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Biomedical subjects

S Zanconato

Publications and source records attributed to S Zanconato.

At least 19 recordsLinked to original sources

3-Nitrotyrosine, a marker of nitrosative stress, is increased in breath condensate of allergic asthmatic children.

BACKGROUND: Asthmatic patients have high exhaled nitric oxide (NO) levels. NO-mediated inflammatory actions are mainly due to NO conversion into reactive nitrogen species, which can lead to nitrotyrosine formation. The aim of this study was to assess 3-nitrotyrosine (3-NT) levels in exhaled breath condensate (EBC) of asthmatic and healthy children and to investigate whether there is any relationship with exhaled NO (FE(NO)) and lung function. METHODS: The study included 20 asthmatic children (10 steroid-naive with intermittent asthma, 10 steroid-treated with unstable persistent asthma) and 18 healthy controls. They underwent FE(NO) measurement, EBC collection and spirometry. 3-NT was measured by a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in isotopic dilution. RESULTS: The median EBC concentration of 3-NT (expressed as nitrotyrosine/tyrosine ratio x 100) in asthmatic children was fivefold higher than in healthy subjects [0.23% (0.12-0.32) vs 0.04% (0.02-0.06), P < 0.001] with no difference between steroid-naive and unstable steroid-treated asthmatic patients. FE(NO) levels were higher in asthmatic [44.6 ppb (36.0-66.0)] than in healthy children [7.5 ppb (6.0-8.8), P < 0.001]. No correlation was found among 3-NT, FE(NO) and lung function parameters. CONCLUSION: Nitrotyrosine is high in EBC of asthmatic children and could be considered as a noninvasive marker of nitrosative events in the airways.

Adolescent↗

Acid-base equilibrium in exhaled breath condensate of allergic asthmatic children.

BACKGROUND: The dysregulation of airway pH control may have a role in asthma pathophysiology. The measurement of exhaled breath condensate (EBC) pH and ammonia levels may be used as a noninvasive method to study acid-base status in the airway of asthmatics. METHODS: Exhaled breath condensate from 29 allergic stable asthmatic children and 13 healthy controls was collected by cooling exhaled air during tidal breathing. Ammonia was measured by high-performance liquid chromatography with fluorescence detection. pH was measured after deaeration of EBC samples by bubbling with argon. The children also underwent FENO measurement. RESULTS: Both pH and ammonia values in EBC were significantly lower in the asthmatics than in the control group [pH: ICS-treated (median and interquartile range) 7.70 (7.62-7.74), steroid-naive 7.53 (7.41-7.68), controls 7.85 (7.80-7.90), P <0.01 and P <0.001, respectively; ammonia: ICS-treated 476.17 microM (282.50-594.80), steroid-naive 253.24 microM (173.43-416.08), controls 788.30 microM (587.29-1310.39), P < 0.05 and P <0.001, respectively]. Both pH and ammonia values were higher in ICS-treated than in steroid-naive asthmatic children. There was a significant correlation between EBC pH and ammonia concentrations. CONCLUSIONS: These data show that EBC pH values of stable asthmatic children are lower compared with those of healthy controls and positively correlated with ammonia concentrations, supporting the hypothesis that airway acidification may have a role in the pathobiology of allergic asthma.

Acid-Base Equilibrium↗

Nasal nitric oxide is low early in life: case study of two infants with primary ciliary dyskinesia.

Nasal nitric oxide levels are low in patients with primary ciliary dyskinesia, but it is not known whether this defect is already present in the first months of life. The current authors measured nasal nitric oxide in two infants with situs inversus and primary ciliary dyskinesia, diagnosed by electron microscopy at 4 and 6 months of age, and in five healthy control infants. Nasal nitric oxide values in the primary ciliary dyskinesia infants (85 and 115 parts per billion (ppb)) were markedly lower than in the healthy controls (mean: 295 ppb, range: 225-379 ppb). This is the first report to show that nasal nitric oxide values are already low in early life in primary ciliary dyskinesia children, supporting the hypothesis that a reduced production of nasal nitric oxide is an intrinsic feature of this disease. The current authors suggest that the nasal nitric oxide test may be a useful, noninvasive method for screening young children for primary ciliary dyskinesia in clinical practice.

Ciliary Motility Disorders↗

Safety and success of exhaled breath condensate collection in asthma.

BACKGROUND: Exhaled breath condensate (EBC) is a rapidly expanding area of research to study airway inflammation through the detection of volatile and non-volatile substances in the airways. AIMS: To determine the safety and feasibility of EBC procedure in a group of children with asthma of varying severity. METHODS: In a cross sectional study of children aged 4-17 years, 18 healthy and 91 asthmatic children (69 in stable condition and 22 with asthma exacerbation) underwent the EBC procedure. Outcomes assessed included completion of the procedure, decrease in FEV1, change in fractional exhaled nitric oxide (FE(NO)), and adverse effects. No pretreatment with beta2 agonists was given. All children were able to successfully complete the EBC procedure. RESULTS: Median fall in FEV1 after the procedure was -1% (IQR -3.5, 1.8) in asthmatics and was comparable to that observed in healthy children. In only one asthmatic child did the drop in FEV1 exceed 12%. No significant changes in FE(NO) were observed after EBC. CONCLUSION: This study suggests that EBC is a simple and well tolerated method for evaluating biological samples from the lower airway. The procedure was safe in children with asthma exacerbation, and the success rate was 100% in children aged 4 years and above.

Adolescent↗

Cysteinyl leukotrienes and 8-isoprostane in exhaled breath condensate of children with asthma exacerbations.

BACKGROUND: Cysteinyl leukotrienes (Cys-LTs) and isoprostanes are inflammatory metabolites derived from arachidonic acid whose levels are increased in the airways of asthmatic patients. Isoprostanes are relatively stable and specific for lipid peroxidation, which makes them potentially reliable biomarkers for oxidative stress. A study was undertaken to evaluate the effect of a course of oral steroids on Cys-LT and 8-isoprostane levels in exhaled breath condensate of children with an asthma exacerbation. METHODS: Exhaled breath condensate was collected and fractional exhaled nitric oxide (FE(NO)) and spirometric parameters were measured before and after a 5 day course of oral prednisone (1 mg/kg/day) in 15 asthmatic children with an asthma exacerbation. Cys-LT and 8-isoprostane concentrations were measured using an enzyme immunoassay. FE(NO) was measured using a chemiluminescence analyser. Exhaled breath condensate was also collected from 10 healthy children. RESULTS: Before prednisone treatment both Cys-LT and 8-isoprostane concentrations were higher in asthmatic subjects (Cys-LTs, 12.7 pg/ml (IQR 5.4-15.6); 8-isoprostane, 12.0 pg/ml (9.4-29.5)) than in healthy children (Cys-LTs, 4.3 pg/ml (2.0-5.7), p=0.002; 8-isoprostane, 2.6 pg/ml (2.1-3.0), p<0.001). After prednisone treatment there was a significant decrease in both Cys-LT (5.2 pg/ml (3.9-8.8), p=0.005) and 8-isoprostane (8.4 pg/ml (5.4-11.6), p=0.04) concentrations, but 8-isoprostane levels remained higher than in controls (p<0.001). FE(NO) levels, which fell significantly after prednisone treatment (p<0.001), did not correlate significantly with either Cys-LT or 8-isoprostane concentrations. CONCLUSION: After a 5 day course of oral prednisone there is a reduction in Cys-LT and 8-isoprostane levels in EBC of children with an asthma exacerbation, although 8-isoprostane levels remain higher than in controls. This finding suggests that corticosteroids may not be fully effective in reducing oxidative stress in children with an exacerbation of asthma.

Adolescent↗

A case if infant botulism due to neurotoxigenic Clostridium butyricum type E associated with Clostridium difficile colitis.

Reported here is the sixth case of intestinal toxemia botulism caused by Clostridium butyricum type E in Italy since 1984. In this case, the patient was concomitantly affected with colitis due to Clostridium difficile toxin. A review of previously reported cases revealed that some of these patients may also have had intestinal toxemia botulism associated with Clostridium difficile colitis, based on the reported symptoms. Given that this association has been shown to exist not only in Italy but also in the USA, it is recommended that individuals with intestinal botulism and symptoms of colitis undergo testing for Clostridium difficile and its toxins in fecal samples.

Anti-Bacterial Agents↗

Anaphylactic reaction after skin-prick testing in an 8-year-old boy.

This paper presents the case of an 8-year-old boy who developed an anaphylactic reaction after skin-prick testing (SPT). The tests were performed with commercial extracts and were strongly positive for dog and grass. The boy had no incidence of anaphylaxis reported in his history. At the time tests were performed, he had been admitted to the hospital because of persistent wheezing and had a dog at home for a few days. Although anaphylaxis is very rare after SPTs, these tests should always be peformed in a place equipped to treat anaphylaxis.

Allergens↗

Effect of montelukast added to inhaled corticosteroids on fractional exhaled nitric oxide in asthmatic children.

The aim of this prospective, self-controlled, single-blind study was to assess the effect of montelukast added to maintenance therapy with inhaled corticosteroids (ICS) on fractional exhaled nitric oxide (FENO) in asthmatic children. Thirty-five children (age 11.2+/-0.4 yrs (mean+/-SEM)) with mild-to-moderate persistent asthma treated with low to medium doses of ICS and FENO > 20 parts per billion (ppb) were included. The patients were randomly assigned to two groups: 17 patients continued ICS (group C) and 18 had montelukast added to ICS for 3 weeks (group M). FENO measurements were performed in both groups at baseline (T1) and after 3 weeks (T2), and in group M also after 2 weeks of washout. FENO was measured by a chemiluminescence analyser using an on-line method (50 mL x s(-1)) with nitric oxide-free air. The overall mean daily dose of ICS was equivalent to 530+/-58 microg x day(-1) of beclomethasone in group M and to 564+/-55 microg x day(-1) of beclomethasone in group C. There were no significant differences in baseline FENO and forced expiratory volume in one second (FEV1) between the two groups. After 3 weeks there was a significant reduction of FENO values in patients of group M (T1 52.2+/-7.8 ppb, T2 36.1+/-4.6 ppb) but no significant changes in group C (T1 43.5+/-6.0 ppb, T2 47.8+/-9.4 ppb). In group M after 2 weeks of montelukast withdrawal, FENO rose to baseline values (55.6+/-8.7 ppb). In conclusion, after montelukast treatment there is a fractional exhaled nitric oxide reduction in asthmatic children receiving maintenance therapy with inhaled corticosteroids. This suggests an anti-inflammatory effect of montelukast additive to that of inhaled corticosteroids.

Acetates↗

Budesonide but not nedocromil sodium reduces exhaled nitric oxide levels in asthmatic children.

Exhaled nitric oxide (ENO) has been proposed as a marker of airway inflammation in asthma and could be useful to evaluate the response to anti-inflammatory treatment. We investigated the effect of budesonide and nedocromil sodium on ENO levels and lung function in asthmatic children. Twenty stable steroid-naïve asthmatic children were randomized in a single blind, cross-over study to receive inhaled budesonide (group A) or nedocromil sodium (group B) for 6 weeks. ENO was measured with a chemiluminescence analyser at baseline and at the end of each treatment period. Repeated-measures ANOVA was carried out. In asthmatic baseline ENO levels [mean 32.5 ppb, 95% confidence interval (CI) 26.4 to 38.7] were significantly higher compared to reference values (8.7 ppb, 95% CI 8.1 to 9.2, P<0.001). There were no treatment-order effect, no carry-over effect and in both groups the response pattern was the same: budesonide significantly lowered ENO levels from 41.0 ppb to 22.8 ppb in group A (mean, P<0.01) and from 22.6 ppb to 13.0 ppb in group B, (mean, P<0.05), while nedocromil did not reduce ENO values (from 24.4 ppb to 22.6 ppb in group B and from 22.8 ppb to 38.0 ppb in group A, mean, P = NS and P<0.01 respectively). After budesonide treatment ENO values of asthmatics were still significantly higher than in healthy children The baseline values of FEV1 and FEF(25-75) were normal in both groups and no significant changes were observed during the study. In conclusion, our study shows that budesonide, but not nedocromil sodium, significantly reduces ENO levels in stable asthmatic children even in absence of changes in the lung function.

Adolescent↗

Exhaled nitric oxide and exercise-induced bronchoconstriction in asthmatic children.

It is known that exhaled nitric oxide (ENO) is increased in asthmatic individuals, probably as an expression of airway inflammation, but no studies have been reported of ENO and exercise-induced bronchoconstriction (EIB). We assessed the effect of a treadmill exercise challenge on ENO concentration in 24 asthmatic children aged 11.2 +/- 0.4 yr (mean +/- SEM). According to the presence or absence of EIB, the children were divided into an EIB group (n = 10) and a non-EIB group (n = 14). ENO was measured with a single-breath reservoir technique. FEV(1), ENO, and heart rate were measured at baseline and 1, 6, 12, and 18 min after the end of exercise. We also measured ENO in 18 healthy control children aged 10.8 +/- 0.6 yr, of whom nine underwent an exercise challenge identical to that of the asthmatic children. After the exercise test, the mean decrease in FEV(1) was 34% in the EIB group and 5% in the non-EIB group. The EIB group had higher baseline ENO values (12.3 +/- 1.6 ppb) than the healthy children (6.1 +/- 0.2 ppb) (p < 0.01). The time course of ENO was similar in the EIB, non-EIB, and control groups, with no significant changes after exercise (p = NS). In the overall group of asthmatic children there was a significant correlation (r = 0.61, p < 0.01) between baseline (preexercise) ENO and magnitude of the maximal decrease in FEV(1) after exercise. In conclusion, our study shows that ENO levels do not change during acute airway obstruction induced by exercise challenge in asthmatic children. In addition, baseline ENO values correlate with the magnitude of postexercise bronchoconstriction, suggesting that NO may be a predictor of airway hyperresponsiveness to exercise.

Adolescent↗

A simple flow-driven method for online measurement of exhaled NO starting at the age of 4 to 5 years.

NO is increased in exhaled air of asthmatic patients, and may be used as a marker of airway inflammation. The online method is a standardized technique for measuring exhaled nitric oxide (ENO). However, this method has proven difficult for some children, who may have trouble maintaining a constant expiratory flow. The aim of this study was to validate a modified technique for online ENO measurement that utilizes a flow regulator to overcome the patient problem of having to actively maintain a constant expiratory flow. We measured ENO levels with two methods in 105 asthmatic and 10 healthy subjects, comparing the standardized (ST) single-breath method with a modified single-breath, flow-driven (FD) method. With the ST method and visual monitoring, the subjects inhaled NO-free air to TLC, and exhaled with a target flow of 50 ml/s. With the FD method, the subjects exhaled from TLC and flow was kept constant (50 ml/s) by the operator, using a flow regulator. The subjects were divided into two groups, one consisting of children aged 4 to 8 yr (n = 74) and the other of children aged 9 to 16 yr (n = 41). In the group aged 4 to 8 yr, 38 children (51%) were unable to perform the ST method, whereas only five children (7%) failed to perform the FD technique. In the group aged 9 to 16 yr, only four children (10%) were unable to perform the ST maneuver, and all successfully performed the FD maneuver. The mean concentrations of ENO in the 73 children who performed both types of maneuver were similar (36.1 +/- 3.4 [mean +/- SEM] ppb with the ST method and 33.8 +/- 3.3 ppb with the FD technique, p = NS) and were highly correlated with one another (r = 0.99, p < 0.0001). ENO values were significantly higher in steroid-naive than in steroid-treated asthmatic children. In conclusion, we describe a modified online method for measuring ENO that is simple, does not require active cooperation to maintain a constant expiratory flow, and can be easily performed by children from 4 to 5 yr of age onward.

Adolescent↗

Corticosteroids decrease exhaled nitric oxide in children with acute asthma.

OBJECTIVES: Nitric oxide (NO) produced in human airways seems to have both homeostatic and proinflammatory actions in the respiratory system. NO production has been shown to be higher in the exhaled air of asthmatic adults than in normal subjects. The aim of this study was to evaluate exhaled NO production during asthma exacerbation in children and the effect of a rescue course of oral steroid therapy. STUDY DESIGN: We measured NO in the exhaled air of 16 children (8 girls and 8 boys, aged 6 to 13 years) with an acute asthmatic episode before and after 5 days of therapy with prednisone, and in 16 healthy children. To measure NO, children inhaled NO-free air and, breathing at tidal volume, exhaled in a circuit from which a chemiluminescence analyzer sampled continuously. To assess the effect of acute changes in bronchial caliber on exhaled NO levels, we measured NO before and after a positive bronchodilation test result with albuterol in seven children with asthma whose disease was stable. RESULTS: In the group with acute asthma (forced expiratory volume in 1 second 62% +/- 4.4% predicted, mean +/- SEM), NO levels were significantly higher (31.3 +/- 4.2 parts per billion [ppb]) than in healthy children (5.4 +/- 0.4 ppb, p < 0.001). Administration of prednisone (1 mg/kg per day orally) for 5 days resulted in a mean decrease of 46% +/- 4% in exhaled NO concentrations (16.5 +/- 2.3 ppb, p < 0.001) compared with baseline, accompanied by a significant improvement in lung function (forced expiratory volume in 1 second 90.7% +/- 4.3% predicted). However, in patients with asthma exhaled NO levels remained significantly higher than in control children (p < 0.001) after steroid treatment. When exhaled NO was measured before and after a positive result after bronchodilator reversibility testing, we found no difference in exhaled NO levels (24 +/- 3.8 ppb vs 23.8 +/- 3 ppb; difference not significant). This demonstrates that inhaled albuterol and acute changes in bronchial caliber do not affect exhaled NO measurement. CONCLUSIONS: These data show that children with asthma exacerbation have high levels of exhaled NO that rapidly decrease with oral steroid therapy. We suggest that measurement of exhaled NO may represent a noninvasive method of monitoring airway inflammation in children with asthma.

Acute Disease↗

Effect of hypoxia on lung, heart, and liver insulin-like growth factor-I gene and receptor expression in the newborn rat.

OBJECTIVES: We examined the effect of 7 days of hypoxia in the newborn rat on: a) body, heart, and lung growth; b) circulating insulin-like growth factor-I (IGF-I); c) lung, heart, and liver IGF-I gene expression; and d) lung IGF-I type 1 receptor gene expression and IGF-I receptor binding. We hypothesize that hypoxic exposure would modify body and organ growth and alter IGF-I gene and receptor expression in an organ specific manner. DESIGN: Randomized, controlled prospective study. SETTING: University research laboratory. SUBJECTS: Eleven newborn rat litters (n = 10 per litter) comprised the hypoxia-exposed group and 11 litters comprised the control group (room air). INTERVENTIONS: Hypoxia-group rats were placed in a chamber with an FIO2 of 0.12 on postnatal day 1. Control group rats breathed room air. Exposure to hypoxia continued for 7 days. MEASUREMENTS AND MAIN RESULTS: Hepatic, lung, and cardiac IGF-I mRNA levels and lung IGF-I type 1 receptor mRNA were analyzed, using the ribonuclease protection assay. Crude membrane extracts were used for competitive binding studies with IGF-I and insulin. Somatic growth in the hypoxic group was reduced by 22% (final weight: hypoxic, 14.8 +/- 1.2 g; control, 17.1 +/- 1.5 g; p < .001). The relative weight (organ weight/body weight [mg/g]) of the heart was increased by 39% (p < .001) in the hypoxic pups compared with the normoxic animals, while the relative weight of the lung was unchanged. With hypoxia, IFG-I mRNA concentrations were significantly increased both in the heart and lung (30% and 33%, respectively, p < .02); but, in contrast, IGF-I mRNA concentrations were not significantly different in the liver. The IGF-I receptor mRNA in the lung was increased by 200% (p < .02) in hypoxia compared with controls. There was no effect of hypoxia on specific or nonspecific binding of IGF-I or insulin in the lung tissue. However, specific binding was 33% greater in the IGF-I compared with the insulin experiments. CONCLUSIONS: a) Hypoxia increased IGF-I mRNA in the heart, and increased both IGF-I mRNA and IGF-I type 1 receptor mRNA in the lung. b) The effects of hypoxia on IFG-I are tissue-specific.

Animals↗

Calf muscle cross-sectional area and peak oxygen uptake and work rate in children and adults.

It is often assumed that the inherent peak muscle metabolic capacity scales in direct proportion to muscle cross-sectional area and is the same in small and large animals (A. V. Hill. Sci. Prog. 38: 208-230, 1950). We wondered whether this relationship between size and function was true during the period of growth and development in humans. Magnetic resonance imaging (MRI) was used to determine calf muscle cross-sectional area (CSA) in 20 children (6-11 yr old, 11 boys) and in 18 adults (23-42 yr old, 10 men). Progressive cycle ergometer exercise was performed to determine peak oxygen uptake (VO2peak) and work rate (WRpeak). The scaling factor (determined by allometric analysis) relating maximal O2 uptake (VO2max) to muscle CSA for the whole sample population was 1.04 +/- 0.12 (SE), but the scaling factor relating WRpeak to muscle CSA was significantly greater (1.37 +/- 0.12). Consistent with this, VO2max/CSA was not affected by body weight, but the WRpeak/CSA increased as a function of weight both in males (P < 0.005) and females (P < 0.05). No differences in VO2max/CSA were found between children and adults. WRpeak/CSA was significantly higher in adults compared with children (P < 0.05). It appears that the inherent peak muscle metabolic capacity is smaller in children than in adults. Moreover, the coupling of muscle capacity with whole body metabolic rate changes during growth in humans.

Adult↗

Effect of training and growth hormone suppression on insulin-like growth factor I mRNA in young rats.

The growth hormone (GH)-insulin-like growth factor I (IGF-I) axis plays a role in the adaptation to exercise training, but IGF-I gene expression in response to exercise training and GH suppression has not been studied. Twenty female rates underwent a 4-wk treadmill training program begun in the prepubertal period (day 14 of life). In 10 of the training rats, GH production was suppressed by anti-GH-releasing hormone antibodies (GH suppressed). IGF-I mRNA and protein levels were measured in liver and hindlimb skeletal muscle. GH suppression reduced IGF-I mRNA expression in the liver to a much greater extent than in the muscle. In the GH control rats, training induced significant increases in hepatic exon 1-derived IGF-I mRNA (mean increase 30%; P < 0.05) and muscle exon 2-derived mRNA (mean increase 35%; P < 0.05). In the GH-suppressed rats, only muscle exon 1-derived transcripts were significantly increased by training (55%; P < 0.05) and this was associated with a significant increase in muscle IGF-I protein levels (P < 0.05). We speculate that the anabolic response to training may involve both GH-dependent increases in IGF-I mRNA in the liver and GH-independent increases in the muscle.

Actins↗

Muscle energetics and pulmonary oxygen uptake kinetics during moderate exercise.

The present study tested whether, during moderate exercise, 1) the dynamic responses of ADP and changes in free energy of ATP hydrolysis (delta GATP) were similar to those of phosphocreatine [PCr; as would be expected for a simple controller of muscle respiration (QO2)] and 2) the rise in pulmonary O2 uptake (VO2) during cycle exercise would reflect the rise in muscle QO2 indicated by the calf PCr kinetics. The responses of PCr, Pi, ADP, and delta GATP were measured from the calf in five subjects during supine treadle exercise using 31P-magnetic resonance spectroscopy and compared with those for VO2, measured breath by breath during upright cycle exercise. The time constants for delta GATP [24.2 +/- 14.2 (SE) s] were not significantly different from those for PCr (26.3 +/- 17.3 s) and Pi (30.7 +/- 22.5 s) (P > 0.05). The time constants for phase 2 VO2 (29.9 +/- 16.8 s) were also similar to those of PCr. In contrast, the dynamics of ADP were distorted from those of PCr due to dynamic changes in pH. These results are consistent with mechanisms of respiratory control that feature substrate control by PCr or thermodynamic control through changes in delta GATP. However, these results are not consistent with substrate control by ADP in a simple fashion. Furthermore, the similarity of time constants for phase 2 VO2 and muscle PCr suggests that phase 2 VO2 kinetics reflect those of muscle QO2 in healthy subjects during moderate exercise.

Adenine Nucleotides↗