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

Non-steroidal anti-inflammatory drug (NSAID)-induced increased small-intestinal permeability appears to be a prerequisite for the development of NSAID enteropathy, which is a cause of much morbidity in patients with rheumatoid arthritis. We assessed, with a combined absorption-permeability test, the effects of Carbopol (a polyacrylic acid polymer capable of increasing mucus strength and viscosity) on intestinal function and whether it protected against indomethacin-induced increased intestinal permeability. Using a test solution of 3-0-methyl-D-glucose, D-xylose, L-rhamnose, and 51Cr-labelled ethylenediaminetetraacetic acid with 5-h urine collections for marker analyses, we tested 16 subjects, as base line, after 20 ml Carbopol 4 times daily for 4 days, after indomethacin alone (75 + 75 mg), and after coadministration of Carbopol and indomethacin. Carbopol had no significant effect on the permeation or absorption of the test substances. Indomethacin increased intestinal permeability significantly, and this was unaffected when Carbopol was coadministered with indomethacin, showing that Carbopol does not limit the immediate damage of NSAIDs on the small intestine.
 ...
PMID:The effect of polyacrylic acid polymers on small-intestinal function and permeability changes caused by indomethacin. 189 8

Increased small intestinal permeability caused by non-steroidal anti-inflammatory drugs (NSAIDs) is probably a prerequisite for NSAID enteropathy, a source of morbidity in patients with rheumatoid arthritis. This increased small intestinal permeability may be a summation of a local effect during drug absorption, a systemic effect after absorption, and a local effect of the drug excreted in bile, but the relative contribution made by these factors is unknown. We assessed the effect of indomethacin and nabumetone on intestinal permeability. The principal active metabolite of nabumetone, 6-methoxy-2-naphthylacetic acid, is not subject to appreciable enterohepatic recirculation. Twelve volunteers were studied before and after one week's ingestion of indomethacin (150 mg/day) and nabumetone (1 g/day) with a combined absorption/permeability test. Neither drug had a significant effect on the permeation of 3-0-methyl-D-glucose, D-xylose, and L-rhamnose. Indomethacin increased the permeation of radioactive 51chromium ethylenediaminetetra-acetic acid (51Cr EDTA) significantly from baseline (mean (SEM) 0.63 (0.09)% v 1.20 (0.14)%, p less than 0.01) but nabumetone did not (0.70 (0.10)% p greater than 0.1). These results were supported by the 51Cr EDTA/L-rhamnose urine excretion ratios, which reflect changes in intestinal permeability. They suggest that NSAIDs increase intestinal permeability during absorption or after biliary excretion and that the systemic effect is of minor importance.
 ...
PMID:Importance of local versus systemic effects of non-steroidal anti-inflammatory drugs in increasing small intestinal permeability in man. 190 63

Interleukin 1 (IL-1) exerts biological properties on various immune and nonimmune cell types and tissues and thus may play an important role during chronic inflammatory processes. Here we have examined the IL-1 biosynthesis in adherent synovial lining cell (ASLC) cultures obtained from patients with rheumatoid arthritis (RA). We report that ASLCs in culture showed heterogeneous endogenous levels of IL-1 alpha and beta expression. Recombinant interleukin 1 (rIL-1) alpha or beta induced increases of IL-1 alpha and beta mRNA and proteins levels in ASLCs. Although IL-1 synthesis is enhanced by rIL-1 treatment, no soluble IL-1 alpha or beta could be detected by specific enzyme-linked immunosorbent assays. A pretreatment with recombinant IFN gamma (rIFN gamma) down-regulated the effect of rIL-1 on IL-1 synthesis in ASLCs. Actinomycin D suppressed the endogeneous and rIL-1-induced IL-1 mRNA expression Indomethacin, in the presence of rIL-1 alpha or beta, up-regulates the level of expression of IL-1 beta in ASLCs pretreated with rIFN gamma, but has the opposite effect in non-pretreated cells. The increase of IL-1 gene expression by rIL-1 in human ASLCs from RA patients may contribute as an amplification of the disease progress. These studies may also explain the beneficial effects of IFN gamma in experimental models of IL-1-induced bone and cartilage degradation and in patients with diseases involving IL-1.
 ...
PMID:Autocrine stimulation of interleukin 1 in human adherent synovial lining cells: down regulation by interferon gamma. 191 93

We studied the upper gastrointestinal (GI) tract lesions by endoscopy, and evaluated the relationship between the lesions and clinical characteristics in 154 patients with rheumatoid arthritis (RA). Eighty-six (55.8%) had drug-induced ulcers and/or erosions, which were present mostly at the antrum as multiple lesions. A history of gastric ulcer, positive tests for fecal occult blood and progression of anemia were noticed more frequently in the patients with gastric ulcers and/or erosions, compared to those with normal mucosa. Indomethacin and prednisolone (15mg/day) were also used more frequently in the patients with gastric ulcers. Twelve patients showed amyloid depositions in the gastric mucosa, of which 8 patients had gastric ulcers and/or erosions. These results indicate that the incidence of GI tract lesions is significantly high in RA patients and that the endoscopic examination should be performed during the course of RA treatment.
 ...
PMID:[Upper gastrointestinal tract lesions in rheumatoid arthritis]. 194 53

Indomethacin, which is thought to exert its therapeutic effect by inhibiting the synthesis of PGE2, is a commonly used first-line agent in the treatment of rheumatoid arthritis (RA). However, the effect of this drug on the humoral immune response in RA remains unclear. In this study, modulation of the in vitro synthesis of IgM and IgM-rheumatoid factor (RF) by indomethacin and prostaglandin E2 was examined in 11 patients with active RA and 10 normal controls. Indomethacin at a final concentration of 1 microgram/ml significantly enhanced IgM production (P less than 0.01) and RF production (P less than 0.02) in Staphylococcus aureus Cowan I (SAC) stimulated RA cultures when compared to controls in whom no net enhancement effect was observed. In the patients, this increase in IgM production was more pronounced than the corresponding increase in RF synthesis (P = 0.078), suggesting that IgM and IgM-RF-secreting RA plasma cells have different susceptibilities to PGE2 mediated suppression. Nonetheless, addition of PGE2 (10(-8) M final concentration) to the cultures inhibited IgM and RF production to a similar degree in the patient and control cultures. These findings demonstrate that PGE2 causes suppression of IgM and IgM auto-antibody production in vitro and that inhibition of endogenous PGE2 synthesis in RA patients treated with indomethacin results in a marked increase in the production of these antibodies.
 ...
PMID:Induction of IgM and IgM-rheumatoid factor synthesis in vitro by indomethacin. 204 81

Prostaglandin E1 (PGE1) and oils enriched in its precursor fatty acids suppress inflammation and joint tissue injury in several animal models. Since synovial cell proliferation is a hallmark of rheumatoid arthritis, we studied the effect of dihomo-gamma-linolenic acid (DGLA), an immediate precursor of PGE1, on the growth of human adherent synovial cells (ASC) in tissue culture. When stimulated by appropriate concentrations of recombinant interleukin-1 beta (rIL-1 beta), ASC proliferate and produce PGE. DGLA-enriched medium suppressed both baseline and rIL-1 beta-stimulated ASC growth fivefold, compared with medium supplemented with arachidonic acid. Indomethacin reduced the effect of the DGLA. Synovial cells incorporated the DGLA, and rIL-1 beta-stimulated cells that were incubated with DGLA exhibited a 14-fold increase in PGE1 (to 25.2 +/- 6.0 ng/ml, mean +/- SD) and a 70% decrease in PGE2 (to 25.2 +/- 4.2 ng/ml) compared with cells in control medium. At equivalent concentrations (5 x 10(-7) M), PGE1 increased the level of cellular cAMP to a greater extent than did PGE2 (16.8 +/- 2.0 pmoles versus 4.3 +/- 1.9 pmoles, mean +/- SEM). Exogenous PGE1 was also a more effective inhibitor of cell growth. Similarly, cAMP concentrations in cells exposed to DGLA for 6 hours were greater than concentrations in arachidonic acid-enriched cultures (17.8 +/- 3.3 pmoles versus 2.1 +/- 2.0 pmoles). These observations suggest that DGLA can restrain ASC growth, an effect which may be due to its capacity to increase PGE1 production and subsequent cellular cAMP concentration.
 ...
PMID:Suppression of human synovial cell proliferation by dihomo-gamma-linolenic acid. 255 25

When activated in autologous mixed leukocyte reactions (auto-MLR) in vitro, T cells from normal individuals produce a suppressor factor(s) which inhibits the Epstein-Barr virus (EBV)-induced proliferation of normal B cells. In contrast, T cells from patients with rheumatoid arthritis (RA) are deficient in their ability to generate this suppressor factor in auto-MLR. Addition of tilomisole (Wy-18,251; 33(p-chlorophenyl)thiazolo[3,2-a]benzimidazole-2-acetic acid) to the auto-MLR (0.1-100 micrograms/ml) did not alter the production of suppressor activity by normal T cells, but 100 micrograms/ml tilomisole restored to normal the defective factor production by RA T cells. Indomethacin (1 microgram/ml) but not levamisole (0.1-100 micrograms/ml) had a similar effect, which suggests that the action of tilomisole in this system is due to its ability to inhibit prostaglandin biosynthesis. Nonetheless, the ability of tilomisole to down-regulate B cell function may contribute to the compound's antiarthritic activity.
 ...
PMID:Effects of tilomisole, indomethacin and levamisole on regulation of Epstein Barr virus-induced B cell proliferation by peripheral blood mononuclear cells from normal individuals and patients with rheumatoid arthritis. 282 78

Despite the extensive use of sulfasalazine (SAS) and/or 5-aminosalicylic acid (5-ASA) in patients with inflammatory bowel disease and, more recently, rheumatoid arthritis, their mode of action has not been elucidated so far. None of the numerous pharmacological and biochemical effects described, including immunosuppressive, antifolate, and modulatory actions on lymphocyte and leukocyte functions, could be defined unequivocally as mediating their beneficial activity. Recently, interest has focused on actions of SAS and 5-ASA on the various enzymes of the arachidonic acid cascade. Mucosa of patients with inflammatory bowel disease generates excessive amounts of cyclooxygenase products such as prostaglandins (PG) as well as 5-lipoxygenase products such as leukotriene (LT) B4 and sulfidopeptide-LT. Both PG and LT exert proinflammatory actions and are potentially important mediators of mucosal inflammation. SAS and 5-ASA, however, have been found to inhibit PG synthesis under certain experimental conditions only, while increasing PG formation under other conditions. While SAS was found to inhibit colonic LTB4 synthesis, 5-ASA was reported to selectively affect the cyclooxygenase pathway of arachidonate metabolism in this tissue. Our results demonstrate that, like the parent compound, the metabolite 5-ASA in a dose-dependent manner inhibits release of LTB4 and sulfidopeptide-LT from normal human colonic mucosa (IC50 3.5 and 3.7 mmol/liter, respectively). Indomethacin, which has no efficacy in the treatment of patients with inflammatory bowel disease, on the other hand, selectively inhibited PGE2 formation in normal and inflamed colonic mucosa (IC50 1.7 and 1.0 mmol/liter, respectively) without reducing synthesis of LTB4 or sulfidopeptide-LT.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Possible mode of action of 5-aminosalicylic acid. 289 68

Human PHA-stimulated mononuclear cells produce a factor which inhibits synovial cell collagen and non-collagen protein synthesis, whereas it enhances hyaluronic acid (HA) production. Indomethacin (10(-4)-10(-6) M), a cyclo-oxygenase inhibitor, suppresses this effect, suggesting that the mechanism is prostaglandin-mediated. The active material, of apparent molecular weight 12 000-20 000, also displays the properties of the mononuclear cell factor (MCF) previously described by others, since its stimulates collagenase and PGE2 release by the cultured synovial cells. Furthermore, it co-purifies with interleukin 1 (IL 1) as shown by lymphocyte-activating factor activity. This strongly suggests that IL 1 could be responsible for some (or all) the effects observed on MCF-exposed synovial cells. From these data, we deduce the possibility that mononuclear cells may participate in limiting synovial collagen deposition in rheumatoid arthritis.
 ...
PMID:Mononuclear cell-mediated modulation of synovial cell metabolism. I. Collagen synthesis. 298 10

In a group of 70 patients of both sexes been treated with antiinflammatory drugs, affected by Rheumatoid Arthritis in activity, we have found the presence of lesions, erosions and gastroduodenal ulcers in 40% by endoscopic examination (26% erosions and 14% ulcers), without any relation with clinical symptoms. Those patients who received larger doses than 30mgr./kg./day of AAS suffered most frequently lesions (43.8%). These 28 patients with lesions have been studied prospectively in a double blind method, and treated twice a day with 150 mgs. doses of Ranitidine or Placebo, throughout a period of 5 weeks without discontinuing the treatment with anti-inflammatories (AAS, Indomethacin, steroids). At the end of the trial those patients who failed in healing their lesions were treated with Ranitidine in the same doses for another period of 5 weeks. The treatment with Ranitidine in doses of 300 mgr/day has resulted curative of the gastroduodenal lesions, although maintaining the aggressive drugs, in the 87% of the patients. We have observed that the treatment with Placebo is less effective and that difference has high statistical significance (p 0.005).
 ...
PMID:[Gastroduodenal lesions in rheumatoid arthritis. Evaluation and treatment]. 307 9


<< Previous 1 2 3 4 5 6 7 Next >>