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)

This report describes a 63-yr-old man with lung cancer accompanying hypertension, hyperpigmentation, muscle weakness, psychosis, hypokalemia, hyperglycemia, hyponatremia, massive natriuresis and lower serum osmolality than urine osmolality. Elevated levels of plasma and urine corticosteroids and of plasma immunoreactive adrenocorticotropic hormone (ACTH) were not altered by the administration of large amounts of dexamethasone. Elevated plasma antidiuretic hormone (ADH) values were also demonstrated. Postmortem examinations revealed small cell lung carcinoma with extensive metastasis, bilateral adrenocortical hyperplasia and Crooke's degeneration of the pituitary gland. Immunoradiological and immunohistochemical studies demonstrated the presence of immunoreactive ACTH, ADH and gastrin-releasing peptide in the tumor tissue. Beta-melanocyte-stimulating hormone, calcitonin and carcinoembryonic antigen were also detected by one of the methods. Hence, this is a rare case of lung cancer with multiple hormone production and clinical and laboratory evidence of both the ectopic ACTH and ADH syndromes.
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PMID:Small cell lung carcinoma with ectopic adrenocorticotropic hormone and antidiuretic hormone syndromes: a case report. 632 89

A 37-year-old woman presented with acute psychosis and cognitive impairment. Skull x-ray showed an enlarged sella turcica with erosion of the floor. Endocrinologic workup suggested the diagnosis of Cushing's disease and hyperprolactinemia. She had no cushingoid feature, and the only physical sign was mild generalized obesity. She showed a paradoxic response to dexamethasone suppression, and underwent trans-sphenoidal resection of a pituitary macroadenoma. Electron microscopy showed the tumor to be a Crooke's cell adenoma. Results of immunohistochemical staining were positive only for ACTH and beta-endorphin. The neuropsychiatric manifestations resolved after surgery.
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PMID:Occult Cushing's disease presenting with acute psychosis. 671 82

The endorphin neuropeptides may have neuroleptic-like effects on dopamine function and may be antischizophrenic. Ten chronic psychotic patients with neuroleptic-induced tardive dyskinesia and parkinsonism received placebo and des-tyrosine-gamma-endorphin (DT gamma E). Drug effects on movement disorders and eye-blinking rates were assessed by blind evaluations of randomly sequenced videotapes made during standardized examinations before and 30, 60, and 120 minutes after each injection and at 24 hours postinjection on days of consecutive treatment. Changes in schizophrenic symptoms were evaluated openly with the schizophrenia subscale of the Comprehensive Psychiatric Rating Scale. There were no significant effects of DT gamma E on any parameter and no side effects. This suggests that DT gamma E, within the tested dose range, does not influence the pathophysiology of neuroleptic-induced dyskinesias or chronic schizophrenia or have neuroleptic properties. However, DT gamma E is well tolerated and should be tested with higher doses during prolonged treatment.
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PMID:Effect of des-tyrosine-gamma-endorphin in tardive dyskinesia. 701 Dec 48

The neuropeptide (des-tyrosine1)-gamma-endorphin (DT gamma E; beta-LPH 62-77) was given to 10 schizophrenic patients who had been free of neuroleptic medication for at least 3 weeks. DT gamma E was injected intramuscularly in a dose of 1 mg daily for 10 days following a double-blind placebo-controlled crossover design. In 4 of the 10 patients a pronounced antipsychotic effect was observed; in 3 a temporary or slight reduction of psychotic symptoms occurred; and in 3 no response was noted. DT gamma E led to decreased plasma levels of prolactin and in some patients to increased concentrations of homovanillic acid in cerebrospinal fluid (CSF). Neither plasma levels of growth hormone and cortisol nor CSF concentrations of 5-hydroxyindoleacetic acid were affected by DT gamma E. These data confirm that DT gamma E has antipsychotic properties in a number of schizophrenic patients and suggest an interaction between DT gamma E and central dopaminergic systems.
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PMID:(Des-tyrosine1)-gamma-endorphin in schizophrenia: clinical, biochemical, and hormonal aspects. 703 28

Animal experiments have shown that the gamma-endorphin fragment des-enkephalin-gamma-endorphin (DE gamma E; beta-lipotropin 66-77) is the shortest sequence with neuroleptic-like activity with potency comparable to des-tyrosine-gamma-endorphin. We postulated that DE gamma E may be an endogenous peptide implicated in psychopathologic disease, particularly schizophrenia. To investigate the purported antipsychotic action of DE gamma E, 23 patients with different types of relapsing schizophrenia were treated with DE gamma E dissolved in saline or placebo. Neuroleptic medication was continued during the experimental period. In the first single-blind trial, two patients were treated with 1 mg of DE gamma E and two with 10 mg of DE gamma E intramuscularly (IM) daily for ten days. In the second double-blind placebo-controlled trial 13 patients were treated with 3 mg of DE gamma E IM daily for ten days and six received placebo. Of the 17 patients treated with DE gamma E, two did not respond, 11 had a slight to moderate effect, and four responded markedly. No side effects were observed. The response to DE gamma E appeared to be negatively correlated with the dosage of neuroleptic medication and the duration of the last psychotic episode. These results support the hypothesis that disturbances in gamma-endorphin fragmentation might contribute to the pathogenesis of schizophrenic psychoses.
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PMID:Antipsychotic properties of Des-enkephalin-gamma-endorphin in treatment of schizophrenic patients. 709 98

The beta-lipotrophin fragment des-tyrosine-gamma-endorphin (DT gamma E) has been reported to have antipsychotic properties. We administered the compound without other psychoactive drugs to a subpopulation of schizophrenic subjects. Male patients with chronic psychotic illness and previous long-term neuroleptic therapy were given DT gamma E at a similar dose and duration of treatment that have been reported to be effective. No improvement in psychotic symptoms occurred; plasma prolactin level, a parameter characteristically altered by neuroleptic treatment, did not change. The beneficial effects of DT gamma E in schizophrenia may be specific to a diagnostic category, may be dependent on past pharmacologic treatment, or may occur only in combination with other drugs.
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PMID:Des-tyrosine-gamma-endorphin administration in chronic schizophrenics. A preliminary report. 721 42

Since 1975, different morphinomimetic peptides have been isolated from hypophyseal-hypothalamic extracts: the pentapeptides methionine-enkephalin and leucine-enkephalin, and the longer peptides alpha-, beta- and gamma-endorphin. The primary structure of most of these peptides is also present in that of beta-lipotropin. The morphinomimetic properties of endorphins can be blocked with opiate-antagonists. In rats, moreover, the endorphins influence behavior which cannot be blocked with opiate antagonists. On the basis of the hypothesis that hyperactivity of endorphin systems may be involved in the pathogenesis of schizophrenia and manic syndromes, the effect of opiate antagonists on psychotic and manic symptoms has been examined in a number of clinical studies in the past few years. A transient therapeutic effect has been demonstrated in about 30% of the patients so treated. Our own double-blind controlled study of 5 schizophrenic and 5 manic patients in the context of a World Health Organization project failed to reveal any therapeutic effect after subcutaneous injection of 20 mg naloxone. The possible reasons of the negative results are discussed.
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PMID:Use of naloxone in schizophrenic psychoses and manic syndromes. 723 53

The brain is an important target organ for both endogenous and synthetic corticosteroid hormones, but the nature of steroid action there is complex. We review a series of studies that was designed to elucidate possible relationships between the behavioral and biological effects of exogenous corticosteroids. In these studies, corticosteroids were administered to intact animals or to currently healthy volunteers, and behavioral and biological indices of corticosteroid effects were jointly assessed. In the first study, chronic corticosterone administration to intact rats resulted in increased locomotor activity (consistent with increased caudate or nucleus accumbens dopamine activity) and increased caudate homovanillic acid (HVA) levels. In the second study, acute dexamethasone administration to healthy human volunteers resulted in increased plasma HVA levels. These findings in animals and humans may help explain vulnerability factors for experiencing psychotic reactions during chronic corticosteroid treatment. To more closely mimic clinical conditions in which "steroid psychoses" develop, we administered a higher dose and more chronic corticosteroid medication (prednisone, 80 mg/day for 5 days) in a double-blind manner to healthy volunteers. Consistent with prior clinical observations, behavioral changes were variable across subjects. Seventy-five percent of the individual volunteers developed mild behavioral side effects during prednisone administration; in addition, significant, specific deterioration in cognitive performance was observed. Prednisone administration was also associated with significant decreases in plasma levels of adrenocorticotropic hormone (ACTH), cortisol, and 3-methoxy,4-hydroxyphenyl glycol (MHPG) and in cerebrospinal fluid (CSF) levels of ACTH, beta-endorphin (BE), beta-lipotropin (BLPH), somatostatin-like immunoreactivity (SLI), and norepinephrine (NE). It was also associated with significant slowing of brain wave electrical activity (viz., an increase in theta wave activity) on quantitative electroencephalography. Several behavioral changes, particularly those relating to mood or cognition, were related to changes in CSF levels of NE, MHPG, ACTH, BE, BLPH, and SLI and to the slowing of brain wave activity. Our preliminary data raise the possibility that the behavioral effects of exogenous corticosteroids have specific neural concomitants and that the pattern of biological changes produced contributes to the behavioral variability observed. Steroid effects on levels of biogenic amines, pro-opiomelanocortin (POMC)-related peptides and somatostatin, among others, as well as on brain electrophysiology, may be behaviorally relevant and are highlighted as being worthy of further investigation.
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PMID:Prospective controlled studies of the behavioral and biological effects of exogenous corticosteroids. 751 7

Three hundred thirteen patients with first-episode psychosis were assessed using the Royal Park Multidiagnostic Instrument for Psychosis (RPMIP) to determine differences among seven DSM-III-R diagnoses in the comparative frequencies and diagnostic efficiencies of DSM-III-R schizophrenia prodromal symptoms. Patients with a diagnosis of schizophrenia and schizophreniform disorder were significantly more likely to evince prodromal symptoms. A multinomial logit model suggested that individual prodromal symptoms were relatively poor at distinguishing between diagnoses. This was confirmed when sensitivity, specificity, and positive (PPP) and negative (NPP) predictive power of individual prodromal symptoms were examined. Although DSM-III-R schizophrenia prodromal symptoms do occur more commonly in schizophrenia, they are by no means pathognomonic of that disorder.
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PMID:Prodromal symptoms of schizophrenia in first-episode psychosis: prevalence and specificity. 755 67

Interactions between the hypothalamic-pituitary-adrenal (HPA) axis and central dopamine systems have been hypothesized to play a role in the pathophysiology of psychosis, but the normal physiology of HPA axis-dopamine interactions has not been fully defined. We report results from two uncontrolled pilot studies which explored the effects of ovine corticotropin-releasing hormone (CRH) on dopamine activity in healthy human subjects. Administration of CRH did not produce changes in plasma levels of homovanillic acid (HVA), the major dopamine metabolite, over the subsequent 3.5 hours. However, when the effects of CRH were followed over a longer period in a small subgroup, we found that CRH administration produced a two-fold rise in plasma HVA levels 20 hours later, without affecting plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), a major metabolite of norepinephrine. Thus, the findings of these pilot studies suggest that CRH may exert delayed but not acute effects on dopamine activity in man.
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PMID:Acute and delayed effects of corticotropin-releasing hormone on dopamine activity in man. 783 28


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