Nitric Oxide Concentrations In Patients Research Articles

A Single-Center, Randomized, 3-Way, Crossover Study to Evaluate the Effect of an Exhalation Delivery System on Nasal Nitric Oxide Concentrations in Patients with Chronic Rhinosinusitis Compared with Healthy Participants

Nasal nitric oxide (nNO) is produced within the sinuses and has anti-inflammatory activity. In patients with chronic rhinosinusitis (CRS), nNO is depressed, likely because inflammation restricts nNO release from the sinuses. The positive pressure produced by the Exhalation Delivery System (EDS) in the nasal cavity has the potential to open up the sinus ostia, allowing release of nNO. Increasing nNO may improve patient symptoms.

A Single-Center, Randomized, 3-Way, Crossover Study to Evaluate the Effect of an Exhalation Delivery System on Nasal Nitric Oxide Concentrations in Patients with Chronic Sinusitis

A Single-Center, Randomized, 3-Way, Crossover Study to Evaluate the Effect of an Exhalation Delivery System on Nasal Nitric Oxide Concentrations in Patients with Chronic Sinusitis

Comparison of Saliva Nitric Oxide between Chronic Kidney Disease Before and After Dialysis and with Control Group

Introduction:Chronic Kidney Disease (CKD) is a chronic progressive disorder and a major cause of death and disability in all countries. In the kidneys, Nitric Oxide (NO) has involved in several important cellular processes including glomerular and modular hemodynamics set-out, tubular - glomerular feedback reaction, renin releasing and extracellular fluid volume but NO can act as an inflammatory mediator and oxidative stress factor in high levels.Aim:The aim of this study was to evaluate salivary levels of NO in patients with chronic kidney disease on dialysis compared to the healthy subjects and evaluate the effect of dialysis on the level of NO in saliva.Materials & Methods:In this case-control study, 30 hemodialysis patients and 30 healthy controls that were matched for age and sex were selected. Unstimulated saliva samples were collected from all subjects. In the patient’s group, half an hour before starting dialysis first sampling and two hours after the completion of dialysis second sampling were collected. NO concentration in the samples was measured by using the Griess method. For data analysis, SPSS software version 16, Mann Whitney-U and Wilcoxon test were used. The level of significance was considered 0.05.Results:Mann-Whitney U test showed that the average concentration of salivary NO in patients with CKD (pre-dialysis and after dialysis) was higher than in the control group. The average concentration of salivary NO in patients with CKD was reduced after hemodialysis.Conclusion:Hemodialysis reduces salivary NO levels in CKD patients. It seems that hemodialysis has a role in decreasing the concentration of this inflammatory mediator and oxidative stress.

Significance of Measurment of the Fractional Exhaled Nitric Oxide Concentrations in Patients with Eosinophilic Chronic Rhinosinusitis

Significance of Measurment of the Fractional Exhaled Nitric Oxide Concentrations in Patients with Eosinophilic Chronic Rhinosinusitis

Measurement of exhaled nitric oxide concentration in patients with obstructive sleep apnea: A meta-analysis.

Exhaled nitric oxide (eNO) has been proposed as a noninvasive measure of airway inflammation. However, its value in patients with obstructive sleep apnea (OSA) is still controversial. The authors aim to assess the difference in eNO levels between patients with OSA and controls by a meta-analysis. A systematic search was performed in the PubMed, EMBASE, the Cochrane Library, and MEDLINE databases to collect relevant studies published from 1996 to 2016. Eligible studies that reported eNO levels in patients with OSA were included. STATA (version 12.0) was used for data analysis. Two hundred eighty-four studies were reviewed for inclusion, with 16 studies pooled for analysis (16 studies for fractional exhaled nitric oxide [FENO], 5 for alveolar nitric oxide [CANO], and 4 for the maximum airway wall flux of nitric oxide [J'awNO]). The FENO levels were significantly higher in patients with OSA compared with that in the control groups (6.32 ppb, 95% confidence interval [CI] 4.46-8.33, P < 0.001). Furthermore, FENO was significantly increased (4.00 ppb, 95% CI 1.74-6.27, P = 0.001) after overnight sleep in patients with OSA, but not in healthy controls. Additionally, long-term continuous positive airway pressure (CPAP) therapy reduced FENO levels (-5.82 ppb, 95% CI -9.6 to -2.01, P < 0.001). However, the CANO (-0.01 ppb, 95% CI -1.66 to 1.64, P = 0.989) and J'awNO levels (220.32 pl/s, 95% CI -49.31 to 489.94, P = 0.109) were not significantly different between the OSA groups and non-OSA groups. The results of the meta-analysis suggest that OSA is significantly associated with airway inflammation and elevated FENO levels can be modified by long-term CPAP therapy. J'awNO and CANO levels were not significantly different between the OSA groups and control groups.

好酸球性副鼻腔炎診療における呼気中一酸化窒素測定の意義

好酸球性副鼻腔炎診療における呼気中一酸化窒素測定の意義

Óxido nítrico plasmático y doppler de las arterias uterinas en preeclámpticas y embarazadas normotensas sanas

ObjectiveTo establish plasma nitric oxide concentrations in patients with preeclampsia and healthy normotensive pregnant women and to relate doppler findings to serum concentrations. MethodWe selected 160 patients, of which 47 had severe preeclampsia (group A), 33 had mild preeclampsia (group B), and 80 were healthy pregnant women with a similar age to patients in the study groups who served as controls (group C). Blood samples for determination of nitric oxide and doppler measurements were taken in all patients before labour and immediately after diagnosis in the study group. ResultsPlasma nitric oxide (nitrites/nitrates) concentrations were lower in groups A and B than in group C (P<.05). Measurements of the pulsatility index, resistance index and systolic/diastolic blood flow ratio of uterine arteries were higher in both groups of preeclamptic patients (P<.05). Correlations of plasma nitric oxide concentrations with doppler velocimetry values showed a negative and significant association with all the evaluated parameters (P<.05). ConclusionPlasma nitric oxide concentrations were higher in preeclamptic patients than in normotensive pregnant women and there was a significant correlation between plasma concentrations and parameters of doppler velocimetry of uterine arteries.

Association Analysis for Neuronal Nitric Oxide Synthase Gene Polymorphism with Plasma Nitrite/Nitrate Concentration in Schizophrenia

Summary Background: Single nucleotide polymorphisms (SNP) of many genes, including the gene for neuronal nitric oxide syn-thase (NOS1), were found significantly associated with schizo-phrenia. According to our previously published results of increased plasma nitric oxide concentration in patients with schizophrenia, we hypothesized that the NOS1 gene polymorphism might be a cause of increased nitric oxide production in patients with schizophrenia and tested the interdependence between plasma nitrite/nitrate concentrations and SNP (a CT transition located in exon 29) of the human NOS1 gene. Methods: Nitrite/nitrate concentration was measured in blood plasma of 38 patients with schizophrenia and of 39 age and gender matched healthy persons by the colorimet-ric test. The NOS1 gene polymorphism was determined by polymerase chain reaction analysis. Results: A significantly higher plasma nitrite/nitrate concentration was found in patients with schizophrenia (97.5±33.3 μmol/L, p&lt;0.001) in comparison with controls (61.4±18.9 μmol/L). No T/T genotype was found in healthy individuals and there was a significant difference in the genotype distribution between patients and controls (χ2=24.54, p=0.0000047). Furthermore, a significant difference in the allele frequencies between patients and controls (χ2=19.00, p&lt;0.000013, OR=4.45, 95% CI=2.12–9.39) was noted. Also, a significant difference in plasma nitrite/nitrate concentration was observed between patients having the C/T genotype (99.97±33.83 μmol/L) and the corresponding control (C/T) subgroup (63.88±10.26 μmol/L, p&lt;0.01). However, there were no significant differences in nitrite/nitrate concentration between the patient subgroups with different genotypes (C/C, C/T, T/T). Conclusions: CT transition located in exon 29 of the human NOS1 gene may be responsible for the increased plasma nitrite/nitrate levels.

Nitric oxide plasma concentration associated with cognitive impairment in patients with recurrent depressive disorder

Background/aimDepressive disorders are multifactorial diseases, in which cognitive impairment is one of the characteristic feature. One of the molecules that regulate of various cognitive, emotional and behavioural processes is nitric oxide (NO), synthesized from l-arginine by a family of isoformic enzymes known as nitric oxide synthases (NOS). NO is a gaseous compounds that acts as a biological second messenger in a number of organ system. In addition, NO is a ubiquitous free radical (NO) that affects many normal physiologic functions but is also implicated in the etiology and progression of many diseases. The aim of the study was to determine the concentration of NO in patients with recurrent depressive disorder (rDD) and to define relationship between plasma NO levels and the cognitive performance. MethodsThe study comprised 78 subjects: patients with rDD (n=45), healthy controls (CG, n=33). Cognitive function assessment was based on: TMT, The Stroop Test, VFT, AVLT. ResultsStatistically significant differences were found among patients with rDD in the intensity of depression symptoms, measured by the HDRS on therapy onset vs. the examination results after 8 weeks of treatment (p<0.001). The level of NO was substantially higher in patients with rDD compared to CG. For all examined subjects (p<0.001), elevated levels of NO in blood plasma adversely affect the efficiency of visual–spatial and auditory-verbal working memory as well as short-term declarative memory. For rDD patients, elevated NO levels were associated with worse cognitive test performance. The higher was the concentration of plasma NO, the greater was the severity of depressive symptoms measured by HDRS (p=0.03). Conclusions(1) Higher concentration of plasma NO in rDD patients is associated with the severity of depressive symptoms. (2) Elevated levels of plasma NO are related to impairment of visual–spatial and auditory-verbal working memory as well as to impairment of short-term declarative memory.

Serum nitric oxide concentrations in patients with multiple sclerosis and patients with epilepsy

Nitric oxide (NO), a neurotransmitter and a free radical, has been purported to be involved in numerous neurological diseases. We investigated the serum nitric oxide concentration in 30 patients with multiple sclerosis (MS), in 30 patients with epilepsy and in 30 control subjects. The aim was also to determine whether a statistically significant difference in serum NO concentrations exists between the groups of interest. The total serum nitric oxide concentration was measured using the Griess reaction after reducing nitrates to nitrites with elemental zinc. In the group multiple sclerosis, the mean NO concentrations were X±SEM=31.02±1.79μmol/l, in the control group X±SEM=25.31±1.44μmol/l and in the group epilepsy X±SEM=22.51±1.28μmol/l. Student's t test showed a statistically significant difference between subjects with multiple sclerosis and the control group (p=0.013), as well as between the groups multiple sclerosis and epilepsy (p=0.0002). This data confirms that NO may play an important role in the pathogenesis of multiple sclerosis, whereas its role in epilepsy still remains unclear.

Exhaled Nitric Oxide in Patients with Esophagitis

Assessment of nitric oxide (NO) concentration in exhaled air is broadly used to monitor the airway inflammation in asthma. High level of NO are also observed in paranasal sinuses and gastrointestinal tract (GT). The intact esopahageal sphincters are responsible for maintain the NO within the GT. It is not known how much the GT and especially esophageal motility disorders can affect the FeNO measurements. The aim of the study was to assess if the gastroesophageal reflux disease has any impact on level of NO in exhaled air in patients who do not suffer from any airway disease. In 51 patients, in whom asthma, nasal polyps or atopy were excluded, gastroscopy with biopsy was performed. In 13 of them no esophageal pathology was found and they were considered as the control group. In the other 38 patients the esophagitis was diagnosed based on Los Angeles classification. The concentration of NO in exhaled air in patients with endoscopical gastro-esophageal changes did not differ significantly from the NO concentration in patients without inflammatory changes in stomach and esophagus (p = 0.68). Moreover, the presence of hiatal hernia did not affect the FeNO (p = 0.67). There was also no significant dependence between NO level and infection with Helicobacter pylori (p = 0.18). The gastroesophageal pathologies did not significantly affect NO concentration in exhaled air.

The relationship between platelet count with splenic arterial blood flow and plasma nitric oxide concentration in patients with hypersplenism

Objective To investigate the relationship between platelet count with splenic arterial blood flow (SAF) and the plasma nitric oxide (NO) concentration in patients with hypersplenism. Methods Platelet count,SAF and plasma NO concentration were measured in 36 cases of cirrhotic patients with hyper-splenism (hypersplenism group) and 10 cases of healthy volunteers (control group). Results Platelet count in hypersplenism group and control group was (60.75±27.77)×10~9/L and (212.40±71.76)×10~9/L re-spectively (P<0.01) ; SAF was (482.50±263.61) and (181.20±61.85) ml/min (P<0.01) ; plasma NO concentrations were (97.646±20.990) and (50.774±19.400) μmol/L (P<0.01). There was a correla-tion between platelet count and SAF in hypersplenism group (r=-0.422,P<0.05),SAF and plasma NO concentration (r=0.746,P<0.01). Conclusion The increase in SAF induced by the increase of plasma NO concentration may play an important role in the occurrence and development of hypersplenism. Key words: Portal hypertension; Hyporsplenism; Splenic artery; Nitric oxide

The Role of Nitric Oxide and Ferritin in the Pathogenesis of Alcoholic Liver Disease: a Controlled Clinical Study

The role of ferritin in fibrogenesis of liver parenchyma in patients with alcoholic liver disease has been investigated in previous studies. Ferritin was shown to be an indirect marker of ferum deposition in liver parenchyma in alcohol liver disease. The aim of the present study was to examine the role of nitric oxide (NO) in the pathogenesis of alcoholic liver disease as well as the influence of NO on iron (ferritin) metabolism in patients with alcoholic liver disease. Serum concentrations of NO and iron markers (iron, total iron binding capacity, ferritin) were measured in 30 male patients (aged 20-60 years) with alcoholic liver disease, as well as from a control group (30 male patients (aged 20-60 years) without liver disease). NO concentration was detected by measuring production of nitrates and nitrites using classical colorimetric Griess reactions. There was a statistically significant increase in serum NO concentration in patients with alcoholic liver disease compared to the control group (mean +/- SEM; 41,2 +/- 25,3 vs. 28,9 +/- 12,3 mmol/dm3, respectively; p<0,03). Similarly, serum iron levels (18,7 +/- 8,2 vs. 13,2 +/- 10,2 g/100 cm3, respectively; p<0,03) and serum total iron binding capacity (51,3 +/- 13,9 vs. 41,4 +/- 11,4 micromol/dm3, respectively; p<0,005) were also significantly higher in patients with alcoholic liver disease compared to control patients. The serum concentration of ferritin was 27% higher in patients with alcoholic liver disease than in the control group; however this was not statistically significant (283,2 +/- 291,0 vs. 222,9 +/- 252,0 g, respectively; p<0,4). There was no correlation between NO and ferritin in the investigated groups. These results suggest a possible role of NO and iron in the pathogenesis of alcoholic liver disease. NO and iron may be used as non-invasive predictors of liver damage. Also the role of iron in sera, and its deposition in liver parenchyma, could be used in clinical practice, especially in regards to assessing the fibrogenesis of liver parenchyma induced by ferritin.

Effect of Treatment on Maxillary Sinus and Nasal Nitric Oxide Concentrations in Patients With Nosocomial Maxillary Sinusitis

In maxillary nosocomial sinusitis (MNS) related to severe sepsis, nitric oxide (NO) concentration in the maxillary sinuses is drastically reduced secondarily to a downregulation of type-2 NO synthase. NO plays a major role in nonspecific immune defense of sinuses. We therefore aimed to study maxillary NO concentration during the treatment of MNS with drainage, daily lavage, and removal of any nasally introduced tube. Nine patients were studied during the first 4 days of treatment of MNS. We measured the concentration of NO gas in the maxillary sinus and in the nasal cavity, and the NO metabolite levels (nitrites/nitrates [NOx]) in the sinus lavages. Maxillary NO concentration (median [25 to 75 percentile]) increased from 70 parts per billion (ppb) [40 to 100 ppb] to 2,050 ppb (1,700 to 3,000 ppb) after 4 days of treatment of MNS (p < 0.0001). In the meantime, nasal NO increased from a median of 100 ppb (98 to 148 ppb) to 180 ppb (180 to 188 ppb) [p < 0.001]. At any time, there was a correlation between maxillary NO (logarithmic value) and nasal NO (r2 = 0.57, p < 0.0001). NOx levels remained stable in the lavages. We conclude that the treatment of the sinusitis with drainage, daily lavage, and removal of the gastric tube lead to a spectacular increase of maxillary and nasal NO concentrations.

Serum Interleukin-2, Interleukin-6, Tumour Necrosis Factor-Alpha and Nitric Oxide Levels in Patients With Behçet’s Disease

Introduction: Behçet’s disease (BD) is a chronic systemic disorder characterised by oral and genital ulcerative lesions, ocular and cutaneous manifestations. Cytokines are the major mediators of immunologic and inflammatory reactions. Nitric oxide is reactive nitrogen intermediate which plays a key role in pathogenesis of many inflammatory and autoimmune skin diseases. The study was conducted to determine serum interleukin-2 (IL-2), interleukin-6 (IL-6), tumour necrosis factor (TNF)-alpha and nitric oxide levels in relation to the pathogenesis of Behçet’s disease. Materials and Methods: Serum IL-2, IL-6, and TNF-alpha levels were measured with test kits by enzyme-linked immunosorbent assay (ELISA) method, while serum nitric oxide levels were determined with a test kit by colorimetric method. Serum IL-2, IL-6, TNF-alpha and nitric oxide concentrations in 27 patients with Behçet’s disease and in 16 healthy controls were determined by extrapolation from their standard curves. The significance of the mean differences between the 2 groups was assessed by the Mann-Whitney U test. Results: The serum levels of IL-2, IL-6, TNF-alpha, and nitric oxide concentrations in patients with BD were significantly higher than those of the controls (P &lt;0.001). Conclusion: Our results suggest that elevated levels of IL-2, IL-6, TNF-alpha, and nitric oxide in Behçet’s disease appear to be related to the disease.

Effect of intravenous L‐NMMA on nitric oxide production in collagenous colitis

Background: Nitric oxide (NO) is greatly increased in the colon of patients with inflammatory bowel disease of different aetiology, including collagenous colitis. In man, NO can be generated from NO synthases as well as from non‐enzymatic sources. The source of the NO found in luminal intestinal gas has not been exactly pinpointed. We investigated the effect of the NO synthase inhibitor L‐NMMA on intestinal concentrations of NO in patients with clinically active collagenous colitis. In addition, we measured NO levels from the respiratory tract. Methods: Ten patients with active collagenous colitis were studied. NO levels were measured from the respiratory tract and in the rectum before and after i.v. administration of L‐NMMA (7.5 mg/kg) using a chemiluminescence method. Results: Airway NO release decreased markedly, and mean arterial blood pressure increased in all patients following L‐NMMA treatment. Basal rectal NO levels were high (median >10 000 ppb) and decreased markedly in 5 patients after L‐NMMA. In contrast, NO levels remained completely unchanged or even increased in the other 5 patients. Conclusion: Rectal levels of NO are greatly increased in patients with symptomatic collagenous colitis. Intravenous administration of an NO synthase inhibitor reduced rectal NO only in half of the patients despite clear evidence of effective systemic NO synthase inhibition. This could indicate alternative NOS‐independent sources of intestinal NO in this disease.

Increased inducible nitric oxide synthase expression and nitric oxide concentration in patients with aplastic anemia.

Nitric oxide (NO) is a biological mediator that is synthesized from L-arginine by the nitric oxide synthase (NOS) family. We investigated the expression of iNOS in bone marrow (BM) mononuclear cells (MNCs) using a reverse transcriptase polymerase chain reaction (RT-PCR) assay and the concentration of NO from BM serum by measuring the metabolite NO(2)(-) in 13 patients with aplastic anemia (AA) compared with 10 normal controls who were donors for allogeneic bone marrow transplantation (BMT). All samples of BM MNCs in patients with AA expressed iNOS mRNA, but iNOS was not expressed in patients who were treated successfully with allogeneic BMT. Normal control samples and samples from leukemia patients who had bone marrow aplasia after chemotherapy did not show significant iNOS expression. When we measured the density of bands for both iNOS and beta(2)-microglobin expressed as the iNOS/beta(2)-microglobin density ratio, there was a significant difference in the ratio between AA and normal controls (0.88+/-0.15 vs 0.26+/-0.05, P<0.001). The BM serum NO(2)(-) concentration in the patients with AA was significantly higher than that of normal controls (88.1+/-32.8 microM vs 48.8+/-8.6 microM, P=0.002). In addition, there was a significant correlation between the NO(2)(-) concentration and the calculated iNOS/beta(2)-microglobin density ratio (r=0.567, P=0.01). These findings suggest that upregulation of iNOS expression for local NO production may contribute in part to the pathogenesis of AA.

Nasal nitric oxide.

Nasal nitric oxide.

Elevated levels of nitrate in rheumatoid arthritis

Nitric oxide (NO) is a free radical that plays important roles in many physiological and pathological processes. Evidence suggests that NO participates in the pathogenesis of inflammatory reactions in many autoimmune and inflammatory diseases such as rheumatoid arthritis (RA). The purpose of this study was to evaluate serum concentrations of NO in patients with RA and to determine whether they correlate with clinical and laboratory parameters of RA disease activity. Twenty-seven RA patients were recruited for the study and compared with 20 healthy subjects. Serum NO concentrations were measured indirectly in terms of nitrate using colorimetric assay. Disease activity was determined by laboratory and clinical findings. Mean serum concentrations of nitrate were significantly higher than those of healthy controls (P < 0.05). Among the disease activity parameters, C-reactive protein, number of swollen and tender joints, Ritchie articular index, and disease activity scores correlated significantly with serum NO levels. Our results suggest that these levels can serve as a reliable parameter of disease activity in patients with RA. Further knowledge about the precise role of NO may lead to better understanding of the pathogenesis of RA. Furthermore, modulation of NO synthesis may represent a new approach to the treatment of inflammatory and autoimmune conditions.

Impairment of airway mucociliary transport in patients with sinobronchial syndrome: role of nitric oxide.

Nitric oxide (NO) produced within the respiratory tract can stimulate ciliary motility of airway epithelial cells and hence mucociliary transport. In this study, to determine the role of NO in mucociliary dysfunction in sinobronchial syndrome (SBS), we measured NO concentrations in the exhaled air by chemiluminescence analyzer and nasal clearance time (NCT) by saccharin test. Exhaled NO concentrations in patients with SBS were 39% of those in healthy nonsmokers and 55% of those in healthy smokers. The patients also showed prolonged NCT compared with healthy subjects, and there was a significant negative correlation between exhaled NO concentrations and NCT. Furthermore, concentrations of chloride (Cl) in the sputum supernatant were higher in SBS patients than in healthy subjects, and there was a significant negative correlation between sputum Cl concentrations and exhaled NO concentrations. These results suggest that airway mucociliary clearance is impaired in patients with SBS and that this impairment might result from the reduced production of NO and the impaired availability of the molecule in the mucociliary apparatus.