1.Peripheral serotoninergic response to physical exercise in athletic horses.
Daniela ALBERGHINA ; Claudia GIANNETTO ; Giuseppe PICCIONE
Journal of Veterinary Science 2010;11(4):285-289
The purpose of this study was to evaluate the influence of exercise on plasma tryptophan (TRP) and free serotonin (f5-HT), whole blood-5-HT (WB-5-HT) and f5-HT/WB-5-HT ratio in Italian Saddle horses. Six clinically healthy Italian Saddle horses were subjected to a 450 meters obstacles course. Blood samples were collected from each horse by jugular venipuncture using vacutainer tubes with K3-EDTA at rest, immediately after exercise, and after 30 min. TRP, f5-HT and WB-5-HT were analyzed by HPLC. Immediately after exercise, statistically significant increases of f5-HT (p<0.001) and WB-5-HT (p<0.001) were observed. After 30 min, f5-HT and WB-5-HT decreased compared to immediately after exercise, but were still significantly higher than rest values (p<0.01 and p<0.05, respectively). A significant linear regression between f5-HT and WB-5-HT was observed during experimental conditions. f5-HT and WB-5-HT modifications after exercise suggest an important role of peripheral serotoninergic markers in response to physical activity. The possible source of extra serotonin detected after show jumping should be clarified by further investigation.
Animals
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Biological Markers/blood
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Female
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Horses/*blood/*metabolism
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Linear Models
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Male
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*Physical Conditioning, Animal/physiology
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Serotonin/*blood
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Tryptophan/blood
2.Association Study of Tyrosine Hydroxylase and Tryptophan Hydroxylase with Schizophrenia.
Kyu Young TOH ; Seung Kyu BANG ; In Ho PAIK
Journal of Korean Neuropsychiatric Association 2000;39(3):638-646
Neurochemical investigation has played a major role in the search for the cause of schizophrenia. Among many hypotheses, dopamine hypothesis of schizophrenia prevails despite much criticism and qualification. Recently, evidences showing the atypical antipsychotics act via serotonergic mechanism suggest serotonin system as an etiologic factor for schizophrenia. We examined the possibility of the association of enzymes critical for the synthesis of serotonin (tryptophan hydroxylase, TPH) and dopamine (tyrosine hydroxylase, TH) with schizophrenia. The regions of DNA that has been known to be polymorphic were amplified using polymerase chain reaction from the peripheral blood cells of 374 biologically unrelated schizophrenic patients and 393 healthy controls. RFLP (A218C) and VNTR polymorphism (intron 1) were examined for TPH and TH, respectively. The patterns of polymorphisms and the frequencies of each allele were not significantly different between the control and the patient groups, suggesting no possible associations of the genetic polymorphisms of TPH and TH genes and schizophrenia. However, in schizophrenics, the frequency of A type allele was significantly higher in positive group than negative group. Thess findings suggest the association of positive schizophrenia with A type allele of TH gene.
Alleles
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Antipsychotic Agents
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Blood Cells
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DNA
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Dopamine
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Genetics
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Humans
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Polymerase Chain Reaction
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Polymorphism, Genetic
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Polymorphism, Restriction Fragment Length
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Schizophrenia*
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Serotonin
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Tryptophan Hydroxylase*
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Tryptophan*
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Tyrosine 3-Monooxygenase*
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Tyrosine*
3.Research Progress on role of Abnormal Tryptophan Metabolism in Immune Thrombocytopenia.
Zhao-Jian LI ; Xiao-Qian LIU ; Jun-Qing XU ; Xiao-Xia CHU
Journal of Experimental Hematology 2015;23(6):1813-1816
Immune thrombocytopenia (ITP) is a common acquired autoimmune hematological disorders. Platelet autoantibodies lead to the decrease of platelet production and (or) increase of its destruction. The latest researches showed that the abnormal tryptophan metabolism mediated by indoleamine-2, 3-dioxygenase(IDO) is related with the pathogenesis of ITP. The patients with ITP show less expression of IDO, reduction of Treg cells and increase of autoreactive T cells and autoantibodies. CTLA-4-Ig can improve the expression of IDO in the patients with ITP, which also can inhibit the proliferation and activation of self-reactive T cells. Thus, clarifying the abnormal tryptophan metabolism mediated by IDO may provide a new idea for improving the understand of the pathogenesis and treatment of ITP. This review focuses on reasearch progress of the tryptophan metabolism mediated by IDO and ITP.
Autoantibodies
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Blood Platelets
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Humans
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Indoleamine-Pyrrole 2,3,-Dioxygenase
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Thrombocytopenia
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Thrombopoiesis
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Tryptophan
4.Plasma metabonomics study of ischemic cerebral apoplexy rats treated with Tongsaimai pellets.
Jiayu TU ; Jiye A ; Guangji WANG ; Hongmei WEN ; Aiyun WANG ; Liuqing DI ; Bei CAO ; Linsheng LIU
China Journal of Chinese Materia Medica 2012;37(7):1028-1033
OBJECTIVETo observe abnormal metabolic changes caused by ischemic cerebral apoplexy and the regulating action of Tongsaimai pellets on abnormal metabolism by analyzing the change of small molecules in plasma of ischemic cerebral apoplexy rat. To find the potential biomarkers, and to explore metabolic mechanisms of Tongsaimai pellets.
METHODRat models of middle cerebral artery occlusion was established with electric coagulation, and rats were divided into 4 groups, model group, sham-operation group, Tongsaimai pellets group and positive control group. Tongsaimai pellets and positive control group were orally administrated by 13.2 g x kg(-1) x d(-1) of crude drugs and 32 mg x kg(-1) x d(-1) of Nimodipine respectively, m odel and sham-operation group by equal volume of distilled water for a week. Plasma of model and sham-operation group were collected, and plasma of Tongsaimai pellets and positive control group were collected on the 1st, 3rd , 7th day after administration. Endogenous metabolites of four groups were determined with GC-MS. Partial least squares discriminant analysis (PLS-DA) was applied to analyze multivariate data and set up model, and T-test was used in significant statistical analysis.
RESULTCompared with sham-operation group rats, pyruvic acid, taurine and hydroxyproline obviously increased in model group rats, while lactic acid, glyceric acid, aminomalonic acid, fructose, tryptophan and leucine significantly decreased, so these metabolites were potential metabolic biomarkers. These endogenous metabolites except taurine got restoration in Tongsaimai group rats.
CONCLUSIONAbnormal metabolite level in plasma can be certainly recovered by Tongsaimai pellets, and the treatment of Tongsaimai pellets can be connected with the regulation of related metabolic pathways.
Animals ; Brain Ischemia ; blood ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Fructose ; blood ; Glyceric Acids ; blood ; Hydroxyproline ; blood ; Lactic Acid ; blood ; Leucine ; blood ; Male ; Malonates ; blood ; Metabolomics ; methods ; Pyruvic Acid ; blood ; Rats ; Rats, Sprague-Dawley ; Stroke ; blood ; drug therapy ; Taurine ; blood ; Tryptophan ; blood
5.Targeted Plasma Metabolite Profiling of Metformin in Healthy Korean Volunteers.
Ho Seob LIHM ; Jaemin CHA ; Jeong Ju SEO ; Jeonghyeon PARK ; Joomi LEE ; Hae Won LEE ; Kyun Seop BAE ; Woomi KIM ; Young Ran YOON
Journal of Korean Society for Clinical Pharmacology and Therapeutics 2012;20(2):175-181
BACKGROUND: Metformin is an effective oral antihyperglycaemic agent for type 2 diabetes mellitus, with a variety of metabolic effects. In addition to controlling blood glucose level, it has been appeared to decrease the long-period complications of diabetes, including macrovascular disease. Few reports have addressed the metabolite profiling of metformin. The study was to evaluate if targeted metabolic profiling approach is sensitive enough to predict the therapeutic effects of metformin after a single oral dose. METHODS: A randomized, open-label, single-dose study was conducted in twenty eight healthy Korean male volunteers. To determine the concentrations of endogenous metabolites in their pre-dose and post-dose plasma samples, blood samples were collected before and at 2 and 6 h after a single oral dose of 500 mg metformin. Both Modular P/Modular D analyzer and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)-based metabolic profiling was performed. RESULTS: We quantified pre-dose and post-dose creatinine, blood urea nitrogen (BUN), lactic acid, 7 amino acids (lysine, glutamic acid, alanine, valine, leucine, phenylalanine, tryptophan), and 5 lysophosphatidylcholines (14:0, 16:0, 17:0, 18:0, and 18:1) using autoanalyser and UPLC-MS/MS. The postdose levels of alanine, lactic acid, glutamic acid, lysine, valine, leucine, phenylalanine, tryptophan, and lysoPC (18:1) were slightly decreased with statistical significance, but there is no clinical significance. CONCLUSION: In order to explore the potential endogenous metabolites associated with the therapeutic effects of metformin, further study including non-targeted (global) metabolite profiling is needed.
Alanine
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Amino Acids
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Blood Glucose
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Blood Urea Nitrogen
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Chromatography, Liquid
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Creatinine
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Diabetes Mellitus, Type 2
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Glutamic Acid
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Humans
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Lactic Acid
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Leucine
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Lysine
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Lysophosphatidylcholines
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Male
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Metformin
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Phenylalanine
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Plasma
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Tandem Mass Spectrometry
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Tryptophan
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Valine
6.Targeted Plasma Metabolite Profiling of Metformin in Healthy Korean Volunteers.
Ho Seob LIHM ; Jaemin CHA ; Jeong Ju SEO ; Jeonghyeon PARK ; Joomi LEE ; Hae Won LEE ; Kyun Seop BAE ; Woomi KIM ; Young Ran YOON
Journal of Korean Society for Clinical Pharmacology and Therapeutics 2012;20(2):175-181
BACKGROUND: Metformin is an effective oral antihyperglycaemic agent for type 2 diabetes mellitus, with a variety of metabolic effects. In addition to controlling blood glucose level, it has been appeared to decrease the long-period complications of diabetes, including macrovascular disease. Few reports have addressed the metabolite profiling of metformin. The study was to evaluate if targeted metabolic profiling approach is sensitive enough to predict the therapeutic effects of metformin after a single oral dose. METHODS: A randomized, open-label, single-dose study was conducted in twenty eight healthy Korean male volunteers. To determine the concentrations of endogenous metabolites in their pre-dose and post-dose plasma samples, blood samples were collected before and at 2 and 6 h after a single oral dose of 500 mg metformin. Both Modular P/Modular D analyzer and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)-based metabolic profiling was performed. RESULTS: We quantified pre-dose and post-dose creatinine, blood urea nitrogen (BUN), lactic acid, 7 amino acids (lysine, glutamic acid, alanine, valine, leucine, phenylalanine, tryptophan), and 5 lysophosphatidylcholines (14:0, 16:0, 17:0, 18:0, and 18:1) using autoanalyser and UPLC-MS/MS. The postdose levels of alanine, lactic acid, glutamic acid, lysine, valine, leucine, phenylalanine, tryptophan, and lysoPC (18:1) were slightly decreased with statistical significance, but there is no clinical significance. CONCLUSION: In order to explore the potential endogenous metabolites associated with the therapeutic effects of metformin, further study including non-targeted (global) metabolite profiling is needed.
Alanine
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Amino Acids
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Blood Glucose
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Blood Urea Nitrogen
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Chromatography, Liquid
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Creatinine
;
Diabetes Mellitus, Type 2
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Glutamic Acid
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Humans
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Lactic Acid
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Leucine
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Lysine
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Lysophosphatidylcholines
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Male
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Metformin
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Phenylalanine
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Plasma
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Tandem Mass Spectrometry
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Tryptophan
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Valine
7.Metabonomic study on the anti-liver injury effect of Si-Ni-San on rats by using UPLC-MS/MS.
Li-Na YANG ; Jing WEN ; Yi SUN ; Jia-Jia LIANG ; Wei-Hua ZHENG ; Li-Li ZHANG ; Yu-Jie ZHOU ; Zhi-Li XIONG
Acta Pharmaceutica Sinica 2014;49(3):368-373
A UPLC-MS/MS method based on metabonomic skills was developed to study the serum metabolic changes of rats after acute liver injury induced by CCl4 and to evaluate the action mechanism of Si-Ni-San. The integrated data were exported for principal components analysis (PCA) by using SIMCA-P software, in order to find the potential biomarkers. It showed that clear separation of healthy control group, model group, silymarin group, Si-Ni-San group was achieved by using the PCA method. Nine significantly changed metabolites were identified as potential biomarkers of acute liver injury. Compared with the health control group, the model group rats showed higher levels of phenylalanine, tryptophan and GCDCA together with lower levels of LPC 16 : 0, LPC 18 : 0, LPC 18 : 1, LPC 16 : 1, LPC 20 : 4 and LPC 22 : 6. These changes of serum metabolites suggested that the disorders of amino acid metabolism, lipid metabolism, bile acid biosynthesis and anti-oxidative damage were related to acute liver injury induced by CCl4. Si-Ni-San might have the anti-liver injury effect on all these four metabolic pathways.
Animals
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Carbon Tetrachloride Poisoning
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Chemical and Drug Induced Liver Injury
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blood
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etiology
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Chromatography, High Pressure Liquid
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methods
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Drugs, Chinese Herbal
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isolation & purification
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pharmacology
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Glycodeoxycholic Acid
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blood
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Lysophosphatidylcholines
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blood
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Male
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Metabolomics
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Phenylalanine
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blood
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Plants, Medicinal
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chemistry
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Principal Component Analysis
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Random Allocation
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Rats
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Rats, Sprague-Dawley
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Tandem Mass Spectrometry
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Tryptophan
;
blood
8.The effect of amino acid nutritional support on serum tryptophan and melatonin in lung cancer patients receiving chemotherapy.
Shi YIN ; Shi-lian HU ; Gan SHEN ; Wei-dong WANG ; Bing HU ; Wei-ping XU ; Hua WANG ; Qi ZHANG
Chinese Journal of Oncology 2006;28(11):840-843
OBJECTIVETo investigate the effect of amino acid parenteral nutritional (PN) support on serum tryptophan and melatonin in non-small cell lung cancer (NSCLC) patients receiving chemotherapy.
METHODSSeventy-two patients with inoperable NSCLC were divided into three groups randomly: control group, 250 ml/d amino acids PN therapy group and 500 ml/d amino acids PN therapy group. The same NP (cisplatin + vinorelbine) chemotherapy was carried out in all the three groups. During three sessions of chemotherapy,amino acids PN therapy was given to the amino acids PN therapy groups. Serum tryptophan and melatonin concentration changes were assessed before and after chemotherapy.
RESULTSAfter chemotherapy the concentration of MT and Try were much lower than that before chemotherapy in the three group patients (P < 0.05). But the concentration of MT and Try in the PN group patients was higher than that in control group patients. The concentration of MT and Try in the 500 ml/d amino acid parenteral nutritional support group patients were significantly higher than that in the 250 ml/d group patients, the difference was significant (P < 0.05).
CONCLUSIONAmino acid parenteral nutritional support is beneficial to improve the lower concentration of serum MT and Try in NSCLC patients receiving chemotherapy, and a more significant effect can be achieved by the 500 ml/d amino acid parenteral nutritional support treatment.
Aged ; Amino Acids ; administration & dosage ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; blood ; drug therapy ; therapy ; Cisplatin ; administration & dosage ; Female ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; therapy ; Male ; Melatonin ; blood ; Neoplasm Staging ; Parenteral Nutrition ; Treatment Outcome ; Tryptophan ; blood ; Vinblastine ; administration & dosage ; analogs & derivatives