Increased urinary nitric oxide metabolites in patients with multiple                 sclerosis correlates with early and relapsing disease

Giovannoni, Gavin; Silver, Nicholas; O'Riordan, J I; Miller, Riva; Heales, Simon; Land, John M.; Elliot, Mark A.; Feldmann, M; Miller, David H.; Thompson, E. J.

doi:10.1177/135245859900500506

Cited by 41 publications

(13 citation statements)

References 35 publications

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“…These data suggest that in the short-term (9 to 18 months) increased serum NO metabolites may be associated with a better clinical outcome in the form of a non-progressive clinical course and fewer clinical relapses. This finding is corroborated by a large cross-sectional study in which the urinary excretion of NO x was significantly higher in patients with clinically isolated syndromes compatible with demyelination and patients with relapsing remitting MS than in patients with progressive disease [15].…”

Section: Discussionmentioning

confidence: 62%

Serum inflammatory markers and clinical/MRI markers of disease progression in multiple sclerosis

Giovannoni

Miller

Losseff

et al. 2001

Journal of Neurology

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The aim of this study was to assess whether mean serum levels of inflammatory markers when measured serially correlate with disease progression or putative MRI markers of axonal loss in a cohort of well-characterised multiple sclerosis (MS) patients. Serial serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), nitric oxide metabolites nitrate and nitrite (NOx), C-reactive protein (CRP), neopterin and tumour necrosis factor alpha (TNF-alpha) were measured in 29 MS patients, 13 with a relapsing remitting (RR) and 16 with a secondary progressive (SP) course, who were participating in a phase II clinical trial of anti-CD4 therapy. Short-term whole blood stimulated TNF-alpha production was also measured. Patients were studied 12 times over an 18-month period. MRI variables included the number and volume of Gd-enhancing lesions and the change in T2-hyperintense, T1-hypointense lesions and cerebral volume between the baseline and exit studies. Disease progression required a sustained change in the EDSS. There was no correlation between mean levels of inflammatory markers over the study period and disease progression or changes in any of the MRI measures. However, mean sICAM-1 levels from the first 6 months of the study were higher in patients who progressed during the study than in those that did not (443 (SD439) vs. 235 (SD162) ng/mL, p=0.05). Mean levels of NOx were significantly higher in patients with RR MS than in patients with SP disease (59.1 micromol/L (SD 12.8) vs. 48.7 micromol/L (SD 11.9), p=0.02). Patients with either a single relapse or no relapse had significantly higher NOx levels than to patients with multiple relapses during the 18 month follow-up (59.0 micromol/L (SD 12.3) vs. 47.9 micromol/L (SD 12.0), p=0.02). The mean levels of the other inflammatory markers did not correlate with disease course or relapse-rate. Serum levels of many inflammatory markers do not correlate with short-term disease progression. Some of the data suggest that the effects of inflammation on disease progression are delayed. In addition raised levels of serum nitric oxide metabolites are associated with a lower number of clinical relapses and a non-progressive disease course. These findings, although preliminary, pose interesting questions on the role of nitric oxide in the pathogenesis of MS. Inducible NO production in the early stages of the disease may be beneficial.

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Section: Discussionmentioning

confidence: 62%

Serum inflammatory markers and clinical/MRI markers of disease progression in multiple sclerosis

Giovannoni

Miller

Losseff

et al. 2001

Journal of Neurology

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“…4 It has been reported that acute axonal damage in MS correlated with inflammatory markers and was most extensive in early disease with gradual decrease over time. 29 In that context, the finding of higher CSF NOx levels in patients with milder disability and less severe disease course compared with those with advanced disease is interesting and seems to indicate the predominant involvement of NO in the early phase of the disease.…”

Section: Discussionmentioning

confidence: 99%

“…4 Particularly, the intrathecal NOx production was prominent in acute relapse, [5][6][7] but raised CSF NOx concentrations were also reported in progressive disease. 8 Although these studies implicate NO in the pathogenesis of MS, the pathologic events related to elevation of NOx are not fully understood.…”

mentioning

confidence: 97%

CSF nitric oxide metabolites are associated with activity and progression of multiple sclerosis

Rejdak¹,

et al. 2004

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“…Urine samples were collected on each visit for clinical evaluation at 0 (baseline), 3,6,9,12,15,18,21,24 months. Urine specimens were collected on different days after injection of IFNb.…”

Section: Biological Sample Collectionmentioning

confidence: 99%

“…serum23 and urine24 in patients with different clinical types of MS suggest that NOx may be an indicator of an ongoing inflammatory process. It has previously been demonstrated that progressive patients Urinary neopterin/creatinine (UNCR) mean values (mmol/mol) in IFNb-1a treated patients with disease progression (o, n ¼ 15) or without disease progression («, n ¼ 14) as assessed on Expanded Disability Status Scale over 2-year followup based on intention-to-treat analysis using Mann-WhitneyWilcoxon test (*p ¼ 0.002; U ¼ 38.0).…”

mentioning

confidence: 98%

Urinary neopterin and nitric oxide metabolites as markers of interferon β-1a activity in primary progressive multiple sclerosis

et al. 2010

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Increased urinary nitric oxide metabolites in patients with multiple sclerosis correlates with early and relapsing disease

Cited by 41 publications

References 35 publications

Serum inflammatory markers and clinical/MRI markers of disease progression in multiple sclerosis

Serum inflammatory markers and clinical/MRI markers of disease progression in multiple sclerosis

CSF nitric oxide metabolites are associated with activity and progression of multiple sclerosis

Urinary neopterin and nitric oxide metabolites as markers of interferon β-1a activity in primary progressive multiple sclerosis

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