Chronic inflammatory polyarthriti

There is a long-standing hypothesis that the microvasculature plays a pathological role in forms of chronic inflammatory polyarthritis, particularly RA (Rothschild and Masi, 1982). One of the proposed mechanisms of vascular damage in connective tissue disease is the direct action of a cytotoxic serum factor inducing endothelial cell damage. Blake et al. (1985) have su ested that the vascular abnormalities associated with RA may be linked to oxidized lipoproteins because they are cytotoxic to endothelial cells. 

Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory joint disease. It is a progressive symmetrical, destructive and deforming polyarthritis affecting proxi-... 

Two commonly used models to detect anti-inflammatory activity are carrageenan-induced paw edema and adjuvant-induced polyarthritis in rats. The former represents an acute and the latter a chronic inflammatory process. Non-steroidal anti-inflammatory agents inhibit the formation of carrageenan-induced paw edema. However, to detect activity in the developing and established phases of chronic inflammation, the polyarthritis model is well accepted. In both tests the measured endpoint is volume of the hind paw. This is done by immersing the hind paw in the well of a mercury displacement... 

Rheumatoid arthritis (RA) is the commonest inflammatory and destructive arthropathy in the world with a prevalence of 1000 per 100000. It is characterized by a chronic symmetrical polyarthritis that leads to joint damage in most patients. The commonest affected joints are the small joints of the hands and feet but it can involve any synovial joint. Rheumatoid factor is present in over 70% of the patients. The long-term prognosis of RA is poor as most patients develop significant disability despite treatment (1). Hence it is a major socio-economical burden. In the UK, the cost of RA was estimated at 1.3 bUlion/year in 1992 (2). 

Clinical use Phenylbutazone (Brogden, 1986) is a nonsteroidal anti-inflammatory drug used for the acute treatment of ankylosing spondylitis, chronic polyarthritis and gout. Phenylbutazone on its own shows only weak inhibition of COX-1 and COX-2 with IC50s >30 pM (Brideau et al., 1996) and active metabolites are mainly responsible for its actions. 

In contradistinction to the various types of chemically-induced and anaphylactic arthritis which have been mentioned above, adjuvant arthritis appears to simulate closely the inflammatory reactions seen in rheumatoid arthritis in humans. Stoerk, Bielinski and Budzilovitch first reported the development of a chronic polyarthritis in rats, and this work was later elaborated by a number of other workers " . The reaction seems to be a type of delayed hypersensitivity response , although recent work suggests that this may not be so. ... 

Miscellaneous - Specific amino acids have been studied for anti-inflammatory activity. Thus, the combination of calcium D,L-aspartate/indometha-cin has been repor gd to be effective in primary chronic polyarthritis Dilauroyl-L-lyslne and trans U-aminomethyl-cyclohexane-l-carboxylic acid (tranexamic acid) have anti-inflammatory properties. The activity of tranexamic acid was not attributed to anti-plasmin action. Detailed pharmacology on SKF 17,910-A (X) has been published. This anti-inflammatory and diuretic agent shares some biological properties with glucocorticoids. 

Several small uncontrolled pilot studies have indicated that most patients with psoriatic arthritis improve when treated with etretinate at 0.5-1 mg/kg/day (Brackertz and Muller, 1979 Rosenthal 1979 Stollenwerk et al., 1981 Kaplan etal., 1983). In one report the etretinate-induced improvement allowed patients to decrease or discontinue their use of nonsteroidal anti-inflammatory agents. In another report patients with chronic polyarthritis similarly improved. RePUVA also led to improvement in five of six patients with psoriatic arthritis. However, because healing of cutaneous lesions of psoriasis with PUVA is associated with an improvement in joint disease, controlled studies are needed to confirm that etretinate is effective in psoriatic arthritis and that the effect is not secondary to cutaneous improvement. 

The presence of acute inflammatory manifestations (i.e., erythema nodosum, polyarthritis, and fever), termed Lofgren s syndrome, portends an excellent prognosis, with high rates (>85%) of SRs (9,14,33,37,38). Conversely, the following factors were associated with a worse prognosis in sarcoidosis age onset >40 years (9,36), hypercalcemia (9), extrathoracic disease (9,20), lupus pernio (9), splenomegaly (36), pulmonary infiltrates on chest radiograph (9,36), chronic uveitis, cystic bone lesions, nasal mucosal sarcoidosis (9), and lower annual family income (14). 

In rat models of acute inflammation and chronic arthritic inflammation, oral administration of extracts (alcohol and supercritical fluid) of wild, green celery seed suppressed NSAID-and ethanol-induced gastric injury, whereas against ibuprofen-induced gastrotoxicity, most commercial flavorant celery seed oils (derived from aged, brown seeds) were inactive. A similar outcome was found from celery seed products in a rat model of polyarthritis, some being effective anti-inflammatories (notably one made from wild, green seeds), whereas the majority were ineffective. ... 

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