Simultaneous extraction and determination of monoamine neurotransmitters in human urine for clinical routine testing based on a dual functional solid phase extraction assisted by phenylboronic acid coupled with liquid chromatography-tandem mass spectrometry.

The major monoamine neurotransmitters, serotonin (5-HT) and catecholamines (i.e., norepinephrine (NE), epinephrine (E), and dopamine (DA)), are critical to the nervous system function, and imbalances of the neurotransmitters have been connected to a variety of diseases, making their measurement useful in a clinical setting. A simple, rapid, robust, sensitive, and specific LC-MS/MS method has been developed and validated for the simultaneous quantitation of urinary serotonin and catecholamines with low cost, which is ideal for routine clinical applications. A simple extraction from complex urine was accomplished using tailored solid phase extraction incorporating phenylboronic acid complexation on a 96-well HLB microplate for the sample extraction and resulted in significantly improved throughput, selectivity, and extraction recovery. Compared to 1-10 mL of urine typically used, this method required only 10 µL. A rapid chromatographic elution with a total cycle time of 6 min per sample compared to reported run times of 19-75 min was achieved on a PFP column. The sensitivity of l and 2 ng mL-1 for the detection of low abundant E and NE combined with the high coverage of 1024 ng mL-1 for DA enabled the multi-analyte detection of these biogenic amines in a single run. Good linearity (2.0-512, 1.0-512, 4.0-1024, and 4.0-1024 ng mL-1 for NE, E, DA, and 5-HT, respectively), accuracy (87.6-104.0%), precision (≤8.0%), extraction recovery (69.6-103.7%), and matrix effect (87.1-113.1% for catecholamines and 63.6-71.4% for 5-HT) were obtained. No autosampler carryover was observed. The analytes were stable for 5 days at 20 °C, 14 days at 4 °C, and 30 days at -20 °C and five freeze-thaw cycles. The easy sample preparation, rapid LC, and multi-analyte MS detection allow two 96-well plates of samples to be extracted within 2 h and analyzed on an LC-MS/MS system within 24 h. The applicability and reliability of the assay were demonstrated by assessment of the reference interval for authentic urine specimens from 90 healthy individuals. Graphical abstract A simple, rapid, robust, sensitive and specific LC-MS/MS method combined with a dual functional solid phase extraction has been developed and validated for the simultaneous extraction and quantitation of monoamine neurotransmitters in human urine with low cost.

High-fat simple carbohydrate feeding impairs central and peripheral monoamine metabolic pathway triggering the onset of metabolic syndrome in C57Bl/6J mice.

BACKGROUND: Previous studies have shown disturbances in an individual monoamine pathway but have not studied metabolic pathways at the onset and progression of metabolic syndrome (MetS). Aims, Settings, and Design: The aim of this study was to investigate the effect of high-fat simple carbohydrate (HFSC) diet on central (hypothalamic) and peripheral (plasma and urine) monoamine metabolic pathways during the development of metabolic syndrome in C57BL/6J mice. MATERIALS AND METHODS: Monoamines were analyzed in the 1st, 2nd, 3rd, 4th, and 5th month after feeding mice the HFSC diet or the control diet using the high performance liquid chromatography (HPLC) system (Shimadzu, Japan). Data was statistically analyzed (by Student's t-test) using Graph Pad Instat Version 3.1. Post statistical analysis, Bonferroni correction was applied to the results of 2nd, 3rd, 4th, and 5th month in order to calculate the correct error in the study. RESULTS: Significantly lower hypothalamic, plasma, and urine dopamine, and higher hypothalamic and plasma levels of norepinephrine and normetanephrine levels were observed in the HFSC diet fed C57BL/6J mice as compared to the control diet fed C57BL/6J mice after 5 months of feeding. No consistent changes were observed in other brain regions. The turnover ratio indicated that the lower dopamine levels in the HFSC diet fed C57BL/6J mice was due to the increased formation of norepinephrine and homovanillic acid. CONCLUSION: HFSC diet impairs the central and peripheral dopaminergic and noradrenergic pathways in mice as evidenced by the disturbances in their hypothalamic, plasma, and urine levels and this might be one of the early factors contributing towards the development of the MetS.

The effects of sapropterin on urinary monoamine metabolites in phenylketonuria.

BACKGROUND: Sapropterin dihydrochloride (BH4, tetrahydrobiopterin) can lower plasma phenylalanine (Phe) concentrations for a subset of patients with phenylketonuria (PKU), an inborn error of metabolism. Studies suggest that monoamine neurotransmitter concentrations are low in PKU patients. Sapropterin functions as a cofactor for hydroxylases specific to Phe, tyrosine, and tryptophan metabolism, pathways essential for catecholamine and serotonin synthesis. OBJECTIVE: The objective of this study is to determine the impact of sapropterin on monoamine neurotransmitter status in patients with PKU. DESIGN: 58 PKU subjects were provided 20 mg/kg of sapropterin for 1 month. Those who responded with at least a 15% decrease in plasma Phe received sapropterin for 1 year, while Non-responders discontinued it. After an additional 3 months, Responders who demonstrated increased Phe tolerance and decreased medical food dependence were classified as Definitive, whereas Responders unable to liberalize their diet without compromising plasma Phe control were identified as Provisional. At study visits, patients provided blood for plasma amino acids, 3-day diet records, and 12-hour urine samples analyzed for epinephrine (E), dopamine (DA), dihydroxyphenylacetate (DOPAC), homovanillic acid (HVA), 3-methoxytyramine (3MT), serotonin (5HT), and 5-hydroxyindole acetic acid (5HIAA) using HPLC with electrochemical detection. RESULTS: Compared with healthy non-PKU controls, subjects with PKU had significantly lower baseline concentrations of DA, HVA, 3MT, 5HT, and 5HIAA (p < 0.001 for all). Medical food protein intake had a direct association with DA, HVA, 5HT, and 5HIAA during the study (p < 0.05 for all), while plasma Phe had an inverse association with these markers (p < 0.01 for all). DOPAC was also associated with plasma Phe throughout the year (p = 0.035), although not at baseline. Patients with PKU had a significant increase in HVA (p = 0.015) after 1 month of sapropterin. When stratifying by Responder and Non-Responder status, significance of HVA increase in Non-responders (p = 0.041) was confirmed, but not in Responders (p = 0.081). A declining trend in urinary 5HIAA, significant only after controlling for plasma Phe (p = 0.019), occurred for Definitive Responders during the 1-year study. CONCLUSION: Urinary monoamine concentrations are low in patients with PKU and are influenced by oral sapropterin and medical food intake, highlighting the importance of these therapies to neurotransmitter metabolism in phenylketonuria.

Neurobiological and psychopathological variables related to emotional instability: a study of their capability to discriminate patients with bulimia nervosa from healthy controls.

OBJECTIVE: To analyze the capability of a set of neurobiological and psychopathological variables to discriminate bulimia nervosa (BN) patients from healthy controls. METHOD: Seventy-five female patients with purging BN and 30 healthy controls were compared for psychopathology (impulsivity, borderline personality traits, depressive symptoms and self-defeating personality traits) and neurobiological parameters reflecting hypothalamic-pituitary-adrenal axis activity (morning serum cortisol before and after dexamethasone) and monoamine activity (24-hour urinary excretion of norepinephrine, serotonin, dopamine, and their main metabolites: 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, and homovanillic acid). Furthermore, the relationships between the 2 sets of variables were compared in the 2 samples. RESULTS: BN patients displayed higher impulsivity, more severe depressive features, and more borderline and self-defeating personality traits than controls. The 4 psychopathological variables were strongly interrelated in patients, whereas only depressive features correlated with self-defeating personality traits in controls. Patients had lower 24-hour excretion of serotonin and dopamine than controls, as well as lower ability to suppress cortisol. The relations between the biochemical and the psychopathological variables were only significant in the BN patients, but not in the control group. When discriminant analysis methods were applied, patients and controls differed for psychopathology (impulsive behaviors and borderline personality traits) and biological parameters (baseline cortisol and dopamine excretion), but when the variables were analyzed together, the differences in neurobiological parameters appeared as mediated by the psychopathological status. DISCUSSION: Our results suggest that hypothalamic-pituitary-adrenal axis activity, dopamine activity and other biological parameters are worthy of further study as potential dimensional markers of BN, although they seem to depend on the psychopathological status of the patients, in such a way that the psychopathological items associated with emotional instability (impulsivity and borderline personality traits) seem to be more reliable as clinical markers at the time being.

Mechanisms of change in negative thinking and urinary monoamines in depressed patients during acute treatment with group cognitive behavior therapy and antidepressant medication.

UNLABELLED: This naturalistic study investigated the mechanisms of change in measures of negative thinking and in 24-h urinary metabolites of noradrenaline (norepinephrine), dopamine and serotonin in a sample of 43 depressed hospital patients attending an eight-session group cognitive behavior therapy program. Most participants (91%) were taking antidepressant medication throughout the therapy period according to their treating Psychiatrists' prescriptions. The sample was divided into outcome categories (19 Responders and 24 Non-responders) on the basis of a clinically reliable change index [Jacobson, N.S., & Truax, P., 1991. CLINICAL SIGNIFICANCE: a statistical approach to defining meaningful change in psychotherapy research. Journal of Consulting and Clinical Psychology, 59, 12-19.] applied to the Beck Depression Inventory scores at the end of the therapy. Results of repeated measures analysis of variance [ANOVA] analyses of variance indicated that all measures of negative thinking improved significantly during therapy, and significantly more so in the Responders as expected. The treatment had a significant impact on urinary adrenaline and metadrenaline excretion however, these changes occurred in both Responders and Non-responders. Acute treatment did not significantly influence the six other monoamine metabolites. In summary, changes in urinary monoamine levels during combined treatment for depression were not associated with self-reported changes in mood symptoms.

Amino bearing core-shell structured magnetic covalent organic framework nanospheres: Preparation, postsynthetic modification with phenylboronic acid and enrichment of monoamine neurotransmitters in human urine.

Covalent organic frameworks (COFs) have been increasingly employed in separation science, including sample preparation. Herein we fabricated the amino bearing core-shell structured COFs nanospheres [Fe3O4@TpBD(NH2)2], and a novel magnetic boronate affinity adsorbent was synthesized by postsynthetic modification of the Fe3O4@TpBD(NH2)2 with 2-formylphenylboronic acid. The magnetic boronate affinity adsorbent possesses fast magnetic response and high binding capacity up to 1037 µmol g-1 for dopamine. Besides, it was used as an adsorbent for extraction of urinary monoamine neurotransmitters at neutral pH. A method for detection of the monoamine neurotransmitters was developed by coupling the magnetic solid phase extraction with high-performance liquid chromatography-fluorescence detection. Under the optimized conditions, a good analytical method was obtained in the linear dynamic range of 2-200 ng mL-1 with R2 between 0.9917 and 0.9966, with low limit of detection (0.31-0.54 ng mL-1) and limit of quantification (1.04-1.80 ng mL-1). The recoveries of the monoamine neurotransmitters were in the range of 86.3-115%, with relative standard deviations of 2.34-10.5% (intra-day) and 2.84-14.4% (inter-day). The method was successfully applied to the determination of the monoamine neurotransmitters in human urine samples. This work is of great importance for preparing functionalized core-shell structured magnetic covalent organic framework nanospheres, it also demonstrates the feasibility of the functionalized magnetic COFs as adsorbents in sample pretreatment.

Comprehensive, robust, and sensitive UPLC-MS/MS analysis of free biogenic monoamines and their metabolites in urine.

Biogenic monoamines, including catecholamines and serotonin are important hormones and neurotransmitters. Abnormal urinary levels of biogenic monoamines and their metabolites are associated with smoking, neuroendocrine tumors, as well as neurological and cardiovascular diseases. Measurements of free biogenic monoamines and their metabolites have been challenging because of low concentrations in complex biological matrices. Current methods require extensive enrichment and removal of interfering substances and can analyze only basic or acidic compounds in a single run. We developed a simple and robust dilute-and-shoot method capable of measuring 10 analytes, including free biogenic monoamines and their metabolites in human urine. The assay enables sensitive measurements of analytes within expected sample concentration ranges. To assess the assay's efficacy, we measured urinary levels of free biogenic monoamines and their metabolites in 255 non-smokers and 191 smokers. Our data show that while smokers had significantly higher urinary levels of free catecholamines and metanephrines, there was a decrease in levels of biogenic amine metabolites synthesized through the monoamine oxidase pathway - homovanillic acid and vanillylmandelic acid. The method could be used for high throughput measurement of the range of free biogenic amines and their metabolites in urine under a variety of different conditions.

Differentiating Medicated Patients Suffering from Major Depressive Disorder from Healthy Controls by Spot Urine Measurement of Monoamines and Steroid Hormones.

Introduction: Major Depressive Disorder (MDD) is a common psychiatric disorder. Currently, there is no objective, cost-effective and non-invasive method to measure biological markers related to the pathogenesis of MDD. Previous studies primarily focused on urinary metabolite markers which are not proximal to the pathogenesis of MDD. Herein, we compare urinary monoamines, steroid hormones and the derived ratios amongst MDD when compared to healthy controls. Methods: Morning urine samples of medicated patients suffering from MDD (n = 47) and healthy controls (n = 41) were collected. Enzyme-linked immunosorbent assay (ELISA) was performed to measure five biomarkers: cortisol, dopamine, noradrenaline, serotonin and sulphate derivative of dehydroepiandrosterone (DHEAS). The mean urinary levels and derived ratios of monoamines and steroid hormones were compared between patients and controls to identify potential biomarkers. The receiver operative characteristic curve (ROC) analysis was conducted to evaluate the diagnostic performance of potential biomarkers. Results: Medicated patients with MDD showed significantly higher spot urine ratio of DHEAS/serotonin (1.56 vs. 1.19, p = 0.004) and lower ratio of serotonin/dopamine (599.71 vs. 888.60, p = 0.008) than healthy controls. A spot urine serotonin/dopamine ratio cut-off of >667.38 had a sensitivity of 73.2% and specificity of 51.1%. Conclusions: Our results suggest that spot urine serotonin/dopamine ratio can be used as an objective diagnostic method for adults with MDD.

Analysis of amino acid and monoamine neurotransmitters and their metabolites in rat urine of Alzheimer's disease using in situ ultrasound-assisted derivatization dispersive liquid-liquid microextraction with UHPLC-MS/MS.

Neurotransmitters (NTs) may play an important role in neurodegenerative disorders such as Alzheimer's disease (AD). In order to investigate the potential links, a new simple, fast, accurate and sensitive analytical method, based on in situ ultrasound-assisted derivatization dispersive liquid-liquid microextraction (in situ UA-DDLLME) coupled with ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS), has been developed and validated. The quantitation of amino acid neurotransmitters (AANTs) and monoamine neurotransmitters (MANTs) in urine of AD rats were performed in this work. The in situ UA-DDLLME procedure involved the rapid injection of the mixture of low toxic 4-bromoanisole (extractant) and acetonitrile (dispersant), which containing the new designed and synthesized 4'-carbonyl chloride rosamine (CCR) as derivatization reagent, into the aqueous phase of real sample and buffer. Under the selected conditions, the derivatization and microextraction of analytes were simultaneously completed within 1min. Good linearity for each analyte (R>0.992) was observed with low limit of detections (LODs, S/N>3). Moreover, the proposed method was compared with direct detection or other reported methods, and the results showed that low matrix effects and good recoveries results were obtained in this work. Taken together, in situ UA-DDLLME coupled with UHPLC-MS/MS analysis was demonstrated to be a good method for sensitive, accurate and simultaneous monitoring of AANTs and MANTs. This method would be expected to be highly useful in AD diseases' clinical diagnostics and may have potential value in monitoring the efficacy of treatment.

Determination of monoamine neurotransmitters in human urine by carrier-mediated liquid-phase microextraction based on solidification of stripping phase.

A novel method was developed for the analysis of monoamine neurotransmitters (MNTs) in human urine by carrier-mediated liquid-phase microextraction based on solidification of stripping phase method (CM-LPME-SSP) coupled with high performance liquid chromatography-electrochemical detector (HPLC-ECD). By adding an appropriate carrier in organic phase, simultaneous extraction of hydrophilic analytes, MNTs, with high enrichment factors (22.6-36.1 folds) and excellent sample cleanup was achieved. A new strategy, solidifying the aqueous stripping phase in the back-extraction process, was developed to facilitate the collection of the stripping phase as small as a few microliters. Combined with HPLC-ECD analysis, the linear ranges of the established method were 0.015-2.0 µg/mL for NE, E, DA, and 0.020-2.0 µg/mL for 5-HT. The limits of detection and quantification were in the range of 5.5-10.8 ng/mL and 15-20 ng/mL, respectively. The relative recoveries were in the range of 87-108%, with intraday and interday relative standard deviations lower than 13%. This method was successfully applied to analysis of MNTs in real urine.

Determination of putrescine, cadaverine, spermidine and spermine in different chemical matrices by high performance liquid chromatography-electrospray ionization-ion trap tandem mass spectrometry (HPLC-ESI-ITMS/MS).

The goal of this work was to establish a simple HPLC-ESI-ITMS/MS procedure, suitable for the determination of four common aliphatic polyamines in two different types of biological matrices. To this end, 1,6-diaminohexane was used as the internal standard (IS) and 4-fluoro-3-nitrobenzenotrifluoride (FNBT) as the derivatizing agent. Formation of fully derivatized compounds was confirmed by high resolution ESI-QTOFMS and MS/MS analysis. Reversed phase chromatographic separation was carried out by gradient elution with 0.1% (v/v) formic acid and methanol. In a positive ESI mode, the following pairs of precursor/quantifier ions were used for multiple reaction monitoring: 467.4/261.0 for PUT, 481.2/461.1 for CAD, 713.7/261.0 for SPD, 959.8/507.2 for SPM and 495.3/475.2 for IS. On-column instrumental detection limits of four polyamines were in the range 0.62-2.14fmol (0.039-0.215ng/ml). Versatility was demonstrated by analyzing plant extracts and human urine; prior to derivatization, all samples were cleaned-up by dichloromethane extraction. The evaluated signal suppression/enhancement was in the range 82.3-115.4% and the percentage recoveries obtained in the method of standard addition were in the range 83.7-114.4%. Statistically significant differences in polyamines concentrations were found in garden cress exposed to Cd(II) versus control seedlings (t-test, p<0.05); results obtained for urine from healthy volunteers and diabetic patients at different clinical conditions suggested possible utility of free polyamines as biomarkers of progressive diabetes.

Reward dependence is positively related to urinary monoamines in normal men.

According to Cloninger, three major personality dimensions, novelty seeking, harm avoidance, and reward dependence, are dependent on central monoaminergic systems. This study examined the relationship between the urinary levels of different monoamines and the above personality dimensions. Fifty normal men answered the Tridimensional Personality Questionnaire (TPQ); their levels of dopamine, norepinephrine, epinephrine, normetanephrine, metanephrine, 3-methoxy-4-hydroxyphenylglycol, vanilmandelic acid, homovanilic acid, and serotonin metabolite 5-hydroxyindolacetic acid were measured in urine on two consecutive nights. Significant and positive correlations were found between reward dependence, 3-methoxy-4-hydroxyphenylglycol, and epinephrine (r = .50 and r = .51, respectively). Monoamine levels explained 44% of the variance of reward dependence. Cluster analysis identified three groups of subjects presenting specific patterns of monoamine excretion. The TPQ scores could discriminate among subjects belonging to these clusters. These results point out a narrow relationship between urinary monoamine excretion and the basic personality dimension of reward dependence.

Comparative investigation of the effect of moclobemide and toloxatone on monoamine oxidase activity and psychometric performance in healthy subjects.

The effects of moclobemide and toloxatone, two reversible monoamine oxidase-A inhibitors, on biochemical parameters that reflect monoamine metabolism and on psychomotor performance parameters were investigated in a study in 12 healthy volunteers. Treatments were given double-blind in a randomized, placebo-controlled cross-over design, with 1 week wash-out between the treatments. Drugs were given thrice daily in the following doses: moclobemide 150-150-150 mg and toloxatone 400-200-400 mg. All assessments were performed on day 8 under standardized conditions. There was no difference with regard to adverse events between moclobemide and toloxatone: both drugs induced a slight decrease in both supine and standing heart rate. Judged on the basis of the area under the curve, the two MAO-inhibitors reduced the plasma levels of DHPG and HVA, with more pronounced effects for moclobemide than for toloxatone. After moclobemide MAO-A inhibition was almost constant over 24 h, whereas the effect of toloxatone was short lasting after each dose. The same differences were reflected in plasma 5-HIAA concentrations and urinary excretion of 3-methoxytyramine and normetanephine. Neither of the compounds tested had any influence on the memory, vigilance, mood, or sleeping habits of the subjects.

The development of conditioned blocking and monoamine metabolism in children with attention-deficit-hyperactivity disorder or complex tics and healthy controls: an exploratory analysis.

Conditioned blocking (CB) measures the transient suppression of learning that a new stimulus, added during learning, has the same consequences as the conditioned stimulus already present. Normal CB increases between the age of 8 and 20 years (Oades, R.D., Roepcke, B. and Schepker, R., A. test of conditioned blocking and its development in childhood and adolescence: relationship to personality and monoamine metabolism, Dev. Neuropsychol., 12 (1996) 207-230). In the present study CB development is compared between healthy children (CN), children with attention deficit (ADHD) and those with complex tics or Tourette's syndrome (TS) with mean ages of 10-11 years. All children needed fewer learning trials with increasing age: the ADHD group showed a slight impairment. Only controls improved CB with increasing age. A trend for worse CB in the TS than the other groups was significant for those over 11 years. While ADHD children over 11 years showed less CB than controls, younger ADHD children showed more. A correlational analysis of the status of monoamine metabolism in 24 h urine samples showed a positive relationship for CB with dopamine metabolism in controls and TS children, but a negative relationship in ADHD children. In contrast, increases of serotonin metabolism were negatively related to CB in TS but positively in ADHD patients. In conclusion, when selective information processing abilities reflected by CB start to develop at puberty-onset, there is a relative worsening in ADHD patients. But TS patients show an impairment independent of age. Changes in the balance between dopamine and serotonin systems may contribute to normal and abnormal cognitive development.

IDRD2 TaqIA polymorphism is associated with urinary homovanillic acid levels in a sample of Spanish male alcoholic patients.

The TaqIA1 allele of the dopamine receptor gene D2 (DRD2) has been associated with alcoholism, as well as with other addictive behaviours. The exact nature of how the presence of this allele can be a vulnerability factor in the development of alcoholism remains unclear. In this study we found that the presence in the DRD2 genotype of the TaqIA1 allele in Spanish alcoholics is associated with higher levels of urine homovanillic acid (HVA) when compared to patients homozygous for the TaqIA2 allele. A sample of 142 Spanish male alcoholic patients was split into 2 groups on the basis of the presence or absence of the A1 allele in their genotype. The urine sample was analyzed by high performance liquid cromatography (HPLC), and the concentration of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and vanilylmandelic acid (VMA) was determined. We found a statistical difference in the concentration of HVA between the groups, that suggests this polymorphism could be related to the variance of urine HVA levels.

The comparative effects of single and multiple doses of RS-8359, moclobemide and placebo on psychomotor function in healthy subjects.

Electro-oculogram (including saccadic eye movements), auditory-evoked potentials and visual analogue scales for a subjective impression of effects were used to evaluate some pharmacodynamic properties of RS-8359. In the electro-oculogram, administration of central nervous system-stimulating drugs is expected to decrease latency and fixation time and to increase angular velocity. As no significant effect on these parameters was found after any dose of RS-8359, within the limitations of the methods used, it seems unlikely that any appreciable direct stimulation of the central nervous system occurs with this agent, and significant central nervous system side effects also seem unlikely. Moreover, the data on auditory-evoked potentials suggest that RS-8359 may improve cognitive performance, which is often impaired in major depressive disorders. However, the doses used in these studies were associated with nausea and vomiting, possibly caused by increased serotonergic activity secondary to monoamine oxidase A inhibition. The results indicate that RS-8359 has no apparent sedative liability, which should benefit patients who need to remain in work, to drive or to continue other activities requiring a normal level of alertness.

Effects of piracetam on retention and biogenic amine turnover in albino rats.

The chronic effects of orally administered 2-pyrrolidone acetamide (piracetam) on one-trial, passive avoidance task were studied in albino rats. The effects on the contents of norepinephrine (NE), dopamine (DA), and serotonin (5-HT) in the brain and on the levels of their metabolites both in the brain and urine were also assessed. Significant improvement was observed in the retention ability compared with saline-administered controls. The contents of NE, DA, and 5-HT and their metabolites in the brain were significantly decreased after piracetam administration. The urinary metabolite levels were also significantly decreased except total 3-methoxy-4-hydroxyphenyl glycol (MHPG). These data indicate that piracetam causes an overall decrease in the turnover of central monoamines. Thus, the results of this study implicate the involvement of NE, DA, and 5-HT systems in learning and memory processes. Piracetam did not exert any GABAergic effect as shown by the absence of change in the brain GABA levels.

Alterations of monoamine metabolites and neurobehavioral function in lead-exposed workers.

Neurobehavioral and neurochemical effects of occupational lead exposure were investigated by WHO Neurobehavioral Core Test Battery (NCTB) testing and a series of monoamine neurotransmitters and their metabolites analyzing in workers from lead smeltery and storage-battery manufacturing factory and matched controls. Indicators of lead exposure, the blood lead (PbB) and zinc protophorphyrin (ZPP) levels were found significantly higher in the exposed group compared with that of the controls (70.55 micrograms/dL vs 3.67 micrograms/dL; and 294.92 micrograms/dL vs 38.32 micrograms/dL, respectively). Furthermore, elevated urinary homovanillic acid (HVA) and impairment of certain neurobehavioral performances were also found in the lead exposed workers; the latter included attention/response speed, manual dexterity, perceptual-motor speed, visual perception/memory, and motor speed/steadiness. Positive or negative correlations were observed between certain parameters. Thus, homovanillic acid (HVA) is positively correlated with PbB and ZPP; dopamine (DA) negatively correlated with Benton visual retention (BVR); and HVA negatively correlated with digit symbol (DSy), BVR, and pursuit aiming (PA). It is suggested that the alterations of dopamine and its metabolites HVA in urine associated with impairment of neurobehavioral function might be served as biomarkers of lead-induced neurotoxicity.

Neurohumoral reactions to long-term vestibular stimulation in man.

NASA: The main purposes of present work were: 1) to examine neurohumoral reactions to long-term vestibular stimulation provocative for MS symptoms in man; 2) to compare the peculiarities of neuroendocrine reactions to short-term and to long-term vestibular stimulation; 3) to analyze the received results from the position of neuroendocrine adaptive reactions biological conformity to natural laws, and its physiological importance for human organisms; 4) to make some prognostic points of neurohumoral reaction changes on health and capacity for work in subjects influenced by professional conditions, provocative for MS manifestation development.^ieng