Peculiarities of changes of the endothelium-dependent and endothelium-independent vascular reactions of relaxation, and the content of oxygen free radicals and stable metabolites of nitric oxide (NO) were studied in the aorta preparations of BALB/c mice of the two age groups (6 and 18 months), which were born and lived in the Chernobyl alienation zone. The results obtained showed no endothelium-dependent reactions of aortal smooth muscles relaxation to acetylcholine and only partially impaired endothelium-independent reactions to sodium nitroprusside in animals of both age groups. There was a significant decrease in the content of high-molecular nitrosothiols (HMNT) in old animals, which may signify a depletion of NO depot in the aorta. A decrease of HMNT levels induced an increase of the shares of anion nitrite and low-molecular nitrosothiols (LMNT) in the total amount of endogenous donors of NO in the aorta of old animals. Exposure of old animals to low doses of radiation resulted in an over 3-fold increase of LMNT. In old mice the levels of oxygen active forms, superoxide and hydroxyl radicals increase, while the level of H2O2 remained unchanged.
Occurrence of airway irritation among indoor swimming pool personnel was investigated. The aims of this study were to assess trichloramine exposure levels and exhaled nitric oxide in relation to the prevalence of airway symptoms in swimming pool facilities and to determine protein effects in the upper respiratory tract.
The presence of airway symptoms related to work was examined in 146 individuals working at 46 indoor swimming pool facilities. Levels of trichloramine, as well as exhaled nitric oxide, were measured in five facilities with high prevalence of airway irritation and four facilities with no airway irritation among the personnel. Nasal lavage fluid was collected, and protein profiles were determined by a proteomic approach.
17 % of the swimming pool personnel reported airway symptoms related to work. The levels of trichloramine in the swimming pool facilities ranged from 0.04 to 0.36 mg/m(3). There was no covariance between trichloramine levels, exhaled nitric oxide and prevalence of airway symptoms. Protein profiling of the nasal lavage fluid showed that the levels alpha-1-antitrypsin and lactoferrin were significantly higher, and S100-A8 was significantly lower in swimming pool personnel.
This study confirms the occurrence of airway irritation among indoor swimming pool personnel. Our results indicate altered levels of innate immunity proteins in the upper airways that may pose as potential biomarkers. However, swimming pool facilities with high prevalence of airway irritation could not be explained by higher trichloramine exposure levels. Further studies are needed to clarify the environmental factors in indoor swimming pools that cause airway problems and affect the immune system.
Three vital respiratory gases-oxygen (O(2)), nitric oxide (NO), and carbon dioxide (CO(2))-intersect at the level of the human red blood cell (RBC). In addition to hemoglobin (Hb)'s central role in O(2) transport, interaction of Hb with the Band 3 metabolon balances RBC energy flow. 2,3-Diphosphoglycerate enhances O(2) transport across the placenta and plays an important role in regulating RBC plasticity. NO is a key mediator of hypoxic vasodilation, but the precise role of RBC Hb remains controversial. In addition to established theories that depend on RBC uptake, delivery, and discharge of NO or its metabolites, an alternative hypothesis based on RBC permeability is suggested. NO depletion by free Hb may account for several clinical features seen during intravascular hemolysis or during deliberate infusion of Hb solutions used as RBC substitutes. CO(2) released by tissues triggers oxygen release through a series of well-coordinated reactions centered on the Band 3 metabolon. While RBC carbonic anhydrase and the Band 3 anion exchanger are central to this process, there is surprisingly little research on the kinetics of CO(2) clearance by transfusion. The three RBC gases are directly related to the three principal gases of Earth's atmosphere. Human fossil fuel consumption dumps 90 million metric tons of carbon into the atmosphere annually. Increasing CO(2) levels are linked to global warming, melting Arctic ice, rising sea levels, and climate instability. Just as individual cells depend on balance of the three vital gases, so too will their balance determine survival of life on Earth.
276 Patients with bronchial asthma of different degree of severity have been observed. An increase in processes of lipid peroxidation, depression of antioxidant protection, increase in oxide nitrogen metabolites in blood serum and condensate of exhaled air were detected. These pathological changes may be considered as manifestation of system oxidative stress more expressed in bronchi.
Our aim was to study the role of oxidant and nitric oxide (NO)-derived damage in human breast carcinomas by studying the expression of nitrotyrosine in tumor tissue. To elucidate whether nitrotyrosine levels associate with NO synthesis and have an effect on antioxidative enzyme response or angiogenesis, we also studied the expression of all three nitric oxide synthases (NOS), manganese superoxide dismutase (MnSOD), catalase and vascular endothelial growth factor (VEGF) in the tumors. A large set of breast cancer samples in microarray blocks were stained with antibodies to nitrotyrosine, iNOS, eNOS, nNOS, MnSOD, catalase and VEGF. Nitrotyrosine expression was seen in 56% of the cases. There was a close relationship between the expression of nitrotyrosine and all three NOS isoforms (for all p
This study was designed to evaluate whether plasma asymmetric dimethylarginine (ADMA) has any role in predicting hemodynamic responses in clinically healthy young subjects. ADMA, as an endogenous nitric oxide (NO) synthase inhibitor, has been demonstrated to associate with hypertension and vascular reactivity in experimental but not undoubtedly in physiological settings.
A total of 199 subjects aged 31.4 years (range 24-39 years) were studied. Plasma ADMA and symmetric dimethylarginine (SDMA) were assessed by isocratic high-pressure liquid chromatography using precolumn derivatization with o-phtaldialdehyde at baseline. Blood pressure (BP) was measured by casual measurements in the beginning of the study and after a follow-up period of 2.45 +/- 0.42 years (range, 1.86-3.19 years). Hemodynamic regulation was assessed by noninvasive methods after a follow-up.
Plasma ADMA had a negative association with resting systemic vascular resistance index (SVRI) (r = -0.23, P
Studies of children's blood lipid profiles in relation to asthma are few, and the results are ambiguous.
We sought to examine whether the lipid profile is associated with concurrent asthma, altered lung function, and allergic sensitization in children.
High-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were measured at ages 5 to 7 years in the Copenhagen Prospective Studies on Asthma in Childhood2000 at-risk birth cohort. Asthma and allergic rhinitis were diagnosed based on predefined algorithms at age 7 years along with assessments of lung function, bronchial responsiveness, fraction of exhaled nitric oxide (Feno), and allergic sensitization. Associations between lipid levels and clinical outcomes were adjusted for sex, passive smoking, and body mass index.
High levels of low-density lipoprotein cholesterol were associated with concurrent asthma (adjusted odds ratio [aOR], 1.93; 95% CI, 1.06-3.55; P = .03) and airway obstruction: 50% of forced expiratory flow (aß coefficient, -0.13 L/s; 95% CI, -0.24 to -0.03 L/s; P = .01) and specific airway resistance (aß coefficient, 0.06 kPa/s; 95% CI, 0.00-0.11 kPa/s; P = .05). High levels of high-density lipoprotein cholesterol were associated with improved specific airway resistance (aß coefficient, -0.11 kPa/s; 95% CI, -0.21 to -0.02; P = .02), decreased bronchial responsiveness (aß coefficient, 0.53 log-µmol; 95% CI, 0.00-1.60 log-µmol; P = .05), decreased risk of aeroallergen sensitization (aOR, 0.27; 95% CI, 0.01-0.70; P = .01), and a trend of reduced Feno levels (aß coefficient, -0.22 log-ppb; 95% CI, -0.50 to 0.01 log-ppb; P = .06). High triglyceride levels were associated with aeroallergen sensitization (aOR, 2.01; 95% CI, 1.14-3.56; P = .02) and a trend of increased Feno levels (aß coefficient, 0.14 log-ppb; 95% CI, -0.02 to 0.30 log-ppb; P = .08).
The blood lipid profile is associated with asthma, airway obstruction, bronchial responsiveness, and aeroallergen sensitization in 7-year-old children. These findings suggest that asthma and allergy are systemic disorders with commonalities with other chronic inflammatory disorders.
The reciprocal changes of NOS and arginase activity during acute myocardial ischaemia (90 min) and reperfusion (180 min) was shown in experiments on chest-closed dogs with spontaneous breathing. NOS activity in the ischemia injured myocardial decreased on 60% while arginase activity increased on 487%. Levels of both alternative pathways of L-arginine metabolism altered reciprocally too. NO2(-)-level was reduced on 57%, and urea level increased on 665%. The same changes were in arterial blood, started from 10 min of ischemia. These changes can play an important role for development of acute ischaemia treatment.
To better understand asthma pathogenesis, we characterized airway responsiveness, lung inflammation, and mediator production of alveolar macrophages (AM) after allergen sensitization and challenge in two strains of rats showing different susceptibilities in developing airway allergic reactions. Airway responsiveness to acethylcholine was measured 24 h after ovalbumin (OVA) challenge, whereas bronchoalveolar lavages were performed 5 min, 8 h, and 24 h after challenge. Brown Norway rats showed airway hyperresponsiveness after challenge, whereas lung resistance remained unchanged in Sprague-Dawley rats. Interestingly, Sprague-Dawley rats developed a neutrophilic inflammation, whereas both neutrophils and eosinophils were increased in Brown Norway rats. AM mediator production varied with time with a lower tumor necrosis factor (TNF) and interleukin (IL)-10 release at 8 h after challenge. OVA challenge stimulated spontaneous TNF and IL-10 release by AM isolated 24 h after challenge in both strains of rats, although AM from Brown Norway rats released significantly more IL-10 and TNF. Furthermore, nitric oxide production was increased only in OVA-challenged (24 h) Brown Norway rats. Our results suggest that AM may participate to the expansion of Th2 inflammation in Brown Norway rats and that differences in AM mediator production may explain, in part, distinct allergic susceptibilities in these two strains of rats.
Patients with cirrhosis often develop a systemic vasodilatation and a hyperdynamic circulation with activation of vasoconstrictor systems such as the renin-angiotensin-aldosterone system (RAAS), and vasopressin. Increased nitric oxide (NO) synthesis has been implicated in the development of this state of vasodilation and pulmonary dysfunction including increased exhaled NO concentrations. Circulating metabolites (NO(x)) may affect the systemic and pulmonary NO-generation. However, the relations of these abnormalities to the haemodynamic changes remain unclear.
The aims of the present study were to measure changes in exhaled NO in relation to circulating NO(x), RAAS, and haemodynamics.
Twenty patients (eight child class A and 12 class B patients) underwent a liver vein catheterization with determination of splanchnic and systemic haemodynamics. Circulating NO(x) and exhaled NO were determined in the supine and sitting positions and related to haemodynamics, RAAS and lung diffusing capacity (D(L)CO). Eight matched healthy individuals served as controls.
All patients with cirrhosis had portal hypertension. We found no significant difference in exhaled NO between patients and controls and no changes from the supine to the sitting position. Exhaled NO in the patients correlated significantly with plasma volume, heart rate and D(L)CO. NO(x) concentrations were not significantly increased in the patients. NO(x) correlated with portal pressure and haemodynamic indicators of vasodilatation, but not with exhaled NO concentrations.
In patients with moderate cirrhosis, exhaled NO is normal. Circulating NO(x) do not seem to reflect pulmonary and systemic NO release, but NO(x) seems to reflect systemic and splanchnic haemodynamic changes in cirrhosis.