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)

Sodium aurothiomalate (ATM), gold keratinate and five different tetracyclines were investigated for activity against M. arthritidis strain ATCC 14124 and M. pulmonis strain JB, both in vitro and in rodents with arthritis caused by these mycoplasmas. In vitro, ATM had only slight activity against M. arthritidis and M. pulmonis, while gold keratinate was virtually inactive against M. pulmonis. In contrast, the tetracyclines were highly active against both mycoplasmas. The tetracyclines and the gold salts were both predominantly mycoplasmastatic. In both rats and mice, parenteral administration of ATM, begun shortly before or after infection of rodents with mycoplasmas, prevented the development of arthritis. ATM or gold keratinate, given subcutaneously to mice already arthritic from infection with M. pulmonis, reduced the severity of the arthritis, even although gold keratinate was inactive aganist this mycoplasma in vitro. Moreover, direct testing of serum, collected from mice treated with gold keratinate, failed to demonstrate antimycoplasmal activity in vitro. These results suggest that the action of gold-containing drugs in mycoplasmal arthritis is due to biological properties of gold other than antimycoplasmal activity. Tetracyclines were also found to be effective in preventing arthritis in rats and mice when given subcutaneously. With high doses, subcutaneous, but not oral, therapy significantly reduced the severity of established arthritis in mice infected with M. pulmonis. The blood levels achieved with the different tetracyclines, when related to their therapeutic activity, indicated that good antimycoplasmal activity and adequate absorption from the gut were not the only properties needed for optimal effectiveness. The results are discussed in relation to treatment of rheumatoid patients with tetracycline HCl.
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PMID:Sodium aurothiomalate, gold keratinate, and various tetracyclines in mycoplasma-induced arthritis of rodents. 40 75

A slow-release zinc complex, zinc monoglycerolate (ZMG) was examined for its potential gastroprotective activity in various gastric ulcer models. These models comprised (a) oral or parenteral non-steroidal anti-inflammatory drugs (NSAIDs) given to rats whose gastrointestinal mucosa was pre-sensitized by prior development of arthritis, oleyl alcohol-induced inflammation and cold exposure, (b) oral ethanol (12.5-100%) with and without added 4% HCl, (c) intraperitoneal reserpine (5 mg kg-1) in arthritic and normal rats and in normal mice, (d) oral NSAIDs given to mice in which acid and pepsin production was stimulated by co-administration of intraperitoneal bethanechol chloride (5 mg kg-1) to enhance ulcer development, and (e) NSAIDs given to carrageenan-inflamed rats to determine effects of ZMG on paw inflammation. In these models, ZMG given orally was effective in preventing development of gastric lesions, except with propionic acid NSAIDs; the effective doses being apparently dependent on the severity of the mucosal injury. In many of the models ZMG was superior to zinc sulphate and other zinc salts or metal ion complexes investigated but was slightly more effective or equipotent compared with zinc acexamate. ZMG did not impair the anti-oedemic effects of NSAIDs. ZMG is thus an effective agent in preventing ulcer development in a wide range of model systems and may be more effective than zinc salts because of the controlled slow-release of zinc from the complex.
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PMID:Anti-ulcer activity of a slow-release zinc complex, zinc monoglycerolate (Glyzinc). 135 71

Anti-inflammatory, analgesic and anti-pyretic activities of orally administered TA were investigated in experimental animals. Against acetic acid-induced vascular permeability in mice, carrageenin-induced hind paw edema in rats and ultra-violet ray-induced erythema in guinea pigs, TA produced a dose related inhibition at doses of 40-160 mg/kg, 10-40 mg/kg and 10-40 mg/kg, respectively. TA produced no inhibition against histamine-induced vascular permeability even at a dose of 200 mg/kg in rats. Cotton pellet-induced granuloma and adjuvant-induced arthritis in rats were significantly inhibited by repeated administration of TA at a dose of 50 mg/kg/day for 6 days and 25 mg/kg/day for 6 days, respectively. TA showed a dose related analgesic effect at a dose of 50-200 mg/kg in acetic acid writhing, Randall-Selitto and adjuvant arthritic pain methods. A high dose of TA was needed to produce an analgesic effect in the pressure method using mice. TA produced an anti-pyretic effect against the pyrexia induced by yeast in rats. On the other hand, TA showed no effect against normal body temperature in rats. These results suggest that anti-inflammatory, analgesic and anti-pyretic activities of TA are generally a little weaker than those of ibuprofen, and the mode of action of TA is similar to that of a typical acidic non-steroidal anti-inflammatory drug such as ibuprofen, indomethacin or phenylbutazone. The ulcerogenic activity of TA was about 2 and 4 times weaker than that of ibuprofen in rats and mice, respectively. TA showed a protective effect against gastric necrosis induced by HCl.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Anti-inflammatory, analgesic and anti-pyretic activities of a new anti-inflammatory compound, 2-[4-(3-methyl-2-butenyl)phenyl] propionic acid (TA), in experimental animals]. 349 51

High-density cultures of chick embryonic chondrocytes were exposed to intermittent compressive force (ICF) of physiologic magnitude for 24 hours. Proteoglycan synthesis was significantly increased in chondrocyte cultures exposed to ICF as compared with control cultures. Similar effects were found in explants of epiphyseal cartilage. Proteoglycans extracted with guanidine-HCl from cultures exposed to ICF aggregated better with hyaluronic acid than did control cultures, as shown by Sepharose 2B gel chromatography. In addition, the amount of non-extractable proteoglycans was increased in ICF cultures. We conclude that ICF not only increases the synthesis of proteoglycans but also improves the aggregating capacity of proteoglycans and the coherence of proteoglycans with other matrix components. High-density cultures of epiphyseal chondrocytes provide a suitable model to study the processes involved in the perception of and the subsequent cellular response to compressive force by cartilage.
Arthritis Rheum 1985 Apr
PMID:Cartilage response to mechanical force in high-density chondrocyte cultures. 398 7

Two distinct nuclear antigens, designated NSpI and NSpII, have been characterized and differentiated from the centromeric antigen that reacts with sera from patients with the CREST syndrome. Both NSpI and NSpII produce a speckled pattern of indirect immunofluorescence on HEp-2 cells that resembles the pattern seen with anticentromere antibodies (ACA). They are differentiated from the ACA staining pattern by the absence of metaphase chromatin staining by NSpI antisera and by the absence of a discrete speckled pattern of staining by NSpII. Further, both NSpI and NSpII stain predominantly the peritubular nuclei of mouse kidney cryostat sections. NSpII is sensitive to trypsin, proteinase K, and HCI extraction, suggesting that it is a relatively soluble nuclear protein. NSpI was also sensitive to protease treatment but was not extracted with 0.1N HCl, suggesting that it is a tightly bound nuclear protein.
Arthritis Rheum 1984 Jan
PMID:Speckled pattern antinuclear antibodies resembling anticentromere antibodies. 619 78

D-Penicillamine (D-PA), 80-100 mg/kg/day enhanced the early phase of adjuvant arthritis (AA) in rats when it was administered orally for about 4 weeks after the adjuvant injection day, whereas dexamethasone (1 mg/kg/day, p.o.) and chloroquine diphosphate (25 mg/kg/day, p.o.) inhibited AA in the same dosing regimen. On the other hand, subcutaneous injection of sodium aurothiomalate (12.5 mg/kg/day) enhanced AA initially, but inhibited it later. The enhancing effect of D-PA on the early phase of AA was observed also at doses of 50 mg/kg/day and 200 mg/kg/day, but, in the case of 200 mg/kg/day, inhibited the later phase of AA. When the administration of D-PA was started before the adjuvant injection, it showed a tendency to suppress AA on proportion to the dosing period. The effect of D-PA, however, was not observed in the model when the drug administration was started after the establishment of arthritis. The co-administration pyridoxine HCl did not influence the effect of D-PA on AA. A good correlation was not obtained between the inflammatory score and the PPD induced skin reaction, serum metals level and histopathological changes of lymph node in the AA rats treated with D-PA. Thus the effect of D-PA on AA was related to dose, timing and duration of the administration. It was suggested that the enhancing and inhibitory effects of D-PA on AA were not based on vitamin B6, depletion, but rather were caused by inhibition of T1 and T2 lymphocytes which may be regulating this arthritis process.
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PMID:[Studies of D-penicillamine (5): effects on rat adjuvant arthritis (author's transl)]. 679 66

Sera from 10 patients with juvenile arthritis (JA), 2 seropositive and 8 with hidden rheumatoid factor (RF), were subjected to affinity chromatography on a rabbit anti-human IgM column. Material retained by the column was eluted sequentially by 1M NH3 and 0.1M glycine-HCl buffer, pH 3.0. The affinity fractions contained both 19S IgM RF and IgG, while corresponding fractions from healthy controls contained neither. Sera from 15 patients with JA, 1 seropositive and 11 with hidden RF, were subjected to 4% polyethylene glycol precipitation followed by acid dissociation of the precipitate. Ten of 15 resultant fractions contained both IgM RF and IgG, while corresponding fractions from healthy controls contained only traces of IgG. Sera from 7 of these JA patients were subjected to sucrose density gradient centrifugation and the resultant fractions analyzed for the presence of immune complexes by the C1q solid-phase assay. Immune complexes were detected at and ahead of the IgM marker, as expected for IgM RF-IgG complexes. These combined data show that the majority of JA patients with classic or hidden 19S IgM RF have immune complexes containing IgM RF and IgG in their sera.
Arthritis Rheum 1983 Feb
PMID:Separation and characterization of immune complexes containing 19S IgM rheumatoid factor-IgG in juvenile arthritis. 682 13

1. An enzyme that degrades proteoglycan at neutral pH was extracted with 4 M-guanidine hydrochloride from the articular cartilage of rabbits with antigen-induced arthritis. 2. The enzyme had an apparent molecular weight on Ultrogel AcA 54 of about 8000 and was optimally active at pH 7.5 in Tris/HCl buffer containing 0.2 M-NaCl. The partially purified preparation was totally inhibited by 0.01 mM-N-acetyldialanylprolylvalylchloromethane, severely inhibited by 2 mM-phenylmethanesulphonyl fluoride and soya-bean trypsin inhibitor (200 microgram/ml) and slightly inhibited by 10 mM-EDTA. Marked inhibition was also obtained with a cytosolic fraction prepared from rabbit polymorphonuclear leucocytes. 3. All properties of the enzyme were virtually identical with those of an 'elastase-like' proteinase that was isolated from rabbit polymorphonuclear-leucocyte granules. 4. The results are consistent with the idea that cartilage proteoglycan degradation in acute joint inflammation is due at least partly to the diffusion into the cartilage of proteinases derived from synovial-fluid polymorphonuclear leucocytes.
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PMID:Evidence for polymorphonuclear-leucocyte-derived proteinases in arthritic cartilage. 703 Mar 7

Investigative attempts to identify novel therapy for inflammatory connective tissue diseases continue to evolve. Amiprilose hydrochloride (amiprilose HCl) is a synthetic carbohydrate shown to have anti-inflammatory effects in animal models of inflammatory arthritis and in a multicenter clinical trial. Interleukin-1 (IL-1) is an important mediator of immune regulation, inflammation and joint destruction in arthritis. In the present study, the effects of amiprilose HCl on IL-1 activity, production and receptor distribution were investigated. Drug effects on IL-2 production and receptor distribution on lymphocytes were also explored. Potential regulation of IL-1 activity was determined by monitoring the effects of amiprilose HCl on IL-1 stimulated proliferation of murine thymocytes and human synovial cells. Inhibitory effects on IL-1 beta and IL-2 production by stimulated human peripheral blood monocytes were measured by ELISA and lymphocyte IL-1 beta and IL-2 receptor distribution were analyzed by flow cytometry. The results from in vitro studies demonstrated that low concentrations of amiprilose HCl (1-100 micrograms/ml) stimulated thymocyte proliferation and enhanced the proliferative response of IL-1 stimulated human synovial fibroblasts. IL-1 beta production in cultures of human peripheral blood monocytes was significantly decreased after exposure of the cultures to varying doses of amiprilose HCl as determined by ELISA. Exposure of mitogen activated human peripheral blood lymphocytes to amiprilose HCl resulted in decreased IL-2 production at high concentrations of drug as compared to control. However, at doses of amiprilose HCl previously found to stimulate thymocyte proliferation (1-10 micrograms/ml), increased levels of culture supernatant IL-2 were observed. No amiprilose HCl mediated changes in lymphocyte IL-1 beta or IL-2 receptor expression were observed. The regulatory effects of amiprilose HCl on cytokines support the potential of this drug as a therapeutic agent for the treatment of inflammatory arthritis.
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PMID:Immunoregulatory effects of a synthetic monosaccharide. 857 39

Cam-2445 is a selective, high-affinity NK1 receptor antagonist that is a potentially useful treatment for arthritis, asthma, migraine, anxiety, psychosis, and emesis. Cam-2445 exhibits low aqueous solubility and high lipophilicity and has a molecular weight of 470. Cam-2445 has poor oral bioavailability and the purpose of this research was to examine the potential barriers to the oral bioavailability of Cam-2445. Cam-2445 was relatively stable at 37 degrees C in 0.1 N HCl, 5 microM alpha-chymotrypsin, rat intestinal perfusate, and in rat jejunal brush border membrane suspension. High permeability was observed from CACO-2 cells and from rat single-pass intestinal perfusions. Cam-2445 was administered as a solution to rats by intravenous (i.v.), oral (p.o.), intraduodenal (i.d.), and intraportal (i.p.v.) routes. The total oral bioavailability was poor at 1.4%. Absorption appeared to be rapid after i.d. dosing; bioavailability was 26%, and 54% of the dose was absorbed intact into the portal system. After i.p.v. dosing, 48% of the dose was available to the systemic circulation. The elimination t1/2 after i.d. dosing (2.91 h) was comparable to that i.v. dosing (2.93 h), whereas it was significantly longer after p.o. dosing (12.4 h). The p.o. dose apparently precipitated in the gastrointestinal (GI) tract, resulting in low oral bioavailability. These results indicated that neither stability in the GI tract nor membrane transport were major obstacles to the absorption of Cam-2445. While hepatic extraction of 52% was significant, the low aqueous solubility of Cam-2445, as well as the differences noted between p.o. and i.d. studies, strongly support GI dissolution and/or precipitation as the limiting factor for the oral bioavailability of the compound.
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PMID:Absorption of Cam-2445, and NK1 neurokinin receptor antagonist: in vivo, in situ, and in vitro evaluations. 869 23


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