UMLS:C0003864 - FACTA Search

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)

The effects of an experimentally induced arthritis on immunoreactivity of putative primary afferents neurotransmitter/neuromodulators were examined. Immunoreactive staining for substance P (SP), calcitonin gene-related peptide (CGRP) and glutamate (Glu) in the monkey dorsal horn was examined following inflammation of one knee joint induced by injection of 5% kaolin and 5% carrageenan. Spinal cords were examined at different time periods after induction of arthritis (2.5, 4, 6 and 8 h). Side to side differences in immunoreactivity were determined by a computer assisted quantitation system. A significant overall decrease in immunoreactivity of the lumbar versus the cervical dorsal horn was found for SP. The decrease for SP showed maximal changes of 68.3% at 4 h and 54.7% at 6 h. Immunoreactivity for CGRP was decreased 31.5% at 8 h and variable at other time points. Immunoreactivity for Glu, showed an ipsilateral increase of 31.4% at 4 h, 33.7% at 6 h, 39.9% at 8 h and a significant effect for lumbar versus cervical. Repetitive peripheral stimulation of the joint was shown to be important for changes in SP and Glu immunoreactivity. Without frequent peripheral stimulation in the early stages of the development of arthritis, SP showed no quantitative side to side differences. Increases in Glu immunoreactivity were present but not as prominent with minimal joint manipulation. These studies suggest that Glu may be involved in the aching pain of inflammation at rest whereas SP, CGRP and Glu may mediate pain induced by joint movement.
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PMID:Neural changes in acute arthritis in monkeys. III. Changes in substance P, calcitonin gene-related peptide and glutamate in the dorsal horn of the spinal cord. 137 98

Extracellular levels of amino acids were measured during the development of experimental arthritis in anesthetized monkeys. Levels of glutamate, aspartate, glycine, serine, glutamine, taurine, cysteic acid and asparagine were each measured in consecutive 30 min samples before, during and for several hours after injection of kaolin and carrageenan into the articular capsule of one knee. Samples were obtained via a microdialysis probe placed in the lumbar dorsal horn ipsilateral to the injected knee and assayed using HPLC with fluorescence detection. Glutamate, aspartate, glycine and serine increased transiently following intra-articular injection of inflammatory agents. During this period glutamine levels decreased. A second phase of release then occurred which included more prolonged changes in amino acid levels that were sometimes of greater magnitude than those immediately following the injection. In animals which were later observed to have depletion of SP in the dorsal horn of the inflamed side, taurine levels increased starting after the Glu, Asp and Gly had plateaued at near baseline concentrations. Thus during the first stages of joint inflammation EAAs are released into the dorsal horn, followed by increased levels of IAAs, possibly representing activation of the descending endogenous analgesia system. This phase is followed by a semiacute response consisting in part of increased extracellular levels of SP and Tau. While SP is presumably part of an ascending nociceptive transmission system, Tau could be part of a second system aimed at reducing excessive neural activity including neural transmission resulting in intense maintained pain.
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PMID:Neural changes in acute arthritis in monkeys. IV. Time-course of amino acid release into the lumbar dorsal horn. 163 74

An experimental arthritis induced by injection of kaolin and carrageenan into the knee joint resulted in a temporal relationship between glutamate dorsal horn content and paw withdrawal latency (PWL) which was positively correlated. Limping, guarding, increased response to heat stimuli (hyperalgesia) and altered staining patterns for glutamate (GLU), substance P (SP), and calcitonin gene-related peptide (CGRP) were monitored in the awake behaving arthritic rat over a 1 week time course. A decrease in PWL occurred on the side ipsilateral to the inflamed knee as early as 4 h after the induction of arthritis indicating the animals are hyperalgesic. The PWL remained decreased through the first 24 h. Computer-assisted quantification of the density of immunohistochemical staining indicated the content of GLU, SP and CGRP was altered differentially throughout the time course of the arthritis. The changes observed for all three substances occurred across the entire superficial dorsal horn. There was an initial depletion of SP followed by an increase in both SP and CGRP content which was maintained through 1 week. The GLU content was increased during the hyperalgesic period. The GLU changes followed the same time course and were positively correlated with the changes in PWL. In a small group of animals injected with kaolin and carrageenan, hyperalgesia did not develop. In this group of animals, no change in dorsal horn GLU or SP content occurred. Rather, there was an increase in CGRP content in the middle portion of the superficial dorsal horn which is the termination site of knee joint afferents. These data indicate that the development of heat hyperalgesia is dependent on GLU and possibly SP. Since inflammation of the knee joint does not involve the foot pad, the heat hyperalgesia observed during the first 24 h following induction of arthritis represents a central neuronal sensitization.
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PMID:Behavioral and immunohistochemical changes in an experimental arthritis model in rats. 751 59

Following induction of acute knee joint arthritis in rats, an increase in the release of amino acids in the spinal dorsal horn occurs in two phases: (1) at the time of injection for all amino acids tested; and (2) a late prolonged phase for aspartate (Asp) and glutamate (Glu) (3.5-8 h). In the present study, the increased late phase release of Glu was reversed by posttreatment of the spinal cord with the N-methyl-D-aspartate (NMDA) receptor antagonist, AP7, but not with the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Asp late phase release in arthritic animals was unaffected by posttreatment of the spinal cord with either AP7 or CNQX. Arthritic animals became hyperalgesic to radiant heat stimuli by 4 h and this hyperalgesia was reversed by both CNQX and AP7. During the paw withdrawal latency (PWL) test for heat hyperalgesia, there was an increase in the glycine (Gly) and serine (Ser) concentrations in the dorsal horn. This increase in Gly and Ser was blocked by both CNQX and AP7. Indications of inflammation in arthritic animals posttreated with AP7, including increased joint circumference and temperature, were similar to animals that did not receive antagonists. Arthritic animals posttreated with CNQX, however, showed a reduction in the degree of joint swelling. Thus, both non-NMDA and NMDA receptors appear to play a role in the processing of the information evoked by stimuli in the periphery. The arthritis-induced release of Gly and Ser during the PWL test for heat hyperalgesia appears to be dependent on activation of both non-NMDA and NMDA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential effects of N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists on spinal release of amino acids after development of acute arthritis in rats. 789 49

The absence of AIDS-like symptoms in HIV-infected chimpanzees and SIV-infected African Green monkeys (AGMs) may provide important clues about the pathogenic mechanism of AIDS and about mechanisms of resistance. HIV-infected persons and SIV-infected rhesus macaques have, on the average, markedly decreased cysteine, cystine, and glutathione levels and elevated plasma glutamate concentrations. Glutamate inhibits the membrane transport of cystine and a combination of low plasma glutamate and high cystine levels was found to be correlated with high CD4+ T cell numbers even in HIV-negative healthy human individuals. We have now found that glutamate and cystine levels are also correlated with CD4+ T cell numbers in chimpanzees. But infection of chimpanzees, AGMs, and goats with HIV-1, SIV, and caprine arthritis encephalitis virus (CAEV), respectively, does not induce significant changes in plasma cystine or glutamate levels, although infected AGMs and goats have, on the average, significantly elevated plasma levels of the biochemically related amino acid proline.
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PMID:Plasma amino acid dysregulation after lentiviral infection. 790 43

An experimental arthritis, induced by injection of the knee joint with kaolin and carrageenan, results in guarding of and decreased weight bearing on the limb. At the time of injection, a transient increased release of all amino acids examined is measurable in samples collected by microdialysis. A second and prolonged increase of aspartate (ASP), glutamate (GLU), and glutamine (GLN) concentrations follows after 3 h. The increased release at time of injection is blocked by microdialysis application of a non-N-methyl-D-aspartate (non-NMDA) or an NMDA receptor antagonist, and the release of ASP, GLU, and GLN in the late phase is blocked by pretreatment with a non-NMDA (CNQX), an NMDA (AP7) or a neurokinin 1 (NK1; CP-96,345) antagonist. Dorsal horn immunoreactive staining of GLU, substance P (SP), and calcitonin gene-related peptide (CGRP) is reflective of the events occurring in the late phase of amino acid release since GLU release is positively correlated with GLU staining density. Increased immunoreactivity for GLU, SP, and CGRP at 8 hr in the arthritic animals is differentially altered by pretreatment of the spinal cord dorsal horn with non-NMDA, NMDA, or NK1 receptor antagonists. The differential staining pattern for GLU, SP, and CGRP, the differential release of ASP and GLU, and the differential activation of the EAA and NK1 receptors implies that ASP, GLU, SP, and CGRP are each involved in the processing of sensory information and that their roles in the central sensitization occurring with the inflammatory process, are unique.
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PMID:Spinal cord amino acid release and content in an arthritis model: the effects of pretreatment with non-NMDA, NMDA, and NK1 receptor antagonists. 790 87

After the injection of kaolin and carrageenan into the knee joint of rats, there was a decrease in paw withdrawal latency (PWL) to radiant heat ipsilaterally, which indicates hyperalgesia. This decrease was blocked by pretreatment of the spinal cord dorsal horn with the gamma-aminobutyric acid (GABAA) receptor antagonist, bicuculline but not with the GABAB receptor antagonist, CGP35348, administered by microdialysis. The inflammation-induced release of amino acids from the spinal dorsal horn occurred in two phases: 1) an early phase at the time of injection and 2) a late phase at 3.5 to 8 hr. The amino acids released in the late phase included aspartate (ASP), glutamate (GLU) and glutamine. During the PWL test, there was also the release of the inhibitory amino acids, serine and glycine, after the induction of arthritis. The increased release of excitatory amino acids at the time of injection was unaffected by pretreatment with either bicuculline or CGP35348. The release of amino acids during the late phase and during the PWL test was blocked by pretreatment with bicuculline but not CGP35348. The increase in joint circumference typical of this model did not occur with pretreatment with the GABAA receptor antagonist. The change in joint circumference was positively correlated with the late phase release of ASP and GLU. In bicuculline-treated arthritic animals in which joint inflammation was minimal, concentrations of ASP and GLU did not increase above base line.
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PMID:Inflammation-induced release of excitatory amino acids is prevented by spinal administration of a GABAA but not by a GABAB receptor antagonist in rats. 796 59

We have sequenced and studied the expressed protein of an HPRT mutation characterized by 5-12% residual erythrocyte activity, for which affected males exhibit hyperuricemia, arthritis and renal disease but are without severe neurological involvement. The HPRTMoose Jaw mutation is due to a single C to G transversion at nucleotide 582 relative to initiation of translation corresponding to substitution of aspartate 194 by glutamate. The mutant and wild type proteins were expressed and purified using the bacterial expression vector, pMAL-c2. The Km for hypoxanthine was increased 12-fold from 0.94 +/- 0.26 to 11.5 +/- 1.3 microM for control and mutant respectively. The apparent Km for PP-ribose-P was increased 44-fold from 6.8 +/- 0.6 to 295 +/- 7 microM for control and mutant respectively. Although the kcat of the mutant protein was equivalent to wild type, the catalytic efficiency, kcat/Km, of the purified mutant protein was only 6 and 3% of wild type with hypoxanthine and PP-ribose-P respectively. The mutant protein also exhibited positive cooperativity with PP-ribose-P, having a Hill coefficient of 2.3. The decreased substrate affinities and PP-ribose-P associated cooperativity of HPRTMoose Jaw provide additional evidence for the influence of carboxy-terminal residues of HPRT in specific catalytic functions.
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PMID:Sequence, expression and characterization of HPRTMoose Jaw: a point mutation resulting in cooperativity and decreased substrate affinities. 798 18

Release of excitatory amino acids (EAA's) in the dorsal horn of awake rats was monitored by microdialysis during the development of arthritis induced by injection of 3% kaolin and 3% carrageenan into the knee joint. Concentrations of EAA's in the dialysate samples were measured by high performance liquid chromatography at baseline, during delivery of EAA antagonists, and for the first 8 h of arthritis. An initial increase in aspartate (ASP) and glutamate (GLU) was observed on injection of the knee joint in rats made arthritic. Subsequently, there was a prolonged release phase after 3 h which persisted at least 8 h. Specific EAA antagonists to non-N-methyl-D-aspartate (non-NMDA; CNQX) and to NMDA (AP7) receptors were used to block the effects seen in the untreated arthritic animals. The increase in ASP and GLU release seen at the time of injection in untreated arthritic animals did not occur in arthritic animals treated with EAA receptor antagonists (CNQX or AP7). In arthritic animals treated with CNQX, the prolonged release phase was delayed and attenuated for GLU and decreased below baseline for ASP. In the AP7-treated arthritic animals, no change from baseline concentration was observed for ASP until 7 h, and GLU decreased minimally. The data indicate that this arthritis model is accompanied by an initial increased release of EAA's at the time of injection which is dependent on the activation of both non-NMDA and NMDA receptors. Subsequent development of arthritis, manifested as an inflamed joint and a delayed and prolonged release of ASP and GLU, is dependent on the initial activation of these EAA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An experimental arthritis model in rats: the effects of NMDA and non-NMDA antagonists on aspartate and glutamate release in the dorsal horn. 809 22

In Sprague-Dawley rats, Freund-adjuvant-induced arthritis (AIA) results in an increase in the amplitude of ultradian growth-hormone (GH)-secretory episodes without modification of their frequency. This is most apparent at the time of maximal inflammation, i.e. 14-21 days after inoculation of the adjuvant. GH responsiveness to a maximal dose of clonidine (10 micrograms/100 g body weight, BW), a secretagogue known to act at the hypothalamic level, is comparable in AIA and control rats. In contrast, GH response to a maximal dose of GH-releasing hormone (GHRH, 1 microgram/100 g BW), a peptide acting directly on pituitary somatotropes, is greater in AIA than in control rats. Furthermore AIA affects significantly neither hypothalamic somatostatin and GHRH mRNA levels nor pituitary GH content. In adult rats treated neonatally with monosodium glutamate (MSG), a neurotoxin which destroys the majority of GHRH neurons of the arcuate nucleus and reduces considerably plasma GH levels, clinical symptoms observed 14 days after inoculation of the Freund adjuvant are more marked than in AIA. The MSG-treated rats exhibit in particular a significantly higher increase in hindpaw diameter. Pulsatile administration of GH (40 micrograms/day/rat, with successive periods of 2 h of GH and 4 h of mineral oil) restoring the endogenous GH-secretory pattern throughout the 15-day period of arthritis development prevents hindpaw diameter increase. These results indicate that the impact of AIA on GH regulation occurs at the pituitary but not the hypothalamic level and suggest that increased GH secretion observed in AIA rats is an adaptive mechanism involved in the regulation of the inflammatory process.
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PMID:The increase in growth hormone secretion in experimentally induced arthritic rats is an adaptive process involved in the regulation of inflammation. 883 59

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