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The role of nitric oxide (NO) in childhood bacterial meningitis was investigated by determining the levels of nitrate/nitrite, stable end products of NO metabolism, in cerebrospinal fluid (CSF). Eighteen children with bacterial meningitis and 18 as a control group were included in the study. Mean (+/- SD) CSF nitrate/nitrite levels were 27.6 +/- 26 micromol/l in the bacterial meningitis group and 3.2 +/- 1.8 micromol/l in the control group (p = 0.0005). We found no correlation between CSF nitrate/nitrite levels and CSF white blood cell count (r = 0.22), protein (r = 0.26) or tumour necrosis factor alpha (TNF-alpha) levels (r = 0.046), but a moderate negative correlation between CSF nitrate/nitrite and glucose levels (r = -0.46).

To study the role of the nitric oxide(NO) in patients with cerebral infarction, NO in cerebrospinal fluid was determined in cerebral infarction group(15 cases) and control group(10 cases). Infarct volume was determined by CT between the second and the 7th day after the onset of symptoms. The severity of neurological deficits was assessed with the stroke scale of Ministry of Public Healthy(China). The results showed that NO was higher in cerebral infarction group (3.12 +/- 1.60) than that in control group(1.19 +/- 1.01) (P < 0.01). The concentration of NO was positively correlated with infarction volume(r = 0.57, P < 0.05) and severity of neurological of deficits(r = 0.54, P < 0.05), respectively. The results support the conclusion that NO produced in large amounts in the postischemic tissue contributes to the progression of the brain damage, which was demonstrated in animal models of focal cerebral ischemia.

A human immunodeficiency virus type 1 (HIV)-seropositive, antiretroviral-naive patient presented with significant cognitive dysfunction. Neuropsychologic, neuroradiologic, immunologic, and virologic studies confirmed HIV-associated dementia (HAD). After 12 weeks of highly active antiretroviral therapy (HAART) with ibuprofen, dramatic improvements were demonstrated in neurologic function and were sustained for > 1 year. HIV-1 RNA in cerebrospinal fluid (CSF) decreased from 10(5) to 10(4) copies/mL after 4 weeks. After 20 weeks of therapy, plasma viremia decreased from 10(6) copies/mL to undetectable (< 96 copies/mL). Assays of neurotoxins (tumor necrosis factor-alpha, quinolinic acid, and nitric oxide) in plasma and CSF were considerably elevated at presentation and significantly decreased after therapy. Baseline plasma and CSF demonstrated neurotoxic activities in vitro, which also reduced markedly. These data, taken together, support the notion that HAD is a reversible metabolic encephalopathy fueled by viral replication. HAART used with nonsteroidal antiinflammatory agents leads to the suppression of inflammatory neurotoxins and can markedly improve neurologic function in HAD.

It has been suggested that nitric oxide (NO) plays an important role in the pathogenesis of severe falciparum malaria. Since NO has a very short half-life, nitrate and nitrite (NOx) levels, stable metabolites of NO, are used as measures of NO production. We measured plasma NOx levels in 24 adults with severe falciparum malaria on the Thai-Burmese border. After correction for renal function, there was no correlation between plasma NOx levels, or the total amount of NOx excreted in the urine, and disease severity. Plasma NOx levels decreased after the first 48 hr in all patients (P = 0.007), suggesting decreased NO production. The NOx levels in cerebrospinal fluid (CSF) correlated well with plasma NOx levels, but these did not show a correlation with coma depth, and were not significantly different from those in a healthy control group. These findings do not support the hypothesis that excessive NO production contributes to the pathogenesis of severe falciparum malaria. However, local changes in NO production, e.g., in the central nervous system, might not be reflected in the total NOx production or NOx levels in the CSF.

A retrospective study of nitrate concentration in serum and cerebrospinal fluid (CSF) from vervet monkeys (Cercopithecus aethiops) infected with Trypanosoma brucei was undertaken. Serum nitrate was significantly elevated in parasitaemic animals. CSF nitrate detection correlated with the presence of parasites in the CNS. The results provide evidence for the production of nitric oxide (NO) in response to infection in a primate model of human African trypanosomiasis and provide the basis for the use of such a model in studies of the immunopathological effects of NO in human trypanosomiasis.

Objective: To probe into the significance of Nitric Oxide (NO) in ischemic cerebral damage and effect of ligustrazine on it., Methods: The NO contents in cerebrospinal fluid (CSF) and plasma of 20 controls and 62 patients with arteriosclerotic thrombotic cerebral infarction (ligustrazine group and common treatment group) were determined with Griess method before and after treatment., Results: The NO content in CSF before treatment was higher in severe type, it was higher than that in moderate type, and than that in mild type, again higher than that in control group (all P < 0.05) and was positively correlated with the size of infarction (P < 0.01). There was no significant difference between the plasma NO content of patients and that of control group (P > 0.05), but there was a trend that plasma NO content decreased as the patient's condition worsened. After treatment, the curative effect and plasma NO content of ligustrazine group were both markedly higher than those of common treatment group (P < 0.05). There were no significant differences between CSF NO contents of the two groups, respectively, and that of control group (P > 0.05)., Conclusions: Excessive NO produced in brain tissue and insufficient plasma NO participate the course of ischemic brain damage. Ligustrazine could increase the contents of plasma NO selectively.

Streptococcus pneumoniae is a common cause of meningitis. Nitric oxide (NO) has been implicated in causing cerebral edema. Modulating NO production in cerebrospinal fluid (CSF) may have a role in the treatment of bacterial meningitis. Experimental S. pneumoniae meningitis was induced in a rabbit model to determine CSF parameters and NO concentrations. An electrochemical probe in the CSF throughout the 7-hour experiment monitored NO concentrations. The animals had S. pneumoniae (10(5)) injected intracisternally and incubated for 1 hour. Cerebrospinal fluid 200-300 microl was obtained by intracisternal puncture at zero, 2, 4, and 7 hours after drug administration to measure glucose, protein, and lactic acid by standard chemical methods. White blood cell count was measured by hemocytometry. Three groups of five animals were used-control (C), ceftriaxone (CTX), and ceftriaxone plus dexamethasone (CTX+D). Ceftriaxone concentrations in CSF were obtained by microdialysis and analyzed by high-performance liquid chromatography. Mean (+/- SEM) CSF white blood cell count was significantly higher at 2 hours in the C group than in the other two groups (C 7307 +/- 1302, CTX 605 +/- 345, CTX+D 730 +/- 43/mm3, p<0.002). Ceftriaxone induced a significant rise in protein at 4 hours compared with the other groups (C 364 +/- 107, CTX 1158 +/- 797, CTX+D 365 +/- 100 mg/dl, p<0.02). Cerebrospinal fluid lactic acid was significantly different at 4 and 7 hours between C and CTX+D groups (4-hr C 8.0 +/- 2.2, CTX+D 2.0 +/- 0.4 mmol/L, p<0.05; 7-hr C 10.2 +/- 2.4, CTX+D 2.8 +/- 0.8 mmol/L, p<0.01). Median NO concentrations were significantly elevated in the control group compared with the other two groups (C 11.7, CTX 6.8, CTX+D 6.5 micro, p<0.02 C vs CTX, p<0.01 C vs CTX+D). Average (+/- SEM) NO concentrations were significantly higher in the C group at 4 hours (18.1 +/- 0.4, CTX 5.8 +/- 1.8 microM, p<0.05; CTX+D 11.5 +/- 4.0 microM, p>0.05), whereas they did not rise significantly until 7 hours in the CTX group (CTX 18.7 +/- 0.7, C 8.9 +/- 0.4 microM, p=0.055; CTX+D 8.1 +/- 2.2 microM, p<0.05). These results indicate that ceftriaxone with or without dexamethasone significantly decreases lactic acid concentrations and white cell penetration into the CSF in an experimental model of S. pneumoniae meningitis. In addition, ceftriaxone induced a significant elevation in CSF protein. Median NO production in the CSF was significantly attenuated by ceftriaxone.

Cerebrospinal fluid samples from 130 children who presented with cerebral malaria were investigated to elucidate the impact of biopterin production, NO formation, and local immune activation on the clinical course of this disease. Biopterin levels were significantly lower in patients who were in a deeper coma (P = .02). Cerebrospinal fluid concentrations of NO were significantly higher in children who died than in survivors (P = .037); however, this was not the case for macrophage activation markers, neopterin, and soluble tumor necrosis factor receptor p75 (sTNFR-75). Biopterin, neopterin, and sTNFR-75 but not NO concentrations were significantly related to each other. Low biopterin levels in deep coma are compatible with an impaired local Th1 response, but the low levels could also be due to the scavenging of radicals or to decreased neurotransmitter synthesis. Local production of NO, most likely by nonimmune mechanisms, may be detrimental in cerebral malaria; however, this appears not to be the case for local Th1-mediated immune pathways.

To investigate the involvement of nitric oxide (NO) in childhood meningitis, we measured the concentrations of NO2- (a stable metabolite of NO) in serial samples of cerebrospinal fluid (CSF) from 11 children with septic and 7 with aseptic meningitis and 26 control patients without meningitis. The mean concentration of NO2- in samples obtained during the early stages of septic meningitis, but not aseptic meningitis, was significantly higher than in control samples. Clinical and laboratory improvement following administration of antibiotics and dexamethasone was associated with a fall in CSF [NO2-] to normal levels in these patients. CSF [NO2-] remained almost consistently within the normal range in patients with aseptic meningitis. Our findings indicate that NO production is enhanced in the CSF compartment of children with septic meningitis and support the hypothesis that NO is involved in the pathophysiology of septic meningitis.

The concentration of the nitric oxide (NO) metabolites nitrite (NO2-) and nitrate (NO3-) in the cerebrospinal fluid from patients with Alzheimer's disease (AD), vascular dementia of the Binswanger type (VDBT) or multiple small infarct type (MSID), and controls were determined using high performance liquid chromatography. The nitrite concentration was significantly higher in VDBT/MSID patients than in controls (p < 0.005). The nitrate concentration and the combined nitrite and nitrate concentration was significantly higher in both AD (p < 0.05) and VDBT/MSID (p < 0.001) patients than in controls, with these concentrations being significantly greater in VDBT/MSID than AD patients (p < 0.005). The combined nitrite and nitrate concentration significantly decreased as the severity of dementia progressed in AD (rs=0.70, p < 0.01), but remained elevated in all stages of VDBT/MSID. These results suggest that NO production or oxidation in the brain increases in the early stage of AD and then decreases as neuronal cell loss progresses, but increases throughout the course of disease in VDBT/MSID, which may in part contribute to neuronal degeneration in both conditions.

Histological studies have detected nitric oxide (NO) synthase in the central nervous system of all vertebrates examined, from lampreys to mammals. However, there are still very few comparative physiological studies on the function of NO synthase in the brain of non-mammalian vertebrates. So far, we know that acetylcholine can cause an NO-dependent increase in brain blood flow in turtles and some fish species (crucian carp and rainbow trout), whereas some other fishes appear to lack such a mechanism. Hypercapnia can induce NO-dependent cerebral vasodilation in mammals, but such a mechanism appears to be lacking in the ectothermic vertebrates examined. The number of species studied needs to be expanded before we can draw any firm conclusions about the origin of NO-dependent brain blood flow regulation: if it has evolved more than once or if it has been occasionally lost during evolution. We conclude that NO synthase may be present in all vertebrate brains but that its functions can vary, as judged from its role in cerebral blood flow regulation. The diversity of functions that NO has proven to have within the mammalian brain is likely to be paralleled by the same degree of diversity of function between vertebrate groups.

Objective: To investigate nitric oxide (NO) metabolism after subarachnoid hemorrhage (SAH)., Methods: We measured the concentrations of the NO metabolites, nitrite and nitrate, in cerebrospinal fluid (CSF) obtained from the cisternal drainage of patients with SAH. Studies were performed for 31 patients who had undergone surgical obliteration of bleeding aneurysms within 3 days of their hemorrhage. The concentrations of nitrite and nitrate in the CSF were measured for 14 days using a nitrate/nitrite kit and samples that were obtained on a daily basis from the cisternal drainage., Results: Compared with the control values in the CSF (2.6 +/- 0.4 mumol/L, n = 14) obtained from patients with hemifacial spasm, trigeminal neuralgia, or nonruptured aneurysms, the concentrations of nitrite and nitrate in the CSF were significantly elevated in the acute stage of SAH and remained elevated. The concentration of NO metabolites may correlate with the amount of bleeding, inasmuch as the values in patients in Fisher Group 3 (n = 25) were higher than those in patients in Fisher Group 2 (n = 6). The concentration of nitrate was higher than that of nitrite, suggesting that NO in the subarachnoid space is mainly absorbed by hemoglobin and degraded to nitrate. No differences were demonstrated in patients treated with high doses of methylprednisolone (n = 17) compared with those treated with usual-dose steroids (n = 14). Steroids are known to prevent the formation of inducible NO synthase mediated by inflammatory cytokines., Conclusion: NO metabolism in the brain is stimulated after SAH. Nitrate is the dominant NO metabolite in CSF after SAH. The involvement of inducible NO synthase in the pathophysiology of NO metabolism after SAH was not clearly suggested based on the present data.

Nitric oxide is an important host defence molecule as well as being a mediator in many pathophysiological processes. To investigate its role in severe malaria, we measured plasma nitrate and nitrite concentrations in 70 children with malaria (54 with severe malaria) and 48 control subjects (33 with medical conditions and 15 surgical patients). We related these measurements to plasma lactate concentrations, an established marker of disease severity in malaria. Plasma lactate levels were significantly elevated in patients with deep coma (P = 0.0007) and those with a fatal outcome, but mean nitrogen oxide concentrations were not significantly different in the 2 outcome categories and were not related to depth of coma (P > 0.5). In patients whose cerebrospinal fluid (CSF) was examined, lactate concentrations were elevated in fatal cases (geometric mean 8.2 mmol/L, n = 5) compared with survivors (3.4 mmol/L, n = 13; P = 0.032); corresponding CSF nitrogen oxide concentrations were 10.7 microM in fatal cases compared with 12.5 microM in survivors (P = 0.5). Plasma nitrogen oxide concentrations were negatively correlated with admission parasitaemia (r = -0.41, n = 70; P < 0.0001). In our population, elevations of plasma lactate, but not nitrite or nitrate, reflected disease severity in malaria.

The aim of the present study was to investigate some putative neurotransmitters involved in nociception and pain in parturients during active labour experiencing intense visceral pain. The concentration of the excitatory amino acid aspartate was significantly increased, and there was a tendency for an increase in glutamate, in lumbar cerebrospinal fluid (CSF) of parturients in active vaginal labour compared with control patients without pain subjected to elective caesarean section. The CSF concentration of the nitric oxide breakdown product nitrate was significantly decreased in parturients compared with control patients and healthy volunteers. No significant differences in the concentrations of substance P, substance P-endopeptidase or met-enkephalin were detected between parturients and controls. Our data suggest a paradoxical negative relationship between CSF concentrations of excitatory amino acids and nitric oxide in labour pain. The mechanisms behind this finding is unclear at present.

The contents of NO, TNF-alpha and IL-8 in the cerebrospinal fluids (CSF) of patients with tuberculous and cryptococcic meningitis were detected. The results showed that the concentration of NO2-/NO3- and the levels of TNF-alpha and IL-8 in CSF of the two kinds of meningitis were higher than those of normal CSF, and the concentration of NO2-/NO3- correlated positively to the content of TNF-alpha. The results indicate that the over production of NO, TNF-alpha and IL-8 in CSF may involve in the tissue inflammation and damage of central nerve system infection.

Twenty seven children with a documented bacterial (BM)-, 73 with viral (mumps and enteroviral) meningitis and 51 controls were included. CSF white blood cell counts, glucose and protein concentrations were determined routinely. CSF nitrite and nitrate levels (the stable degradation product of NO) were determined by a modified Griess reaction. The mean +/- levels of nitrite and nitrate in CSF on admission were higher in patients with BM in comparison with controls and in children with viral meningitis. In 10 patients dexamethasone therapy was started about 10 minutes before the first antibiotic dose and given every 12 hours of 0.4 mg/kg for 2 days. At 24 to 48 hours those who received dexamethasone therapy had a significantly lower mean +/- SD CSF nitrite concentration compared with that in non-steroid treated patients. In all patients with meningitis a significant positive correlation was found between CSF nitrite and CSF granulocyte counts and also CSF protein concentration. Increased production of NO in the CSF compartment during the acute phase of BM may contribute to the inflammatory process and tissue injury. Dexamethasone therapy administered before the first parenteral antibiotic dose reduces the production of NO in the CSF during BM.

To investigate the role of nitric oxide (NO) in bacterial meningitis, concentrations in serum, cerebrospinal fluid (CSF), or both of the precursor (L-arginine) and degradation products of NO (nitrate, nitrite) and tumor necrosis factor (TNF)-alpha were measured in 35 patients and 30 controls. CSF nitrate levels were significantly elevated, mainly due to increased blood-brain barrier permeability, and are therefore not a good parameter for gauging endogenous NO production in the CSF compartment. CSF NO/nitrite levels were significantly elevated in patients. NO/nitrite levels decreased over time (26%/6 h; P < .001). CSF levels of NO/nitrite correlated with those of TNF-alpha (r = .55; P = .001) and glucose (r = -.43; P = .02). CSF levels of L-arginine were lower in patients than in controls (P < .001). Dexamethasone did not exert a significant effect on NO metabolism. In conclusion, enhanced NO production may contribute to anaerobic glycolysis and neurologic damage in bacterial meningitis.

It has previously been observed that nitric oxide (NO) and the opioids Met- and Leu-enkephalin contribute to hypoxia-induced pial artery dilation in the newborn pig. The present study was designed to investigate the relationship between NO and opioids in hypoxic pial dilation. Piglets equipped with closed cranial windows were used to measure pial artery diameter and collect cortical periarachnoid cerebrospinal fluid (CSF) for assay of opioids. Sodium nitroprusside (SNP; 10(-8) and 10(-6) M) elicited pial dilation that was blunted by the soluble guanylate cyclase inhibitor LY-83583 (10(-5) M; 10 +/- 1 and 23 +/- 1 vs. 3 +/- 1 and 7 +/- 1% for 10(-8) and 10(-6) M SNP before and after LY-83583, respectively). SNP-induced dilation was accompanied by increased CSF Met-enkephalin, and coadministration of LY-83583 with SNP blocked these increases in CSF opioid concentration (1,144 +/- 59, 2,215 +/- 165, and 3,413 +/- 168 vs. 1,023 +/- 16, 1,040 +/- 18, and 1,059 +/- 29 pg/ml for control and 10(-8) and 10(-6) M SNP before and after LY-83583, respectively). SNP-induced release of CSF Leuenkephalin was also blocked by LY-83583. Similar blunted vascular and biochemical effects of SNP were observed with coadministration of the purported guanosine 3', 5'-cyclic monophosphate (cGMP) antagonist, the phosphorothioate analogue of 8-bromo-cGMP (BrcGMP) [(R)-p-BrcGMP[S]; 10(-5) M]. The cGMP analogue, BrcGMP, elicited dilation that was also accompanied by increased CSF Met- and Leu-enkephalin. Vascular and biochemical effects of BrcGMP were blunted by (R)-p-cGMP[S] and unchanged by LY-83583. Hypoxia-induced pial artery dilation was attenuated by N omega-nitro-L-arginine (L-NNA; 10(-6) M), an NO synthase inhibitor (25 +/- 2 vs. 14 +/- 1%). Hypoxic pial dilation was accompanied by increased CSF Met-enkephalin, and these increases were attenuated by L-NNA (1,137 +/- 60 and 3,491 +/- 133 vs. 927 +/- 25 and 2,052 +/- 160 pg/ml for control and hypoxia before and after L-NNA, respectively). Hypoxia also increased CSF Leuenkephalin, and these CSF changes were similarly attenuated by L-NNA. These data show that cGMP increases CSF Met- and Leu-enkephalin. Furthermore, these data suggest that NO contributes to hypoxic dilation, at least in part, via formation of cGMP and the subsequent release of opioids.

It has been suggested that nitric oxide could be implicated in the neuronal degeneration of substantia nigra compacta in patients with Parkinson's disease. Recently, it has been reported decreased CSF nitrate levels (oxidation product that provides an indirect estimation of nitric oxide) in Parkinson's disease patients, assessed with a colorimetric method. We studied the CSF and plasma levels of nitrate with a kinetic cadmium-reduction method in 31 Parkinson's disease patients and 38 matched controls. The CSF and plasma nitrate levels were not correlated either in patient or in the control group, and they did not differ significantly between the two study groups. They were not influenced significantly by antiparkinsonian drugs in patients, although there was a trend for CSF nitrate levels to be higher in patients treated with levodopa or with dopamine agonists. CSF and plasma nitrate levels did not correlate with age at onset, duration, scores of the unified Parkinson's disease rating scales and Hoehn & Yahr staging in the patients group. These date suggest that CSF and plasma levels of nitrate are apparently unrelated with the risk for PD.