Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01889 (ankylosing spondylitis)
 5,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There has been doubt as to whether elevated levels of parathyroid hormone, reported previously by radioimmunoassay, reflect increased concentrations of the biologically active hormone. The application of a recently developed, highly sensitive bioassay has shown considerable disparity between bioactivity and immunoreactivity in 5 rheumatic conditions and in normal subjects. Six patients with chondrocalcinosis had elevated levels; 3 of these did not have hypercalcaemia or any obvious cause other than possible subclinical hyperparathyroidism. One patient, assayed during an acute episode, had an elevated concentration of the hormone which reverted to normal when she was asymptomatic. Most patients with osteoarthrosis (13 our of 15) had low normal levels; 2 showed unexplained slightly elevated concentrations. Of 6 patients with haemochromatosis 3 had elevated levels, though this may have been related to the associated presence of diabetes mellitus. A third of patients with ankylosing spondylitis (10 out of 30) showed elevated parathyroid hormone levels but without hypercalcaemia. A number of spondylitic patients also showed anomalous results in this assay, possibly due to the presence of an antagonist. This would be consistent with the absence of clinical or biochemical evidence of hyperparathyroidism.
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PMID:Circulating levels of biologically active parathyroid hormone in rheumatic diseases. 698 29

Bisphosphonates are endogenous pyrophosphate analogs in which a carbon atom replaces the central atom of oxygen. They are indicated in non-neoplastic diseases including osteoporosis, corticosteroid-induced bone loss, Paget disease, and in cancer-related diseases such as neoplastic hypercalcemia, multiple myeloma and bone metastases secondary to breast and prostate cancer. There is now extensive in vitro evidence suggesting a direct antitumor effect of bisphosphonates at different levels of action. Some new in vitro and in vivo studies support the cytostatic effects of bisphosphonates on tumor cells, and the effects on the regulation of cell growth, apoptosis, angiogenesis, cell adhesion, and invasion, with particular attention to biological properties. Well designed clinical trials are necessary to investigate whether the antitumor potential of bisphosphonates may be clinically relevant. On the basis of their effects on macrophages, we may divide bisphosphonates into two distinct categories: aminobisphosphonates, which sensitize macrophages to an inflammatory stimulus inducing an acute-phase response, and non-aminobisphosphonates that can be metabolized into macrophages and that may inhibit the inflammatory response of macrophages. There is evidence of aminobisphosphonate-induced pro-inflammatory response, in particular, related to modifications of the cytokine network. Several in vivo studies have demonstrated an acute-phase reaction after the first administration of aminobisphosphonates, with a significant increase in the main pro-inflammatory cytokines. However, a peculiar aspect concerning the action of non-aminobisphosphonates seems to be an anti-inflammatory activity caused by the inhibition of the release of inflammatory mediators from activated macrophages, such as interleukin (IL)-6, tumor necrosis factor-alpha and IL-1. The inhibition of inflammatory responses is demonstrated in both in vivo and in vitro models. This activity suggests the use of non-aminobisphosphonates in several inflammatory diseases characterized by macrophage-mediated production of acute-phase cytokines, as prevention of erosions in rheumatoid arthritis, and of loosening of joint prostheses, as well as possibly in osteoarthritis, ankylosing spondylitis, myelofibrosis, and hypertrophic pulmonary osteoarthropathy.
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PMID:Bisphosphonate effects in cancer and inflammatory diseases: in vitro and in vivo modulation of cytokine activities. 1524 2

Infliximab is a chimeric monoclonal antibody to TNF-alpha which acts on both the soluble and transmembrane forms of TNF-alpha. It has been used successfully for the treatment of psoriasis and psoriatic arthritis, rheumatoid arthritis, Crohn's disease and ankylosing spondylitis either as monotherapy or in combination with drugs such as methotrexate. To date, over 20,440 patients with moderate-to-severe psoriasis have been treated with infliximab worldwide. Opportunistic infections and reactivation of underlying latent infections are an area of concern with the use of infliximab particularly when used in conjunction with other immunosuppresants. The authors report a case of histoplasmosis presenting with signs of severe hypercalcemia and renal failure in a patient on infliximab for approximately three years in combination with low dosages of methotrexate and prednisone. This report stresses the importance of maintaining a high index of suspicion for unusual pathogens while managing patients receiving TNF-alpha inhibitors, particularly when used in combination with other immunosuppressants. In addition, the authors emphasize the role of a multi-disciplinary approach and appropriate coordination among caregivers.
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PMID:Atypical presentation of histoplasmosis in a patient with psoriasis and psoriatic arthritis on infliximab therapy. 2012 Apr 26