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)

To determine the influence of colchicine on adrenocortical function in vivo, we gave significant amounts subcutaneously to rats and observed the distribution to the anterior pituitary and adrenal glands. Corticosteroids in the serum and adrenal gland were increased remarkably by the administration of colchicine in a dose-dependent manner. Maximum elevation was achieved around 2.5 hours after the injection and continued for at least 4 hours. Maximum levels produced by the injection of 0.1 U/rat of adrenocorticotropic hormone, the latter producing temporary increases in corticosteroids in the serum and adrenal gland. A significant augmentation of corticosteroids in the serum and adrenal gland resulted when colchicine was administered 60 minutes prior to the injection of adrenocorticotropic hormone. The pattern of intracellular distribution of corticosteroids in the adrenal glands of rats given colchicine was the same as that seen in rats given adrenocorticotropic hormone. In the in vitro experiment, only high concentrations of colchicine such as 10(-3) M added to the incubation system of the adrenal quarters suppressed the release of corticosteroids from the adrenal gland. Thus, the continuous stimulation of the synthesis and secretion of adrenocortical hormone seen with the administration of colchicine may explain why this drug is effective in the treatment of gouty arthritis.
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PMID:Effect of colchicine on steroid secretion from rat adrenal gland. 23 4

In male rats, inoculation of Freund's complete adjuvant (FCA, 0.5 mg/rat of Mycobacterium butyricum in paraffin oil) induced high levels of ornithine decarboxylase (ODC) in the hypothalamus and pituitary gland (285% and 245% of controls, respectively, within 12 h to 2 days). ODC activity also was altered in the cerebellum and left neocortex, but not in the right neocortex. This activity reflected a dynamic equilibrium which is influenced by ODC synthesis, degradation, activation, etc. The circadian rhythms of pituitary ODC activity and plasma prolactin level, 3-4 days after FCA, showed that enhancement of enzymatic activity during the dark phase correlated with a marked release of prolactin (Prl). During this early period after FCA, changes in plasma levels of other pituitary hormones were not significant or were less important. Pretreatment with bromocriptine microcapsules inhibited both basal and FCA-induced pituitary ODC activity, as well as Prl secretion. Further, significant increases in plasma luteinizing hormone and adrenocorticotropic hormone were noted from days 4 and 8, respectively, and onwards. Finally, a phase of reduced corticosterone secretion occurred during the latency period. This study shows that FCA influences central nervous system pathways and supports the idea that endogenous Prl is involved in some early events which lead to the development of adjuvant arthritis.
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PMID:Freund's complete adjuvant induces ornithine decarboxylase activity in the central nervous system of male rats and triggers the release of pituitary hormones. 215 4

One hundred male patients who presented with acute gouty arthritis were alternately assigned to 2 treatment groups. Seventy-six patients completed the study protocol, in which each gout attack during a 1-year period was treated. For each gout episode, 36 patients received a single intramuscular injection of 40 IU of adrenocorticotropic hormone (ACTH), and 40 patients received oral indomethacin, 50 mg 4 times daily with meals, until the pain abated. The time interval until the pain was relieved, as well as any untoward effects, were recorded for each gout attack treated. Both groups were of similar age, and had similar values for intercritical serum uric acid, 24-hour urinary uric acid, and creatinine clearance (1 month after entry into the study). The mean interval (+/- SD) to relief of pain was significantly shorter for the ACTH group (3 +/- 1 hours) than for the indomethacin group (24 +/- 10 hours). No side effects were noted in the ACTH group. However, of the 40 patients receiving indomethacin, 22 had abdominal discomfort of dyspepsia, 15 had headaches, and 12 had difficulty with mentation. Single-dose parenteral ACTH appeared to be effective more rapidly and was associated with fewer side effects than oral indomethacin in the treatment of acute gout.
Arthritis Rheum 1988 Jun
PMID:Comparison of parenteral adrenocorticotropic hormone with oral indomethacin in the treatment of acute gout. 245 35

Adjuvant arthritis was induced in female Fisher rats by injecting their right hind paw with 0.1 ml Freund's complete adjuvant. The development of adjuvant arthritis was inhibited by hypophysectomy and by daily treatment of intact animals with the dopaminergic agent bromocriptine. Adjuvant arthritis developed normally if hypophysectomized or bromocriptine-suppressed animals were treated with either prolactin or growth hormone. Additional treatment with adrenocorticotropic hormone inhibited this restoration. Treatment of hypophysectomized rats with follicle-stimulating hormone, luteinizing hormone, and thyroid-stimulating hormone had no effect. These results indicate that prolactin and/or growth hormone are necessary for the development of adjuvant arthritis, whereas adrenocorticotropic hormone has an inhibitory effect.
Arthritis Rheum 1984 Jun
PMID:The influence of pituitary hormones on adjuvant arthritis. 632 36

Treatment of rats with the dopaminergic ergot alkaloid bromocriptine (BRC) inhibited the following immune reactions: contact sensitivity skin reaction to dinitrochlorobenzene (DNCB); antibody formation to sheep red blood cells and to bacterial lipopolysaccharide; adjuvant arthritis; and experimental allergic encephalitis. Immunosuppressive doses of BRC (5 mg/kg) decreased the serum prolactin (PRL) levels from 84.8 +/- 15.9 ng/ml to 4.9 +/- 1.6 ng/ml. Further studies on DNCB contact sensitivity and on antibody formation revealed that the immunocompetence of BRC-suppressed animals could be restored by additional treatment with either prolactin (PRL) or growth hormone (GH). Treatment with adrenocorticotropic hormone antagonized the restoring effect of PRL and GH. These results suggest that BRC suppressed immunity by its inhibition of PRL, and possibly also by inhibition of GH secretion.
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PMID:Immunomodulation by bromocriptine. 635 9

Endogenous opioid peptides have an essential role in the intrinsic modulation and control of inflammatory pain, which could be therapeutically useful. In this study, we established a muscular electroporation method for the gene transfer of pro-opiomelanocortin (POMC) in vivo and investigated its effect on inflammatory pain in a rat model of rheumatoid arthritis. The gene encoding human POMC was inserted into a modified pCMV plasmid, and 0-200 microg of the plasmid-POMC DNA construct was transferred into the tibialis anterior muscle of rats treated with complete Freund's adjuvant (CFA) with or without POMC gene transfer by the electroporation method. The safety and efficiency of the gene transfer was assessed with the following parameters: thermal hyperalgesia, serum adrenocorticotropic hormone (ACTH) and endorphin levels, paw swelling and muscle endorphin levels at 1, 2 and 3 weeks after electroporation. Serum ACTH and endorphin levels of the group into which the gene encoding POMC had been transferred were increased to about 13-14-fold those of the normal control. These levels peaked 1 week after electroporation and significantly decreased 2 weeks after electroporation. Rats that had received the gene encoding POMC had less thermal hypersensitivity and paw swelling than the non-gene-transferred group at days 3, 5 and 7 after injection with CFA. Our promising results showed that transfer of the gene encoding POMC by electroporation is a new and effective method for its expression in vivo, and the analgesic effects of POMC cDNA with electroporation in a rat model of rheumatoid arthritis are reversed by naloxone.
Arthritis Res Ther 2004
PMID:Intramuscular electroporation with the pro-opiomelanocortin gene in rat adjuvant arthritis. 1497 33

Gouty arthritis is a characteristically intense acute inflammatory reaction that erupts in response to articular deposits of monosodium urate (MSU) crystals. Important recent molecular biologic advances in this field have given us a clear picture of the mechanistic basis of gouty inflammation. The innate immune inflammatory response is critically involved in the pathology of gout. Specifically, MSU crystals promote inflammation directly by stimulating cells via Toll-like receptor signaling and by providing a surface for cleavage of C5 and formation of complement membrane attack complex (C5b-9), culminating in secretion of cytokines, chemokines, and other inflammatory mediators with a dramatic influx of neutrophils into the joint. Despite the detailed mechanistic picture for gouty inflammation, there are no placebo-controlled, randomized clinical studies for any of the therapies commonly used, although comparative studies have demonstrated that many nonsteroidal anti-inflammatory drugs are equivalent to indomethacin with respect to controlling acute gouty attacks. In general, the first line of anti-inflammatory therapy for acute gout is nonsteroidal anti-inflammatory drugs, and the selective cyclo-oxygenase-2 inhibitor celecoxib can be used where appropriate. The second line of treatment is glucocorticosteroids, given systemically (oral, intravenous, or intramuscular) or intra-articularly. Alternatively, synthetic adrenocorticotropic hormone is effective, partly via induction of adrenal glucocorticosteroids and partly via rapid peripheral suppression of leukocyte activation by melatonin receptor 3 signaling. The third line of treatment is oral colchicine, which is highly effective when given early in an acute gouty attack, but it is poorly tolerated because of predictable gastrointestinal side effects.
Arthritis Res Ther 2006
PMID:The inflammatory process of gout and its treatment. 1700 28

Leptin, a hormone regulating body weight, food intake, and metabolism, is associated with activation of immune cells and inflammation. In this study we analyzed levels of leptin, adrenocorticotropic hormone (ACTH), corticosterone, interleukin 1beta (IL-1beta), and nitric oxide (NO) production on days 10 and 22 of adjuvant arthritis (AA) in male Long Evans rats to ascertain possible relationship of leptin with its modulators during the early and late phases of chronic inflammation. The circulating leptin levels were significantly reduced already on day 10 of AA compared to controls (1.97+/-0.22 ng/ml vs. 3.08+/-0.25 ng/ml, p<0.05); on day 22 no significant further drop was observed (1.06+/-0.21 ng/ml). Leptin mRNA in epididymal fat tissue was reduced in arthritic animals compared to controls on day 22 (0.61+/-0.09 vs. 1.30+/-0.1 arbU/GAPDH (p<0.01). IL-1beta concentration in spleen was enhanced on day 10 of AA (24.55+/-4.67 pg/100 microg protein vs. 14.33+/-1.71 pg/100 microg protein; p<0.05); on day 22 it did not differ from controls. ACTH and corticosterone levels were significantly elevated only on day 22 of AA (ACTH: 306.17+/-42.22 pg/ml vs. 157.61+/-23.94 pg/ml; p<0.05; corticosterone: 5.24+/-1.38 microg/100 ml vs. 1.05+/-0.23 microg/100 ml; p<0.01). Nitrate levels were enhanced similarly on days 10 (49.86+/-1.83 microM) and 22 of AA (43.58+/-2.17 microM), compared to controls (23.42+/-1.39 microM, p<0.001). These results show that corticosterone does not stimulate leptin production during AA. The suppression of leptin may be a consequence of permanent activation of NO, IL-1beta, and of lower weight gain. Circulating leptin does not seem to play a key role in the progression of chronic arthritis.
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PMID:Relationship among nitric oxide, leptin, ACTH, corticosterone, and IL-1beta, in the early and late phases of adjuvant arthritis in male Long Evans rats. 1696 44

Gout, a common inflammatory arthritis, can be diagnosed with absolute certainty. Gout results from the body's reaction to urate crystals deposited in tissues, and this pathophysiology is well understood. If used appropriately, available therapies can be entirely effective in not only treating the symptoms of gout, but also in eliminating the excess urate from the body, thereby eradicating the disease. Because of these facts, management of patients with gout should be successful. However, management of gout is particularly challenging in the elderly, even though the principles of management are the same for all age groups. The purpose of this article is to review these principles and discuss them as they pertain to the elderly. The classic gout attack is acute in onset, extremely painful and associated with marked swelling, warmth, erythema and tenderness of a single joint. However, the diagnosis of gout may be challenging in the elderly because atypical presentations are more common in this group. Treatment of acute gout involves the use of NSAIDs, colchicine, corticosteroids or corticotropin (adrenocorticotropic hormone). Unfortunately, co-morbid conditions such as chronic kidney disease, peptic ulcer disease and congestive heart failure may make the use of these agents dangerous or contraindicated. Thus, it is important to try to treat an acute flare of gout at the earliest sign, because the sooner treatment is initiated, the faster the inflammation will resolve. Urate-lowering agents include allopurinol and uricosuric agents. These also must be used judiciously in the elderly. However, if used at the lowest dose that maintains the serum urate level below 5.0-6.0 mg/dL, the excess urate in the body will be eliminated, acute flares will no longer occur and tophi will resolve. Gout is often seen in association with hypertension, excessive alcohol consumption, obesity and hypertriglyceridaemia. These conditions and the medications used to treat them may contribute to the hyperuricaemia. Treating these conditions and using medications that do not promote hyperuricaemia will aid in the management of gout. Despite the challenges that often complicate the management of gout in the elderly, an understanding of the pathophysiology of the disease and both the indications and limitations of the medications used should allow successful treatment.
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PMID:Management of gout in older adults: barriers to optimal control. 1723 45

It is important to distinguish between therapy used to reduce acute inflammation in gout and therapy used to manage hyperuricaemia in patients with chronic gouty arthritis. This article discusses treatments for acute gout, emphasizing the use of corticotrophin (adrenocorticotropic hormone; ACTH) and the evidence on which we base our treatment of acute gout. There are no formal guidelines for the treatment of acute gout and only a few randomized controlled trials have been conducted to evaluate the efficacy of the various treatments for acute gout. The options available for the treatment of acute attacks of gout are NSAIDs, colchicine, corticosteroids, corticotropin and intra-articular corticosteroids. Most rheumatologists practicing in the US use combination therapy to treat acute gout, a practice that merits study. In a patient without complications, NSAIDs are the preferred therapy. The most important determinant of therapeutic success is not which NSAID is chosen, but rather how soon NSAID therapy is initiated. Exciting new research shows that corticotropin acts peripherally by activation of the melanocortin type 3 receptor, and this could be responsible, at least in part, for its efficacy in acute gout. Hopefully, this will lead to renewed interest in corticotropin as a treatment for acute gout.
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PMID:Overview of the management of acute gout and the role of adrenocorticotropic hormone. 1831 60


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