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)

A 9-year-old boy with varicella had an encephalitis with an unusually long and fluctuating course. Improvement in his deteriorating clinical condition coincided with the initiation of corticotropin therapy and the child recovered completely. Computed tomographic scan of the brain initially showed extensive areas of low absorption in white matter compatible with demyelination, which later resolved. These findings suggest that the pathologic changes of postvaricella encephalitis may be associated with a reversible demyelinative process.
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PMID:Postvaricella encephalitis. 632 14

The neurotropic murine coronavirus, MHV-JHM (JHMV) causes encephalitis and paralytic-demyelinating disease in susceptible strains of mice and rats, serving as a model for human demyelinating diseases such as multiple sclerosis. In this communication, we report that a single intracerebral administration of the naturally occurring neuropeptide, beta-endorphin, reduced the incidence of JHMV-induced paralytic-demyelinating disease 40-50% in C57Bl/6 mice. Protection from disease was accompanied by significantly reduced virus replication in the brain as early as 3 days post-infection and did not occur in irradiated, or immunoincompetent mice. The data suggest that beta-endorphin engages immune mechanisms of host resistance to JHMV infection to protect the mice from disease.
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PMID:Beta-endorphin protects mice from neurological disease induced by the murine coronavirus MHV-JHM. 822 10

The endocrine system participates in the regulation of the immune and neural systems and therefore hormonal factors probably play an important role in the development and course of multiple sclerosis (MS). Specifically, the hypothalamic-pituitary-adrenal (HPA) system seems crucial because (a) the inflammatory response is accompanied by HPA activation; (b) animal models with an inherited HPA defect are prone to developing experimental autoimmune encephalitis; and (c) most important, corticosteroids are still the most widely used treatment. We administered a recently developed neuroendocrine function test that combines dexamethasone suppression (1.5 mg orally at 2300 h) and corticotropin-releasing hormone (CRH) stimulation (100 micrograms i.v. at 1500 h the following day) and measured the response of plasma cortisol and corticotrophin (ACTH) secretion in 19 patients with an acute exacerbation of MS. These patients had a significantly higher mean plasma cortisol response than age-matched controls (peak minus baseline; 48.1 +/- 10.5 ng/ml [mean +/- SEM] versus 19.8 +/- 4.2 ng/ml; p < 0.05), but the corresponding ACTH values for the two groups were indistinguishable (13.4 +/- 1.4 pg/ml [mean +/- SEM] versus 11.3 +/- 1.4 pg/ml; n.s.). The response range in the patients was broader and we identified six patients with excessive cortisol release (peak minus baseline: 100.5 +/- 14.4 ng/ml [mean +/- SEM]), whereas four patients failed to respond at all. The hormonal response patterns were not related to previous treatments with corticosteroids or other immunosuppressants or to psychopathological features. These results point to a heterogeneity of HPA system function, most likely at the corticosteroid receptor level, which has clinical implications for all those treatments that affect the HPA system and the course of MS.
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PMID:Heterogeneity of hypothalamic-pituitary-adrenal system response to a combined dexamethasone-CRH test in multiple sclerosis. 875 May 68

Inflammatory processes contribute to neurodegenerative disease, stroke, encephalitis, and other central nervous system (CNS) disorders. Activated microglia are a source of cytokines and other inflammatory agents within the CNS and it is therefore important to control glial function in order to preserve neural cells. Melanocortin peptides are pro-opiomelanocortin-derived amino acid sequences that include alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH). These peptides have potent and broad anti-inflammatory effects. We tested effects of alpha-MSH (1-13), alpha-MSH (11-13), and ACTH (1-24) on production of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and nitric oxide (NO) in a cultured murine microglial cell line (N9) stimulated with lipopolysaccharide (LPS) plus interferon gamma (IFN-gamma). Melanocortin peptides inhibited production of these cytokines and NO in a concentration-related fashion, probably by increasing intracellular cAMP. When stimulated with LPS + IFN-gamma, microglia increased release of alpha-MSH. Production of TNF-alpha, IL-6, and NO was greater in activated microglia after innmunoneutralization of endogenous alpha-MSH. The results suggest that alpha-MSH is an autocrine factor in microglia. Because melanocortin peptides inhibit production of pro-inflammatory mediators by activated microglia they might be useful in treatment of inflammatory/degenerative brain disorders.
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PMID:Melanocortin peptides inhibit production of proinflammatory cytokines and nitric oxide by activated microglia. 962 Jun 67

It is clear that inflammatory processes contribute to neurodegenerative disease, stroke, closed head injury, encephalitis, and other CNS disorders. These inflammatory processes are marked by local increases in cytokines, in particular tumor necrosis factor-alpha (TNF-alpha). It is important to control such CNS inflammation in order to preserve neural function. The neuroimmunomodulatory peptide alpha-melanocyte-stimulating hormone (alpha-MSH) has been shown to modulate peripheral inflammation by acting on melanocortin receptors in host cells (macrophages, neutrophils) to inhibit production of such proinflammatory agents. Our results indicate that alpha-MSH likewise acts directly within the brain to modulate local inflammation. To determine if microglia are involved in anti-inflammatory responses to alpha-MSH within the brain, murine cells were tested; they produced TNF-alpha and nitric oxide in response to challenge, and production of both was reduced by alpha-MSH. In tests on human astrocytes, both alpha-MSH (1-13) and alpha-MSH (11-13) reduced TNF-alpha. Ischemia/reperfusion in the posterior circulation in dogs causes inflammatory reactions and disturbance of function, estimated from decreases in auditory-evoked potentials. These deficits were reduced by administering alpha-MSH systemically during reperfusion, moreso when the peptide was given during both ischemia and reperfusion. The results indicate that, much as for inflammation in the periphery, alpha-MSH modulates brain inflammatory responses mediated by proinflammatory agents.
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PMID:Peptide modulation of inflammatory processes within the brain. 973 Jun 84

The neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) modulates inflammation by inhibiting production of proinflammatory cytokines. Using a plasmid vector encoding alpha-MSH, we examined whether autocrine alpha-MSH inhibits activation of the nuclear transcription factor NF-kappaB, a factor that is essential to expression of proinflammatory cytokines, in human glioma cells (A-172). Electrophoretic mobility shift assays of nuclear extracts demonstrated that NF-kappaB activation induced by lipopolysaccharide was inhibited in glioma cells transfected with alpha-MSH vector. Western blot analysis revealed that this inhibition was linked to preservation of expression of IkappaBalpha protein. Chloramphenicol acetyltransferase assay indicated that NF-kappaB-dependent reporter gene expression was suppressed in A-172 cells transfected with alpha-MSH vector. Finally, fluorescence staining confirmed that A-172 cells bear alpha-MSH receptors. The findings are consistent with the idea that, in central nervous system (CNS) inflammation, autocrine alpha-MSH exerts anti-inflammatory actions via modulation of NF-kappaB activation by preservation of IkappaBalpha protein. Based on this action of the peptide, it should be possible to treat neurodegenerative disease, stroke, encephalitis, trauma, and other CNS disorders that have an inflammatory component through gene therapy with alpha-MSH vector.
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PMID:Autocrine alpha-melanocyte-stimulating hormone inhibits NF-kappaB activation in human glioma. 1056 96

A 49-year-old man with herpes simplex encephalitis at age 22 was admitted with hypotension (90/60 mm Hg) and hypothermia (33.7 degrees C). His blood pressure was 80-90/50-60 mm Hg, with temperatures averaging 35 degrees C, for at least 3 years before admission. Evaluation of his hypothermia and hypotension revealed a low free triiodothyronine, low normal thyrotropin, luteinizing hormone < 2 mIU/L, follicle stimulating hormone <3 mIU/L, and low testosterone of 1.39 ng/dL. A baseline cortisol of 13.9 microg/dL was stimulated to 41.8 microg/dL with corticotropin, indicating he had partial anterior hypopituitarism with an intact pituitary-adrenal axis. Posterior pituitary function was normal. MRI revealed a "bright" posterior pituitary on a T1-weighted image, further indicating a normal posterior pituitary. Extensive decreased T1-weighting on MRI in the right and left temporal lobes was consistent with encephalomalacia. With thyroid hormone replacement, his blood pressure increased to 110/70 mm Hg with a temperature of 37 degrees C.
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PMID:Post-herpes encephalitic anterior pituitary insufficiency with hypothermia and hypotension. 1106 53

The amygdala is known to regulate neuroendocrine and behavioral responses to a variety of stimuli. Herpes simplex virus-1 (HSV-1) is the common cause of viral encephalitis, manifested by hypothalamic-pituitary-adrenal (HPA) axis activation, fever, hypermotor activity and aggression. We examined here the role of the central amygdala (cAMG) in regulating the HPA axis function, febrile and behavioral responses to HSV-1 infection in rats. Bilateral electrolytic lesions were performed in the cAMG. HSV-1 encephalitis was induced by intracerebroventricular (ICV) inoculation of purified virions. Motor activity and body temperature were examined by a biotelemetric system. ICV inoculation of HSV-1 caused a marked time-dependent increase in serum corticotropin (ACTH) and corticosterone at 4 and 24 h post-infection. These responses were attenuated in rats with bilateral lesions of the cAMG. HSV-1 infection induced fever, motor hyperactivity and aggressive behavior. These responses were also attenuated in rats with cAMG lesions. The cAMG plays an important role in mediating the neuroendocrine, febrile and behavioral responses to HSV-1 infection.
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PMID:Role of the central amygdala in modulating the pituitary-adrenocortical and clinical responses in experimental herpes simplex virus-1 encephalitis. 1613 13

Japanese encephalitis (JE) virus is a mosquito-borne virus belonging to the flavivirus family, including the West Nile and St Louis encephalitis viruses endemic to North America. JE virus is prevalent in East Asian countries and can cause acute lethal encephalitis. Although vaccination programs have decreased the incidence of JE in Japan, the cases that do occur are often fatal or associated with considerable clinical sequelae. We report, for the first time to our knowledge, a patient who had repetitive bouts of hyperthermia in the summertime after recovery from acute JE. An insulin challenge test revealed only marginal increases in the levels of beta-endorphin and growth hormone, indicating partial medial hypothalamic dysfunction. Magnetic resonance imaging showed T2 hyperintensity in both thalamic paraventricular subcortical regions, known to project to the hypothalamic paraventricular nucleus. We thus attributed the episodes of hyperthermia to secondary hypothalamic impairment with thalamic lesions.
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PMID:A case of post-Japanese encephalitis with partial hypothalamic dysfunction showing repetitive hyperthermia in summertime. 1625 37

Here we report an infant who had herpes simplex virus (HSV) encephalitis and sustained severe bilateral damage to the posterior frontal lobes, postcentral gyri, and the thalami despite intravenous acyclovir treatment. At 7 months of age, the patient developed infantile spasms and was treated with corticotropin injections. After 10 days of corticotropin treatment, she developed lethargy, fever, and opisthotonic posturing. Her cerebrospinal fluid again was positive for HSV DNA, indicating recurrent HSV encephalitis, and repeat MRI revealed new lesions of the right frontal, parietal, temporal, and occipital lobes. Immunosuppression by corticotropin may have led to the reactivation of the HSV encephalitis. Corticotropin should be relatively contraindicated for use when a patient has a history of HSV infection, or intravenous acyclovir should be administered concurrently.
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PMID:Herpes simplex virus central nervous system relapse during treatment of infantile spasms with corticotropin. 1660 80


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