Institute of Bone and Joint Surgery

Pseudoporphyria (PP) is characterized by skin fragility, blistering and scarring in sun-exposed skin areas without abnormalities in porphyrin metabolism. The phenylpropionic acid derivative group of nonsteroidal anti-inflammatory drugs (NSAID), especially naproxen, is known to cause PP. Naproxen is currently one of the most prescribed drugs in the therapy of juvenile idiopathic arthritis (JIA). The prevalence of PP was determined in a 9-year retrospective study of children with JIA and associated diseases.

The antibody-mediated targeted delivery of cytokines to sites of disease is a promising avenue for the therapy of cancer, but is largely unexplored for the treatment of chronic inflammatory conditions. Using both radioactive and fluorescent techniques, the human monoclonal antibodies L19 and G11 (specific to two markers of angiogenesis which are virtually undetectable in normal adult tissues) were found to selectively localize at arthritic sites in the murine collagen-induced model of rheumatoid arthritis, following intravenous administration.

Multipotent mesenchymal stromal cells isolated from bone marrow and other sites are currently being studied to determine their potential role in the pathogenesis and/or management of autoimmune diseases. In vitro studies have shown that they exhibit a dose-dependent antiproliferative effect on T and B lymphocytes, dendritic cells, natural killer cells and various B cell tumour lines – an effect that is both cell contact and soluble factor dependent.

Osteoarthritis (OA) is a degenerative disease which disrupts collagenous matrix of articular cartilage, and is difficult to cure because articular cartilage is a nonvascular tissue. Treatment of OA has targeted macromolecular substitutes for cartilage components, such as hyaluronic acid or genetically engineered materials. However, the goal of this study is to examine whether intra-articular injection of the elementary nutrients restores the matrix of arthritic knee joints of mature animals.

Inhibition of TNFalpha with biological molecules has proven an effective treatment for rheumatoid arthritis achieving a 20% improvement in ACR score in up to 65% of patients. The main drawback to these and many other biological treatments has been their expense, which has precluded their widespread application. Biological molecules could alternatively be delivered by gene therapy as the encoding DNA. We have developed novel plasmid vectors termed pGTLMIK and pGTTMIK from which luciferase and a dimeric TNFRII (dTNFR) are respectively expressed in a doxycycline (Dox) regulated manner.

Innervation of the joint with sensory thinly myelinated and unmyelinated nerve fibres is crucial for the occurrence of joint pain. During inflammation in the joint sensory fibres show changes in the expression of receptors which are important for the activation and sensitization of the neurones and the generation of joint pain. We recently reported that both neurokinin 1 receptors and bradykinin 2 receptors are upregulated in dorsal root ganglion neurones (the cell bodies of sensory fibres) in the course of acute and chronic antigen-induced arthritis in the rat.

We have recently demonstrated that the rheumatoid arthritis (RA) shared epitope (SE) acts as a ligand that triggers nitric oxide (NO) signaling in opposite cells. Given the known pro-oxidative effect of NO and the proposed role of oxidative stress in the pathogenesis of RA, this study explores whether SE-triggered signaling can increase cellular oxidative stress. Cyclic AMP (cAMP) levels, adenylyl cyclase (AC) activity and protein kinase A (PKA) activity were measured using commercial kits.

Both selective cyclooxygenase (COX)-2 inhibitors and NSAIDs have been beneficial pharmacological agents for many patients suffering from arthritis pain and inflammation. However, selective COX-2 inhibitors and traditional NSAIDs are both associated with heightened risk of myocardial infarction (MI). Possible pro-atherogenic mechanisms of this inhibition have been suggested, including an imbalance in prostanoid production leaving the pro-aggregatory prostaglandins unopposed, but the precise mechanisms involved have not been elucidated.

Hi I am Sreeram Penna, one of the surgical trainee in UK. My career plan is to become a Orthopaedics Surgeon. One of my dream is to create a Institute for Orthopaedics training. IBJS.org is the offspring of my dream. Purpose of this website is to promote Orthopaedic Training, which will be achived through interaction of surgeons and trainees. This website is under construction.

Sreeram Penna