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1.
Article in English | WPRIM | ID: wpr-922588

ABSTRACT

OBJECTIVES@#To explore the metabolite characteristics in medial prefrontal cortex (mPFC) by @*METHODS@#A total of 46 patients with the first-episode schizophrenia (FES), 49 people with clinical high risk (CHR), 61 people with genetic high risk (GHR), and 58 healthy controls (HC) were enrolled. The levels of N-acetylaspartylglutamate+N-acetylaspartate (tNAA), choline-containing compounds (Cho) and myo-inositol (MI), glutamate+glutamine (Glx) in medial prefrontal cortex were measured by single-voxel @*RESULTS@#There were significant differences in Glx, tNAA, and MI concentrations among 4 groups (all @*CONCLUSIONS@#The decreased levels of MI and Glx in the FES patients suggest that there may be glial functional damage and glutamatergic transmitter dysfunction in the early stage of the disease. The compensatory increase of metabolites may be a protective factor for schizophrenia in the genetic individuals.


Subject(s)
Aspartic Acid , Glutamic Acid , Glutamine , Humans , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Proton Magnetic Resonance Spectroscopy , Schizophrenia
2.
Article in English | WPRIM | ID: wpr-816616

ABSTRACT

BACKGROUND: We evaluated the association of visceral-to-subcutaneous fat ratio (VSR) with nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis degree based on noninvasive serum fibrosis markers in the general population with NAFLD.METHODS: This is a cross-sectional study, in 7,465 Korean adults who underwent health screening examinations. NAFLD was defined as fatty liver detected on ultrasonography, and visceral and subcutaneous abdominal fat was measured using computed tomography. We predicted fibrosis based on the fibrosis-4 (FIB-4) score and aspartate aminotransferase-to-platelet ratio index (APRI) and categorized the risk for advanced fibrosis as low, indeterminate, or high.RESULTS: The multivariable-adjusted prevalence ratios for indeterminate to high risk of advanced fibrosis based on FIB-4, determined by comparing the second, third, and fourth quartiles with the first quartile of VSR, were 3.38 (95% confidence interval [CI], 0.64 to 17.97), 9.41 (95% CI, 1.97 to 45.01), and 19.34 (95% CI, 4.06 to 92.18), respectively. The multivariable-adjusted prevalence ratios for intermediate to high degree of fibrosis according to APRI also increased across VSR quartiles (5.04 [95% CI, 2.65 to 9.59], 7.51 [95% CI, 3.91 to 14.42], and 19.55 [95% CI, 9.97 to 38.34], respectively). High VSR was more strongly associated with the prevalence of NAFLD in nonobese subjects than in obese subjects, and the associations between VSR and intermediate to high probability of advanced fibrosis in NAFLD were stronger in obese subjects than in nonobese subjects.CONCLUSION: High VSR values predicted increased NAFLD risk and advanced fibrosis risk with NAFLD, and the predictive value of VSR for indeterminate to high risk of advanced fibrosis was higher in obese subjects than in nonobese subjects.


Subject(s)
Abdominal Fat , Adult , Aspartic Acid , Cross-Sectional Studies , Fatty Liver , Fibrosis , Humans , Intra-Abdominal Fat , Liver Cirrhosis , Mass Screening , Non-alcoholic Fatty Liver Disease , Prevalence , Subcutaneous Fat, Abdominal , Ultrasonography
3.
Biol. Res ; 53: 36, 2020. tab, graf
Article in English | LILACS | ID: biblio-1131882

ABSTRACT

BACKGROUND: To investigate the thalamic neurotransmitters and functional connections in the development of chronic constriction injury (CCI)-induced neuropathic pain. METHODS: The paw withdrawal threshold was measured by mechanical stimulation the right hind paw with the von frey hair in the rats of CCI-induced neuropathic pain. The N-acetylaspartate (NAA) and Glutamate (Glu) in thalamus were detected by magnetic resonance spectrum (MRS) process. The thalamic functional connectivity with other brain regions was scanned by functional magnetic resonance image (fMRI). RESULTS: The paw withdrawal threshold of the ipsilateral side showed a noticeable decline during the pathological process. Increased concentrations of Glu and decreased levels of NAA in the thalamus were significantly correlated with mechanical allodynia in the neuropathic pain states. The thalamic regional homogeneity (ReHo) decreased during the process of neuropathic pain. The functional connectivity among the thalamus with the insula and somatosensory cortex were significantly increased at different time points (7, 14, 21 days) after CCI surgery. CONCLUSION: Our study suggests that dynamic changes in thalamic NAA and Glu levels contribute to the thalamic functional connection hyper-excitation during CCI-induced neuropathic pain. Enhanced thalamus-insula functional connection might have a significant effect on the occurrence of neuropathic pain.


Subject(s)
Animals , Rats , Thalamus/metabolism , Wounds and Injuries/physiopathology , Neurotransmitter Agents/metabolism , Neuralgia , Thalamus/physiopathology , Aspartic Acid/analogs & derivatives , Aspartic Acid/metabolism , Glutamic Acid/metabolism , Constriction , Hyperalgesia
4.
Electron. j. biotechnol ; 42: 49-55, Nov. 2019. tab, ilus, graf
Article in English | LILACS | ID: biblio-1087461

ABSTRACT

Background: Protein glutaminase specifically deamidates glutamine residue in protein and therefore significantly improves protein solubility and colloidal stability of protein solution. In order to improve its preparation efficiency, we exploited the possibility for its secretory expression mediated by twin-arginine translocation (Tat) pathway in Bacillus licheniformis. Results: The B. licheniformis genome-wide twin-arginine signal peptides were analyzed. Of which, eleven candidates were cloned for construction of expression vectors to mediate the expression of Chryseobacterium proteolyticum protein glutaminase (PGA). The signal peptide of GlmU was confirmed that it significantly mediated PGA secretion into media with the maximum activity of 0.16 U/ml in Bacillus subtilis WB600. A mutant GlmU-R, being replaced the third residue aspartic acid of GlmU twin-arginine signal peptide with arginine by site-directed mutagenesis, mediated the improved secretion of PGA with about 40% increased (0.23 U/ml). In B. licheniformis CBBD302, GlmU-R mediated PGA expression in active form with the maximum yield of 6.8 U/ml in a 25-l bioreactor. Conclusions: PGA can be produced and secreted efficiently in active form via Tat pathway of B. licheniformis, an alternative expression system for the industrial-scale production of PGA.


Subject(s)
Bacillus licheniformis/enzymology , Glutaminase/metabolism , Arginine , Plasmids , Prostaglandins A/chemistry , Bacillus subtilis , Protein Sorting Signals , Base Sequence , Mutagenesis, Site-Directed , Aspartic Acid , Escherichia coli , Bacillus licheniformis/genetics , Glutaminase/genetics
5.
Article in English | WPRIM | ID: wpr-764981

ABSTRACT

BACKGROUND: Acute necrotizing encephalopathy (ANE) is a rare, but potentially life threatening neurological condition in children. This study aimed to investigate its clinical spectrum, diagnostic and therapeutic dilemma, and prognosis. METHODS: Twelve children with ANE were included in the study. The diagnosis was made by clinical and radiological characteristics from January 1999 to December 2017 and their clinical data were retrospectively analyzed. RESULTS: A total of 12 children aged 6 to 93 months at onset (5 male: 7 female) were evaluated. The etiology was found in 4 of them (influenza A, H1N1; coxsackie A 16; herpes simplex virus; and RANBP2 gene/mycoplasma). The most common initial presentations were seizures (67%) and altered mental status (58%). The majority of the subjects showed elevation of aspartate aminotransferase/alanine aminotransferase with normal ammonia and increased cerebrospinal fluid protein without pleocytosis. Magnetic resonance imaging revealed increased T2 signal density in bilateral thalami in all patients, but the majority of the subjects (67%) also had lesions in other areas including tegmentum and white matter. Despite the aggressive immunomodulatory treatments, the long-term outcome was variable. One child and two sisters with genetic predisposition passed away. CONCLUSION: ANE is a distinctive type of acute encephalopathy with diverse clinical spectrum. Even though the diagnostic criteria are available, they might not be watertight. In addition, treatment options are still limited. Further studies for better outcome are needed.


Subject(s)
Ammonia , Aspartic Acid , Brain Diseases , Cerebrospinal Fluid , Child , Diagnosis , Genetic Predisposition to Disease , Humans , Leukocytosis , Magnetic Resonance Imaging , Male , Prognosis , Retrospective Studies , Seizures , Siblings , Simplexvirus , White Matter
6.
Article in English | WPRIM | ID: wpr-760061

ABSTRACT

PURPOSE: To evaluate the effects of idiopathic infantile nystagmus (IN) and bilateral ametropic amblyopia on metabolites in the occipital cortex by magnetic resonance spectroscopy. METHODS: The children included in this prospective study were divided into three groups. Group 1 consisted of 11 patients with idiopathic IN, group 2 consisted of 10 patients with bilateral ametropic amblyopia and group 3 consisted of nine normal children. A single-voxel magnetic resonance spectroscopy examination was performed by placing a region of interest on the occipital cortex of each participant. N-acetyl aspartate (NAA), creatine (Cr) and choline (Cho) concentrations were measured in the occipital cortex. This was followed by calculating and comparing the NAA/Cr and Cho/Cr ratios between the three groups. The Kruskal-Wallis test, Mann-Whitney U-test, and chi-square test were used for statistical analysis. RESULTS: There was no statistically significant difference in NAA/Cr ratios between patients with idiopathic IN and normal children, but there was a statistically significant difference between these groups when Cho/Cr ratios were compared; the ratio was higher in the idiopathic IN group. There were no statistically significant differences in NAA/Cr or Cho/Cr ratios between patients with bilateral ametropic amblyopia and normal children. CONCLUSIONS: Our findings suggest that the neurochemical profile of the occipital cortex is partially affected by idiopathic IN, but not by bilateral ametropic amblyopia.


Subject(s)
Amblyopia , Aspartic Acid , Child , Choline , Creatine , Humans , Magnetic Resonance Spectroscopy , Occipital Lobe , Prospective Studies
7.
Article in English | WPRIM | ID: wpr-764307

ABSTRACT

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver and the third most common cause of cancer-related death worldwide. HCC is caused by infection of hepatitis B/C virus and liver dysfunctions, such as alcoholic liver disease, nonalcoholic fatty liver disease, and cirrhosis. Amino acids are organic substances containing amine and carboxylic acid functional groups. There are over 700 kinds of amino acids in nature, but only about 20 of them are used to synthesize proteins in cells. Liver is an important organ for protein synthesis, degradation and detoxification as well as amino acid metabolism. In the liver, there are abundant non-essential amino acids, such as alanine, aspartate, glutamate, glycine, and serine and essential amino acids, such as histidine and threonine. These amino acids are involved in various cellular metabolisms, the synthesis of lipids and nucleotides as well as detoxification reactions. Understanding the role of amino acids in the pathogenesis of liver and the effects of amino acid intake on liver disease can be a promising strategy for the prevention and treatment of liver disease. In this review, we describe the biochemical properties and functions of amino acids and to review how they have been applied to treatment of liver diseases.


Subject(s)
Alanine , Amino Acids , Amino Acids, Essential , Aspartic Acid , Carcinoma, Hepatocellular , Fibrosis , Glutamic Acid , Glycine , Hepatitis , Histidine , Liver Diseases , Liver Diseases, Alcoholic , Liver , Metabolism , Non-alcoholic Fatty Liver Disease , Nucleotides , Serine , Therapeutic Uses , Threonine
8.
Article in English | WPRIM | ID: wpr-763401

ABSTRACT

Sarcopenia (loss of muscle mass and/or strength) frequently complicates liver cirrhosis and adversely affects the quality of life; cirrhosis related liver decompensation and significantly decreases wait-list and post-liver transplantation survival. The main therapeutic strategies to improve or reverse sarcopenia include dietary interventions (supplemental calorie and protein intake), increased physical activity (supervised resistance and endurance exercises), hormonal therapy (testosterone), and ammonia lowering agents (L-ornithine L-aspartate, branch chain amino acids) as well as mechanistic approaches that target underlying molecular and metabolic abnormalities. Besides other factors, hyperammonemia has recently gained attention and increase sarcopenia by various mechanisms including increased expression of myostatin, increased phosphorylation of eukaryotic initiation factor 2a, cataplerosis of α ketoglutarate, mitochondrial dysfunction, increased reactive oxygen species that decrease protein synthesis and increased autophagy-mediated proteolysis. Sarcopenia contributes to frailty and increases the risk of minimal and overt hepatic encephalopathy.


Subject(s)
Ammonia , Aspartic Acid , Fibrosis , Hepatic Encephalopathy , Hyperammonemia , Liver , Liver Cirrhosis , Metabolism , Motor Activity , Myostatin , Peptide Initiation Factors , Phosphorylation , Proteolysis , Quality of Life , Reactive Oxygen Species , Sarcopenia , Testosterone
9.
Psychiatry Investigation ; : 745-750, 2019.
Article in English | WPRIM | ID: wpr-760906

ABSTRACT

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD). This study evaluated the antidepressant effect of rTMS and examined how it affected N-asetyl aspartate (NAA), choline (Cho), creatine (Cr), lactate (Lac), myoinositol (mIns), glutamate (Glu), glutathione (GSH), and glutamine (Gln) metabolite levels in the left dorsolateral prefrontal cortex (DLPFC) of MDD patients who were not receiving antidepressant medication. METHODS: In total, 18 patients (10 female, 8 male) were evaluated. Each patient underwent H magnetic resonance spectroscopy (H-MRS) before and within 3 days of completion of TMS therapy. All patients completed 20 sessions of rTMS directed at the left DLPFC over a 2-week period. The Hamilton Depression Scale (HAMD) scores of patients were calculated, and their responses to treatment were assessed within 1–3 days of completion of TMS. RESULTS: We found statistically significant differences in HAMD scores before and after rTMS. Moreover, the peak metabolite ratios of NAA/Cr, GSH/Cr, and Gln/Cr were significantly higher after rTMS compared to those before rTMS. CONCLUSION: Increased understanding of the mechanism of action of TMS will improve its application and may stimulate development of new-generation therapeutic agents.


Subject(s)
Aspartic Acid , Choline , Creatine , Depression , Depressive Disorder, Major , Female , Glutamic Acid , Glutamine , Glutathione , Humans , Inositol , Lactic Acid , Magnetic Resonance Spectroscopy , Prefrontal Cortex , Transcranial Magnetic Stimulation
10.
Article in English | WPRIM | ID: wpr-760635

ABSTRACT

BACKGROUND/OBJECTIVES: The leaves of Moringa oleifera (MO) and Moringa stenopetala (MS) commonly grown in Ethiopia possess potential nutritional and medicinal value. The aim of this study was to evaluate the nutritional and functional characteristics of the dried leaf powder from two Moringa species to develop sustainable nutritional supplements for Ethiopians from locally grown plant sources. SUBJECTS/METHODS: Freshly harvested and air-dried MO and MS leaves were authenticated and the nutritional contents, such as protein, ash, lipids, and selected vitamins and minerals, were analyzed using standard analytical procedures. Amino acid compositions were also determined by an amino acid analyzer. Nine-week-old mice were randomly divided into four groups to investigate the anti-obesity effects of Moringa. The first group was fed a basal diet, the second group a high-fat diet, and the others were fed a high-fat diet containing 0.1% Moringa leaf powder from each species. After seven weeks, serum indices related to lipid profiles from each mouse were analyzed. RESULTS: The present study revealed high protein (28–29%) and ash (7–11%) contents. Glutamic acid, aspartic acid, proline, and leucine were the most abundantly found amino acids in both species. The predominant minerals in the leaf powder were calcium (826–1,530 mg/100 g), potassium (794–904 mg/100 g), and magnesium (286-431 mg/100 g). Pyridoxine (475.06 mg/100 g) and vitamin E (34.2 mg/100 g) were found only in MS. Niacin was found only in MO at 32.21 mg/100 g, whereas ascorbic acid was found in both species (3.89 and 6.19 mg/100 g dry weight for MO and MS, respectively). The results of the animal study showed that mice on a high-fat diet containing 0.1% MO leaf powder alleviated the elevation of cholesterol, triglycerides, and low-density lipoprotein cholesterol induced by the high fat diet. MO was more effective than MS in preventing hypercholesterolemia and fat deposition. CONCLUSIONS: The findings in this work confirmed that Moringa leaves of both MO and MS possessed high nutritional value but MO was better at preventing the harmful effects of the high-fat diet than MS.


Subject(s)
Amino Acids , Animals , Ascorbic Acid , Aspartic Acid , Calcium , Cholesterol , Diet , Diet, High-Fat , Ethiopia , Glutamic Acid , Hypercholesterolemia , Leucine , Lipoproteins , Magnesium , Mass Screening , Mice , Minerals , Miners , Moringa oleifera , Moringa , Niacin , Nutritive Value , Plants , Potassium , Proline , Pyridoxine , Triglycerides , Vitamin E , Vitamins
11.
Journal of Experimental Hematology ; (6): 1156-1161, 2018.
Article in Chinese | WPRIM | ID: wpr-689513

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the changes of cerebral metabolism in rabbit model of hemorrhagic shock by using proton magnetic resonance spectroscopy(PMRS).</p><p><b>METHODS</b>Ten New Zealand white rabbits were used for construction of the model of acute hemorrhagic anemia. 1H-MRS was performed before and at the time-peint of 30, 90, and 180 min after hemorrhagic shock. The concentrations of NAA, Cr, Cho, Lac, and NAA/Cr and Cho/Cr ratios were estimated.</p><p><b>RESULTS</b>Hemorrhagic shock was associated with significant reductions in red blood cell count, hemoglobin level, hematocrit, pH, and PaCO, and elevations of blood lactate and PaO. The ratios of NAA/Cr at 30 min, 90 min and 180 min after shock were (1.50±0.09), (1.37±0.09) and (1.27±0.10), respectively, which were significantly lower than those before shock (2.11±0.16) (P <0.05) (1.16±0.05) and (0.97±0.04) at 30 min and 90 min after shock, respectively, which were significantly lower than those pre-shock (1.38±0.08) (P <0.05). The ratis of Cho/Cr at 30 min and 90 min were (1.16±0.05) and (0.97±0.04), respectively, which were significantly lower than those before shock (1.38±0.08) (P <0.05).</p><p><b>CONCLUSION</b>MRS can noninvasively and dynamically detect brean metabolic changes in early hemorrhagic shock, and has positive significance for early diagnosis and prognosis assessment of hemorrhagic shock.</p>


Subject(s)
Animals , Aspartic Acid , Brain , Choline , Disease Models, Animal , Magnetic Resonance Spectroscopy , Proton Magnetic Resonance Spectroscopy , Protons , Rabbits , Shock, Hemorrhagic
12.
Article in English | WPRIM | ID: wpr-715047

ABSTRACT

Hangover is characterized by a number of unpleasant physical and mental symptoms that occur after heavy alcohol drinking. In addition, consistently excessive alcohol intake is considered as a major reason causes liver disease. The present study investigated the in vivo effects of DA-5513 (Morning care® Kang Hwang) on biological parameters relevant to hangover relief and alcoholic fatty liver. Blood alcohol and acetaldehyde concentrations were determined in rats administered a single dose of alcohol and treated with DA-5513 or commercially available hangover relief beverages (Yeomyung® and Ukon®). The effects of DA-5513 on alcoholic fatty liver were also determined in rats fed alcohol-containing Lieber-DeCarli diets for 4 weeks. Serum liver function markers (aspartate and alanine aminotransferase activities) and serum/liver lipid levels were assessed. Blood alcohol and acetaldehyde concentrations were lower in the groups treated with DA-5513 or Yeomyung®, as compared with control rats. However, Ukon® did not produce any significant effects on these parameters. Treatment with DA-5513 significantly reduced serum aspartate and alanine aminotransferase activities and markedly reduced serum cholesterol and triglyceride levels, as compared with control rats. Histological observations using Oil Red O staining found that DA-5513 delayed the development of alcoholic fatty liver by reversing hepatic fat accumulation. These findings suggest that DA-5513 could have a beneficial effect on alcohol-induced hangovers and has the potential to ameliorate alcoholic fatty liver.


Subject(s)
Acetaldehyde , Alanine Transaminase , Alcohol Drinking , Alcoholics , Animals , Aspartic Acid , Beverages , Cholesterol , Diet , Fatty Liver, Alcoholic , Humans , Liver , Liver Diseases , Metabolism , Rats , Triglycerides
13.
Gut and Liver ; : 324-330, 2018.
Article in English | WPRIM | ID: wpr-714608

ABSTRACT

BACKGROUND/AIMS: The treatment with daclatasvir plus asunaprevir (DCV+ASV) is associated with potent antiviral effects in patients with genotype 1b hepatitis C virus (HCV) infection. We investigated the real-world efficacy, changes in liver stiffness and noninvasive fibrosis markers, and the safety of DCV+ASV treatment in Korean patients. METHODS: In total, 363 patients with chronic hepatitis C were treated with DCV+ASV between August 2015 and January 2017. Finally, we analyzed the data of 270 patients who were monitored for at least 12 weeks after the end of treatment. RESULTS: The mean age was 60.7 years, and females predominated (60.4%). Most patients (64.8%) were treatment-naïve, and 56 patients (20.7%) had cirrhosis. Two hundred fifty-seven (95.2%) and 251 (93.0%) patients achieved end-of-treatment responses and sustained virological responses at 12 weeks posttreatment (SVR12), respectively. The SVR12 rates were higher in patients who were < 65 years of age, males, without cirrhosis and had lower HCV RNA levels. All LS values and fibrosis-4 and aspartate aminotransferase-to-platelet ratio index values declined from baseline to the time of assessment of SVR12. CONCLUSIONS: The DCV+ASV therapy resulted in a high SVR12 and improved liver fibrosis; the treatment was well tolerated in patients with genotype 1b HCV infections.


Subject(s)
Aspartic Acid , Female , Fibrosis , Genotype , Hepacivirus , Hepatitis C , Hepatitis C, Chronic , Hepatitis , Humans , Liver Cirrhosis , Liver , Male , RNA
14.
Article in English | WPRIM | ID: wpr-714219

ABSTRACT

PURPOSE: Various inflammation-based prognostic biomarkers such as the platelet to lymphocyte ratio and neutrophil to lymphocyte ratio, are related to poor survival in patients with intrahepatic cholangiocarcinoma (ICC). This study aims to investigate the prognostic value of the aspartate aminotransferase to neutrophil ratio index (ANRI) in ICC after hepatic resection. MATERIALS AND METHODS: Data of 184 patients with ICC after hepatectomy were retrospectively reviewed. The cut-off value of ANRI was determined by a receiver operating characteristic curve. Preoperative ANRI and clinicopathological variables were analyzed. The predictive value of preoperative ANRI for prognosis of ICC was identified by univariate and multivariate analyses. RESULTS: The optimal cut-off value of ANRI was 6.7. ANRI was associated with tumor size, tumor recurrence, white blood cell, neutrophil count, aspartate aminotransferase, and alanine transaminase. Univariate analysis showed that ANRI, sex, tumor number, tumor size, tumor differentiation, lymph node metastasis, resection margin, clinical TNM stage, neutrophil count, and carcinoembryonic antigen were markedly correlated with overall survival (OS) and disease-free survival (DFS) in patients with ICC. Multivariable analyses revealed that ANRI, a tumor size > 6 cm, poor tumor differentiation, and an R1 resection margin were independent prognostic factors for both OS and DFS. Additionally, preoperative ANRI also had a significant value to predict prognosis in various subgroups of ICC, including serum hepatitis B surface antigen‒negative and preoperative elevated carbohydrate antigen 19-9 patients. CONCLUSION: Preoperative declined ANRI is a noninvasive, simple, and effective predictor of poor prognosis in patients with ICC after hepatectomy.


Subject(s)
Alanine Transaminase , Aspartate Aminotransferases , Aspartic Acid , Biomarkers , Blood Platelets , Carcinoembryonic Antigen , Cholangiocarcinoma , Disease-Free Survival , Hepatectomy , Hepatitis B , Humans , Leukocytes , Lymph Nodes , Lymphocytes , Multivariate Analysis , Neoplasm Metastasis , Neutrophils , Prognosis , Recurrence , Retrospective Studies , ROC Curve
15.
Article in English | WPRIM | ID: wpr-742411

ABSTRACT

This study aimed to develop a UPLC-MS/MS method for determining plasma levels of L-aspartic acid and L-asparagine and the activity of L-asparaginase. L-aspartic acid, L-asparagine, and L-aspartic acid-2,3,3-d3 were extracted from human plasma by protein precipitation with sulfosalicylic acid (30%, v/v). The plasma samples were analyzed using an Imtakt Intrada amino acid analysis column with 25 mM ammonium formate and 0.5% formic acid in acetonitrile as the mobile phase with step gradient method at a flow rate of 0.5 mL/min. The injection volume was 5 µL, and the total run time was 15 min. Inter- and intra-batch accuracies (%) ranged from 96.62–106.0% for L-aspartic acid and 89.85–104.8%, for L-asparagine, and the coefficient of variation (CV%) did not exceed 7%. The validation results for L-aspartic acid and L-asparagine satisfied the specified criterion, however, the results for L-asparaginase activity assay showed a borderline validity. This study could be a foundation for further development of therapeutic drug monitoring systems using UPLC-MS/MS.


Subject(s)
Ammonium Compounds , Asparagine , Aspartic Acid , Drug Monitoring , Humans , Methods , Plasma
16.
Article in English | WPRIM | ID: wpr-718133

ABSTRACT

PURPOSE: Obesity is associated with metabolic dysregulation, but the underlying metabolic signatures involving clinical and inflammatory profiles of obese asthma are largely unexplored. We aimed at identifying the metabolic signatures of obese asthma. METHODS: Eligible subjects with obese (n = 11) and lean (n = 22) asthma underwent body composition and clinical assessment, sputum induction, and blood sampling. Sputum supernatant was assessed for interleukin (IL)-1β, -4, -5, -6, -13, and tumor necrosis factor (TNF)-α, and serum was detected for leptin, adiponectin and C-reactive protein. Untargeted gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)-based metabolic profiles in sputum, serum and peripheral blood monocular cells (PBMCs) were analyzed by orthogonal projections to latent structures-discriminate analysis (OPLS-DA) and pathway topology enrichment analysis. The differential metabolites were further validated by correlation analysis with body composition, and clinical and inflammatory profiles. RESULTS: Body composition, asthma control, and the levels of IL-1β, -4, -13, leptin and adiponectin in obese asthmatics were significantly different from those in lean asthmatics. OPLS-DA analysis revealed 28 differential metabolites that distinguished obese from lean asthmatic subjects. The validation analysis identified 18 potential metabolic signatures (11 in sputum, 4 in serum and 2 in PBMCs) of obese asthmatics. Pathway topology enrichment analysis revealed that cyanoamino acid metabolism, caffeine metabolism, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, pentose phosphate pathway in sputum, and glyoxylate and dicarboxylate metabolism, glycerolipid metabolism and pentose phosphate pathway in serum are suggested to be significant pathways related to obese asthma. CONCLUSIONS: GC-TOF-MS-based metabolomics indicates obese asthma is characterized by a metabolic profile different from lean asthma. The potential metabolic signatures indicated novel immune-metabolic mechanisms in obese asthma with providing more phenotypic and therapeutic implications, which needs further replication and validation.


Subject(s)
Adiponectin , Alanine , Aspartic Acid , Asthma , Body Composition , C-Reactive Protein , Caffeine , Chromatography, Gas , Glutamic Acid , Interleukins , Leptin , Mass Spectrometry , Metabolism , Metabolome , Metabolomics , Obesity , Pentose Phosphate Pathway , Phenylalanine , Pilot Projects , Sputum , Tryptophan , Tumor Necrosis Factor-alpha , Tyrosine
17.
Biol. Res ; 51: 21, 2018. graf
Article in English | LILACS | ID: biblio-950905

ABSTRACT

OBJECTIVE: To explore the precise mechanism of electroacupuncture (EA) to delay cognitive impairment in Alzheimer disease. Methods N -Acetylaspartate (NAA), glutamate (Glu) and myoinositol (mI) metabolism were measured by magnetic resonance spectroscopy, learning and memory of APP/PS1 mouse was evaluated by the Morris water maze test and the step-down avoidance test, neuron survival number and neuronal structure in the hippocampus were observed by Nissl staining, and BDNF and phosphorylated TrkB detected by Western blot. RESULTS: EA at DU20 acupuncture significantly improve learning and memory in behavioral tests, up-regulate NAA, Glu and mI metabolism, increase the surviving neurons in hippocampus, and promote the expression of BDNF and TrkB in the APP/PS1 transgenic mice. CONCLUSION: These findings suggested that EA is a potential therapeutic for ameliorate cognitive dysfunction, and it might be due to EA could improve NAA and Glu metabolism by upregulation of BDNF in APP/PS1 mice.


Subject(s)
Animals , Male , Mice , Electroacupuncture/methods , Aspartic Acid/analogs & derivatives , Glutamic Acid/metabolism , Hippocampus/chemistry , Learning/physiology , Memory/physiology , Protein-Tyrosine Kinases/analysis , Magnetic Resonance Imaging , Membrane Glycoproteins/analysis , Mice, Transgenic , Magnetic Resonance Spectroscopy , Random Allocation , Blotting, Western , Aspartic Acid/metabolism , Maze Learning , Brain-Derived Neurotrophic Factor , Models, Animal , Exercise Test , Hippocampus/diagnostic imaging , Inositol/analysis
18.
Article in English | WPRIM | ID: wpr-184079

ABSTRACT

BACKGROUND/AIMS: Amino acids have many physiological activities. We report the correlation between gastric emptying and gastric adaptive relaxation using tryptophan and amino acids with a straight alkyl chain, hydroxylated chain, and branched chain. Here we sought to further clarify the correlation between gastric emptying and gastric adaptive relaxation by using other amino acids. METHODS: In Sprague-Dawley rats, gastric emptying was evaluated by a breath test using [1-¹³C] acetic acid. The expired ¹³CO₂ pattern, T(max), C(max), and AUC(120min) values were used as evaluation items. Gastric adaptive relaxation was evaluated in a barostat experiment. Individual amino acids (1 g/kg) were administered orally 30 minutes before each breath test or barostat test. RESULTS: L-phenylalanine and L-tyrosine did not influence gastric emptying. All other amino acids, ie, L-proline, L-histidine, L-cysteine, L-methionine, L-aspartic acid, L-glutamic acid, L-asparagine, L-arginine, L-glutamine, and L-lysine significantly delayed and inhibited gastric emptying. L-Cysteine and L-aspartic acid significantly enhanced and L-methionine and L-glutamine significantly inhibited gastric adaptive relaxation. L-Phenylalanine moved the balloon toward the antrum, suggesting strong contraction of the fundus. T(max) showed a significant positive correlation (r = 0.709), and C(max) and AUC(120min) each showed negative correlations (r = 0.613 and 0.667, respectively) with gastric adaptive relaxation. CONCLUSION: From the above findings, it was found that a close correlation exists between gastric emptying and adaptive relaxation, suggesting that enhanced gastric adaptive relaxation inhibits gastric emptying.


Subject(s)
Acetic Acid , Amino Acids , Animals , Arginine , Asparagine , Aspartic Acid , Breath Tests , Cysteine , Gastric Emptying , Glutamic Acid , Glutamine , Histidine , Lysine , Methionine , Phenylalanine , Proline , Rats , Rats, Sprague-Dawley , Relaxation , Tryptophan , Tyrosine
19.
Chinese Medical Journal ; (24): 957-963, 2017.
Article in English | WPRIM | ID: wpr-266879

ABSTRACT

<p><b>BACKGROUND</b>In head and neck neoplasm survivors treated with brain irradiation, metabolic alterations would occur in the radiation-induced injury area. The mechanism of these metabolic alterations has not been fully understood, while the alternations could be sensitively detected by proton (1H) nuclear magnetic resonance spectroscopy (MRS). In this study, we investigated the metabolic characteristics of radiation-induced brain injury through a long-term follow-up after radiation treatment using MRS in vivo.</p><p><b>METHODS</b>A total of 12 adult Sprague-Dawley rats received a single dose of 30 Gy radiation treatment to semi-brain (field size: 1.0 cm × 2.0 cm; anterior limit: binocular posterior inner canthus connection; posterior limit: external acoustic meatus connection; internal limit: sagittal suture). Conventional magnetic resonance imaging and single-voxel 1H-MRS were performed at different time points (in month 0 before irradiation as well as in the 1st, 3rd, 5th, 7th, and 9th months after irradiation) to investigate the alternations in irradiation field. N-acetylaspartate/choline (NAA/Cho), NAA/creatinine (Cr), and Cho/Cr ratios were measured in the bilateral hippocampus and quantitatively analyzed with a repeated-measures mixed-effects model and multiple comparison test.</p><p><b>RESULTS</b>Significant changes in the ratios of NAA/Cho (F = 57.37, P<sub>g < 0.001), NAA/Cr (F = 54.49, P<sub>g < 0.001), and Cho/Cr (F = 9.78, P<sub>g = 0.005) between the hippocampus region of the irradiated semi-brain and the contralateral semi-brain were observed. There were significant differences in NAA/Cho (F = 9.17, P<sub>t < 0.001) and NAA/Cr (F = 13.04, P<sub>t < 0.001) ratios over time. The tendency of NAA/Cr to change with time showed no significant difference between the irradiated and contralateral sides. Nevertheless, there were significant differences in the Cho/Cr ratio between these two sides.</p><p><b>CONCLUSIONS</b>MRS can sensitively detect metabolic alternations. Significant changes of metabolites ratio in the first few months after radiation treatment reflect the metabolic disturbance in the acute and early-delayed stages of radiation-induced brain injuries.</p>


Subject(s)
Animals , Aspartic Acid , Metabolism , Brain , Radiation Effects , Choline , Metabolism , Male , Proton Magnetic Resonance Spectroscopy , Methods , Radiation Injuries , Diagnosis , Metabolism , Rats , Rats, Sprague-Dawley
20.
Article in Korean | WPRIM | ID: wpr-66961

ABSTRACT

BACKGROUND: The aspartate transaminase (AST)/alanine transferase (ALT) ratio increases with alcohol consumption. This study investigated AST/ALT ratio according to alcohol drinking and predictive power of AST/ALT ratio for heavy drinking in Korean men. METHODS: In 2015, 830 men with no history of disease or medication affecting liver function values were selected. Using 14 g of alcohol as the standard glass, odd ratios (ORs) of AST/ALT ratio over 1 among the drinking group were compared with the non-drinking group by multiple logistic analyses. Screening of heavy drinkers was conducted according to both NIAAA and Korean guidelines. Using AST/ALT ratio >1, sensitivity, specificity, positive predictive values, negative predictive values, positive likelihood ratios, negative likelihood ratios and odds ratios were investigated. RESULTS: After correcting for age, body mass index, exercising, and smoking history, ORs (95% confidence interval) of AST/ALT >1 were 1.607 (1.048-2.464) in 14 glasses group. When AST/ALT >1 in the drinking group, sensitivity, specificity, positive predictive values, negative predictive values, likelihood ratios (LR)+, LR- and OR according to NIAAA guidelines, were 57.2%, 52.7%, 23.2%, 76.8%, 1.21 (1.04-1.41), 0.81 (0.67-0.98), and 1.49 (1.05-2.01), respectively. By Korean guidelines, these values were 55.2%, 55.3%, 33.7%, 66.3%, 1.24 (1.03-1.36), 0.84 (0.72-0.98), and 1.40 (1.04-1.89), respectively. CONCLUSIONS: Healthy male adults showed a positive correlation between risk of AST/ALT >1 and drinking amount compared to the non-drinking group. Use of the AST/ALT >1 in combination with other blood markers to predict excessive drinking is advisable.


Subject(s)
Adult , Alanine Transaminase , Alanine , Alcohol Drinking , Aspartate Aminotransferases , Aspartic Acid , Body Mass Index , Drinking , Eyeglasses , Glass , Humans , Liver , Male , Mass Screening , Odds Ratio , Sensitivity and Specificity , Smoke , Smoking , Transferases
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