Tag: Oxide

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The dangers of widespread nitric oxide screening for primary ciliary dyskinesia.

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The dangers of widespread nitric oxide screening for primary ciliary dyskinesia.

Thorax. 2016 Feb 19;

Authors: Collins SA, Behan L, Harris A, Gove K, Lucas JS

Abstract
Primary ciliary dyskinesia (PCD) is underdiagnosed and requires complex testing at specialist diagnostic centres. Measurement of nasal nitric oxide (nNO) has good sensitivity and specificity screening for PCD, but is currently usually measured at PCD centres rather than prior to referral. Proposals to include NO testing for asthma diagnoses could widen access to PCD screening if nasal mode analysers are available. Data from 282 consecutive referrals to our PCD diagnostic centre (31 PCD positive) were used to model predictive values for nNO testing with varying pretest probability and showed that predictive values were good in the referral population, but extending screening to more general populations would result in excessive false positives that may overwhelm diagnostic services. Although nNO remains a useful test, a ‘normal’ result with classical clinical history should still be considered for further testing.

PMID: 26896442 [PubMed – as supplied by publisher]

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Evolution of exhaled nitric oxide levels throughout development and aging of healthy humans.

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Evolution of exhaled nitric oxide levels throughout development and aging of healthy humans.

J Breath Res. 2015;9(3):036005

Authors: Jacinto T, Malinovschi A, Janson C, Fonseca J, Alving K

Abstract
It is not fully understood how the fraction of exhaled nitric oxide (FeNO) varies with age and gender in healthy individuals. We aim to describe the evolution of FeNO with age, giving special regard to the effect of gender, and to relate this evolution to natural changes in the respiratory tract.We studied 3081 subjects from NHANES 2007-08 and 2009-10, aged 6-80?years, with no self-reported diagnosis of asthma, chronic bronchitis or emphysema, and with normal values of blood eosinophils and C-reactive protein. The relationship of the mean values of FeNO to age, in all participants and divided by gender, was computed, and compared with changes in anatomic dead space volume and forced vital capacity. A change-point analysis technique and subsequent piecewise regression was used to detect breakpoints in the evolution of FeNO with age.Three distinct phases in the evolution of FeNO throughout the age range 6-80?years can be seen. FeNO values increase linearly between 6-14?years of age in girls and between 6-16?years of age in boys, in parallel with somatic growth. After that, FeNO levels plateau in both genders until age 45?years in females and age 59?years in males, when they start to increase linearly again. This increase continues until age 80.Our data clearly show a triphasic evolution of FeNO throughout the human age range in healthy individuals. This should be accounted for in development of reference equations for normal FeNO values.

PMID: 25993061 [PubMed – in process]

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Researchers Use Reduced Airflow, Elevated Exhaled Nitric Oxide to Identify … – Lung Disease News

Researchers Use Reduced Airflow, Elevated Exhaled Nitric Oxide to Identify …
Lung Disease News
In this study, the research team showed that individuals with severe uncontrolled asthma should be re-examined frequently to decrease exacerbations and to identify patients with constant airflow limitation. Asthma is a chronic lung disease …

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Zinc oxide nanoparticles affect the expression of p53, Ras p21 and JNKs: an ex vivo/in vitro exposure study in respiratory disease patients.

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Zinc oxide nanoparticles affect the expression of p53, Ras p21 and JNKs: an ex vivo/in vitro exposure study in respiratory disease patients.

Mutagenesis. 2014 Nov 6;

Authors: Kumar A, Najafzadeh M, Jacob BK, Dhawan A, Anderson D

Abstract
Zinc oxide (ZnO) nanoparticles are the mostly used engineered metal oxide nanoparticles in consumer products. This has increased the likelihood of human exposure to this engineered nanoparticle (ENPs) through different routes. At present, the majority of the studies concerning ZnO ENPs toxicity have been conducted using in vitro and in vivo systems. In this study, for the first time we assessed the effect of ZnO ENPs on the major cellular pathways in the lymphocytes of healthy individuals as well as in susceptible patients suffering from lung cancer, chronic obstructive pulmonary disease (COPD) and asthma. Using the differential expression analysis, we observed a significant (P < 0.05) dose-dependent (10, 20 and 40 µg/ml for 6h) increase in the expression of tumour suppressor protein p53 (40, 60 and 110%); Ras p21 (30, 52 and 80%); c-Jun N-terminal kinases; JNKs) (28, 47 and 78%) in lung cancer patient samples treated with ZnO ENPs compared to healthy controls. A similar trend was also seen in COPD patient samples where a significant (P < 0.05) dose-dependent increase in the expression of tumour suppressor protein p53 (26, 45 and 84%), Ras p21 (21, 40 and 77%), JNKs (17, 32 and 69%) was observed after 6h of ZnO ENPs treatment at the aforesaid concentrations. However, the increase in the expression profile of tested protein was not significant in the asthma patients as compared to controls. Our results reiterate the concern about the safety of ZnO ENPs in consumer products and suggest the need for a complete risk assessment of any new ENPs before its use.

PMID: 25381309 [PubMed – as supplied by publisher]

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Bidirectional Cross-Regulation between the Endothelial Nitric Oxide Synthase and ?-Catenin Signaling Pathways.

Bidirectional Cross-Regulation between the Endothelial Nitric Oxide Synthase and ?-Catenin Signaling Pathways.

Cardiovasc Res. 2014 Jul 25;

Authors: Warboys CM, Chen N, Zhang Q, Shaifta Y, Vanderslott G, Passacquale G, Hu Y, Xu Q, Ward JP, Ferro A

Abstract
AIMS: ?-catenin has been shown to be regulated by inducible nitric oxide synthase (NOS) in endothelial cells. We investigated here whether ?-catenin interacts with and regulates endothelial NOS (eNOS) and whether eNOS activation promotes ?-catenin signaling.
METHODS AND RESULTS: We identified ?-catenin as a novel eNOS binding protein in human umbilical vein endothelial cells (HUVECs) by mass spectroscopy and western blot analyses of ?-catenin and eNOS immunoprecipitates. This was confirmed by in situ proximity ligation assay. eNOS activity, assessed by cGMP production and eNOS phosphorylation (Ser1177), was enhanced in ?-catenin(-/-) mouse pulmonary endothelial cells (MPECs) relative to wild type MPECs. eNOS activation (using adenosine, salbutamol, thrombin or histamine), or application of an NO donor (spermine NONOate) or cGMP-analogue (8-bromo-cGMP) caused nuclear translocation of ?-catenin in HUVEC as shown by western blotting of nuclear extracts. Exposure to spermine NONOate, 8-bromo-cGMP or sildenafil (a phosphodiesterase type 5 inhibitor) also increased the expression of ?-catenin-dependent transcripts, IL-8 and cyclin D1. Stimulation of wild type MPECs with basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), spermine NONOate, 8-bromo-cGMP or sildenafil increased tube length relative to controls in an angiogenesis assay. These responses were abrogated in ?-catenin(-/-) MPECs, with the exception of that to bFGF which is NO-independent. In C57BL/6 mice, subcutaneous VEGF-supplemented Matrigel plugs containing ?-catenin(-/-) MPECs exhibited reduced angiogenesis compared to plugs containing wild type MPECs. Angiogenesis was not altered in bFGF-supplemented Matrigel.
CONCLUSIONS: These data reveal bidirectional cross talk and regulation between the NO-cGMP and ?-catenin signaling pathways.

PMID: 25062958 [PubMed – as supplied by publisher]

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Guideline-Recommended Fractional Exhaled Nitric Oxide is a Poor Predictor of Health Care Use Among Inner-city Children and Adolescents Receiving Usual Asthma Care.

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Guideline-Recommended Fractional Exhaled Nitric Oxide is a Poor Predictor of Health Care Use Among Inner-city Children and Adolescents Receiving Usual Asthma Care.

Chest. 2013 Jun 13;

Authors: McCormack MC, Aloe C, Curtin-Brosnan J, Diette GB, Breysse PN, Matsui EC

Abstract
ABSTRACT BACKGROUND: Recent American Thoracic Society (ATS) guidelines support use of FENO in patients with asthma and highlight gaps in the evidence base. Little is known about use of FENO to predict asthma exacerbations among high-risk, urban, minority populations receiving usual care. METHODS: 138 children with persistent asthma were enrolled in a prospective observational cohort study and skin tested at baseline (wheal?3mm=+SPT). Fractional exhaled nitric oxide (FENO) levels, lung function, and asthma-related health care use were assessed at baseline and every three months thereafter for one year. Relationships between FENO and health care utilization in the subsequent three months were examined. Final models accounted for repeated outcome measures and were adjusted for age, gender and lung function. RESULTS: The mean age was 11 years (range 5-17), and most were male (57%), African American (91%), and atopic (90%). At baseline, FENO was (median [IQR]: 31.5ppb [16-61]) and FEV1/FVC was (mean ± SD: 80.7±9.6%). There were 237 acute asthma-related health care visits, 105 unscheduled doctor (UD) visits, 125 ED visits, and 7 hospitalizations during the follow-up period. FENO was not a significant predictor of acute visits, ED visits, UD visits, or hospitalization in either unadjusted or adjusted analyses. Use of recommended cutpoints did not improve the predictive value of FENO (PPV 0.6-32.8%), nor did application of the guideline-based algorithm to assess change over time. CONCLUSIONS: FENO may not be a clinically useful predictor of health care use for asthma exacerbations in urban minority children with asthma.

PMID: 23764806 [PubMed – as supplied by publisher]

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