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Cerebrospinal fluid and urinary biogenic amines in depressed patients and healthy controls.

The National Institute of Mental Health-Clinical Research Branch Collaborative Study investigated 132 drug-free, severely depressed patients and 80 healthy controls. Forty-five percent of the depressed patients excreted markedly elevated levels of urinary epinephrine (E) and metanephrine (MET), while only 5% of healthy controls did so. Using gaussian mixture distributions, we identified two subgroups of depressed patients: one excreting normal levels and the other excreting high levels of urinary E, MET, norepinephrine, and normetanephrine. Cerebrospinal fluid homovanillic acid levels were low in a subgroup of depressed patients. When analyzed by subgroup, the elevated E + MET group had markedly lower cerebrospinal fluid homovanillic acid levels than controls, whereas depressed patients with normal catecholamine levels did not. Since it has been postulated that there are two subgroups of depressed patients, those with low 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and normal 5-hydroxyindoleacetic acid (5-HIAA) levels and those with normal MHPG levels and low 5-HIAA levels, several analyses were performed to see if such a group could be identified. Our analysis failed to find evidence of a subgroup of depressives with low MHPG and normal 5-HIAA levels or normal MHPG and low 5-HIAA levels.

Biogenic Amines↗

Cerebrospinal fluid concentrations of somatostatin and biogenic amines in grown primates reared by mothers exposed to manipulated foraging conditions.

BACKGROUND: In an earlier study, infant primates were nursed by mothers randomly assigned to variable foraging demand (VFD) or nonvariable foraging conditions (non-VFD). A group of grown VFD-reared subjects demonstrated elevations of cisternal cerebrospinal fluid (CSF) corticotropin-releasing factor concentrations and decreased CSF cortisol levels vs non-VFD counterparts. To further characterize neurobiological sequelae of disturbed early rearing, CSF concentrations of serotonin, dopamine, and norepinephrine metabolites (5-hydroxyindoleacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenethyleneglycol [MHPG], respectively) and of somatostatin were determined. METHODS: Second CSF taps were obtained from the previously studied cohort of 30 subjects and from 28 age-matched ad libitum-reared control subjects. Relevant assays were performed. RESULTS: All neurochemicals assayed except MHPG were elevated in the VFD-reared compared with non-VFD subjects. In the VFD group, statistically significant positive correlations between corticotropin-releasing factor and each neurochemical was found, except for MHPG. In the non-VFD subjects, no significant correlations with corticotropin-releasing factor were observed. No effect of age was evident. CONCLUSIONS: Reducing the predictability of maternal foraging demand during early rearing was associated with elevations of cisternal somatostatin and of serotonin and dopamine metabolite concentrations in grown offspring. The corticotropin-releasing factor elevations reported previously were positively correlated with all the elevated CSF parameters of the current study. The findings support the notion that adverse early rearing experiences in primates have longstanding and complex effects on a range of neurochemicals relevant to emotional regulation. Replication in prospective age-controlled studies is warranted.

Animals↗

Effect of active molluscicidal component of spices on different enzyme activities and biogenic amine levels in the nervous tissue of Lymnaea acuminata.

In vivo exposure of Lymnaea acuminata to thymol and [6]-gingerol (active molluscicidal components of Trachyspermum ammi and Zingiber officinale, respectively) indicates that they significantly alter acetylcholinesterase, lactic dehydrogenase, succinic dehydrogenase and cyto-oxidase activity in the nervous -tissue of snails. In vitro exposure showed that, except for acetylcholinesterase and lactic dehydrogenase, no significant changes were observed in cyto-oxidase and succinic dehydrogenase activity in the nervous tissue of L. acuminata. Sublethal exposure to thymol and [6]-gingerol reduced the levels of 5-hydroxytryptamine (5-HT) and dopamine (DA) in the nervous tissue of L. acuminata. There was, however, no significant change in the level of 5-hydroxy indol acetic acid (5-HIAA). Thymol and [6]-gingerol thus affects all the known neurotransmission mechanisms in the snail either separately or through a complex interaction between the different neurotransmitters. This may account for their toxicity to snails.

Acetylcholinesterase↗

Periodic maternal separation of neonatal rats produces region- and gender-specific effects on biogenic amine content in postmortem adult brain.

Early environment exerts profound effects on mammalian behavioral and neural development. The aim of this study was to describe changes in adult neurochemistry in the rat following repeated neonatal maternal separation (RMS) during the preweaning period, a procedure known to induce enduring behavioral effects. Following RMS, rats show an attenuated locomotor response to novelty, to D-amphetamine, and attenuated behavioral responses for conditioned incentives as adults. These behavioral effects are broadly opposite in direction to those found following postweaning isolation rearing. Isolation rearing-induced behavioral changes are associated with profound changes in central monoamine function. Following RMS, adult rats had increased tissue levels of dopamine in both dorsal and ventral striatum. The turnover of dopamine, as determined by the ratio of DOPAC to dopamine, was decreased in the mPFC of RMS subjects. Serotonin levels were reduced in dorsal hippocampus of RMS rats of both sexes and in the mPFC of male RMS rats. Noradrenaline levels were increased in the dorsal hippocampus in female, but not in male, RMS rats. These data provide evidence that, in addition to the adult behavioral consequences, RMS leads to profound, region-, and gender-specific changes in brain monoamine content. The developmental specificity of these results is discussed with respect to their possible role in altered behavioral development and psychopathology.

Animals↗

Copper, biogenic amines, and amine oxidases.

Amine oxidases have been classified in the past on the basis of either (a) the structural requirements in the substrate or (b) the tissue (or species) of origin, or both. As knowledge about the chemistry of these enzymes grows, their classification on the basis of chemical structure is becoming possible. Currently, many amine oxidases can be categorized according to whether they contain riboflavin (e.g. the monoamine oxidases -- EC 1.4.3.4) or copper (e.g. the amine oxidases of plasma and the diamine oxidases EC 1.4.3.6 -- found prominently in pig kidney cortex, placenta, and pea seedlings). The copper-linked oxidases are inhibited by cyanide and by semicarbazide. The nature of the carbonyl compound(s) in the various enzyme molecules is not yet known. Nutritional deficiencies of copper and treatment of animals with copper-chelating agents are reflected in reduced activity of one or more of these enzymes. The ultimate effects of copper deficiency and copper excess on amine metabolism in vivo are described.

Adrenalectomy↗

Positron emission tomographic study of D2 dopamine receptor binding and CSF biogenic amine metabolites in Rett syndrome.

We report on the first positron emission tomographic study of dopamine receptor binding in Rett syndrome. The patient is a 25 year old Austrian woman diagnosed at age 2 and followed since then by Rett. A computed axial tomogram (CT scan) showed cortical atrophy, and enlarged ventricles but normal structure of the caudate/putamen. Following the CT scan 20 mCi of 11 C N-methyl spiperone, a butyrophenone with a high affinity for dopamine D2 receptors was administered intravenously. The patient was found to have dopamine D2 receptor binding activity in the low normal range. The caudate/cerebellar activity ratio was below the mean regression line (p = 0.10) that relates the CA/CB ratio as a function of age. Levels of cerebrospinal fluid neurotransmitter metabolites were normal.

Adult↗

Effect of biogenic amines on oxidation of farmorubicin by Fenton-like reagents.

The aim of this study was to investigate the effect of dopa and catecholamines on the generation of oxygen active species during oxidation of farmorubicin by "Fenton-like" reagents using chemiluminescent and spectrophotometric techniques. The tested catechols were found to reduce the light emission accompanying oxidation of farmorubicin by Co(II) + H2O2 and Cu(II) + H2O2 mixtures. The quenching effect was followed by their rapid oxidation to aminochromes possessing toxic activities.

Biogenic Amines↗

Identification of alkaloids; the condensation products of biogenic amines with formaldehyde, enzymatically formed from 5-methyltetrahydrofolic acid.

The use of thin-layer chromatography has demonstrated that incubations of indoleamines with 5-methyl[14-C]tetrahydrofolic acid and an enzyme previously described as an N-methyltransferase, do not yield Nw, N1, or O-methylated products. Further elucidation by thin-layer chromatography, gas chromatography, mass spectrometry and selected ion monitoring enabled us to identify the reaction products as tetrahydroisoquinolines and tetrahydro-beta-carbolines in mixtures incubated respectively with catecholamines and indoleamines in the presence of 5-methyl[14-C]tetrahydrofolic acid and enzyme. The alkaloids have been shown to originate from a spontaneous condensation of the corresponding amines with formaldehyde, this latter being formed in the first stage of the reaction by enzymatic conversion from 5-methyltetrahydrofolic acid.

Alkaloids↗

The role of biogenic amines in foods.

Biologically active amines are normal constituents of many foods for example cheese, plant foods and wines. These low molecular weight organic based do not represent any hazard to individuals, unless large quantities are ingested or natural mechanism of their catabolism are inhibited. Investigations were performed concerning the histamine and tyramine content of the Hungarian made cheese, domestic vegetables, fruits and some other foods. In this paper we should like to draw the attention to the problems of amines from the point of view of food hygiene and food-drug interactions.

Biogenic Amines↗

The effects of acetylcholine, biogenic amines and other vasoactive agents on the cardiovascular functions of the Eel, Anguilla japonica.

The blood pressure in the cardinal vein, cardiac chambers and ventral and dorsal aortae have been recorded from conscious eels in water. At low doses, acetylcholine reduced the heart rate but increased the transbranchial differential blood pressure. The effects were abolished by atropine but not by tubocurarine. At doses in excess of 0.1 mug/kg, a secondary rise in arterial blood pressure was observed which could be abolished by bretylium, phentolamine or phenoxybenzamine. Catecholamines did not affect the heart rate although a transient bradycardia due to reflex inhibition could be observed with adrenaline and noradrenaline. Catecholamines increased the cardiac contractile force through an alpha-adrenergic mechanism which was blocked by phentolamine but not by propranolol. The relative potency was noradrenaline greater than adrenaline greater than isoprenaline. A beta-adrenergic receptor located in the branchial circulation led to vasodilation and decrease in transbranchial differential pressure. Both alpha-(vasoconstriction) and beta-(vasodilation) adrenergic receptors were present in the systemic circulation. Dopamine, 5-HT, GABA and bradykinin caused bradycardia abolishable by vagotomy or atropine treatment. Angiotensin II was hypertensive but did not affect the heart rate nor the transbranchial differential pressure. Tyramine caused release of endogenous catecholamines. With repeated doses, tachyphylaxis to the drug was observed. Histamine was without any obvious cardiovascular effects in the eel.

Acetylcholine↗