Catecholamine metabolic process

Abstract: Recurrent hereditary polyserositis (RHP) or familial Mediterranean fever (FMF) is a chronic inherited illness of obscure aetiology. The disease is characterised by paroxysmal attacks of fever, peritonitis, pleuritis or arthritis, and predominantly affects Sephardic Jews, Arabs, Turks and Armenians. In this study, we report our 11-year experience of 175 Arab patients with this disease. As with other ethnic groups, the most common manifestation (93.7 per cent) was peritonitis. Arthritis (33.7 per cent) and pleurisy (32 per cent) were next in frequency. Adult patients in this series unlike those in other ethnic groups, rarely presented with arthritis. Similarly rare were amyloidosis, rashes, splenomegaly, hepatomegaly or lymphadenopathy. The aetiology of this disease is not clear but we suspect that abnormalities in catecholamine metabolism may be a factor in the pathogenesis.

Abstract: One of the major problems associated with long-term neuroleptic treatment is persistent tardive dyskinesia (TD), for which there is no satisfactory treatment. We have recently proposed that some cases of TD are associated with neuronal dysfunction resulting from excess free radical production occurring during catecholamine metabolism. We therefore decided to assess the efficacy of a powerful free radical scavenging agent, alpha-tocopherol (vitamin E), on the clinical signs of TD. We treated 15 patients with persistent TD with alpha-tocopherol and matched placebo in a randomized crossover design. Patients demonstrated a significant overall reduction in scores on the Abnormal Involuntary Movements Scale (AIMS) after treatment with alpha-tocopherol, but not after placebo. The mean reduction in the AIMS score with alpha-tocopherol was 43 percent, with seven patients showing a greater than 50 percent reduction in their dyskinesia. There was also a trend for a decrease in scores on the Brief Psychiatric Rating Scale, but no change was observed in scores on the Simpson-Angus Scale for Extrapyramidal Side Effects. Our findings are consistent with the possibility that alpha-tocopherol is beneficial in the treatment of some patients with TD, but further research is necessary to establish the efficacy of this agent.

Abstract: Previous studies indicating the importance of catecholamine metabolism in neuroblastoma were briefly reviewed. Metabolic pathways were presented showing how the major urinary metabolites 3-methoxy-4-hydroxymandelic acid (VMA) and 3-methoxy-4-hydroxy-phenylacetic acid (HVA) are formed from norepinephrine and from dopamine plus 3,4-dihydroxyphenylalanine (DOPA), respectively. For 289 neuroblastoma patients at the time of diagnosis, the urinary excretion of VMA was significantly elevated in 75%, and HVA was elevated in 80%. Periodic assay of these metabolites during the course of the disease revealed that the excretion trends were of prognostic value with 80-90% reliability. By contrast, when the excretion in only the initial urine specimens was considered, the survival rate was the same for patients with normal, and with significantly elevated, excretion. Review of the results of tracer studies aimed at elucidating the in vivo metabolic origins of the urinary metabolites suggested that a) in neuroblastoma, the catecholamines were largely inactivated by intracellular metabolism in the tumor cells; b) there was excess production and excretion of the norepinephrine precursors, DOPA and dopamine; and c) in the tumors of most neuroblastoma patients, the initial enzyme in catecholamine synthesis, tyrosine hydroxylase, had an activity comparable with that in normal adrenal glands. The importance of the metabolism of catecholamines in patients with neuroblastoma was stressed: a) The excretion of elevated levels of urinary catecholamine metabolites were useful in diagnosis and in following the course of the disease, and b) study of the catecholamine metabolism in these patients permitted examination of possible relationships between the activity of the enzymes involved in catecholamine synthesis and the malignancy of this tumor.

Abstract: The effects of streptozotocin-induced (STZ) diabetes on neuroendocrine and sexual function were evaluated in adult male rats. Adult male rats were injected with STZ (50 mg/ kg) or vehicle and tested for copulatory behavior 7, 14, and 21 days later. The rats were killed 1 month after STZ or vehicle treatment for measurement of plasma hormone levels, hypothalamic catecholamine turnover, LHRH content, and in vitro pituitary function. The STZ rats showed significant deficits in mount, intromission, and ejaculatory behaviors. Plasma levels of testosterone, LH, FSH, and PRL were all significantly reduced in the STZ compared to the control rats, but in vitro LH secretion was enhanced after STZ treatment. In vitro PRL secretion and the inhibitory response to dopamine did not differ between the two groups. The levels of LHRH were reduced in the medial basal hypothalamus (MBH), but LHRH levels in the median eminence (ME) and anterior hypothalamus (AH) were unchanged after STZ treatment. Norepinephrine turnover was ...