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)

Extensive research is under way to develop pharmacotherapeutic agents that will prevent the exacerbations and the progression of neurologic disability associated with multiple sclerosis (MS). The most intensive research strategy has involved agents intended to limit demyelination by reducing inflammation and modifying the immune response. In this category are interferon beta-1b, the first compound approved for use outside of clinical trials; interferon beta-1a; and copolymer 1. Experimental agents include other interferons, methotrexate, linomide, monoclonal antibodies, T-cell receptor peptides, and 2-chlorodeoxyadenosine. Although they have been used effectively to treat exacerbations of MS, corticosteroids and corticotropin are now under evaluation as disease-modifying agents. A second strategy, enhancing remyelination by limiting demyelination and oligodendrocyte injury, is represented by protein growth factors. A third therapeutic approach, improving conduction in demyelinated fibers, is represented by the potassium channel blockers 4-aminopyridine and 3,4-diaminopyridine.
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PMID:Current and investigational therapies used to alter the course of disease in multiple sclerosis. 911 24

We investigated the basal and dynamic regulation of the hypothalamo-pituitary-adrenal (HPA), hypothalamo-pituitary-thyroid (HPT) and hypothalamo-pituitary-gonadal axes and prolactin secretion in 52 patients with clinically definite multiple sclerosis. These patients also had gadolinium enhanced brain MRI scans and were divided into relapsing-remitting, secondary progressive and primary progressive subgroups. These subgroups were compared with healthy controls and a group of patients with other neurological diseases. The cortisol diurnal rhythm was preserved in all groups of patients. The time-integrated cortisol response to human corticotropin-releasing hormone (CRH) stimulation was lower in the patients with secondary progressive multiple sclerosis, compared with patients with primary progressive multiple sclerosis and healthy subjects. The time-integrated beta-endorphin response to CRH was greater in the patients with relapsing-remitting multiple sclerosis compared with the others. Feedback regulation assessed by dexamethasone suppression was normal. Serum testosterone was low in 24% of male multiple sclerosis patients and oestradiol was low in 25% of pre-menopausal female multiple sclerosis patients, whereas prolactin and the HPT function were normal. Correlations with C-reactive protein (CRP) and MRI suggest that activation of the HPA axis in multiple sclerosis patients is secondary to an active inflammatory stimulus.
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PMID:The neuroendocrine axis in patients with multiple sclerosis. 921 89

Intracerebral administration of adrenocorticotropic hormone (ACTH) elicits in experimental animals a yawning stretching behavior which is believed to reflect an arousal response mediated through the septohippocampal cholinergic neurons. A surge in plasma ACTH levels at night and just prior to awakening from sleep is also associated in humans with yawning and stretching behavior. Recurrent episodes of uncontrollable yawning and body stretching, identical to those observed upon awakening from physiological sleep, occur in a subset of patients with multiple sclerosis (MS) during transcranial therapeutic application of AC pulsed electromagnetic fields of picotesla flux density. This behavioral response has been observed exclusively in young female patients who are fully ambulatory with a relapsing remitting course of the disease who also demonstrate a distinctly favorable therapeutic response to magnetic stimulation. ACTH is employed for the treatment of MS due to its immunomodulatory effects and a surge in its release in response to AC pulsed magnetic stimulation could explain some of the mechanism by which these fields improve symptoms of the disease.
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PMID:Yawning and stretching--a behavioral syndrome associated with transcranial application of electromagnetic fields in multiple sclerosis. 984 21

Nitric oxide is a free radical gas, NO, of paramount relevance in biology. The enzymes responsible for the synthesis of NO from L-arginine in mammalian tissues are known as nitric oxide synthases (NOS). The inducible NOS (iNOS) is associated with the development of a number of autoimmune diseases. iNOS is induced on monocytes, cells playing a key role in the initiation and progression of the immune response. Induction of the enzyme is effected by proinflammatory cytokines, immunomodulating peptides, and even beta-endorphin through a mechanism involving an increase in cAMP. An excessive production of NO has been implicated in the severe lesions observed in multiple sclerosis (MS). Nitrosation of proteins caused by NO in monocytes may contribute to the formation of new epitopes involved in the autoimmune response. Monocytes/macrophages enhance also their cytotoxic capacity through an increase in NO. iNOS seems to establish a link between neuroendocrine and immune system through beta-endorphin explaining stress-related relapses in MS. One of the causes of demyelination is the lysis of oligodendrocytes by cytotoxic T lymphocytes (CTLs); and T cell response is also known to be modulated by NO.
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PMID:The role of nitric oxide in the pathogenesis of multiple sclerosis. 1022 14

Amantadine, originally used in the treatment and prophylaxis of influenza infection, has also proved beneficial in drug-induced Parkinsonism, Parkinson's disease, traumatic head injury, dementia, multiple sclerosis and cocaine withdrawal. Amantadine appears to act through several pharmacological mechanisms, none of which has been identified as the one chief mode of action. It is a dopaminergic, noradrenergic and serotonergic substance, blocks monoaminoxidase A and NMDA receptors, and seems to raise beta-endorphin/beta-lipotropin levels. However, it is still uncertain which of these actions are relevant in therapeutic doses. One new aspect is the antiviral effect of amantadine on Borna disease virus, which it is suspected may possibly play a role in affective disorders. All of these actions could constitute an antidepressant property, and it is suggested that amantadine might work as an antidepressant not through one, but through several mechanisms thought to be related to antidepressant activity. Effects of amantadine on symptoms of affective disorders have been demonstrated in several trials administering it for varying purposes. Additionally, animal studies as well as clinical trials in humans have hinted at an antidepressant activity of amantadine. We present here an overview of the current data. However, only a limited body of evidence is available, and further studies are needed to investigate the efficacy of amantadine as well as its modes of action in depression.
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PMID:Possible use of amantadine in depression. 1033 62

High-frequency electrical stimulations of thalamic nuclei are currently used for the suppression of parkinsonian or essential tremor and for the relief of some types of intractable pain in man. However, the mechanisms by which such stimulations exert their therapeutic effects are essentially unknown. Attempts were made to provide some insight into these mechanisms by measuring the levels of the dopamine metabolites homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and met-enkephalin-like immunoreactivity in ventricular cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD) or multiple sclerosis (MS) after a 30-minute therapeutic electrical stimulation of the ventralis intermedius nucleus of the thalamus. In nonstimulated control patients, the levels of these compounds did not significantly differ in two CSF samples taken 30 minutes apart. In stimulated patients, a decrease in dopamine metabolite levels associated with a relative increase in met-enkephalin-like immunoreactivity were observed in the CSF sample taken after the 30-minute stimulation as compared to the sample taken immediately before the stimulation. In contrast, the levels of 5-HIAA remained unaffected by the stimulation. These data confirmed the existence of negative interactions between dopaminergic and enkephalinergic systems in man similar to those previously demonstrated in rats. In addition, they suggest that alterations in dopaminergic or enkephalinergic neurotransmission might be involved in the therapeutic action of thalamic electrical stimulation in patients with parkinsonian symptoms and other patients.
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PMID:Opposite changes in dopamine metabolites and met-enkephalin levels in the ventricular CSF of patients subjected to thalamic electrical stimulation. 1044 54

Basic and clinical research suggest that disturbed neuroendocrine function may be involved in the pathogenesis and course of autoimmune diseases including multiple sclerosis (MS). Dehydroepiandrosterone (DHEA) in this connection is of particular interest as it appears to have effects on the immune system. Moreover, DHEA levels are decreased in chronic inflammatory diseases. To further investigate the role of DHEA in MS, we administered the adrenocorticotropin (ACTH) stimulation test and the combined dexamethasone and corticotropin-releasing hormone (DEX-CRH) test to 24 patients with active MS (13 women, 11 men; age 39 +/- 2 years, mean +/- SEM; Expanded Disability Status Scale, EDSS score 4.4 +/- 0. 4, mean +/- SEM; 12 with acute relapse, 12 with chronic progression) and to 18 healthy controls matched for age and sex (8 women, 10 men; age 37 +/- 3 years). There were no statistically significant differences in the plasma cortisol response to ACTH between any groups. In the DEX-CRH test, plasma cortisol concentrations showed higher values before (DEX-pretreated) and after CRH stimulation in the MS patients than in the controls (AUC(cortisol) 738.3 +/- 154.5 vs. 295.7 +/- 55.8; p < 0.05), this finding was more pronounced in chronic progressive patients. DHEA concentrations were decreased in MS patients (AUC (DHEA) 14.4 +/- 1.6 vs. 23 +/- 2.4; p < 0.05) and cortisol/DHEA ratios were increased in the patients compared to the controls (p < 0.05). There was a positive correlation between the EDSS score and maximum cortisol/DHEA ratio (r = 0.45; p = 0.031). As with the hypothalamic-pituitary-adrenal axis system, our results suggest a dysfunction in the DHEA secretion in patients with MS.
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PMID:Dehydroepiandrosterone response to the adrenocorticotropin test and the combined dexamethasone and corticotropin-releasing hormone test in patients with multiple sclerosis. 1065 36

Certain functional interactions between the nervous, endocrine, and immune systems are mediated by cytokines. The pro-inflammatory cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF) were among the first to be recognized in this regard. A modulator of these cytokines, IL-10, has been shown to have a wide range of activities in the immune system; in this review, we describe its production and actions in the hypothalamic-pituitary-adrenal (HPA) axis. IL-10 is produced in pituitary, hypothalamic, and neural tissues in addition to lymphocytes. IL-10 enhances corticotropin releasing factor (CRF) and corticotropin (ACTH) production in hypothalamic and pituitary tissues, respectively. Further downstream in the HPA axis endogenous IL-10 has the potential to contribute to regulation of glucocorticosteroid production both tonically and following stressors. Our studies and those of others reviewed here indicate that IL-10 may be an important endogenous regulator in HPA axis activity and in CNS pathologies such as multiple sclerosis. Thus, in addition to its more widely recognized role in immunity, IL-10's neuroendocrine activities described here point to its role as an important regulator in communication between the immune and neuroendocrine systems.
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PMID:IL-10 as a mediator in the HPA axis and brain. 1069 24

We conducted a meta-analysis of randomized controlled clinical trials on steroid treatment for multiple sclerosis and optic neuritis. Of the 25 trials comparing steroids and controls without steroid treatment that we identified 12 were selected for this review. A meta-analysis was conducted to calculate the overall odds ratio across the studies for the numbers of patients without functional improvement and with new relapses. The trials included a total of 1714 patients: 998 with multiple sclerosis and 716 with optic neuritis. Any type of corticosteroids or adrenocorticotropic hormone (ACTH) treatment was considered, as was any dosage, route of administration, and length of treatment. Main outcome measures were: (a) number of multiple sclerosis patients who did not improve by at least one point on the EDSS or equivalent scale, or number of optic neuritis patients without complete recovery of visual acuity at 8 or 30 days and at longer follow-up; (b) number of multiple sclerosis patients with at least one new relapse, or number of optic neuritis patients in whom definite multiple sclerosis was diagnosed at longer follow-up. We found that corticosteroids or ACTH produced a significant improvement in disability or visual acuity at 30 days (odds ratio 0.49; 95% CI 0.37-0.64). The improvement was not statistically significant at longer follow-up (0.85; 95% CI 0.67-1.09). The treatment did not significantly reduce the number of patients with relapses (0.74; 95% CI 0.54-1.01). Both low and high doses were effective for 30-day improvement, but only high-dose and short-term therapy were factors that identified subgroups with some reduction in the risk of new relapse. However, the power of the statistical analysis to detect a reliable difference in the subgroups was low. Steroid treatment is therefore effective in accelerating short-term recovery in patients with multiple sclerosis or optic neuritis. Whether steroids are also effective in reducing the risk of relapse, and the optimal dose and length of treatment must still be determined.
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PMID:Steroids for multiple sclerosis and optic neuritis: a meta-analysis of randomized controlled clinical trials. 1092 72

Hypothalamo-pituitary-adrenal (HPA) dysregulation has recently been demonstrated in multiple sclerosis (MS) by means of combined dexamethasone corticotropin-releasing hormone (Dex-CRH) suppression tests. Authors found a correlation with course of disease and to a lesser extent with depressive symptoms. In this study, we aimed to further evaluate whether HPA disturbances in MS are correlated with cognitive impairment, disability status, and fatigue. Dex-CRH tests were performed in a total of 40 patients and 11 healthy controls. Concomitantly, cognitive impairment was evaluated using the symbol digit modalities test and fatigue was assessed by different fatigue severity scales. When comparing patient subpopulations to healthy subjects, Dex-CRH stimulation tests indicated an HPA hyperactivity in primary and secondary progressive MS, while relapsing-remitting patients had response patterns similar to controls. However, results were only significant for one of the six analysed parameters, i.e. area under the curve calculations of ACTH stimulation. Within the patient sample, clear-cut differences emerged between groups of different cognitive impairment, being significant for all ACTH response parameters. Our results suggest an HPA hyperactivation related to increased cognitive impairment. Indicators of HPA axis activation further correlated substantially with neurologic disability, but only moderately with duration of disease and even less with depressive symptoms and fatigue. We conclude that the observed dysregulation is more likely a secondary effect of the extent of brain damage rather than primarily involved in the pathogenesis of MS.
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PMID:Cognitive impairment correlates with hypothalamo-pituitary-adrenal axis dysregulation in multiple sclerosis. 1191 2


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