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PubMed1984

3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, and homovanillic acid in human cerebrospinal fluid. Storage and measurement by reversed-phase high-performance liquid chromatography and coulometric detection using 3-methoxy-4-hydroxyphenyllactic acid as an internal standard.

To simultaneously measure 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5HIAA), and homovanillic acid (HVA) in human cerebrospinal fluid (CSF), we used an acetonitrile protein precipitation, reversed-phase high-performance liquid chromatography with coulometric detection, and 3-methoxy-4-hydroxyphenyllactic acid (MHPLA) as an internal standard for all three metabolites. MHPG, 5HIAA, HVA, and MHPLA were stable for one month when stored in CSF at -70 degrees C. Three determinations were made in triplicate for each of seven subjects over a 30-day storage period and the coefficients of variation within subject for these determinations ranged from 0.075 to 0.165 for MHPG, 0.045 to 0.148 for 5HIAA and 0.053 to 0.181 for HVA. Means and standard deviations of CSF concentrations were 10.7 +/- 3.0 ng/ml for MHPG, 22.4 +/- 9.9 ng/ml for 5HIAA, and 39.9 +/- 21.4 ng/ml for HVA. This method provides simple sample preparation, sensitivity, and cost advantages, as well as simultaneous extraction and quantitation of MHPG, 5HIAA, and HVA using an internal standard.

Chromatography, High Pressure Liquid↗
PubMed1982

Renal excretion of vanillylmandelic acid and homovanillic acid in rats with paw edema or adjuvant arthritis.

1. Urinary excretion of unconjugated vanillylmandelic acid (VMA) and homovanillic acid (HVA) was found to be decreased in adjuvant arthritic rats. The decrease is apparently not due to impaired animal activity, but it could be explained by the reduction of catecholamine biosynthesis and/or release induced by E prostaglandins the biosynthesis of which is increased in the inflammation. It could also be caused by an increased "consumption" of catecholamines during prostaglandin biosynthesis. 2. Both the reduction of biosynthesis or release and an increased "consumption" of catecholamines would mean that inflammation is characterized by deficiency of the anti-inflammatory catecholamines. 3. The investigations failed to demonstrate an adequate decrease of the urinary excretion of VMA and HVA in rats with edemas induced by carrageenin, serotonin, formaline, silver nitrate, kaolin, dextran and baker's yeast, respectively. The experiments should be repeated with other catecholamine metabolites.

Animals↗
PubMed1987

Seasonal variations in vanillylmandelic acid and homovanillic acid in infants' urine.

Seasonal variations in urinary levels of vanillylmandelic acid (VMA) and homovanillic acid (HVA) have been investigated over a two-year period, using 31,466 filter-paper specimens of urine from infants of 6 months of age who underwent Sapporo City's screening for neuroblastoma. Levels of both VMA and HVA (micrograms/mg creatinine) were significantly higher in summer (11.48 +/- 7.40, n = 7,569, and 18.70 +/- 8.18, n = 7,582, respectively) than in winter (10.72 +/- 5.76, n = 8,143, and 16.46 +/- 7.17, n = 8,148, respectively) throughout the two years (P less than 0.01, t-test). Although the cause of this difference could not be found, its actual clinical relevance was thought to be small since there was no significant relation between monthly rate of re-screened infants and monthly mean levels of VMA or HVA (P greater than 0.05, Spearman-Rank correlation).

Chromatography, High Pressure Liquid↗
PubMed1990

Fluctuation in the concentrations of vanillylmandelic acid and homovanillic acid in mass screening for neuroblastoma.

Fluctuations in the amount of vanillylmandelic acid (VMA) and homovanillic acid (HVA) were studied in random urine samples from 13 infants with neuroblastoma. In patients with a small tumour, many samples contained amounts below the cut off values, suggesting that detection of a patient with neuroblastoma depended on mathematical probability. Using high performance liquid chromatography a patient with a tumour of about 10 g may well be overlooked, whereas a patient whose tumour weighs over 30 g would probably be detected. With qualitative screening, although more likely to miss a patient with low VMA excretion, a patient with a tumour weighing over 50 g would be detected. In a thorough hospital examination care should be exercised in interpreting borderline values of VMA and HVA; excretion information suggesting the existence of a tumour may aid localization by radiological imaging procedures.

Adrenal Gland Neoplasms↗
PubMed1986

Liquid-chromatographic assay of urinary vanillylmandelic acid and homovanillic acid, with clean-up by on-column injection of acetonitrile or methanol.

To separately measure vanillylmandelic acid (VMA) and homovanillic acid (HVA) in urine, the sample is diluted 10-fold with 50 mmol/L phosphoric acid, then exactly 5 microL is injected directly onto a 50 X 4.6 mm column of Nucleosil 3C18. Samples can be injected at 5-min intervals because all peaks after these compounds of interest are washed away. VMA is eluted from the column after 2.8 min with 50 mmol/L phosphate buffer, pH 2.2, and measured by electrochemical detection. All peaks eluting after VMA are washed away together, by injection of 50 microL of acetonitrile onto the column. HVA is eluted from the column after 3.3 min with a 100/10 (by vol) mixture of the phosphate buffer and acetonitrile. All later-eluting peaks are washed away together, by injection of 50 microL of methanol onto the column. Analytical recoveries of VMA and HVA were 98.5% and 100.6%, respectively; the CVs for various concentrations of either in urine were about 3%.

Acetonitriles↗
PubMed1975

Reduced cerebrospinal fluid 5-hydroxyindoleacetic acid and homovanillic acid in children with epilepsy.

Cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and probenecid were examined in 14 children with epilepsy (ages 6 months to 17 years) and 17 controls (ages 14 months to 16 years). The concentrations of amine metabolites were significantly correlated with probenecid concentrations in both groups of children. Cerebrospinal fluid concentrations of 5-HIAA were 63.6 ng per milliliter plus or minus 8.23 S.E.M. and 117 ng per milliliter plus or minus 11.6 S.E.M. for the epilepsy and control groups respectively. HVA averaged 89.1 ng per milliliter plus or minus 15.2 S.E.M in epilepsy and 172 ng per milliliter plus or minus 19.2 S.E.M. in the control group. These findings indicate a significant difference between epilepsy and control groups. Probenecid concentrations were similar in each group. The reduced cerebrospinal fluid amine metabolite concentrations in children with epilepsy were not related to age, anticonvulsant medication, cerebrospinal fluid folate or protein concentration, or cerebrospinal fluid cell count. Our findings suggest a relationship between brain amines and epilepsy.

Acetazolamide↗
PubMedDate not supplied

Vanilmandelic acid and homovanillic acid levels in patients with neural crest tumor: 24-hour urine collection versus random sample.

Neuroblastoma is the most common solid tumor in childhood and is the most frequent neural crest tumor (NCT). More than 90% of the patients excrete high levels of vanilmandelic acid (VMA) and homovanillic acid (HVA) in the urine. Original biochemical methods for measuring these two metabolites of catecholamines employed a collection of urine for 24 hours to avoid errors related to circadian cycle variations. More recently, attempts have been made to replace the 24-hour collections by random samples (RSs). This has practical advantages particularly for young children. The objective of this study is to assess whether urinary VMA related to urinary creatinine levels can be determined reliably by the method of Pisano et al. from RSs in patients with NCT. The determination of the consumption of VMA in urine stored for prolonged periods of time was also studied. We found a good correlation between the values of metabolites of catecholamines in RSs compared with 24-hour urine collections. There was consumption of VMA in urine samples after storage. We conclude that determination of VMA in RSs of urine by Pisano's method may identify NCT production of catecholamines and that the consumption of these catecholamines is an important factor to consider in the interpretation of values obtained with stored urine specimens.

Adolescent↗
PubMed1987

Probenecid-induced accumulation of 5-hydroxyindoleacetic acid and homovanillic acid in rat brain.

The accumulation of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in rat brain has been examined after probenecid infusion over 8 h. At plasma probenecid concentrations of 200-400 micrograms mL-1 a steady state level in the accumulation of 5-HIAA and HVA was achieved, the increase above the endogenous levels being 135% and 65%, respectively. When the plasma concentration of probenecid rose above 400 micrograms mL-1 there was further accumulation of both 5-HIAA and HVA probably induced by increased neuronal activity or toxicity due to probenecid. The explanation for the plateau of 5-HIAA and HVA obtained over the plasma probenecid concentration interval of 200-400 micrograms mL-1 could be that the levels were reached when there was complete inhibition of active transport, and when the rate of formation of the metabolites equalled the rate of elimination by alternative routes i.e. bulk flow and diffusion. Therefore when probenecid is used to inhibit the active transport of acid monoamine metabolites across the blood-brain barrier, its plasma concentration should be within the range of 200-400 micrograms mL-1.

Animals↗
PubMed1983

Simultaneous determination of 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, and homovanillic acid in cerebrospinal fluid with high-performance liquid chromatography using electrochemical detection.

An improved high-performance liquid chromatographic method with electrochemical detection (HPLC-EC) for the simultaneous determination of 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) in cerebrospinal fluid (CSF) of humans and nonhuman primates is described. Quantitation is based on the use of an internal standard, 5-fluoro-HVA. Sample preparation consists of mixing an aliquot of CSF with a solution of the internal standard followed by ultrafiltration. The precision of the method is high, with within-run and between-run coefficients of variation of 2-6% and less than 10%, respectively, in the concentration ranges of the metabolites encountered in human lumbar CSF. Accuracy was tested by comparing the present HPLC method with specific gas chromatographic-mass spectrometric (GS-MS) assays for MHPG and HVA and a GC-MS-validated HPLC assay for 5-HIAA: the correlations obtained were 0.968 for MHPG, 0.989 for 5-HIAA, and 0.999 for HVA, with no systematic bias between the methods. The use of ascorbate as a preserving agent for monoamine metabolites in CSF was not found to be necessary when proper care was exercised in sample handling and storage. The analysis of samples with up to 2% ascorbic acid was possible as well, but MHPG had to be assayed separately using an extraction procedure and an alternative internal standard, 3-ethoxy-4-hydroxyphenylglycol.

Animals↗
PubMed1983

Concentrations of 5-hydroxyindoleacetic acid and homovanillic acid in the cerebrospinal fluid of chronic therapy-resistant schizophrenics before and after hemodialysis therapy.

The concentrations of the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) have been determined by high-performance liquid chromatography in samples of lumbar cerebrospinal fluid from chronic therapy-resistant schizophrenics, both before and after either inactive or active hemodialysis for 10 weeks. A reasonable test-retest reliability was found for 5-HIAA during the inactive dialysis, but this was not found during active dialysis.

Adult↗
PubMed1981

Cerebrospinal fluid adenosine 3',5'-monophosphate, 5-hydroxyindoleacetic acid and homovanillic acid in patients with sleep apnoea syndrome.

Adenosine 3',5'-monophosphate (cyclic AMP), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were determined in the cerebrospinal fluid of patients with respiratory disorder and hypersomnia and in control patients. Patients with the sleep apnoea syndrome confirmed polygraphically showed elevated levels of cyclic AMP and 5-HIAA. Cyclic AMP levels were inversely correlated with arterial Po(2), measured under resting conditions. The level of HVA also was raised, but the change was not statistically significant.

Cyclic AMP↗
PubMed2004

Difficulties in establishing reference intervals for special fluids: the example of 5-hydroxyindoleacetic acid and homovanillic acid in cerebrospinal fluid.

Biochemical measurements in "special fluids" are complicated with the problem of reference intervals. Reference intervals are difficult to establish for these types of samples since they are usually only collected in patients with clinical suspicion of disease. Determination of neurotransmitter metabolites in cerebrospinal fluid illustrates this difficulty. This paper will review the factors and circumstances that have been identified or are suspected to modify the concentration of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in cerebrospinal fluid. In addition to obvious parameters such as age-related variation that can affect the concentration of 5-HIAA and HVA in cerebrospinal fluid, a variety of other factors can explain the wide range of "control" group sizes reported in the literature. Reference intervals must take into account the purpose of cerebrospinal fluid examinations, whether they be prospective studies to explore physio-pathologic relationships or for diagnostic purposes. In the latter case, certain neurological disorders cannot be excluded if a single measured value is within the reference interval.

Biogenic Monoamines↗
PubMed1986

Motor activity increases tryptophan, 5-hydroxyindoleacetic acid, and homovanillic acid in ventricular cerebrospinal fluid of the conscious rat.

An investigation was made into the effects of running (1 h at 20 m/min) on central serotonergic and dopaminergic metabolism in trained rats. Methodology involved continuous withdrawal of cerebrospinal fluid (CSF) from the third ventricle of conscious rats and measurements of tryptophan (TRP), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) levels during a 2 h post-exercise period. All three compounds were increased during the hour following exercise and returned to their basal values within an hour later. CSF flow rate was stable when metabolite levels were elevated. Brain determinations indicated that CSF metabolite variations only qualitatively paralleled brain changes. Indeed, post-exercise TRP, 5-HIAA, and HVA levels were increased to a greater extent in brain when compared to CSF. It is suggested that increased serotonergic and dopaminergic metabolism, caused by motor activity, may be involved in the behavioral effects of exercise.

Animals↗
PubMedDate not supplied

5-Hydroxyindoleacetic acid and homovanillic acid in cerebrospinal fluid of children with febrile convulsions.

5-Hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured by high-performance liquid chromatography (HPLC) in lumbar cerebrospinal fluid (CSF) obtained from febrile children subdivided according to the presence or absence of convulsions. Lumbar puncture was made either early (mean time 2 h) or late (3-6 days) after the febrile convulsion. The level of 5-HIAA was significantly decreased in children early and late after the febrile convulsion as compared with the convulsion-free group, but the HVA level was reduced only early after the febrile convulsion. These results support the hypothesis that a decrease in CSF 5-HIAA may be a biologic marker of susceptibility to convulsions and indicate that the transient decrease in HVA is a secondary phenomenon related to occurrence of convulsions.

Child, Preschool↗
PubMed1985

Two-dimensional high-performance liquid chromatographic determination of 5-hydroxyindoleacetic acid and homovanillic acid in urine.

The biomedically and neurochemically important compounds 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) have been simultaneously determined in human urine after reverse-phase two-dimensional high-performance liquid chromatography. A 10-fold-diluted urine sample (20 microliters) is first separated on a C18 column (30 X 0.39 cm) using an 85% pH 6.0 phosphate buffer/15% methanol solvent system. The elution volume containing both 5-HIAA and HVA (Rt approximately 3 min) is collected. Recoveries (mean +/- SD) for this purification step, which is monitored using fluorometric detection, were usually above 90%. After acidification of the approximately 2 ml collected fraction, 100 microliters is reinjected on a C18 column and separated (Rt: 5-HIAA, 4 min; HVA 5.5 min) using an 80% pH 3.5 phosphate buffer/20% methanol mobile phase. The compounds are determined by flow-through amperometry with absolute detection limits of approximately 25 pg. Both 5-HIAA and HVA are well resolved from other electroactive species present and are easily determined at normal and greatly reduced concentrations in human urine.

Chemical Phenomena↗
PubMed2004

5-Hydroxyindoleacetic acid and homovanillic acid concentrations in cerebrospinal fluid in patients with Alzheimer's disease, depression and mild cognitive impairment.

In this study we investigated the cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in Alzheimer (AD) patients (n=75), patients with mild cognitive impairment (MCI, n=9) and patients with depression (n=7). CSF HVA was significantly elevated in AD with depression (Geriatric Depression Scale, 15 point version GDS>5) in comparison to AD without depression (p<0.05, ANOVA) and CSF HVA showed a significant positive correlation with the GDS score of AD-patients (p=0.03, Spearman Rho: 0.38, Spearman Rank Correlation). In the group of AD patients CSF 5-HIAA was positively correlated with cerebrospinal fluid beta-amyloid 1-42 (Abeta42), p<0.05, Spearman Rho: 0.3, Spearman Rank Correlation, but not with CSF tau. Additionally, there was a significant positive correlation between cerebrospinal fluid 5-HIAA and HVA in the group of AD patients (p<0.0001, Rho: 0.47, Spearman Rank correlation). Neither 5-HIAA nor HVA in CSF could differentiate between mild cognitive impairment, depression and AD. The results of this study support the hypothesis that the serotonergic system plays a role in the course of AD. They further suggest an important role of dopamine metabolism in depression within AD patients.

Aged↗
PubMed2002

5-Hydroxyindolacetic acid and homovanillic acid are not involved in the cerebrospinal fluid after a seizure in patients with Delirium Tremens.

Little is known about 5-hydroxyindolacetic acid (5-HIAA) and homovanillic acid (HVA) levels in cerebrospinal fluid of patients with Delirium Tremens revealed at onset by seizures. The aim of the study is to understand the biochemical abnormalities induced by seizures in the cerebrospinal fluid of patients involved by Delirium Tremens. Nine patients 42-62 years of age, who had experienced a Delirium Tremens after alcohol withdrawal, with one or two seizures at onset, were included in this study. The lumbar puncture (and a CT scan) were performed after the last seizure. Nine patients with neither Delirium Tremens nor seizure, needing a lumbar puncture for their medical problem, were matched by sex and by age. For the measures of 5-HIAA and HVA, we systematically took the first cm3. The mean value of 5-HIAA levels were 12.70 ng ml(-1) in the group of nine patients with Delirium Tremens versus 13.45 ng ml(-1) in the control group. The mean value of HVA levels were 19.81 ng ml(-1) in the group of nine patients with Delirium Tremens versus 25.25 ng ml(-1) in the control group. The differences were not statistically significant. During a Delirium Tremens with seizure at onset, there are no statistically significant changes in 5-HIAA and HVA levels in the cerebrospinal fluid. Our work raises the question of the role of Delirium Tremens in the normalization of the levels of neuro-mediators that usually decrease soon after seizures.

Adult↗
PubMed1990

Estimation of human blood plasma 5-hydroxyindoleacetic acid and homovanillic acid.

A method for simultaneous quantification of plasma homovanillic acid and 5-hydroxyindoleacetic acid has been developed, permitting more efficient neurochemical examinations of these often interrelated biogenic amine systems. Zinc sulphate and sodium hydroxide solutions were used for precipitating the protein in plasma prior to injection on the column. This technique allows for cleaner chromatography, greater sensitivity and high precision. The method uses high performance liquid chromatographic separations of these compounds on C18 reversed phase columns with electrochemical detection. The detailed results from controls and untreated parasuicide patients are given.

Chromatography, High Pressure Liquid↗