Urinary Urea, Uric Acid and Hippuric Acid as Potential Biomarkers in Multiple Sclerosis Patients (original) (raw)
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Potential of Urinary Metabolites for Diagnosing Multiple Sclerosis
ACS Chemical Biology, 2013
A definitive diagnostic test for multiple sclerosis (MS) does not exist; instead physicians use a combination of medical history, magnetic resonance imaging, and cerebrospinal fluid analysis (CSF). Significant effort has been employed to identify biomarkers from CSF to facilitate MS diagnosis; however, none of the proposed biomarkers have been successful to date. Urine is a proven source of metabolite biomarkers and has the potential to be a rapid, noninvasive, inexpensive, and efficient diagnostic tool for various human diseases. Nevertheless, urinary metabolites have not been extensively explored as a source of biomarkers for MS. We demonstrate that urinary metabolites have significant promise for monitoring disease-progression, and response to treatment in MS patients. NMR analysis of urine permitted the identification of metabolites that differentiate experimental autoimmune encephalomyelitis (EAE)-mice (prototypic disease model for MS) from healthy and MS drug-treated EAE mice.
European Journal of Neurology, 2002
Several findings suggest lower levels of serum uric acid in multiple sclerosis (MS) patients. The aim of this study is to investigate relationships of uric acid serum levels in relapse-remitting (RR) MS patients with clinical activity of disease and blood-brain barrier (BBB) condition. Sixty-three definite RRMS patients and 40 controls divided into two groups: 20 healthy donors and 20 patients with other inflammatory neurological diseases (OINDs) were analysed. By using a quantitative enzymatic assay according to the manufacture's protocol and a commercial uric acid standard solution, serum uric acid levels were measured and the results were standardized. To investigate BBB function, magnetic resonance imaging after administration of gadolinium was used. MS patients were found to have significantly lower serum uric acid levels (193.89 ± 49.05 lmol/l; mean value ±SD) in comparison with healthy donors (292.7 ± 58.65 lmol/l; P ¼ 0.000) and OIND patients (242.7 ± 46.66 lmol/l; P ¼ 0.001). We found that MS patients with relapse had significantly lower serum uric acid levels (161.49 ± 23.61 lmol/l) than MS patients with remission (234.39 ± 41.96 lmol/l; P ¼ 0.000) and more over, MS patients with BBB disruption had significantly lower serum uric acid levels (163.95 ± 26.07 lmol/l) than those with normal BBB (252.48 ± 25.94 lmol/l; P ¼ 0.000). Further, we also found that serum uric acid level independently correlated with disease activity, BBB disruption, and gender. These results indicate that lower uric acid levels in MS patients are associated with relapse and suggest that uric acid might be beneficial in the treatment of MS.
Serum Uric Acid Levels in Patients with Relapsing-Remitting Multiple Sclerosis
European Journal of General Medicine
Results: In the present study, mean serum UA levels were lower in RRMS and relapse patients with MS than in the other neurological diseases (OND) group, but the difference did not reach significance level. UA levels did not correlate with clinical activity, EDSS score and disease duration either in relapse or remitting or both of them.
A Urinary Metabolic Signature for Multiple Sclerosis and Neuromyelitis Optica
Journal of proteome research, 2016
Urine is a metabolite rich bio-fluid that reflects the body's effort to maintain chemical and osmotic homeostasis. Clinical diagnosis routinely relies on urine samples since the collection process is easy and non-invasive. Despite these advantages, urine is an under-investigated source of biomarkers for multiple sclerosis (MS). Nuclear magnetic resonance spectroscopy (NMR) has become a common approach for analyzing urinary metabolites for disease diagnosis and biomarker discovery. To illustrate the potential of urinary metabolites for diagnosing and treating MS patients, and for differentiating between MS and other illnesses; 38 urine samples were collected from healthy controls, MS patients, and neuromyelitis optica-spectrum disorder (NMO-SD) patients and analyzed with NMR and multivariate statistics. Urine from MS patients exhibited a statistically distinct metabolic signature from healthy and NMO-SD controls. A total of 27 metabolites were differentially altered in the urine ...
Cerebrospinal fluid and serum uric acid levels in patients with multiple sclerosis
Clinical Chemistry and Laboratory Medicine, 2000
Peroxynitrite was hypothesized to be involved in the pathogenesis of multiple sclerosis (MS) through its various neurotoxic effects. Uric acid (UA) was shown to be a strong peroxynitrite scavenger. We analyzed cerebrospinal fluid (CSF) and serum UA concentrations in 30 MS patients and 20 controls with non-inflammatory neurological diseases (NIND) and correlated these findings with demographic and clinical characteristics of MS patients. Disease activity was assessed by brain magnetic resonance imaging (MRI) and the CSF/serum albumin quotient as an indicator of the state of blood-brain-barrier (BBB). Serum UA concentrations were found to be significantly lower in MS patients compared with controls (p=0.019). CSF UA concentrations were lower in MS patients as compared to controls, as well as in patients with active MS (clinical and/or MRI activity) in comparison to patients with inactive MS or controls, but these differences were not statistically significant. Significant correlation was found between CSF and serum UA concentrations (p=0.016) in MS patients, but not in controls; and between CSF UA concentrations and the CSF/serum albumin quotient in MS patients (p=0.043), but not in controls. Our results support the significance of UA in the pathogenesis of MS. Decreased serum UA concentrations in MS patients might be due to both intrinsically reduced antioxidant capacity and increased UA consumption in MS. CSF UA concentrations may not be a reliable marker of disease activity in MS since its concentration is dependent on leakage of UA molecules from serum through the damaged BBB and the balance between consumption/production within the central nervous system (CNS).
Serum Metabolic Profile in Multiple Sclerosis Patients
Multiple Sclerosis International, 2011
Multiple sclerosis (MS) is a progressive demyelinating process considered as an autoimmune disease, although the causes of this pathology have not been yet fully established. Similarly to other neurodegenerations, MS is characterized by a series of biochemical changes affecting to different extent neuronal functions; great attention has been given to oxidative/nitrosative stress and to alterations in mitochondrial functions. According to previous data, MS patients show significant changes in the circulating concentrations of different metabolites, although it is still unclear whether uric acid undergoes to decrease, increase, or no change under this pathological condition. In this study, we report the serum metabolic profile in terms of purines, pyrimidines, creatinine, malondialdehyde, ascorbic acid, nitrite, and nitrate in a group of 170 MS patients. The results show increase in circulating uric acid and other oxypurines (hypoxanthine and xanthine), as well as in uridine and β-pseudouridine. The concomitant increase in circulating creatinine, malondialdehyde, nitrite, and nitrate, and decrease in ascorbic acid, demonstrates that MS induces alteration in energy metabolism and in oxidants/antioxidants balance that can be monitored in serum of MS patients.