Biomedical subjects

Eamonn S Molloy

Publications and source records attributed to Eamonn S Molloy.

5 recordsLinked to original sources

PubMed2006

Advances in the treatment of small vessel vasculitis.

The systemic small vessel vasculitides encompass Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. The traditional approach to therapy, which incorporates cytotoxic drugs and glucocorticoids, is associated with a significant risk of relapse and treatment-related toxicity. The formation of multicenter collaborative groups has facilitated the execution of randomized controlled trials, and has led to the identification of several effective therapeutic options. This article reviews the existing data and refers to studies in progress that may answer some of the questions that remain regarding the treatment of the small vessel vasculitides.

Anti-Inflammatory Agents↗

PubMed2006

Basic calcium phosphate crystals: pathways to joint degeneration.

PURPOSE OF REVIEW: Basic calcium phosphate crystals have long been associated with rheumatic syndromes. Although an understanding of the molecular mechanisms involved in generating these pathological effects has been significantly advanced in recent years, it is still incomplete. RECENT FINDINGS: Basic calcium phosphate crystals have been shown to increase prostaglandin E(2) production in human fibroblasts, mediated by the induction of both cyclooxygenases 1 and 2. Basic calcium phosphate crystals have also been found to upregulate IL-1beta in fibroblasts and chondrocytes. The upregulation of inducible nitric oxide synthase and stimulation of nitric oxide production in chondrocytes by octacalcium phosphate crystals has been demonstrated. The involvement of protein kinase C isoforms in basic calcium phosphate crystal-mediated matrix metalloproteinase 1 and 3 expression in human fibroblasts has been clarified. Two pathways are involved: protein kinase Calpha mediates the calcium-dependent pathway, whereas protein kinase Cmu activates the extracellular-regulated kinase pathway in a calcium-independent cascade. In addition, basic calcium phosphate crystals activate the transcription factor Egr-1, an effect that may contribute to the mitogenic effect of these crystals on fibroblasts. SUMMARY: Recent findings have emphasized the potential for basic calcium phosphate crystals to stimulate the production of a variety of inflammatory mediators such as prostaglandin E(2), nitric oxide, IL-1beta and matrix metalloproteinases, and have helped to elucidate the mechanisms of these effects. Such advances are essential for the ongoing search for effective therapies for basic calcium phosphate crystal-associated diseases.

Calcinosis↗

PubMed2005

Eicosanoids, osteoarthritis, and crystal deposition diseases.

PURPOSE OF REVIEW: Eicosanoids are produced by chondrocytes, synoviocytes, and subchondral osteoblasts within the osteoarthritic joint and are involved in normal joint physiology as well as in the pathogenesis of joint disorders such as osteoarthritis. Calcium-containing crystals are found in most osteoarthritic joints and have been implicated in osteoarthritis. Recent advances in the understanding of the potential role of eicosanoids in the pathogenesis of osteoarthritis and in potential therapeutic targeting of eicosanoid pathways are reviewed. RECENT FINDINGS: The ability of interleukin-1beta to upregulate microsomal prostaglandin E2 synthase-1 in synovial fibroblasts and chondrocytes of patients with osteoarthritis has been demonstrated. A potential role for prostaglandin E2 in downregulating interleukin-1beta-induced inflammatory responses has also been described. Basic calcium phosphate crystals can upregulate cyclooxygenase-1 and cocylooxygenase-2 expression, both of which contributed to the observed increase in prostaglandin E2 production in human fibroblasts. Novel potential mechanisms of inhibition of eicosanoid synthesis are also discussed. Last, further evidence of amelioration of osteoarthritis in animal models by the dual 5-lipoxygenase/cyclooxygenase inhibitor licofelone has been reported. SUMMARY: The inhibition of prostaglandin synthesis has long been a ornerstone of the pharmacologic treatment of osteoarthritis. Nevertheless, prostaglandins may have potentially beneficial as well as deleterious effects in osteoarthritis. In addition, other eicosanoids such as leukotrienes have also been implicated in the pathogenesis of osteoarthritis. Therefore, more selective inhibition of prostaglandin pathways and/or inhibition of leukotriene activity may prove to be effective therapeutic strategies in osteoarthritis.

Animals↗

PubMed2004

How crystals damage tissue.

Basic calcium phosphate, calcium pyrophosphate dihydrate, and monosodium urate crystals are the most common types of crystals associated with human disease. Although there is a well-established association between these crystals and various forms of joint disease, recent evidence points to an association of basic calcium phosphate crystals with breast cancer and atherosclerosis. Crystal-induced tissue damage is affected by degradative proteases, cytokines, chemokines, and prostanoids produced by cells stimulated by crystals. In the case of basic calcium phosphate and calcium pyrophosphate dihydrate crystals, these responses are augmented by the cellular proliferation that results from their induction of mitogenesis. The understanding of the molecular mechanisms involved in generating these pathologic effects has been significantly advanced in recent years. Such advances are essential to the ongoing search for more effective therapies for crystal-associated diseases.

Arteriosclerosis↗

PubMed2003

Hydroxyapatite deposition disease of the joint.

Basic calcium phosphate (BCP) crystals include partially carbonate-substituted hydroxyapatite, octacalcium phosphate, and tricalcium phosphate. They may form deposits, which are frequently asymptomatic but may give rise to a number of clinical syndromes including calcific periarthritis, Milwaukee shoulder syndrome, and osteoarthritis, in and around joints. Recent data suggest that magnesium whitlockite, another form of BCP, may play a pathologic role in arthritis. Data from the past year have provided further understanding of the mechanisms by which BCP crystals induce inflammation and degeneration. There remains no specific treatment to modify the effects of BCP crystals. Although potential drugs are being identified as the complex pathophysiology of BCP crystals is unraveled, much work remains to be done in order to translate research advances to date into tangible clinical benefits.

Calcium Metabolism Disorders↗