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ID PMID Title PublicationDate abstract
18973788 The role and regulation of 11beta-hydroxysteroid dehydrogenase type 1 in the inflammatory 2009 Mar 25 Cortisone, a glucocorticoid hormone, was first used to treat rheumatoid arthritis in humans in the late 1940s, for which Hench, Reichstein and Kendall were awarded a Nobel Prize in 1950 and which led to the discovery of the anti-inflammatory effects of glucocorticoids. To be effective, the intrinsically inert cortisone must be converted to the active glucocorticoid, cortisol, by the intracellular action of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). Whilst orally administered cortisone is rapidly converted to the active hormone, cortisol, by first pass metabolism in the liver, recent work has highlighted an anti-inflammatory role for 11beta-HSD1 within specific tissues, including in leukocytes. Here, we review recent evidence pertaining to the anti-inflammatory role of 11beta-HSD1 and describe how inhibition of 11beta-HSD1, as widely proposed for treatment of metabolic disease, may impact upon inflammation. Finally, the mechanisms that regulate 11beta-HSD1 transcription will be discussed.
18823045 Molecular and functional characteristics of proton-coupled folate transporter. 2009 May Proton-coupled folate transporter (PCFT) has recently been identified as the molecular entity of the carrier-mediated intestinal folate transport system. PCFT has been demonstrated to be most abundantly expressed in the upper small intestine, localizing at the brush border membrane of epithelial cells, transport folate and its analogs more efficiently at lower (acidic) pH by a H(+)-coupled cotransport mechanism, and have a high affinity for folate with a Michaelis constant (K(m)) of a few microM at pH 5.5 and somewhat lower affinities for reduced folates and methotrexate (MTX). A loss of PCFT function due to a homozygous mutation in its gene has been indicated to be responsible for hereditary folate malabsorption. Thus, PCFT has all the characteristics of the brush border H(+)-coupled cotransporter for folate and analogs, which has long been suggested to be present in the intestine. Furthermore, sulfasalazine was found to be a potent inhibitor of PCFT, suggesting that it is a risk factor that would cause malabsorption of folate and also MTX, when coadministered in the treatment of rheumatoid arthritis. Understanding the molecular and functional characteristics of PCFT should be important and helpful in exploring therapeutic strategies for folate malabsorption and in optimizing therapies using antifolate drugs.
22282669 Age and anthropometric traits predict handgrip strength in healthy normals. 2010 Dec Hand grip strength is an inevitable component in the evaluation of rheumatoid arthritis, neuromuscular, preoperative, post operative patients and community dwelling older adults' functional capacity. Hand grip varies greatly with age, gender and the anthropometric measures when measured by hand dynamometer. The influence of above variables on hand grip when measured by modified sphygmomanometer is unknown. Further, the prediction of hand grip from age and anthropometric traits is unknown. 229 subjects (115 males and 114 females) with age 23 ± 2 and 21 ± 2 respectively were included in the study after informed c nsent. Weight and height were obtained using standard techniques. Hand grip was measured using a modified sphygmomanometer. Information regarding physical activity and health status was obtained by interview, clinical screening and stratified. Stepwise multiple regression analysis was sought out for any influence of age, height, weight and Body Mass Index (BMI) on hand grip strength. Grip strength correlated moderate to high with age (r = 0.44, p = 0.00), height (r = 0.57, p = 0.00), weight (r = 0.57, p = 0.00) and BMI (r = 0.29, p = 0.00). The regression model for handgrip strength is Hand grip = -1790.54 + 4.93557 × Age-11.7429 × Weight + 1083.4 × Height + 34.194 × BMI. Age, height and weight are the i portant determinants of the handgrip evaluation. In clinical setting, the influence of age and anthropo etric traits on handgrip shall be borne in mind when measuring handgrip by modified sphygmomanometer in age group of 20-25 year patients.
19817678 Denileukin diftitox: a novel immunotoxin. 2009 Nov OBJECTIVE: To review FDA approved and other potential uses of Ontak, denileukin diftitox. METHODS: Information was obtained via the internet and a journal literature review. RESULTS: In 1999, the FDA approved the use of denileukin diftitox for patients with persistent or relapsed CD25-positive cutaneous T-cell lymphoma (CTCL), but Ontak has been reported to be an effective therapy for other neoplastic and non-neoplastic conditions. Oncological uses include therapy for CD25-negative T-cell lymphoma, recurrent and refractory chronic lymphocytic leukemia (CLL), non-Hodgkin's B-cell lymphoma (NHL), and human T-cell lymphotropic virus- 1 (HTLV-1)-associated adult T-cell leukemia/lymphoma (ATL). Potential additional uses of Ontak include: therapy of graft-versus-host disease (GvHD) and autoimmune conditions, including psoriasis, rheumatoid arthritis (RA), systemic lupus, scleroderma and vasculitis. Denileukin diftitox's effect has also been studied for patients with hepatocellular carcinoma (HCC) and HIV, but conclusive data are still pending. CONCLUSION: There are many potential uses for denileukin diftitox, in both malignant and benign disorders. More human trials are needed to demonstrate further efficacy for a wide range of diseases.
19714703 Molecular mechanisms mediated by human endogenous retroviruses (HERVs) in autoimmunity. 2009 Sep Eight per cent of the human genome is derived from the integration of retroviral sequences that were incorporated in our DNA more than 25 million years ago. Although some of these elements show mutations and deletions, some HERVs are transcriptionally active and produce functional proteins. Different mechanisms have been described which link HERVs to some chronic diseases such as several cancers, nervous system diseases and autoimmune rheumatic and connective tissue diseases. They could cause disease because of their capacity for being moved and inserted next to certain genes whose expression would be consequentially altered. Another way in which disease could potentially arise is when HERV-encoded proteins are expressed. These proteins would be considered as [foreign] and they could trigger B-cells to produce antibodies against them, which, in turn, might cross-react with other proteins of our bodies. This mechanism could give rise to autoimmune diseases such as rheumatoid arthritis (RA), lupus erythematosus, Sjögren's syndrome (SJS), mixed connective tissue diseases and inflammatory neurological disease. Furthermore, it should be pointed out that HERV-proteins may act as superantigens. Interestingly, some environmental agents seem to induce the expression of HERVs. Thus, ultraviolet light and several chemical agents could reactivate such sequences by altering their structure without modifying their nucleotide composition when the methylation pattern is changed. Therefore, the epigenetic changes observed in pathological conditions such as systemic lupus erythematosus (SLE) or cancer could be translated into an effect on the activation of some of the retroelements present in our genome which ultimately could have a direct or indirect role on the initiation and clinical evolution of certain chronic diseases.
19409515 Cysteine cathepsins are not critical for TNF-alpha-induced cell death in T98G and U937 cel 2009 Sep The tumor necrosis factor (TNF) is a cytokine known to be an important mediator of apoptosis and inflammation. It has been implicated in the pathogenesis of a number of diseases, including cancer and rheumatoid arthritis. TNF apoptosis has been known for a number of years to be critically dependent on caspases; however, recently it has been suggested that cysteine cathepsins might also be involved in the pathway. In the present work the hypothesis that cathepsins can act as an essential downstream mediator of TNF-alpha-triggered apoptosis was tested. The TNF-alpha apoptosis was investigated in two tumor-cell lines: U937 and T98G. Based on the use of pharmacological caspase inhibitors, the TNF-alpha induced caspase-dependent apoptotic cell death in both cell lines, which was accompanied by lysosomal destabilization and the release of cathepsins in the cytosol. However, blocking cysteine cathepsins with a broad-spectrum inhibitor, E64d, or a more specific cathepsin B inhibitor, CA-074Me, had no effect on the progression of the apoptosis in both cell lines, suggesting that the TNF-alpha apoptosis is not critically dependent on the cathepsins in these two cellular models.
20395193 Polyglandular autoimmune diseases in a dermatological clinical setting: vitiligo-associate 2010 May Vitiligo is an acquired hypomelanotic disorder characterized by depigmented macules resulting from the loss of functional melanocytes. Many different etiological hypotheses have been suggested for vitiligo, the most recent of which involves a combination of interacting environmental and genetic factors. Among the various pieces of evidence in support of an autoimmune origin of vitiligo, there is the epidemiological association with several autoimmune diseases. The most frequently reported association is with autoimmune thyroiditis; however, other diseases such as rheumatoid arthritis, diabetes mellitus, pernicious anemia and chronic urticaria have been described in variable percentages, depending upon the genetics of the population studied. Among the diseases described in association with vitiligo there are the so-called autoimmune polyglandular syndromes (APS). Here we report 31 cases of APS diagnosed in 113 vitiligo patients, according to the newest classification. Autoimmune association was more present in generalized non segmental vitiligo and was more frequent in females. The most frequent association was with thyroid autoimmune disease, followed by autoimmune gastritis and alopecia areata. ANA positivity was similar to that reported previously in the general population. We stress the importance of an assessment for autoimmune diseases in vitiligo patients.
20121624 Pathological and biochemical effects of therapeutic and supratherapeutic doses of celecoxi 2010 Oct Celecoxib is intended for acute pain, menstrual cramps, pain, and inflammation of osteoarthritis and rheumatoid arthritis. The aim of this study was to evaluate the effects of celecoxib (10 and 50 mg/kg/day) treatment on rats orally for 28 days. We examined effects on some biochemical parameters and kidney and liver tissues of celecoxib-treated Wistar albino male rats. At the end of the study, hepatic and renal function tests were performed and liver and kidney of rats were microscopically examined to detect systemic toxicity of celecoxib. Celecoxib-treated rats had statistically significant decreases of cholesterol, total bilirubin, total protein, urea, globulin, blood urea nitrogen, phosphorus, and calcium. Serum gamma glutamyl transferase levels increased in 10- and 50-mg/kg/day celecoxib-treated rats. Histological examinations showed mononuclear cell infiltration, hyperplasia, and cellular degeneration in liver and tubular damage and mononuclear cell infiltration in kidney. We suggest that high doses of celecoxib may cause changes in liver and kidney histopathology, liver function, and in some biochemical parameters.
20017890 Matrix metalloproteinases and their inhibitors: promising novel biomarkers in severe sepsi 2009 The multicenter study conducted by Lorente and coworkers published in the previous issue of Critical Care demonstrates that matrix metalloproteinase (MMP)-9 and MMP-10 and their inhibitor tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) are promising novel biomarkers to predict severity and outcome of sepsis. In recent years MMPs have emerged as biomarkers in a variety of diseases, such as sepsis, coronary artery disease, cancer, heart failure, chronic lung disease and rheumatoid arthritis. MMPs constitute a family of proteinases that are expressed during developmental, physiological, and pathophysiological processes, for example as a response to infection. Excessive inflammation following infection may cause tissue damage, and MMPs are implicated in causing this immunopathology. The activity of MMPs is regulated by secretion of specific inhibitors (TIMPs). Studies using MMP inhibitors and MMP knockout mice indicate that MMPs play an essential role in infection and in the host response to infection. The measurement of MMP-9 and MMP-10 and their inhibitor TIMP-1 in the intensive care setting could be an attractive noninvasive tool for determination of outcome of septic patients.
19937376 Fibromyalgia unique temporal brain activation during experimental pain: a controlled fMRI 2010 Jan Studies with functional neuroimaging support the hypothesis of central pain augmentation in fibromyalgia syndrome (FMS) with functional differences in areas of the medial pain system. To clarify whether these findings are unique to patients with FMS, BOLD-signal patterns during and before tonic experimental pain were compared to healthy controls and patients with rheumatoid arthritis (RA) as a chronic pain disorder of somatic origin. We expected different BOLD-signal patterns in areas of the medial pain system that were most pronounced in patients with FMS. An fMRI-block design before, during and after an incision was performed in patients with FMS (n = 17), RA (n = 16) and in healthy controls (n = 17). A 2-factorial model of BOLD-signal changes was designed to explore significant differences of brain activation between the groups during the pain stimulus. Additionally, the correlation of brain activity during the anticipation of pain with the amount of the impending pain was determined. We observed a FMS-unique temporal brain activation of the frontal cortex in patients with FMS. Moreover, areas of the motor cortex and the cingulate cortex presented a FMS-specific relation between brain activity during pain anticipation and the magnitude of the subsequent pain experience. Our results support the hypothesis that central mechanisms of pain processing in the frontal cortex and cingulate cortex may play an important role in patients with FMS.
19922020 Small bone lesions resembling erosions can frequently be found in bilateral wrist MRI of h 2009 Nov OBJECTIVE: To examine magnetic resonance imaging (MRI) scans for bone lesions typical of rheumatoid arthritis (RA) in the wrist joints of healthy individuals. METHODS: Thirty-one symptomless healthy persons (13/18 men/women), mean age 49 years (range 32-64 years), were included. MRI scans and radiographs of both wrists were obtained (62 wrists). The MRI scans and the radiographs were evaluated by two specialists according to the OMERACT recommendations and the Larsen method, respectively. RESULTS: MRI showed erosive-like lesions in either one or both wrists in 14 [45%, 95% confidence interval (CI) 27-64] out of 31 subjects. Altogether, 24 erosive-like changes were found in the 930 wrist bones evaluated (15 bones in each wrist). No more than two lesions per wrist were detected. All the changes were small (22 were grade 1 and two were grade 2; scale 0-10) and were found more often in the older subjects (55 vs. 43 years, p<0.001). Most lesions (54%) were located on the volar side of the wrist and adjacent to the ligament insertions. Intravenous administration of the contrast medium gadolinium diethylenetriaminepentaacetate (Gd-DTPA) was used in 10 subjects, and mild to moderate Gd-DTPA enhancement in the synovial compartments was seen in six of them: five had enhancement in both wrists and one in one wrist. The plain radiographs showed one erosive-like change in the wrist (pisiforme) that was not recorded with MRI. CONCLUSIONS: A few small bone lesions that could potentially be confused as erosions were detected in about half of the normal volunteers. These findings should always be evaluated with reference to the clinical picture.
19819109 Recent insights in the epidemiology of autoimmune diseases: improved prevalence estimates 2009 Nov Previous studies have estimated a prevalence of a broad grouping of autoimmune diseases of 3.2%, based on literature review of studies published between 1965 and 1995, and 5.3%, based on national hospitalization registry data in Denmark. We examine more recent studies pertaining to the prevalence of 29 autoimmune diseases, and use these data to correct for the underascertainment of some diseases in the hospitalization registry data. This analysis results in an estimated prevalence of 7.6-9.4%, depending on the size of the correction factor used. The rates for most diseases for which data are available from many geographic regions span overlapping ranges. We also review studies of the co-occurrence of diseases within individuals and within families, focusing on specific pairs of diseases to better distinguish patterns that may result in insights pertaining to shared etiological pathways. Overall, data support a tendency for autoimmune diseases to co-occur at greater than expected rates within proband patients and their families, but this does not appear to be a uniform phenomenon across all diseases. Multiple sclerosis and rheumatoid arthritis is one disease pair that appears to have a decreased chance of coexistence.
19703541 In vivo anti-inflammatory and wound healing activities of Centaurea iberica Trev. ex Spren 2009 Dec 10 AIM OF THE STUDY: Several Centaurea species (Asteraceae) are used in Turkish folk medicine to alleviate pain and inflammatory symptoms in rheumatoid arthritis, high fever, head ache and for wound healing. Particularly, the aerial part of Centaurea iberica Trev. ex Spreng. has been practiced on wounds for healing. In order to evaluate the anti-inflammatory and wound healing activities of the plant, extracts were prepared with variety of solvents: hexane, chloroform, ethyl acetate and aqueous methanol (85%) from the aerial parts of Centaurea iberica. MATERIALS AND METHODS: The incision by using tensiometer and excision models were used in order to assess the effect of the plant extracts on wound healing in mice and rats. Results were also evaluated histopathologically. In vivo inhibitory effect of the extracts on acetic acid-induced increase in capillary permeability was studied for the assessment of anti-inflammatory activity. RESULTS: The wound healing effect was comparatively evaluated with a reference ointment Madecassol. Noteworthy wound healing activity was observed for the ointment formulation prepared with 1% methanol extract. The results of histopathological evaluation supported the outcome of both incision and excision wound models. Moreover, the methanol extract exerted remarkable wound healing activity and also demonstrated a significant and dose-dependent anti-inflammatory activity. CONCLUSION: The experimental study revealed that Centaurea iberica displays remarkable wound healing and anti-inflammatory activity.
19639286 A3 adenosine receptor: pharmacology and role in disease. 2009 The study of the A(3) adenosine receptor (A(3)AR) represents a rapidly growing and intense area of research in the adenosine field. The present chapter will provide an overview of the expression patterns, molecular pharmacology and functional role of this A(3)AR subtype under pathophysiological conditions. Through studies utilizing selective A(3)AR agonists and antagonists, or A(3)AR knockout mice, it is now clear that this receptor plays a critical role in the modulation of ischemic diseases as well as in inflammatory and autoimmune pathologies. Therefore, the potential therapeutic use of agonists and antagonists will also be described. The discussion will principally address the use of such compounds in the treatment of brain and heart ischemia, asthma, sepsis and glaucoma. The final part concentrates on the molecular basis of A(3)ARs in autoimmune diseases such as rheumatoid arthritis, and includes a description of clinical trials with the selective agonist CF101. Based on this chapter, it is evident that continued research to discover agonists and antagonists for the A(3)AR subtype is warranted.
19622170 Annexin V and anti-Annexin V antibodies: two interesting aspects in acute myocardial infar 2009 Jul 21 BACKGROUND: Myocardial infarction is the combined result of environmental factors and personal predispositions. Prothrombotic factors might play an important role in this phenomenon. Annexin V (ANV) is a calcium-dependent glycoprotein widely present in various tissues exerting a potent anticoagulant effect in vitro by reducing plaque adhesion and aggregation. Anti-annexin V antibodies (aANVAs) are detected in various diseases like rheumatoid arthritis, systemic lupus erythematosus and anti-phospholipid antibody syndrome. The study of ANV in Acute Myocardial Infarction (AMI) might shed light on hypercoagulability mechanisms in the pathogenesis of acute coronary syndromes. This study was conducted to investigate the association of plasma ANV, aANVAs and anti-cardiolipin antibodies (aCLAs) with AMI. METHODS: This study recruited 45 patients with the diagnosis of AMI according to WHO criteria in their first 24 hours of admission. 36 matched individuals were studied as the control group with normal coronary artery angiography. Plasma levels of ANV, aANVAs and aCLAs were determined by enzyme-linked immunosorbent assay and the results were compared. RESULTS: Plasma ANV levels in the patients with AMI on admission were significantly lower than those in the control group (p = 0.002). Positive test for aANVAs were found to be present in a significant number of our patients (p = 0.004). The studied groups were similar in their rate of patients with positive aCLAs tests. ANV, aANVAs and aCLAs were not correlated with hypertension, diabetes mellitus, hyperlipidemia, sex, age and smoking. CONCLUSION: Our findings suggest that low plasma ANV levels along with positive aANVAs tests in patients with AMI are indicative of hypercoagulable state that is not related to the traditional cardiovascular risk factors.
19616319 Interleukin-21 as a new therapeutic target for immune-mediated diseases. 2009 Aug Cytokines have a decisive role in initiating and shaping pathologic responses in patients with various immune-inflammatory diseases. Recent studies indicate that interleukin (IL)-21, a cytokine produced mostly by activated CD4+ T cells, participates in the tissue damage in various tissues, owing to its ability to regulate the function of immune and non-immune cells. For instance, IL-21 controls the differentiation and functional activity of T cells, B cells and NK cells, limits the differentiation of inducible regulatory T cells (Tregs), and makes T cells resistant to the Treg-mediated immunesuppression. It also stimulates epithelial cells and fibroblasts to produce inflammatory mediators. Here, we focus on data supporting the pathogenic role of IL-21 in human inflammatory diseases and discuss pre-clinical studies that suggest that neutralization of IL-21 in vivo could be a new biological therapy to combat immune-mediated pathologies, such as inflammatory bowel diseases, diabetes, rheumatoid arthritis and systemic lupus erythematosus.
19616137 The epidemiology of insomnia: associations with physical and mental health. The HUNT-2 stu 2009 Aug OBJECTIVE: The aim of the present study was to examine the association of insomnia symptoms with demographic and physical and mental conditions in a large population-based study. METHODS: Cross-sectional data on insomnia and comorbid conditions were gathered from 47,700 individuals aged 20-89 in Norway. Comorbid conditions included anxiety and depression and the following physical conditions: asthma, allergy, cancer, hypertension, diabetes, migraine, headache, osteoporosis, fibromyalgia rheumatoid arthritis, arthrosis, Bechterew's disease, musculoskeletal disorders, and obesity (body mass index >30). RESULTS: Insomnia symptoms were found in 13.5% of the population and were more prevalent among women, older adults, and in individuals with less education. Reporting insomnia symptoms significantly increased the associations with a range of conditions, especially mental conditions, pain conditions with uncertain etiology and, to a lesser extent, chronic pain conditions. These findings remained significant also when adjusting for a range of potential confounders, whereas the association between insomnia and somatic conditions was largely reduced to a nonsignificant level in the fully adjusted analyses. CONCLUSION: This study demonstrates that insomnia symptoms are associated with a range of different conditions. The findings suggest that the independent contribution of insomnia is strongest on conditions characterized by some level of psychological or psychosomatic properties.
19569977 Briakinumab. 2009 Aug BACKGROUND: Psoriasis is a chronic, autoimmune, T-cell mediated, inflammatory disease. An improved understanding of the pathogenesis of the autoimmune response has led to the development of targeted biologic therapies. Briakinumab is a human monocolonal antibody that blocks the activity of the cytokines IL-12 and IL-23. Immune dysregulation has been implicated in multiple inflammatory disorders and briakinumab has been investigated for the treatment of psoriasis, rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. OBJECTIVES: This review focuses on briakinumab and its use in chronic plaque-type psoriasis. METHODS: A literature review was performed, searching Medline and the clinicaltrials.gov database for all articles with the keywords ABT-874, IL-12/IL-23 and psoriasis. CONCLUSIONS: Although limited by small sample sizes, length of follow-up, and a lack of direct comparisons with other psoriasis treatments, initial data regarding the safety and efficacy of briakinumab for the treatment of psoriasis is promising. Ongoing Phase III trials may provide additional information regarding the relative efficacy and safety of briakinumab.
19519590 CTLA-4Ig: uses and future directions. 2009 Jun Cytotoxic lymphocyte-associated molecule-4 (CTLA-4, CD152) is a member of the CD28 receptor family. Blocking CD28 interaction with its ligands through the use of CTLA-4Ig might contribute to better control of dysregulated immune response processes. The ligands binding to CTLA-4 are the B7 family members, B7-1 (CD80) and B7-2 (CD86). CTLA-4Ig is now a Food and Drug Administration-approved drug for use treating patients with Rheumatoid arthritis (RA) but its use is explored also in other autoimmune diseases, transplantation as well as allergic diseases. Patents related to CTLA-4 function as well as possible clinical applications are discussed in this paper.
19507632 B cell activating factor, its role in autoimmunity, and targeting in autoimmune diseases. 2009 B cell activation factor (BAFF), a recently identified member of the tumour necrosis factor (TNF) family, is a key survival factor during B cell maturation and is essential for the development of B cell tolerance. Breakdown of the regulation of BAFF expression results in excessive BAFF production that impairs B cell tolerance and leads to autoimmune phenomena. Consistent with this, BAFF levels are elevated in plasma of patients with various autoimmune diseases. BAFF is considered to be one of the principal factors that regulate the size and composition of B cell compartment. BAFF acts as an important driving factor for B cell hyperplasia and autoantibody production in autoimmune processes. Thus BAFF has become a very attractive target for the treatment of autoimmune diseases with an altered B cell function. Results of clinical trials have confirmed a crucial role of BAFF in the pathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). BAFF inhibitors in the treatment of RA, SLE and other autoimmune diseases are under intensive investigation. However, BAFF biology remains poorly understood. Nonetheless, results of the ongoing studies may enable the development of a new generation of BAFF inhibitors with more selective efficacy and increased safety (Fig. 2, Ref. 92). Full Text (Free, PDF) www.bmj.sk.