Differences of Plasma Levels of Tryptophan, Serotonin, 5-Hydroxyindole Acetic Acid, and Kynurenine between Healthy People and Patients of Major Monopolar Depression at Various Age and Gender

Background: It is not well analyzed whether there are differences in plasma levels of tryptophan (TRP) metabolites between healthy control people (HC) and patients of major monopolar depression (MMD). Methods: Ultra high-speed liquid chromatography/mass spectrometry has been used for the simultaneous determination of plasma levels of tryptophan metabolites in depressive patients. Results: There are no significant differences between plasma levels of TRP between HC and MMD. Plasma levels of TRP of HC are higher in young men, young women, old men, and old women in this order. Serotonin (5-HT) levels are higher in MMD than HC. Plasma levels of 5-HIAA of HC are also higher than those of patients of MMD. Plasma levels of kynurenine (KYN) of healthy old men and old women are higher than those of young men and old women. Plasma levels of KYN are higher in old women and young men of MMD than those of HC. Conclusion: Plasma levels of 5-HT are higher in patients of MMD than those of HC, which may suggest that use of drugs inhibiting the 5-HT transportation may increase plasma levels of 5-HT in MMD.

Synthesis and In Vitro Antiviral Activities of Some New 2-Arylthiomethyl-4-tertiaryaminomethylsubstituted Derivatives of 6-Bromo-3-ethoxycarbonyl-5-hydroxyindoles

Some new derivatives of 3-ethoxycarbonyl-6-bromo-5-hydroxyindoles were designed and prepared, their antiviral activity were determined in cell culture with virus cytopathic effect assay. The results showed compound Ⅶ b, Ⅶ h exhibited potential antiviral activity.

A型性格、冠心病与血浆5－羟色胺的关系

Ａ型性格者的５－羟色胺（５－ＨＴ）、５－羟吲哚乙酸（５－ＨＩＡＡ）值显著高于Ｂ型性格者；Ａ、Ｂ型性格冠心病发作患者５－ＨＴ、５－ＨＩＡＡ值分别较Ａ和Ｂ型性格对照组升高，其中以Ａ型性格冠心病者升高最为显著；Ａ和Ｂ型性格冠心病发作缓解后５－ＨＴ值均显著下降，但前者仍显著高于Ａ型性格对照组，提示５－ＨＴ与Ａ型性格及冠心病发病关系密切。

黄芪注射液治疗心脑血管病合并失眠症的作用机理

目的 观察黄芪注射液对心脑血管病合并失眠患者睡眠时间的影响 ,并探讨其作用机理。方法 将 16 4例心脑血管病合并失眠症的患者随机分为黄芪注射液组 (84例 )和灯盏花素注射液组 (80例 ) ,疗程均为 2周。观察两组患者夜间睡眠时间、 5 -HT、 5 -HIAA及TNF -α浓度的变化。结果 (1)两组患者疗效间差别有显著性意义 (P<0 0 5 ) ;(2 )治疗前、后两组患者血浆 5 -HT、 5 -HIAA及血清TNF -α含量间差别均有显著性意义 (P <0 0 5 )。结论 黄芪注射液能明显延长失眠患者的睡眠时间 ,其主要作用机制可能是通过提高TNF -α含量 ,促进脑内 5 -HT的更新和功能 ,促进慢波睡眠 ,减少觉醒。

Measurement of Tryptophan Metabolites in Healthy Old Men and Patients of Type 2 Diabetes Mellitus (T2DM)

Background: Plasma levels of tryptophan (TRP) metabolites have not been measured extensively in patients of type 2 diabetes mellitus (T2DM). Methods: Metabolites analysis was performed by a liquid chromatograph tandem mass spectrometer, the LCMS-8060 quadrupole mass spectrometer combined with Nexera X2 liquid chromatograph system (Shimadzu Corporation, Kyoto, Japan). Body mass index (BMI) and TRP metabolites have been measured in healthy old men (n = 20) and patients of T2DM (n = 20). TRP metabolites were measured by using the ultrahigh speed liquid chromatography-mass spectros-copy (Shimadzu Corporation). Results: The plasma levels of 5-hydroxytryptophan (5-HTRP), 5-hydroxyindoleacetic acid (5-HIAA), kynurenic acid (KNA), 3-hydroxykynurenine (3-HKN), and 3-hydroxyanthranilic acid (3-HAA) were higher in patients of T2DM than healthy old men. Since 5HTRP and 5-HIAA belong to the serotonin pathway, and KNA, 3-HKN, and 3-HAA belong to the KN pathway of TRP metabolism, these pathways were activated more in the patients of T2DM. Since plasma levels of Indole-3-acetic acid were not elevated in T2DM, that pathway was not activated more in T2DM. Serotonin levels were not increased but 5-HIAA levels were increased in the plasma of T2DM patients, which may mean that serotonin was quickly metabolized to 5-HIAA in the patients of T2DM. Conclusion: Plasma levels of tryptophan metabolites in serotonin and kynurenine pathways increased in T2DM patients. Obesity expressed by BMI may not influence tryptophan metabolism in healthy old men and T2DM patients. These results indicate that our new method of the simultaneous measurements of all the tryptophan metabolites is the powerful measure to identify factor related to endogenous stresses seen in DM.

Grape Seed Extract (<i>Vitisvinifera</i>) Alleviate Neurotoxicity and Hepatotoxicity Induced by Lead Acetate in Male Albino Rats

Grape seed extracts (GSE) are very potent antioxidant and exhibit numerous interesting pharmacologic activities, including an antioxidant property, and has been suggested to be of use in treatment of several diseases. The present study has been undertaken to investigate the protective and therapeutic effect of GSE against lead-induced neuro and hepatotoxicity in rat. Male albino rats were divided into six groups: the 1st group, rats were injected daily with saline vehicle and served as negative control, the 2nd group (positive control group), the rats were injected (i.p.) with subacute dose (100 mg/kg b·w/day) of lead acetate (LA). The 3rd group (protective group), the rats were injected (i.p.) with LA (100 mg/kg b·w/day) for 7 days after treatment with GSE (100 mg/kg b·w/day) for 3 weeks. The 4th, 5th and 6th groups (therapeutics groups), rats were injected (i.p.) with subacut dose (100 mg/kg b·w/day) of lead acetate for 7 days, then treated with GSE (100 mg/kg b·w/day) for one, two and three weeks, respectively. The level of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and 5-hydroxyindol acetic acid (5-HIAA) were evaluated in brain regions (cerebellum, brainstem, striatum, cerebral cortex, hypothalamus and hippocampus). The result indicated that the administration of subacute dose of LA (100 mg/kg/day, i.p.) induce a significant decrease in NE, DA, 5-HT and 5-HIAA content in all tested brain regions. Also the obtained data showed significant increase in liver enzymes: serum glutamate oxaloacetate transaminase (GOT), serum glutamate pyruvate transaminase (GPT) and Lactate dehydrogenase (LDH) level in group 2 (positive control). There is an improvement in neurotransmitters content. Also the obtained data showed significant in- crease in liver enzymes of protective (G3) and therapeutics groups (G4, G5 and G6) which received GSE compared with animal group that received lead acetate (G2). This is may be the presence of proanthocyanidins and procyanidins which have antioxidant and free radical scavenging activities. The result suggests that grape seed extract may prevent lead-induced neurotoxicity and hepatotoxicity.

Effects of Gender, Age, and Clot Formation on the Measurements of Tryptophan Metabolites in Blood

Background: Tryptophan metabolism plays important roles in health and diseases. Although simultaneous measurements of tryptophan metabolites are successfully measured, influences of age, gender, and clot formation on the measurements have not been reported. Methods: We took blood from young and old Japanese men and women and compared plasma levels of tryptophan metabolites. We also took plasma and serum from the blood of middle-aged men (n = 10). Metabolites analysis was performed by a liquid chromatograph tandem mass spectrometer, the LCMS-8060 quadrupole mass spectrometer combined with Nexera X2 liquid chromatograph system (Shimadzu Corporation, Kyoto, Japan). Body mass index (BMI) and TRP metabolites have been measured in healthy young men (n = 48), young women (n = 47), old men (n = 44), and old women (n = 39). TRP metabolites were measured by using the ultrahigh speed liquid chromatography-mass spectroscopy (Shimadzu Corporation). Results: Tryptophan and its metabolites such as serotonin, 5-hydroxyindole acetic acid, indole-3-acetic acid, kynurenine, anthranilic acid, were higher in young women and old men than young men and old women. Plasma levels of 3-hydroxykynurenine and xanthurenic acid were lower in young women and old men. Comparison of plasma and serum indicates that most of metabolites were higher in serum than plasma except for 3-hydroxy-kynurenine and quinolinic acid. Conclusion: Metabolites of the upper stream of degradation of tryptophan were higher in young women and old men than young men and old women, which suggests that the degradation of tryptophan was accelerated in young men and old women than young women and old men. Serum preparation may activate tryptophan degradation resulting in higher levels of metabolites in serum than in plasma.

Comparison of Plasma Levels of Tryptophan Metabolites between Healthy People and Patients of Bipolar Depression at Various Age and Gender

Background: It is not well analyzed whether there are differences in plasma levels of tryptophan (TRP) metabolites between healthy control people (HC) and patients of type II bipolar depression (BDII). Methods: Ultra high-speed liquid chromatography/mass spectrometry has been used for the simultaneous determination of plasma levels of tryptophan metabolites in depressive patients. Results: Plasma levels of TRP are not different between HC and patients of BDII. Serotonin (5-HT) levels are higher in BDII than HC. Plasma levels of 5-HIAA of HC are higher than those of old women of BDII, but lower in young women of BDII. Plasma levels of kynurenine (KYN) of HC are not different from those of patients of BDII. Conclusion: Plasma levels of 5-HT are higher in patients of BDII than those of HC, which may suggest that use of drugs inhibiting the 5-HT transportation and lower transporter biding may increase plasma levels of 5-HT in patients of BD.

Comparison of Age and Gender Differences of Tryptophan Metabolites in Patients of Major Monopolar and Bipolar Depression

Background: No research has been done for the determination of plasma levels of tryptophan metabolites in patients of monopolar and bipolar depression. Methods: Ultra high-speed liquid chromatography/mass spectrometry has been used for the simultaneous determination of plasma levels of tryptophan metabolites in depressive patients. Results: No significant age and gender differences were shown in monopolar depressive patients and some differences were shown in bipolar patients. The administration of drugs such as antidepressants, antipsychotics, mood stabilizers do not seem to have affected the results. Conclusion: In patients of major monopolar depression age and gender differences of plasma levels of tryptophan metabolites disappear although significant differences are observed in healthy volunteers. Some differences of age and gender differences were shown between monopolar and bipolar depressive patients.

A three-pronged analysis confirms the association of the serotoninergic system with attention deficit hyperactivity disorder

Background The serotonin transporter(SERT),encoded by the solute carrier family 6 number 4(SLC6A4)gene,controls serotonin(5-HT)availability and is essential for the regulation of behavioral traits.Two SLC6A4 genetic variants,5-HTTLPR and STin2,were widely investigated in patients with various neurobehavioral disorders,including attention deficit hyperactivity disorder(ADHD).Methods We analyzed the association of the 5-HTTLPR(L/S)and STin2(10/12)variants,plasma 5-HT,and 5-hydroxyindole acetic acid(5-HIAA),as well as SERT messenger RNA(mRNA)with ADHD in the eastern Indian subjects.Nuclear families with ADHD probands(n=274)and ethnically matched controls(n=367)were recruited following the Diagnostic and Statistical Manual of Mental Disorders.Behavioral traits,executive function,and intelligence quotient(IQ)of the probands were assessed using the Conner's Parent Rating Scale–Revised,Parental Account of Children’s Symptoms(PACS),Barkley Deficit in Executive Functioning—Child and Adolescent Scale,and Wechsler Intelligence Scale for Children-III,respectively.After obtaining informed written consent,peripheral blood was collected to analyze genetic variants,plasma 5-HT,5-HIAA,and SERT mRNA expression.Results ADHD probands showed a higher frequency of the 5-HTTLPR“L”allele and“L/L”genotype(P<0.05),lower 5-HIAA level,and higher SERT mRNA expression.Scores for behavioral problems and hyperactivity were higher in the presence of the“S”allele and“S/S”genotype,while executive deficit was higher in the presence of the“L”allele.IQ score was lower in the presence of the STin2“12”allele and L-12 haplotype.Conclusion Data obtained indicate a significant association of the serotoninergic system with ADHD,warranting further in-depth investigation.