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PubMed2005

Breath acetone predicts plasma ketone bodies in children with epilepsy on a ketogenic diet.

OBJECTIVE: The high-fat ketogenic diet has long been used to treat refractory childhood seizures, but whether there is a relation between the degree of ketosis and effectiveness of seizure control remains unclear. Frequent measurements of plasma ketones are difficult in children so the goal was to determine the utility of breath acetone as a marker of systemic ketosis and seizure control in children given the ketogenic diet because of seizures refractory to medication. METHODS: In experiment I, breath acetone and plasma ketones were assessed every 2 h during an 8-h test day in seven children. In experiment II, a preliminary assessment of the possible relation between breath acetone and seizure frequency was made over 14 d in five children and one adolescent on the ketogenic diet. RESULTS: Breath acetone was positively and curvilinearly related to plasma acetone (r2 = 0.99, P < 0.0001), plasma acetoacetate (r2 = 0.89, P < 0.0001), and plasma beta-hydroxybutyrate (r2 = 0.94, P < 0.0001). No significant relation was found between breath acetone and seizure frequency or change in seizure frequency. CONCLUSIONS: Breath acetone is indicative of systemic ketosis while on the ketogenic diet. However, owing to the wide range of seizure types and plasma acetone, more subjects will be needed to determine whether there is a clear link between breath acetone and seizure frequency or decreased seizure frequency while on the high-fat ketogenic diet.

Adolescent↗
PubMed2003

Evaluation of objective measures of smoking status--a prospective clinical study in a group of head and neck cancer patients treated with radiotherapy.

The present study was undertaken to evaluate objective measures of the smoking status of head and neck cancer patients during the course of radiotherapy. This was done by conducting a weekly structured interview, and measurement of carbon monoxide in expired air and of serum concentration of cotinine, the major metabolite of nicotine. These methods were tested prospectively in a series of 20 patients with head and neck cancer treated with radiotherapy. The results showed significant differences in the levels of end-expired carbon monoxide as well as serum cotinine among the different self-reported smoking groups. Combining the two objective measures and the interview data, the study revealed that up to 50% of self-reported non-smokers were in fact smoking actively. Measurement of end-expired carbon monoxide levels was found to be a precise indicator of smoking in the hours preceding measurement. Serum cotinine was a valuable measure of true smoking status. Assuming that this assay reflects the true smoking status, sensitivity, specificity and positive predictive value of self-reporting in this patient population was 79%, 80%, and 92%, respectively. In research aiming to investigate possible relations between smoking and radiotherapy, it is recommended that patients' smoking status be evaluated objectively as a supplement to self-reporting, at least in the head and neck cancer patients.

Aged↗
PubMed1991

Biomarkers of aging: changes in circadian rhythms related to the modulation of metabolic output.

Twenty-four hour (circadian) rhythmicity is an important component of biological variability associated with studies relating to biomarkers of aging. Chronobiological testing techniques must be utilized because (1) many variables that are related to the modulation of metabolic output vary dramatically at different times of the day; (2) various experimental variable and treatment groups must be synchronized with environmental cues that control circadian rhythms; and (3) multiple circadian variables may interact together to modulate the rate of aging. The rhythm for physiological factors such as whole animal metabolic output, body temperature, heart rate, urine flow, potassium, etc. were found to be dissociated or altered by the senescence process; behavioral variables such as spontaneous activity, wheel running, feeding and drinking, verbal performance, as well as sleep-wakefulness rhythms, seem to be accurate predictors of biological age. Circadian rhythms for a variety of enzymes of intermediary metabolism which are directly associated with energy metabolism have been well documented. These well-defined rhythms of enzyme activity have also been shown to degenerate with aging. Rhythms tend to lose amplitude as activity falls with age and as a general loss of regulation (especially time of day where maximal activity might be found) of activity across the 24-h span occurs. As with behavioral variables, changes in enzyme rhythms appear to accurately predict aging. Generally speaking, the loss of temporal organization with age, characterized by decreased circadian amplitude, loose internal synchronization, and poor response to external environmental time queues, is associated with poor health states and decreased longevity. Temporal rhythms for whole animal parameters are highly correlated with molecular events, such as regulation of cellular metabolism. DNA repair, and gene expression. Automated data acquisition and process control systems will be required for future chronobiological studies to develop biomarkers of aging.

Aging↗
PubMedDate not supplied

Marriage of a medium-term liver model to surrogate markers--a practical approach for risk and benefit assessment.

The need for a reliable medium-term alternative to traditional long-term rodent test protocols for carcinogen risk assessment is pressing given the immense variety of compounds being developed for introduction into the human environment. The established lack of a complete correlation between mutagenicity and carcinogenicity means that recourse must be made to an in vivo model. Optimally, this model should be able to detect not only complete carcinogenic or promoting potential but also any ability to inhibit neoplasia. In order to be effective, it must take into account the available detailed knowledge on mechanisms of action of carcinogens and modulating agents. The Ito model, for which a uniquely comprehensive set of background data has already been accumulated, has a solid scientific basis; this model utilizes quantitative data for glutathione S transferase-positive foci as the preneoplasia-based surrogate end point (PSE). A very practical candidate for routine application, its predictive power, its flexibility, and its capacity to incorporate a range of mechanism-based surrogate end points (MSEs) provide a powerful tool for attainment of the twin goals of detecting carcinogenic agents and identifying promising chemopreventors.

Animals↗
PubMed2005

Sensitive and accurate analyses of free 3-nitrotyrosine in exhaled breath condensate by LC-MS/MS.

The quantitative determination of 3-nitro-l-tyrosine, a biological marker for inflammatory processes, in exhaled breath condensate (EBC) is described. The clean-up and preconcentration was performed by solid phase extraction (SPE). After liquid chromatography the specific detection was performed by tandem mass spectrometry using electron spray ionisation and selected reaction monitoring (SRM). 13C9-3-nitrotyrosine was used as an internal standard. For reliability, tests for the precision of the method, the losses during preparation, a test for nitrating artifacts and the comparibility of calibrants in EBC and buffer solution were performed. The calibration of the method was linear over a range of 10-500 pg/mL. The within-run coefficients of variation (CV) of the samples were found to be 8.4% at 25 pg/mL and 8.3% at 250 pg/mL. The day-to-day CV was found to be 11.2%. The limit of quantification was 3.9 pg/mL. The losses during preparation were 15%. The discrepancy between the calibration with EBC and buffer solution was below 10%. No artificial production of 3-nitrotyrosine was observed during the procedure. The application of the method on the EBC samples of healthy smokers (N=10) and non-smokers (N=10) showed no difference between the two groups. The concentration of 3-nitrotyrosine ranged between the limit of quantification and 184 pg/mL and was distinctly lower than data detected by an immunoassay procedure. The procedure was proven to be accurate, sensitive and in contrast to GC methods less elaborate and is recommended for the determination of 3-nitrotyrosine in exhaled breath condensate.

Adult↗
PubMed2004

The effects of exercise on markers of lipid peroxidation in renal dialysis patients compared with control subjects.

PURPOSE: The purpose of this study was to compare the susceptibility to exercise-induced lipid peroxidation of patients on chronic maintenance dialysis (CMD) and non-CMD control subjects. DESIGN: Cross-sectional comparison of exercise-induced changes in breath ethane and pentane flux between patients on CMD (group A) and an age-, gender-, medical diagnosis-, smoking-, and ethanol consumption-matched comparison group (group B). Breath ethane and pentane were measured at rest before exercise, during cardiopulmonary exercise stress testing (CPX) at lactic acidosis threshold (Vo2lat), and 5 minutes after CPX. RESULTS: Group comparisons of clinical characteristics reveal that the groups were similar in terms of age, ethnicity, comorbid diagnoses, prevalence of medication use, BMI, measurements of aerobic exercise capacity, cigarette smoking and ethanol consumption behaviors. All subjects successfully completed the CPX protocol achieving Vo2lat. There were significant differences in breath ethane flux between group A and B subjects, with greater pre-exercise, Vo2lat, and postexercise ethane levels in group A compared with group B subjects, and significant group differences, with lower breath ethane/pentane flux ratios at rest, Vo2lat, and recovery with lower ratios in group B than group A subjects. DISCUSSION/CONCLUSIONS: This study shows that patients on CMD have greater lipid peroxidation compared with control subjects at rest and during and after physical exercise. In addition, compared with control subjects, patients on CMD preferentially peroxidize n-3 polyunsaturated fatty acids at rest and during physical exercise and recovery. The lipid peroxidation profile may result in an unfavorable endoperoxide shift and should be evaluated further, along with modalities to reduce oxidative stress among patients on CMD.

Adult↗
PubMed2002

Exhaled nitric oxide and exercise tolerance in severe COPD patients.

To answer the question as to whether pulmonary rehabilitation programs (PRP) induced increase in exercise tolerance (ET) is associated with increased levels of exhaled nitric oxide (eNO) in COPD patients of different degrees of severity, we designed a prospective and controlled study. Forty-seven stable COPD patients underwent an 8-week outpatient multidisciplinary PRP including supervised incremental exercise. Fractional eNO concentration (FE(NO)) and peak work-rate (W(peak) were assessed baseline (T-1), atthe end of 1-month run-in period (T0), and after (T1) the PRP. Lung function, walking test, health-related quality of life (HRQL) were also recorded. Patients were divided into three groups according to disease severity: 17 severe [FEV1 35 (5)% pred] COPD patients, seven of them with cor pulmonale; 15 mild [FEV1 78 (6)% pred], and 15 moderate [FEV1 56 (6)% pred] COPD patients. FE(NO) did not differ at T-1 and T0 (mean absolute change (SD): 0.03 (0.09) 95% CI-0.01, 0.16, 0.06 (1.03) 95% CI 0.03, 0.75 and 0.05 (0.06) 95% CI 0.02, 0.11 ppb in mild, moderate and severe patients, respectively). As compared to T0, both W(peak) (by 17,15 and 10%, respectively) and FE(NO) (by 29, 24 and 16%, respectively) significantly increased in all groups, but not in patients with cor pulmonale. A significant correlation between pre- and post-PRP changes in Wpeak and FE(NO) was found both in mild to moderate (r = 0.79, P < 0.00001) and severe (r = 0.76, P < 0.001) COPD patients. After a PRP, improvement in ET is associated with an increase in eNO also in most severe COPD patients, but not in those with cor pulmonale.

Aged↗
PubMed1998

[Usefulness of CO measurement in expired air in the study of tobacco consumption by youths and adolescents].

The objective of our work was to know the relationship between carbon monoxide (CO) levels in expired air and smoking habits among school youths and the relationships that can be established between CO level and some peculiar attitudes regarding consume by youths, such as the number of cigarettes, inhaling technique and time elapsed since the last cigarette was smoked. The study, of cross-sectional design, was performed in two high school centres and a total of 777 students who answered a questionnaire and had an expired air CO sample in their own schoolroom tested were enrolled. CO determination in the schoolroom was a simple and attainable technique for the pupils, as only 32 cases (4.1%) had to be excluded due to poor collaboration or poor technique. The mean (mean and SD) CO level in the control group (n = 247), made up by non-smokers nor tobacco tasters was 4.75 (2.46) ppm, statistically lower than among smokers (p < 0.001), but with no differences compared with non smokers (n = 563), who had a CO level of 5.23 (3.4) ppm. This figure was also lower (p < 0.001) than that obtained in the smokers (12.6 [6.3] ppm), made up of 214 pupils, with a mean consume of 2.7 (1.69) cigarettes/day. Among smokers the mean abstinence time since the last cigarette was smoked was 26 (44) minutes and 54% of them admitted to have smoked in the last 10 minutes. CO in expired air correlated significantly with the number of smoked cigarettes (r = 0.58; p < 0.001). Likewise, it correlated significantly with abstinence minutes (r = -0.38; p < 0.001). The time required for CO level to decrease below 10 ppm was 140 minutes in four cases and 120 minutes in 33 cases.

Adolescent↗
PubMed1997

Increased nitric oxide in exhaled air of patients with systemic lupus erythematosus.

OBJECTIVE: In experimental animals, elevated nitric oxide (NO) production has been implicated in the pathogenesis of a lupus-like syndrome. Abnormalities of lung function tests are reported in a high proportion of patients with systemic lupus erythematosus (SLE). We investigated whether NO output in exhaled air might be increased in patients with SLE and whether it is related to disease activity and to respiratory function abnormalities. METHODS: Lung volume, maximal expiratory flow at 50 and 25% of vital capacity (MEF50 and MEF25), diffusion coefficient for carbon monoxide (KCO), and NO in the exhaled air were measured in 27 outpatients with SLE (23 women, age 39.2 +/- 16.3). NO in exhaled air was also measured in 30 healthy control subjects. Disease activity was assessed by the European Consensus Lupus Activity Measurement (ECLAM) scoring system. RESULTS: Mean values of peak concentrations of NO exhaled air were 64.8 +/- 27.9 parts per billion (ppb) in patients and 31.6 +/- 7.7 ppb in controls, p < 0.001. Peak NO concentration was directly related to ECLAM activity score (p < 0.05) and inversely related to MEF25 (p < 0.05). CONCLUSION: NO in exhaled air is significantly increased and correlated with disease activity in patients with SLE. Whether increased NO output depends on respiratory tract inflammation, as the relationship with MEF25 may suggest, or on circulating cytokines produced elsewhere remains to be investigated.

Adolescent↗
PubMed2005

Liquid chromatography/mass spectrometry analysis of exhaled leukotriene B4 in asthmatic children.

BACKGROUND: The role of leukotriene (LT) B4, a potent inflammatory mediator, in atopic asthmatic and atopic nonasthmatic children is largely unknown. The lack of a gold standard technique for measuring LTB4 in exhaled breath condensate (EBC) has hampered its quantitative assessment in this biological fluid. We sought to measure LTB4 in EBC in atopic asthmatic children and atopic nonasthmatic children. Exhaled nitric oxide (NO) was measured as an independent marker of airway inflammation. METHODS: Fifteen healthy children, 20 atopic nonasthmatic children, 25 steroid-naïve atopic asthmatic children, and 22 atopic asthmatic children receiving inhaled corticosteroids were studied. The study design was of cross-sectional type. Exhaled LTB4 concentrations were measured using liquid chromatography/mass spectrometry-mass spectrometry (LC/MS/MS) with a triple quadrupole mass spectrometer. Exhaled NO was measured by chemiluminescence with a single breath on-line method. LTB4 values were expressed as the total amount (in pg) of eicosanoid expired in the 15-minute breath test. Kruskal-Wallis test was used to compare groups. RESULTS: Compared with healthy children [87.5 (82.5-102.5) pg, median and interquartile range], exhaled LTB4 was increased in steroid-naïve atopic asthmatic [255.1 (175.0-314.7) pg, p < 0.001], but not in atopic nonasthmatic children [96.5 (87.3-102.5) pg, p = 0.59)]. Asthmatic children who were receiving inhaled corticosteroids had lower concentrations of exhaled LTB4 than steroid-naïve asthmatics [125.0 (25.0-245.0) pg vs 255.1 (175.0-314.7) pg, p < 0.01, respectively]. Exhaled NO was higher in atopic nonasthmatic children [16.2 (13.5-22.4) ppb, p < 0.05] and, to a greater extent, in atopic steroid-naïve asthmatic children [37.0 (31.7-57.6) ppb, p < 0.001] than in healthy children [8.3 (6.1-9.9) ppb]. Compared with steroid-naïve asthmatic children, exhaled NO levels were reduced in asthmatic children who were receiving inhaled corticosteroids [15.9 (11.5-31.7) ppb, p < 0.01]. CONCLUSION: In contrast to exhaled NO concentrations, exhaled LTB4 values are selectively elevated in steroid-naïve atopic asthmatic children, but not in atopic nonasthmatic children. Although placebo control studies are warranted, inhaled corticosteroids seem to reduce exhaled LTB4 in asthmatic children. LC/MS/MS analysis of exhaled LTB4 might provide a non-invasive, sensitive, and quantitative method for airway inflammation assessment in asthmatic children.

Asthma↗
PubMed2005

Pulmonary infections increase exhaled nitric oxide in lung transplant recipients: a longitudinal study.

The aim of this longitudinal study was to test whether pulmonary infections influence fractional exhaled nitric oxide levels (FENO) in otherwise clinically-stable lung transplant recipients. Levels of FENO were measured at least on 11 occasions in nine lung transplant recipients who attended for routine or urgent clinical review over 27.0 +/- 3.2 months period. Diagnosis of infection was based on clinical symptoms, functional measurements and radiological findings. Concentrations of FENO were also determined in 12 healthy volunteers. During follow-up, six patients had one, two had three, and one had four episodes of pulmonary infections. Overall, six upper and 10 lower respiratory tract infections were noted. Recipients with active infections developed increased FENO levels as compared with their own baseline levels measured in the clinically well period (10.8 +/- 1.3 vs. 7.6 +/- 1.1 ppb, p < 0.05). After antibiotic treatment, elevated FENO concentrations returned to baseline in association with full clinical recovery. Baseline FENO levels in lung transplant recipients and in healthy volunteers (6.0 +/- 0.5 ppb) were similar. The sensitivity and specificity of FENO measurement in detecting pulmonary infections were 57 and 96%, respectively. Our data suggest that pulmonary infections are associated with increased FENO levels in patients with lung allografts. Nevertheless, the measurement of FENO by itself as a screening tool for infections seems to be limited by its low sensitivity.

Adult↗
PubMed2001

Exhaled and nasal nitric oxide as a marker of pneumonia in ventilated patients.

Because inflammation stimulates the expression of inducible nitric oxide (NO) synthase (iNOS) with an associated increased local NO production, we hypothesized that patients with pneumonia would have increased excretion of NO into their airways. To test this hypothesis, NO was measured in the exhaled air and from the nasal cavities of 49 consecutively intubated and mechanically ventilated patients in our ICU. After excluding NO gas contamination in the inspiratory circuit, nasal NO and end-expiratory and mean exhaled tracheal NO levels and plasma nitrate concentrations were measured using a fast response chemiluminescence analyzer. Twenty-one patients (43%) presented with infectious pneumonia. End- expiratory exhaled NO concentrations were significantly higher in patients with pneumonia as compared with patients without pneumonia (5.9 +/- 1 ppb versus 3.2 +/- 0.5 ppb, p < 0.01). Similarly, mean nasal NO was higher in patients with pneumonia (1039 +/- 138 ppb versus 367 +/- 58 ppb, p = 0.003). Plasma nitrate levels did not differ between patient groups. Threshold values of tracheal or nasal NO were defined and subsequently validated in 60 other patients. Positive and negative values of a maximal tracheal level > 5 ppb for pneumonia were 74% and 89%, respectively. Thus tracheal and nasal NO levels may be of help in distinguishing patients with acute pneumonia from other causes. Furthermore, because these differences in airway NO levels were not paralleled in blood nitrite concentrations, we conclude that pneumonia per se is not associated with systemic NO production.

Biomarkers↗
PubMed2006

Correlates of B-type natriuretic peptide and 6-min walk in heart failure patients.

BACKGROUND: B-type natriuretic peptide (BNP) and 6-min walk test (6MWT) are both related to the severity and prognosis in chronic heart failure (CHF), but may reflect different aspects of CHF. We related BNP and 6MWT to left ventricular ejection fraction (LVEF), New York Heart Association functional class (NYHA), and two indices of quality of life (physical subscales): the Minnesota Living with Heart Failure Questionnaire (MLwHFQph) and the RAND-36ph. METHODS: Plasma BNP and 6MWT were measured at discharge in 229 patients who had been admitted for CHF. LVEF and NYHA were determined, and patients completed the MLwHFQ and RAND-36 questionnaires. RESULTS: BNP was weakly correlated to LVEF (r=-0.29, P<0.01) and NYHA (r=0.20, P<0.01), but not to MLwHFQph and RAND-36ph. On the other hand, 6MWT is related to MLwHFQph (r=-0.23, P<0.01), RAND-36ph (r=0.52, P<0.01), and NYHA (r=-0.46, P<0.01), but not to LVEF (r=-0.15, P=0.05). There is also no correlation between BNP and 6MWT (r=-0.01, P=0.87). CONCLUSIONS: The present data show that BNP and 6MWT represent different aspects of the clinical syndrome of CHF. The outcomes of this study suggest that BNP plasma levels are more related to cardiac function, while 6MWT reflects functional capacity and quality of life.

Aged↗
PubMed2005

Self-reported smoking status and exhaled carbon monoxide: results from two population-based epidemiologic studies in the North of England.

STUDY OBJECTIVES: To investigate the validity of self-reported responses to questions on current smoking in two cohorts based in Northern England. DESIGN: A cross-sectional population-based study (the Newcastle Heart Project [NHP]) and a follow-up of the Newcastle Thousand Families birth cohort established in 1947. PATIENTS OR PARTICIPANTS: Participants included 1,189 members of the NHP and 410 members of the Newcastle Thousand Families cohort who completed a health and lifestyle questionnaire, including questions on current smoking, and attended a clinical examination, including testing for exhaled carbon monoxide between April 1993 and December 1998. RESULTS: The number of self-reporting smokers for whom very low (ie, < 6 ppm) exhaled carbon monoxide levels were recorded varied between 9% in the Newcastle Thousand Families Study and 26% among the members of the NHP who were of South Asian origin. Using a cutoff of 8 ppm, 80% of self-reported smokers were identified in both the Newcastle Thousand Families study and in the NHP European population, but only 60% were identified in the NHP South Asian population. In each population, < 7% of nonsmokers had exhaled carbon monoxide measurements of > 6 ppm, with nonsmoking men more likely to have higher levels than nonsmoking women. Among the nonsmokers, the levels of exhaled carbon monoxide did not vary with respect to the smoking status of a partner or socioeconomic status. CONCLUSIONS: Using a cutoff value of 6 ppm would potentially miss a large number of smokers, although this may vary with ethnicity. Epidemiologic studies should continue to use biochemical markers to validate responses to smoking surveys. However, the use of exhaled carbon monoxide measurements as a method of assessing the validity of self-reported smoking status may require additional analyses of whether the cutoff level should vary for different populations.

Adult↗
PubMed2006

The effect of allergic rhinitis on adenosine concentration in exhaled breath condensate.

BACKGROUND: Patients with allergic rhinitis (AR) frequently develop asthma. This initiating inflammation in the lower airways may result in increased levels of inflammatory mediators such as adenosine in the exhaled breath. OBJECTIVE: We compared adenosine levels in exhaled breath condensate (EBC) and both exhaled and nasal nitric oxide (NO) levels of AR patients and healthy control subjects. We also tested whether inhalation through inflamed nasal cavity during EBC sampling influences adenosine concentrations in exhaled air. METHODS: Exhaled and nasal NO levels were measured and EBC samples (at oral inhalation) were collected from 27 patients and 15 healthy controls. EBC collection was repeated after 15 min with subjects inhaling through their nose. Adenosine was measured by HPLC and NO was determined by chemiluminescence. RESULTS: The concentration of EBC adenosine was higher in patients with AR than in healthy controls (12.4+/-1.3 nM vs. 6.5+/-0.7 nM, P=0.0019) and this was accompanied by an increase in the concentration of exhaled NO (10.2+/-1.3 ppb vs. 5.3+/-0.5 ppb; P=0.0099, respectively). No difference in nasal NO was detected. EBC adenosine concentration showed a significant positive correlation with the level of exhaled NO. In contrast to healthy control subjects, patients with rhinitis had higher levels of exhaled adenosine when inhaling via the nose instead of the mouth (17.7+/-2.8 nM, P=0.007). CONCLUSION: When compared with healthy subjects, patients with AR exhibit an increased concentration of exhaled adenosine and a related increase in exhaled NO concentration. EBC adenosine is further increased when rhinitis patients inhale through their nose than via their mouth. Our data suggest that non-asthmatic patients with rhinitis may have subclinical inflammation in their lower airways.

Adenosine↗
PubMed2000

The use of structure-activity relationships and markers of cell toxicity to detect non-genotoxic carcinogens.

In contrast to the situation for genotoxic carcinogens, few in vitro tests exist that can detect early markers of the events thought to be associated with non-genotoxic carcinogenesis. Also, comparatively little is known about the quantitative structure-activity relationships (Q)SARs of these agents. This review discusses published SAR studies conducted on non-genotoxic carcinogens, in relation to the use of several markers of in vitro cell toxicity (inhibition of gap-junctional intercellular communication, inhibition of tubulin polymerization, modulation of apoptosis and induction of cell proliferation), which are used as endpoints for screening this class of carcinogen. Much of the work has involved the identification of new biophores (substructural features of molecules associated with toxicity), as well as other structural features, which are thought to predispose the chemicals to ligand binding with specific target molecules acting as possible receptors (e.g. protein kinase C, the oestrogen, peroxisome-proliferator and tubulin protein receptors), implicated in the mechanism of toxicity involved. It is concluded that (a) there is an urgent need for more information on (Q)SARs for non-genotoxic carcinogens; (b) this information should be acquired by using several different approaches in a variety of laboratories; and (c) such research should proceed together with more studies on the mechanisms of cell toxicity caused by these chemicals, including the identification and characterisation of further specific receptors involved in mediating the various types of cell toxicity associated with this type of carcinogenesis.

Animals↗
PubMed2005

Exhaled breath condensate cysteinyl leukotrienes are increased in children with exercise-induced bronchoconstriction.

BACKGROUND: It is recognized that airway inflammation has a central role in the pathogenesis of asthma, but how it relates to exercise-induced bronchoconstriction (EIB) is not completely understood. OBJECTIVE: The aim of our study was to investigate the relationship between EIB and baseline concentrations of cysteinyl leukotrienes (Cys-LTs) and other inflammatory markers in exhaled breath condensate (EBC). METHODS: EBC was collected, and the fraction of exhaled nitric oxide (FE NO ) was measured in a group of 19 asthmatic children, after which they performed a treadmill exercise test. Fourteen healthy children were enrolled as control subjects. RESULTS: The asthmatic children were divided into the EIB group (decrease in FEV 1 , > or =12%) and the non-EIB group. The EBC was analyzed for the presence of Cys-LTs, leukotriene B 4 , and ammonia. Asthmatic patients with EIB (mean FEV 1 decrease, 23% +/- 3%) had higher Cys-LT concentrations than either asthmatic patients without EIB or control subjects (42.2 pg/mL [median] vs 11.7 pg/mL and 5.8 pg/mL; P < .05 and P < .001, respectively). Ammonia concentrations were lower in both the EIB and non-EIB groups than in control subjects (253.2 microM and 334.6 microM vs 798.4 microM; P < .01 and P < .05, respectively). No difference in EBC leukotriene B 4 levels was found among the 3 groups. Both asthmatic groups had higher FE NO levels than control subjects ( P < .001). EBC Cys-LT ( P < .01; r = 0.7) and FE NO ( P < .05; r = 0.5) values both correlated significantly with the postexercise FEV 1 decrease. CONCLUSION: this study shows that EBC Cys-LT values are higher in asthmatic children with EIB and correlate with the decrease in FEV 1 after exercise. These findings suggest that the pathways of both Cys-LT and nitric oxide are involved in the pathogenesis of EIB.

Acetates↗
PubMed2006

Exhaled nitric oxide as a diagnostic test for asthma in rhinitic patients with asthmatic symptoms.

BACKGROUND: Rhinitis is a major risk factor for asthma, so that evaluation of the lower airways is recommended in patients with rhinitis. Exhaled nitric oxide (FE(NO)) is considered a marker of airway inflammation and it has been found to be useful for the screening of patients with suspected diagnosis of asthma. Our aim was to assess the validity and accuracy of FE(NO) to identify patients with asthma in 48 non-smoking patients with persistent rhinitis and asthma-like symptoms. METHODS: Asthma was diagnosed on the basis of 12% improvement in FEV1 after salbutamol or a methocholine PD(20)FEV1<800 microg. Prior to lung function FE(NO) was measured with the single exhalation method at 50 ml/s. RESULTS: The geometric mean (95% confidence interval) FE(NO) was significantly higher in the 18/48 asthmatics than in the non-asthmatic patients (60 ppb, CI 95%: 50-89, versus 30 ppb, CI 95%: 28-45, P=0.001). Receiver operating characteristic (ROC) curve for the diagnosis of asthma indicated that FE(NO) is an acceptable discriminator between patients with and without asthma (area under the ROC curve=0.78). None of the asthmatic patients had FE(NO) values<25 ppb and all the patients with FE(NO)>100 ppb (n=5) were asthmatics. The sensitivity and specificity of FE(NO) for detecting asthma, using 36 ppb as cut-off point, were 78% and 60% and the positive and negative predictive values were 54% and 82%, respectively. CONCLUSIONS: Measuring FE(NO) may be useful for the screening of rhinitic patients with asthma-like symptoms.

Adolescent↗