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

1999 ◽  
Vol 5 (5) ◽  
pp. 335-341 ◽  
Author(s):  
Gavin Giovannoni ◽  
N C Silver ◽  
J O'Riordan ◽  
R F Miller ◽  
S J.R. Heales ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Progressive Disease ◽  
Demyelinating Disease ◽  
Neuronal Loss ◽  
Clinical Relapse ◽  
Potential Mediator ◽  
Relapsing Remitting ◽  
Nitric Oxide Metabolites ◽  
Nitrate And Nitrite

Nitric oxide (•NO) has been implicated in the immunopathogenesis of MS as a potential mediator of neuronal loss. To investigate the role of .NO in the development of progressive disease we measured the .NO metabolites (nitrate and nitrite) and neopterin, in the urine of 129 patients with demyelinating disease (DD): 23 with clinically isolated syndromes compatible with demyelination and in 46 relapsing remitting (RR) and 60 patients with progressive MS. Eighty-nine of these 129 patients underwent Gd-enhanced MRI. In addition 58 normal control subjects (NC), 19 AIDS and 35 rheumatoid arthritis (RA) patients were studied. Patients with DD, AIDS and RA had significantly elevated urinary nitrate plus nitrite (nit: creat.urine) and neopterin (neopt: creat.urine) to creatinine ratios compared to NC subjects. (Median[25th-75th%] nit: creat.urine: NC=1183[962-1365] vs DD=1245[875-2403], AIDS=1686[1231-2531], and RA=1950[1214-2726] mmol/mol, P50.001 and median[25th-75th%] neopt: creat.urine: NC=99[76-151] vs DD=163[119-266], AIDS=972[653-1456], and RA=389[257-623] mmol/mol, P50.001). Patients with early DD and RR MS had significantly elevated nit: creat.urine compared to patients with progressive MS (nit: creat.urine: 1612[1020-2733] vs 1159[790-1641] mmol/mol, P=0.006). The nit: creat.urine and neopt: creat.urine did not correlate with clinical relapse or MRI activity. Excretion of .NO metabolites is increased in patients with early or relapsing-remitting disease. .NO appears to be a double-edged sword, mediating tissue damage and modulating complex immunological functions which may be protective in MS.

Cerebrospinal fluid brain specific proteins in relation to nitric oxide metabolites during relapse of multiple sclerosis

2008 ◽  
Vol 14 (1) ◽  
pp. 59-66 ◽  
Author(s):  
K. Rejdak ◽  
A. Petzold ◽  
Z. Stelmasiak ◽  
G. Giovannoni
Keyword(s):  
Nitric Oxide ◽  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Nitrosative Stress ◽  
Study Groups ◽  
Relapsing Remitting ◽  
Specific Proteins ◽  
Nitric Oxide Metabolites ◽  
Nitrate And Nitrite

This study investigated the cerebrospinal fluid (CSF) levels of ferritin, S100B as biomarkers for glial activation and NfHSM135 — a biomarker of axonal damage — in relation to nitric oxide (NO) metabolites: nitrate and nitrite (NOx) during acute multiple sclerosis (MS) relapse. Thirty-four relapsing—remitting MS (RR-MS) patients during acute relapse and 12 controls were enrolled. Patients were assessed on Expanded Disability Status Scale (EDSS) and underwent lumbar puncture within two weeks following relapse. Twenty patients were available for further follow-up and were assessed on EDSS 6—8 weeks since the relapse onset. The CSF NOx ( P < 0.0001), NfHSM135 ( P = 0.01) and S100B ( P = 0.009) but not ferritin ( P > 0.05) were significantly raised in MS group. There was a significant correlation between CSF ferritin and S100B in RR-MS group ( P = 0.004). CSF NOx did not correlate with S100B and ferritin in study groups. RR-MS patients with detectable NfHSM135 levels had higher NOx compared with subjects having undetectable NfHSM135 ( P = 0.03). In the follow-up study, raised baseline levels of NOx ( P = 0.016) or NfHSM135 ( P = 0.04) inversely correlated with the clinical recovery grade expressed as relative EDSS change between baseline and follow-up. In conclusion, NO metabolites were increased and because of their correlation with a biomarker of axonal degeneration (neurofilaments) and a measure for clinical disability (EDSS), relapse-related nitrosative stress is likely to be relevant to the development of sustained disability in an individual patient. Multiple Sclerosis 2008; 14: 59—66. http://msj.sagepub.com

Multiple sclerosis attacks are associated with picornavirus infections

2004 ◽  
Vol 10 (2) ◽  
pp. 145-148 ◽  
Author(s):  
John D Kriesel ◽  
Andrea White ◽  
Frederick G Hayden ◽  
S L Spruance ◽  
Jack Petajan
Keyword(s):  
Multiple Sclerosis ◽  
At Risk ◽  
Demyelinating Disease ◽  
Respiratory Infections ◽  
Risk Period ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Upper Respiratory ◽  
Polymerase Chain

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system, which often follows a relapsing-remitting (RR) course with discrete attacks. MS attacks have been associated with upper respiratory infections (URIs), but the specific viruses responsible have not been identified. We studied a cohort of 16 RRMS patients experiencing URI and followed them for clinically identifiable attacks. The viral causes of 21 separate URIs were investigated using culture and polymerase chain reactio n (PCR) of nasal swab specimens, and by serology. Sibley’s ‘at-risk’ period for MS attacks, beginning two weeks before and continuing for five weeks after a URI, was used for the analysis. Seven of the nine (78%) URIs due to picornaviruses were associated with an MS attack during the at-risk period. By contrast, only two of 12 (17%) picornavirus-negative URIs were associated with an MS attack (P =0.01). The possible role of picornaviruses in the patho genesis of MS deserves further study.

Level of Nitrogen Oxide and Indicators of Oxidative-Antioxidative Status in the Gingival Tissues, Blood Plasma in Experimental Chronic Gastritis and Duodenitis and Drug Correction

2017 ◽  
Vol 31 ◽  
pp. 83-90
Author(s):  
Y.G. Romanenko
Keyword(s):  
Nitric Oxide ◽  
Calcium Carbonate ◽  
Blood Plasma ◽  
Chronic Gastritis ◽  
Gingival Tissue ◽  
Control Group ◽  
Treatment Level ◽  
Antioxidative Status ◽  
Nitric Oxide Metabolites

model of chronic gastritis and duodenitis was conducted in 48 immature Wistar rats both gender by intragastric injection of medical bile. Control group consisted of 10 animals. After approximation model of the gastritis and duodenitis rats were divided into five subgroups: the 1st subgroup (before treatment, 9 rats), subgroup 2 (10 animals) received the antioxidant, subgroup 3 (11 animals) – received NO donator, subgroup 4 (10 animals) - received an antioxidant and NO donator, subgroup 5 (8 animals) – received the antioxidant, NO donator and calcium carbonate. In rats with gastritis and duodenitis was observed redistribution of stable metabolites of nitric oxide: decreasing level in the gingival homogenates and increasing in the blood plasma. Level of malondialdehyde and aldehyddehydrogenase in the gingival tissue increased, and in the blood plasma decreased, on a background of catalase activation; content of ketone phenilhydrazone remained in the level of control group. Decreasing markers of oxidation lipids and proteins in the blood plasma, on a background of increasing levels of catalase and nitric oxide metabolites (in 14 times), indicates about a key role of NO in the antioxidant protection of organism in a case of disease.Application of antioxidant could not impact on the indicators of oxidation lipids and proteins. It had been shown decreasing content of the nitric oxide metabolites in the gingival tissues and blood plasma. Drug correction with donator of nitric oxide have to increase markers of oxidation lipids and proteins in the gingival tissues, on a background of high catalase activity and low levels of nitric oxide metabolites. In the blood plasma content of nitric oxide metabolites was higher, which indicated about an active inflammatory process in the stomach and duodenum mucosa. Indicators of the protein molecules fragmentation and malondialdehyde were not differ from those before treatment. Level of catalase was in two times higher, than in the control group, but level of superoxide dismutase was decreased. Complex of antioxidant and donator of nitric oxide helped to stabilise the indicators of oxidation lipids and proteins, although level of nitric oxide metabolites in the gingiva was significantly decreased. Application complex from the antioxidant, donator of nitric oxide and calcium carbonate at the treatment of chronic gastritis and duodenitis restored an oxidative-antioxidative status in the blood plasma and gingival tissues, increasing the production of nitric oxide to a level in the control group.

Inhibition of cystathionine-β-synthase activity during renal ischemia-reperfusion: role of pH and nitric oxide

2008 ◽  
Vol 295 (4) ◽  
pp. F912-F922 ◽  
Author(s):  
Gamika A. Prathapasinghe ◽  
Yaw L. Siow ◽  
Zhibin Xu ◽  
Karmin O
Keyword(s):  
Nitric Oxide ◽  
Ischemia Reperfusion ◽  
Left Kidney ◽  
Kidney Tissue ◽  
Sprague Dawley ◽  
Rate Limiting Step ◽  
Transsulfuration Pathway ◽  
Effects Of Ph ◽  
Nitrate And Nitrite

Our recent study (Prathapasinghe GA, Siow YL, O K. Am J Physiol Renal Physiol 292: F1354–F1363, 2007) indicates that homocysteine (Hcy) plays a detrimental role in ischemia-reperfusion-induced renal injury. Elevation of renal Hcy concentration during ischemia-reperfusion is attributed to reduced activity of cystathionine-β-synthase (CBS) that catalyzes the rate-limiting step in the transsulfuration pathway for the metabolism of the majority of Hcy in the kidney. However, the mechanisms of impaired CBS activity in the kidney are unknown. The aim of this study was to investigate the effects of pH and nitric oxide (NO) on the CBS activity in the kidney during ischemia-reperfusion. The left kidney of a Sprague-Dawley rat was subjected to ischemia-reperfusion. The CBS activity was significantly reduced in kidneys subjected to ischemia alone (15–60 min) or subjected to ischemia followed by reperfusion for 1–24 h. The pH was markedly reduced in kidneys upon ischemia. Injection of alkaline solution into the kidney partially restored the CBS activity during ischemia. Further analysis revealed that reduction of CBS activity during reperfusion was accompanied by an elevation of NO metabolites (nitrate and nitrite) in the kidney tissue. Injection of a NO scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO), restored the CBS activity in the kidneys subjected to ischemia-reperfusion. Treatment with PTIO could abolish ischemia-reperfusion-induced lipid peroxidation and prevent cell death in the kidney. These results suggested that metabolic acidosis during ischemia and accumulation of NO metabolites during reperfusion contributed, in part, to reduced CBS activity leading to an elevation of renal Hcy levels, which in turn, played a detrimental role in the kidney.

Cerebrospinal fluid and serum nitric oxide metabolites in patients with multiple sclerosis

1998 ◽  
Vol 4 (1) ◽  
pp. 27-30 ◽  
Author(s):  
G Giovannoni
Keyword(s):  
Nitric Oxide ◽  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Blood Brain Barrier ◽  
Neurological Diseases ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Blood Brain ◽  
Nitric Oxide Metabolites ◽  
Nitrate And Nitrite

Nitric oxide is hypothesised to play a role in the immunopathogenesis of multiple sclerosis. Raised cerebrospinal fluid and serum levels of the nitric oxide metabolites nitrate and nitrite have been described in patients with multiple sclerosis. Cerebrospinal fluid and serum nitrate and nitrite were measured in patients with multiple sclerosis, inflammatory and non-inflammatory neurological diseases, and correlated with the albumin quotient, an index of blood-brain-barrier dysfunction. Patients undergoing diagnostic lumbar and vene puncture were prospectively recruited, clinical data were obtained from the hospital records, and the CSF and serum nitrate and nitrite levels were measured by the nitrate reductase and Griess reaction methods. Nitrate and nitrite, were raised in the CSF and serum of patients with multiple sclerosis and other inflammatory neurological diseases compared to patients with non-inflammatory neurological disorders (median nitrate and nitrite: cerebrospinal fluid=10.3 μM vs 15.4 μMvs 6.6 μM, P50.001, and serum=49.0 μM vs 46.4 μM vs 38.8 μM, P=0.02, respectively). CSF nitrate and nitrite levels correlated with the albumin quotient (n=59, r=0.42, P50.001). This study provides further evidence for a role of nitric oxide in the immunopathogenesis of multiple sclerosis and supports a role for nitric oxide as a possible mediator of inflammatory blood-brain-barrier dysfunction.

The potential role of nitric oxide in multiple sclerosis

1998 ◽  
Vol 4 (3) ◽  
pp. 212-216 ◽  
Author(s):  
G Giovannoni ◽  
S J.R. Heales ◽  
J M Land ◽  
E J Thompson
Keyword(s):  
Nitric Oxide ◽  
Multiple Sclerosis ◽  
Blood Brain Barrier ◽  
Demyelinating Disease ◽  
Brain Barrier ◽  
Aetiological Factor ◽  
Barrier Dysfunction ◽  
Respiratory Chain Complexes ◽  
Blood Brain ◽  
Nitrate And Nitrite

Nitric oxide (.NO) and its reactive derivative peroxynitrite (ONOO7) have been implicated in the pathogenesis of multiple sclerosis (MS). They are cytotoxic to oligodendrocytes and neurones in culture by inhibiting the mitochondrial respiratory chain (complexes II/III and IV) and inhibiting certain key intracellular enzymes. Recently .NO has been implicated as a possible aetiological factor in reversible conduction block in demyelinated axons. Inducible nitric oxide synthase (iNOS) is upregulated in the central nervous system of animals with experimental allergic encephalomyelitis (EAE) and in patients with MS. In some EAE models inhibiting iNOS activity decreases disease severity whilst in other models disease activity is exacerbated. Raised levels of nitrate and nitrite, stable end-products of .NO/ONOO7, are found in the cerebrospinal fluid, serum and urine of patients with MS. CSF levels of nitrate and nitrite correlate with blood-brain-barrier dysfunction, which suggests that .NO may play a role in inflammatory blood-brain-barrier dysfunction. In a longitudinal study on 24 patients with relapsing remitting and secondary progressive MS, raised serum nitrate and nitrite levels correlated with a relapsing course and infrequent relapses. However, no correlation was found between raised serum levels of nitrate and nitrite and MRI activity, disease progression, or the development of cerebral atrophy. In autoimmune mediated CNS demyelinating disease .NO may be a double-edged sword, mediating tissue damage on the one hand and on the other hand modulating complex immunological functions which may be protective.

scholarly journals What Guides Peripheral Immune Cells into the Central Nervous System?

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2041
Author(s):  
Theresa Greiner ◽  
Markus Kipp
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune Cells ◽  
Progressive Disease ◽  
Demyelinating Disease ◽  
Disease Stage ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Peripheral Immune Cells

Multiple sclerosis (MS), an immune-mediated demyelinating disease of the central nervous system (CNS), initially presents with a relapsing-remitting disease course. During this early stage of the disease, leukocytes cross the blood–brain barrier to drive the formation of focal demyelinating plaques. Disease-modifying agents that modulate or suppress the peripheral immune system provide a therapeutic benefit during relapsing-remitting MS (RRMS). The majority of individuals with RRMS ultimately enter a secondary progressive disease stage with a progressive accumulation of neurologic deficits. The cellular and molecular basis for this transition is unclear and the role of inflammation during the secondary progressive disease stage is a subject of intense and controversial debate. In this review article, we discuss the following main hypothesis: during both disease stages, peripheral immune cells are triggered by CNS-intrinsic stimuli to invade the brain parenchyma. Furthermore, we outline the different neuroanatomical routes by which peripheral immune cells might migrate from the periphery into the CNS.

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