Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mean plasma total tryptophan concentration of 13 long-standing rheumatoid arthritis patients was found to be lower than that of seven nonrheumatoid control subjects, but the plasma nicotinic acid concentration was unchanged. In the rheumatoid patients the urinary excretion of the tryptophan metabolites, kynurenine, xanthurenic acid and 3-hydroxyanthranilic acid, was increased several fold, but the excretion of N-methylnicotinamide was normal. These findings are discussed in relationship to the dietary intakes of tryptophan, nicotinic acid and pyridoxine, the effect of antirheumatoid drugs on plasma tryptophan and liver tryptophan pyrrolase, and requirement of rheumatoid patients for pyridoxine.
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PMID:Metabolic abnormalities of tryptophan and nicotinic acid in patients with rheumatoid arthritis. 15 76

In patients with rheumatoid arthritis neither indomethacin nor aspirin influenced the levels of the erythrocyte sedimentation rate (e.s.r) or serum acute-phase proteins fibrinogen, haptoglobin, C-reactive protein and alphaI acid-glycoprotein). Treatment with D-penicillamine, sodium aurothiomalate, or alclofenac produced a significant reduction both in acute-phase protein levels and in e.s.r. Each of the drugs displaced L-tryptophan from plasma proteins in vivo but withdrawal of indomethacin and aspirin was followed immediatley by excessive binding of this amino acid to circulating proteins:this phenomenon was not observed when alclofenac, sodium aurothiomalate or D-penicillamine were withdrawn. It has been demonstrated that disease activity in rheumatoid arthritis is reflected in acute-phase protein concentrations and in the extent to which L-tryptophan is bount to plasma protein. It is suggested that drugs which profoundly affect these parameters provide not only symptomatic relieft but also possible beneficial effects upon the disease process itself.
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PMID:A study of the influence of various antirheumatic drug regimens on serum acute-phase proteins, plasma tryptophan, and erythrocyte sedimentation rate in rheumatoid arthritis. 23 74

The potential advantage to patients with chronic rheumatic diseases of an effective, non-steroidal analgesic/anti-inflammatory drug which causes insignificant gastric bleeding was a decisive factor leading to the introduction of alclofenac. Short-term double-blind trials showed that alclofenac has analgesic/anti-inflammatory activities equivalent to phenylbutazone, indomethacin and aspirin, but superior to the fenemates and propionic acid derivatives. Long-term controlled studies, ranging from 5 months to 3-1/2 years and using reliable, objective measures revela, however, that patients with rheumatoid arthritis improve in functional status and graduate to less severe classes of disease activity, a phenomenon not observed with either indomethacin or aspirin administered to matched patients over the same periods of time. So far, clinical improvement on alclofenac has been matched only by treatment with gold, D-penicillamine and the immunosuppressive anti-proliferative drugs. This clinical improvement on alclofenac is reflected in haematological and serological indices, and research shows that alclofenac, like these other antirheumatoid drugs, has a pronounced effect upon the acute-phase protein response and the extent to which L-tryptophan is bound to plasma protein. The clinical data reviewed suggest that alclofenac represents an advance in the therapy of the rheumatic diseases.
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PMID:Clinical studies on alclofenac in the treatment of rheumatic diseases: a drug in question. 24 97

Alclofenac and D-penicillamine were compared under controlled, double-blind conditions in the treatment of 35 patients with active rheumatoid arthritis over a period of 26 weeks. The principal aim of the study was to investigate any relationships between changes in clinical status and changes in concentrations of three serum acute-phase proteins (fibrinogen, C-reactive protein, and haptoglobin), plasma free and protein-bound L-tryptophan, and the erythrocyte sedimentation rate. Both alclofenac and D-penicillamine were clearly effective: all patients showed steady improvement on the seven clinical indices of response employed. Drug management was easiest with alclofenac. Both drugs produced a significant reduction in acute-phase proteins, E.S.R. and protein-bound plasma tryptophan. Since it has previously been established that the course of rheumatoid arthritis is reflected in the acute-phase protein levels and the extent to which L-tryptophan is bound to plasma protein, it is suggested that drugs, such as D-penicillamin and alclofenac which profoundly affect these parameters, provide not only symptomatic relief but also possible beneficial effects on the disease process itself.
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PMID:The influence of alclofenac treatment on acute-phase proteins, plasma tryptophan, and erythrocyte sedimentation rate in patients with rheumatoid arthritis. 24 98

The results are presented for the first 11 patients in an on-going 3-month study of 1 g. alclofenac t.d.s. or matching placebo added to the drug regime of patients with active rheumatoid arthritis uncontrolled by full doses of analgesic/anti-inflammatory medication. Two patients dropped out, 1 due to a rash on alclofenac and 1 for incidental reasons. The numbers at this stage are too small for meaningful statistical comparison, but show an apparent trend towards clinical improvement and increase in the free:bound plasma tryptophan ratio in the alclofenac-treated patients. Three acute phase proteins, C-reactive protein, alpha-acid glycoprotein and alpha-1 antitrypsin, were measured. They did not correlate with the E.S.R. and did not appear to be useful additional predictors of disease progression. It is hoped that the results from the rest of the participants in the trial will allow more meaningful discussion of the place of these tests in the assessment of rheumatoid arthritis.
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PMID:The effect of alclofenac on clinical and laboratory measures of disease activity in rheumatoid arthritis: preliminary results. 24 99

Rheumatoid arthritis and schizophrenia have been described in early surveys as mutually exclusive disorders. Such claims are seen as especially interesting in view of: (1) indications that both illnesses often follow prodromes of severe psychological stress, (2) theories regarding hypermethylation of indoleamines producing endogenous psychotogens in schizophrenia, and (3) studies of rheumatoid arthritis reporting excessive binding of L-tryptophan to plasma protein, abnormalities of urinary tryptophan metabolites, decreased serotonin binding capacity of thrombocytes, and decreased MAO activity in joint fluid. Further comparative studies of tryptophan metabolism in schizophrenia and rheumatoid arthritis might enhance knowledge of pathogenesis in either or both diseases.
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PMID:Schizophrenia, rheumatoid arthritis and trytophan metabolism. 65 73

Abnormalities of tryptophan metabolism have been reported in patients with rheumatoid arthritis (RA) and it has been suggested that these abnormalities are the result of disordered vitamin B6 metabolism. Fasting serum pyridoxal, assayed by an automated microbiological system, was found to be below normal in 35 out of 42 patients with RA while a similar abnormality was found in 8 out of 35 patients with osteoarthrosis (OA). Within the RA group the abnormality could not be related to the age, sex, or drug therapy of individuals but of the 8 patients with OA and a low serum pyridoxal, 7 were receiving indomethacin either alone or in conjunction with aspirin.
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PMID:Serum pyridoxal in patients with rheumatoid arthritis. 94 75

Tryptophan metabolites through kynurenine pathway and 5-hydroxytryptophan pathway in the synovial fluid, blood and urine of patients with rheumatoid arthritis and those with osteoarthritis were investigated in order to know the specificity of the tryptophan metabolism, especially the role of serotonin in the joint diseases. A metabolic map of tryptophan in the synovial fluid was also made. It was found that tryptophan in rheumatoid arthritis was metabolized mainly to anthranilic acid through kynurenine in the kynurenine pathway, whereas in osteoarthritis the pathway of kynurenic acid and nicotinic acid was characteristic. Otherwise in 5-hydroxytryptophan pathway there were no significant differences in the levels of 5-hydroxytryptamine and 5-hydroxyindole acetic acid in the synovial fluid between rheumatoid arthritis and osteoarthritis but the activity of monoamine oxidase in the synovial fluid was higher in osteoarthritis than in rheumatoid arthritis.
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PMID:Tryptophan metabolism in the joint diseases. 124 92

We investigated the relationship between use of L-tryptophan and development of eosinophilic fasciitis by two methods: a retrospective patient survey and a case-control study of patients with eosinophilic fasciitis diagnosed at the Mayo Clinic between 1977 and 1989. Before 1986, no traceable patients with eosinophilic fasciitis had taken L-tryptophan. Between Jan. 1, 1986, and July 31, 1989, 8 of 34 patients had ingested L-tryptophan (P less than 0.001). In the case-control study, traceable patients with eosinophilic fasciitis were matched with patients who had systemic sclerosis or rheumatoid arthritis and healthy control subjects who had undergone a general medical examination. Of the 60 matched control subjects, 2 had used L-tryptophan. Thus, the odds ratio was 19, indicating a 19-fold greater likelihood of use of L-tryptophan in patients with eosinophilic fasciitis than in the control group. A retrospective assessment of clinical features, response to treatment, and blinded review of biopsy specimens of skin and fascia in patients who had eosinophilic fasciitis with or without exposure to L-tryptophan disclosed no significant differences in the two groups. This retrospective study confirms a strong association between consumption of L-tryptophan and development of eosinophilic fasciitis in some patients. No clinical or histopathologic features were detected that distinguished this disorder on the basis of previous exposure to L-tryptophan.
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PMID:Eosinophilic fasciitis associated with use of L-tryptophan: a case-control study and comparison of clinical and histopathologic features. 192 98

NAD acts not only as a coenzyme in oxidation-reduction processes but also as substrate for adenoribosylation of different proteins. Patients suffering from rheumatoid arthritis show a disturbance in their tryptophan metabolism. Since tryptophan represents a precursor of NAD we turned our attention to the activity of the ADPR transferase, being the enzyme of adenoribosylation, as well as to the synthesis of NAD derived from nicotinamide in human lymphocytes. Lymphocytes of patients with rheumatoid arthritis did not show any differences in their activities as compared with those of control persons, regardless of different measures applied to the patients.
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PMID:NAD synthesis and ADPR transferase activity in blood lymphocytes of patients suffering from rheumatoid arthritis and of control persons. 259 Nov 27


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