Clinical significance of vanillylmandelic acid in neuroblastoma

Background: The second most common solid tumor in children is Neuroblastoma (NB). In about 90% of cases of NB, elevated levels of catecholamines or its metabolites are found in the urine or blood which includes Vanillylmandelic Acid (VMA) and Homovanillic Acid (HVA). Ferritin, Neuron-Specific Enolase (NSE) and Lactate Dehydrogenase (LDH) are commonly assessed in children suspected to have NB, and the levels of these markers are commonly used for differential diagnosis. Multiple clinical and imaging tests are needed for accurate patient assessment. Iodine 123(123I) Metaiodobenzylguanidine (MIBG) is the first-line functional imaging agent used in neuroblastoma imaging. To evaluate the utility of these marker present study was undertaken with 91 NB patients and 40 normal healthy control.Methods: The study comprised of blood samples and 24 hour抯 urine sample from 40 normal healthy subjects and 91 untreated patients with histologically proven Stage III and IV NB cases referred to our institute. Method used for NSE was Enzyme Immunoassay (Elisa), serum Ferritin was MIA, LDH-photometry and VMA by Column Chromatography.Results: Amongst the parameters studied VMA showed highest sensitivity (91%), specificity (94.4%) positive predictive value (97.8%) and 85% negative predictive value at the cut off levels of 7mg/ ml of creatinine as compared to other studied parameters.Conclusions: This study suggests that the detection of VMA in combination with routine histological examination, MIBG scan, serum NSE and LDH may improve the diagnosis of Neuroblastoma.

Duloxetine, a Selective Noradrenaline Reuptake Inhibitor, Increased Plasma Levels of 3-Methoxy-4-hydroxyphenylglycol but Not Homovanillic Acid in Patients with Major Depressive Disorder

OBJECTIVE: We investigated the effects of duloxetine on the plasma levels of catecholamine metabolites and serum brain-derived neurotrophic factor (BDNF) in 64 patients with major depressive disorder (MDD). METHODS: Major depressive episode was diagnosed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-fourth edition (DSM-IV) according to the DSM-IV text revision (DSM-IV-TR) criteria. The severity of depression was evaluated using the 17-item Hamilton Rating Scale for Depression (HAMD-17). Blood sampling and clinical evaluation were performed on days 0, 28, and 56. RESULTS: Duloxetine treatment for 8 weeks significantly increased the plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels but not the homovanillic acid (HVA) levels in responders with MDD. CONCLUSION: These results imply that noradrenaline plays an important role in alleviating depressive symptoms.

Simultaneous determination of vanillylmandelic acid, homovanillic acid and creatinine in random urine by high performance capillary electrophoresis / 中华检验医学杂志

Objective To establish a method for detecting urinary vanillylmandelic acid (VMA), homovanillic acid (HVA) and creatinine (Cr) simultaneously by high performance capillary electrophoresis (HPCE). Methods The separations were carried out using a 120 mmol/L phosphate buffer (pH 6.80) in a fused-silica capillary tube of 47 cm×75 μm I.D. by capillary zone electrophoresis (CZE). Injections were made by using the pressure mode for 4 s at 1 p. s. i. after samples were centrifuged and diluted. The detections were monitored by a diode-array detector (DAD) at 200 nm after samples were separated at a voltage of 20 kV. The method developed was validated systematically and applied to urine samples from healthy adults (n = 100) and children (n = 100) for establishing the reference ranges of VMA/Cr and HVA/Cr, respectively. Results Under these conditions, the separations of VMA, HVA and Cr could be completed within 13 min. The linearity ranges of VMA, HVA and Cr were 0-500, 0-500 and 0-4 000 μmol/L, respectively, with the correlation coefficients (r) between 0.997 2 and 0. 999 1 (P < 0.01). The detection limits (S/N= 3) were 1.0 μmol/L for VMA, 1.0 μmol/L for HVA and 50.0 μmol/L for Cr. The mean within-run (n = 10) CVs of migration time for VMA, HVA and Cr in urine were 0.58%, 0.56% and 0.25% respectively, while the mean between-run (n = 10) CVs of migration time were 0.95%, 1.00% and 0.48% respectively. The mean within-run (n = 10) CVs of peak area for VMA, HVA and Cr were 3.78%, 3.97% and 2.76% respectively, while the mean between-rim (n = 10) CVs of peak area were 4.60%, 4.08% and 4.42% respectively. The average recoveries were 98.36% for VMA, 93.56% for HVA and 98.85% for Cr. Other compounds in human urine such as catecholamines, 5-hydroxytryptamine and albumen didn't interfere with the assay. The correlation between CE method and HPLC method was good. And the correlation coefficients (r) of VMA and HVA were 0.954 9(P <0.01) and 0.945 1 (P < 0.01), respectively. Skewness distributions were presented for VMA/Cr and HVA/Cr in random urine from both adults and children, and the 95% reference ranges were established by the percentile method. For adults, the reference ranges of VMA/Cr and HVA/Cr were 0-4. 26 and 0-1.69 (μmol/mmol), respectively. For children, the reference ranges of VMA/Cr and HVA/Cr were 0-10.39 and 0-4.31 (μmol/mmol), respectively. Conclusions The CE method devised here for direct measurement of urinary VMA, HVA and Cr is simple, fast,precise and automatic with good repeatability. It is an ideal method for routine detection and mass screening of pheochromocytoma and neuroblastoms.

The Relationship between the Age of Onset and Concentrations of Plasma Homovanillic Acid and 3-Methoxy-4-Hydroxyphenylglycol before and after the Neuroleptic Treatment in Patients with Schizophrenia / 신경정신의학

OBJECTIVES: The authors investigated the possibility of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations in plasma to be biological markers before and after the pharmacological treatment of schizophrenia. METHODS: Twenty-six patients with schizophrenia were enrolled after two week washout of neuroleptics. Baseline sampling was done after washout. Consequent samplings were done at two and four week time-points after neuroleptic treatment. The concentrations of HVA and MHPG were analysed with clinical variables, such as age, age of onset, duration of illness, period of hospitalization, and changes of clinical state. The HVA and MHPG were assayed using high pressure liquid chromatographyelectrochemical detection method. RESULTS: A significant association was observed between the age of onset and plasma HVA concentration in washout state of antipsychotics. The earlier onset group had lower plasma HVA concentration than the late onset group. A significant association was observed between the age of onset and plasma MHPG concentration in washout state of antipsychotics. The earlier onset group had lower plasma MHPG concentration than the late onset group. CONCLUSIONS: The present findings suggest that the activities of dopamine and norepinephrine are different with respect to age of onset in the neuroleptic-naive schizophrenia. Plasma HVA and MHPG concentration can be biological markers for the subgrouping of schizophrenia.

The Association between Polymorphism of the Dopamine D3 Receptors and Concentrations of Plasma Homovanillic and 5-hydroxyindoleacetic Acid, and Therapeutic Response of chronic Schizophrenic Patients

OBJECTIVES: Schizophrenia manifests a variety of interindividual differences in therapeutic response to antipsychotics. This might be attributable to dopamine and serotonin receptors that a important target for various antipsychotics, and the D3 receptor(DRD3) alleles they carry. The purpose of our study was to investigate whether the plasma levels of homovanillic acid(HVA) and 5-hydroxyindoleacetic acid(HIAA), and the polymorphism of DRD3 can be held as a predictor of treatment response ni chronic schizophrenic patients. METHODS: Therapeutic response for 16 korean schizophrenia patient treated during 48 weeks were assessed by PANSS used as the clinical symptom rating scales. The levels of concentration of HVA and 5-HIAA were examined by HPLC at baseline and at 48 weeks. We classified the polymorphism of DRD3 receptor using amplifying by polymerase chain reaction(PCR). RESULTS: Neither concentrations of HVA and 5-HIAA nor genotype of dopamine 3 receptor were not significantly associated with the therapeutic response. But, the patients who has A1 alleles of DRD3 gene showed poor therapeutic responses. CONCLUSION: A1 allele of DRD3 gene is associated with poor prognosis of chronic schizophrenia.

Diurnal and insulin-Induced Variations of Plasma Homovanillic Acid Concentrations

The authors tried to confirm the significant changes of plasma homovanillic acid(HVA) concentration after insulin administration in comparison with those of usual diurnal variation in the same subjects. Male patients with schizophrenia taking neuroleptics were participated in a study of diurnal variation and insulin induced dopaminergic perturbation, with multiple samplings at baseline. 30minutes, 60minutes and 90minutes after insulin administration(n=18). Ten patients were sampled at baseline and 60minutes after insulin administration. There was a diurnal variation of plasma HVA concentrations, which decreased gradually from 8 am to 9 : 30 am. We confirmed that regular insulin(0.1 unit/kg) blocked the normal diurnal variations and increased plasma HVA concentrations. This pattern was not correlated with clinical variables, such as age, onset age, duration of illness and presence of family history. Schizophrenic patients were grouped by the positive and negative syndrome scale. In contrast to our previous study, the concentrations of positive and negative groups were similar at baseline. The HVA concentrations of negative group after insulin administration were higher than those of positive group without statistical significance. We have a plan modify the current insulin-HAV method. In the near future, we will try to confirm whether the modified insulin-HVA method can be used as a biological indicator for the elucidation of complex clinical manifestations of schizophrenia.

Plasma Homovanillic Acid Level in Posttraumatic Stress Disorder / 대한정신약물학회지

This research was performed to investigate whether or not the psychobiology of posttraumatic stress disorder is related to dopamine systems. Plasma homovanillic acid levels were measured in 16 male patients with posttraumatic stress disorder and in 16 nonpsychiatric normal males. Posttraumatic stress disorder was diagnosed using the DSM-IV. Plasma homovanillic acid levels were significantly higher in patients with posttraumatic stress disorder than in normal control subjects(p<0.05). The findings of this study suggest that hyperactivity of dopamine systems may be related to the psychobiology of posttraumatic stress disorder.

Relationships among Plasma Homovanillic Acid, 5-hydroxyindoleacetic Acid Concentrations and the Psychopathology of Schizophrenic Patients

The recent hypothesis about the pathophysiology of schizophrenia has been centered mainly on two theories, i.e. dopamine hypothesis and serotonin hypothesis. We investigate the correlations between plasma metabolite concentrations and clinical symptoms in schizophrenic patients. The purpose of our study was to examine whether the plasma levels of HVA(homovanillic acid) and 5-HIAA(hydroxyindoleacetic acid) are significantly different in schizophrenics, compared to normal controls. And, with the intention of clarifying the interaction between dopaminergic system and serotoninergic system, the ratio of HVA/5-HIAA also was measured. The second purpose was whether the basal(pre-treatment) levels of these metabolites show the correlation with clinical symptoms. Finally, third purpose was whether basal HVA and 5-HIAA levels can be held as a predictor of treatment response. We used scale for the Assessment of Positive Symptoms(SAPS) and Scale for the Assessment of Negative Symptoms(SANS) as the clinical symptom rating scales. Our results were as followed, 1) only the level of basal plasma HVA was significantly differ in schizophrenics. 5-HIAA and HVA/5-HIAA were not. 2) basal HVA showed significant correlation with SAPS score, especially delusion subscale. 3) the higher was the basal HVA level, the more improvement in clinical symptoms was observed. The basal 5-HIAA level and the HVA/5-HIAA ratio did not show any significant findings. These results support the dopamine hypothesis of schizophrenia, but fail to examine on the possible involvement of serotonin in schizophrenia.

Simultaneous Determination of Homovanillia Acid and Vanillymandelic Acid in Human Urine by HPLC / 环境与健康杂志

Objective To establish an HPLC-FLD method for simultaneous determination of homovanillic acid(HVA) and vanilmandelic acid(VMA) in human urine.Methods After being filtered with 0.45 ?m membrane,the samples of urine were injected directly into an ODS column(250 mm?4.6 mm,5.0 ?m) at the room temperature.The samples of urine were carried with the mobile phase comprised of methanol-0.1mol/L phosphate buffered solution(20:80,V/V).The flow rate was 1 ml/min,the injection volume was 10 ?l,the detection was taken at ?ex=277 nm,?em=320 nm.Results The determination was finished in 15 min,the retention time was 3.18 min for VMA and 6.72 min for HVA respectively.The detection limit of HVA was 0.15 ?g/ml,the linear range was 0-25 ?g/ml,the recovery rates were between 84.53%-106.1%,the relative standard deviation(RSD)

HPLC-EC DETERMINATION ON THE CONTENTS OF DOPAMINE AND ITS METABOLITES IN BILATERAL STRIATA OF SUBSTANTIA NIGRA LESIONED RATS / 解剖学报

The contents of dopamine (DA) and its metabolites, homovanillic acid (HVA) and 3,4-dihydroxyphenyl acetic acid(DOPAC), in both striata were determined with HPLC-EC technique in each of 28 albino rats, which were divided into 3 groups (bilateral lesioned, unilateral lesioned and healthy control groups). Among the unilateral lesioned rats, three indices such as DA, HVA/DA and DOPAC/DA in the lesioned striata were 22.27％, 420.00％ and 199.75％ of those of the intact striata, respectively. This suggests that there may be an enhanced compensatory DA release in the striatum ipsilateral to the lesion of the rat. Having compared the lesioned striata of unilateral lesioned rats with those of bilateral lesioned animals, and the intact striata of unilateral lesioned rats with those of the control ones, we did not find any significant differences in DA, HVA/DA or DOPAC/DA. The result implies that the compensatory DA release in the lesioned striatum probably accounts for the mechanism of the ipsilateral nigrostriatal system, not for the crossed nigrostriatal fibers.