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)

Human polymorphonuclear neutrophil (PMN) granule extract (25 mug of protein) released 60 percent of the available 35SO4 from labeled rabbit articular cartilage in 0.5 hour at neutral pH. N-acetyl-L-alanyl-L-alanyl-L-prolyl-L-alanine choloromethyl ketone (NAcAAPACK), a specific elastase inhibitor, was only minimally effective against whole granule extract, and N-alpha-tosyl-L-lysine chloromethyl ketone, which inhibits trypsin but not elastase, was completely ineffective. Preparative disc-gel electrophoresis of PMN granule extract revealed two separate regions with independent activity against 35SO4-labeled cartilage. One region contained elastases and when tested alone, was completely inhibited by NAcAAPACK. The other contained lysozyme and two esterases active against N-acetyl-L-phenylalanine-alpha-naphthol. Purified lysozyme proved inactive, suggesting that the chymotrypsin-like esterases were responsible for proteoglycan degradation by this region of the gel.
Arthritis Rheum
PMID:Identification of neutral proteases in human neutrophil granules that degrade articular cartilage proteoglycan. 23 25

Fourteen consecutive daily subcutaneous injections of 4 mg/kg of the muramyl dipeptide analogue MDP-Lys(L18) into rats caused arthritis characterized by swelling of the tarsal joint, increases in lymphocytes and monocytes in the peripheral blood, and elevated serum immunoglobulin G (IgG). The present study was performed to evaluate the effects of indomethacin, phenylbutazone, dexamethasone, D-penicillamine, aurothioglucose, cyclophosphamide and cyclosporin A on this arthritis. Administration of indomethacin, phenylbutazone or dexamethasone inhibited the development of the tarsal joint swelling, suggesting that prostaglandins may be involved in the pathogenesis of the arthritis. Cyclophosphamide reduced the arthritis, together with decreases in the lymphocyte count and the serum IgG level. Cyclosporin A worsened the arthritis in a dose-dependent manner and increased the neutrophil count without raising the serum IgG level, but inhibited the induction of adjuvant arthritis in rats with Mycobacterium bacilli. MDP-Lys(L18) may therefore induce arthritis differing in mechanism from adjuvant arthritis.
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PMID:Pharmacological aspects of arthritis induced by a muramyl dipeptide analogue in rats. 144 19

We examined changes of blood cell counts and development of arthritis induced by daily subcutaneous injections of MDP-Lys(L18), an analogue of muramyl dipeptide (MDP), in rats. The numbers of neutrophils markedly increased in the peripheral blood 4 hr after the 1st, 7th, and 14th administrations of MDP-Lys(L18), but they recovered to the control levels within 24 hr. Monocyte and lymphocyte counts increased after the 7th and 14th administrations, respectively, although both decreased after the 1st dosing. Serum inflammatory markers, such as albumin, globulin, mucoprotein, sialic acid, and iron, showed marked changes after the 1st administration. Histopathologically, the synovial membrane of the tarsal joint showed a multilayer arrangement of synoviocytes with vesicular cytoplasms and infiltration of neutrophils from 6 hr after the 1st administration of the drug. The acute synovitis was gradually enhanced until 24 hr later. The synovitis was greatly decreased in degree after the 3rd administration, but increased again later. After the 7th and 14th administrations, mononuclear cells and lymphocytes, respectively, infiltrated the synovial membrane, in a manner corresponding to the hematological findings. However, exudative changes and neutrophilic infiltration were still observed after the 14th drug administration, and the synovitis was repaired after a 7-day recovery period.
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PMID:Arthritis and hematological changes induced by an analogue of muramyl dipeptide in rats. 159 64

A novel cationic immune-complex-mediated arthritis (ICA) model was developed in mice. The highly cationic protein lysozyme was coupled to poly-L-lysine (PLL) and injected intra-articularly into the knee joint of the mouse, shortly after systemic administration of specific antibodies. A vehement joint inflammation developed, characterized by severe joint swelling and the influx of predominantly polymorphonuclear (PMN) leukocyte. Unique properties were combined in this protein. First, an excellent retention of the antigen in joint structures was found, facilitating sufficient IC formation in the synovial tissue and at the cartilage surface. Secondly, PLL.lysozyme appeared to be a potent inducer of interleukin-1 (IL-1). Similar IL-1 production was measured at 6 hours, in both immune or nonimmune mice. Neutralization with antibodies against either IL-1 alpha or IL-1 beta revealed that IL-1 alpha was the dominant cytokine. Resident cells were responsible for this IL-1 production since a comparable IL-1 signal was measured after intra-articular injection of PLL.lys in neutropenic mice. We further investigated whether IL-1 and complement factors were involved in the onset of this ICA. Neutralizing the IL-1 production with antibodies directed against IL-1 alpha and beta showed a significant decrease in joint swelling. Complement depletion by cobra venom factor also prevented the onset of arthritis for the greater part. Only a minor swelling remained at 6 hours after eliciting arthritis, which was similar to the swelling after injecting the antigen alone and probably reflects IL-1 mediated inflammation. In this study, the authors show a synergistic action of IL-1 and complement in the onset of cationic ICA. Unique properties of the antigen such as excellent retention and its ability to induce IL-1 are combined within one molecule and make this antigen arthritogenic in the presence of antibodies and complement activation.
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PMID:Cationic immune complex arthritis in mice--a new model. Synergistic effect of complement and interleukin-1. 160 10

To define the structure of the caprine arthritis-encephalitis virus (CAEV) env gene and characterize genetic changes which occur during antigenic variation, we sequenced the env genes of CAEV-63 and CAEV-Co, two antigenic variants of CAEV defined by serum neutralization. The deduced primary translation product of the CAEV env gene consists of a 60- to 80-amino-acid signal peptide followed by an amino-terminal surface protein (SU) and a carboxy-terminal transmembrane protein (TM) separated by an Arg-Lys-Lys-Arg cleavage site. The signal peptide cleavage site was verified by amino-terminal amino acid sequencing of native CAEV-63 SU. In addition, immunoprecipitation of [35S]methionine-labeled CAEV-63 proteins by sera from goats immunized with recombinant vaccinia virus expressing the CAEV-63 env gene confirmed that antibodies induced by env-encoded recombinant proteins react specifically with native virion SU and TM. The env genes of CAEV-63 and CAEV-Co encode 28 conserved cysteines and 25 conserved potential N-linked glycosylation sites. Nucleotide sequence variability results in 62 amino acid changes and one deletion within the SU and 34 amino acid changes within the TM.
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PMID:Structure and genetic variability of envelope glycoproteins of two antigenic variants of caprine arthritis-encephalitis lentivirus. 165 67

The tuftsin retro-inverso analogue H-Thr psi[NHCO](R,S)Lys-Pro-Arg-OH was synthesized through a novel procedure for the high-yield incorporation of isolated retro-inverso bonds into peptide chains and the use of the new Meldrum's acid derivative (CH3)2C(OCO)2CH(CH2)4NHCOCF3 followed by its efficient coupling in solution to trimethylsilylated H-D-Thr(t-Bu)NH2. Closely related peptide impurities were eliminated both from the crude final peptide and the fully protected tetrapeptide amide precursor via ion-exchange and reversed-phase displacement chromatography, respectively. The tuftsin retro-inverso analogue proved to be completely resistant to enzymatic degradation in vitro, either against isolated aminopeptidases or human plasma proteolytic enzymes. When administered either orally or intravenously, it was significantly more active than normal tuftsin in increasing the number of specific antibody secreting cells in spleen of mice immunized with sheep erythrocytes. Furthermore, the analogue exerted an enhanced stimulatory effect on the cytotoxic activity of splenocytes against YAC-1 tumor cells. Finally, retro-inverso-tuftsin was about 10-fold more potent than the native peptide in reducing rat adjuvant arthritis. The resistance of the retro-inverso analogue to peptidases might explain the increased in vivo activities and allows its further immunopharmacological characterization.
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PMID:Immunostimulation by a partially modified retro-inverso-tuftsin analogue containing Thr1 psi[NHCO](R,S)Lys2 modification. 176 1

1. The effects of paracetamol and lysine acetylsalicylate (L-AS) on high-threshold mechanonociceptors have been investigated by recording neural activity from the inflamed ankle joint in anaesthetized rats with mild adjuvant-induced monoarthritis. 2. Paracetamol (50 mg kg-1, i.v.) and L-AS (100 mg kg-1, i.v., equivalent to 50 mg kg-1 aspirin) both caused a maximal reduction of about 40% in mechanically-evoked discharge and of 30% in ongoing (spontaneous) activity by about 15 min after the injection: a second dose of either drug did not have any significant additional effect on discharge. 3. The prostanoid IP receptor agonist, cicaprost (0.1-0.5 micrograms), increased both mechanically-evoked and ongoing discharge to pre-paracetamol levels when injected close-arterially 30-50 min after paracetamol, whereas prostaglandin E2 (PGE2) was relatively ineffective at restoring activity. 4. The results suggest that prostacyclin (PGI2) contributes to the sensitization of high-threshold joint mechanonociceptors in adjuvant-induced monoarthritis, and that paracetamol and L-AS both act to reduce discharge by inhibiting the synthesis of prostacyclin in the joint capsule. 5. Paracetamol has a direct peripheral action affecting joint capsule mechanonociceptors in rat adjuvant-induced arthritis which is very similar to that of the soluble aspirin preparation, L-AS. These findings, together with the existing literature concerning the anti-arthritic effects of paracetamol, are relevant to the treatment of chronic inflammatory disorders such as rheumatoid arthritis.
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PMID:Effects of paracetamol and aspirin on neural activity of joint mechanonociceptors in adjuvant arthritis. 178 10

Chronic monarticular arthritis can be induced in ovalbumin-sensitized rabbits by intraarticular injection of ovalbumin (antigen-induced arthritis) or in naive rabbits by injecting hyaluronic acid mixed with the polycation poly-D-lysine (polycation-induced arthritis). Both models show some points of similarity, including joint swelling, the presence of inflammatory leukocytes and the inflammatory mediator prostaglandin E2, and the kinetics of cartilage proteoglycan loss. However, the assessment of the capacity of synovial lining and articular cartilage to synthesize and secrete neutral metalloproteinases reveals a difference between these models. We found that articular cartilage from the inflamed joints of rabbits with antigen-induced arthritis did not synthesize neutral metalloproteinases, although the synovial lining did. In contrast, both the synovial lining and the articular cartilage from the inflamed joints of rabbits with polycation-induced arthritis synthesized neutral metalloproteinases. These findings suggest that in inflammatory synovitis, different mechanisms can operate to produce damage to the matrix of articular cartilage.
Arthritis Rheum 1990 Feb
PMID:Metalloproteinases and cartilage proteoglycan depletion in chronic arthritis. Comparison of antigen-induced and polycation-induced arthritis. 210 25

Previous studies have shown that chronic murine allergic arthritis can only be induced with cationized BSA, related to excellent retention of the cationic antigen in the joint. We now investigate the impact of size of cationic proteins on their potential to induce this form of arthritis. After intra-articular injection, antigen retention is much enhanced with high molecular weight cationized proteins, like albumin or immunoglobulin, compared to small-sized proteins like myoglobulin and lysozyme. Consequently, severe chronic arthritis was only found with the former ones. The role of size is further substantiated with poly-L-lysine-coupled lysozyme. This derivative shows excellent retention in vivo and causes a chronic destructive arthritis in preimmunized mice, in contrast to the poor arthritis seen with native cationic lysozyme. Control experiments made it clear that antigen retention is the most important denominator and that differences in chronicity are not related to gross variations in T-cell reactivity. Retention studies in vitro revealed that the potential to bind to joint structures is similar for the various proteins, suggesting that in vivo conditions determine size-related differences in antigen clearance. Our data indicate that cationicity per se does not make a protein a proper arthritogen.
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PMID:Allergic arthritis induced by cationic proteins: role of molecular weight. 276 9

Pharmacological properties of LFP83, a non-steroidal analgesic and antipyretic drug, were studied in mice, rats and rabbits. LFP83 is a prodrug of flurbiprofen (FP) which is its active major metabolite in vivo. In experimental models of acetic acid writhing, the Randall and Selitto method, arthritic pain, yeast fever, LPS fever, carrageenin edema and adjuvant arthritis, LFP83 (i.v.) showed remarkable analgesic, antipyretic and antiinflammatory activities; and it was more potent than ketoprofen (i.m.) and aspirin DL-lysine (i.v.). The analgesic activity of LFP83 was equal to or more potent than that of pentazocine, and its duration was longer than those of aspirin DL-lysine and pentazocine. In addition, the analgesic potency of LFP83 was approximately the same or more potent than that of FP (p.o.), and the onset of this analgesic effect began earlier. On the other hand, the ulcerogenic activity of LFP83 on rat gastric mucosa was less than that of FP (p.o.) in both single and consecutive (7 days) administrations. The safety index (UD50/ED50) of LFP83 was three to ten-fold higher than that of FP (p.o.). As mentioned above, LFP83 is a potent analgesic, antipyretic and antiinflammatory drug; and in comparison to oral FP, it has a more potent and immediate effect, weak gastric irritation and high safety index.
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PMID:[Pharmacological studies of a non-steroidal analgesic and antipyretic drug of LFP83]. 278 48


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