OBJECTIVE: We undertook this study to investigate the discriminant metabolites in urine from patients with established rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and from healthy individuals. METHODS: Urine samples were collected from 148 RA patients, 41 SLE patients and 104 healthy participants. The urinary metabolomic profiles were assessed using 1H nuclear magnetic resonance spectroscopy. The relationships between discriminant metabolites and clinical variables were assessed. Collagen-induced arthritis was induced in mice to determine if a choline-rich diet reduces arthritis progression. RESULTS: The urinary metabolic fingerprint of patients with established RA differs from that of healthy controls and SLE patients. Markers of altered gut microbiota (trimethylamine-N-oxide, TMAO), and oxidative stress (dimethylamine) were upregulated in patients with RA. In contrast, markers of mitochondrial dysfunction (citrate and succinate) and metabolic waste products (p-cresol sulfate, p-CS) were downregulated in patients with RA. TMAO and dimethylamine were negatively associated with serum inflammatory markers in RA patients. In particular, patients with lower p-CS levels exhibited a more rapid radiographic progression over two years than did those with higher p-CS levels. The in vivo functional study demonstrated that mice fed with 1% choline, a source of TMAO experienced a less severe form of collagen-induced arthritis than did those fed a control diet. CONCLUSION: Patients with RA showed a distinct urinary metabolomics pattern. Urinary metabolites can reflect a pattern indicative of inflammation and accelerated radiographic progression of RA. A choline-rich diet reduces experimentally-induced arthritis. This finding suggests that the interaction between diet and the intestinal microbiota contributes to the RA phenotype.
Animals ; Arthritis* ; Arthritis, Experimental ; Arthritis, Rheumatoid* ; Choline ; Dermatoglyphics ; Diet* ; Gastrointestinal Microbiome ; Healthy Volunteers ; Humans ; Inflammation ; Lupus Erythematosus, Systemic ; Magnetic Resonance Spectroscopy ; Metabolome* ; Metabolomics ; Mice ; Oxidative Stress ; Phenotype* ; Spectrum Analysis ; Waste Products

The proton magnetic resonance spectroscopy (¹H-MRS) is a tool used to detect concentrations of brain metabolites such as N-acetyl aspartate, choline, creatine, glutamate, and gamma-amino butyric acid (GABA). It has been widely used because it does not require additional devices other than the conventional magnetic resonance scanner and coils. Demyelination, or the neuronal damage due to loss of myelin sheath, is one of the common pathologic processes in many diseases including multiple sclerosis, leukodystrophy, encephalomyelitis, and other forms of autoimmune diseases. Rodent models mimicking human demyelinating diseases have been induced by using virus (e.g., Theiler's murine encephalomyelitis virus) or toxins (e.g., cuprizon or lysophosphatidyl choline). This review is an overview of the MRS findings on brain metabolites in demyelination with a specific focus on rodent models.
Animals* ; Aspartic Acid ; Autoimmune Diseases ; Brain ; Butyric Acid ; Choline ; Creatine ; Demyelinating Diseases* ; Encephalomyelitis ; Glutamic Acid ; Humans ; Models, Animal* ; Multiple Sclerosis ; Myelin Sheath ; Neurons ; Pathologic Processes ; Proton Magnetic Resonance Spectroscopy ; Rodentia ; Spectrum Analysis*

Water soluble extract (WSE) is an important index for the quality evaluation of Astragali Radix (AR). In this study, the WSE of the wild AR from Shanxi province (SX) and the cultivated AR from Gansu Province (GS) were compared. The WSEs of two types of AR were determined according to the appendix of Chinese pharmacopoeia. Then the WSEs were subjected to NMR analysis, and the obtained data were analyzed using HCA, PCA, OPLS-DA, microarray analysis, and Spearman rank analysis. In addition, the Pearson correlation of differential metabolites were also calculated. The results showed that the WSE content of GS-AR (37.80%) was higher than that of SX-AR (32.13%). The main constituent of WSE was sucrose, and other 18 compounds, including amino acids, organic acids, were also detected. Multivariate analysis revealed that SX-AR contained more choline, succinic acid, citric acid, glutamate, taurine and aspartate, while GS samples contained more sucrose, arginine and fumaric acid. In addition, the Pearson correlations between different metabolites of the two types of AR also showed apparent differences. The results suggested that the WSE of two types of AR differs not only in the content, but also in the chemical compositions. Thus, the cultivation way is important to the quality of AR. This study supplied a new method for the comparison of extract of herbal drugs.
Arginine ; analysis ; Aspartic Acid ; analysis ; Choline ; analysis ; Citric Acid ; analysis ; Drugs, Chinese Herbal ; analysis ; chemistry ; Fumarates ; analysis ; Glutamic Acid ; analysis ; Magnetic Resonance Spectroscopy ; Multivariate Analysis ; Phylogeography ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Succinic Acid ; analysis ; Sucrose ; analysis ; Taurine ; analysis

Normal aging causes changes in the brain volume, connection, function and cognition. The brain changes with increases in age and difference of gender varies at all levels. Studies about normal brain aging using various brain magnetic resonance imaging (MRI) variables such as gray and white matter structural imaging, proton spectroscopy, apparent diffusion coefficient, diffusion tensor imaging and functional MRI are reviewed. Total volume of brain increases after birth but decreases after 9 years old. During adulthood, total volume of brain is relatively stable. After 35 years old, brain shrinks gradually. The changes of gray and white matters by aging show different features. N-acetylaspartate decreases or remains unchanged but choline, creatine and myo-inositol increase with aging. Apparent diffusion coefficient decreases till 20 years old and then becomes stable during adulthood and increase after 60 years old. Diffusion tensor properties in white matter tissue are variable during aging. Resting-state functional connectivity decreases after middle age. Structural and functional brain changes with normal aging are important for studying various psychiatric diseases such as dementia, schizophrenia and bipolar disorder. Our review may be helpful for studying longitudinal changes of these diseases and successful aging.
Adult ; Aging* ; Bipolar Disorder ; Brain* ; Child ; Choline ; Cognition ; Creatine ; Dementia ; Diffusion ; Diffusion Tensor Imaging ; Humans ; Magnetic Resonance Imaging* ; Middle Aged ; Parturition ; Protons ; Schizophrenia ; Spectrum Analysis ; Young Adult

PURPOSE: To investigate the feasibility of in vivo proton magnetic resonance spectroscopy (MRS) for evaluation of lung cancer. MATERIALS AND METHODS: This prospective study was approved by the institutional review board of our hospital and informed consent was obtained in all patients. Ten patients (7 men, 3 women; mean age, 64.4) with pathologicallyproven lung cancer (mean, 56.8 mm; range, 44-77 mm) were enrolled to 1.5 T MRS using a single-voxel respiration-triggered point-resolved spectroscopic sequence. Technical success rate and the reason of technical failure, if any, were investigated. RESULTS: Out of 10 lung cancers, analyzable MRS spectra were obtained in 8 tumors (technical success rate, 80%). Two MRS datasets were not able to be analyzed due to serious baseline distortion. Choline and lipid signals were detected as major metabolites in analyzable MRS spectra. CONCLUSION: In vivo proton MRS method using a single-voxel respiration-triggered point-resolved spectroscopic sequence is feasible in obtaining the MR spectra of lung cancer because these spectra were analyzable and high success rate was shown in our study although there was the limitation of small patient group.
Choline ; Ethics Committees, Research ; Humans ; Informed Consent ; Lung ; Lung Neoplasms ; Magnetic Resonance Spectroscopy ; Magnetics ; Magnets ; Male ; Prospective Studies ; Protons ; Spectrum Analysis

OBJECTIVETo investigate action of hydrophilic constituents from Coptidis Rhizoma on glucose-lowering effect metabolism of berberine in HepG2 cells.

METHODHydrophilic fractions of Coptidis Rhizoma were prepared by high speed counter current chromatography and separated by silica gel column chromatography. MTT assay was used to monitor the proliferation of HepG2 cells, and Kit was used to test the glucose consumption in culture solution.

RESULTCholine was separated from Coptidis Rhizoma for the first time. Cell assay showed choline can significantly increase the glucose lowering effect of berberine and improve the cytotoxicity of berberine within test concentration. Compared with same dose of berberine, berberine 38 mg x L(-1) in combination with choline 100 mg x L(-1) can make glucose consumption increase by 34% and elevate cell livability up to 75% in HepG2 cells.

CONCLUSIONThe results suggest that choline had a synergistic effect on improving glucose absorption of berberine and decreasing cytotoxicity of berberine.

Absorption ; drug effects ; Berberine ; pharmacology ; Cell Proliferation ; drug effects ; Choline ; analysis ; chemistry ; isolation & purification ; pharmacology ; Chromatography, High Pressure Liquid ; Drug Synergism ; Drugs, Chinese Herbal ; chemistry ; Glucose ; metabolism ; Hep G2 Cells ; Humans ; Hydrophobic and Hydrophilic Interactions

OBJECTIVE: To examine the changes of metabolites in the bilateral thalamus of patients with secondarily generalized tonic-clonic seizure (SGTCS) and to explore the mechanism of SGTCS. METHODS: Thirty patients with SGTCS (epilepsy group) and 30 matched healthy controls (control group) were examined by 1H-magnetic resonance spectroscopy (1H-MRS). The levels of N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine phosphocreatine (Cr-PCr), and myo-inositol (mI) of the bilateral thalamus were measured in both the epilepsy group and the control group. The ratios of NAA/Cr-PCr, NAA/(Cr-PCr+Cho), Cho/Cr-PCr and mI/Cr-PCr were compared and analyzed in the 2 groups. RESULTS: The ratios of NAA/Cr-PCr, and NAA/(Cr-PCr+Cho)(1.7074 ± 0.2214; 0.9333 ± 0.2173) in the left thalamus in the epilepsy group were significantly lower than those in the control group(1.8834 ±0.2093; 1.1243 ±0.2447)(P<0.05). The ratios of NAA/Cr-PCr, and NAA/(Cr- PCr+Cho) (1.7472 ±0.2439; 0.9165 ±0.2462) in the right thalamus in the epilepsy group were also significantly lower than those in the control group(1.8925 ± 0.2004; 1.0941 ± 0.2372)(P<0.05). There were no significant differences in the ratios of NAA/Cr-PCr, NAA/(Cr-PCr+Cho), Cho/Cr- PCr, and mI/Cr-PCr between the bilateral thalamis in the epilepsy group (P>0.05). CONCLUSION There is neuronal dysfunction in the bilateral thalamus in the epilepsy group. Abnormal changes of the bilateral thalamus are involved in the mechanism of SGTCS.
Adolescent ; Adult ; Aspartic Acid ; analogs & derivatives ; analysis ; Brain Chemistry ; Case-Control Studies ; Choline ; analysis ; Energy Metabolism ; physiology ; Epilepsy, Generalized ; metabolism ; physiopathology ; Epilepsy, Tonic-Clonic ; metabolism ; physiopathology ; Female ; Humans ; Magnetic Resonance Spectroscopy ; methods ; Male ; Middle Aged ; Thalamus ; metabolism ; physiopathology ; Young Adult

BACKGROUND AND OBJECTIVEProton magnetic resonance spectroscopy (MRS) of the liver in vivo is in experimental phase. MRS observation on liver cancer after transcatheter arterial chemoembolization (TACE) has seldom been reported. This study was to investigate the value of MRS in assessing the metabolic changes of hepatocellular carcinoma (HCC) after TACE.

METHODSTwenty-five consecutive patients with pathologically-confirmed HCC received 1H MRS of all hepatic lesions using 1.5T whole body MR scanner before TACE and at 3-10 days after TACE. Choline-to-lipid (Cho/Lip), glucogen/glucose-to-lipid (Glu/Lip), and glytamine/glutamate-to-lipid (Glx/Lip) ratios were measured and analyzed statistically.

RESULTSThe Cho/Lip, Glu/Lip, and Glx/Lip ratios were 0.21 +/- 0.08, 0.11 +/- 0.05, 0.28 +/- 0.10 before TACE, respectively, and were 0.10 +/- 0.08, 0.07 +/- 0.07, 0.18 +/- 0.12 after TACE, respectively, with significant differences (P < 0.05).

CONCLUSIONSUsing MRS can evaluate the early metabolic responses of HCC to TACE.

Adult ; Aged ; Carcinoma, Hepatocellular ; metabolism ; therapy ; Chemoembolization, Therapeutic ; Choline ; metabolism ; Female ; Glucose ; metabolism ; Glutamic Acid ; metabolism ; Glutamine ; metabolism ; Glycogen ; metabolism ; Humans ; Lipids ; analysis ; Liver Neoplasms ; metabolism ; therapy ; Magnetic Resonance Spectroscopy ; methods ; Male ; Middle Aged

OBJECTIVEThis study examined the biochemical metabolism by proton magnetic resonance spectroscopy ('H-MRS) in order to explore the value of 'H-MRS in idiopathic epilepsy in children.

METHODSThirty-three children with idiopathic epilepsy (14 cases with history of febrile seizures and 19 cases without) and six normal controls experienced MRI of the skull and brain and single-voxel 'H-MRS examinations of the hippocampi-temporal lobe. The signal intensities of N-acetylaspartate (NAA), eatine+phosphocreatine (Cr), choline-containing compounds (Cho) and lactate (Lac) and the ratios of NAA/ (Cho+Cr) and Lac/Cr were compared between the patients and normal controls.

RESULTSMRI examination showed that only one child with epilepsy had myelin dysplasia. 'H-MRS examination showed that the ratio of NAA/ (Cho+Cr) in the epilepsy group was lower than that in the control group (0.64+/-0.07 vs 0.73+/-0.05; P<0.01). The epileptic children with history of febrile seizures had a more decreased ratio of NAA/ (Cho+Cr) compared with those without the history (0.61+/-0.07 vs 0.66+/-0.06; P<0.05). There were no significant differences in the ratio of Lac/Cr between the epilepsy and the control groups.

CONCLUSIONS'H-MRS may provide early information on brain injury sensitively and non-invasively in children with epilepsy. It may be used for diagnosis and prognosis evaluation of epilepsy.

Aspartic Acid ; analogs & derivatives ; analysis ; Child ; Child, Preschool ; Choline ; analysis ; Epilepsy ; diagnosis ; metabolism ; Female ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; methods ; Male ; Phosphocreatine ; analysis ; Protons

PURPOSE: To investigate the 3-bond and spatial connectivity of human brain metabolites by scalar coupling and dipolar nuclear Overhauser effect/enhancement (NOE) interaction through 2D- correlation spectroscopy (COSY) and 2D- NOE spectroscopy (NOESY) techniques. MATERIALS AND METHODS: All 2D experiments were performed on Bruker Avance 500 (11.8 T) with the zshield gradient triple resonance cryoprobe at 298 K. Human brain metabolites were prepared with 10% D2O. Two-dimensional spectra with 2048 data points contains 320 free induction decay (FID) averaging. Repetition delay was 2 sec. The Top Spin 2.0 software was used for post-processing. Total 7 metabolites such as N-acetyl aspartate (NAA), creatine (Cr), choline (Cho), glutamine (Gln), glutamate (Glu), myo-inositol (Ins), and lactate (Lac) were included for major target metabolites. RESULTS: Symmetrical 2D-COSY and 2D-NOESY spectra were successfully acquired: COSY cross peaks were observed in the only 1.0-4.5 ppm, however, NOESY cross peaks were observed in the 1.0-4.5 ppm and 7.9 ppm. From the result of the 2-D COSY data, cross peaks between the methyl protons (CH3(3)) at 1.33 ppm and methine proton (CH(2)) at 4.11 ppm were observed in Lac. Cross peaks between the methylene protons (CH2(3,H alpha)) at 2.50ppm and methylene protons (CH2,(3,HB)) at 2.70 ppm were observed in NAA. Cross peaks between the methine proton (CH(5)) at 3.27 ppm and the methine proton (CH(4,6)) at 3.59 ppm, between the methine proton (CH(1,3)) at 3.53 ppm and methine proton (CH(4,6)) at 3.59 ppm, and between the methine proton (CH(1,3)) at 3.53 ppm and methine proton (CH(2)) at 4.05 ppm were observed in Ins. From the result of 2-D NOESY data, cross peaks between the NH proton at 8.00 ppm and methyl protons (CH3) were observed in NAA. Cross peaks between the methyl protons (CH3(3)) at 1.33 ppm and methine proton (CH(2)) at 4.11 ppm were observed in Lac. Cross peaks between the methyl protons (CH3) at 3.03 ppm and methylene protons (CH2) at 3.93 ppm were observed in Cr. Cross peaks between the methylene protons (CH2(3)) at 2.11 ppm and methylene protons (CH2(4)) at 2.35 ppm, and between the methylene protons(CH2 (3)) at 2.11 ppm and methine proton (CH(2)) at 3.76 ppm were observed in Glu. Cross peaks between the methylene protons (CH2 (3)) at 2.14 ppm and methine proton (CH(2)) at 3.79 ppm were observed in Gln. Cross peaks between the methine proton (CH(5)) at 3.27 ppm and the methine proton (CH(4,6)) at 3.59 ppm, and between the methine proton (CH(1,3)) at 3.53 ppm and methine proton (CH(2)) at 4.05 ppm were observed in Ins. CONCLUSION: The present study demonstrated that in vitro 2D-COSY and NOESY represented the 3-bond and spatial connectivity of human brain metabolites by scalar coupling and dipolar NOE interaction. This study could aid in better understanding the interactions between human brain metabolites in vivo 2DCOSY study.
Aspartic Acid ; Brain ; Choline ; Creatine ; Glutamic Acid ; Glutamine ; Humans ; Lactic Acid ; Protons ; Spectrum Analysis