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MD Biosciences Blog

Cardiovascular Disease & Underlying Inflammatory Events

Posted by MD Biosciences on May 10, 2011 3:51:00 PM

Cardiovascular disease (CVD) including heart disease, vascular disease and atherosclerosis are the most critical global health threats.

An estimated 26 million people are living with the effects of heart disease and is a major cause of death in western society. Until recently the widely held belief was that the CVD is simply the process as a build up of fat on the surface of artery walls. Eventually, this build up of fat blocks the artery and a heart attack or stroke occurs. However, the process has now been identified as a disease of the inner artery wall (intima) and inflammation is a key factor in its progression.

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Topics: Inflammation, Cardiovascular

Link Between TH17 & Osteoclast Function in RA

Posted by MD Biosciences on Apr 19, 2011 12:33:00 PM

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects approximately 1% of the population, and in 2010 cost the US alone $39.2 billion (1,2).  The disease is characterized by bone erosion, cartilage damage, synovial hyperplasia and cellular infiltration, all of which result in debilitating joint pain and stiffness (1,3,4).  Studying preclinical models such as the collagen-induced arthritis (CIA) model and the anti-collagen antibody induced arthritis (ACAIA) model, which show the above hallmarks of disease has allowed the identification of the cells and cytokines involved in the pathogenesis of the disease (5,6).
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Topics: Inflammation

Adipose Tissue - A Site of Inflammation?

Posted by MD Biosciences on Apr 12, 2011 12:41:00 PM

Inflammatory Events Associated With Obesity

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Topics: Inflammation

Suitable Preclinical Models Needed For Novel Asthma Treatments

Posted by MD Biosciences on Apr 6, 2011 12:08:00 PM

There is a major unmet need in the treatment of asthma which is growing in incidence and prevalence in industrialized countries. The prevalence of asthma has doubled in the Western world over the previous 20 years. In addition to the estimated 180,000 asthma related deaths per year, there is a substantial economic burden due to lost school/work days and increased medical costs.

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Topics: Inflammation

T-cells in Rheumatoid Arthritis | Where, Why & When?

Posted by MD Biosciences on Mar 28, 2011 1:02:00 PM

The role of T-cells and their actions in rheumatoid arthritis (RA) has been the focus of a great deal of research for some time [1], mainly as a result of many observations in human patients and experimental animal models.  The association of Human Leukocyte Antigen (HLA) DR, a MHC class II cell surface receptor, in RA provides the strongest evidence that CD4+ T-cells are involved in the development of disease [2, 3, 6]. Many other types of T-cells, including CD8+, regulatory T-cells and γδ T-cells have been shown to play different roles in the progression of RA [1, 2, 3, 8]. The mechanisms of disease involved in RA are still unknown; however the main hypothesis theorizes that auto antigens are presented to auto reactive T helper cells, which then orchestrate the inflammatory processes which are characteristic of the disease [3]. The nature of the antigens involved is unknown however several candidates have been suggested, most recently, citrullinated proteins [5, 6].

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Topics: Inflammation

Part 2 | Cutting Edge Rheumatoid Arthritis Model Readouts

Posted by MD Biosciences on Aug 10, 2010 8:54:00 AM

Continuing the discussion of imaging technologies, this week we will cover biofluorescence and bioluminescence as readouts for RA models.

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Topics: Inflammation

Cutting Edge Rheumatoid Arthritis Models

Posted by MD Biosciences on Jul 5, 2010 11:10:00 AM

Rheumatoid arthritis is a chronic and progressive inflammatory condition estimated to affect between 0.5% and 1% of the world’s population, with more women being affected than men. RA is a systemic disease manifesting mainly as a disabling destruction of the synovial joints of the hands and feet.  In addition to the disability and decreased quality of life caused by RA, patients are at increased risk of developing cardiovascular disease. Joint destruction is induced by dysregulated immune activation of both the innate and adaptive immune responses resulting in alterations in the synovium, cartilage and bone.  The normal joint has a thin synovial lining (intimal lining layer), 1-3 cells thick. Beneath this is a sub-lining layer of connective tissue scattered with immune cells, blood vessels and nerve cells.  Together these layers form the synovium, which produces the synovial fluid that serves to lubricate the joint. Disease initiation results in profound changes in the structure and composition of the synovium and synovial fluid; with the infiltration of inflammatory cells, synovial cell hyperplasia, increased angiogenesis, fibroblast proliferation and extracellular matrix production. This increase in synovial cell proliferation can result in the lining increasing up to five times its original size and can result in pannus formation. The culmination of these events is bone and cartilage erosion and loss of joint function.

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Topics: Inflammation

Screening Assays | Targeting Fibroblast-like Synovioctyes

Posted by MD Biosciences on May 13, 2010 9:39:00 AM

Rheumatoid arthritis (RA) is a chronic autoimmune joint disease characterized by inflammation of the synovium and destruction of cartilage and bone. During synovial inflammation, inflammatory cells (macrophages, mast cells, dentritic cells and lymphocytes) are recruited while resident cells (fibroblast synoviocytes, chondrocytes, osteoclasts, and osteoblasts) are altered to support the inflammatory process.  Together, these events create a pathological tissue response.
 
The synovium consists of two layers, the sublining and intimal lining.  In RA, the sublining becomes infiltrated with mononuclear cells, B lymphocytes produce autoantibodies, blood vessels proliferate, lymphoid aggregates form and the intimal lining shows increased cellularity.  Macrophages in the synovium produce pro-inflammatory cytokines, chemokines and growth factors which in turn activate fibroblast-like synoviocytes (FLS) to produce their own array of mediators (e.g. proteolytic enzymes, chemokines and cytokines).  This produces a paracrine/autocrine network that leads to synovitis, the recruitment of new cells and the destruction of the extracellular matrix.  Fibroblast-like synoviocytes have emerged as key pro-inflammatory cells promoting the disease, largely due to their ability to produce massive amounts of degradative enzymes.
 
The availability of biological therapies has improved clinical outcomes by decreasing inflammation and joint destruction, however only about half of the patients exhibit substantial efficacy. Targeting FLS may further improve clinical outcomes without suppressing systemic immunity.  In vitro FLS assays can be used to evaluate effective therapies for arthritis. Using FLS obtained from normal, RA and OA patients, we can evaluate a compound's effect on the production of pro-inflammatory mediators in a preclinical in vitro model. 

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Topics: Inflammation

Efficacy of anti-CD20 Therapy in Rhuematoid Arthritis

Posted by MD Biosciences on May 11, 2010 12:46:00 PM

We read an interesting article published this week in Journal of Immunology (v184 Bottaro & co.) on the efficacy of anti-CD20 therapy in RA. The article highlights the continuing uncertaintity over the mode of action of B-cell directed therapy in Rheumatoid Arthritis (RA) [review of the differing theories is presented in Clin Exp Immunol. 2009 Aug;157(2):191-7].

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Topics: Inflammation

Determine Immunomodulatory Mechanism of Action for Compounds

Posted by MD Biosciences on May 5, 2010 10:42:00 AM

Determine immunomodulatory mechanism of action for compounds in indication discovery or respositioning of approved therapies.

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Topics: Inflammation