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1.
ObjectiveMetabolomics is a promising approach to the identification of biomarkers in plasma. Here, we performed a population-based, cross-sectional study to identify potential biomarkers of alcohol intake and alcohol-induced liver injury by metabolomic profiling using capillary electrophoresis-mass spectrometry (CE-MS).MethodsFasting plasma samples were collected from 896 Japanese men who participated in the baseline survey of the Tsuruoka Metabolomics Cohort Study, and 115 polar metabolites were identified and absolutely quantified by CE-MS. Information on daily ethanol intake was collected through a standardized, self-administered questionnaire. The associations between ethanol intake and plasma concentration of metabolites were examined. Relationships between metabolite concentrations or their ratios and serum liver enzyme levels in the highest ethanol intake group (>46.0 g/day) were then examined by linear regression analysis. Replication analysis was conducted in 193 samples collected from independent population of this cohort.ResultsNineteen metabolites were identified to have an association with daily alcohol consumption both in the original and replication population. Three of these metabolites (threonine, glutamine, and guanidinosuccinate) were found to associate well with elevated levels of serum liver enzymes in the highest ethanol intake group, but not in the non-drinker group. We also found that the glutamate/glutamine ratio had a much stronger relation to serum γ-glutamyltransferase, aspartate transaminase, and alanine transaminase than glutamate or glutamine alone (standardized beta = 0.678, 0.558, 0.498, respectively).ConclusionsWe found 19 metabolites associated with alcohol intake, and three biomarker candidates (threonine, guanidinosuccinate and glutamine) of alcohol-induced liver injury. Glutamate/glutamine ratio might also be good biomarker.

Electronic supplementary material

The online version of this article (doi:10.1007/s12199-015-0494-y) contains supplementary material, which is available to authorized users.  相似文献   

2.
Sepsis is a whole-body inflammatory response to infection with high mortality and is treated in intensive care units (ICUs). In the present study, to identify metabolic biomarkers that can differentiate sepsis models induced by caecal ligation puncture (CLP) or Staphylococcus aureus (S. aureus), small molecular metabolites in the serum were measured by liquid chromatography quadruple time-of-flight mass spectrometry (LC-QTOF-MS) and analysed using the multivariate statistical analysis (MVA) of partial least square-discrimination analysis (PLS-DA) method. The results demonstrated that the body showed obvious metabolic disorders in the sepsis groups compared with the control group. A total of 8 potential biomarkers were identified in the CLP group, and 10 potential biomarkers were identified in the S. aureus group. These potential biomarkers primarily reflected an energy metabolism disorder, inflammatory response, oxidative stress and tissue damage, which occur during sepsis, and these markers might potentially be used to differentiate CLP from Staphylococcus aureus sepsis.  相似文献   

3.
目的 探讨睡眠剥夺对小鼠肝脏中不同代谢物代谢稳态的影响及其关联的代谢通路,阐释睡眠不足对健康影响的代谢相关机制。方法 2月龄C57BL/6J小鼠随机分为睡眠剥夺组和正常对照组,每组4只,普通饲料喂养。睡眠剥夺组利用小鼠睡眠剥夺仪,每日剥夺睡眠20 h,连续10 d;对照组小鼠同样设备条件下自由睡眠10 d。采集动物肝脏,制取上清液,以液相色谱-质谱联用(LC - MS)法检测两组小鼠的肝脏代谢物谱,对差异代谢物进行主成分分析(PCA)和正交偏最小二乘法 - 判别分析(OPLS - DA),并通过MetPA数据库分析差异代谢物的代谢通路。结果 相较于对照组,睡眠剥夺组小鼠共检出11种差异代谢物。代谢通路的权重分析表明,睡眠剥夺对小鼠肝脏物质代谢通路影响较大的主要有嘧啶代谢、氨基酸代谢、谷胱甘肽代谢及花生四烯酸代谢。其关键差异代谢物依次为尿苷、谷氨酸、5’ - 甲基硫代腺苷(MTA)、谷胱甘肽和花生四烯酸。结论 短期睡眠剥夺即可引起机体谷胱甘肽代谢、嘧啶代谢、氨基酸代谢及花生四烯酸代谢等多重代谢紊乱,有损代谢健康。  相似文献   

4.
Metabolomics has been increasingly used to evaluate metabolic changes associated with morbidities. The objective of this study is to assess the metabolic profile before and after intervention with mixed dietary fiber in overweight and obese hypertensive women. This is an intervention study, and the sample consists of 14 women aged 28 to 58 years. An intervention with 12 g of mixed soluble and insoluble fiber is performed for a period of eight weeks. Serum metabolites are identified using a Bruker 1H NMR spectrometer at 400 MHz. Multivariate data analysis, including principal component analysis (PCA), is used to differentiate the two groups. After supplementation with dietary fiber, there is a significant increase in the peak intensity values of the metabolites HDL-C (0.0010*), choline (0.0012*) and hydroxybutyrate (0.0010*) as well as a decrease in systolic (0.0013*) and diastolic (0.0026*) blood pressure. The analysis of the metabolomic profile allows the identification of metabolites that have been associated in the literature with hypertension and excess weight (choline, hydroxybutyrate and amino acids) and with fiber intake (choline, hydroxybutyrate and amino acids) in addition to an increase in HDL-C. The increase in the detection of the described metabolites possibly occurs due to the presence of pathologies and the use of fiber in the intervention, which also contributes to elevated HDL-c and reduced blood pressure.  相似文献   

5.
目的评价脑脊液腺苷脱氨酶(ADA)在小儿结核性脑膜炎中的诊断价值及动态变化观察。方法应用P800全自动生化分析仪检测100例结脑患儿和35例非结脑患儿的脑脊液ADA活性。结果结脑患儿脑脊液ADA活性明显高于非结脑患儿,差异有统计学意义(p<0.01);结脑组治疗前后脑脊液ADA活性相比差异有统计学意义(p<0.01)。结论脑脊液ADA活性测定是鉴别结核性脑膜炎及非结核性脑膜炎的一个良好的辅助诊断指标,且ADA变化可作为结核性脑膜炎的治疗效果指标。  相似文献   

6.
Rabies, caused by rabies virus (RABV), is still one of the deadliest infectious diseases. Host metabolomic changes against RABV infection has not yet been fully understood. We performed untargeted metabolomics to discover the metabolites associated with RABV infection. The brain tissues from 20 RABV infected mice and 10 mock infected mice were used for this method. A total of 1352 differential metabolites were identified after the first-run screen, and the number reduced to 75 after second-run screen. Multivariate analysis using PLS-DA and OPLS-DA clearly discriminated the RABV infected samples from controls. Pathways enrichment analysis revealed that most differential metabolites were associated with metabolism of nucleotide and amino acid, and aminoacyl - tRNA biosynthesis and purine metabolism were the most active pathways. The findings presented in our study would promote the understanding of metabolomics changes in brains of mice after RABV infection as well as a new perspective to study the relationship between RABV and host.  相似文献   

7.
目的 检测结核性脑膜炎(TBM)及非TBM患者脑脊液中单核细胞内早期分泌靶抗原6(ESAT-6)阳性细胞百分率及其动态变化,评价ESAT-6在TBM早期诊断中的价值。方法 以临床诊断的40例TBM患者(TBM组)及40例非TBM患者(对照组,其中化脓性脑膜炎9例,病毒性脑膜炎24例,新型隐球菌脑膜炎3例,脑囊虫病3例,神经梅毒1例)为研究对象。入院后除常规检查外,行免疫细胞化学染色检测脑脊液中单核细胞内ESAT-6,并进行比较。结果 TBM组脑脊液中单核细胞内ESAT-6阳性细胞百分率为24%,对照组为0,两组比较差异有统计学意义(P<0.01)。绘制受试者工作特征(ROC)曲线,以ESAT-6阳性细胞百分率≥8.5%判定为阳性,<8.5%判定为阴性,则IBM组ESAT-6阳性35例,对照组阳性4例,ESAT-6诊断TBM的灵敏度为87.5%,特异度为90.0%。TBM组30例入院前未行抗结核治疗者在抗结核治疗2周后复查脑脊液中单核细胞内ESAT-6,治疗前阳性率为93.3% (28/30),治疗后为46.7%(14/30),差异有统计学意义(P=0.000)。结论 早期检测单核细胞内ESAT-6阳性细胞百分率诊断TBM灵敏度及特异度较高;动态观察ESAT-6阳性细胞百分率对TBM病情判断有实用价值。  相似文献   

8.
Selective pressure from antibiotic use is one of the most important risk factors associated with the development of drug resistance in Mycobacterium tuberculosis (MTB). However, the mechanisms underlying drug resistance at the molecular level remain partly unclear. Therefore, the purpose of this study was to investigate the potential functional effect of novel mutations arising from anti-tuberculosis treatment. We analyzed two multidrug-resistant TB (MDR-TB) isolates from the same patient; one collected before and one almost a year after commencing MDR-TB treatment. The post-treatment isolate exhibited elevated ethambutol resistance. We sequenced the whole genomes of the two clinical isolates and detected six novel polymorphisms affecting the genes Rv1026, nc0021, Rv2155c, Rv2437, and Rv3696c, and the intergenic region between Rv2764c and Rv2765. Metabolomics approach was used to reveal the effect of the found variation on the metabolic pathways of MTB. Partial least squares–discriminant analysis showed a clear differentiation between the two isolates, involving a total of 175 metabolites. Pathway analysis showed that these metabolites are mainly involved in amino sugar and nucleotide sugar metabolism, β-alanine metabolism, sulfur metabolism, and galactose metabolism. The increased ethambutol resistance exhibited by the post-treatment MDR-TB strain could speculatively be linked to the identified genetic variations, which affected the synthesis of a number of metabolites associated with sources of carbon and energy. This may have been the main factor underlying the increased ethambutol resistance of this isolate.  相似文献   

9.
目的 探讨结核性脑膜炎(结脑)和隐球菌性脯膜炎(隐脑)的临床和脑脊液鉴别要点。方法 回顾性调查并比较1993年2月~2003年12月收治的42例结脑和39例隐脑患者的临床表现和特效治疗前的脑脊液结果:结果 4.8%的结脑和513%的隐脑以头痛为首发症状,结脑和隐脑发生视力改变、听力下降、肢体瘫痪的比例分别为9.5%和56.4%、0和12.8%、21.4%和0:视神经乳头水肿的发生率分别为14.3%和69.2%,且隐脑患者多为中、重度水肿。7.1%的结脑和94.9%的隐脑患者脑脊液压力大于400mmH2O243.6%的隐脑患者脑脊液中蛋白质含量正常,有升高者大部分为轻度升高,大于2g/L者仅占7.7%。而结脑均有蛋白质含量升高,且52.4%的患者大于2g/L:结论 患者具有下列特征时考虑隐脑可能性大:起病时以头痛为主而不伴发热,听力损害出现早,中、重度视神经乳头水肿,脑脊液压力显著升高,蛋白质正常。而感染中毒症状突出,脑脊液中蛋白质含量明显升高,特别是大于2g/L时,结脑的可能性较大,  相似文献   

10.
Metabolomics is improving the understanding of the mechanisms of the health effects of diet. Previous research has identified several metabolites associated with the Mediterranean Diet (MedDiet), but knowledge about longitudinal changes in metabolic biomarkers after a MedDiet intervention is scarce. A subsample of 48 firefighters from a cluster-randomized trial at Indianapolis fire stations was randomly selected for the metabolomics study at 12 months of follow up (time point 1), where Group 1 (n = 24) continued for another 6 months in a self-sustained MedDiet intervention, and Group 2 (n = 24), the control group at that time, started with an active MedDiet intervention for 6 months (time point 2). A total of 225 metabolites were assessed at the two time points by using a targeted NMR platform. The MedDiet score improved slightly but changes were non-significant (intervention: 24.2 vs. 26.0 points and control group: 26.1 vs. 26.5 points). The MedDiet intervention led to favorable changes in biomarkers related to lipid metabolism, including lower LDL-C, ApoB/ApoA1 ratio, remnant cholesterol, M-VLDL-CE; and higher HDL-C, and better lipoprotein composition. This MedDiet intervention induces only modest changes in adherence to the MedDiet and consequently in metabolic biomarkers. Further research should confirm these results based on larger study samples in workplace interventions with powerful study designs.  相似文献   

11.
Abstract

Morphological assessment is currently the primary technique for selection of viable embryos for uterine transfer during assisted reproductive techniques, however this method has limited predictive power. The objective of this study was to employ NMR based metabolic profiling analysis of spent embryo culture media to identify novel biomarkers of embryo viability and provide insight into the metabolism of a viable embryo. A total of 37 patients undergoing IVF/ICSI treatment were recruited and 58 media samples were collected from embryos that were transferred back to the uterus. 1H NMR spectra were acquired and analyzed resulting in the quantification of 12 metabolites in the media samples. Analysis of metabolite ratios revealed significant differences between those patients with positive (n?=?27) and negative (n?=?31) urinary βhCG results. Some of the most biologically relevant differences include a 17% increase in the formate to glycine ratio and a 22% decrease in the citrate to alanine ratio in the spent embryo media from the positive pregnancy group. Overall, the results indicate that metabolic profiling may provide a means of identifying biomarkers that aid selection of viable embryos.  相似文献   

12.
Objectives: Iron deficiency (ID) anemia leads to long-term neurodevelopmental deficits by altering iron-dependent brain metabolism. The objective of the study was to determine if ID induces metabolomic abnormalities in the cerebrospinal fluid (CSF) in the pre-anemic stage and to ascertain the aspects of abnormal brain metabolism affected.

Methods: Standard hematological parameters [hemoglobin (Hgb), mean corpuscular volume (MCV), transferrin (Tf) saturation, and zinc protoporphyrin/heme (ZnPP/H)] were compared at 2, 4, 6, 8, and 12 months in iron-sufficient (IS; n?=?7) and iron-deficient (ID; n?=?7) infant rhesus monkeys. Five CSF metabolite ratios were determined at 4, 8, and 12 months using 1H NMR spectroscopy at 16.4?T and compared between groups and in relation to hematologic parameters.

Results: ID infants developed ID (Tf saturation?P?P?=?0.02). ZnPP/H, an established blood marker of pre-anemic ID, was positively correlated with the CSF citrate/glutamine ratio (marginal correlation, 0.34; P?Discussion: Metabolomic analysis of the CSF is sensitive for detecting the effects of pre-anemic ID on brain energy metabolism. Persistence of a lower PCr/Cr ratio at 8 months, even as hematological measures demonstrated recovery from anemia, indicate that the restoration of brain energy metabolism is delayed. Metabolomic platforms offer a useful tool for early detection of the impact of ID on brain metabolism in infants.  相似文献   

13.
目的评价外周血结核分枝杆菌γ-干扰素体外释放试验(TB-IGRA)对结核性脑膜炎早期辅助诊断的价值。方法收集2015年1—12月四川大学华西医院住院治疗的56例结核性脑膜炎患者(实验组)及56例非结核性脑膜炎患者(对照组)的TB-IGRA、脑脊液结核分枝杆菌培养、脑脊液TB-DNA的检查结果,计算各诊断方法的灵敏度和特异度。结果 TB-IGRA、脑脊液培养、脑脊液TB-DNA诊断结核性脑膜炎的灵敏度分别为87.5%(49/56)、19.6%(11/56)、60.7%(34/56),特异度分别为89.3%(50/56)、100.0%(56/56)、76.8%(43/56)。TBIGRA诊断结核脑膜炎的灵敏度高于脑脊液TB-DNA检查和脑脊液结核分枝杆菌培养,且TB-IGRA特异度高于脑脊液TB-DNA(89.3%76.8%),三者两两相比,差异均具有统计学意义(均P0.01)。其中脑脊液培养确诊的11例病例中,有10例TB-IGRA阳性,阳性率为90.9%(10/11);45例临床诊断+抗结核治疗有效的病例中,TB-IGRA阳性39例,阳性率为86.7%(39/45)。结论 TB-IGRA协助结核性脑膜炎患者的早期诊断具有高灵敏度和特异度,其检查方便、快速、有效,值得临床推广。  相似文献   

14.
ObjectivesThe proteomic analysis of voriconazole resistant Candida glabrata strain has not yet been investigated. In this study, differentially expressed proteins of intracellular and membrane fraction from voriconazole-susceptible, susceptible dose-dependent (S-DD), resistant C. glabrata strains were compared with each other and several proteins were identified.MethodsThe proteins of intracellular and membrane were isolated by disrupting cells with glass bead and centrifugation from voriconazole susceptible, S-DD, and resistant C. glabrata strains. The abundance of expressed proteins was compared using two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis and proteins showing continuous twofold or more increase or reduction of expression in resistant strains compared to susceptible and S-DD strain were analyzed by liquid chromatography/mass spectrometry-mass spectrometry method.ResultsOf 34 intracellular proteins, 15 proteins showed expression increase or reduction (twofold or more). The identified proteins included regulation, energy production, carbohydrate transport, amino acid transport, and various metabolism related proteins. The increase of expression of heat shock protein 70 was found. Among membrane proteins, 12, 31 proteins showed expression increase or decrease in the order of susceptible, S-DD, and resistant strains. This expression included carbohydrate metabolism, amino acid synthesis, and response to stress-related proteins. In membrane fractions, the change of expression of 10 heat shock proteins was observed, and 9 heat shock protein 70 (Hsp70) showed the reduction of expression.ConclusionThe expression of Hsp70 protein in membrane fraction is related to voriconazole resistant C. glabrata strains.  相似文献   

15.
目的探讨单绒毛膜双羊膜囊双胎选择性宫内生长受限(sIUGR)的脐血代谢物构成及生长受限胎儿与正常胎儿的代谢差异。方法采用单卵双胎配对设计,通过气相色谱-飞行时间质谱进行sIUGR双胎脐血代谢组学检测,采用主成分分析和偏最小二乘法判别分析(PLS-DA)对质谱数据建模,对变量投影重要度(VIP)值1的差异点进行非参数检验,寻找差异代谢物。结果 sIUGR大小胎儿脐血血浆样品点在PLS-DA得分图中存在分离趋势。通过对VIP值大于1的差异点进行Wilcoxon符号秩检验及数据库比对,筛选出10种体现出大小胎儿代谢差别的脐血潜在标志物,在生长受限胎儿脐血代谢水平上调的代谢物包括山梨醇、肌醇、甘氨酸、吡啶甲酸,下调的包括亮氨酸、缬氨酸、棕榈酸、硬脂酸、胆固醇和肌酸。结论 sIUGR生长受限胎儿与正常胎儿的脐血代谢物构成存在差异,可能与碳水化合物、氨基酸及脂代谢异常相关。  相似文献   

16.
 目的 探讨发热、血钠联合中性粒细胞百分比对肺结核继发结核性脑膜炎(TBM)的诊断价值。方法 收集2015年10月—2018年10月某院收治的肺结核患者临床资料,将146例诊断为肺结核继发TBM的患者作为研究组,按入院时间以1∶4的比例分层抽取584例肺结核未继发TBM的患者作为对照组,比较两组患者血钠、中性粒细胞百分比、临床发热症状指标及三者联合诊断肺结核继发TBM的效能,计算曲线下面积(AUC)并确定临界点。结果 30条纤维支气管镜使用后未清洗前,内镜外表面RLU中位值为911.5,合格率为16.7%;酶洗后机洗前,内镜外表面RLU中位值为234.0,合格率为43.3%。每组30条纤维支气管镜经消毒剂分别浸泡消毒5、3 min后的气管镜外表面RLU中位值分别为25.0、23.5,合格率均为100.0%。血钠及中性粒细胞百分比诊断肺结核继发TBM患者的临界点分别为135.30 mmol/L、73.40%。发热、血钠、中性粒细胞百分比及三者联合诊断肺结核继发TBM的AUC(95%CI)分别为0.732(0.688~0.776)、0.768(0.719~0.818)、0.727(0.679~0.776)、0.845(0.807~0.882),差异均有统计学意义(均P<0.05);敏感度分别为80.82%、56.85%、65.07%、63.70%,特异度分别为65.58%、87.50%、73.46%、89.38%,前三者曲线下面积差异无统计学意义,三者联合诊断效能更高。结论 发热、血钠<135.30 mmol/L或血中性粒细胞百分比>73.40%对肺结核继发TBM均有诊断意义,三者无明显优劣之分,但三者联合对肺结核继发TBM有更高的诊断价值。  相似文献   

17.
ObjectiveTo describe the clinical manifestations and treatment outcomes of patients with VZV meningitis and encephalitis consulting at two medical centers in Lebanon.MethodsRetrospective study of patients with VZV meningitis and/or encephalitis confirmed by positive cerebrospinal fluid (CSF) VZV PCR.ResultsTwenty patients were identified (13 males). The average age was 49.7 ± 22.2 years. The most common complaint was headache (n = 17/20). Common comorbidities included hypertension (n = 7/20) and diabetes mellitus (n = 5/20). Immunosuppression was reported in two patients. Vesicles were only observed in eight patients. Altered mental status, focal neurological deficits, and fever were documented in six, two, and four patients respectively. All patients had CSF leukocytosis with lymphocytic predominance, normal CSF/serum glucose ratio, and high CSF protein. Eighteen patients had brain CT scans showing no relevant findings. Two of 12 patients with brain MRI had focal abnormalities. Unilateral temporal slow waves were observed in three of four patients who underwent electroencephalograms. Four patients had encephalitis and 16 had meningitis. Eighteen patients received an antiviral therapy. Treatment either included intravenous acyclovir or oral valacyclovir. The encephalitis and meningitis groups had comparable mean duration of treatment (13.5 ± 6.6 vs. 12.2 ± 5.4, respectively). All admitted patients showed clinical cure with no reported neurological sequelae.ConclusionVZV infection should be suspected in any patient with signs and symptoms of viral meningitis or encephalitis, irrespective of age, immune status, presence or absence of vesicles, fever, or neck stiffness.  相似文献   

18.
检测脑脊液结核抗体对结核性脑膜炎的诊断价值   总被引:2,自引:0,他引:2  
目的观察脑脊液中结核分枝杆菌特异性抗体检测对结核性脑膜炎(tuberculous meningitiS,TBM)的诊断价值。方法按照TBM的临床诊断标准和排除标准,选择临床确诊TBM病例30例为研究对象,并选择35例非结核性中枢神经系统疾病作为对照组。收集每个病人在首次腰穿的脑脊液和当天的静脉血标本,用胶体金标记方法进行检测。结果实验组脑脊液检测的阳性率显著高于对照组(P〈0.01),实验组血清的检测阳性率也显著高于对照组(P〈0.01)。脑脊液的敏感度为83.33%,特异度为88.57%;血清的敏感度为70%,特异度为77.14%。脑脊液与血清的检测的阳性率比较无显著差异(P〉0.05)。结论此种混合抗原是一种简便、快捷的诊断TBM的辅助方法。  相似文献   

19.
Dairy products are an important component in the Western diet and represent a valuable source of nutrients for humans. However, a reliable dairy intake assessment in nutrition research is crucial to correctly elucidate the link between dairy intake and human health. Metabolomics is considered a potential tool for assessment of dietary intake instead of traditional methods, such as food frequency questionnaires, food records, and 24-h recalls. Metabolomics has been successfully applied to discriminate between consumption of different dairy products under different experimental conditions. Moreover, potential metabolites related to dairy intake were identified, although these metabolites need to be further validated in other intervention studies before they can be used as valid biomarkers of dairy consumption. Therefore, this review provides an overview of metabolomics for assessment of dairy intake in order to better clarify the role of dairy products in human nutrition and health.  相似文献   

20.

Objective

Cerebrospinal fluid (CSF) leukocytes analysis is commonly used to diagnose meningitis and to differentiate bacterial from viral meningitis. Interpreting CSF monocytes can be difficult for physicians, especially in France where lymphocytes and monocytes results are sometimes pooled.

Patients and methods

We assessed SF monocytes in patients presenting with microbiologically confirmed meningitis (CSF leukocyte count > 10/mm3 for adults or > 30/mm3 for children < 2 months), i.e. bacterial meningitis (BM), viral meningitis (VM), and neuroborreliosis (NB).

Results

Two-hundred patients (82 BM, 86 VM, and 32 NB) were included. The proportions of monocytes were higher in VM (median 8%; range 0–57%) than in BM (median 5%; range 0–60%, P = 0.03) or NB (median 5%; range 0–53%, P = 0.46), with a high value overlap between conditions.

Conclusion

CSF monocytes should not be used to discriminate BM from VM and NB because of value overlaps.  相似文献   

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