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ID PMID Title PublicationDate abstract
19482664 The mosaic of autoimmunity: the role of environmental factors. 2009 Jun 1 The "mosaic of autoimmunity" describes the multifactorial origin and diversity of expression of autoimmune diseases in humans. The term implies that different combinations of the many factors that are involved in auto-immunity produce varying and unique clinical pictures in a wide spectrum of autoimmune diseases. Most of the factors involved in autoimmunity can be categorized into four groups: genetic, immune defects, hormonal and environmental factors. In this communication, only the environmental factors are reviewed such as: infectious agents (represented by Epstein-Barr virus and cytomegalovirus), vaccines as triggers of autoimmunity, smoking and its relationship with rheumatoid arthritis, systemic lupus erythematosus, thyroid disease, multiple sclerosis and inflammatory bowel diseases. Some aspects of stress as implicated in causing autoimmunity and the processes leading to autoimmunity are reviewed as well.
19442167 Probiotics, immune function, infection and inflammation: a review of the evidence from stu 2009 A number of studies have been performed examining the influence of various probiotic organisms, either alone or in combination, on immune parameters, infectious outcomes, and inflammatory conditions in humans. Some components of the immune response, including phagocytosis, natural killer cell activity and mucosal immunoglobulin A production (especially in children), can be improved by some probiotic bacteria. Other components, including lymphocyte proliferation, the production of cytokines and of antibodies other than immunoglobulin A appear less sensitive to probiotics. Probiotics, including lactobacilli and bifidobacteria, administered to children can reduce incidence and duration of diarrhoea, but the precise effects depend upon the nature of the condition. Probiotic supplementation can reduce the risk of travellers' diarrhoea in adults, but does not affect duration. The effect of probiotics on other infectious outcomes is less clear. Probiotics may benefit children and adults with irritable bowel syndrome and adults with ulcerative colitis; studies in Crohn's Disease are less clear. Probiotics have little effect in rheumatoid arthritis. Probiotic supplementation, especially with lactobacilli and bifidobacteria, can reduce risk and severity of allergic disease, particular atopic dermatitis; early supplementation appears to be effective. Overall, the picture that emerges from studies of probiotics on immune, infectious and inflammatory outcomes in humans is mixed and there appear to be large species and strain differences in effects seen. Other reasons for differences in effects seen will include dose of probiotic organism used, duration of supplementation, characteristics of the subjects studied, sample size, and technical differences in how the measurements were made.
19442142 Role, metabolism, chemical modifications and applications of hyaluronan. 2009 Hyaluronan (hyaluronic acid, HA) is a linear naturally occurring polysaccharide formed from repeating disaccharide units of N-acetyl-D-glucosamine and D-glucuronate. Despite its relatively simple structure, HA is an extraordinarily versatile glycosaminoglycan currently receiving attention across a wide front of research areas. It has a very high molar mass, usually in the order of millions of Daltons, and possesses interesting visco-elastic properties based on its polymeric and polyelectrolyte characteristics. HA is omnipresent in the human body and in other vertebrates, occurring in almost all biological fluids and tissues, although the highest amounts of HA are found in the extracellular matrix of soft connective tissues. HA is involved in several key processes, including cell signaling, wound repair and regeneration, morphogenesis, matrix organization and pathobiology. Clinically, it is used as a diagnostic marker for many disease states including cancer, rheumatoid arthritis, liver pathologies, and as an early marker for impending rejection following organ transplantation. It is also used for supplementation of impaired synovial fluid in arthritic patients, following cataract surgery, as a filler in cosmetic and soft tissue surgery, as a device in several surgical procedures, particularly as an anti-adhesive following abdominal procedures, and also in tissue engineering. This review will provide an overview of the structure and physiological role of HA, as well as of its biomedical and industrial applications. Recent advances in biotechnological approaches for the preparation of HA-based materials, and as a component of tissue scaffolding for artificial organs will also be presented.
19350430 Post-traumatic growth in people living with a serious medical condition and its relations 2009 PURPOSE: The diagnosis of a life-threatening illness can be an extremely stressful, traumatic experience. However, many survivors report also various positive changes, referred in empirical literature as post-traumatic growth (PTG). Empirical studies that documented stress disorders and PTG in patients and survivors of life-threatening diseases are reviewed in three areas: Predictors of PTG, relationships between PTG and indicators of mental health and the impact of PTG on the process of convalescence. METHOD: The literature review was completed by making use of three major databases - PsycINFO, PILOTS and Medline. RESULTS: The majority of the studies investigated PTG and its relationships to health indicators after the diagnosis of cancer, HIV/AIDS, cardiac disease, multiple sclerosis and rheumatoid arthritis. The review indicated that quality of social support, patients' coping strategies and several indicators of mental and physical health were consistently associated with post-traumatic growth. Associations between growth and health-related variables (e.g. physical deficits, pain, depression, anxiety) varied depending on different study design (cross-sectional versus longitudinal) and the sample composition (patients versus symptom-free survivors). Several findings are disease-specific. CONCLUSIONS: The results point to the potential adaptive significance of PTG. More research is needed to investigate specific disease-related profiles of PTG and the complex mechanisms, which underlie the relationships between PTG and the process of convalescence. This knowledge may help to foster the overall positive adjustment of chronically ill patients.
21977173 Systemic inflammation and early atheroma formation: are they related? 2010 Dec Atherosclerosis is a chronic inflammatory disease started by endothelial injury and defined by arterial wall load with free and esterified cholesterol, followed by subintimal focal recruitment of circulating monocytes and T-lymphocytes that heals by fibrosis and calcification. Inflammation plays a crucial role in atherogenesis either by local cellular mechanisms or humoral consequences easily measurable in plasma. In most cases inflammation and endothelial dysfunction are triggered by cardiovascular risk factors: hypercholesterolemia, hypertension, smoking or diabetes. In other cases inflammation precedes atherosclerotic changes that occur in autoimmune diseases, as systemic lupus erythematosus and rheumatoid arthritis. In these diseases atherogenesis is mostly independent from conventional risk factors. Irrespective of its cause systemic inflammation is correlated with cardiovascular events, but currently there are controversial results regarding inflammatory markers and early atherosclerotic process. We designed a study to identify if the amplitude of inflammation expressed by multiple serum markers is correlated with the severity of the atherosclerotic process measured by coronary atheroma volume and carotid intima-media thickness. The selected inflammatory markers are associated with different pathogenic steps in atherogenesis: acute phase reactants (C-reactive protein); pro-inflammatory cytokines (TNF-alpha, interleukin-6 and -18); endothelium activation markers (soluble VCAM-1, ICAM-1); and specific factors (anticardiolipinic antibodies). We aim to enrol the two different patient subsets with early atherosclerosis: one with conventional risk factors and one with autoimmune diseases without traditional risk factors, in whom inflammation is part of the systemic disease progression.
21742279 Tai Chi research review. 2011 Aug This review briefly summarizes recent Tai Chi research on physical benefits including balance and muscle strength and psychological benefits including attentiveness, sleep and anxiety. Cardiovascular changes following Tai Chi include decreased heart rate and blood pressure, increased vagal activity and decreased cholesterol. Pain syndromes that have been affected include fibromyalgia, osteoarthritis and rheumatoid arthritis. Autoimmune and immune conditions recently researched and reviewed here include osteoporosis, diabetes and HIV. Methodological problems with this research include the variability in forms (series of postures) used across studies as well as the intensity of the Tai Chi schedule. Further, most of the studies are based on within group changes rather than attention control group comparisons. Nonetheless, significant clinical improvements have been noted.
21535545 Evaluation of antioxidant and inhibitory activities for different subclasses flavonoids on 2010 Sep Antioxidant activities of flavonoids were decreased in the order of flavonols > flavanones > flavones. Inhibitory intensities for hyaluronidase and collagenase reaction differed clearly according to flavonoid subclasses. Kaempferol, quercetin, myricetin, and rutin in flavonols inhibited hyaluronidase reaction specifically, while apigenin, luteolin, baicalin, and baicalein in flavones showed specific inhibition to collagenase reaction. In addition, the flavonoids, except baicalin and catechin, inhibited potently LPS-induced nitrite production in a dose-dependent manner, which might be mainly due to the suppression of inducible nitric oxide (NO) synthase. Quercetin and luteolin showed the strongest inhibitory activities on 15-lipoxygenase (LOX), and quercetin showed relatively potent inhibition on cyclooxygenase-1 (COX-1) reaction. Otherwise, all tested flavonoids possessed the inhibitory activity to COX-2 reaction, and especially luteolin, kaempferol, hesperetin, and naringin showed relatively the potent inhibition on COX-2 reaction. This report elucidated the anti-inflammatory activities, such as the antioxidant property, inhibition of NO production, and inhibition of inflammatory enzymes (hyaluronidase, collagenase, LOX, and COXs) of several subclass flavonoids.
21133662 Vitamin D: emerging roles in infection and immunity. 2010 Dec In the preantibiotic era, TB of the skin was treated successfully with UV light. By the 1920s, pulmonary TB was being treated with regular sun exposure. During the last decade, basic laboratory research into the antimicrobial actions of vitamin D has provided new insights into these historical observations. Vitamin D has a critical role in the innate immune system through the production of antimicrobial peptides - particularly cathelicidin. Vitamin D would appear to have an important role in respiratory tract, skin and potentially gut health. A number of autoimmune diseases, including multiple sclerosis, Type I diabetes, systemic lupus erythematosus and rheumatoid arthritis, are associated with vitamin D deficiency. Vitamin D could have an important role in the prevention and possible treatment of these conditions; however, much of the current evidence relates to basic science and epidemiological research. In many situations, appropriate double-blind, randomized controlled trial data to guide clinicians treating infectious and autoimmune disease is still lacking.
20942939 Lack of association of the CIITA -168A→G promoter SNP with myasthenia gravis and its rol 2010 Oct 13 BACKGROUND: The major histocompatibility complex class II transactivator (CIITA) regulates MHC class II gene expression. A promoter SNP -168A→G (rs3087456) has previously been shown to be associated with susceptibility to several immune mediated disorders, including rheumatoid arthritis (RA), multiple sclerosis (MS) and myocardial infarction (MI). Myasthenia gravis (MG) is an autoimmune disorder which has previously been shown to be associated with polymorphisms of several autoimmune predisposing genes, including IL-1, PTPN22, TNF-α and the MHC. In order to determine if allelic variants of rs3087456 increase predisposition to MG, we analyzed this SNP in our Swedish cohort of 446 MG patients and 1866 controls. RESULTS: No significant association of the SNP with MG was detected, neither in the patient group as a whole, nor in any clinical subgroup. The vast majority of previous replication studies have also not found an association of the SNP with autoimmune disorders. CONCLUSIONS: We thus conclude that previous findings with regard to the role of the CIITA -168A→G SNP in autoimmunity may have to be reconsidered.
20929432 All trans retinoic acid and cancer. 2011 Jun All-trans retinoic acid (ATRA) is an active metabolite of vitamin A under the family retinoid. Retinoids, through their cognate nuclear receptors, exert potent effects on cell growth, differentiation and apoptosis, and have significant promise for cancer therapy and chemoprevention. Differentiation therapy with ATRA has marked a major advance and become the first choice drug in the treatment of acute promyelocytic leukemia (APL). Conversions of 13-cis-retinoic acid and 9-cis-retinoic acid to all-trans-retinoic acid is very rapid. Currently, two distinct families of retinoid responsive nuclear receptors have been identified and characterized: retinoic acid receptors (RARs) and retinoid receptors (RXRs), each of which include three isoforms, α,β,and γ. ATRA is being increasingly included in anti-tumour therapeutical schemes for the treatment of various tumoral diseases such as Kaposi's sarcoma, head and neck squamous cell carcinoma, ovarian carcinoma, bladder cancer, neuroblastoma and has shown antiangiogenic effects in several systems, inhibiting proliferation in vascular smooth muscle cells (VSMCs) and anti-inflammatory in rheumatoid arthritis. This review helps to understand in details about the ATRA and its role on cancer and it is predicted that modulating the activity of ATRA will soon provide novel prevention and treatment approaches for the cancer patients.
20857817 [Results of surgical resection for patients with pulmonary cryptococcosis]. 2010 Sep 1 Pulmonary cryptococcosis is a fungal infection caused by inhalation of Cryptococcus neoformans. Pulmonary cryptococcal infections tend to occur in immunocompromised individuals, although they can occasionally develop even in immunocompetent hosts. This report presents a retrospective clinical study of 8 patients who underwent a surgical resection for pulmonary cryptococcosis between 1999 and 2008. The age of the patients ranged from 49 to 85 years old (mean 62.6). There were 4 male and 4 female patients. All patients except for 1 had no symptoms. Two patients were immuno-compromised hosts undergoing corticosteroid therapy due to myasthenia gravis and rheumatoid arthritis, respectively. There were 7 patients with a single nodule and 1 patient with multiple nodules. The tumors ranged from 9 to 21 mm in diameter. None of the patients were definitely diagnosed prior to the surgical resection. The surgical procedures included 5 partial resections, 1 segmentectomy and 2 lobectomies. It is often difficult to make a differential diagnosis between lung cancer and pulmonary cyptococosis, because pulmonary cyptococosis shows similar imaging findings in CT. Therefore, a surgical resection is recommended if an observation of the pulmonary nodes is required to make a differential diagnosis of malignant tumors. All of the patients in the current series showed a good outcome without any relapse including cryptococcal meningitis after a surgical resection.
20842829 [Rituximab in systemic lupus erythematosus. Part I. Theoretical basis]. 2010 Aug Rituximab is a chimeric human-mouse monoclonal antibody, which binds to the CD20 antigen on B lymphocytes and causes depletion of CD20+ cells in the mechanism of complement-dependent and independent cytolysis, cell cytotoxicity and antibody-dependent mechanism and apoptosis. Rituximab is currently registered for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and rheumatoid arthritis. Rituximab also demonstrated efficacy in a number of other autoimmune diseases, including systemic lupus erythematosus. In patients with systemic lupus erythematosus rituximab decreases the number of autoreactive VH4.34 B cells, what contributes to sustaining B cell homeostasis and immune tolerance. A decrease in levels of circulating anti-dsDNA antibodies and an increase of C3 concentration is observed parallel to clinical improvement. Diagnostic procedures performed before initiation of rituximab therapy and during treatment include basic laboratory tests as well as exclusion of heart insufficiency and infections.
20688047 Nature or nurture: let food be your epigenetic medicine in chronic inflammatory disorders. 2010 Dec 15 Numerous clinical, physiopathological and epidemiological studies have underlined the detrimental or beneficial role of nutritional factors in complex inflammation related disorders such as allergy, asthma, obesity, type 2 diabetes, cardiovascular disease, rheumatoid arthritis and cancer. Today, nutritional research has shifted from alleviating nutrient deficiencies to chronic disease prevention. It is known that lifestyle, environmental conditions and nutritional compounds influence gene expression. Gene expression states are set by transcriptional activators and repressors and are often locked in by cell-heritable chromatin states. Only recently, it has been observed that the environmental conditions and daily diet can affect transgenerational gene expression via "reversible" heritable epigenetic mechanisms. Epigenetic changes in DNA methylation patterns at CpG sites (epimutations) or corrupt chromatin states of key inflammatory genes and noncoding RNAs, recently emerged as major governing factors in cancer, chronic inflammatory and metabolic disorders. Reciprocally, inflammation, metabolic stress and diet composition can also change activities of the epigenetic machinery and indirectly or directly change chromatin marks. This has recently launched re-exploration of anti-inflammatory bioactive food components for characterization of their effects on epigenome modifying enzymatic activities (acetylation, methylation, phosphorylation, ribosylation, oxidation, ubiquitination, sumoylation). This may allow to improve healthy aging by reversing disease prone epimutations involved in chronic inflammatory and metabolic disorders.
20559736 Application of the health assessment questionnaire disability index to various rheumatic d 2010 Nov PURPOSE: To investigate whether the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) can serve as a generic instrument for measuring disability across different rheumatic diseases and to propose a scoring method based on item response theory (IRT) modeling to support this goal. METHODS: The HAQ-DI was administered to a cross-sectional sample of patients with confirmed rheumatoid arthritis (n = 619), osteoarthritis (n = 125), or gout (n = 102). The results were analyzed using the generalized partial credit model as an IRT model. RESULTS: It was found that 4 out of 8 item categories of the HAQ-DI displayed substantial differential item functioning (DIF) over the three diseases. Further, it was shown that this DIF could be modeled using an IRT model with disease-specific item parameters, which produces measures that are comparable for the three diseases. CONCLUSION: Although the HAQ-DI partially functioned differently in the three disease groups, the measurement regarding the disability level of the patients can be made comparable using IRT methods.
20435169 The telomere/telomerase system in autoimmune and systemic immune-mediated diseases. 2010 Aug Telomeres are specialized nucleoproteic structures that cap and protect the ends of chromosomes. They can be elongated by the telomerase enzyme, but in telomerase negative cells, telomeres shorten after each cellular division because of the end replicating problem. This phenomenon leads ultimately to cellular senescence, conferring to the telomeres a role of biological clock. Oxidative stress, inflammation and increased cell renewal are supplementary environmental factors that accelerate age-related telomere shortening. Similar to other types of DNA damage, very short/dysfunctional telomeres activate a DNA response pathway leading to different outcomes: DNA repair, cell senescence or apoptosis. During the last 10 years, studies on the telomere/telomerase system in autoimmune and/or systemic immune-mediated diseases have revealed its involvement in relevant physiopathological processes. Here, we present a literature review of telomere and telomerase homeostasis in systemic inflammatory diseases including systemic lupus erythematosus, rheumatoid arthritis and granulomatous diseases. The available data indicate that both telomerase activity and telomere length are modified in various systemic immune-mediated diseases and appear to be connected with premature immunosenescence. Studies on the telomere/telomerase system open new research avenues for the basic understanding and for therapeutic approaches of these pathologies.
20425017 The long-term impact of rituximab for childhood immune thrombocytopenia. 2010 Apr Rituximab administered at standard doses induces universal B-cell depletion. It shows good efficacy in patients with a variety of autoimmune diseases and has been licensed for use in rheumatoid arthritis. Despite prolonged B-cell depletion, side effects appear to be minimal. The use of B-cell depletion in children in whom the immune system is more immature may have other unknown complications, although the literature remains sparse. This review summarizes the available studies of rituximab in children with immune thrombocytopenia and assesses some of the short-term and potential long-term consequences of B-cell depletion. Overall, rituximab appears well-tolerated in children. The incidence of serum sickness may be higher than it is in adults, but infections remain infrequent and occur mostly in patients with an underlying predisposition to infections. Finally, although data remain limited, it is recommended to perform vaccinations before administration of rituximab or after B-cell return.
20397073 CXCR4 in clinical hematology. 2010 Pharmacological manipulation of CXCR4 has proven clinically useful for mobilization of stem and progenitor cells and in several preclinical models of disease. It is a key component in the localization of leukocytes and stem cells. For patients with multiple myeloma and non-Hodgkin's Lymphoma, treatment with plerixafor, an inhibitor of CXCL12 binding to CXCR4, plus G-CSF mobilizes stem cells for autologous transplantation to a greater degree than the treatment with G-CSF alone, and in some cases when patients could not be mobilized with cytokines, chemotherapy, or the combination. Stem cells from healthy donors mobilized with single agent plerixafor have been used for allogeneic transplantation in acute myelogenous leukemia (AML) patients, although this is still in the early phase of clinical development. Plerixafor is also undergoing evaluation to mobilize tumor cells in patients with AML and chronic lymphocytic leukemia (CLL) to enhance the effectiveness of chemotherapy regimens. Plerixafor's effect on neutrophils may also restore circulating neutrophil counts to normal levels in patients with chronic neutropenias such as in WHIMs syndrome. Other areas where inhibition of CXCR4 may be useful based upon preclinical or clinical data include peripheral vascular disease, autoimmune diseases such as rheumatoid arthritis, pulmonary inflammation, and HIV.
20359616 [Clinical study of interstitial lung disease in mixed connective tissue disease]. 2010 Mar Mixed connective tissue disease (MCTD) is characterized by a combination of clinical features of progressive systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, polymyositis/dermatomyositis, with a high anti-snRNP antibody titer. Respiratory manifestations, such as interstitial lung disease (ILD), are not well-described. Thirteen patients who met the diagnostic criteria for MCTD and showed ILD on high-resolution CT were analysed retrospectively. A restrictive pattern was found in 73% of cases and TLCO abnormalities in 90%. Exercise hypoxemia was observed in nine out of ten cases. The CT-scan pattern was compatible with non-specific interstitial pneumonia in seven cases and with usual interstitial pneumonia in five. Bronchoalveolar lavage showed lymphocytic alveolitis in two patients, neutrophil alveolitis in eight. Fifty percent ILD patients respond to steroids and immunosuppressive drugs. Progressive ILD (six in 13; 46%) compared with non-progressive ILD associated more systemic sclerosis manifestations (p<0.05). Progressive ILD tend to have more frequent pulmonary hypertension, neutrophilic alveolitis and honey combing pattern. MCTD-ILD characteristics are not specific. When systemic sclerosis manifestations are present, MCTD-ILD seems to associate more frequently pulmonary hypertension and progressive ILD.
22096364 Current and emerging strategies for the treatment and management of systemic lupus erythem 2010 Lupus is a chronic, systemic inflammatory condition in which eicosanoids, cytokines, nitric oxide (NO), a deranged immune system, and genetics play a significant role. Our studies revealed that an imbalance in the pro- and antioxidants and NO and an alteration in the metabolism of essential fatty acids exist in lupus. The current strategy of management includes administration of nonsteroidal anti-inflammatory drugs such as hydroxychloroquine and immunosuppressive drugs such as corticosteroids. Investigational drugs include the following: 1) belimumab, a fully human monoclonal antibody that specifically recognizes and inhibits the biological activity of B-lymphocyte stimulator, also known as B-cell-activation factor of the TNF family; 2) stem cell transplantation; 3) rituximab, a chimeric monoclonal antibody against CD20, which is primarily found on the surface of B-cells and can therefore destroy B-cells; and 4) IL-27, which has potent anti-inflammatory actions. Our studies showed that a regimen of corticosteroids and cyclophosphamide, and methods designed to enhance endothelial NO synthesis and augment antioxidant defenses, led to induction of long-lasting remission of the disease. These results suggest that methods designed to modulate molecular signatures of the disease process and suppress inflammation could be of significant benefit in lupus. Some of these strategies could be vagal nerve stimulation, glucose-insulin infusion, and administration of lipoxins, resolvins, protectins, and nitrolipids by themselves or their stable synthetic analogs that are known to suppress inflammation and help in the resolution and healing of the inflammation-induced damage. These strategies are likely to be useful not only in lupus but also in other conditions, such as rheumatoid arthritis, scleroderma, ischemia-reperfusion injury to the myocardium, ischemic heart disease, and sepsis.
21528751 T helper 17 cell population in lupus erythematosus. 2010 Lupus erythematosus (LE) is an autoimmune inflammatory disease that involves many organs and systems. Immunological factors seem to play a key-role in LE pathogenesis. LE patients have T lymphocytes dysfunctions.Th17 is implicated in the pathogenesis of various autoimmune diseases like psoriasis, multiple sclerosis or rheumatoid arthritis. The purpose of this study was to evaluate the circulating Th17 cell population in LE patients. MATERIAL AND METHODS: A total of 15 LE patients were recruited and divided into three groups: systemic lupus erythematosus (SLE), discoid lupus (DLE) and subacute lupus (SCLE). Serum IL-17A, IL-17F and IL-23 were detected. Th17 circulating cells were evaluated by flow cytometry. RESULTS: Serum IL-17A and IL-17F levels were higher in SLE, DLE and SCLE patients compared to healthy controls. The number of Th17 cells were higher in SLE and DLE patients (p<0.05). the number of CD3+IL-17+ cells were higher in SLE, DLE and SCLE patients (p<0.05). CONCLUSION: Th17 lymphocytes are implicated in LE pathogenesis. Our findings suggest that IL-17 is implicated not only in SLE but also in DLE and SCLE immunopathogenesis.