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1.
Josef Marksteiner Imrich Blasko Georg Kemmler Therese Koal Christian Humpel 《Metabolomics : Official journal of the Metabolomic Society》2018,14(1):1
Introduction
There is still a clear need for a widely available, inexpensive and reliable method to diagnose Alzheimer’s disease (AD) and monitor disease progression. Liquid chromatography–mass spectrometry (LC-MS) is a powerful analytic technique with a very high sensitivity and specificity.Objectives
The aim of the present study is to measure concentrations of 20 bile acids using the novel Kit from Biocrates Life Sciences based on LC-MS technique.Methods
Twenty bile acid metabolites were quantitatively measured in plasma of 30 cognitively healthy subjects, 20 patients with mild cognitive impairment (MCI) and 30 patients suffering from AD.Results
Levels of lithocholic acid were significantly enhanced in plasma of AD patients (50?±?6 nM, p?=?0.004) compared to healthy controls (32?±?3 nM). Lithocholic acid plasma levels of MCI patients (41?±?4 nM) were not significantly different from healthy subjects or AD patients. Levels of glycochenodeoxycholic acid, glycodeoxycholic acid and glycolithocholic acid were significantly higher in AD patients compared to MCI patients (p?<?0.05). All other cholic acid metabolites were not significantly different between healthy subjects, MCI patients and AD patients. ROC analysis shows an overall accuracy of about 66%. Discriminant analysis was used to classify patients and we found that 15/23 were correctly diagnosed. We further showed that LCA levels increased by about 3.2 fold when healthy subjects converted to AD patients within a 8–9 year follow up period. Pathway analysis linked these changes to a putative toxic cholesterol pathway.Conclusion
In conclusion, 4 bile acids may be useful to diagnose AD in plasma samples despite limitations in diagnostic accuracy.2.
Zoe M. Matthews Patrick J. B. Edwards Ariane Kahnt Mark G. Collett Jonathan C. Marshall Ashton C. Partridge Scott J. Harrison Karl Fraser Mingshu Cao Peter J. Derrick 《Metabolomics : Official journal of the Metabolomic Society》2018,14(5):61
Introduction
Photosensitization is a common clinical sign in cows suffering from liver damage caused by the mycotoxin sporidesmin. This disease, called facial eczema (FE), is of major importance in New Zealand. Current techniques for diagnosing animals with subclinical sporidesmin-induced liver damage (i.e. without photosensitization) are nonspecific. In addition, little is known of the mechanisms involved in sporidesmin resistance, nor the early effects seen following low-dose sporidesmin intoxication.Objective
The objective of this study was to identify individual metabolites or metabolic profiles that could be used as serum markers for early stage FE in lactating cows.Methods
Results are presented from a 59-day sporidesmin challenge in Friesian-cross dairy cows. Serum metabolite profiles were obtained using reversed phase ultra-performance liquid chromatography (UPLC) electrospray ionization mass spectrometry (MS) and UPLC tandem MS. Multivariate and time series analyses were used to assess the data.Results
Statistical analysis, both with and without the temporal component, could distinguish the profiles of animals with clinical signs from the others, but not those affected subclinically. An increase in the concentrations of a combination of taurine- and glycine-conjugated secondary bile acids (BAs) was the most likely cause of the separation. This is the first time that MS methods have been applied to FE and that bile acids changes have been detected in cattle exposed to sporidesmin.Conclusions
It is well known that BA concentrations increase during cholestasis due to damage to bile ducts and leakage of the bile. This is the first study to investigate metabolomic changes in serum following a sporidesmin challenge. Further work to establish the significance of the elevation of individual BAs concentrations in the serum of early-stage sporidesmin-poisoned cows is necessary.3.
Huey-Ling Chen Shang-Hsin Wu Shu-Hao Hsu Bang-Yu Liou Hui-Ling Chen Mei-Hwei Chang 《Journal of biomedical science》2018,25(1):75
Background
Jaundice is a common symptom of inherited or acquired liver diseases or a manifestation of diseases involving red blood cell metabolism. Recent progress has elucidated the molecular mechanisms of bile metabolism, hepatocellular transport, bile ductular development, intestinal bile salt reabsorption, and the regulation of bile acids homeostasis.Main body
The major genetic diseases causing jaundice involve disturbances of bile flow. The insufficiency of bile salts in the intestines leads to fat malabsorption and fat-soluble vitamin deficiencies. Accumulation of excessive bile acids and aberrant metabolites results in hepatocellular injury and biliary cirrhosis. Progressive familial intrahepatic cholestasis (PFIC) is the prototype of genetic liver diseases manifesting jaundice in early childhood, progressive liver fibrosis/cirrhosis, and failure to thrive. The first three types of PFICs identified (PFIC1, PFIC2, and PFIC3) represent defects in FIC1 (ATP8B1), BSEP (ABCB11), or MDR3 (ABCB4). In the last 5 years, new genetic disorders, such as TJP2, FXR, and MYO5B defects, have been demonstrated to cause a similar PFIC phenotype. Inborn errors of bile acid metabolism also cause progressive cholestatic liver injuries. Prompt differential diagnosis is important because oral primary bile acid replacement may effectively reverse liver failure and restore liver functions. DCDC2 is a newly identified genetic disorder causing neonatal sclerosing cholangitis. Other cholestatic genetic disorders may have extra-hepatic manifestations, such as developmental disorders causing ductal plate malformation (Alagille syndrome, polycystic liver/kidney diseases), mitochondrial hepatopathy, and endocrine or chromosomal disorders. The diagnosis of genetic liver diseases has evolved from direct sequencing of a single gene to panel-based next generation sequencing. Whole exome sequencing and whole genome sequencing have been actively investigated in research and clinical studies. Current treatment modalities include medical treatment (ursodeoxycholic acid, cholic acid or chenodeoxycholic acid), surgery (partial biliary diversion and liver transplantation), symptomatic treatment for pruritus, and nutritional therapy. New drug development based on gene-specific treatments, such as apical sodium-dependent bile acid transporter (ASBT) inhibitor, for BSEP defects are underway.Short conclusion
Understanding the complex pathways of jaundice and cholestasis not only enhance insights into liver pathophysiology but also elucidate many causes of genetic liver diseases and promote the development of novel treatments.4.
Renato de Souza Pinto Lemgruber Kaspar Valgepea Mark P. Hodson Ryan Tappel Sean D. Simpson Michael Köpke Lars K. Nielsen Esteban Marcellin 《Metabolomics : Official journal of the Metabolomic Society》2018,14(3):35
Introduction
Quantification of tetrahydrofolates (THFs), important metabolites in the Wood–Ljungdahl pathway (WLP) of acetogens, is challenging given their sensitivity to oxygen.Objective
To develop a simple anaerobic protocol to enable reliable THFs quantification from bioreactors.Methods
Anaerobic cultures were mixed with anaerobic acetonitrile for extraction. Targeted LC–MS/MS was used for quantification.Results
Tetrahydrofolates can only be quantified if sampled anaerobically. THF levels showed a strong correlation to acetyl-CoA, the end product of the WLP.Conclusion
Our method is useful for relative quantification of THFs across different growth conditions. Absolute quantification of THFs requires the use of labelled standards.5.
Sonia Liggi Christine Hinz Zoe Hall Maria Laura Santoru Simone Poddighe John Fjeldsted Luigi Atzori Julian L. Griffin 《Metabolomics : Official journal of the Metabolomic Society》2018,14(4):52
Introduction
Data processing is one of the biggest problems in metabolomics, given the high number of samples analyzed and the need of multiple software packages for each step of the processing workflow.Objectives
Merge in the same platform the steps required for metabolomics data processing.Methods
KniMet is a workflow for the processing of mass spectrometry-metabolomics data based on the KNIME Analytics platform.Results
The approach includes key steps to follow in metabolomics data processing: feature filtering, missing value imputation, normalization, batch correction and annotation.Conclusion
KniMet provides the user with a local, modular and customizable workflow for the processing of both GC–MS and LC–MS open profiling data.6.
N. Cesbron A.-L. Royer Y. Guitton A. Sydor B. Le Bizec G. Dervilly-Pinel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(8):99
Introduction
Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.Objectives
In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.Methods
The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.Results
A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.Conclusion
The workflow generated repeatable and informative fingerprints for robust metabolome characterization.7.
Nadine Strehmel David Strunk Veronika Strehmel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(11):135
Introduction
Aqueous–methanol mixtures have successfully been applied to extract a broad range of metabolites from plant tissue. However, a certain amount of material remains insoluble.Objectives
To enlarge the metabolic compendium, two ionic liquids were selected to extract the methanol insoluble part of trunk from Betula pendula.Methods
The extracted compounds were analyzed by LC/MS and GC/MS.Results
The results show that 1-butyl-3-methylimidazolium acetate (IL-Ac) predominantly resulted in fatty acids, whereas 1-ethyl-3-methylimidazolium tosylate (IL-Tos) mostly yielded phenolic structures. Interestingly, bark yielded more ionic liquid soluble metabolites compared to interior wood.Conclusion
From this one can conclude that the application of ionic liquids may expand the metabolic snapshot.8.
Ulrike E. Rolle-Kampczyk Jan Krumsiek Wolfgang Otto Stefan W. Röder Tibor Kohajda Michael Borte Fabian Theis Irina Lehmann M. von Bergen 《Metabolomics : Official journal of the Metabolomic Society》2016,12(4):76
Introduction
A general detrimental effect of smoking during pregnancy on the health of newborn children is well-documented, but the detailed mechanisms remain elusive.Objectives
Beside the specific influence of environmental tobacco smoke derived toxicants on developmental regulation the impact on the metabolism of newborn children is of particular interest, first as a general marker of foetal development and second due to its potential predictive value for the later occurrence of metabolic diseases.Methods
Tobacco smoke exposure information from a questionnaire was confirmed by measuring the smoking related metabolites S-Phenyl mercapturic acid, S-Benzyl mercapturic acid and cotinine in maternal urine by LC–MS/MS. The impact of smoking on maternal endogenous serum metabolome and children’s cord blood metabolome was assessed in a targeted analysis of 163 metabolites by an LC–MS/MS based assay. The anti-oxidative status of maternal serum samples was analysed by chemoluminiscence based method.Results
Here we present for the first time results of a metabolomic assessment of the cordblood of 40 children and their mothers. Several analytes from the group of phosphatidylcholines, namely PCaaC28:1, PCaaC32:3, PCaeC30:1, PCaeC32:2, PCaeC40:1, and sphingomyelin SM C26:0, differed significantly in mothers and children’s sera depending on smoking status. In serum of smoking mothers the antioxidative capacity of water soluble compounds was not significantly changed while there was a significant decrease in the lipid fraction.Conclusion
Our data give evidence that smoking during pregnancy alters both the maternal and children’s metabolome. Whether the different pattern found in adults compared to newborn children could be related to different disease outcomes should be in the focus of future studies.9.
Michael R. La Frano Suzan L. Carmichael Chen Ma Macy Hardley Tong Shen Ron Wong Lorenzo Rosales Kamil Borkowski Theresa L. Pedersen Gary M. Shaw David K. Stevenson Oliver Fiehn John W. Newman 《Metabolomics : Official journal of the Metabolomic Society》2018,14(11):151
Background
Population-based biorepositories are important resources, but sample handling can affect data quality.Objective
Identify metabolites of value for clinical investigations despite extended postcollection freezing delays, using protocols representing a California mid-term pregnancy biobank.Methods
Blood collected from non-pregnant healthy female volunteers (n?=?20) underwent three handling protocols after 30 min clotting at room temperature: (1) ideal—samples frozen (??80 °C) within 2 h of collection; (2) delayed freezing—samples held at room temperature for 3 days, then 4 °C for 9 days, the median times for biobank samples, and then frozen; (3) delayed freezing with freeze–thaw—the delayed freezing protocol with a freeze–thaw cycle simulating retrieved sample sub-aliquoting. Mass spectrometry-based untargeted metabolomic analyses of primary metabolism and complex lipids and targeted profiling of oxylipins, endocannabinoids, ceramides/sphingoid-bases, and bile acids were performed. Metabolite concentrations and intraclass correlation coefficients (ICC) were compared, with the ideal protocol as the reference.Results
Sixty-two percent of 428 identified compounds had good to excellent ICCs, a metric of concordance between measurements of samples handled with the different protocols. Sphingomyelins, phosphatidylcholines, cholesteryl esters, triacylglycerols, bile acids and fatty acid diols were the least affected by non-ideal handling, while sugars, organic acids, amino acids, monoacylglycerols, lysophospholipids, N-acylethanolamides, polyunsaturated fatty acids, and numerous oxylipins were altered by delayed freezing. Freeze–thaw effects were assay-specific with lipids being most stable.Conclusions
Despite extended post-collection freezing delays characteristic of some biobanks of opportunistically collected clinical samples, numerous metabolomic compounds had both stable levels and good concordance.10.
Strategies to assess and optimize stability of endogenous amines during cerebrospinal fluid sampling
Marek J. Noga Ronald Zielman Robin M. van Dongen Sabine Bos Amy Harms Gisela M. Terwindt Arn M. J. M. van den Maagdenberg Thomas Hankemeier Michel D. Ferrari 《Metabolomics : Official journal of the Metabolomic Society》2018,14(4):44
Introduction
Metabolic profiling of cerebrospinal fluid (CSF) is a promising technique for studying brain diseases. Measurements should reflect the in vivo situation, so ex vivo metabolism should be avoided.Objective
To investigate the effects of temperature (room temperature vs. 4 °C), centrifugation and ethanol, as anti-enzymatic additive during CSF sampling on concentrations of glutamic acid, glutamine and other endogenous amines.Methods
CSF samples from 21 individuals were processed using five different protocols. Isotopically-labeled alanine, isoleucine, glutamine, glutamic acid and dopamine were added prior to sampling to trace any degradation. Metabolomics analysis of endogenous amines, isotopically-labeled compounds and degradation products was performed with a validated LC–MS method.Results
Thirty-six endogenous amines were quantified. There were no statistically significant differences between sampling protocols for 31 out of 36 amines. For GABA there was primarily an effect of temperature (higher concentrations at room temperature than at 4 °C) and a small effect of ethanol (lower concentrations if added) due to possible degradation. O-phosphoethanolamine concentrations were also lower when ethanol was added. Degradation of isotopically-labeled compounds (e.g. glutamine to glutamic acid) was minor with no differences between protocols.Conclusion
Most amines can be considered stable during sampling, provided that samples are cooled immediately to 4 °C, centrifuged, and stored at ??80 °C within 2 h. The effect of ethanol addition for more unstable metabolites needs further investigation. This was the first time that labeled compounds were used to monitor ex vivo metabolism during sampling. This is a useful strategy to study the stability of other metabolites of interest.11.
Elif Erdem Ibrahim Inan Harbiyeli Hazal Boral Macit Ilkit Meltem Yagmur Reha Ersoz 《Mycopathologia》2018,183(3):521-527
Purpose
To evaluate the efficiency of corneal collagen cross-linking (CXL) in addition to topical voriconazole in cases with mycotic keratitis.Design
Retrospective case series in a tertiary university hospital.Participants
CXL was performed on 13 patients with mycotic keratitis who presented poor or no response to topical voriconazole treatment.Methods
The clinical features, symptoms, treatment results and complications were recorded retrospectively. The corneal infection was graded according to the depth of infection into the stroma (from grade 1 to grade 3). The visual analogue scale was used to calculate the pain score before and 2 days after surgery.Main Outcome Measures
Grade of the corneal infection.Results
Mean age of 13 patients (6 female and 7 male) was 42.4 ± 17.7 years (20–74 years). Fungus was demonstrated in culture (eight patients) or cytological examination (five patients). Seven of the 13 patients (54%) were healed with topical voriconazole and CXL adjuvant treatment in 26 ± 10 days (15–40 days). The remaining six patients did not respond to CXL treatment; they initially presented with higher grade ulcers. Pre- and post-operative pain score values were 8 ± 0.8 and 3.5 ± 1, respectively (p < 0.05).Conclusions
The current study suggests that adjunctive CXL treatment is effective in patients with small and superficial mycotic ulcers. These observations require further research by large randomized clinical trials.12.
Ying Wang Brian D. Carter Susan M. Gapstur Marjorie L. McCullough Mia M. Gaudet Victoria L. Stevens 《Metabolomics : Official journal of the Metabolomic Society》2018,14(10):129
Introduction
Processing delays after blood collection is a common pre-analytical condition in large epidemiologic studies. It is critical to evaluate the suitability of blood samples with processing delays for metabolomics analysis as it is a potential source of variation that could attenuate associations between metabolites and disease outcomes.Objectives
We aimed to evaluate the reproducibility of metabolites over extended processing delays up to 48 h. We also aimed to test the reproducibility of the metabolomics platform.Methods
Blood samples were collected from 18 healthy volunteers. Blood was stored in the refrigerator and processed for plasma at 0, 15, 30, and 48 h after collection. Plasma samples were metabolically profiled using an untargeted, ultrahigh performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) platform. Reproducibility of 1012 metabolites over processing delays and reproducibility of the platform were determined by intraclass correlation coefficients (ICCs) with variance components estimated from mixed-effects models.Results
The majority of metabolites (approximately 70% of 1012) were highly reproducible (ICCs?≥?0.75) over 15-, 30- or 48-h processing delays. Nucleotides, energy-related metabolites, peptides, and carbohydrates were most affected by processing delays. The platform was highly reproducible with a median technical ICC of 0.84 (interquartile range 0.68–0.93).Conclusion
Most metabolites measured by the UPLC–MS/MS platform show acceptable reproducibility up to 48-h processing delays. Metabolites of certain pathways need to be interpreted cautiously in relation to outcomes in epidemiologic studies with prolonged processing delays.13.
Markus Rotter Stefan Brandmaier Cornelia Prehn Jonathan Adam Sylvia Rabstein Katarzyna Gawrych Thomas Brüning Thomas Illig Heiko Lickert Jerzy Adamski Rui Wang-Sattler 《Metabolomics : Official journal of the Metabolomic Society》2017,13(1):4
Introduction
Few studies have investigated the influence of storage conditions on urine samples and none of them used targeted mass spectrometry (MS).Objectives
We investigated the stability of metabolite profiles in urine samples under different storage conditions using targeted metabolomics.Methods
Pooled, fasting urine samples were collected and stored at ?80 °C (biobank standard), ?20 °C (freezer), 4 °C (fridge), ~9 °C (cool pack), and ~20 °C (room temperature) for 0, 2, 8 and 24 h. Metabolite concentrations were quantified with MS using the AbsoluteIDQ? p150 assay. We used the Welch-Satterthwaite-test to compare the concentrations of each metabolite. Mixed effects linear regression was used to assess the influence of the interaction of storage time and temperature.Results
The concentrations of 63 investigated metabolites were stable at ?20 and 4 °C for up to 24 h when compared to samples immediately stored at ?80 °C. When stored at ~9 °C for 24 h, few amino acids (Arg, Val and Leu/Ile) significantly decreased by 40% in concentration (P < 7.9E?04); for an additional three metabolites (Ser, Met, Hexose H1) when stored at ~20 °C reduced up to 60% in concentrations. The concentrations of four more metabolites (Glu, Phe, Pro, and Thr) were found to be significantly influenced when considering the interaction between exposure time and temperature.Conclusion
Our findings indicate that 78% of quantified metabolites were stable for all examined storage conditions. Particularly, some amino acid concentrations were sensitive to changes after prolonged storage at room temperature. Shipping or storing urine samples on cool packs or at room temperature for more than 8 h and multiple numbers of freeze and thaw cycles should be avoided.14.
Elizabeth A. Scoville Margaret M. Allaman Caroline T. Brown Amy K. Motley Sara N. Horst Christopher S. Williams Tatsuki Koyama Zhiguo Zhao Dawn W. Adams Dawn B. Beaulieu David A. Schwartz Keith T. Wilson 《Metabolomics : Official journal of the Metabolomic Society》2018,14(1):17
Introduction
Biomarkers are needed in inflammatory bowel disease (IBD) to help define disease activity and identify underlying pathogenic mechanisms. We hypothesized that serum metabolomics, which produces unique metabolite profiles, can aid in this search.Objectives
The aim of this study was to characterize serum metabolomic profiles in patients with IBD, and to assess for differences between patients with ulcerative colitis (UC), Crohn’s disease (CD), and non-IBD subjects.Methods
Serum samples from 20 UC, 20 CD, and 20 non-IBD control subjects were obtained along with patient characteristics, including medication use and clinical disease activity. Non-targeted metabolomic profiling was performed using ultra-high performance liquid chromatography/mass spectrometry (UPLC-MS/MS) optimized for basic or acidic species and hydrophilic interaction liquid chromatography (HILIC/UPLC-MS/MS).Results
In total, 671 metabolites were identified. Comparing IBD and control subjects revealed 173 significantly altered metabolites (27 increased and 146 decreased). The majority of the alterations occurred in lipid-, amino acid-, and energy-related metabolites. Comparing only CD and control subjects revealed 286 significantly altered metabolites (54 increased and 232 decreased), whereas comparing UC and control subjects revealed only five significantly altered metabolites (all decreased). Hierarchal clustering using significant metabolites separated CD from UC and control subjects.Conclusions
We demonstrate that a number of lipid-, amino acid-, and tricarboxylic acid cycle-related metabolites were significantly altered in IBD patients, more specifically in CD. Therefore, alterations in lipid and amino acid metabolism and energy homeostasis may play a key role in the pathogenesis of CD.15.
I. O Yuksel G. Cagirci E. Koklu A. Yilmaz S. Kucukseymen H. Y. Ellidag S. Cay N. Yilmaz S. Arslan 《Netherlands heart journal》2016,24(10):609-616
Objective
Erythropoietin (EPO) improves cardiac function and induces neovascularisation in post-myocardial infarction heart failure. The aim of this study was to analyse the association between the serum erythropoietin level and coronary collateral development in patients with coronary artery disease and chronic total occlusion.Methods
A total of 168 patients consisting of 117 with coronary artery disease (CAD, (62 with chronic total occlusion (CTO), 55 without CTO)) and 51 with healthy coronary arteries were included in the study. The patients were assigned as coronary artery disease without CTO (group 0), CAD with CTO (group 1: poor collateral development, group 2: good collateral development) and normal coronary arteries (group 3).Results
There was a significant positive correlation between serum EPO levels and the Rentrop scores in angiography (r = 0.243, p = 0.001). Similarly, a positive correlation was found between serum EPO levels and the Syntax scores (r = 0.253, p = 0.001). Echocardiography revealed a negative correlation between serum EPO levels and the cardiac ejection fraction (r = ?0.210, p = 0.006).Conclusions
Serum EPO is a useful biomarker for coronary collateral development in patients with CTO.16.
Yingfeng Wang Xutao Wang Xiaoqin Zeng 《Metabolomics : Official journal of the Metabolomic Society》2017,13(10):116
Introduction
Tandem mass spectrometry (MS/MS) has been widely used for identifying metabolites in many areas. However, computationally identifying metabolites from MS/MS data is challenging due to the unknown of fragmentation rules, which determine the precedence of chemical bond dissociation. Although this problem has been tackled by different ways, the lack of computational tools to flexibly represent adjacent structures of chemical bonds is still a long-term bottleneck for studying fragmentation rules.Objectives
This study aimed to develop computational methods for investigating fragmentation rules by analyzing annotated MS/MS data.Methods
We implemented a computational platform, MIDAS-G, for investigating fragmentation rules. MIDAS-G processes a metabolite as a simple graph and uses graph grammars to recognize specific chemical bonds and their adjacent structures. We can apply MIDAS-G to investigate fragmentation rules by adjusting bond weights in the scoring model of the metabolite identification tool and comparing metabolite identification performances.Results
We used MIDAS-G to investigate four bond types on real annotated MS/MS data in experiments. The experimental results matched data collected from wet labs and literature. The effectiveness of MIDAS-G was confirmed.Conclusion
We developed a computational platform for investigating fragmentation rules of tandem mass spectrometry. This platform is freely available for download.17.
Tanushri Chatterji Suruchi Singh Manodeep Sen Ajai Kumar Singh Pradeep Kumar Maurya Nuzhat Husain Janmejai Kumar Srivastava Sudhir Kumar Mandal Raja Roy 《Metabolomics : Official journal of the Metabolomic Society》2016,12(8):130
Introduction
Meningitis, a morbidly infectious central nervous system pathology is accompanied by acute inflammation of the meninges, causing raised intracranial pressure linked with serious neurological sequelae.Objective
To observe the variation in the metabolic profile, that may occur in serum and urine along with CSF in adults using 1H NMR spectroscopy, with an attempt of appropriate and timely treatment regimen.Methods
The 1H NMR-based metabolomics has been performed in 115 adult subjects for differentiating bacterial meningitis (BM) and tubercular meningitis (TBM).Results
The discriminant function analysis (DFA) of the three bio-fluids collectively identified 3-hydroxyisovalerate, lactate, glucose, formate, valine, alanine, ketonic bodies, malonate and choline containing compounds (choline and GPC) as significant metabolites among cases versus control group. The differentiation of bacterial meningitis and tuberculous meningitis (BM vs. TBM) can be done on the basis of identification of 3-hydroxyisovalerate, isobutyrate and formate in case of CSF (with a correct classification of 78 %), alanine in serum (correct classification 60 %), valine and acetone in case of urine (correct classification 89.1 %). The NMR spectral bins based orthogonal signal correction principal component analysis score plots of significant metabolites obtained from DFA also provided group classification among cases versus control group in CSF, serum and urine samples. The variable importance in projection scores also identified similar significant metabolites as obtained from DFA, collectively in CSF, serum and urine samples, responsible for differentiation of meningitis.Conclusion
The CSF contained metabolites which are formed during infection and inflammation, and these were also found in significant quantity in serum and urine samples.18.
Homeira Rashidi Hajieh Shahbazian Forogh Nokhostin Seyed Mahmood Latifi Mehrian Jafarizade 《生物学前沿》2018,13(6):452-457
Background and Aim
The prevalence of metabolic syndrome (MS) increased in recent years in both adolescents and children groups. The aim of the study is evaluating the relationship between insulin and uric acid (UA) level in MS in adolescentsMaterials and Methods
we studied 120 adolescence aged 10 to 19 in two groups: control group without metabolic syndrome and case group with metabolic syndrome. The Criteria of ATP III was considered as a diagnosis factor for metabolic syndrome.Discussion
Various studies have been conducted in various populations to evaluate the relationship between UA level and MS in adolescents. Abdominal obesity, low HDL, hypertriglyceridemia and hypertension are associated with high UA level. In their analysis, the MS OR in UA level?4.9, 4.9-5.8 and ?5.8 mg/dl was 1, 2.53 and 9.03, respectively, which were higher than our findings in current study. Hyperinsulinemia caused by insulin resistance is one of the complications associated with MS, which puts individuals at risk of diabetes and cardiovascular events.Results
Uric acid level in the Case group was significantly higher than the control group (p = 0.0001, 43.8±1.4 vs. 4.1±1 mg/dl, respectively). Insulin level was significantly higher in the case group in compare to the control group (p = 0.008, 9.8± 5.3 vs. 12.2±6 μU/ml, respectively).Conclusion
The findings of this case-control study showed that adolescents with metabolic syndrome have a higher uric acid and insulin level in compare to normal subjects. We hypothesis that increase in serum insulin and uric acid level can be a risk factor in the development of metabolic syndrome.19.
Objectives
To use permeabilized cells of the fission yeast, Schizosaccharomyces pombe, that expresses human UDP-glucose 6-dehydrogenase (UGDH, EC 1.1.1.22), for the production of UDP-glucuronic acid from UDP-glucose.Results
In cell extracts no activity was detected. Therefore, cells were permeabilized with 0.3 % (v/v) Triton X-100. After washing away all low molecular weight metabolites, the permeabilized cells were directly used as whole cell biocatalyst. Substrates were 5 mM UDP-glucose and 10 mM NAD+. Divalent cations were not added to the reaction medium as they promoted UDP-glucose hydrolysis. With this reaction system 5 mM UDP-glucose were converted into 5 mM UDP-glucuronic acid within 3 h.Conclusions
Recombinant permeabilized cells of S. pombe can be used to synthesize UDP-glucuronic acid with 100 % yield and selectivity.20.
Arianna Filntisi Charalambos Fotakis Pantelis Asvestas George K. Matsopoulos Panagiotis Zoumpoulakis Dionisis Cavouras 《Metabolomics : Official journal of the Metabolomic Society》2017,13(12):146