130 may enhance pain not only indirectly through their proinflammatory actions but also through a direct action on nociceptors (i.e., on neurons activated by painful stimuli). We found indeed that the IL-6/gp130 ligand-receptor complex induced heat hypersensitivity both in vitro and in vivo. This process was mediated by activation of PKC-delta via Gab1/2/PI(3)K and subsequent regulation of TRPV1, a member of the transient receptor potential (TRP) family of ion channels. To assess the relevance of this direct pain promoting effect of IL-6, we generated conditional knock-out mice, which lack gp130 specifically in nociceptors, and tested them in models of inflammatory and tumor-induced pain. These mice showed significantly reduced levels of inflammatory and tumor-induced pain but no changes in immune reactions or tumor growth. Our results uncover the significance of gp130 expressed in peripheral pain sensing neurons in the pathophysiology of major clinical pain disorders and suggest their use as novel pain relieving agents in inflammatory and tumor pain.
19853667 TNF-alpha inhibitors in asthma and COPD: we must not throw the baby out with the bath wate 2010 Apr Tumor necrosis factor (TNF)-alpha, a pleiotropic cytokine that exerts a variety of effects, such as growth promotion, growth inhibition, angiogenesis, cytotoxicity, inflammation, and immunomodulation, has been implicated in several inflammatory conditions. It plays a significant role in many inflammatory diseases of lungs. Given that there is significant literature supporting the pathobiologic role of TNF-alpha in asthma, mainly in severe refractory asthma, and COPD, TNF-alpha inhibitors (infliximab, golimumab and etanercept) are now regarded as the potential new medications in asthma and COPD management. The studies reported in literature indicate that TNF-alpha inhibitors are effective in a relatively small subgroup of patients with severe asthma, possibly defined by an increased TNF axis, but they seem to be ineffective in COPD, although an observational study demonstrated that TNF-alpha inhibitors were associated with a reduction in the rate of COPD hospitalisation among patients with COPD receiving these agents to treat their rheumatoid arthritis. These findings require a smart approach because there is still good reason to target TNF-alpha, perhaps in a more carefully selected patient group. TNF-alpha treatment should, therefore, not be thrown out, or abandoned. Indeed, since severe asthma and COPD are heterogeneous diseases that have characteristics that occur with different phenotypes that remained poorly characterized and little known about the underlying pathobiology contributing to them, it is likely that definition of these phenotypes and choice of the right outcome measure will allow us to understand which kind of patients can benefit from TNF-alpha inhibitors.
19847319 Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of 2009 Oct 9 Previous studies have shown that undenatured type II collagen (UC-II) is effective in the treatment of rheumatoid arthritis, and preliminary human and animal trials have shown it to be effective in treating osteoarthritis (OA). The present clinical trial evaluated the safety and efficacy of UC-II as compared to a combination of glucosamine and chondroitin (G+C) in the treatment of OA of the knee. The results indicate that UC-II treatment was more efficacious resulting in a significant reduction in all assessments from the baseline at 90 days; whereas, this effect was not observed in G+C treatment group. Specifically, although both treatments reduced the Western Ontario McMaster Osteoarthritis Index (WOMAC) score, treatment with UC-II reduced the WOMAC score by 33% as compared to 14% in G+C treated group after 90 days. Similar results were obtained for visual analog scale (VAS) scores. Although both the treatments reduced the VAS score, UC-II treatment decreased VAS score by 40% after 90 days as compared to 15.4% in G+C treated group. The Lequesne's functional index was used to determine the effect of different treatments on pain during daily activities. Treatment with UC-II reduced Lequesne's functional index score by 20% as compared to 6% in G+C treated group at the end of 90-day treatment. Thus, UC-II treated subjects showed significant enhancement in daily activities suggesting an improvement in their quality of life.
19663196 [Combined treatment of gastric ulcers induced by nonsteroid antiinflammatory drugs. Result 2009 AIM: To study efficacy of a combination of proton pump inhibitor (PPI) and bismuth tripotassium dicitrate (BTD) in gastric ulcers (GU) induced by non-steroid anti-inflammatory drugs (NSAD) in rheumatic patients with factors affecting PPI efficacy. MATERIAL AND METHODS: Fifty rheumatic patients entered the study (5 males and 45 females, mean age 63.5 +/- 6.2 years) with NSAD-induced GU. Criteria of participation in the study: ulcer size > 1.0 cm, 2 and more ulcers, administration of glucocorticoids (GC) and/or cytotoxic drugs. The patients were divided into two groups. Group 1 patients received omeprasol 20 mg twice a day + BTD 240 mg twice a day; group 2 patients received omeprasol alone 20 mg twice a day. The groups were matched by demographic and clinical parameters, consisted mainly of women with rheumatoid arthritis, most of the patients took GC, methotrexate or leflunamid. The result of the treatment was evaluated by the findings of endoscopic examination 4 and 8 weeks after treatment. RESULTS: Three patients from group 1 and 2 patients from group 2 were withdrawn from the study. For 4 weeks ulcer heeling was achieved in 15 patients of group 1 (68.2%) and 8 patients of group 2 (34.8%), p = 0.038. On week 8 ulcers healed in 86.3 and 78.3% patients, respectively. Severe side effects were absent. CONCLUSION: Combination of omeprasol with BTD stimulated heeling of NSAD-induced gastric ulcer.
19642367 [The clinical and laboratory characteristics of T cell large granular lymphocyte leukemia] 2009 Mar OBJECTIVE: To analyze the characteristics of T-cell large granular lymphocyte leukemia (T-LGLL). METHODS: Retrospectively analyze the clinical and laboratory data of 27 patients with T-LGLL diagnosed between 1999 and 2007 in our hospital. RESULTS: The median age at diagnosis was 48 years. All patients were symptomatic, mainly complaining of fatigue. Of the 27 patients, 14 (51.9%) had splenomegaly, and 4(14.8%) hepatomegaly. Rheumatoid arthritis was not present in any patients. The most frequent hematological abnormality was anemia (24 patients, 88.9%) with a median Hb level of 57.5 g/L. Pure red cell aplasia was found in 18 patients (66.67%). The median WBC count was 4.24 x 10(9)/L and 19 cases were neutropenia (ANC < 1.5 x 10(9)/L). The median LGL count in peripheral blood was 1.45 x 10(9)/L and most of them (77.8%) were less than 2.0 x 10(9)/L. Twenty-two patients (81.5%) showed the CD3+ CD8+ CD57+ CD56(-) LGL phenotype. With immunosuppressive therapy, 91.3% of patients responded and complete hematological remission rate was 65.2%. CONCLUSION: T-LGLL mainly presented with anemia and complete hematological remission rate was 65.2%. Pure red cell aplasia was commonly associated with the disease. The patients had a good response to immunosuppressive therapy.
19622756 Denosumab in osteoporosis and oncology. 2009 Sep OBJECTIVE: To review the pharmacology, pharmacokinetics, pharmacodynamics, safety, efficacy, and use of denosumab in osteoporosis, breast cancer, prostate cancer, and multiple myeloma. DATA SOURCES: Studies and abstracts were identified through MEDLINE and International Pharmaceutical Abstracts (1966-July 2009). Key search terms include denosumab, AMG-162, and receptor activator of nuclear factor-kappaB ligand system. Information available in abstract form was retrieved from major oncology and bone metabolism meetings. Additional data were obtained from the manufacturer. STUDY SELECTION AND DATA EXTRACTION: All available studies in humans were included except for studies in rheumatoid arthritis and giant cell tumor of the bone. DATA SYNTHESIS: In patients with osteoporosis, denosumab significantly reduces bone resorption and fractures. Studies of denosumab in the prevention and treatment of osteoporosis have demonstrated significantly increased bone mineral density and reduced bone turnover markers. Studies of denosumab versus placebo in the treatment of osteoporosis have demonstrated reductions in vertebral, hip, and nonvertebral fractures. In oncology, positive results from clinical trials in patients receiving endocrine therapy for breast and prostate cancer demonstrated decreases in bone loss and skeletal-related events. Denosumab seems to be at least as effective in reducing bone turnover markers as intravenous bisphosphonates in the oncology setting. The most common adverse effects in patients with osteoporosis were arthralgia, nasopharyngitis, back pain, and headache. The most common adverse effects in patients with cancer were infection, pain in the extremities, arthralgia, bone pain, fatigue, and pain. Serious adverse effects include infections requiring hospitalization. CONCLUSIONS: Denosumab has documented efficacy and safety in patients with osteoporosis, breast cancer, and prostate cancer. Additional clinical trial data are needed to more completely establish the effectiveness of denosumab in the treatment of osteoporosis and neoplastic disease as well as its cost-effectiveness and long-term safety.
19493057 Receptor crosstalk: reprogramming B cell receptor signalling to an alternate pathway resul 2009 Jun Receptor crosstalk: reprogramming B cell receptor signalling to an alternate pathway results in expression and secretion of the autoimmunity-associated cytokine, osteopontin (Review). J Intern Med 2009; 265: 632-643.Intracellular signalling emanating from the B-cell antigen receptor is considered to follow a discrete course that requires participation by a set of mediators, grouped together as the signalosome, in order for downstream events to occur. Recent work indicates that this paradigm is true only for naïve B cells. Following engagement of the IL-4 receptor, a new, alternate pathway for B-cell receptor (BCR)-triggered intracellular signalling is established that bypasses the need for signalosome elements and operates in parallel with the classical, signalosome-dependent pathway. Reliance on Lyn and sensitivity to rottlerin by the former, but not the latter, distinguishes these two pathways. The advent of alternate pathway signalling leads to production and secretion by B cells of osteopontin (Opn). As Opn is a polyclonal B-cell activator that is strongly associated with a number of autoimmune diseases including lupus and rheumatoid arthritis, this novel finding is likely to be clinically relevant. Our results highlight the potential role of B-cell-derived Opn in immunity and autoimmunity and suggest that stress-related IL-4 expression might act to strengthen immunoglobulin secretion at the risk of autoantibody formation. Further, these results illustrate receptor crosstalk in the form of reprogramming, whereby engagement of one receptor (IL-4R) produces an effect that persists after the original ligand (IL-4) is removed and results in alteration of the pathway, and outcome, of signalling via a second receptor (BCR) following its activation.
19474110 Therapeutic targeting of Toll-like receptors for infectious and inflammatory diseases and 2009 Jun Since first being described in the fruit fly Drosophila melanogaster, Toll-like receptors (TLRs) have proven to be of great interest to immunologists and investigators interested in the molecular basis to inflammation. They recognize pathogen-derived factors and also products of inflamed tissue, and trigger signaling pathways that lead to activation of transcription factors such as nuclear factor-kappaB and the interferon regulatory factors. These in turn lead to induction of immune and inflammatory genes, including such important cytokines as tumor necrosis factor-alpha and type I interferon. Much evidence points to a role for TLRs in immune and inflammatory diseases and increasingly in cancer. Examples include clear roles for TLR4 in sepsis, rheumatoid arthritis, ischemia/reperfusion injury, and allergy. TLR2 has been implicated in similar pathologic conditions and also in systemic lupus erythematosus (SLE) and tumor metastasis. TLR7 has also been shown to be important in SLE. TLR5 has been shown to be radioprotective. Recent advances in our understanding of signaling pathways activated by TLRs, structural insights into TLRs bound to their ligands and antagonists, and approaches to inhibit TLRs (including antibodies, peptides, and small molecules) are providing possiblemeans by which to interfere with TLRs clinically. Here we review these recent advances and speculate about whether manipulating TLRs is likely to be successful in fighting off different diseases.
19436333 Immunoregulatory role of TNFalpha in inflammatory kidney diseases. 2009 Aug Tumor necrosis factor alpha (TNFalpha), a pleiotropic cytokine, plays important inflammatory roles in renal diseases such as lupus nephritis, anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis and renal allograft rejection. However, TNFalpha also plays critical immunoregulatory roles that are required to maintain immune homeostasis. These complex biological functions of TNFalpha are orchestrated by its two receptors, TNFR1 and TNFR2. For example, TNFR2 promotes leukocyte infiltration and tissue injury in an animal model of immune complex-mediated glomerulonephritis. On the other hand, TNFR1 plays an immunoregulatory function in a murine lupus model with a deficiency in this receptor that leads to more severe autoimmune symptoms. In humans, proinflammatory and immunoregulatory roles for TNFalpha are strikingly illustrated in patients on anti-TNFalpha medications: These treatments are greatly beneficial in certain inflammatory diseases such as rheumatoid arthritis but, on the other hand, are also associated with the induction of autoimmune lupus-like syndromes and enhanced autoimmunity in multiple sclerosis patients. The indication for anti-TNFalpha treatments in renal inflammatory diseases is still under discussion. Ongoing clinical trials may help to clarify the potential benefit of such treatments in lupus nephritis and ANCA-associated glomerulonephritis. Overall, the complex biology of TNFalpha is not fully understood. A greater understanding of the function of its receptors may provide a framework to understand its contrasting proinflammatory and immunoregulatory functions. This may lead the development of new, more specific anti-inflammatory drugs.
19391122 Omega-3 polyunsaturated fatty acids and human health outcomes. 2009 May Current intakes of very long chain omega-3 fatty acids, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are low in most individuals living in Western countries. A good natural source of these fatty acids is seafood, especially oily fish. Fish oil capsules contain these fatty acids too. Very long chain omega-3 fatty acids are readily incorporated from capsules into transport, functional, and storage pools. This incorporation is dose-dependent and follows a kinetic pattern that is characteristic for each pool. At sufficient levels of incorporation, EPA and DHA influence the physical nature of cell membranes and membrane protein-mediated responses, eicosanoid generation, cell signaling and gene expression in many different cell types. Through these mechanisms, EPA and DHA influence cell and tissue physiology, and the way cells and tissues respond to external signals. In most cases, the effects seen are compatible with improvements in disease biomarker profiles or in health-related outcomes. As a result, very long chain omega-3 fatty acids play a role in achieving optimal health and in protection against disease. Long chain omega-3 fatty acids protect against cardiovascular morbidity and mortality, and might be beneficial in rheumatoid arthritis, inflammatory bowel diseases, childhood learning, and behavior, and adult psychiatric and neurodegenerative illnesses. DHA has an important structural role in the eye and brain, and its supply early in life is known to be of vital importance. On the basis of the recognized health improvements brought about by long chain omega-3 fatty acids, recommendations have been made to increase their intake.
19330725 Veltuzumab, an anti-CD20 mAb for the treatment of non-Hodgkin's lymphoma, chronic lymphocy 2009 Apr Veltuzumab is a humanized, second-generation anti-CD20 mAb currently under development by Immunomedics Inc for the potential treatment of B-cell non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Licensee Nycomed is developing veltuzumab for the potential treatment of rheumatoid arthritis and immune thrombocytopenic purpura (ITP). Veltuzumab contains 90 to 95% human antibody sequences with identical antigen framework regions to epratuzumab (a humanized anti-CD22 mAb) and similar antigen-binding determinants to rituximab (chimeric, anti-CD20 mAb and the first-line treatment of aggressive and indolent NHL). In vitro studies have demonstrated that veltuzumab has enhanced binding avidities and a stronger effect on complement-dependent cytotoxicity compared with rituximab in selected cell lines. In dose-finding phase I/II clinical trials in patients with low-grade NHL, intravenous veltuzumab demonstrated a substantial rate of complete responses in concurrence with shorter and more tolerable infusions compared with rituximab. Currently there has been no evidence of an immune response to repeated administrations, and no serious adverse events related to veltuzumab treatment in patients with NHL. Veltuzumab is undergoing clinical trials using a low-dose subcutaneous formulation in patients with NHL, CLL and ITP. Prospective, randomized clinical trials are needed to clarify the role veltuzumab will play in a market where the therapy of B-cell lymphoproliferative disorders is dominated by rituximab.
18612638 A population-based study of prevalence and hospital charges in total hip and knee replacem 2009 Aug The purpose of this study was to explore the increasing prevalence of factors affecting hospital charges for primary total hip replacement/total knee replacement (THR/TKR). This study analysed 37,918 THR and 76,727 TKR procedures performed in Taiwan from 1996 to 2004. Odds ratio (OR) and effect size (ES) were calculated to assess the relative change rate. Multiple regression models were employed to predict hospital charges. The following factors were associated with increased hospital charges: age younger than 65 years old; increased disease severity (Charlson comorbidity index [CCI] = 1 or > or = 2); absence of primary diagnoses of osteoarthritis (OA), rheumatoid arthritis (RA), avascular necrosis (AVN); treatment at a hospital or by a surgeon performing a high volume of operations; and longer average length of stay (ALOS). The Bureau of National Health Insurance (BNHI) should ensure that surgeons take precautionary measures to minimise complications and maximise quality of life after surgery. Use of joint prostheses from different manufacturers can reduce costs without compromising patient satisfaction.
21216608 Phosphonic pseudopeptides as human neutrophil elastase inhibitors--a combinatorial approac 2011 Feb 1 Here we present a simple and rapid method for the construction of phosphonic peptide mimetic inhibitor libraries-products of Ugi and Passerini multicomponent condensations-leading to the selection of new biologically active phosphonic pseudopeptides. As the starting isonitriles, 1-isocyanoalkylphosphonate diaryl ester derivatives were applied. The structure of the synthesized inhibitors was designed to target human neutrophil elastase, a serine protease whose uncontrolled activity may lead to development of several pathophysiological states such as rheumatoid arthritis, cystic fibrosis or tumor growth and invasion. After screening the inhibitory activity of our constructed libraries, the most active compounds were synthesized as single molecules. One of the obtained inhibitors, Cbz-Met-O-Met-Val(P)(OC(6)H(4)-p-Cl)(2), displayed apparent second-order inhibition value at 40,105M(-1)s(-1) as the diastereomers mixture. Inhibition potency and selectivity of action toward other serine proteases as well as the results of initial in vitro experiments regarding inhibitors influence on cancer cell proliferation are presented.
21208525 Scavenging of reactive oxygen and nitrogen species by the prodrug sulfasalazine and its me 2010 Sulfasalazine is a prodrug composed by a molecule of 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP), linked by an azo bond, which has been shown to be effective in the therapy of inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease, as well as of rheumatic diseases, such as rheumatoid arthritis and ankylosing spondylitis. The precise mechanism of action of sulfasalazine and/or its metabolites has not been completely elucidated, though its antioxidant effects are well established and are probably due to its scavenging effects against reactive oxygen and nitrogen species (ROS and RNS), as well as metal chelating properties, in association to its inhibitory effects over neutrophil oxidative burst. The present work was focused on screening and comparing the potential scavenging activity for an array of ROS (O(2)(•-), H(2)O(2), (1)O(2), ROO(•) and HOCl) and RNS ((•)NO and ONOO(-)), mediated by sulfasalazine and its metabolites 5-ASA and SP, using validated in vitro screening systems. The results showed that both 5-ASA and sulfasalazine were able to scavenge all the tested ROS while SP was practically ineffective in all the assays. For HOCl, (1)O(2), and ROO(•), 5-ASA showed the best scavenging effects. A new and important finding of the present study was the strong scavenging effect of 5-ASA against (1)O(2). 5-ASA was shown to be a strong scavenger of (•)NO and ONOO(-). Sulfasalazine was also able to scavenge these RNS, although with a much lower potency than 5-ASA. SP was unable to scavenge (•)NO in the tested concentrations but was shown to scavenge ONOO(-), with a higher strength when the assay was performed in the presence of 25 mM bicarbonate, suggesting further scavenging of oxidizing carbonate radical. In conclusion, the ROS- and RNS-scavenging effects of sulfasalazine and its metabolites shown in this study may contribute to the anti-inflammatory effects mediated by sulfasalazine through the prevention of the oxidative/nitrative/nitrosative damages caused by these species.
21208219 Anti-tumor necrosis factor-alpha treatment reduces allergic responses in an allergic rhini 2011 Feb BACKGROUND:   Tumor necrosis factor (TNF)-α is a principal mediator of the acute inflammatory response, including allergic rhinitis. TNF-α inhibitors are widely used for the treatment of inflammatory conditions such as rheumatoid arthritis and inflammatory bowel diseases; however, the effects of TNF-α inhibitors on allergic rhinitis are not well established. We aimed to investigate the effects of infliximab, a TNF-α inhibitor, on allergic rhinitis in a mouse model. METHODS:   BALB/c mice were sensitized with ovalbumin (OVA) and alum, and challenged intranasally with OVA. The TNF-α inhibitor, infliximab was administered intraperitoneally, and multiple parameters of allergic responses were evaluated to determine the effects of infliximab. RESULTS:   Infliximab reduced allergic symptoms and eosinophilic infiltration into the nasal mucosa. It also suppressed total and OVA-specific IgE levels, and inhibited local Th2 cytokine transcription in the nasal mucosa and systemic Th2 cytokine production by splenocytes. Furthermore, the expression of E-selectin, neither intercellular adhesion molecule 1 (ICAM-1) nor vascular cell adhesion molecule 1 (VCAM-1), in the nasal mucosa was suppressed in the infliximab-treated group when compared to the nontreated group. CONCLUSION:   This study shows that the TNF-α inhibitor infliximab induces anti-allergic effects by decreasing local and systemic Th2 cytokine (IL-4) production, total and OVA-specific IgE levels, adhesion molecule (E-selectin) expression, and eosinophil infiltration into the nasal mucosa in an allergic rhinitis model. Therefore, infliximab should be considered as a potential agent in treating allergic rhinitis.
20957678 Prevalence of connective tissue disease in silicosis (1985-2006)-a report from the state o 2011 Apr BACKGROUND: The risk of developing clinical connective tissue disease (CTD) has been reported to be increased among individuals with silica exposure. METHODS: We reviewed the medical records of individuals reported to the Michigan Silicosis Surveillance system from 1985 to 2006 to confirm the diagnosis of silicosis and determine the presence of CTDs. RESULTS: From 1985 to 2006, 1,022 cases were confirmed to have silicosis. Medical records of 790 cases were available. Thirty-three individuals had rheumatoid arthritis (RA) [prevalence 4.2% (prevalence ratio (RR) ranged from 2.26, 95% CI: 1.57-3.25 to 6.96, 95% CI: 2.93-16.53) depending on the reference rate used], two had scleroderma [prevalence 0.3% (RR 28.3, 95% CI: 6.09-129.98)], one had systemic lupus erythematosus [prevalence 0.1% (RR 2.53, 95% CI: 0.30-21.64)], two had Sjogrens syndrome [prevalence 0.3% (RR 0.42, 95% CI: 0.09-2.08)], and six had anti-neutrophil cytoplasm antibody (ANCA) vasculitis [prevalence 0.8% (RR 25.3, 95% CI: 6.34-101.04)]. There was no difference between those with and without CTD with respect to age, race, industry type, history of tuberculosis, application for workers' compensation, or severity of fibrotic changes on chest X-ray. CONCLUSIONS: A two- to eightfold risk for RA and systemic lupus erythematosus, with a greater than 24-fold risk for scleroderma and ANCA vasculitis was found in individuals with silicosis. The most common CTD among silicotics in the Michigan disease registry was RA. Though not classically included in the category of CTD, ANCA-associated vasculitis was found to have a much greater prevalence amongst silicosis patients than the general population.
20957100 3D-QSAR and molecular docking studies on fused pyrazoles as p38α mitogen-activated protei 2010 Sep 17 The p38α mitogen-activated protein kinase (MAPK) has become an attractive target for the treatment of many diseases such as rheumatoid arthritis, inflammatory bowel disease and Crohn's disease. In this paper, 3D-QSAR and molecular docking studies were performed on 59 p38α MAPK inhibitors. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were applied to determine the structural requirements for potency in inhibiting p38α MAPK. The resulting model of CoMFA and CoMSIA exhibited good r(2) (cv) values of 0.725 and 0.609, and r(2) values of 0.961 and 0.905, respectively. Molecular docking was used to explore the binding mode between the inhibitors and p38α MAPK. We have accordingly designed a series of novel p38α MAPK inhibitors by utilizing the structure-activity relationship (SAR) results revealed in the present study, which were predicted with excellent potencies in the developed models. The results provided a useful guide to design new compounds for p38α MAPK inhibitors.
20955778 Immune suppression and immune activation in depression. 2011 Feb Depression has been characterized as a disorder of both immune suppression and immune activation. Markers of impaired cellular immunity (decreased natural killer cell cytotoxicity) and inflammation (elevated IL-6, TNFα, and CRP) have been associated with depression. These immunological markers have been associated with other medical illnesses, suggesting that immune dysregulation may be a central feature common to both depression and to its frequent medical comorbidities. Yet the significant associations of findings of both immune suppression and immune activation with depression raise questions concerning the relationship between these two classes of immunological observations. Depressed populations are heterogeneous groups, and there may be differences in the immune profiles of populations that are more narrowly defined in terms of symptom profile and/or demographic features. There have been few reports concurrently investigating markers of immune suppression and immune activation in the same depressed individuals. An emerging pre-clinical literature suggests that chronic inflammation may directly contribute to the pathophysiology of immune suppression in the context of illnesses such as cancer and rheumatoid arthritis. This literature provides us with specific immunoregulatory mechanisms mediating these relationships that could also explain differences in immune disturbances between subsets of depressed individuals We propose a research agenda emphasizing the assessment of these immunoregulatory mechanisms in large samples of depressed subjects as a means to define the relationships among immune findings (suppression and/or activation) within the same depressed individuals and to characterize subsets of depressed subjects based on shared immune profiles. Such a program of research, building on and integrating our knowledge of the psychoneuroimmunology of depression, could lead to innovation in the assessment and treatment of depression and its medical comorbidities.