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

The hypothalamic-pituitary-adrenal (HPA) axis is regulated by stress-related excitatory inputs, and various inhibitory and negative-feedback controls by glucocorticoids and opioids, including pro-opiomelanocortin (POMC)-derived peptides. The role of POMC-derived peptides of pituitary origin in the modulation of brain POMC mRNA expression and opioid receptor binding was investigated using a line of transgenic mice that express a fusion gene composed of the pituitary expression-specific promoter region of the POMC gene driving the herpes simplex viral-1 thymidine kinase (TK). Male adult mice were treated with the antiherpes agent ganciclovir that selectively ablates cells expressing TK. Following treatment, POMC mRNA levels, measured by quantitative solution hybridization/RNase protection assays, were decreased by 48% in the pituitary of the TK+/+ mice, reflecting an expected loss of the pituitary corticotrope POMC cells. This treatment also significantly lowered pituitary beta-endorphin immunoreactivity content and plasma concentrations of corticosterone. In contrast, POMC mRNA levels were increased by 79% in the hypothalamus of the TK+/+ mice with pituitary POMC cell ablation. Binding of [(3)H]DAMGO to mu opioid receptors, as measured by quantitative autoradiography, was significantly reduced in several brain regions including the central grey, median raphe and superficial grey layer of the superior colliculus. These regions are innervated by hypothalamic POMC neurones. No significant differences in binding to either kappa or delta opioid receptors were found in the brain regions studied. These results suggest that POMC-derived peptides of pituitary origin may exert a tonic negative-feedback effect on hypothalamic POMC neurones. In turn, the downregulation of central mu opioid receptors in this model may be mediated through a mechanism related to hypothalamic POMC overexpression.
 ...
PMID:Ablation of pituitary pro-opiomelanocortin (POMC) cells produces alterations in hypothalamic POMC mRNA levels and midbrain mu opioid receptor binding in a conditional transgenic mouse model. 1157 31

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.
 ...
PMID:HIV / STD interactions immunosuppression and future research development. 1228 86

The influence of mexiletine hydrochloride on herpes-related pain responses was examined using mice infected with herpes virus. BALB/c mice were inoculated with herpes simplex virus (HSV; 1 x 10(6) plaque-forming units) on the right hind paw, and the contralateral hind paw was without inoculation. The changes in nociceptive threshold were examined using electric von fray meter. BALB/c mice inoculated with HSV showed a decrease in nociceptive threshold. Intraperitoneal administration of mexiletine prevented the decrease in nociceptive threshold dose-dependently in HSV-inoculated mice, which was firstly observed at a dose of 15.0 mg kg(-1), and peaked at doses more than 17.5 mg kg(-1). This antinociceptive effect of mexiletine attained peaks at 60-90 min after administration and declined gradually to non-treated levels by 150 min. Intraperitoneal administration of mexiletine at a dose of 17.5 mg kg(-1) (but not 10.0 mg kg(-1)) caused significant increase in beta-endorphin levels in the mid brain and hypothalamus of HSV-inoculated mice. However, mexiletine scarcely affected noradrenaline (norepinephrine) levels in the pons and medulla oblongata, even when HSV-inoculated mice were treated with 17.5 mg kg(-1) mexiletine. These results strongly suggested that mexiletine exerts antinociceptive effects on herpes-related pain through enhancement of beta-endorphin levels in the central nervous system in HSV-inoculated mice. It is also suggested that mexiletine will be a good candidate for an antinociceptive drug in the treatment of acute herpetic pain in man.
 ...
PMID:Attenuating effect of mexiletine hydrochloride on herpetic pain in mice infected with herpes simplex virus. 1460 18

Trigeminal neuropathic pain represents a real challenge to therapy because commonly used drugs are devoid of real beneficial effect or patients frequently become intolerant or refractory to some of these compounds. In a rat model of trigeminal neuropathic pain, which shares numerous similarities with human trigeminal neuralgia and trigeminal neuropathic pain, we used a genomic herpes simplex virus-derived vector (HSVLatEnk) to examine the possible effect of a local overproduction of proenkephalin A (PA) targeted to the trigeminal primary sensory neurons. Unilateral peripheral inoculation of recombinant vectors on the vibrissal pad territory resulted in an about ninefold increase in proenkephalin A mRNA levels in trigeminal ganglion ipsilateral to the infected side. Transgene-derived met-enkephalin accumulated in numerous nerve cell bodies of trigeminal ganglion and was transported through the sensory nerve fibers located in the infraorbital nerve. Bilateral mechanical hyperresponsiveness, which developed 2 weeks after chronic constrictive injury of the left infraorbital nerve, was significantly attenuated in animals overproducing PA in the trigeminal ganglion ipsilateral to the lesioned infraorbital nerve. This antiallodynic effect was reversed by both the opioid receptor antagonist naloxone and the peripherally acting antagonist naloxone methiodide. Our data demonstrate that the local overproduction of PA-derived peptides in trigeminal ganglion sensory neurons evoked a potent antiallodynic effect through the stimulation of mainly peripherally located opioid receptors and suggest that targeted delivery of endogenous opioids may be of interest for the treatment of some severe forms of neuropathic pain.
 ...
PMID:Attenuation of pain-related behavior in a rat model of trigeminal neuropathic pain by viral-driven enkephalin overproduction in trigeminal ganglion neurons. 1577 63

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.
 ...
PMID:Role of the central amygdala in modulating the pituitary-adrenocortical and clinical responses in experimental herpes simplex virus-1 encephalitis. 1613 13

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.
 ...
PMID:Herpes simplex virus central nervous system relapse during treatment of infantile spasms with corticotropin. 1660 80

The influence of artemin (AR) on herpes-related pain responses was examined using mice infected with herpes simplex virus (HSV). BALB/c mice were inoculated with HSV (1x10(6) plaque-forming units) on the right hind paw, while the contralateral hind paw was without inoculation. The changes in nociceptive threshold were examined using an electric Von Fray meter. Intraperitoneal administration of AR prevented a decrease in nociceptive threshold dose-dependently in HSV-inoculated mice, which was first observed at a dose of 1.0 mg/kg and peaked at doses higher than 1.5 mg/kg. This antinociceptive effect of AR attained peaks at 120 min after administration and declined gradually to non-treated levels by 270 min. Intraperitoneal administration of AR at a dose of 1.5 mg/kg scarcely affected beta-endorphin and noradrenaline levels in the central nervous system of HSV-inoculated mice. However, AR caused a significant decrease of the dynorphin levels in spinal cord. These results strongly suggest that AR exerts antinociceptive effects on herpes-related pain through changes of the dynorphin levels in the central nervous system of HSV-inoculated mice. It is also suggested that AR will be a good candidate as an antinociceptive drug for the treatment of acute herpetic pain in humans.
 ...
PMID:Attenuating effect of artemin on herpes-related pain responses in mice infected with herpes simplex. 1690 Jul 85

This study assessed the efficacy of pancreatic surface delivered enkephalin (ENK)-encoding herpes simplex virus type 1 (HSV-1) on spontaneous behaviors and spinal cord and pancreatic enkephalin expression in an experimental pancreatitis model. Replication-defective HSV-1 with proenkephalin complementary DNA (cDNA) (HSV-ENK) or control beta-galactosidase cDNA (HSV-beta-gal), or media vehicle (Veh) was applied to the pancreatic surface of rats with dibutyltin dichloride (DBTC)-induced pancreatitis. Spontaneous exploratory behavioral activity was monitored on days 0 and 6 post DBTC and vector treatments. The pancreas, thoracic dorsal root ganglia (DRG, T9-10), and spinal cord (T9-10) were immunostained for met-enkephalin (met-ENK), beta-gal, and HSV-1 proteins. Spinal cord was also immunostained for c-Fos, and pancreas was stained for the inflammatory marker regulated on activation, normal T-cells expressed and secreted (RANTES), mu-opioid receptor, and hemotoxylin/eosin. On day 6, compared to pancreatitis and vector controls, the DBTC/HSV-ENK treated rats had significantly improved spontaneous exploratory activities, increased met-ENK staining in the pancreas and spinal cord, and normalized c-Fos staining in the dorsal horn. Histopathology of pancreas in DBTC/HSV-ENK treated rats showed preservation of acinar cells and cytoarchitecture with minimal inflammatory cell infiltrates, compared to severe inflammation and acinar cell loss seen in DBTC/HSV-beta-gal and DBTC/Veh treated rats. Targeted transgene delivery and met-ENK expression successfully produced decreased inflammation in experimental pancreatitis.
 ...
PMID:Treatment of inflamed pancreas with enkephalin encoding HSV-1 recombinant vector reduces inflammatory damage and behavioral sequelae. 1756 49

Chronic morphine exposure induces physical dependence and tolerance. Previous studies have shown that there is a decrease in met-enkephalin levels in states of morphine physical dependence, and that increasing enkephalin during opiate physical withdrawal ameliorates the severity of the morphine withdrawal syndrome. In order to investigate the role of spinal opioid peptide in the phenomenon of naloxone-precipitated withdrawal we examined the effect of herpes simplex virus vector-mediated overexpression of proenkephalin in lumbar dorsal root ganglia in rats with neuropathic pain treated with morphine. The morphine physical dependence was induced by chronic administration of intraperitoneal (IP) morphine for 2 weeks. Rats with neuropathic pain inoculated subcutaneously with the vector-mediated overexpression of proenkephalin showed a significant reduction in jumps, 'wet-dog' shakes, diarrhea and ptosis precipitated by naloxone after 2 weeks of morphine treatment. The global withdrawal score was also reduced significantly by vector-mediated overexpression of proenkephalin. These studies demonstrate a role for opioid peptide in the spinal cord in mediating some of the withdrawal response.
 ...
PMID:Transgene-mediated enkephalin expression attenuates signs of naloxone-precipitated morphine withdrawal in rats with neuropathic pain. 1876 80


<< Previous 1 2