Anti-inflammatory Activity of Sambucus Plant Bioactive Compounds against TNF-α and TRAIL as Solution to Overcome Inflammation Associated Diseases: The Insight from Bioinformatics Study

Inflammation is the crucial biological process of immune system which acts as body's defense and protective response against the injuries or infection. However, the systemic inflammation devotes the adverse effects such as multiple inflammation associated diseases. One of the best ways to treat this entity is by blocking the tumor necrosis factor alpha (TNF-α) and TNF-related apoptosis-inducing ligand (TRAIL) to avoid the proinflammation cytokines production. Thus, this study aims to evaluate the potency of Sambucus bioactive compounds as anti-inflammation through in silico approach. In order to assess that, molecular docking was performed to evaluate the interaction properties between the TNF-α or TRAIL with the ligands. The 2D structure of ligands were retrieved online via PubChem and the 3D protein modeling was done by using SWISS Model. The prediction results of the study showed that caffeic acid (−6.4 kcal/mol) and homovanillic acid (−6.6 kcal/mol) have the greatest binding affinity against the TNF-α and TRAIL respectively. This evidence suggests that caffeic acid and homovanillic acid may potent as anti-inflammatory agent against the inflammation associated diseases. Finally, this study needs further examination and evaluation to validate the potency of Sambucus bioactive compounds.

Effects of (−)-Sesamin on Memory Deficits in MPTP-lesioned Mouse Model of Parkinson's Disease

This study investigated the effects of (−)-sesamin on memory deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (PD). MPTP lesion (30 mg/kg/day, 5 days) in mice showed memory deficits including habit learning memory and spatial memory. However, treatment with (−)-sesamin (25 and 50 mg/kg) for 21 days ameliorated memory deficits in MPTP-lesioned mouse model of PD: (−)-sesamin at both doses improved decreases in the retention latency time of the passive avoidance test and the levels of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid, improved the decreased transfer latency time of the elevated plus-maze test, reduced the increased expression of N-methyl-D-aspartate (NMDA) receptor, and increased the reduced phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-response element binding protein (CREB). These results suggest that (−)-sesamin has protective effects on both habit learning memory and spatial memory deficits via the dopaminergic neurons and NMDA receptor-ERK1/2-CREB system in MPTP-lesioned mouse model of PD, respectively. Therefore, (−)-sesamin may serve as an adjuvant phytonutrient for memory deficits in PD patients.

Effects of Gypenosides on Dopaminergic Neuronal Cell Death in 6-Hydroxydopamine-lesioned Rat Model of Parkinson's Disease with Long-term L-DOPA Treatment

The goal of this study was to determine whether gypenosides (GPS) exert protective effects against dopaminergic neuronal cell death in a 6-hydroxydopamine (OHDA)-lesioned rat model of Parkinson's disease (PD) with or without long-term 3,4-dihydroxyphenylalanine (L-DOPA) treatment. Rats were injected with 6-OHDA in the substantia nigra to induce PD-like symptoms; 14 days after injection, groups of 6-OHDA-lesioned animals were treated for 21 days with GPS (25 or 50 mg/kg) and/or L-DOPA (20 mg/kg). Dopaminergic neuronal cell death was assessed by counting tyrosine hydroxylase (TH)-immunopositive cells in the substantia nigra and measuring levels of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the striatum. Dopaminergic neuronal cell death induced by 6-OHDA lesions was ameliorated by GPS treatment (50 mg/kg). L-DOPA treatment exacerbated 6-OHDA-induced dopaminergic neuronal cell death; however, these effects were partially reversed by GPS treatment (25 and 50 mg/kg). These results suggest that GPS treatment is protective against dopaminergic neuronal cell death in a 6-OHDA-lesioned rat model of PD with long-term L-DOPA treatment. Therefore, GPS may be useful as a phytotherapeutic agent for the treatment of PD.

Determination of four biogenic amine metabolites in urine by high-performance liquid chromatography / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To establish a method for simultaneously determining vanilmandelic acid (VMA), 5-hydroxyindoleacetic (5-HIAA), 3, 4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in urine by high-performance liquid chromatography (HPLC).</p><p><b>METHODS</b>After being filtered with a 0.45 µm membrane syringe filter, the urinary samples were injected directly into the HPLC system using a C18 chromatographic column and a fluorescence detector. The excitation and emission wavelengths were chose as 280 nm and 315 nm, respectively, and the urinary samples were carried with a mobile phase of methanol-0.1 mol/L phosphate buffered solution (V/V = 20:80) at a flow rate of 1.0 ml/min and an injection volume of 20 µl.</p><p><b>RESULTS</b>Using the method reported here, the correlation coefficients of VMA, 5-HIAA, DOPAC, and HVA were 0.9999, 0.9998, 0.9997, 0.9999, respectively, over linear ranges of 0-2.5, 0-2.0, 0-2.0, and 0-2.5 µg/ml, the minimum detectable concentrations were 0.006, 0.008, 0.012, and 0.0082 µg/ml, the average precisions were 4.2%, 3.7%, 4.9%, and 3.6%, and the recovery rates were 91%∼102%, 93%∼101%, 94%∼101%, and 89%∼ 102%.</p><p><b>CONCLUSION</b>This determination method is simple, efficient, accurate, and sensitive for the simultaneous detection of VMA, 5-HIAA, DOPAC, and HVA in urine.</p>

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.

Therapeutic effect of a natural squamosamide derivative FLZ on Parkinson's disease model mice induced by LPS plus MPTP / 药学学报

The aim of this study is to investigate the protective effect of N-[2-(4-hydroxyphenyl)ethyl]-2-(2, 5-dimethoxyphenyl)-3-(3-methoxy-4-hydroxyphenyl)acrylamide (FLZ), a novel synthetic squamosamide cyclic derivative, against Parkinson's disease (PD) model mice induced by the inflammatory bacterial endotoxin, lipopolysaccharides (LPS) and the neurotoxin 1-methy-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). C57/BL mice were ip injected LPS (5 mg x kg(-1)) once. One week following the LPS injection, mice received a subcutaneous injection of MPTP (25 mg x kg(-1)) once daily for 2 days. Eight weeks later, FLZ (25, 50 and 75 mg x kg(-1)) was orally administered to mice once daily for 60 days. The motor ability of the mice was evaluated by rod climbing test and footprint test. The dopamine (DA) levels in mouse striatum were determined by high performance liquid chromatography system. The tyrosine hydroxylase (TH)-positive cells were showed by immunohistochemical analysis. FLZ treatment significantly improved motor dysfunction of mice challenged by LPS plus MPTP. The increase of TH-positive cell numbers and elevation of DA levels may be contributed to the beneficial effects of FLZ on motor behavior. This study showed FLZ has significant therapeutic effect on LPS plus MPTP induced chronic PD model, which indicates its potential as a new candidate drug to treat PD.

Therapeutic effect of human amniotic epithelial cell transplantation into the lateral ventricle of hemiparkinsonian rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Human amniotic epithelial cells (HAECs) are able to secrete biologically active neurotrophins such as brain-derived neurotrophic factor and neurotrophin-3, both of which exhibit trophic activities on dopamine neurons. Previous study showed that when human amniotic epithelial cells were transplanted into the striatum of 6-hydroxydopamine (6-OHDA)-induced Parkinson disease rats, the cells could survive and exert functional effects. The purpose of this study was to investigate the survival and the differentiation of human amniotic epithelial cells after being transplanted into the lateral ventricle of Parkinson's disease (PD) rats, and to investigate the effects of grafts on healing PD in models.</p><p><b>METHODS</b>The Parkinson's model was made with stereotactic microinjection of 6-hydroxydopamine (6-OHDA) into the striatum of a rat. The PD models were divided into two groups: the HAECs group and the normal saline (NS) group. Some untreated rats were taken as the control. The rotational asymmetry induced by apomorphine of the HAECs group and the NS group were measured post cell transplantation. The expression of nestin and vimentin in grafts were determined by immunohistology. Ten weeks after transplantation the density of tyrosine hydroxylase positive cells in the substantia nigra of the HAECs group, NS group and the untreated group was determined. The differentiation of grafts was determined by TH immunohistology. High performance liquid chromatography (HPLC) was used to determine monoamine neurotransmitter levels in the striatum.</p><p><b>RESULTS</b>The rotational asymmetry induced by apomorphine of the HAECs group was ameliorated significantly compared to the NS group two weeks after transplantation (P < 0.01). The grafts expressed nestin and vimentin five weeks after transplantation. TH immunohistochemistry indicated that the TH positive cells in the substantia nigra of the HAECs group increased significantly compared to the NS group (P < 0.01). Tyrosine hydroxylase (TH) positive cells in the substantia nigra of the HAEC group and the NS group were decreased compared to the untreated group (P < 0.01). Dopamine and DOPAC levels in the striatum of the HAECs group increased significantly compared to the NS group (P < 0.05). Homovanillic acid (HVA) levels in the striatum of the HAECs group increased significantly compared to the NS group (P < 0.01). In addition dopamine, DOPAC, and HVA levels in the striatum and dopamine levels in the cerebrospinal fluid of the HAECs group and the NS group were decreased compared to the untreated group (P < 0.05).</p><p><b>CONCLUSIONS</b>Human amniotic epithelial cells could be used to ameliorate the rotational asymmetry induced by apomorphine of the PD models. This could have been due to the increased content of dopamine and its metabolic products, DOPAC and HVA, in the striatum in the PD models.</p>

Effect and mechanism on dopamine contents of striatum in rat model of Parkinson's disease ginsenoside Rg1 / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate effect and mechanisms on dopamine contents of striatum (Str) in the 6-OHDA induced rat model of Parkinson's disease (PD) by ginsenoside Rg1.</p><p><b>METHOD</b>Ovariectomized PD rats were treated with vehicle, ginsenoside Rg1, (10 mg x kg(-1)) or estrogen receptor (ER) antagonist ICI 182,780 for 14 d. The change of apomorphine-linduced rotational behavior in PD rats were observed. The high performance lipid chromotophotography (HPLC) was used to determine the contents of DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)in striatum.</p><p><b>RESULT</b>Rg1 treatment could ameliorate the PD rat's rotational behavior induced by apomorphine (P < 0.01). This effect could be blocked by ER antagonist ICI 182,780. The DA, DOPAC and HVA levels in the injured side of Str for PD rats were significantly decreased compared with the intact side (P < 0.01). Rg1, treatment could increase DA contents in the injured side of Str (P < 0.01). ICI 182,780 could completely block the neuroprotective effects of Rg1. The DA contents and its metabolites in the injured side of the ICI treatment group were significantly decreased compared with the Rg1 group (P < 0.01).</p><p><b>CONCLUSION</b>Ginsenoside Rg1 may have protective effects on the dopaminergic neurons for the 6-OHDA induced OVX rat model of PD, ER. May be involved in the protection action.</p>

Comparative effects of organic and inorganic mercury on in vivo dopamine release in freely moving rats

The present study was carried out in order to compare the effects of administration of organic (methylmercury, MeHg) and inorganic (mercury chloride, HgCl 2 ) forms of mercury on in vivo dopamine (DA) release from rat striatum. Experiments were performed in conscious and freely moving female adult Sprague-Dawley (230-280 g) rats using brain microdialysis coupled to HPLC with electrochemical detection. Perfusion of different concentrations of MeHg or HgCl 2 (2 muL/min for 1 h, N = 5-7/group) into the striatum produced significant increases in the levels of DA. Infusion of 40 muM, 400 muM, or 4 mM MeHg increased DA levels to 907 ± 31, 2324 ± 156, and 9032 ± 70 percent of basal levels, respectively. The same concentrations of HgCl 2 increased DA levels to 1240 ± 66, 2500 ± 424, and 2658 ± 337 percent of basal levels, respectively. These increases were associated with significant decreases in levels of dihydroxyphenylacetic acid and homovallinic acid. Intrastriatal administration of MeHg induced a sharp concentration-dependent increase in DA levels with a peak 30 min after injection, whereas HgCl 2 induced a gradual, lower (for 4 mM) and delayed increase in DA levels (75 min after the beginning of perfusion). Comparing the neurochemical profile of the two mercury derivatives to induce increases in DA levels, we observed that the time-course of these increases induced by both mercurials was different and the effect produced by HgCl 2 was not concentration-dependent (the effect was the same for the concentrations of 400 muM and 4 mM HgCl 2 ). These results indicate that HgCl 2 produces increases in extracellular DA levels by a mechanism differing from that of MeHg.

Roles of fluoxetine and haloperidol in mouse models of DOI-induced head twitch response / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To develop a mouse model to mimic the behavioral and neurochemical changes of Tourette syndrome (TS) by 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) induction and to investigate the effects of fluoxetine and haloperidol on head twitch response (HTR) induced by DOI.</p><p><b>METHODS</b>1) Preparation of mouse model of TS: Forty mice were randomly divided into experimental and control groups (n=20 each). DOI (1 mg/kg) was administered by peritoneal injection in the experimental group. The control group was injected with normal saline. The levels of dopamine (DA) and homovanillic acid (HVA), the metabolite of DA, in both groups were measured by high performance liquid chromatography and electrochemical detection. 2) Effects of fluoxetine and haloperidol on HTR: Eighty mice were randomly administered with either fluoxetine (2 mg/kg), haloperidol (0.8 mg/kg), fluoxetine + haloperidol or normal saline. DOI (1 mg/kg) was peritoneally injected 20 minutes later (acute trial) or 18-20 hrs after a 21 days injection of fluoxetine or haloperidol (chronic trial). The frequency of DOI induced HTR was observed immediately after DOI injection.</p><p><b>RESULTS</b>The levels of DA and HVA in the experimental group were significantly lower than those in the control group (DA: 45.00 +/-11.24 ng/mg vs 58.16 +/-14.51 ng/mg; HVA:10.54 +/-1.86 ng/mg vs 12.82 +/-2.66 ng/mg). In both acute and chronic trials, the frequency of DOI-induced HTR decreased significantly in mice administered with haloperidol alone or together with fluoxetine (P < 0.05), but it did not change significantly in mice administered with fluoxetine alone compared with the normal saline group.</p><p><b>CONCLUSIONS</b>The levels of DA and HVA are reduced in mice with DOI-induced HTR. DOI-induced mouse mode of HTR can mimic the neurochemical and behavioral changes of TS paritially. Haloperidol can inhibit DOI-induced HTR in mice, but fluoxetine can not.</p>

A Case of Opsoclonus-Myoclonus-Ataxia Syndrome in Ganglioneuroblastoma / 대한소아혈액종양학회지

The presence of rare paraneoplastic syndrome, the opsoclonus-myoclonus-ataxia syndrome (OMA), may strongly signal the presence of neuroblastoma. We report a case of ganglioneuroblastoma presented with OMA. A 26 month-old girl was admitted due to progressive ataxic gait and myoclonic jerking of the limbs. Brain and spine MRI scans were normal and cerebrospinal fluid analysis showed no specific abnormal finding. Abdominal computed tomography (CT) demonstrated about 3x1.5 cm sized well enhancing solid mass originated from the right adrenal gland. Urinary vanillyl mandelic acid (VMA) was mildly elevated and urinary homovanillic acid (HVA) was normal. After complete resection of the tumor, she was diagnosed with ganglioneuroblastoma and her symptomatology had disappeared.

Effects of pyrethroids on dopamine and its metabolites in nigrostriatum of male rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effects of pyrethroids on nigrostriatal dopaminergic pathways in male rats and its mechanism.</p><p><b>METHODS</b>Different doses of permethrin (PM, 200, 400 mg/kg) and deltamethrin (DM, 6.25, 12.50 mg/kg) in corn oil were administered to rats by gavage once daily for ten days, then the contents of dopamine (DA) and its metabolites, 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the substantial nigra and striatum were analyzed by HPLC-fluorescence detection.</p><p><b>RESULTS</b>The contents of DA in striatum in four administered groups were decreased to a certain extent. DA in 6.25 mg/kg DM group [(6.14 +/- 0.57) microg/g wet weight] was lower than that in control group [(9.46 +/- 1.95) microg/g wet weight], P < 0.05. The turnover rate of DA in 200, 400 mg/kg PM and 6.25, 12.5 mg/kg DM groups increased by 133.33%, 166.67%, 166.67%, 266.67% respectively (P < 0.05 or P < 0.01), however there was no significant difference in DA and DOPAC in substantial nigra between control and administered groups.</p><p><b>CONCLUSION</b>DM may inhibit tyrosine hydroxylase and decrease the level of DA in striatum, and both pyrethroid pesticides may increase the metabolism of dopamine in striatum.</p>

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.

Characterization of Norepinephrine Release in Rat Posterior Hypothalamus Using in vivo Brain Microdialysis

In the present study, we used the microdialysis technique combined with high performance liquid chromatography (HPLC) and electrochemical detection to measure the extracellular levels of norepinephrine (NE) in the posterior hypothalamus in vivo, and to examine the effects of various drugs, affecting central noradrenergic transmission, on the extracellular concentration of NE in the posterior hypothalamus. Microdialysis probes were implanted stereotaxically into the posterior hypothalamus (coordinates: posterior 4.3 mm, lateral 0.5 mm, ventral 8 mm, relative to bregma and the brain surface, respectively) of rats, and dialysate collection began 2 hr after the implantation. The baseline level of monoamines in the dialysates were determined to be: NE 0.17 +/- 0.01, 3,4-dihydroxyphenylacetic acid (DOPAC) 0.94 +/- 0.07, homovanillic acid (HVA) 0.57 +/- 0.05 pmol/sample (n=8). When the posterior hypothalamus was perfused with 90 mM potassium, maximum 555% increase of NE output was observed. Concomitantly, this treatment significantly decreased the output of DOPAC and HVA by 35% and 28%, respectively. Local application of imipramine (50microM) enhanced the level of NE in the posterior hypothalamus (maximum 200%) compared to preperfusion control values. But, DOPAC and HVA outputs remained unchanged. Pargyline, an irreversible monoamine oxidase inhibitor, i.p. administered at a dose of 75 mg/kg, increased NE output (maximum 165%), while decreased DOPAC and HVA outputs (maximum 13 and 12%, respectively). These results indicate that NE in dialysate from the rat posterior hypothalamus were neuronal origin, and that manipulations which profoundly affected the levels of extracellular neurotransmitter had also effects on metabolite levels.

The effect of shourong compound formula on levels of dopamine and its metabolites in brain of Parkinson's disease mice induced by reserpine / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of Shourong compound formula on treating Parkinson's disease.</p><p><b>METHOD</b>Parkinson's disease model mice induced by reserpine was used and by HPLC-ED the levels of Dopamine (DA) and its metabolites were determined.</p><p><b>RESULT</b>Madopar could increase the levels of DA in brain of PD mice. The effect of madopar together with Sourong compound formula was better than that of madopar(P < 0.001).</p><p><b>CONCLUSION</b>Shourong compound formula together with madopar has synergic effect on increase of DA level in brain and can reduce clinic dose of madopar so that side effect of madopar can be decreased.</p>

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.

Tic Severities, Plasma Homovanillic Acid and 5-hydroxyindoleacetic Acid Levels according to the Presence of Comorbidities in Patients with Chronic Tic Disorders / 신경정신의학

OBJECTIVES: Contemporary empirical studies have suggested high rates of comorbid attention-deficit hyperactivity disorder(ADHD) or obsessive compulsive disorder(OCD) in children with tic disorders. Not infrequently, ADHD or OCD is as source of greater impairment than are the tic symptoms. The studies in the pathophysiology of tic disorder have implicated abnormalities of dopamine, serotonin and norepinephrine. The studies in pathophysiology of ADHD or OCD also have implicated abnormalities of dopamine, serotonin and norepinephrine. This study was purposed to examine the differences in tic severities and in the levels of plasma homovanillic acid(HVA) and 5-hydroxyin-doleacetic acid(5-HIAA) according to the presence of comorbid ADHD or OCD in patients with chronic tic disorders. METHODS: In fifty chronic tic patients, OCD or ADHD was also diagnosed. And then tic symptoms, obsessive-compulsive symptoms, and attention-deficit hyperactive symptoms were assessed using Yale global tic severity scale(YGTSS), Leyton obsessional inventory-child version(LOI-CV), and Conners parent rating scale. The plasma HVA and 5-HIAA levels were measured using high performance liquid chromatography with electrochemical detection method. RESULTS: Fifty-eight percent of the patients with chronic tic disorders had comorbid ADHD or OCD. But severities of tic did not differ regardless of the presence of comorbid ADHD or OCD. There was a significant positive correlation between tic severities and plasma HVA levels but none between tic severities and plasma 5-HIAA levels. There was a significant inverse correlation between resistance and interference scores and plasma 5-HIAA levels. Plasma HVA levels showed significant positive correlations with plasma 5-HIAA levels. CONCLUSION: These results showed that tic severities didn't vary according to the presence of comorbidities, and that tic severities were correlated with plasma HVA levels, not with plasma 5-HIAA levels. These results suggested that the pathophysiology of chronic tic disorder was strongly correlated with abnormalities of dopaminergic system.

Relationship between First-Episode Schizophrenic Psychopathology and 99m-Tc-ECD SPECT Regional Cerebral Blood Flow and Plasma Homovanillic Acid / 대한정신약물학회지

OBJECTIVE: The purpose of this study was to examine the relative blood flow differences of brain regions between first-episode schizophrenic patients and normal controls and the relationships between these regions and the changes of psychopathology scores, the treatment response, after serotonin dopamine antagonist (SDA) risperidone treatment. Another purpose of this study was to investigate SPECT relative blood flow index as the treatment response predictor of SDA treatment under control of the influences of homovanillic acid (HVA). We hypothesize that there is differences in the brain blood flows examined by SPECT between first-episode schizophrenic patients and normal controls. Relative blood flow index examined by SPECT will be the response predictors of SDA treatment of schizophrenia under control of influences of metabolites. METHODS: The relative blood flows of seventeen first-episode schizophrenic patients and ten normal controls were examined by 99m-Tc ECD SPECT before drug treatment. The patients group was treated for 6 weeks with SDA. The psychopathology was assessed at baseline just before SDA trial and then at 2 weeks and 6 weeks after SDA treatment. At the same time plasma HVA was evaluated by HPLC (high performance liquid chromatography). RESULTS: The cerebral blood flow of first-episode schizophrenic patients was decreased in thalamus and left basal ganglia and the relative blood flow index of schizophrenic patient's left thalamus was significant therapeutic predictor of SDA treatment of positive symptoms under control of the HVA influnences. CONCLUSION: These results suggest that the relative blood flow examined by SPECT will be a therapeutic index of SDA treatment in schizophrenia.

Clinical Psychiatric Drug Trials in Korea: 1962~1998 / 대한정신약물학회지

OBJECTIVE: This investigation was performed to uncover the nature of the clinical drug trials in the past in Korean psychiatry and to prepare some guidelines for the good clinical practice in the future. METHOD: We reviewed total 212 papers of the clinical drug trials in the major Korean psychiatric journals from April 1962 to December 1998. RESULTS: From the year 1985, when the pharmacological and biological organizations in psychiatry were found in our country, the clinical drug trials are rapidly expanding. Although open clinical trials in small sample size less than 30 subjects were the most frequent in the past, some well-designed clinical trials such as multicenter double-blind cross-over study were performed recently. Majority of these 212 clinical trials was done in patients with schizophrenia and mood disorders. Haloperidol was just the drug most frequently evaluated in the clinical trials in our country. As expected, among several clinical rating scales, Brief Psychiatric Rating Scale was the most frequently used. Prolactin and homovanillic acid were the materials frequently measured in the patients with schizophrenia. A few of these clinical trials were performed under the financial supports from the industry, and only one biological research had gained a fund from a national academic institute. To evaluate the researchers' concepts for the medical ethics in the clinical drug trials, we reviewed the description about the informed consent and the approval of institutional review board in all papers. Surprisingly, we found no descriptions about the informed consent in 113 papers(65.8%). Only one clinical trial was performed after the approval of the institutional review board. CONCLUSIONS: We confirmed that the majority of the clinical psychiatric drug trials in the past were performed in lacks of the concept of Good Clinical Practice(GCP). The KGCP guideline did not influenced on the researchers' concepts and performance for the medical ethics at all. Although all of the clinical trials may not need to be done under the guidelines of GCP, clinical researchers' efforts for the medical ethics should be continued for both, the patient and the researcher.

The Influence of Estrogen on Dopamine Metabolites in Schizophrenia

OBJECTIVES: The aims of this study were to discriminate the clinical differences, to measure the estrogen and homovanillic acid levels. to evaluate a correlation between estrogen and homovanillic acid. and to identify an association of cognitive deficit with estrogen and homovanilli acid among male and female schizophrenics. METHODS: In addition to the structured interviews, the plasma estrogen levels by radioimmunoassay and the homovanillic acid levels by HPLC were measured in 20 male and 21 female schizophrenics as well as 10 healthy male and 9 female controls. RESULTS: 1) The plasma estrogen levels were higher in females than males, and significantly higher in female schizophenics than female controls. The homovanillic acid levels were higher in female schizophrenics than female controls, and were lower in male schizophrenics than male controls. 2) The onset age seemed to be earlier in male schizophrenics, and the frequency of admission, duration of antipsychotic drug administration. dosage of antipsychotics and duration of illnesses were more in males. The estrogen and homovanillic acid levels were significantly higher in female schizophrenics. 3) The estrogen levels had a significant positive correlation with sex, age and onset age, while the homovanillic acid levels did with sex. However, estrogen wee not correlated with homovanillic acid levels. 4) The estrogen and homovanillic acid levels were not significantly different between male and female schizophrenics with cognitive deficits. In the schizophrenic patients without cognitive deficits, the estrogen levels were significantly higher in females, while here were no significant sex differences in homovanillic acid. 5) In the male and female schizophrenics predominantly with negative symptoms, there were no significant differences in estrogen and homocanillic acid levels. In those predominantly with positive symptoms, the estrogen levels wee significantly higher in females, while there were no sex differences in homovanillic acid levels. 6) In schizophrenics with undifferentiated subtype, the estrogen and homovanillic acid levels were significantly higher in females. In those with paranoid or disorganized subtypes. the estrogen levels were significantly higher females, while there were no sex differences in the homovanillic acid levels. 7) The mean values of PANSS-negative. PANSS-total, PANSS-CF, MMSE-K and estrogen levels were significantly higher in male schizophrenics with cognitive deficits. The mean values of illness duration, CGI PANSS-positive, PANSS-negative, PANSS-total, PANSS-CF and MMSE-K were significantly higher in female schizophrenics with cognitive deficits. 8) The variables which showed significant correlation with cognitive deficits were PANSS-nagative, PANSS-total, PANSS-CF, MMSE-K and estrogen levels in male schizophrenics. The variables which showed significant correlation with cognitive deficits were subtypes, onset age, illness duration, CGI, PANSS-positive, PANSS-negative, PANSS-total, PANMSS-CF and MMSE-K in female schizophrenics. The estrogen levels were significantly correlated with admission frequencies, history of antipsychotic administration, duration of antipsychotic administration and cognitive deficits in male schizophrenics. while age were not correlated with in females. The homovanillic acid levels had a significant correlation with subtypes and onset age in male schizophrenics, while there were no correlation among variables in females. CONCLUSIONS: Although the plasma concentrations of estrogen and homovaillic acid in female schizophrenics were significantly higher than males, we could not find an association between them. Furthermore, the various factors affecting on the cognitive deficits, estrogen and homovanillic acid levels seemed to be somewhat different according to sex.