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Biochimica Et Biophysica Acta.... Oct 2020A wide array of molecular pathways has been investigated during the past decade in order to understand the mechanisms by which the practice of physical exercise promotes... (Review)
Review
A wide array of molecular pathways has been investigated during the past decade in order to understand the mechanisms by which the practice of physical exercise promotes neuroprotection and reduces the risk of developing communicable and non-communicable chronic diseases. While a single session of physical exercise may represent a challenge for cell homeostasis, repeated physical exercise sessions will improve immunosurveillance and immunocompetence. Additionally, immune cells from the central nervous system will acquire an anti-inflammatory phenotype, protecting central functions from age-induced cognitive decline. This review highlights the exercise-induced anti-inflammatory effect on the prevention or treatment of common chronic clinical and experimental settings. It also suggests the use of pterins in biological fluids as sensitive biomarkers to follow the anti-inflammatory effect of physical exercise.
Topics: Animals; Anti-Inflammatory Agents; Biomarkers; Blood-Brain Barrier; Chronic Disease; Communicable Diseases; Cytokines; Databases, Factual; Exercise; Humans; Immune System; Immunity, Innate; Inflammation; Neopterin; Neuroprotection
PubMed: 32360589
DOI: 10.1016/j.bbadis.2020.165823 -
Bioanalysis Sep 2016The kynurenine (KYN) pathway is implicated in diseases such as cancer, psychiatric, neurodegenerative and autoimmune disorders. Measurement of KYN metabolite levels will...
AIM
The kynurenine (KYN) pathway is implicated in diseases such as cancer, psychiatric, neurodegenerative and autoimmune disorders. Measurement of KYN metabolite levels will help elucidating the involvement of the KYN pathway in the disease pathology and inform drug development.
METHODOLOGY
Samples of plasma, cerebrospinal fluid or brain tissue were spiked with deuterated internal standards, processed and analyzed by LC-MS/MS; analytes were chromatographically separated by gradient elution on a C18 reversed phase analytical column without derivatization.
CONCLUSION
We established an LC-MS/MS method to measure 11 molecules, namely tryptophan, KYN, 3-OH-KYN, 3-OH-anthranilic acid, quinolinic acid, picolinic acid, kynurenic acid, xanthurenic acid, serotonin, dopamine and neopterin within 5.5 min, with sufficient sensitivity to quantify these molecules in small sample volumes of plasma, cerebrospinal fluid and brain tissue.
Topics: Animals; Brain; Chromatography, High Pressure Liquid; Humans; Kynurenine; Mice, Inbred C57BL; Neopterin; Quinolinic Acid; Signal Transduction; Tandem Mass Spectrometry; Tryptophan; ortho-Aminobenzoates
PubMed: 27524289
DOI: 10.4155/bio-2016-0111 -
Psychiatry Research Mar 2021Increasing evidence points to a causal involvement of inflammation in the pathogenesis of neuropsychiatric disorders, including major depressive disorder (MDD) and...
Increasing evidence points to a causal involvement of inflammation in the pathogenesis of neuropsychiatric disorders, including major depressive disorder (MDD) and schizophrenia (SZ). Neopterin and biopterin may link peripheral immune system activation and central neurotransmitter alterations. However, it is not fully established whether these alterations are transdiagnostic or disorder-specific and whether they are associated with reward-related psychopathologies. We investigated group differences in neopterin and biopterin in the plasma of healthy comparison (HC) (n=19), SZ (n=45) and MDD (n=43) participants. We then correlated plasma proteins with CRP as a measure for inflammation. Lastly, plasma proteins were correlated with the reward-related psychopathological domain apathy. We found a trend-level difference in biopterin levels and no significant difference in neopterin levels between groups. Within both patient groups, but not HC, we show a significant positive correlation of CRP with neopterin but not with biopterin. Further, we observed no significant correlations of plasma proteins with reward-related psychopathology in HC, MDD or SZ. While our study shows trend-level alterations of biopterin with relevance for future research, it does not support the hypothesis that peripheral neopterin or biopterin are associated with reward-related psychopathology.
Topics: Biopterins; Depression; Depressive Disorder, Major; Humans; Neopterin; Schizophrenia
PubMed: 33524773
DOI: 10.1016/j.psychres.2021.113745 -
Scientific Reports Oct 2020This study aimed to evaluate the possible changes of neopterin, biopterin levels and tryptophan degradation in diabetes and to compare the results within diabetes groups...
This study aimed to evaluate the possible changes of neopterin, biopterin levels and tryptophan degradation in diabetes and to compare the results within diabetes groups and with healthy subjects. Diabetes mellitus patients and healthy controls were recruited the study. Patients were further subgrouped according to their drug therapy. Serum neopterin concentrations were detected by ELISA. Urinary neopterin, biopterin, serum tryptophan (Trp) and kynurenine (Kyn) levels were detected by HPLC. There was no difference between controls and diabetes patients in serum neopterin, urinary neopterin and biopterin levels (p > 0.05, all). Serum Trp and Kyn levels were significantly different in type 1 diabetes (T1DM) patients compared to controls (p < 0.05, both). Serum neopterin levels were significantly higher in type 2 diabetes patients (T2DM) compared to T1DM (p < 0.05). Urinary biopterin levels of T2DM patients using both metformin and vildagliptin were significantly higher than T1DM patients (p < 0.05). The correlations between serum neopterin and urinary neopterin, Kyn and Kyn/Trp were statistically significant in control and patient groups (p < 0.05, all). The study showed that Kyn/Trp was altered in diabetes patients due to immune modulation. On the other hand, although xenobiotic exposure may change pteridine levels, metformin and/or vildagliptin use in T2DM patients did not have any effect on the measured parameters.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biopterins; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Kynurenine; Male; Metformin; Middle Aged; Neopterin; Tryptophan; Vildagliptin; Young Adult
PubMed: 33046801
DOI: 10.1038/s41598-020-74183-w -
Annals of Clinical and Translational... Aug 2023Infection-triggered encephalopathy syndromes (ITES) are potentially devastating neuroinflammatory conditions. Although some ITES syndromes have recognisable MRI...
OBJECTIVE
Infection-triggered encephalopathy syndromes (ITES) are potentially devastating neuroinflammatory conditions. Although some ITES syndromes have recognisable MRI neuroimaging phenotypes, there are otherwise few biomarkers of disease. Early detection to enable immune modulatory treatments could improve outcomes.
METHODS
We measured CSF neopterin, quinolinic acid, kynurenine and kynurenine/tryptophan ratio using a liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) system. The CSF of 18 children with ITES were compared with acute encephalitis (n = 20), and three control groups, namely epilepsy (n = 20), status epilepticus (n = 18) and neurogenetic controls (n = 20).
RESULTS
The main ITES phenotypes in 18 patients were acute encephalopathy with biphasic seizures and late restricted diffusion (AESD, n = 4), febrile infection-related epilepsy syndrome (FIRES n = 4) and other ITES phenotypes. Influenza A was the most common infectious trigger (n = 5), and 50% of patients had a preceding notable neurodevelopmental or family history. CSF neopterin, quinolinic acid and kynurenine were elevated in ITES group compared to the three control groups (all p < 0.0002). The ROC (area under curve) for CSF neopterin (99.3%, CI 98.1-100) was significantly better than CSF pleocytosis (87.3% CI 76.4-98.2) (p = 0.028). Elevated CSF neopterin could discriminate ITES from other causes of seizures, status epilepticus and febrile status epilepticus (all p < 0.0002). The elevated CSF metabolites normalised during longitudinal testing in two patients with FIRES.
INTERPRETATION
CSF neopterin and quinolinic acid are neuroinflammatory and excitotoxic metabolites. This CSF metabolomic inflammatory panel can discriminate ITES from other causes of new onset seizures or status epilepticus, and rapid results (4 h) may facilitate early immune modulatory therapy.
Topics: Humans; Neopterin; Quinolinic Acid; Kynurenine; Syndrome; Neuroinflammatory Diseases; Chromatography, Liquid; Tandem Mass Spectrometry; Brain Diseases; Seizures; Status Epilepticus; Encephalitis; Biomarkers
PubMed: 37340737
DOI: 10.1002/acn3.51832 -
EBioMedicine May 2023Defining the presence of acute and chronic brain inflammation remains a challenge to clinicians due to the heterogeneity of clinical presentations and aetiologies....
BACKGROUND
Defining the presence of acute and chronic brain inflammation remains a challenge to clinicians due to the heterogeneity of clinical presentations and aetiologies. However, defining the presence of neuroinflammation, and monitoring the effects of therapy is important given its reversible and potentially damaging nature. We investigated the utility of CSF metabolites in the diagnosis of primary neuroinflammatory disorders such as encephalitis and explored the potential pathogenic role of inflammation in epilepsy.
METHODS
Cerebrospinal fluid (CSF) collected from 341 paediatric patients (169 males, median age 5.8 years, range 0.1-17.1) were examined. The patients were separated into a primary inflammatory disorder group (n = 90) and epilepsy group (n = 80), who were compared with three control groups including neurogenetic and structural (n = 76), neurodevelopmental disorders, psychiatric and functional neurological disorders (n = 63), and headache (n = 32).
FINDINGS
There were statistically significant increases of CSF neopterin, kynurenine, quinolinic acid and kynurenine/tryptophan ratio (KYN/TRP) in the inflammation group compared to all control groups (all p < 0.0003). As biomarkers, at thresholds with 95% specificity, CSF neopterin had the best sensitivity for defining neuroinflammation (82%, CI 73-89), then quinolinic acid (57%, CI 47-67), KYN/TRP ratio (47%, CI 36-56) and kynurenine (37%, CI 28-48). CSF pleocytosis had sensitivity of 53%, CI 42-64). The area under the receiver operating characteristic curve (ROC AUC) of CSF neopterin (94.4% CI 91.0-97.7%) was superior to that of CSF pleocytosis (84.9% CI 79.5-90.4%) (p = 0.005). CSF kynurenic acid/kynurenine ratio (KYNA/KYN) was statistically decreased in the epilepsy group compared to all control groups (all p ≤ 0.0003), which was evident in most epilepsy subgroups.
INTERPRETATION
Here we show that CSF neopterin, kynurenine, quinolinic acid and KYN/TRP are useful diagnostic and monitoring biomarkers of neuroinflammation. These findings provide biological insights into the role of inflammatory metabolism in neurological disorders and provide diagnostic and therapeutic opportunities for improved management of neurological diseases.
FUNDING
Financial support for the study was granted by Dale NHMRC Investigator grant APP1193648, University of Sydney, Petre Foundation, Cerebral Palsy Alliance and Department of Biochemistry at the Children's Hospital at Westmead. Prof Guillemin is funded by NHMRC Investigator grant APP 1176660 and Macquarie University.
Topics: Male; Humans; Child; Infant; Child, Preschool; Adolescent; Tryptophan; Kynurenine; Neopterin; Quinolinic Acid; Neuroinflammatory Diseases; Leukocytosis; Inflammation; Biomarkers; Nervous System Diseases
PubMed: 37119734
DOI: 10.1016/j.ebiom.2023.104589 -
Turkish Journal of Medical Sciences 2015Urticaria is a vascular skin reaction characterized with papules and plaques. Neopterin is accepted as an immunologic marker and an indicator of activation of the immune...
BACKGROUND/AIM
Urticaria is a vascular skin reaction characterized with papules and plaques. Neopterin is accepted as an immunologic marker and an indicator of activation of the immune system. Homocysteine and asymmetric dimethylarginine (ADMA) are the markers of increased vascular resistance. Alteration in vascular resistance has a role in the pathogenesis of urticaria. We aimed to investigate whether there is a relationship between urticaria and neopterin, homocysteine, or ADMA.
MATERIALS AND METHODS
The study is designed as a prospective descriptive study and patients with a diagnosis of urticaria in the emergency department were included in the study. Demographic data and characteristics of the disease were recorded. Neopterin, homocysteine, and ADMA levels were measured both during and after urticaria attacks. All data were statistically analyzed.
RESULTS
The differences between neopterin levels measured during and after urticaria attacks were statistically significant (P < 0.001). The differences between homocysteine and ADMA levels measured during and after urticaria attacks were not statistically significant (P > 0.05).
CONCLUSION
Our results indicate that neopterin levels in patients with urticaria attacks are increased and the level of neopterin is also a useful parameter in acute urticaria. Further studies should clarify whether homocysteine levels contribute to diagnosis of acute urticaria. However, no relation was found between ADMA and urticaria.
Topics: Adult; Aged; Arginine; Biomarkers; Emergency Service, Hospital; Female; Homocysteine; Humans; Male; Middle Aged; Neopterin; Prospective Studies; Urticaria; Young Adult
PubMed: 26775378
DOI: 10.3906/sag-1402-14 -
Journal of the American Heart... Feb 2018Neopterin, a metabolite of GTP, is produced by activated macrophages and is abundantly expressed within atherosclerotic lesions in human aorta and carotid and coronary...
BACKGROUND
Neopterin, a metabolite of GTP, is produced by activated macrophages and is abundantly expressed within atherosclerotic lesions in human aorta and carotid and coronary arteries. We aimed to clarify the influence of neopterin on both vascular inflammation and atherosclerosis, as neither effect had been fully assessed.
METHODS AND RESULTS
We investigated neopterin expression in coronary artery lesions and plasma from patients with coronary artery disease. We assessed the atheroprotective effects of neopterin in vitro using human aortic endothelial cells, human monocyte-derived macrophages, and human aortic smooth muscle cells. In vivo experiments included a study of aortic lesions in apolipoprotein E-deficient mice. Neopterin expression in coronary artery lesions and plasma was markedly increased in patients with versus without coronary artery disease. In human aortic endothelial cells, neopterin reduced proliferation and TNF-α (tumor necrosis factor α)-induced upregulation of MCP-1 (monocyte chemotactic protein 1), ICAM-1 (intercellular adhesion molecule 1), and VCAM-1 (vascular cell adhesion molecule 1). Neopterin attenuated TNF-α-induced monocyte adhesion to human aortic endothelial cells and the inflammatory macrophage phenotype via NF-κB (nuclear factor-κB) downregulation. Neopterin suppressed oxidized low-density lipoprotein-induced foam cell formation associated with CD36 downregulation and upregulation of ATP-binding cassette transporters A1 and G1 in human monocyte-derived macrophages. In human aortic smooth muscle cells, neopterin suppressed angiotensin II-induced migration and proliferation via c-Src/Raf-1/ERK1/2 downregulation without inducing apoptosis. Exogenous neopterin administration and endogenous neopterin attenuation with its neutralizing antibody for 4 weeks retarded and promoted, respectively, the development of aortic atherosclerotic lesions in apolipoprotein E-deficient mice.
CONCLUSIONS
Our results indicate that neopterin prevents both vascular inflammation and atherosclerosis and may be induced to counteract the progression of atherosclerotic lesions. Consequently, neopterin could be of use as a novel therapeutic target for atherosclerotic cardiovascular diseases.
Topics: Adult; Aged; Aged, 80 and over; Animals; Aortic Diseases; Apoptosis; Atherosclerosis; Cell Adhesion; Cell Movement; Cell Proliferation; Coculture Techniques; Coronary Artery Disease; Cytokines; Disease Models, Animal; Endothelial Cells; Female; Foam Cells; Humans; Inflammation Mediators; Male; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout, ApoE; Middle Aged; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neopterin; Plaque, Atherosclerotic; Signal Transduction; THP-1 Cells; Vasculitis
PubMed: 29420219
DOI: 10.1161/JAHA.117.007359 -
African Health Sciences Sep 2019Neopterin, a product of cell-mediated immunity, is a non-specific biomarker of inflammation. Plasma/serum is generally the body fluid of choice for neopterin assessment,... (Comparative Study)
Comparative Study
BACKGROUND
Neopterin, a product of cell-mediated immunity, is a non-specific biomarker of inflammation. Plasma/serum is generally the body fluid of choice for neopterin assessment, but urine is often used as it does away with venepuncture. Analysis of urine neopterin is based on collection of a single urine sample and expressed as µmol neopterin/mol creatinine.
OBJECTIVES
To examine published correlations between plasma neopterin levels and urine neopterin:creatinine ratios and to determine whether they are in diagnostic agreement.
METHODS
Literature search was performed by databases and by hand. Databases included Academic Search Complete; Africa-Wide Information; AHFS Consumer Medication Information; eBook Collection (EBSCOhost); Family & Society Studies Worldwide; MasterFILE Premier; MEDLINE; TOC Premier.
RESULTS
Positive correlations of varying statistical significance generally exist between plasma neopterin and urine neopterin: creatinine ratios. With a decline in renal clearance, plasma neopterin over-estimates inflammatory activity. With immune-complex renal disease, urine neopterin:creatinine ratios over-estimate systemic inflammation. The two biomarkers can differ in diagnostic validity.
CONCLUSION
Correlations between plasma neopterin and urine neopterin:creatinine ratios suggest both as suitable biomarkers. However, since correlations reflect equality of means and not individual values, significant correlations, do not necessarily imply diagnostic agreement. Therefore, plasma and urine cannot summarily be assumed interchangeable for diagnostic/prognostic purposes.
Topics: Africa; Biomarkers; Creatinine; Databases, Factual; Humans; Inflammation; Neopterin; Prognosis
PubMed: 32127811
DOI: 10.4314/ahs.v19i3.14 -
Journal of Atherosclerosis and... Nov 2010Inflammation plays a key role in atherosclerosis and plaque vulnerability, and monocyte/macrophage activation contributes to these processes. Neopterin, a by-product of... (Review)
Review
Inflammation plays a key role in atherosclerosis and plaque vulnerability, and monocyte/macrophage activation contributes to these processes. Neopterin, a by-product of the guanosine triphosphate pathway, is produced by activated macrophages on stimulation with interferon-γ released from T lymphocytes, and is an activation marker for monocytes/macrophages. Coronary angiographic studies have shown a relationship between increased circulating levels of neopterin and the presence of complex coronary lesions in patients with unstable angina pectoris (UAP). Furthermore, in an immunohistochemical study performed using coronary atherectomy specimens, a significantly higher prevalence of neopterin-positive macrophages was found in culprit lesions in patients with UAP than in those with stable angina pectoris (SAP). We recently clarified that the presence of complex carotid plaques detected by carotid ultrasound was related to increased circulating levels of neopterin, and immunohistochemical localization of neopterin was observed in complex carotid lesions obtained from carotid endarterectomy in patients with SAP. These findings suggest that neopterin is an important biomarker of plaque instability in both coronary and carotid atherosclerotic lesions.
Topics: Biomarkers; Carotid Artery Diseases; Coronary Artery Disease; Humans; Macrophages; Neopterin; Plaque, Atherosclerotic; Prognosis
PubMed: 20693747
DOI: 10.5551/jat.4606