scholarly journals Metabolomic Analysis of the Cerebrospinal Fluid in Latent Syphilis and Neurosyphilis Patients

2021 ◽  
Author(s):  
Jiaheng Deng ◽  
Dongmei Xu ◽  
Fengxin Chen ◽  
Liguo Liu ◽  
Shengnan Cai ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Linoleic Acid ◽  
Kynurenine Pathway ◽  
Tryptophan Metabolism ◽  
Metabolic Profiles ◽  
Significant Enrichment ◽  
Experimental Process ◽  
Q Exactive ◽  
Acid Metabolites ◽  
Latent Syphilis

Abstract Purpose: The infection rate of syphilis continues to rise, and the difficulty in detecting and treating neurosyphilis promptly needs to be resolved. The metabolic profiles of cerebrospinal fluid (CSF) of different patients were analyzed to understand the pathogenesis of syphilis better. Method: The metabolic profiles of 88 CSF samples from patients were analyzed by UPLC-Q Exactive-MS. The experimental process was evaluated by PCA, PLS-DA, and HCA. T-test statistics were used to compare levels of metabolites to determine significant differences between groups. Pathway analysis was based on the KEGG database.Result: In total, 272 metabolites based on 3937 features obtained in ESI- mode and 252 metabolites based on 3799 features in ESI+ mode were identified. A clear separation between latent syphilis and neurosyphilis was found. Levels of lipid and linoleic acid metabolites, such as 9-OxoODE and 9,10,13-TriHOME, were increased in syphilis patients. In patients with neurosyphilis, significant changes in levels of 5-hydroxy-L-tryptophan (5-HTP) and acetyl-N-formyl-5-methoxykynurenamine (AFMK) in the tryptophan-kynurenine pathway were also detected. Only one metabolite, theophylline, differed significantly between symptomatic and asymptomatic neurosyphilis patients. Additionally, KEGG analysis revealed significant enrichment of tryptophan metabolism pathways, indicating a high correlation between tryptophan metabolism and syphilis symptoms. Conclusions: Levels of linoleic acid metabolites, 5-HTP, AFMK and theophylline were significantly altered in different patients. The role of these differential metabolites in the development of syphilis is worthy of further exploration, probably improving the treatment and diagnosis of neurosyphilis and occult syphilis in the future.

scholarly journals Metabolites of the Kynurenine Pathway of Tryptophan Metabolism in the Cerebrospinal Fluid of Malawian Children with Malaria

2003 ◽  
Vol 188 (6) ◽  
pp. 844-849 ◽  
Author(s):  
Isabelle M. Medana ◽  
Nicholas P. J. Day ◽  
Houta Salahifar‐Sabet ◽  
Roland Stocker ◽  
George Smythe ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Kynurenine Pathway ◽  
Tryptophan Metabolism

Effects of indomethacin and prostacyclin on isolated human pial arteries contracted by CSF from patients with aneurysmal SAH

1981 ◽  
Vol 55 (6) ◽  
pp. 877-883 ◽  
Author(s):  
Lennart Brandt ◽  
Bengt Ljunggren ◽  
Karl-Erik Andersson ◽  
Bengt Hindfelt ◽  
Tore Uski
Keyword(s):  
Cerebrospinal Fluid ◽  
Arachidonic Acid ◽  
Vessel Wall ◽  
Cerebral Arteries ◽  
Pial Arteries ◽  
Content Type ◽  
Cerebral Vasoconstriction ◽  
Arachidonic Acid Metabolites ◽  
Acid Metabolites ◽  
Fine Print

✓ In small human cerebral arteries preincubated with indomethacin, contractions induced by cerebrospinal fluid (CSF), from patients with subarachnoid hemorrhage were markedly increased. Also contractions induced by noradrenaline, but not 5-hydroxytryptamine, were augmented. Prostacyclin and its metabolite 6-keto-prostaglandin (PG)E1 reversed the contractions induced by CSF, as well as by noradrenaline, 5-hydroxytryptamine, and PGF2α. The findings suggest that these substances are able to counteract the influence of vasoconstrictor material in hemorrhagic CSF. If the capacity to synthesize these “protective” arachidonic acid metabolites is reduced, the resulting imbalance between contractile and relaxant forces acting on the vessel wall may lead to sustained cerebral vasoconstriction.

Changes on recovery in the concentrations of tryptophan and the biogenic amine metabolites in the cerebrospinal fluid of patients with affective illness

1973 ◽  
Vol 3 (3) ◽  
pp. 319-325 ◽  
Author(s):  
G. W. Ashcroft ◽  
Ivy M. Blackburn ◽  
D. Eccleston ◽  
A. I. M. Glen ◽  
W. Hartley ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Homovanillic Acid ◽  
Affective Illness ◽  
Normal Limits ◽  
Low Concentrations ◽  
Depressed Group ◽  
Before And After ◽  
Acid Metabolites ◽  
Bipolar Patients ◽  
Manic Patients

SYNOPSISThe concentration of the acid metabolites of dopamine, and 5-hydroxytryptamine (5-HT), homovanillic acid (HVA), and 5-hydroxyindolacetic acid (5-HIAA) respectively, were estimated in the cerebrospinal fluid of patients suffering from either unipolar or bipolar affective illness, both before and after recovery. Significantly low concentrations of HVA and 5-HIAA (P<0·01 and 0·05 respectively) were found in the unipolar depressed group and these did not return to normal on recovery. Depressed bipolar patients had levels within normal limits. In bipolar manic patients the HVA concentration fell on recovery to a level significantly lower (P<0·05) than controls. There was no difference in the levels of tryptophan in the CSF of any of the groups of patients nor was there any alteration on recovery. There was a high correlation between 5-HIAA and HVA in the same CSF. These findings are against the amine hypothesis which postulated in depression a lowered concentration of transmitter amine at synaptic junction.

scholarly journals Correlation of Metabolic Profiles of Plasma and Cerebrospinal Fluid of High-Grade Glioma Patients

Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 133
Author(s):  
Artem D. Rogachev ◽  
Nikolay A. Alemasov ◽  
Vladimir A. Ivanisenko ◽  
Nikita V. Ivanisenko ◽  
Evgeniy V. Gaisler ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Molecular Mechanisms ◽  
High Grade Glioma ◽  
Diagnostic Procedures ◽  
Metabolic Profiles ◽  
High Grade ◽  
Wide Range ◽  
Targeted Screening ◽  
M Estimates ◽  
Metabolite Content

This work compares the metabolic profiles of plasma and the cerebrospinal fluid (CSF) of the patients with high-grade (III and IV) gliomas and the conditionally healthy controls using the wide-range targeted screening of low molecular metabolites by HPLC-MS/MS. The obtained data were analyzed using robust linear regression with Huber’s M-estimates, and a number of metabolites with correlated content in plasma and CSF was identified. The statistical analysis shows a significant correlation of metabolite content in plasma and CSF samples for the majority of metabolites. Several metabolites were shown to have high correlation in the control samples, but not in the glioma patients. This can be due to the specific metabolic processes in the glioma patients or to the damaged integrity of blood-brain barrier. The results of our study may be useful for the understanding of molecular mechanisms underlying the development of gliomas, as well as for the search of potential biomarkers for the minimally invasive diagnostic procedures of gliomas.

scholarly journals The Effects of Naphthenic Acids on Tryptophan Metabolism and Peripheral Serotonin Signalling

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A493-A493
Author(s):  
Laiba Jamshed ◽  
Genevieve A Perono ◽  
Shanza Jamshed ◽  
Kim Ann Cheung ◽  
Philippe J Thomas ◽  
...  
Keyword(s):  
Oil Sands ◽  
Naphthenic Acid ◽  
Kynurenine Pathway ◽  
Naphthenic Acids ◽  
Tryptophan Metabolism ◽  
Lipid Homeostasis ◽  
Prostaglandin E ◽  
Serotonin Synthesis ◽  
Active Metabolites ◽  
Glucose And Lipid Homeostasis

Abstract Introduction: Serotonin produced in the periphery has been shown to affect glucose and lipid homeostasis. The availability of the amino acid tryptophan, the precursor of serotonin, affects serotonin availability. In addition, the metabolism of tryptophan via the kynurenine pathway produces physiologically active metabolites which have been shown to be altered under conditions of increased adiposity and dysglycemia. There is now evidence demonstrating some environmental xenobiotics, known to affect glucose and lipid homeostasis, can also alter serotonin production and key components of the kynurenine pathway. Recent evidence suggests that exposure to compounds present in petroleum and wastewaters from oil and gas extraction sites can impact endocrine signaling and result in aberrant lipid accumulation and altered glycemic control. However, whether any of these changes can be causally ascribed to altered serotonin synthesis/signaling or tryptophan metabolism remains unknown. The goal of this study was to determine the effects of exposure to naphthenic acid (NA), a key toxicant found in wastewater from bitumen (thick crude oil present in oil sands deposits) extraction on the enzymes involved in tryptophan metabolism and serotonin production. Methods: McA-RH7777 rat hepatoma cells, were exposed to a technical NA mixture for 48 hours at concentrations within the reported range of NA found in wastewaters from oil extraction. We assessed mRNA expression for key rate-limiting enzymes involved in tryptophan metabolism that lead to either serotonin [Tph1] and/or kynurenine [Ido2 and Tdo2] production, as well as downstream enzymes in the kynurenine pathway [Afmid, Kyat1, Aadat, Kyat3, Kmo, Haao, Acmsd, Qprt]. We also examined the effects of NA on prostaglandin synthesis [Ptgs1, Ptgs2, Ptges] and signalling [Ptger2, Ptger4] as prostaglandins have been shown to be induced by serotonin and are linked to hepatic fat accumulation. Results: NA treatment significantly increased Tph1 and Ido2 expression; this occurred in association with a significant increase in the expression of the inducible prostaglandin synthase Ptgs2 (COX-2), prostaglandin E synthase Ptges, and prostaglandin receptors Ptger2 and Ptger4. Acmsd was the only downstream enzyme in the kynurenine pathway that was significantly altered by NA treatment. Conclusion: These results provide proof-of-concept that compounds associated with oil sands extraction have the potential to perturb key components of serotonin synthesis (Tph1) and tryptophan metabolism (Ido2, Acmsd). Furthermore, we found that the increase in Tph1 expression paralleled expression of Ptgs2. As increased prostaglandin production has been reported in association with nonalcoholic steatohepatitis, these data provide a potential mechanism by which exposure to NA and other petroleum-based compounds may increase the risk of metabolic disease.

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