Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in substance P (SP) receptor concentration have been implicated in neuropsychiatric disorders, Parkinson's disease, arthritis, inflammatory bowel disease and asthma. Since, SP and peptide analogs are rapidly metabolized and do not penetrate into the CNS, they are not useful for PET. Recently, a non-peptide SP antagonist, (+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994) was developed. As a prelude to PET studies, this compound was radiolabeled with 11C and biodistribution was determined in hamsters. CP-99,994 was radiolabeled by methylation of tert-Boc, desmethyl CP-99,994 with 11CH3I followed by deprotection and HPLC purification. The time required for the synthesis was 40 min from the end of bombardment. Radiochemical purity of the final product was > 95% and specific activity was routinely > 1000 mCi/mumol [EOS]. The biodistribution of 11C-CP-99,994 was determined in groups of six Syrian hamsters at 5 and 30 min after injection. The results of these studies demonstrated that significant concentrations (%ID/g +/- SEM) of CP-99,994 accumulate in most tissues of the hamster. The highest levels of drug were detected in the lung: 21.04 +/- 1.26 (5 min) and 13.49 +/- 1.71 (30 min). Brain accumulation was: 1.44 +/- 0.06 (5 min), 1.32 +/- 0.05 (30 min). These results indicate that 11C-CP-99,994 can be prepared in high purity and specific activity. This new radiopharmaceutical may be useful for studying both central and peripheral SP receptors by PET.
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PMID:Synthesis of a 11C-labeled NK1 receptor ligand for PET studies. 773 67

Leukotriene B4 (LTB4) is a product of the 5-lipoxygenase pathway of arachidonic acid metabolism. LTB4 is a potent chemotactic factor for neutrophils and has been postulated to play an important role in a variety of pathological conditions including rheumatoid arthritis (RA), psoriasis, and inflammatory bowel disease. The role of LTB4 in such diseases has not yet been defined but in this paper we provide direct evidence that LTB4 plays a critical role in a murine model of RA. CP-105,696, (+)-1-(3S,4R)-[3-(4-phenylbenzyl)- 4-hydroxychroman-7-yl]cyclopentane carboxylic acid, is an LTB4 receptor antagonist that inhibits LTB4 binding to human neutrophil membranes with an IC50 of 3.7 nM and inhibits LTB4-induced chemotaxis of these cells with an IC50 of 5.2 nM. CP-105,696 inhibits LTB4-induced neutrophil influx in mouse skin when administered orally with an ED50 of 4.2 mg/kg. CP-105,696 had a dramatic effect on both the clinical symptoms and histological changes of murine collagen-induced arthritis when administered at doses of 0.3-10 mg/kg. Inhibition was not associated with suppression of the humoral immune response to collagen and was equally effective if drug treatment was commenced just prior to the onset of arthritis or throughout the experiment. These results suggest that LTB4 receptor antagonists may be effective therapeutic agents for the treatment of RA.
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PMID:Leukotriene B4 plays a critical role in the progression of collagen-induced arthritis. 783 22

The objective of this study was to review (1) the factors that have been linked to prediction of clinical outcome and survival in amyloidosis and (2) the available studies on the therapy for localized and systemic forms of amyloidosis. We made a retrospective review of the relevant literature on treatment and prognosis in localized and systemic amyloidosis dating back to 1975. The most important prognostic factors in amyloidosis are the presence of congestive heart failure, beta 2-microglobulin, and whether peripheral neuropathy dominates the presentation. The presence of a monoclonal light chain in serum or urine, multiple myeloma, and hepatic involvement are also important adverse factors. Colchicine is beneficial in treating familial Mediterranean fever and may play a role in managing secondary amyloidosis in inflammatory bowel disease. Chlorambucil is particularly useful in juvenile rheumatoid arthritis with amyloidosis. Dimethyl sulfoxide provides benefit in bladder and lichen amyloidosis. A trial of alkylating agent-based chemotherapy is reasonable in symptomatic primary systemic amyloidosis. Advances have been made in the treatment of amyloidosis and include chemotherapy, dialysis, transplantation, and improved supportive care. Definite disease regressions with long-term survival (> 10 years) are seen. Unfortunately, alternatives still need to be developed: Of 859 patients with primary systemic amyloidosis seen at the Mayo Clinic from 1982 to 1992, the median survival was 2.1 years.
Semin Arthritis Rheum 1994 Oct
PMID:Amyloidosis: prognosis and treatment. 783 54

5-Lipoxygenase catalyzes the transformation of arachidonic acid to leukotriene A4. This unstable intermediate can be converted to leukotriene B4 by LTA4-hydrolase or to leukotriene C4 by LTC4-synthase. Leukotrienes are involved in host defense reactions and play an important role in inflammatory diseases like asthma, inflammatory bowel disease and arthritis. The capability to release leukotrienes is restricted to a few cell types. Under pathophysiological conditions, leukotrienes are released from granulocytes, mast cells or macrophages. During hematopoiesis the competence of these cells for leukotriene biosynthesis is supposed to be upregulated. In mature cells, 5-lipoxygenase activity is tightly regulated and seems to be under the control of additional cellular components. One cellular component, a membrane-bound peptide termed FLAP, which is necessary for 5-LO activity in intact cells has been recently identified. Inhibitors of FLAP function prevent translocation of 5-lipoxygenase from cytosol to the membrane and inhibit 5-LO activation. Thus, the understanding of the regulatory mechanisms of cellular leukotriene biosynthesis provides new concepts for the development of antiinflammatory drugs. This review focuses on the regulation of gene expression and activity of 5-lipoxygenase.
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PMID:5-Lipoxygenase: enzyme expression and regulation of activity. 793 75

We describe a 7-year-old child who developed right knee arthritis unresponsive to nonsteroidal anti-inflammatory drug therapy. Additional rheumatologic disorders including pleuropericardial effusion with tamponade supervened before the recognition of Crohn's disease involving the colon. Suppression of all sites of inflammation resulted from corticosteroid therapy. Aspects of diagnosis and treatment of these extraintestinal components of inflammatory bowel disease are discussed.
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PMID:Chronic monoarticular arthritis and acute pericardial tamponade in a child with Crohn's disease. 801 45

Spondyloarthritides are chronic inflammatory disorders, characterized by sacroiliitis, spondylitis, peripheral arthritis, extra-articular manifestations and association with HLA-B27. Specific clinical presentations allow to differentiate between different diseases such as ankylosing spondylitis, reactive arthritis, psoriasis arthritis and arthritis in inflammatory bowel disease. For therapy, regular physiotherapy, ergonomic counselling, anti-inflammatory drugs, disease-modifying drugs and antibiotics for chlamydia-induced reactive arthritis are used.
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PMID:[Spondylarthritis--a family of inflammatory-rheumatic diseases]. 804 22

The clinical, biochemical, morphological, and evolutive features of autoimmune hepatitis associated with serum smooth muscle antibodies of anti-actin specificity were retrospectively analyzed in 31 children and adolescents. Cirrhosis was present at diagnosis in all but six patients, including nine of the 12 diagnosed within 6 months from the onset. In 15 children, one or more associated diseases of an immune-mediated mechanism were present, including chronic arthritis, sclerosing cholangitis, inflammatory bowel disease, and cutaneous vasculitis. All patients were treated with prednisone and azathioprine with normalization or improvement of liver function tests: 28 children are currently alive after a mean follow-up of 4 years, 10 months. Treatment was interrupted in four patients only. Two patients died of liver failure in spite of immunosuppressive therapy before the era of liver transplantation. In spite of prolonged therapy, five other patients ultimately required liver transplantation during adolescence or early adulthood. These results (a) further define a group of autoimmune hepatitis in children characterized by the presence of serum anti-actin antibodies; (b) indicate that immunosuppressive therapy improves liver function, although in most cases it must be continued for a long period to maintain remission; and (c) suggest that progressive liver failure may occur in early adulthood and may require liver transplantation.
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PMID:Autoimmune hepatitis associated with anti-actin antibodies in children and adolescents. 814 91

Uveitis may be an asymptomatic ocular process when it occurs in association with chronic inflammatory bowel disease (IBD). However, the frequency of uveitis in pediatric IBD is not known, as few patients have eye examinations on a routine basis. Experience with a child with Crohn's disease, who had asymptomatic uveitis identified by routine screening initiated because of associated arthritis, prompted us to undertake this evaluation. The purpose of this cross-sectional prospective study was to ascertain the point-prevalence of uveitis in pediatric IBD patients, including 97 with Crohn's disease and 50 with ulcerative colitis. Each child underwent an ophthalmologic assessment, including slit-lamp examination. In Crohn's disease, inflammatory cells and/or flare were observed in the anterior chamber of six (6.2%) patients. These changes were mild in all six patients and required no treatment. In the group with ulcerative colitis, there were no cases of asymptomatic uveitis. There was a higher frequency of asymptomatic transient uveitis in patients with Crohn's colitis (four of 22, 18.2%) than in those of other anatomic subgroups (two of 75, 2.7%; p < 0.05). Frequency of uveitis was also higher in IBD patients having other extraintestinal manifestations (15.0%) than in those without (3.1%; p < 0.10). There was no relationship observed between the activity of bowel disease and presence of ocular inflammation.
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PMID:Asymptomatic uveitis in children with chronic inflammatory bowel diseases. 814 95

The construction of an ileoanal pouch in patients who have undergone total colectomy for ulcerative colitis is claimed to be associated with the development of arthritis. The pattern and prevalence of reported musculoskeletal symptoms in the 15 patients with ileoanal pouches attending our hospital was not significantly different to a control group of 60 patients with an ileostomy for inflammatory bowel disease. There was no clinical or serological evidence of arthritis in the eight patients from the study group reporting symptoms. We conclude that the majority of symptoms occurring following pouch construction are not attributable to an inflammatory arthropathy.
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PMID:Is the construction of an ileoanal pouch associated with the development of arthritis? 816 62

Idiopathic inflammatory bowel disease include basically two disorders: ulcerative colitis and Crohn's disease. Both diseases are chronic and of unknown etiology and extraintestinal manifestations are seen in a high number of these patients. We studied 18 patients (7 female, 11 male) with previous diagnosis of inflammatory bowel disease (14 ulcerative colitis, 2 Crohn's disease, 1 pancolitis, 1 ulcerative proctitis) in order to search for extraintestinal manifestations with emphasis on osteoarticular and ocular involvement. The mean age at the time of diagnosis of the inflammatory bowel disease was 44 years (range 20 to 71 years). Mean time duration of the inflammatory bowel disease was 7 years (range 1 to 24 years) and of the articular manifestations 3.2 years (range 1 to 8 years). The osteoarticular manifestations developed after the diagnosis of the bowel disease in all but one patient (simultaneously) 17/18 patients had artralgias, 7/18 lumbalgia, 3/18 talalgia, 1/18 knee arthritis. (table I) Only six of the 17 patients with orteoarticular involvement has simultaneous activity of the underlying bowel disease. All the 18 patients were taking 2 g/day of sulfasalazine. Radiographic screening in all patients revealed sacroiliitis in 10. (table II) Of the 10 radiographic sacroiliitis 4 were grade I (confirmed by technetium phosphate scans, 2 were grade II and 4 grade III-IV. Three of the ten patients with radiographic sacroiliitis were asymptomatic (table II). Axial computed tomography was performed done in two patients: a) in one case to exclude osteitis condensens ilii, and b) in the other case to exclude septic arthritis. The severity of the sacroiliac damage was related with a longer duration of the inflammatory bowel disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Articular and extraarticular involvement in inflammatory bowel diseases]. 829 15


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