Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacies of corticosteroids and azathioprine (part 1) and of cyclophosphamide, immune globulin, cyclosporine, interferons, copolymer 1, and cladribine (part 2) in patients with multiple sclerosis (MS) are reviewed. MS is an inflammatory, demyelinating disease of the CNS that commonly affects young adults. The involvement of various immune mechanisms in MS suggests a role for immunomodulating therapy. The goals of immunotherapy vary with the clinical stage of the disease and include (1) improving recovery from exacerbations, (2) decreasing the number or severity of relapses, (3) preventing the development of chronic progressive disease from a relapsing-remitting course, and (4) decreasing further progression in patients with chronic progressive disease. In clinical trials, corticotropin and corticosteroids have been found to accelerate recovery from exacerbations. Tapering is often effective after high-dose induction therapy. Long-term maintenance regimens do not alter disease progression and are not recommended. Azathioprine produces modest benefits with respect to relapse rates and disease progression after two or more years of treatment; adverse effects are mild to moderate. Azathioprine should not be used in patients with aggressive disease who may approach severe disability in 6-18 months. Cyclophosphamide, because of its modest impact on disease progression and its potentially severe adverse effects, including cancer, should be reserved for patients with aggressive relapsing-remitting or chronic progressive disease in whom other treatments have failed to work; maintenance therapy is necessary after induction. Intravenous immune globulin may benefit patients with severe relapses; however, its efficacy remains unproven. Cyclosporine also cannot be recommended because of its modest efficacy, marked adverse effects, and high cost. Interferon beta-1b is a more specific immunotherapy that has been found to decrease the number and severity of relapses. This treatment should be considered in patients with relapsing-remitting disease who are having two or more exacerbations per year. Copolymer 1 and cladribine have shown some promising early results. Although various immunotherapeutic drugs can provide relief in patients with MS, none is capable of reversing disease progression, and some can cause serious adverse effects. Better understanding of the immunologic basis of MS may lead to more specific immunotherapies with more lasting benefits.
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PMID:Immunotherapy in multiple sclerosis, Part 1. 852 66

Cyclosporin A (CSA), a potent immunosuppressive drug, has recently been shown to bind with high affinity to the immunophilin, cyclophilin. Calcineurin, the calcium-dependent protein phosphatase, binds the cyclophilin/CSA complex, rendering it inactive and blocking dephosphorylation of phosphoproteins. Very high concentrations of cyclophilin have been reported in the brain with a localization identical to that of calcineurin. We have reported that interleukin-2 (IL-2) releases corticotropin-releasing hormone (CRH) by generation of nitric oxide (NO). Nitric oxide synthase (NOS), the enzyme in nitric oxidergic neurons that converts arginine into citrulline plus NO, is inactive in the phosphorylated state. We hypothesized that cyclosporin might therefore inhibit IL-2-induced acute CRH release by blocking the dephosphorylation of NOS by calcineurin. Consequently, we examined the effect of CSA on the release of CRH from mediobasal hypothalami (MBH) in vitro in 'basal' conditions and in the presence of IL-2, which we had previously shown to stimulate CRH release acutely in this preparation. Incubation of MBH for 30 min with IL-2 (10(-13) M), the concentration that was most effective in previous experiments, evoked a significant release of CRH. CSA at 10(-6) or 10(-8) M did not alter basal release of CRH; however, addition of either concentration completely blocked the IL-2-induced release of CRH. This acute action of CSA within the brain is probably mediated by blockade of the dephosphorylation of NOS by calcineurin.
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PMID:Cyclosporin A inhibits interleukin-2-induced release of corticotropin-releasing hormone. 852 89

The efficacies of corticosteroids and azathioprine (part 1) and of cyclophosphamide, immune globulin, cyclosporine, interferons, copolymer 1, and cladribine (part 2) in patients with multiple sclerosis (MS) are reviewed. MS is an inflammatory, demyelinating disease of the CNS that commonly affects young adults. The involvement of various immune mechanisms in MS suggests a role for immunomodulating therapy. The goals of immunotherapy vary with the clinical stage of the disease and include (1) improving recovery from exacerbations, (2) decreasing the number or severity of relapses, (3) preventing the development of chronic progressive disease from a relapsing-remitting course, and (4) decreasing further progression in patients with chronic progressive disease. In clinical trials, corticotropin and corticosteroids have been found to accelerate recovery from exacerbations. Tapering is often effective after high-dose induction therapy. Long-term maintenance regimens do not alter disease progression and are not recommended. Azathioprine produces modest benefits with respect to relapse rates and disease progression after two or more years of treatment; adverse effects are mild to moderate. Azathioprine should not be used in patients with aggressive disease who may approach severe disability in 6-18 months. Cyclophosphamide, because of its modest impact on disease progression and its potentially severe adverse effects, including cancer, should be reserved for patients with aggressive relapsing-remitting or chronic progressive disease in whom other treatments have failed to work; maintenance therapy is necessary after induction. Intravenous immune globulin may benefit patients with severe relapses; however, its efficacy remains unproven. Cyclosporine also cannot be recommended because of its modest efficacy, marked adverse effects, and high cost. Interferon beta-1b is a more specific immunotherapy that has been found to decrease the number and severity of relapses. This treatment should be considered in patients with relapsing-remitting disease who are having two or more exacerbations per year. Copolymer 1 and cladribine have shown some promising early results. Although various immunotherapeutic drugs can provide relief in patients with MS, none is capable of reversing disease progression, and some can cause serious adverse effects. Better understanding of the immunologic basis of MS may lead to more specific immunotherapies with more lasting benefits.
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PMID:Immunotherapy in multiple sclerosis, Part 2. 853 45

The effect of Freund's adjuvant injection on 24-hour variation of hypothalamic corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH), GH-releasing hormone (GRH) and somatostatin levels was examined in adult rats kept under light between 0800 and 2000 h daily. Groups of rats receiving Freund's complete adjuvant or its vehicle 3 days before sacrifice were killed at six different time intervals throughout a 24-hour cycle. In the median eminence, adjuvant vehicle-injected rats exhibited significant 24-hour variations for the four hormones examined, with maxima at noon. These 24-hour rhythms were inhibited or suppressed by Freund's adjuvant injection. In the anterior hypothalamus of adjuvant vehicle-treated rats, CRH content peaked at 1600 h, while two peaks were found for TRH and GRH levels, i.e., at 2400-0400 h and 1600 h. Freund's adjuvant injection suppressed 24-hour rhythm of anterior hypothalamic CRH, TRH and GRH content and uncovered a peak in anterior hypothalamic somatostatin levels at 0400 h. In the medial hypothalamus of adjuvant vehicle-treated rats, significant 24-hour variations were detectable for TRH (peaks at 1600 and 2400 h) and somatostatin (peak at 2400 h) which disappeared after Freund's adjuvant injection. In the posterior hypothalamus of adjuvant vehicle-treated rats, two peaks were apparent for CRH, TRH and somatostatin levels, i.e. at 1600 h and 2400-0400 h, this hormonal profile remaining unmodified after Freund's adjuvant administration. The administration of the immunosuppressant drug cyclosporine (5 mg/kg, 5 days) impaired the depressing effect of Freund's adjuvant injection on CRH, TRH and somatostatin content in median eminence, but not that on GRH. In the anterior hypothalamus, cyclosporine generally prevented the effect of immunization on hormone levels an revealed a second maximum in TRH at 0400 h. Cyclosporine also restored 24-hour variations in TRH and somatostatin levels of medial hypothalamus of Freund's adjuvant-injected rats but was unable to modify them in the posterior hypothalamus. The results further support the existence of a significant effect of immune-mediated inflammatory response at an early phase after Freund's adjuvant injection on hypothalamic levels which was partially sensitive to immunosuppression by cyclosporine.
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PMID:Twenty-four hour rhythms of hypothalamic corticotropin-releasing hormone, thyrotropin-releasing hormone, growth hormone-releasing hormone and somatostatin in rats injected with Freund's adjuvant. 1021 46