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)

We measured plasma concentration of alpha-melanocyte-stimulating hormone (alpha-MSH), a proopiomelanocortin derivative that modulates pyrogenic and proinflammatory effects of cytokines, in infectious and inflammatory disorders in humans to learn if changes in this peptide take place in naturally occurring disease. alpha-MSH was elevated in HIV-infected patients of the CDC groups III and IV. Although the peptide increased in the circulation of normal subjects injected with endotoxin, it was reduced in patients with septic syndrome. alpha-MSH was found in the synovial fluid of arthritis patients, and its concentration was greater in the forms of arthritis marked by greater inflammation. We found that alpha-MSH is increased in the circulation of patients with acute myocardial infarction receiving thrombolytic therapy. Plasma concentrations of alpha-MSH is increased in the circulation of patients with acute myocardial infarction receiving thrombolytic therapy. Plasma concentrations of alpha-MSH were lower in healthy elderly subjects than in young controls. Because an excess of proinflammatory cytokines can have detrimental effects, we investigated the influences of alpha-MSH on the production of interleukin-1 (IL-1) and tumor necrosis factor (TNF) in HIV-infected patients and in patients with septic syndrome. Production of these cytokines in whole-blood samples stimulated with endotoxin was significantly reduced by treatment of blood with alpha-MSH. alpha-MSH has been injected into at least 106 human subjects to study its effects on pituitary function, menstrual bleeding, and tanning. The peptide was always well tolerated. alpha-MSH administration could open new perspectives in treatment of inflammatory diseases in humans.
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PMID:The neuropeptide alpha-MSH in HIV infection and other disorders in humans. 962 10

To gain insight into the neurochemical pathologies contributing to AIDS dementia complex, neurotransmitter levels were measured in the brains of mice infected with the LP-BM5 leukemia retrovirus. These mice develop immunologic and cognitive deficits analogous to human HIV-1 infection. Met-enkephalin and substance-P levels declined approximately 50% in the striatum and hypothalamus beginning as early as 4 weeks after infection. Hippocampal met-enkephalin levels were reduced to 50% only at 12 weeks after inoculation. Significant decreases (60-70%) in acetylcholine concentrations were observed in the striatum, cerebral cortex and hippocampus by 12 weeks after virus inoculation, while striatal GABA concentrations decreased to 50-60% at 8-12 weeks after infection. Striatal somatostatin levels were unchanged. Administration of the NMDA receptor antagonists MK-801 or LY 274614 ameliorated the decline in striatal met-enkephalin levels observed in mice after 8 weeks of infection. This pattern of neurotransmitter depletion and the ability of NMDA receptor antagonists to attenuate the loss of striatal met-enkephalin are consistent with an excitotoxic lesion. Thus, the elevation of glutamate levels secondary to glial activation may contribute to the contemporaneous development of cognitive deficits observed in mice infected with the LP-BM5 virus.
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PMID:The pattern of neurotransmitter alterations in LP-BM5 infected mice is consistent with glutamatergic hyperactivation. 963 May 62

Melanocortins are proopiomelanocortin-derived peptides that include adrenocorticotropic hormone [ACTH (1-39)], alpha-melanocyte-stimulating hormone [alpha-MSH (1-13)], and related amino acid sequences. Melanocortin peptides have potent antiinflammatory/anticytokine activity. Because cytokines such as interleukin 1 (IL-1) and tumor necrosis factor (TNF) can be detrimental in HIV-infected patients, we investigated the effects of melanocortins on production of IL-1 and TNF alpha in the blood of HIV patients. Cytokine production was measured in whole blood samples stimulated with LPS in the presence or absence of alpha-MSH (1-13), alpha-MSH (11-13), ACTH (1-24), or ACTH (1-39). Melanocortins reduced production of both cytokines in a concentration-dependent fashion. In separate experiments on normal peripheral blood mononuclear cells (PBMC), alpha-MSH (1-13) inhibited production of IL-1 beta and TNF alpha induced by HIV envelope glycoprotein gp 120. These results suggest that stimulation of melanocortin receptors in inflammatory cells could be a novel way to reduce production of cytokines that promote HIV replication.
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PMID:Melanocortin peptides inhibit production of proinflammatory cytokines in blood of HIV-infected patients. 970 Jul 61

We show that infection of primary monocyte-derived macrophages (MDMs) and blood lymphocytes (PBLs) by human immunodeficiency virus type 1 (HIV-1) R5 strains, but not that of PBLs by X4 strain HIV-1LAI, is inhibited by beta-chemokines RANTES and MIP-1alpha. A biotinylated disulfide-bridged peptide mimicking the complete loop of clade B consensus V3 domain of gp120 (V3Cs), but not a biotinylated V3LAI peptide or a control beta-endorphin peptide of approximately the same molecular weight (MW), was found to bind specifically to MDM membrane proteins, in particular two proteins of 42 and 62 kDa migrating as sharp bands after electroblotting onto Immobilon, and this was specifically inhibited by anti-V3 antibodies. When biotinylated V3Cs was incubated with intact MDMs, which were then washed and lysed, and the resulting material was incubated with streptavidin-agarose beads and electroblotted onto Immobilon, fresh V3Cs also bound to proteins of the same molecular weight recovered in the V3Cs-interacting material. This binding was inhibited by anti-V3 antibodies, and no binding occurred with the control peptides. V3Cs also bound to soluble recombinant CD4, and CD4 monoclonal antibody Q4120 specifically recognized the V3Cs-interacting 62-kDa protein, which should thus correspond to CD4. Recombinant radiolabeled RANTES, MIP-1alpha, and MIP-1beta, but not IL-8, also bound to a 42-kDa protein on the membrane of MDMs as well as to the V3Cs-interacting 42-kDa protein, and excess unlabeled V3Cs inhibited such binding. This protein was also recognized by antibodies to CCR5, the RANTES/MIP-1alpha/MIP-1beta receptor. These data show that V3Cs binds to MDM membrane proteins that comprise CD4 and CCR5, and that multimolecular complexes involving at least gp120 V3, CD4, and CCR5 are formed on the surface of MDMs as part of V3-mediated postbinding events occurring during HIV-1 infection.
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PMID:Interaction of human immunodeficiency virus type 1 envelope glycoprotein V3 loop with CCR5 and CD4 at the membrane of human primary macrophages. 987 Mar 13

To determine whether concentrations of the anti-inflammatory peptide alpha-melanocyte stimulating hormone (alpha-MSH) are associated with accelerated or reduced disease progression in patients with HIV infection, plasma concentrations of alpha-MSH and two other anticytokine molecules, interleukin-1 receptor antagonist (IL-1 ra) and soluble tumor necrosis factor receptor (s TNF r), were taken repeatedly from HIV-positive patients over a 1-year period. Samples from 87 patients were collected by using special precautions to ensure accurate measurement of the peptide. Alpha-MSH concentrations were determined by radioimmunoassay; IL-1 ra and s TNF r concentrations were measured by using enzyme-linked immunosorbent assays. Clinical and immunologic variables were recorded to determine whether there is an association between cytokine antagonist concentrations and disease progression. Elevated concentrations of circulating alpha-MSH were associated with reduced progression of the disease. Circulating alpha-MSH was greater in non-progressors than in progressors; the association between elevated alpha-MSH and reduced disease progression was even more pronounced in patients with baseline CD4+ T cell counts less than 200/microL. No such association was observed for the other two anticytokine molecules, and there was no significant correlation between the plasma concentration of either cytokine antagonist and alpha-MSH. The present evidence and previous findings indicate that elevated concentrations of alpha-MSH are associated with reduced disease progression in HIV-infected patients.
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PMID:Elevated concentrations of plasma alpha-melanocyte stimulating hormone are associated with reduced disease progression in HIV-infected patients. 1007 63

The purpose of the present research was to determine if alpha-melanocyte-stimulating hormone (alpha-MSH) and its C-terminal tripeptide [alpha-MSH (11-13), KPV] alter HIV expression in infected cells. The results indicate that chronically HIV-1-infected promonocytic U1 cells produce alpha-MSH and that immunoneutralization of the endogenous peptide enhances HIV expression. Because U1 cells express the alpha-MSH receptor 1 (MC1R), an autocrine-inhibitory circuit based on the peptide and its receptor likely occurs in these cells. To determine effects of pharmacological concentrations of alpha-MSH peptides on HIV expression, we measured p24 antigen release by TNF-alpha-stimulated U1 cells exposed to a wide range of concentrations of synthetic alpha-MSH and KPV. Viral expression was reduced by both peptides. KPV also effectively reduced HIV replication in acutely infected monocyte-derived macrophages (MDM). The basis of the peptide influence on viral replication is at the transcriptional level; KPV inhibited activation of NF-kappaB that is known to enhance viral expression. Endogenous alpha-MSH likely contributes to natural defense against HIV. However, greater concentrations of synthetic peptide are much more effective in reducing HIV expression in infected cells.
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PMID:Alpha-melanocyte-stimulating hormone peptides inhibit HIV-1 expression in chronically infected promonocytic U1 cells and in acutely infected monocytes. 1107 9

Subjects with human immunodeficiency virus type 1 (HIV-1) infection display increased activity of the hypothalamo-pituitary-adrenal (HPA) axis, which may play a role in both HIV-related neurodegenerative processes and disease progression. It has been speculated that the HIV coat protein gp120 may be responsible for these changes, and previous experimental evidence in both transgenic and nontransgenic mice supports this view. We speculated that one of the effects of gp120 in the CNS is to act within the hypothalamus to affect both corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), the principal regulators of HPA axis. We therefore administered i.p. gp120 (100 ng/rat) or vehicle to male Wistar rats and then detected Fos protein (an index of neuronal activation), CRH, and AVP immunoreactivity in the cellular compartments of the hypothalamic paraventricular nucleus (PVN). In addition, we tested the direct effect of various concentrations of gp120 on the release of CRH and AVP from rat hypothalamic explants maintained in vitro. Any modulation of gp120 effects by nitric oxide (NO) pathways was also sought by coadministering i.p. to rats or adding to the hypothalamic preparations the NO synthase inhibitor N(G)-methyl-l-arginine (l-NMMA). Gp120 induced the expression of Fos protein in both the parvo- and the magnocellular PVN, which was significantly attenuated by l-NMMA 10(-6) nM/L (P < 0.001 vs gp120 alone). Double immunochemistry showed costaining for Fos protein and CRH or AVP in the PVN following gp120; the number of double-labeled CRH and AVP cells for Fos protein was markedly reduced (P < 0.001) by coadministration of l-NMMA 10(-6) nM/L. In the in vitro studies, addition of gp120 to the hypothalamic explants in the dose range of 10 pM-1 nM resulted in a clear stimulation of both CRH and AVP release (P < 0.05-0.001 compared to control); in the presence of l-NMMA at 10-fold higher concentrations the stimulatory effect of gp120 on the release of both peptides was completely lost. It would therefore appear that gp120 activates CRH and AVP-producing neurons in the hypothalamic PVN and stimulates the release of both peptides in vitro via NO-dependent mechanisms. These findings, in line with previous evidence, further suggest that the increased activity of the HPA axis associated with HIV infection may be of central origin, due to the effects of gp120 on hypothalamic CRH and AVP release.
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PMID:Stimulating effect of HIV-1 coat protein gp120 on corticotropin-releasing hormone and arginine vasopressin in the rat hypothalamus: involvement of nitric oxide. 1108 2

Adrenal insufficiency is known to be a complication of HIV infection, although estimates of its prevalence and severity vary. Adrenal insufficiency is the most serious endocrine complication that occurs in persons with HIV infection. Patients with acquired immune deficiency syndrome (AIDS) are considered to be at high risk for primary or secondary adrenal insufficiency. We describe 3 patients with AIDS who had clinical features suggestive of adrenal insufficiency, but their corticotropin (ACTH) stimulation tests were normal. Repeat testing confirmed the diagnosis in one patient, and further testing with the overnight metyrapone test revealed evidence of secondary adrenal insufficiency in the other patients. Persistent clinical improvement was evident on subsequent glucocorticoid therapy. A normal response to the ACTH stimulation test can be dangerously misleading. Patients with AIDS and suspected adrenal insufficiency who have normal screening by the ACTH stimulation test should undergo further testing for secondary adrenal disease.
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PMID:Adrenal insufficiency in HIV infection: a review and recommendations. 1121 16

Serum cortisol and adrenocorticotropic hormone (ACTH) values and CD4 cell count were evaluated in 25 perinatally HIV-1-infected children. The children were divided into three groups: group 1 included eight asymptomatic or paucisymptomatic children, group 2 nine moderately symptomatic children, and group 3 eight children with severe clinical manifestations. Group 1 children were without antiretroviral therapy; the remaining children received zidovudine (AZT) treatment. Only one group 3 patient had primary adrenal insufficiency. No significant differences in cortisol and ACTH secretion were found either between all HIV-1-infected and 126 age- and sex-matched normal children or among the three groups of patients. Mean CD4 cell count of each group declined in parallel to disease progression. No correlations were found between cortisol or ACTH values and CD4 cell count. Adrenal failure may be a late complication of HIV-1 infection and should be searched for in severely ill patients. Our data argue against the hypothesis of a cortisol-induced shift from T-helper-1 (Th1) to Th2 cytokine production profile as the pathogenetic mechanism of progression to AIDS.
Pediatr AIDS HIV Infect 1996 Aug
PMID:ACTH and cortisol secretions in children with perinatal HIV-1 infection. 1136 16

Screening for HIV in China began in 1984, with the first AIDS case appearing in 1985. 305,280 sera were tested as of 1992, of which 379 were seropositive for antibodies to HIV. Of these 379 individuals, there were 4 hemophiliacs identified in 1985, 1 homosexual male, 4 individuals returning from Africa, 365 drug addicts and 2 spouses. 68 foreigners and 1 Chinese hemophiliac from Hong Kong also tested seropositive. Concern is expressed over the psychosomatic trials of infected women who feel unable to discuss their HIV status with family members for fear of influencing their role as primary caregivers and sex partners. Without access to medical therapy and support groups, these women no doubt feel isolated. Non-directive counseling is recommended for seropositive women during pregnancy. AIDS patients have reduced natural killer cell cytotoxicity. Seminal plasma also suppresses several immune responses. The pathogenicity of HIV, however, has yet to be determined. Fatty acid metabolism and Beta-endorphin are discussed in the context of therapeutic approaches. HIV/STD interactions are finally considered with individual attention given to bacterial vaginosis, hepatitis B, Chlamydia trachomatis, Herpes Simplex virus, microbiological contaminants of the vagina bacterial vaginosis, syphilis, mycoplasmas/epididymitis, bacterial prostatitis, and IVF culture media infections.
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PMID:HIV / STD interactions immunosuppression and future research development. 1228 86


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