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Sample records for early inhaled nitric

  1. [Inhalation of nitric oxide - dependence: case report

    PubMed

    Carvalho, W B; Matsumoto, T; Horita, S M; Almeida, N M; Martins, F R

    2000-01-01

    OBJECTIVE: Describe the hemodynamic response with rebound of pulmonary hypertension after withdrawal of inhaled nitric oxide (NO) in a pediatric patient with acute respiratory distress syndrome (ARDS). METHODS: Case report of a child with ARDS and pulmonary hypertension evaluated through ecocardiografic with dopller, receiving inhaled NO for a period of 21 days. RESULTS: There was a decrease of the pulmonary artery pressure (PAP) from 52 mmHg to 44 mmHg after the initial titulation of NO inhalation dose. After the withdrawal of inhaled NO an elevation of PAP was observed (55 mmHg). It was necessary to reinstall the inhaled NO to obtain a more appropriate value (34 mmHg). A new attempt of interruption of the inhaled NO after prolonged inhalation (20 days) resulted in a new clinic worsening and increase of PAP, with the indication to reinstall the inhaled NO. In the 24th day of permanence in the intensive care unit the patient died due to multiple organ dysfunction. CONCLUSIONS: The possibility of pulmonary hypertension rebound after withdrawal of inhaled NO is a complication that may have important clinical implications for patients who need a prolonged treatment with NO. This case report emphasizes these implications. PMID:14647690

  2. [Inhaled nitric oxide: one modality in the treatment of ARDS].

    PubMed

    Carrillo-Esper, R; Ramírez-Hernández, J M; Gargallo-Hernández, J J; Hernández-Vásquez, R; Domínguez-Rodríguez, M I; Alemán-Alarcón, C E; Gallegos-Rodríguez, G

    1999-01-01

    We describe a patient with acute respiratory distress syndrome (ARDS), refractory to treatment with conventional mechanical ventilation. The hemodynamic parameters showed severe pulmonary hypertension with increased intrapulmonary shunt. Inhaled nitric oxide was administered and we observed a diminishing in pulmonary hypertension and intrapulmonary shunt with an important increase of oxygen exchange. We reviewed the literature and make a suggestion concerning use of inhaled nitric oxide in patients with ARDS. PMID:10491897

  3. Inhaled nitric oxide to prevent bronchopulmonary dysplasia in preterm neonates.

    PubMed

    Mercier, Jean-Christophe; Olivier, Paul; Loron, Gauthier; Fontaine, Romain; Maury, Laure; Baud, Olivier

    2009-02-01

    Bronchopulmonary dysplasia is a chronic lung disease that affects premature infants and contributes to their morbidity and mortality. With the advent of prenatal steroids and postnatal exogenous surfactant and less aggressive respiratory support, premature infants can develop chronic oxygen dependency without even acute respiratory distress. This 'new bronchopulmonary dysplasia' could be the result of impaired postnatal growth. Several experimental studies have suggested a possible role of the vascular endothelial growth factor/nitric oxide (VEGF/NO) pathway in restoring pulmonary angiogenesis and enhancing distal lung growth. The results of the clinical studies are, however, inconclusive, and it is currently unclear which subsets of premature infants might benefit from inhaled nitric oxide. Besides, severe intracranial haemorrhage and/or cystic periventricular leucomalacia may affect the most immature babies, many of whom are spared from severe initial respiratory disease. Recently, inhaled nitric oxide was shown to significantly decrease the incidence of these neurological events, and to improve the long-term outcome in a few clinical trials. At times neuroprotective, at times neurotoxic, nitric oxide is capable of divergent effects depending upon the extent of cerebral damage, the redox state of the cell, and the experimental model used. Recently, our group found that inhaled nitric oxide had remote effects including angiogenesis and maturation on the developing brain in rodent pups. Thus, we await the results of the recently completed randomised clinical trial of inhaled nitric oxide to prevent bronchopulmonary dysplasia (the European Nitric Oxide or 'EUNO' trial) where, besides the primary endpoint of chronic oxygen dependency reduction at 36 weeks' postconceptional age, long-term lung and brain will be followed-up until 7 years of age. PMID:18986855

  4. Inhaled nitric oxide in chronic obstructive lung disease

    SciTech Connect

    Tiihonen, J.; Hakola, P.; Paanila, J.; Turtiainen . Dept. of Forensic Psychiatry)

    1993-01-30

    During an investigation of the effect of nitric oxide on the pulmonary circulation the authors had the opportunity to give nitric oxide to a patient with longstanding obstructive airway disease, with successful results. A 72-year-old man with chronic obstructive pulmonary disease was referred to the institution for assessment of pulmonary vascular reactivity to acetylcholine and nitric oxide. Acetylcholine was infused into the main pulmonary artery followed 15 min later by an inhalation of 80 parts per million (ppm) nitric oxide. Heart rate and systemic arterial and pulmonary arterial pressures were continuously monitored. Throughout the study the inspired oxygen concentration was kept constant at 98%. Nitrogen dioxide and nitric oxide concentrations were monitored while nitric oxide was delivered. The infusion of acetylcholine resulted in a small increase in pulmonary artery pressure and pulmonary vascular resistance. Nitric oxide produced a substantial fall in pulmonary artery pressure and pulmonary vascular resistance with a concomitant increase in systemic arterial oxygen tension. These results suggest that endothelium-dependent relaxation of the pulmonary vasculature was impaired in the patient and that exogenous nitric oxide was an effective pulmonary vasodilator. In-vitro investigation of explanted airways disease suggests not only that endothelium-dependent pulmonary artery relaxation is impaired but also that the dysfunction is related to pre-existing hypoxemia and hypercapnia. Nitric oxide inhibits proliferation of cultured vascular smooth muscle cells and might alter the pulmonary vascular remodeling characteristic of patients with chronic obstructive airways disease.

  5. Reversibility of heme-nitric oxide reactions for use in an inhaled nitric oxide sensor

    NASA Astrophysics Data System (ADS)

    Parikh, Bhairavi R.; Soller, Babs R.; Rencus, Tal

    1997-06-01

    Nitric Oxide is a simple gaseous compound which serves as a regulatory molecule in a number of physiological processes. Due to its biological role as a potent local vasodilator,there has been widespread interest in the therapeutic use of gaseous nitric oxide a selective pulmonary vasodilator. Our goal is the development of a sensor for the direct and continuous measurement of inhaled nitric oxide concentrations. This study evaluated the reversibility of potential sensing compounds upon reaction with nitric oxide. Previously, absorption spectroscopy was used to study the sensitivity of the Fe II, Fe III and oxygenated forms of three biologically active hemes known to rapidly react with NO: hemoglobin, myoglobin, and cytochrome-c. This study focused on the photo-reversibility of the hem's reaction with nitric oxide. Hemoglobin, myoglobin and cytochrome-c in the Fe III state reversibly reacted with nitric oxide. Hemoglobin and myoglobin in the Fe II state non-reversibly reacted with nitric oxide to form an unstable product. Cytochrome-c (FeII) does not react with nitric oxide. The oxy forms of hemoglobin and myoglobin react with nitric oxide to form their respective met forms, unreversible via photolysis. For all reversible reactions, photolysis was gradual and complete within five minutes.

  6. Pulmonary vasodilation by inhaled nitric oxide after endothelial injury

    SciTech Connect

    Rimar, S.; Gillis, C.N. )

    1992-11-01

    Inhaled nitric oxide gas (NO) has recently been shown to reverse experimentally induced pulmonary vasoconstriction. To examine the effect of free radical injury and methylene blue exposure on inhaled NO-induced pulmonary vasodilation the authors studied ventilated rabbit lungs perfused with Krebs solution containing 3% dextran and indomethacin. When NO gas (120 ppm) was added to the inhaled mixture for 3 min, the elevated pulmonary arterial perfusion pressure (Ppa) induced by the thromboxane analogue U-46619 was significantly reduced [8 [+-] 2 (SE) mmHg]. Acetylcholine similarly reduced Ppa (9 [+-] 1 mmHg). After free radical injury and methylene blue exposure, inhaled NO again produced significant vasodilation (5 [+-] 1 and 9 [+-] 2 mmHg, respectively), but acetylcholine resulted in an increase in Ppa ([minus]9 [+-] 3 and [minus]4 [+-] 1 mmHg, respectively). These data demonstrate that pulmonary vasodilation produced by inhaled NO is unaffected by free radical injury or methylene blue in the intact lung despite concomitant reversal of acetylcholine-induced vasodilation. 21 refs., 4 figs.

  7. 75 FR 43535 - NIH Consensus Development Conference on Inhaled Nitric Oxide Therapy for Premature Infants

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-26

    ... week of pregnancy) with respiratory failure. Inhaled nitric oxide therapy is typically administered in...-term infants, use of this therapy may shorten the length of time respiratory support is required... receive respiratory support? Are there short-term risks of inhaled nitric oxide therapy among...

  8. Inhaled nitric oxide in cardiac surgery: Evidence or tradition?

    PubMed

    Benedetto, Maria; Romano, Rosalba; Baca, Georgiana; Sarridou, Despoina; Fischer, Andreas; Simon, Andre; Marczin, Nandor

    2015-09-15

    Inhaled nitric oxide (iNO) therapy as a selective pulmonary vasodilator in cardiac surgery has been one of the most significant pharmacological advances in managing pulmonary hemodynamics and life threatening right ventricular dysfunction and failure. However, this remarkable story has experienced a roller-coaster ride with high hopes and nearly universal demonstration of physiological benefits but disappointing translation of these benefits to harder clinical outcomes. Most of our understanding on the iNO field in cardiac surgery stems from small observational or single centre randomised trials and even the very few multicentre trials fail to ascertain strong evidence base. As a consequence, there are only weak clinical practice guidelines on the field and only European expert opinion for the use of iNO in routine and more specialised cardiac surgery such as heart and lung transplantation and left ventricular assist device (LVAD) insertion. In this review the authors from a specialised cardiac centre in the UK with a very high volume of iNO usage provide detailed information on the early observations leading to the European expert recommendations and reflect on the nature and background of these recommendations. We also provide a summary of the progress in each of the cardiac subspecialties for the last decade and initial survey data on the views of senior anaesthetic and intensive care colleagues on these recommendations. We conclude that the combination of high price tag associated with iNO therapy and lack of substantial clinical evidence is not sustainable on the current field and we are risking loosing this promising therapy from our daily practice. Overcoming the status quo will not be easy as there is not much room for controlled trials in heart transplantation or in the current atmosphere of LVAD implantation. However, we call for international cooperation to conduct definite studies to determine the place of iNO therapy in lung transplantation and high

  9. [Inhaled nitric monoxide. Application and continuous measurement of concentration].

    PubMed

    Benzing, A; Beyer, U; Kiefer, P; Geiger, K

    1993-03-01

    Inhaled nitric oxide (NO) is a selective pulmonary vasodilator that may be useful in the treatment of patients with severe pulmonary hypertension. We describe a delivery system of inhaled NO that allows safe application and continuous measurement of the inspired NO concentration during mechanical ventilation. From a gas cylinder containing NO in N2 (600 ppm NO), an adjustable amount of gas is introduced into the inspiratory side of the tubing system via a pressure reduction valve, a magnetic valve, and a special injection nozzle. The NO concentration is diluted to the desired value by the tidal volume. The magnetic valve is connected to the ventilator and opens at the beginning of each inspiration and closes after a predetermined time. The gas volume is proportional to the pressure at the magnetic valve and the opening time. To monitor the inspiratory NO concentration, a specimen of gas is taken from an angle-connector and passed over an electrochemical sensor. The second nozzle of the sensor is connected to a water seal, which is adjusted to the positive end-expiratory pressure level of the ventilator to insure that the gas flow over the sensor is limited to inspiration. PMID:8480905

  10. Effect of nitric oxide inhalation on gas exchange in acute severe pneumonia.

    PubMed

    Gómez, Federico P; Amado, Veronica M; Roca, Josep; Torres, Antoni; Nicolas, Josep M; Rodriguez-Roisin, Robert; Barberà, Joan A

    2013-06-15

    Inhaled nitric oxide (NO) causes selective pulmonary vasodilatation and may improve gas exchange. The study was aimed to evaluate the acute effects of inhaled NO on pulmonary gas exchange in severe unilateral pneumonia, where hypoxemia results from increased intrapulmonary shunt. We studied 8 patients without preexisting lung disease (59±18 yr; 4M/4F) with early unilateral severe pneumonia and respiratory failure. Pulmonary and systemic hemodynamics and gas exchange, including ventilation-perfusion (V;A/Q;) distributions, were measured at baseline and while breathing 5 and 40 parts per million (ppm) of NO. Inhaled NO caused a dose-dependent fall in pulmonary vascular resistance (by 12% and 21%, with 5 and 40ppm, respectively; p<0.01, each) and improvement of PaO2 (by 25% and 23%; p<0.05, each), owing to the reduction of intrapulmonary shunt (by 23% and 27%; p<0.05, each), without changes in the amount of perfusion to low V;A/Q; ratio alveolar units. Patients with greater baseline intrapulmonary shunt exhibited greater improvement in arterial oxygenation (r(2)=0.55, p<0.05). We conclude that low doses of inhaled NO improve pulmonary gas exchange in acute severe pneumonia. PMID:23537586

  11. Inhaled aerosolized prostacyclin and nitric oxide as selective pulmonary vasodilators in ARDS--a pilot study.

    PubMed

    Van Heerden, P V; Blythe, D; Webb, S A

    1996-10-01

    Nitric oxide 10 ppm and inhaled aerosolized prostacyclin 50 ng/kg/min were compared as selective pulmonary vasodilators in five patients with hypoxaemia secondary to acute respiratory distress syndrome. Neither agent resulted in systemic haemodynamic changes, indicating true pulmonary selectivity. Inhaled aerolized prostacyclin improved oxygenation to a degree comparable to nitric oxide, as measured by the arterial alveolar oxygen partial pressure gradient and shunt fraction. PMID:8909667

  12. William TG Morton's early ether inhalers: a tale of three inhalers and their inscriptions.

    PubMed

    Haridas, R P

    2009-07-01

    Three ether inhalers with inscriptions stating that they had been used in early ether anaesthesia were found. All three inhalers were initially linked to WTG Morton. Two of the inhalers were probably among several types of inhalers used by Morton. The third inhaler was found to have been incorrectly attributed to Morton. It was first used by John Foster Brewster Flagg, a dentist in Philadelphia. PMID:19705631

  13. Inhaled nitric oxide in acute pulmonary embolism: a systematic review.

    PubMed

    Bhat, Tariq; Neuman, Adi; Tantary, Mohmad; Bhat, Hilal; Glass, Daniel; Mannino, William; Akhtar, Muhammad; Bhat, Alina; Teli, Sumaya; Lafferty, James

    2015-01-01

    Acute pulmonary embolism (PE) is usually a complication secondary to migration of a deep venous clot or thrombi to lungs, but other significant etiologies include air, amniotic fluid, fat, and bone marrow. Regardless of the underlying etiology, little progress has been made in finding an effective pharmacologic intervention for this serious complication. Among the wide spectrum of PE, massive PE is associated with considerable morbidity and mortality, primarily due to severely elevated pulmonary vascular resistance leading to right ventricular failure, hypoxemia, and cardiogenic shock. We currently have limited therapeutic options at our disposal. Inhaled nitric oxide (iNO) has been proposed as a potential therapeutic agent in cases of acute PE in which hemodynamic compromise secondary to increased pulmonary vascular resistance is present, based on iNO's selective dilation of the pulmonary vasculature and antiplatelet activity. A systematic search of studies using the PubMed database was undertaken in order to assess the available literature. Although there are currently no published randomized controlled trials on the subject, except a recently publish phase I trial involving eight patients, several case reports and case series describe and document the use of iNO in acute PE. The majority of published reports have documented improvements in oxygenation and hemodynamic variables, often within minutes of administration of iNO. These reports, when taken together, raise the possibility that iNO may be a potential therapeutic agent in acute PE. However, based on the current literature, it is not possible to conclude definitively whether iNO is safe and effective. These case reports underscore the need for randomized controlled trials to establish the safety and efficacy of iNO in the treatment of massive acute PE. The purpose of this article is to review the current literature in the use of iNO in the setting of PE given how acute PE causes acute onset of pulmonary

  14. Site of pulmonary vasodilation by inhaled nitric oxide in the perfused lung

    SciTech Connect

    Rimar, S.; Gillis, C.N.

    1995-05-01

    Site of pulmonary vasodilation by inhaled nitric oxide in the perfused lung. To determine the site of inhaled nitric oxide (NO)-induced pulmonary vasodilation, a double vascular occlusion technique was used with rabbit lungs ventilated and perfused at 20 ml/min with Krebs solution containing 3% dextran and 30 {mu}M indomethacin. Inhaled NO (120 ppm for 3% min) reduced pulmonary vasoconstriction produced by U-46619 infusion (0.5 -1.2 nmol/min), significantly decreasing total resistance (RT) [1,080 {plus_minus} 51 (SE) vs. 1,545 {plus_minus} 109 mmHg-min/l; P < 0.01]. Acetylcholine infusion (ACh; 2-5 nmol/min) and nitroglycerin (NTG; 0.35 {mu}mol) likewise decreased RT. Arterial resistance (Ra) was also significantly less with inhaled NO, ACh, and NTG compared with U-46619 alone. Venous resistance (Rv), however, was unchanged. When the direction of perfusion was reversed in the lung, inhaled NO, ACh, and NTG significantly decreased RT compared with U-46619 alone, and Rv was also reduced by all three agents. After electrolysis-induced acute lung injury, inhaled NO significantly reduced both RT and Ra compared with U-46619 alone, whereas Rv was unaffected. Our results demonstrate that inhaled NO gas affects primarily the arterial (precapillary) component of the pulmonary circulation but, under conditions of extreme venous constriction, may dilate the postcapillary component as well. 25 refs., 4 figs.

  15. [Clinical application and experimental studies of the pulsed inhaled nitric oxide flow controlling instrument].

    PubMed

    Mo, Xu-ming; Zhao, En-chun; Wang, Min-sheng; Gu, Xinglin; Wang, Zhenxi; Wang, Chunsheng

    2002-01-01

    A flow controlling system for pulsed inhaled nitric oxide has been developed and tested, and here its features and initial animal experiments and clinical applications are described. The physical characteristic test indicates that the practical released dose of NO gas is very close to the theoretical flow of NO gas at variant pressures. Animal experiments demonstrate that inhaled NO gas concentration is lower than the concentration of theoretical inhalation, but the variance is not remarkable (p>0.05). When sixteen cases with CHD and PH were chosen to inhale NO gas (15 ppm, 15 min) PAP and PVR of all cases were reduced after inhalation of NO gas from 617 +/-51.3 dyn x s x cm(-5), 54.4+/-13.1 mmHg to 417+/-36.9 dym x s x cm(-5), 33.8+/-12.3 mmHg (PVR, p<0.01; PAP, p<0.01) respectively. When gas inhalation was stopped, these values returned to their base lines after a short period of time. All these show that the pulsed inhaled NO flow controlling instrument in accordance with the requirements of the designing, can be widely used in clinical diagnoses and treatments and will be a new tool offered for the treatments of the patients with PH. PMID:16104155

  16. Effect of inhaled nitric oxide on pulmonary hemodynamics after acute lung injury in dogs

    SciTech Connect

    Romand, J.A.; Pinsky, M.R.; Firestone, L.; Zar, H.A.; Lancaster, J.R. Jr. )

    1994-03-01

    Increased pulmonary vascular resistance (PVR) and mismatch in ventilation-to-perfusion ratio characterize acute lung injury (ALI). Pulmonary arterial pressure (Ppa) decreases when nitric oxide (NO) is inhaled during hypoxic pulmonary vasoconstriction (HPV); thus NO inhalation may reduce PVR and improve gas exchange in ALI. The authors studied the hemodynamic and gas exchange effects of NO inhalation during HPV and then ALI in eight anesthetized open-chest mechanically ventilated dogs. Right atrial pressure, Ppa, and left ventricular and arterial pressures were measured, and cardiac output was estimated by an aortic flow probe. Shunt and dead space were also estimated. The effect of 5-min exposures to 0, 17, 28, 47, and 0 ppm inhaled NO was recorded during hyperoxia, hypoxia, and oleic acid-induced ALI. During ALI, partial [beta]-adrenergic blockage (propanolol, 0.15 mg/kg iv) was induced and 74 ppm NO was inhaled. Nitrosylhemoglobin (NO-Hb) and methemoglobin (MetHb) levels were measured. During hyperoxia, NO inhalation had no measurable effects. Hypoxia increased Ppa and calculated PVR, both of which decreased with 17 ppm NO. ALI decreased arterial Po[sub 2] and increased airway pressure, shunt, and dead space ventilation. Ppa and PVR were greater during ALI than during hyperoxia. NO inhalation had no measurable effect during ALI before or after [beta]-adrenergic blockage. MetHb remained low, and NO-Hb was unmeasurable. Bolus infusion of nitroglycerin (15 [mu]g) induced an immediate decrease in Ppa and PVR during ALI. Short-term NO inhalation does not affect PVR or gas exchange in dogs with oleic acid-induced ALI, nor does it increase NO-Hb or MetHb. In contrast, NO can diminish hypoxia-induced elevations in pulmonary vascular tone. These data suggest that NO inhalation selectively dilates the pulmonary circulation and specifically reduces HPV but not oleic acid-induced increases in pulmonary vasomotor tone. 28 refs., 3 figs., 2 tabs.

  17. Inhalable microparticles of nitric oxide donors induce phagosome maturation and kill Mycobacterium tuberculosis.

    PubMed

    Verma, Rahul Kumar; Agrawal, Atul Kumar; Singh, Amit Kumar; Mohan, Mradul; Gupta, Anuradha; Gupta, Pushpa; Gupta, Umesh Datta; Misra, Amit

    2013-07-01

    Nitric oxide (NO) kills Mycobacterium tuberculosis (Mtb) in vitro, but gaseous NO is difficult to administer to patients. We evaluated the consequences of intracellular delivery of NO using inhalable microparticles (MP) containing NO donors. MP containing 10% w/w of NO donors alone, or in addition to 25% each of isoniazid (INH) and rifabutin (RFB) in a polylactide-co-glycolide (PLGA) matrix were prepared by spray drying. THP-1-derived macrophages infected with Mtb H37Rv were exposed to MP or soluble NO donors. Phagosome-lysosome fusion (PLF) and bacterial killing were monitored. Colony forming units (cfu) in lungs and spleen of mice infected with a low-dose aerosol and administered inhalations of MP were enumerated. Bacterial DNA in these tissues was estimated by real-time PCR. In vitro studies indicated a bacteriostatic effect of NO donors despite significant enhancement of PLF. Daily inhalation of MP containing 10% diethylenetriamine nitric oxide adduct (DETA/NO) alone reduced log10 cfu in the lungs from 6.1 to 4.4 at the highest dose in four weeks, but did not significantly affect cfu in the spleen. Inhalations of MP containing DETA/NO in combination with INH and RFB significantly (P < 10(-5), ANOVA) reduced cfu in lungs and spleens by 4 log. Gross morphology and histology of the lungs and spleen indicated that inhaled particles were well-tolerated. Inhalable MP containing NO donors need further investigation as an adjunct to standard anti-tuberculosis chemotherapy. PMID:23562366

  18. Echocardiographic investigation of inhaled nitric oxide in newborn babies with severe hypoxaemia.

    PubMed

    Rozé, J C; Storme, L; Zupan, V; Morville, P; Dinh-Xuan, A T; Mercier, J C

    1994-07-30

    Nitric oxide inhalation can benefit newborn babies with right-to-left extrapulmonary shunt (EPS). Using doppler ultrasound, we compared the effects of nitric oxide on systemic oxygenation and mean pulmonary-blood-flow velocity (MPBFV) in severely hypoxic babies with or without EPS. With a median (interquartile range) dose of 20 (32) parts per million, oxygenation index decreased significantly in both groups (EPS, 49 [19] vs 11 [9]; non-EPS, 40 [11] vs 20 [13]). The decrease was significantly greater in the EPS group. MPBFV increased significantly in the EPS group (18 [4] vs 29 [8] m/s) only. Nitric oxide may improve systemic oxygenation in neonates with severe hypoxaemia secondary to EPS by increasing pulmonary blood flow, and in those without EPS by improving ventilation-perfusion matching. PMID:7914264

  19. The Biological Chemistry of Nitric Oxide as It Pertains to the Extrapulmonary Effects of Inhaled Nitric Oxide

    PubMed Central

    Gow, Andrew J.

    2006-01-01

    The chemical properties of nitric oxide (NO) have been studied for over 200 years. However, it is only within the last 20 years that the biological implications of this chemistry have been considered. The classical model of NO action within the vasculature centers on production in the endothelium, diffusion to the smooth muscle, and subsequent activation of guanylate cyclase via binding to its heme iron. In the context of this model, it is difficult to conceptualize extrapulmonary effects of inhaled NO. However, NO possesses complex redox chemistry and is capable of forming a range of nitrogen oxide species and is therefore capable of interacting with a variety of biomolecules. Of particular interest is its reaction with reduced cysteine to form an S-nitrosothiol (SNO). SNOs are formed throughout NO biology and are a post-translational modification that has been shown to regulate many proteins under physiologic conditions. Hemoglobin, which was considered to be solely a consumer of NO, can form SNO in a conformationally dependent manner, which allows for the transport of inhaled NO beyond the realm of the lung. Higher oxides of nitrogen are capable of modifying proteins via nitration of tyrosines, which has been shown to occur under pathologic conditions. By virtue of its redox reactivity, one can appreciate that inhaled NO has a variety of routes by which it can act and that these routes may lead to extrapulmonary effects. PMID:16565423

  20. Inhaled nitric oxide exacerbated phorbol-induced acute lung injury in rats.

    PubMed

    Lin, Hen I; Chu, Shi Jye; Hsu, Kang; Wang, David

    2004-01-01

    In this study, we determined the effect of inhaled nitric oxide (NO) on the acute lung injury induced by phorbol myristate acetate (PMA) in isolated rat lung. Typical acute lung injury was induced successfully by PMA during 60 min of observation. PMA (2 microg/kg) elicited a significant increase in microvascular permeability, (measured using the capillary filtration coefficient Kfc), lung weight gain, lung weight/body weight ratio, pulmonary arterial pressure (PAP) and protein concentration of the bronchoalveolar lavage fluid. Pretreatment with inhaled NO (30 ppm) significantly exacerbated acute lung injury. All of the parameters reflective of lung injury increased significantly except PAP (P<0.05). Coadministration of Nomega-nitro-L-arginine methyl ester (L-NAME) (5 mM) attenuated the detrimental effect of inhaled NO in PMA-induced lung injury, except for PAP. In addition, L-NAME (5 mM) significantly attenuated PMA-induced acute lung injury except for PAP. These experimental data suggest that inhaled NO significantly exacerbated acute lung injury induced by PMA in rats. L-NAME attenuated the detrimental effect of inhaled NO. PMID:14643171

  1. Inhalation of nitric oxide inhibits ADP-induced platelet aggregation and alpha-granule release.

    PubMed

    Hagberg, I A; Sølvik, U Ø; Opdahl, H; Roald, H E; Lyberg, T

    1999-01-01

    To gather further information about the effects on blood platelet activation of in vivo exposure to nitric oxide (NO), platelet reactivity was studied in blood from healthy, non-smoking male volunteers before and after 30 min inhalation of 40 ppm NO. Whole blood was stimulated in vitro with adenosine diphosphate or thrombin receptor activation peptide (TRAP-6). In an ex vivo perfusion model, non-anticoagulated blood was exposed to immobilised collagen at arterial blood flow conditions (2600 s(-1)). Blood samples from both the in vitro and ex vivo experiments were stained with fluorochrome-labelled Annexin-V and antibodies against CD42a, CD45, CD49b, CD61, CD62P and fibrinogen, and analysed with a three-colour flow cytometry technique. NO inhalation reduced the platelet activation response to adenosine diphosphate (ADP) stimulation by decreasing platelet-platelet aggregation, alpha-granule release and platelet-leukocyte conjugate formation. TRAP-stimulated platelet activation, collagen-induced platelet activation and thrombus growth was unaffected by NO inhalation. We therefore suggest an ADP receptor inhibitor mode of action of inhaled NO, selective on the newly suggested G protein- and phospholipase C-coupled P2Y1 receptor. Our results demonstrate that blood platelet activation in healthy subjects is modulated by inhalation of NO in therapeutically relevant doses, although the clinical impact of our findings remains unclear. PMID:16801117

  2. Effect of Inhaled β2-Agonist on Exhaled Nitric Oxide in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Amer, Mostafa; Cowan, Jan; Gray, Andrew; Brockway, Ben

    2016-01-01

    The fractional exhaled nitric oxide measured at an expiratory flow of 50mL/s (FENO50) is a marker of airway inflammation, and high levels are associated with greater response to steroid treatment. In asthma, FENO50 increases with bronchodilation and decreases with bronchoconstriction, the latter potentially causing an underestimate of the degree of airway inflammation when asthma worsens. It is unknown whether the same effect occurs in chronic obstructive lung disease (COPD). Likewise, it is not known whether changes in airway calibre in COPD patients alter flow-independent parameters describing pulmonary nitric oxide exchange, such as the maximal flux of nitric oxide (NO) from the proximal airway compartment (J’awNO) and the distal airway/alveolar concentration of NO (CANO). We recruited 24 patients with COPD and performed FENO analysis at multiple expiratory flows before and after treatment with inhaled β2-agonist bronchodilator therapy. For the 21 patients analysed, FENO50 rose from 17.1 (1.4) ppb (geometric mean (geometric SD)) at baseline, to 19.3 (1.3) ppb after bronchodilator therapy, an increase of 2.2 ppb (95% CI, 0.7–3.6; P = 0.005). There were non-significant changes in flow-independent NO parameters. The change in FENO50 correlated positively with the change in J’awNO (rs = 0.67, P < 0.001; rs = 0.62, P = 0.002 before and after correction for axial back-diffusion respectively) following bronchodilation. Inhaled bronchodilator therapy can increase exhaled nitric oxide measurements in COPD. The standardisation of inhaled bronchodilator therapy before FENO analysis in COPD patients should therefore be considered in both research and clinical settings. PMID:27258087

  3. Effects of inhaled nitric oxide 10 ppm in spontaneously breathing horses anaesthetized with halothane.

    PubMed

    Young, L E; Marlin, D J; McMurphy, R M; Walsh, K; Dixon, P M

    1999-08-01

    Inhaled nitric oxide, a selective pulmonary vasodilator, is known to improve arterial oxygenation after cardiopulmonary bypass and during acute respiratory distress syndrome in humans. During general anaesthesia with spontaneous ventilation, healthy adult horses develop large alveolar-arterial oxygen tension differences. In this study, we have determined the effects of inhaled nitric oxide (10 parts per million (ppm)) on venous admixture and pulmonary haemodynamics in horses anaesthetized with halothane. Seven adult horses were studied twice in random sequence. After premedication with romifidine 100 micrograms kg-1, anaesthesia was induced with ketamine 2.2 mg kg-1 and maintained with 1.1 MAC (0.95%) of halothane in oxygen. Horses breathed spontaneously. After 65 min, each horse had nitric oxide 10 ppm added to the inspired gas for 20 min (procedure HA + NO) or anaesthesia was continued with halothane in oxygen (procedure HA). Cardiac output, minute ventilation, arterial and mixed venous oxygen and carbon dioxide tensions, and mean pulmonary and carotid arterial pressures were measured for 100 min. Shunt fraction and pulmonary and systemic vascular resistances were calculated. Shunt fraction (SF) and mean pulmonary artery pressure (PPA mean) were not different between the two groups after 65 min of general anaesthesia (HA: SF 0.20 (SD 0.06), PPA mean 45 (8) mm Hg; HA + NO: SF 0.21 (0.04), PPA mean 44 (7) mm Hg) or after 85 min (HA: SF 0.22 (0.07), PPA mean 45 (8) mm Hg; HA + NO: SF 0.20 (0.03), PPA mean 43 (7) mm Hg). There were no significant effects of time or nitric oxide inhalation on any other variable. There was a significant correlation (r = 0.80, P < 0.05) between calculated shunt fraction 65 min after induction of anaesthesia and body weight. PMID:10618949

  4. Vasoreactivity to inhaled nitric oxide with oxygen predicts long-term survival in pulmonary arterial hypertension.

    PubMed

    Malhotra, Rajeev; Hess, Dean; Lewis, Gregory D; Bloch, Kenneth D; Waxman, Aaron B; Semigran, Marc J

    2011-04-01

    Pulmonary vasodilator testing is currently used to guide management of patients with pulmonary arterial hypertension (PAH). However, the utility of the pulmonary vascular response to inhaled nitric oxide (NO) and oxygen in predicting survival has not been established. Eighty patients with WHO Group I PAH underwent vasodilator testing with inhaled NO (80 ppm with 90% O(2) for 10 minutes) at the time of diagnosis. Changes in right atrial (RA) pressure, mean pulmonary artery pressure (mPAP), pulmonary capillary wedge pressure, Fick cardiac output, and pulmonary vascular resistance (PVR) were tested for associations to long-term survival (median follow-up 2.4 years). Five-year survival was 56%. Baseline PVR (mean±SD 850±580 dyne-sec/cm(5)) and mPAP (49±14 mmHg) did not predict survival, whereas the change in either PVR or mPAP while breathing NO and O(2) was predictive. Patients with a ≥30% reduction in PVR with inhaled NO and O(2) had a 53% relative reduction in mortality (Cox hazard ratio 0.47, 95% confidence interval (CI) 0.23-0.99, P=0.047), and those with a ≥12% reduction in mPAP with inhaled NO and O(2) had a 55% relative reduction in mortality (hazard ratio 0.45, 95% CI 0.22-0.96, P=0.038). The same vasoreactive thresholds predicted survival in the subset of patients who never were treated with calcium channel antagonists (n=66). Multivariate analysis showed that decreases in PVR and mPAP with inhaled NO and O(2) were independent predictors of survival. Reduction in PVR or mPAP during short-term administration of inhaled NO and O(2) predicts survival in PAH patients. PMID:22020367

  5. Inhalation of nasally derived nitric oxide modulates pulmonary function in humans.

    PubMed

    Lundberg, J O; Settergren, G; Gelinder, S; Lundberg, J M; Alving, K; Weitzberg, E

    1996-12-01

    The vasodilator gas nitric oxide (NO) is produced in the paranasal sinuses and is excreted continuously into the nasal airways of humans. This NO will normally reach the lungs with inspiration, especially during nasal breathing. We wanted to investigate the possible effects of low-dose inhalation of NO from the nasal airways on pulmonary function. The effects of nasal and oral breathing on transcutaneous oxygen tension (tcPO2) were studied in healthy subjects. Furthermore, we also investigated whether restoring low-dose NO inhalation would influence pulmonary vascular resistance index (PVRI) and arterial oxygenation (PaO2) in intubated patients who are deprived of NO produced in the nasal airways. Thus, air derived from the patient's own nose was aspirated and led into the inhalation limb of the ventilator. In six out of eight healthy subjects tcPO2 was 10% higher during periods of nasal breathing when compared with periods of oral breathing. In six out of six long-term intubated patients PaO2 increased by 18% in response to the addition of nasal air samples. PVRI was reduced by 11% in four of 12 short-term intubated patients when nasal air was added to the inhaled air. The present study demonstrates that tcPO2 increases during nasal breathing compared with oral breathing in healthy subjects. Furthermore, in intubated patients, who are deprived of self-inhalation of endogenous NO. PaO2 increases and pulmonary vascular resistance may decrease by adding NO-containing air, derived from the patient's own nose, to the inspired air. The involvement of self-inhaled NO in the regulation of pulmonary function may represent a novel physiological principle, namely that of an enzymatically produced airborne messenger. Furthermore, our findings may help to explain one biological role of the human paranasal sinuses. PMID:8971255

  6. Inhalant Use in Latina Early Adolescent Girls

    ERIC Educational Resources Information Center

    Guzmán, Bianca L.; Kouyoumdjian, Claudia

    2016-01-01

    The purpose of the current study was to examine how lifetime use and extent of use of inhalants by Latina girls is impacted by age, acculturation, grades, ditching, sexual behaviors (light petting, heavy petting, and going all the way) and sexual agency. A total of 273 females who self-identified as being Latina whose mean age was 13.94 completed…

  7. Inhaled nitric oxide: Dose response and the effects of blood in the isolated rat lung

    SciTech Connect

    Rich, G.F.; Roos, C.M.; Anderson, S.M.; Urich, D.C.; Daugherty, M.O.; Johns, R.A. )

    1993-09-01

    Inhaled nitric oxide (NO) is a vasodilator selective to the pulmonary circulation. Using isolated rat lungs, the authors determined the dose-response relationship of NO and the role of blood in mediating pulmonary vasodilation and selectivity. Inhaled 20, 50, 100, and 1,000 ppm NO attenuated (P < 0.001) hypoxic pulmonary vasoconstriction by 16.1 [+-] 4.9, 22.6 [+-] 6.8, 28.4 [+-] 3.5, and 69.3 [+-] 4.2%, respectively. Inhaled 13, 34, 67, and 670 ppm NO attenuated the increase in pulmonary arterial pressure secondary to angiotensin II more (P < 0.001) in Greenberg-Bohr buffer- (GB) than in blood-perfused lungs (51.7 [+-] 0.0, 71.9 [+-] 8.9, 78.2 [+-] 5.3, and 91.9 [+-] 2.1% vs. 14.3 [+-] 4.2, 23.8 [+-] 4.6, 28.4 [+-] 3.8, and 55.5 [+-] 5.9%, respectively). Samples from GB- but not blood-perfused lungs contained NO (93.0 [+-] 26.3 nM). Intravascular NO attenuated the response to angiotensin II more (P < 0.001) in GB- (with and without plasma) than in blood- (hematocrit = 41 and 5%) perfused lungs (75.6 [+-] 6.4 and 70.9 [+-] 4.8% vs. 22.2 [+-] 2.4 and 39.4 [+-] 7.6%). In conclusion, inhaled NO produces reversible dose-dependent pulmonary vasodilation over a large range of concentrations. Inhaled NO enters the circulation, but red blood cells prevent systematic vasodilation and also a significant amount of pulmonary vasodilation. 24 refs., 7 figs., 2 tabs.

  8. Continuous low dose inhaled nitric oxide for treatment of severe pulmonary hypertension after cardiac surgery in paediatric patients.

    PubMed Central

    Beghetti, M.; Habre, W.; Friedli, B.; Berner, M.

    1995-01-01

    OBJECTIVE--To assess the effect of inhaled nitric oxide (NO) on severe postoperative pulmonary hypertension in children after surgical repair of a congenital heart defect. DESIGN--A pilot study of NO administration to 7 consecutive children who required adrenergic support and in whom postoperative mean pulmonary artery pressure was more than two thirds of mean systemic pressure and persisted despite alkalotic hyperventilation. SETTING--Routine care after cardiac surgery for congenital heart disease in a multidisciplinary paediatric intensive care unit. METHODS--Continuous inhalation of NO, initially at 15 ppm. Therefore, daily attempts at complete weaning or at reducing NO to the lowest effective dose. RESULTS--In 6 of the 7 children NO inhalation selectively decreased mean (SD) pulmonary artery pressure from 51 (12) to 31 (9) mm Hg (P < 0.05) while mean systemic arterial pressure was unchanged (68 (10) v 71 (7) mm Hg) (NS) and the arteriovenous difference in oxygen content decreased from 6.7 (0.9) to 4.8 (0.8) vol% (P < 0.05). Concomitantly PaO2 increased from 158 (98) to 231 (79) mm Hg) (P < 0.05). The seventh child showed no response to NO up to 80 ppm, could not be weaned from cardiopulmonary bypass, and died in the operating room. In responders, attempts at early weaning from NO inhalation always failed and NO at concentrations of less than 10 ppm was continuously administered for a median of 9.5 days (range 4 to 16 days) until complete weaning was possible from a mean dose of 3.9 (2.9) ppm. Methaemoglobinaemia remained below 2% and nitrogen dioxide concentrations usually ranged from 0.1 to 0.2 ppm. One child later died and five were discharged. A few months after surgery Doppler echocardiography (and catheterisation in one) showed evidence of regression of pulmonary hypertension in all 5. CONCLUSIONS--Inhalation of NO reduced pulmonary artery pressure in children with severe pulmonary hypertension after cardiac surgery and this effect was maintained over

  9. Pulmonary vascular effects of pulsed inhaled nitric oxide in COPD patients with pulmonary hypertension

    PubMed Central

    Hajian, Bita; De Backer, Jan; Vos, Wim; Van Holsbeke, Cedric; Ferreira, Francisca; Quinn, Deborah A; Hufkens, Annemie; Claes, Rita; De Backer, Wilfried

    2016-01-01

    Introduction Severe chronic obstructive pulmonary disease (COPD) is often associated with secondary pulmonary hypertension (PH), which worsens prognosis. PH can be lowered by oxygen, but also by inhaled nitric oxide (NO), which has the potential to improve the health status of these patients. NO is an important mediator in vascular reactions in the pulmonary circulation. Oral compounds can act through NO-mediated pathways, but delivering pulsed inhaled NO (iNO) directly to the airways and pulmonary vasculature could equally benefit patients. Therefore, a proof-of-concept study was performed to quantify pulmonary blood vessel caliber changes after iNO administration using computed tomography (CT)-based functional respiratory imaging (FRI). Methods Six patients with secondary PH due to COPD received “pulsed” iNO in combination with oxygen for 20 minutes via a nasal cannula. Patients underwent a high-resolution CT scan with contrast before and after iNO. Using FRI, changes in volumes of blood vessels and associated lobes were quantified. Oxygen saturation and blood pressure were monitored and patients were asked about their subjective feelings. Results Pulmonary blood vessel volume increased by 7.06%±5.37% after iNO. A strong correlation (Ω20=0.32, P=0.002) was obtained between ventilation and observed vasodilation, suggesting that using the pulsed system, iNO is directed toward the ventilated zones, which consequently experience more vasodilation. Patients did not develop oxygen desaturation, remained normotensive, and perceived an improvement in their dyspnea sensation. Conclusion Inhalation of pulsed NO with oxygen causes vasodilation in the pulmonary circulation of COPD patients, mainly in the well-ventilated areas. A high degree of heterogeneity was found in the level of vasodilation. Patients tend to feel better after the treatment. Chronic use trials are warranted. PMID:27462149

  10. Inhaled Nitric Oxide Therapy Fails to Improve Outcome in Experimental Severe Influenza

    PubMed Central

    Darwish, Ilyse; Miller, Chris; Kain, Kevin C.; Liles, W. Conrad

    2012-01-01

    In vitro, nitric oxide (NO) has been shown to have antimicrobial activity against a wide range of viruses, including influenza A virus. Therefore, we hypothesized that inhaled nitric oxide (iNO) would increase survival in vivo by reducing the viral load in C57Bl/6 mice infected with a lethal dose of influenza A/WSN/33 (H1N1; WSN/33) virus. NO was delivered to influenza-infected mice either continuously or intermittently at 80 or 160 ppm, respectively, using both prophylactic and post-infection treatment strategies. Murine survival and weight loss were assessed, and lung viral load was quantified via plaque assay. Here, we report that iNO administered prophylactically or post-influenza infection failed to improve survival of infected mice. No difference in lung viral load was observed between experimental groups. Although NO has antiviral activity against influenza A virus in vitro, iNO therapy provided no apparent benefit when used for treatment of influenza A virus infection in vivo. PMID:22253563

  11. Inhalants

    MedlinePlus

    ... Drug Facts Chat Day: Inhalants Drug Facts Chat Day: Inhalants Print Can you get high off of ... Cool Order Free Materials National Drugs & Alcohol Chat Day Newsletter Sign up to receive National Drug & Alcohol ...

  12. Producing nitric oxide by pulsed electrical discharge in air for portable inhalation therapy.

    PubMed

    Yu, Binglan; Muenster, Stefan; Blaesi, Aron H; Bloch, Donald B; Zapol, Warren M

    2015-07-01

    Inhalation of nitric oxide (NO) produces selective pulmonary vasodilation and is an effective therapy for treating pulmonary hypertension in adults and children. In the United States, the average cost of 5 days of inhaled NO for persistent pulmonary hypertension of the newborn is about $14,000. NO therapy involves gas cylinders and distribution, a complex delivery device, gas monitoring and calibration equipment, and a trained respiratory therapy staff. The objective of this study was to develop a lightweight, portable device to serve as a simple and economical method of producing pure NO from air for bedside or portable use. Two NO generators were designed and tested: an offline NO generator and an inline NO generator placed directly within the inspiratory line. Both generators use pulsed electrical discharges to produce therapeutic range NO (5 to 80 parts per million) at gas flow rates of 0.5 to 5 liters/min. NO was produced from air, as well as gas mixtures containing up to 90% O2 and 10% N2. Potentially toxic gases produced in the plasma, including nitrogen dioxide (NO2) and ozone (O3), were removed using a calcium hydroxide scavenger. An iridium spark electrode produced the lowest ratio of NO2/NO. In lambs with acute pulmonary hypertension, breathing electrically generated NO produced pulmonary vasodilation and reduced pulmonary arterial pressure and pulmonary vascular resistance index. In conclusion, electrical plasma NO generation produces therapeutic levels of NO from air. After scavenging to remove NO2 and O3 and filtration to remove particles, electrically produced NO can provide safe and effective treatment of pulmonary hypertension. PMID:26136478

  13. Low-dose inhaled nitric oxide in term and near-term infants with hypoxic respiratory failure: a Malaysian experience.

    PubMed

    Goh, A Y; Lum, L C; Roziah, M

    2001-09-01

    Inhaled nitric oxide (iNO) improves oxygenation in term and near-term infants with persistent pulmonary hypertension of the newborn (PPHN) and decreases the need for treatment with extracorporeal membrane oxygenation (ECMO). This mode of treatment is currently being introduced in Malaysia. We report our preliminary experience using low dose inhaled nitric oxide (20 parts per million) in three newborn infants (meconium aspiration syndrome, primary PPHN and congenital diaphragmatic hernia) with severe PPHN who fulfilled criteria for ECMO with a mean oxygenation index (OI) of 40. Two of the infants showed rapid and sustained improvement in oxygenation with a reduction in oxygenation index (OI) over 24 hours. The infant with diaphragmatic hernia showed an initial improvement in OI, which was unsustained and subsequently died. All three infants did not show significant elevation of methemoglobin or nitrogen dioxide (NO2). Inhaled nitric oxide is an effective and safe treatment for severe PPHN that can be used in a developing country like Malaysia. PMID:11732080

  14. Enhanced nitric oxide and reactive oxygen species production and damage after inhalation of silica.

    PubMed

    Porter, Dale W; Millecchia, Lyndell; Robinson, Victor A; Hubbs, Ann; Willard, Patsy; Pack, Donna; Ramsey, Dawn; McLaurin, Jeff; Khan, Amir; Landsittel, Douglas; Teass, Alexander; Castranova, Vincent

    2002-08-01

    In previous reports from this study, measurements of pulmonary inflammation, bronchoalveolar lavage cell cytokine production and nuclear factor-kappa B activation, cytotoxic damage, and fibrosis were detailed. In this study, we investigated the temporal relationship between silica inhalation, nitric oxide (NO), and reactive oxygen species (ROS) production, and damage mediated by these radicals in the rat. Rats were exposed to a silica aerosol (15 mg/m(3) silica, 6 h/day, 5 days/wk) for 116 days. We report time-dependent changes in 1) activation of alveolar macrophages and concomitant production of NO and ROS, 2) immunohistochemical localization of inducible NO synthase and the NO-induced damage product nitrotyrosine, 3) bronchoalveolar lavage fluid NO(x) and superoxide dismutase concentrations, and 4) lung lipid peroxidation levels. The major observations made in this study are as follows: 1) NO and ROS production and resultant damage increased during silica exposure, and 2) the sites of inducible NO synthase activation and NO-mediated damage are associated anatomically with pathological lesions in the lungs. PMID:12114212

  15. Inhaled nitric oxide and neonatal brain damage: experimental and clinical evidences.

    PubMed

    Sun, Bo

    2012-04-01

    Inhaled nitric oxide (iNO) has been used not only for pulmonary vasodilation in term neonates with hypoxemic respiratory failure, but also in preterm ones at risk of chronic lung disease (CLD) with variable results in prevention and treatment of CLD and/or brain injury. However, meta analysis of clinical trials does not support that iNO should be used routinely in preterm infants with hypoxic respiratory failure as it has no convincing long-term follow-up data to show its advantages in neurodevelopment. Investigation of extra-pulmonary effects of iNO through nitrosothiol hemoglobin-associated hypoxic vasodilation, as well as its intra- and extra-pulmonary anti-inflammation effect, would have biological and physiological potential in the management of the lung and brain injury of prematurity. The eligibility and safety of iNO in these premature infants at high risk of neurodevelopmental disability require more clinical and follow-up effort to test its pharmacological benefit over harm. PMID:22348510

  16. Inhaled nitric oxide protects males but not females from neonatal mouse hypoxia-ischemia brain injury.

    PubMed

    Zhu, Changlian; Sun, Yanyan; Gao, Jianfeng; Wang, Xiaoyang; Plesnila, Nikolaus; Blomgren, Klas

    2013-04-01

    It was recently discovered that while under normal conditions inhaled nitric oxide (iNO) does not affect cerebral blood flow, it selectively dilates arterioles in the ischemic penumbra during experimental cerebral ischemia, thereby increasing collateral blood flow and reducing ischemic brain damage. The mechanism was verified in multiple models, but only in male animals. Our aim was to evaluate the effects of iNO on brain injury in neonatal males and females. Nine-day-old mice were subjected to unilateral hypoxia-ischemia (HI), using 10% oxygen balanced with nitrogen, with or without 50 ppm NO. Brain injury 72 h after HI was reduced by iNO as judged by percentage of injury (-21.7%), atrophy (-23.7%), and total pathological score (-29%). The injury was significantly reduced in males (-32.4%, p<0.05) but not in females (-7.1%, n.s.). Neither the numbers nor the proliferation rates of neural stem cells in the dentate gyrus were affected by iNO. In summary, intraischemic iNO reduced neonatal HI brain injury in a gender-related manner. PMID:24323275

  17. Pulmonary effects of endogenous and exogenous nitric oxide in the pig: relation to cigarette smoke inhalation.

    PubMed Central

    Alving, K.; Fornhem, C.; Lundberg, J. M.

    1993-01-01

    1. Pentobarbitone-anaesthetized pigs were challenged with cigarette smoke (unfiltered or filtered through a Cambridge glass fibre filter to remove the particulate phase including nicotine), as well as nicotine aerosol and the gas phase components nitric oxide (NO) and carbon monoxide (CO); the effects on the bronchial and pulmonary circulations, and pulmonary airway mechanics, were examined. The relative importance of endogenous NO mechanisms in the pig lung was also studied by giving the NO synthesis inhibitor NG-nitro-L-arginine (L-NOARG; 50 mg kg-1) intravenously. Mean arterial pressure and blood flow in the bronchial, pulmonary and femoral circulations were measured, the latter with ultrasonic flow probes around the supplying arteries, and vascular resistance (VR) was calculated. Changes in pulmonary airways resistance (Rpulm) and lung dynamic compliance (Cdyn) were also determined. Finally, the concentration of NO in inhaled air during cigarette smoke and NO gas challenges was continuously monitored by a chemiluminescence method and the relative contribution of NO in cigarette smoke-induced vascular effects in the pig lung was calculated. 2. Cigarette smoke challenge, with or without a Cambridge filter, caused a rapid vasodilator response in the bronchial circulation and the major part (75%) of this response was probably caused by NO present in smoke. NO challenge caused profound bronchial vasodilation with dose-response characteristics between 10 and 100 p.p.m. The small part of the cigarette smoke-induced response not explained by the NO content may be caused by CO, showing weak vasodilator effect in the bronchial circulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8242246

  18. Mean airway pressure and response to inhaled nitric oxide in neonatal and pediatric patients.

    PubMed

    Hoffman, George M; Nelin, Leif D

    2005-01-01

    Inhaled nitric oxide (iNO) can improve oxygenation and ventilation-perfusion (V/Q) matching by reduction of shunt (Qs/Qt) in patients with hypoxemic lung disease. Because the improvement in V/Q matching must occur by redistribution of pulmonary blood flow, and because high airway pressure (Paw) increases physiologic dead space (Vd/Vt), we hypothesized that high Paw may limit the improvement in V/Q matching during iNO treatment. iNO 0-50 ppm was administered during mechanical ventilation. Mechanical ventilator settings were at the discretion of the attending physician. Qs/Qt and Vd/Vt were derived from a tripartite lung model with correction for shunt-induced dead space. Data from 62 patients during 153 trials were analyzed for effects of Paw and iNO on Qs/Qt and Vd/Vt. Baseline Qs/Qt was slightly increased at Paw 16-23 cmH2O (p < 0.05), while Vd/Vt increased progressively with higher Paw (p < 0.002). Therapy with iNO significantly reduced Qs/Qt (p < 0.001) at all levels of mean Paw, reaching a maximum reduction at 16-23 cmH2O (p < 0.05), such that Qs/Qt during iNO treatment was similar at all levels of Paw. During iNO treatment, a reduction in Vd/Vt occurred only at Paw of 8-15 cmH2O (p < 0.05), and the positive relationship between Vd/Vt and Paw was maintained. These differential effects on Qs/Qt and Vd/Vt suggest that both high and low Paw may limit improvement in gas exchange with iNO. Analysis of gas exchange using this corrected tripartite lung model may help optimize ventilatory strategies during iNO therapy. PMID:16465603

  19. Inhalants

    MedlinePlus

    ... Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription Drugs & Cold ... Notes Articles Adolescent Cigarette, Alcohol Use Declines as Marijuana Use Rises ( February 2013 ) Program Helps Troubled Boys ...

  20. [The effect of subchronic inhalations of nitric oxide on metabolic processes in blood of experimental animals].

    PubMed

    Soloveva, A G; Peretyagin, S P

    2016-01-01

    Metabolic processes were investigated in plasma and erythrocytes of Wistar rats exposed to daily 10-min sessions of NO inhalation for 30 days. These included determination of glucose and lactate, catalase activity, and activities of aldehyde dehydrogenase (ALDH), lactate dehydrogenase (LDH), and catalase. NO inhalation in a concentration of 20 ppm, 50 ppm and 100 ppm caused an increase in glucose and lactate. Inhalation of 100 ppm NO also increased catalase activity. Inhalation of all NO concentrations resulted in a decrease of ALDH activity, while the decrease in LDH activity was observed at NO concentrations of 50-100 ppm. PMID:27143382

  1. Is there a place for inhaled nitric oxide in the therapy of acute pulmonary embolism?

    PubMed

    Tanus-Santos, Jose E; Theodorakis, Michael J

    2002-01-01

    Acute pulmonary embolism (PE) is a serious complication resulting from the migration of emboli to the lungs. Although deep venous thrombi are the most common source of emboli to the lungs, other important sources include air, amniotic fluid, fat and bone marrow. Regardless of the specific source of the emboli, very little progress has been made in the pharmacological management of this high mortality condition. Because the prognosis is linked to the degree of elevation of pulmonary vascular resistance, any therapeutic intervention to improve the hemodynamics would probably increase the low survival rate of this critical condition. Inhaled nitric oxide (iNO) has been widely tested and used in cases of pulmonary hypertension of different causes. In the last few years some authors have described beneficial effects of iNO in animal models of acute PE and in anecdotal cases of massive PE. The primary cause of death in massive PE that is caused by deep venous thrombi, gas or amniotic fluid, is acute right heart failure and circulatory shock. Increased pulmonary vascular resistance following acute PE is the cumulative result of mechanical obstruction of pulmonary vessels and pulmonary arteriolar constriction (attributable to a neurogenic reflex and to the release of vasoconstrictors). As such, the vasodilator effects of iNO could actively oppose the pulmonary hypertension following PE. This hypothesis is consistently supported by experimental studies in different animal models of PE, which demonstrated that iNO decreased (by 10 to 20%) the pulmonary artery pressure without improving pulmonary gas exchange. Although maximal vasodilatory effects are probably achieved by less than 5 parts per million iNO, which is a relatively low concentration, no dose-response study has been published so far. In addition to the animal studies, a few anecdotal reports in the literature suggest that iNO may improve the hemodynamics during acute PE. However, no prospective, controlled

  2. Role of Inhaled Nitric Oxide in the Management of Severe Acute Respiratory Distress Syndrome

    PubMed Central

    Hunt, Juliette Lucinda; Bronicki, Ronald A.; Anas, Nick

    2016-01-01

    To date, there have been several systematic reviews with meta-analysis that have shown no reduction in mortality with the use of inhaled nitric oxide (iNO) in patients with acute respiratory distress syndrome (ARDS). Importantly, these reports fail to make a distinction between the pediatric and adult patient. The number of adult patients in these reviews are far greater than the number of pediatric patients, which makes it difficult to interpret the data regarding the role of iNO on the pediatric population. Extrapolating data from the adult population to the pediatric population is complicated as we know that physiology and the body’s response to disease can be different between adult and pediatric patients. iNO has been demonstrated to improve outcomes in term and near-term infants with hypoxic respiratory failure associated with pulmonary hypertension. Recently, Bronicki et al. published a prospective randomized control trial investigating the impact of iNO on the pediatric patient population with acute respiratory failure. In this study, a benefit of decreased duration of mechanical ventilation and an increased rate of ECMO-free survival was demonstrated in patients who were randomized to receiving iNO, suggesting that there may be benefit to the use of iNO in pediatric ARDS (PARDS) that has not been demonstrated in adults. iNO has repeatedly been shown to transiently improve oxygenation in all age groups, and yet neonates and pediatric patients have shown improvement in other outcomes that have not been seen in adults. The mechanism that explains improvement with the use of iNO in these patient populations are not well understood but does not appear to be solely a result of sustained improvement in oxygenation. There are physiologic studies that suggest alternative mechanisms for explaining the positive effects of iNO, such as platelet aggregation inhibition and reduction in systemic inflammation. Hence, the role of iNO by various mechanisms and in various

  3. Inhalants

    MedlinePlus

    ... or LSD. But you may not realize the dangers of substances in your own home. Household products such as glues, hair sprays, paints and lighter fluid can be drugs for kids in search of a quick high. Many young people ... need to know the dangers. Even inhaling once can disrupt heart rhythms and ...

  4. Echocardiographic evidence of improved hemodynamics during inhaled nitric oxide therapy for persistent pulmonary hypertension of the newborn.

    PubMed

    Ochikubo, C G; Waffarn, F; Turbow, R; Kanakriyeh, M

    1997-01-01

    To evaluate the cardiovascular effects of inhaled nitric oxide (NO) on the systemic and pulmonary circulations, 25 consecutive infants with severe persistent pulmonary hypertension of the newborn (PPHN) underwent serial echocardiographic evaluations before and during inhaled NO therapy. Estimation of the systolic pulmonary artery pressure (SPAP) was derived from measurement of a tricuspid regurgitant jet using Bernoulli's equation. We also derived a pulmonary/systemic pressure ratio to evaluate overall cardiopulmonary effects. Paired measurements of estimated SPAP decreased from 62.0 +/- 3.8 mmHg to 44.7 +/- 4.3 mmHg (p < 0.01) during inhaled NO therapy. The pulmonary/systemic pressure ratio decreased from 0.98 +/- 0.06 to 0.59 +/- 0.04 during NO therapy (p < 0.01), indicating a significant decline in the vascular resistance between the two circulations. These changes also correlated with changes in the extrapulmonary shunt patterns at the ductus arteriosus and foramen ovale seen during inhaled NO therapy. The decreased right-to-left shunting was accompanied by a parallel (64%) improvement in systemic oxygenation, with the alveolar-arterial oxygen gradient (A-a DO2) falling from 591 +/- 14 mmHg to 380 +/- 33 mmHg (p < 0.01). We found echocardiography to be a useful clinical tool for evaluating and monitoring pulmonary artery pressure in infants with PPHN. Measurement of the SPAP and the pulmonary/systemic pressure ratio gave a quantitative estimation of the severity of PPHN, and the extrapulmonary shunt flow patterns at the ductus arteriosus and foramen ovale gave qualitative estimates of its severity. Inhaled NO increased pulmonary blood flow and oxygenation and improved the systemic cardiopulmonary hemodynamics in this group of infants. PMID:9175525

  5. [Significance of nitric oxide inhalation (NO) in preterm infants< 34 weeks of gestation].

    PubMed

    Wirbelauer, J; Speer, C P

    2010-03-01

    In 2001, NO was approved as a therapeutic agent in Europe for the treatment of persistent pulmonary hypertension in late preterm infants >34 weeks of gestational age and term newborns. Recent observational studies suggest, that preterm infants <34 weeks of gestation with acute hypoxic lung failure could benefit from inhaled NO (iNO) by improved oxygenation. To date, 21 randomised-controlled trials have enrolled 3 336 preterm infants <34 weeks of gestation for iNO treatment. Overall, iNO treatment does not reduce the rate of bronchopulmonary dysplasia (BPD) or death compared to controls. In addition, iNO treatment of preterm infants with hypoxic respiratory failure or increased risk of BPD does not affect the combined incidence of death and BPD. However, early prophylactic use of iNO in preterm infants with respiratory distress seems to improve survival without BPD or severe cerebral damage. Current data of long term neurological outcome of iNO-treated preterm infants do not seem to justify iNO administration. Outside of well designed clinical trials iNO-treatment of preterm infants can currently not be recommended. PMID:20175046

  6. Fluorescence imaging microscopy of leukocytes-endothelium interaction in rat mesenteric microcirculation after endotoxin injection: role of inhaled nitric oxide

    NASA Astrophysics Data System (ADS)

    Mordon, Serge R.; Neviere, Remi; Marechal, Xavier-Marie; Buys, Bruno; Dhelin, Guy; Lesage, Jean C.; Mathieu, D.; Guery, Benoit; Chopin, Claude

    1999-02-01

    The adhesion of leukocytes to microvascular endothelium has been recognized as an important factor in the development of multiple organ dysfunction after a septic insult. We tested the hypothesis whether inhaled NO would reduce leukocyte rolling and / or leukocyte adhesion in the mesenteric venule preparation in endotoxemic rats. This study was performed with fluorescence imaging microscopy using a closed chamber for in vivo mesentery visualization. Leukocytes were selectively stained with acridine red. Compared to saline, endotoxemia was associated with increases in the flux of rolling leukocytes and in adherent and emigrated leukocytes. Inhaled nitric oxide treatment had no effects on leukocyte behavior in saline treated rats, whereas it reduced adherent and emigrated leukocytes in endotoxin-treated rats. In conclusion, we demonstrated that endotoxemia-induced leukocyte infiltration was related to an increase in the number of rolling leukocytes and subsequent adhesion and emigration in the mesenteric venule. Our results clearly showed that inhaled NO reduces leukocyte adhesion and transmigration in mesenteric venule of endotoxemic rats presumably by interfering with specific cell adhesion molecules.

  7. Dose-dependent onset and cessation of action of inhaled budesonide on exhaled nitric oxide and symptoms in mild asthma

    PubMed Central

    Kharitonov, S; Donnelly, L; Montuschi, P; Corradi, M; Collins, J; Barnes, P

    2002-01-01

    Background: Dose dependent anti-inflammatory effects of inhaled corticosteroids in asthma are difficult to demonstrate in clinical practice. The anti-inflammatory effect of low dose inhaled budesonide on non-invasive exhaled markers of inflammation and oxidative stress were assessed in patients with mild asthma. Methods: 28 patients entered a double blind, placebo controlled, parallel group study and were randomly given either 100 or 400 µg budesonide or placebo once daily, inhaled from a dry powder inhaler (Turbohaler), for 3 weeks followed by 1 week without treatment. Exhaled nitric oxide (NO), exhaled carbon monoxide (CO), nitrite/nitrate, S-nitrosothiols, and 8-isoprostanes in exhaled breath condensate were measured four times during weeks 1 and 4, and once a week during weeks 2 and 3. Results: A dose-dependent speed of onset and cessation of action of budesonide was seen on exhaled NO and asthma symptoms. Treatment with 400 µg/day reduced exhaled NO faster (–2.06 (0.37) ppb/day) than 100 µg/day (–0.51 (0.35) ppb/day; p<0.01). The mean difference between the effect of 100 and 400 µg budesonide was –1.55 ppb/day (95% CI –2.50 to –0.60). Pretreatment NO levels were positively related to the subsequent speed of reduction during the first 3–5 days of treatment. Faster recovery of exhaled NO was seen after stopping treatment with budesonide 400 µg/day (1.89 (1.43) ppb/day) than 100 µg/day (0.49 (0.34) ppb/day, p<0.01). The mean difference between the effect of 100 and 400 µg budesonide was 1.40 ppb/day (95% CI –0.49 to 2.31). Symptom improvement was dose-dependent, although symptoms returned faster in patients treated with 400 µg/day. A significant reduction in exhaled nitrite/nitrate and S-nitrosothiols after budesonide treatment was not dose-dependent. There were no significant changes in exhaled CO or 8-isoprostanes in breath condensate. Conclusion: Measurement of exhaled NO levels can indicate a dose-dependent onset and cessation of anti

  8. Beneficial effects of concomitant neuronal and inducible nitric oxide synthase inhibition in ovine burn and inhalation injury.

    PubMed

    Lange, Matthias; Hamahata, Atsumori; Enkhbaatar, Perenlei; Cox, Robert A; Nakano, Yoshimitsu; Westphal, Martin; Traber, Lillian D; Herndon, David N; Traber, Daniel L

    2011-06-01

    Different isoforms of nitric oxide (NO) synthase are critically involved in the development of pulmonary failure secondary to acute lung injury. Here we tested the hypothesis that simultaneous blockade of inducible and neuronal NO synthase effectively prevents the pulmonary lesions in an ovine model of acute respiratory distress syndrome induced by combined burn and smoke inhalation injury. Chronically instrumented sheep were allocated to a sham-injured group (n = 6), an injured and untreated group (n = 6), or an injured group treated with simultaneous infusion of selective inducible and neuronal NO synthase inhibitors (n = 5). The injury was induced by 48 breaths of cotton smoke and a third-degree burn of 40% total body surface area. All sheep were mechanically ventilated and fluid resuscitated. The injury induced severe pulmonary dysfunction as indicated by decreases in PaO2/FiO2 ratio and increases in pulmonary shunt fraction, ventilatory pressures, lung lymph flow, and lung wet/dry weight ratio. The treatment fully prevented the elevations in lymph and plasma nitrate/nitrite levels, pulmonary shunting, ventilatory pressures, lung lymph flow, and wet/dry weight ratio and significantly attenuated the decline in PaO2/FiO2 ratio. In conclusion, simultaneous blockade of inducible and neuronal NO synthase exerts beneficial pulmonary effects in an ovine model of acute respiratory distress syndrome secondary to combined burn and smoke inhalation injury. This novel treatment strategy may represent a useful therapeutic adjunct for patients with these injuries. PMID:21263377

  9. Nitric oxide and reactive oxygen species production causes progressive damage in rats after cessation of silica inhalation.

    PubMed

    Porter, Dale W; Millecchia, Lyndell L; Willard, Patsy; Robinson, Victor A; Ramsey, Dawn; McLaurin, Jeffery; Khan, Amir; Brumbaugh, Kurt; Beighley, Christoper M; Teass, Alexander; Castranova, Vincent

    2006-03-01

    Our laboratory has previously reported results from a rat silica inhalation study which determined that, even after silica exposure ended, pulmonary inflammation and damage progressed with subsequent fibrosis development. In the present study, the relationship between silica exposure, nitric oxide (NO) and reactive oxygen species (ROS) production, and the resultant pulmonary damage is investigated in this model. Rats were exposed to silica (15 mg/m3, 6 h/day) for either 20, 40, or 60 days. A portion of the rats from each exposure were sacrificed at 0 days postexposure, while another portion was maintained without further exposure for 36 days to examine recovery or progression. The major findings of this study are: (1) silica-exposed rat lungs were in a state of oxidative stress, the severity of which increased during the postexposure period, (2) silica-exposed rats had significant increase in lung NO production which increased in magnitude during the postexposure period, and (3) the presence of silica particle(s) in an alveolar macrophage (AM) was highly associated with inducible nitric oxide synthase (iNOS) protein. These data indicate that, even after silica exposure has ended, and despite declining silica lung burden, silica-induced pulmonary NO and ROS production increases, thus producing a more severe oxidative stress. A quantitative association between silica and expression of iNOS protein in AMs was also determined, which adds to our previous observation that iNOS and NO-mediated damage are associated anatomically with silica-induced pathological lesions. Future studies will be needed to determine whether the progressive oxidative stress, and iNOS activation and NO production, is a direct result of silica lung burden or a consequence of silica-induced biochemical mediators. PMID:16339787

  10. No redistribution of lung blood flow by inhaled nitric oxide in endotoxemic piglets pretreated with an endothelin receptor antagonist.

    PubMed

    Trachsel, Sebastien; Hambraeus-Jonzon, Kristina; Bergquist, Maria; Martijn, Cecile; Chen, Luni; Hedenstierna, Göran

    2015-03-15

    Inhaled nitric oxide (INO) improves ventilation-perfusion matching and alleviates pulmonary hypertension in patients with acute respiratory distress syndrome. However, outcome has not yet been shown to improve, and nonresponse is common. A better understanding of the mechanisms by which INO acts may guide in improving treatment with INO in patients with severe respiratory failure. We hypothesized that INO may act not only by vasodilation in ventilated lung regions, but also by causing vasoconstriction via endothelin (ET-1) in atelectatic, nonventilated lung regions. This was studied in 30 anesthetized, mechanically ventilated piglets. The fall in oxygenation and rise in pulmonary artery pressure during a sepsislike condition (infusion of endotoxin) were blunted by INO 40 ppm. Endotoxin infusion increased serum ET-1, and INO almost doubled the ratio between mRNA expression of endothelin receptor A (mediating vasoconstriction) and B (mediating vasodilation and clearance of ET-1) (ET-A/ET-B) in atelectatic lung regions. INO caused a shift in blood flow away from atelectatic lung regions in the endotoxemic piglets, but not during ET receptor antagonism. We conclude that INO in short-term experiments, in addition to causing selective pulmonary vasodilation in ventilated lung regions, increases the ET-A/ET-B mRNA expression ratio in lung tissue. This might augment the vasoconstriction in atelectatic lung regions, enhancing the redistribution of pulmonary blood flow to ventilated lung regions which are reached by INO. Such vasoconstriction may be an important additional factor explaining the effect of INO. PMID:25549764

  11. Impact of inhaled nitric oxide on the sulfatide profile of neonatal rat brain studied by TOF-SIMS imaging.

    PubMed

    Kadar, Hanane; Pham, Hoa; Touboul, David; Brunelle, Alain; Baud, Olivier

    2014-01-01

    Despite advances in neonatal intensive care leading to an increased survival rate in preterm infants, brain lesions and subsequent neurological handicaps following preterm birth remain a critical issue. To prevent brain injury and/or enhance repair, one of the most promising therapies investigated in preclinical models is inhaled nitric oxide (iNO). We have assessed the effect of this therapy on brain lipid content in air- and iNO-exposed rat pups by mass spectrometry imaging using a time-of-flight secondary ion mass spectrometry (TOF-SIMS) method. This technique was used to map the variations in lipid composition of the rat brain and, particularly, of the white matter. Triplicate analysis showed a significant increase of sulfatides (25%-50%) in the white matter on Day 10 of life in iNO-exposed animals from Day 0-7 of life. These robust, repeatable and semi-quantitative data demonstrate a potent effect of iNO at the molecular level. PMID:24670476

  12. A novel inhaled Syk inhibitor blocks mast cell degranulation and early asthmatic response.

    PubMed

    Ramis, Isabel; Otal, Raquel; Carreño, Cristina; Domènech, Anna; Eichhorn, Peter; Orellana, Adelina; Maldonado, Mónica; De Alba, Jorge; Prats, Neus; Fernández, Joan-Carles; Vidal, Bernat; Miralpeix, Montserrat

    2015-09-01

    Spleen tyrosine kinase (Syk) is essential for signal transduction of immunoreceptors. Inhibition of Syk abrogates mast cell degranulation and B cell responses. We hypothesized that Syk inhibition in the lung by inhaled route could block airway mast cells degranulation and the early asthmatic response without the need of systemic exposure. We discovered LAS189386, a novel Syk inhibitor with suitable properties for inhaled administration. The aim of this study was to characterize the in vitro and in vivo profile of LAS189386. The compound was profiled in Syk enzymatic assay, against a panel of selected kinases and in Syk-dependent cellular assays in mast cells and B cells. Pharmacokinetics and in vivo efficacy was assessed by intratracheal route. Airway resistance and mast cell degranulation after OVA challenge was evaluated in an ovalbumin-sensitized Brown Norway rat model. LAS189386 potently inhibits Syk enzymatic activity (IC50 7.2 nM), Syk phosphorylation (IC50 41 nM), LAD2 cells degranulation (IC50 56 nM), and B cell activation (IC50 22 nM). LAS189386 inhibits early asthmatic response and airway mast cell degranulation without affecting systemic mast cells. The present results support the hypothesis that topical inhibition of Syk in the lung, without systemic exposure, is sufficient to inhibit EAR in rats. Syk inhibition by inhaled route constitutes a promising therapeutic option for asthma. PMID:26051661

  13. Sildenafil to facilitate weaning from inhaled nitric oxide and mechanical ventilation in a patient with severe secondary pulmonary hypertension and a patent foramen ovale.

    PubMed

    Elias, Shlomo; Sviri, Sigal; Orenbuch-Harroch, Efrat; Fellig, Yakov; Ben-Yehuda, Arie; Fridlender, Zvi G; Gilon, Dan; Bayya, Abed

    2011-10-01

    We describe the case of a woman who presented to the intensive care unit with acute respiratory failure that required mechanical ventilation. She had severe pulmonary hypertension secondary to interstitial lung disease, and her history included sarcoidosis and tuberculosis. She was dependent on inhaled nitric oxide (INO) to maintain safe arterial oxygen saturation and could not be weaned from mechanical ventilation. Echocardiography revealed a patent foramen ovale with substantial right-to-left shunt, which probably contributed to her hypoxemia. Sildenafil enabled weaning from INO and substantially reduced the flow through the patent foramen ovale. She was successfully extubated and discharged home. To our knowledge, this is the first report of weaning from INO and mechanical ventilation in a patient with both severe secondary pulmonary hypertension and a right-to-left shunt through a patent foramen ovale. PMID:21513610

  14. Inhaled Nitric Oxide as an Adjunctive Treatment for Cerebral Malaria in Children: A Phase II Randomized Open-Label Clinical Trial

    PubMed Central

    Mwanga-Amumpaire, Juliet; Carroll, Ryan W.; Baudin, Elisabeth; Kemigisha, Elisabeth; Nampijja, Dorah; Mworozi, Kenneth; Santorino, Data; Nyehangane, Dan; Nathan, Daniel I.; De Beaudrap, Pierre; Etard, Jean-François; Feelisch, Martin; Fernandez, Bernadette O.; Berssenbrugge, Annie; Bangsberg, David; Bloch, Kenneth D.; Boum, Yap; Zapol, Warren M.

    2015-01-01

    Background. Children with cerebral malaria (CM) have high rates of mortality and neurologic sequelae. Nitric oxide (NO) metabolite levels in plasma and urine are reduced in CM. Methods. This randomized trial assessed the efficacy of inhaled NO versus nitrogen (N2) as an adjunctive treatment for CM patients receiving intravenous artesunate. We hypothesized that patients treated with NO would have a greater increase of the malaria biomarker, plasma angiopoietin-1 (Ang-1) after 48 hours of treatment. Results. Ninety-two children with CM were randomized to receive either inhaled 80 part per million NO or N2 for 48 or more hours. Plasma Ang-1 levels increased in both treatment groups, but there was no difference between the groups at 48 hours (P = not significant [NS]). Plasma Ang-2 and cytokine levels (tumor necrosis factor-α, interferon-γ, interleukin [IL]-1β, IL-6, IL-10, and monocyte chemoattractant protein-1) decreased between inclusion and 48 hours in both treatment groups, but there was no difference between the groups (P = NS). Nitric oxide metabolite levels—blood methemoglobin and plasma nitrate—increased in patients treated with NO (both P < .05). Seven patients in the N2 group and 4 patients in the NO group died. Five patients in the N2 group and 6 in the NO group had neurological sequelae at hospital discharge. Conclusions. Breathing NO as an adjunctive treatment for CM for a minimum of 48 hours was safe, increased blood methemoglobin and plasma nitrate levels, but did not result in a greater increase of plasma Ang-1 levels at 48 hours. PMID:26309894

  15. Inhaled and systemic corticosteroid response in severe asthma assessed by alveolar nitric oxide: a randomized crossover pilot study of add-on therapy

    PubMed Central

    Williamson, Peter A; Short, Philip M; Vaidyanathan, Sriram; Lipworth, Brian J

    2013-01-01

    AIMS Alveolar nitric oxide (CANO) is a potential biomarker of small airway inflammation. We investigated effects on CANO of the addition of coarse and fine particle inhaled corticosteroids to standard therapy in severe asthma. METHODS Severe asthmatics taking ≥1600 µg day−1 budesonide or equivalent performed a randomized open-label crossover study. Subjects with FEV1 < 80%, gas trapping and CANO≥2 ppb entered a 6 week dose-ramp run-in of fluticasone/salmeterol(FPSM) 250/50 µg twice daily for 3 weeks, then 500/50 µg twice daily for 3 weeks. Patients then received additional HFA-beclomethasone diproprionate (BDP) 200 µg twice daily or FP 250 µg twice daily for 3 weeks in a crossover. Participants then received prednisolone(PRED) 25 mg day−1 for 1 week. Nitric oxide, lung function, mannitol challenge, systemic inflammatory markers and urinary cortisol were measured. RESULTS Fifteen completed per protocol: mean (SD) age 51 (12) years, FEV1 58 (13)% predicted, residual volume 193 (100)% predicted and mannitolPD10 177 (2.8) µg. There was no significant difference between FPSM and add-on therapy for CANO. FPSM/BDP and FPSM/PRED suppressed broncial flux (JawNO) and FENO compared with FPSM alone, but there was no significant difference between FPSM/BDP and FPSM/FP. ECP, e-selectin and ICAM-1 were suppressed by FPSM/PRED compared with FPSM and FPSM/FP but not FPSM/BDP. Plasma cortisol was significantly suppressed by FPSM/PRED. CONCLUSION In severe asthma, CANO is insensitive to changes in dose and delivery of inhaled corticosteroids and is not suppressed by systemic corticosteroids. Additional inhaled HFA-BDP reduced FENO and JawNO without adrenal suppression. There was a trend to reduction in FENO and JawNO with additional FP but this did not reach statistical significance. PRED reduced FENO and JawNO with suppression of systemic inflammatory markers and urinary cortisol. PMID:22568828

  16. Airway nitric oxide in microgravity

    NASA Astrophysics Data System (ADS)

    Linnarsson, D.; Gustafsson, L.; Hemmingsson, Tryggve; Frostell, C.; Paiva, M.

    2005-10-01

    Nitric Oxide (NO), a molecule with a wide range of biological effects, is found in exhaled gas. Elevation of expired NO is an early sign of airway inflammation in asthma and dust inhalation. Animal experiments have demonstrated a marked increase of expired NO after venous gas emboli (bubbles, VGE), which may occur after decompression in conjunction with extravehicular activity (EVA). For this MAP project, astronauts will perform a simple inhalation-exhalation procedure weekly during their flights, and before and after EVA. Furthermore, the microgravity environment offers a possibility to gain new insights into how and where NO is formed in the lungs and what local effects NO may have there. The planned experiments have been made possible by recent developments of new techniques by the team's industrial partners; Aerocrine has developed a highly compact and accurate NO analyser, and Linde Gas Theapeutics has developed a highly compact device for NO administration in the inhaled air.

  17. Are serum cytokines early predictors for the outcome of burn patients with inhalation injuries who do not survive?

    PubMed Central

    Gauglitz, Gerd G; Finnerty, Celeste C; Herndon, David N; Mlcak, Ronald P; Jeschke, Marc G

    2008-01-01

    Introduction Severely burned patients suffering from inhalation injury have a significantly increased risk for mortality compared with burned patients without inhalation injury. Severe burn is associated with a distinct serum cytokine profile and alterations in cytokines that contribute to morbidity and mortality. The aim of the present study was therefore to determine whether severely burned pediatric patients with concomitant inhalation injury who had a fatal outcome exhibited a different serum cytokine profile compared with burn patients with inhalation injury who survived. Early identification followed by appropriate management of these high-risk patients may lead to improved clinical outcome. Methods Thirteen severely burned children with inhalation injury who did not survive and 15 severely burned pediatric patients with inhalation injury who survived were enrolled in the study. Blood was collected within 24 hours of admission and 5 to 7 days later. Cytokine levels were profiled using multiplex antibody coated beads. Inhalation injury was diagnosed by bronchoscopy during the initial surgery. The number of days on the ventilator, peak inspiratory pressure rates, arterial oxygen tension (PaO2)/fraction of inspired oxygen (FiO2) ratio and incidence of acute respiratory distress syndrome were recorded for those patients. Results Significantly altered levels of IL-4, IL-6, IL-7, IL-10, and IL-13 were detected within the first 7 days after admission in serum from burn pediatric patients with concomitant inhalation injury who did not survive when compared with similar patients who did (P < 0.05). Alterations in these cytokines were associated with increased incidence of acute respiratory distress syndrome, number of days under ventilation, increased peak inspiratory pressure, and lower PaO2/FiO2 ratio in this patient population. Multiple logistic regression analysis revealed that patients with increased IL-6 and IL-10 as well as decreased IL-7 serum levels had a

  18. Relationship between the Use of Inhaled Steroids for Chronic Respiratory Diseases and Early Outcomes in Community-Acquired Pneumonia

    PubMed Central

    Almirall, Jordi; Bolíbar, Ignasi; Serra-Prat, Mateu; Palomera, Elisabet; Roig, Jordi; Hospital, Imma; Carandell, Eugenia; Agustí, Mercè; Ayuso, Pilar; Estela, Andreu; Torres, Antoni

    2013-01-01

    Background The role of inhaled steroids in patients with chronic respiratory diseases is a matter of debate due to the potential effect on the development and prognosis of community-acquired pneumonia (CAP). We assessed whether treatment with inhaled steroids in patients with chronic bronchitis, COPD or asthma and CAP may affect early outcome of the acute pneumonic episode. Methods Over 1-year period, all population-based cases of CAP in patients with chronic bronchitis, COPD or asthma were registered. Use of inhaled steroids were registered and patients were followed up to 30 days after diagnosis to assess severity of CAP and clinical course (hospital admission, ICU admission and mortality). Results Of 473 patients who fulfilled the selection criteria, inhaled steroids were regularly used by 109 (23%). In the overall sample, inhaled steroids were associated with a higher risk of hospitalization (OR=1.96, p = 0.002) in the bivariate analysis, but this effect disappeared after adjusting by other severity-related factors (adjusted OR=1.08, p=0.787). This effect on hospitalization also disappeared when considering only patients with asthma (OR=1.38, p=0.542), with COPD alone (OR=4.68, p=0.194), but a protective effect was observed in CB patients (OR=0.15, p=0.027). Inhaled steroids showed no association with ICU admission, days to clinical recovery and mortality in the overall sample and in any disease subgroup. Conclusions Treatment with inhaled steroids is not a prognostic factor in COPD and asthmatic patients with CAP, but could prevent hospitalization for CAP in patients with clinical criteria of chronic bronchitis. PMID:24039899

  19. Multi-detector computed tomography demonstrates smoke inhalation injury at early stage.

    PubMed

    Koljonen, Virve; Maisniemi, Kreu; Virtanen, Kaisa; Koivikko, Mika

    2007-06-01

    A multitrauma victim was transported to our trauma centre. Smoke inhalation injury was suspected based on trauma history and clinical examination. The first trauma computer tomography (CT) obtained 2.8 h after the injury revealed subtle ground-glass opacifications with mainly peribronchial distribution and patchy peribronchial consolidations centrally in the left lung. A repeated scan showed a more distinctive demarcation of the peribronchial opacities, further substantiating the clinically verified smoke inhalation injury. The golden standard for diagnosing smoke inhalation injury still is fibroptic bronchoscopy examination. This paper shows that lesions typical to smoke inhalation injury appear much earlier than previously reported. Whether assessment of smoke inhalation injury severity using CT could clinically benefit patients is controversial and still requires further research. Multi-detector computed tomography is readily available in trauma centres and to simply neglect its potential as a diagnostic tool in some inhalation injury would be unwise. PMID:17285330

  20. Liquid nitrogen cryotherapy of lip mucosa hemangiomas under inhalation general anesthesia with sevoflurane in early infancy.

    PubMed

    Chen, Wei-liang; Zhang, Bin; Li, Jin-song; Yang, Zhao-hui; Wang, Yong-jie; Huang, Zhi-quan; Ye, Yu-shan

    2009-02-01

    Mucous membrane hemangiomas of the lip are common benign vascular tumors of infancy. This clinical study evaluated the efficacy and safety of liquid nitrogen cryotherapy of mucous membrane hemangiomas of the lip in early infancy. It was a retrospective review of 127 pediatric patients with hemangiomas involving the lips who underwent liquid nitrogen cryotherapy under inhalation general anesthesia with sevoflurane. Forty-one males and 86 females were treated. The overall median age at diagnosis of the mucous membrane hemangiomas was 3.6 months (range, 7 days to 18 months). The oral mucous membrane hemangioma involved the vermilion of the lower lip in 78 cases (61.4%), the vermilion of the upper lip in 40 cases (31.5%), and both vermilions in 9 cases (7.1%). No complications because of anesthesia occurred. The mean follow-up was 10 months, with a range of 8 to 14 months; 94 lesions (74.0%) were completely involuted, 22 lesions (17.3%) were mostly involuted, 11 lesions (8.7%) were partially involuted, and no lesion showed a small amount of involution. Liquid nitrogen cryotherapy is an effective, simple, and safe treatment for mucous membrane hemangiomas of the lip in early infancy. PMID:19158525

  1. Inhaled nitric oxide in acute respiratory distress syndrome with and without septic shock requiring norepinephrine administration: a dose–response study

    PubMed Central

    Mourgeon, Eric; Puybasset, Louis; Law-Koune, Jean-Dominique; Lu, Qin; Abdennour, Lamine; Gallart, Lluis; Malassine, Patrick; Rao, GS Umamaheswara; Cluzel, Philippe; Bennani, Abdelhai; Coriat, Pierre; Rouby, Jean-Jacques

    1997-01-01

    Background: The aim of this prospective study was to assess whether the presence of septic shock could influence the dose response to inhaled nitric oxide (NO) in NO-responding patients with adult respiratory distress syndrome (ARDS). Results: Eight patients with ARDS and without septic shock (PaO2 = 95 ± 16 mmHg, PEEP = 0, FiO2 = 1.0), and eight patients with ARDS and septic shock (PaO2 = 88 ± 11 mmHg, PEEP = 0, FiO2 = 1.0) receiving exclusively norepinephrine were studied. All responded to 15 ppm inhaled NO with an increase in PaO2 of at least 40 mmHg, at FiO2 1.0 and PEEP 10 cmH2O. Inspiratory intratracheal NO concentrations were recorded continuously using a fast response time chemiluminescence apparatus. Seven inspiratory NO concentrations were randomly administered: 0.15, 0.45, 1.5, 4.5, 15, 45 and 150 ppm. In both groups, NO induced a dose-dependent decrease in mean pulmonary artery pressure (MPAP), pulmonary vascular resistance index (PVRI), and venous admixture (QVA/QT), and a dose-dependent increase in PaO2/FiO2 (P ≤ 0.012). Dose-response of MPAP and PVRI were similar in both groups with a plateau effect at 4.5 ppm. Dose-response of PaO2/FiO2 was influenced by the presence of septic shock. No plateau effect was observed in patients with septic shock and PaO2/FiO2 increased by 173 ± 37% at 150 ppm. In patients without septic shock, an 82 ± 26% increase in PaO2/FiO2 was observed with a plateau effect obtained at 15 ppm. In both groups, dose-response curves demonstrated a marked interindividual variability and in five patients pulmonary vascular effect and improvement in arterial oxygenation were dissociated. Conclusion: For similar NOinduced decreases in MPAP and PVRI in both groups, the increase in arterial oxygenation was more marked in patients with septic shock. PMID:11056694

  2. Enhancing prediction of inhalant abuse risk in samples of early adolescents: a secondary analysis.

    PubMed

    Crano, William D; Gilbert, Cindy; Alvaro, Eusebio M; Siegel, Jason T

    2008-07-01

    The theory of reasoned action (TRA) was used to estimate adolescents' vulnerability to inhalant abuse, operationalized by intentions to use or avoid inhalants. The model correctly differentiated 78% of all respondents (N=596). A second analysis highlighted variables that discriminated properly identified from misclassified youth. False positives, those defined as being at-risk, but who repudiated inhalants, were significantly less likely than their at-risk peers to have used inhalants; they used inhalants and marijuana less frequently; were monitored more closely by parents; and were less rebellious (all p<.05). False negatives, defined as not at-risk, but who had not unequivocally rejected inhalants, were significantly more likely than their similarly classed peers to have used inhalants and marijuana, and to have used both more frequently; also, they were less highly acculturated. This study reaffirmed the utility of the TRA and underscored factors that might improve classification accuracy. This approach may facilitate prevention efforts, and may be extrapolated to any context in which risk categorization is used as a basis for prevention or amelioration. PMID:18367345

  3. The Evolution of Pressurized Metered-Dose Inhalers from Early to Modern Devices.

    PubMed

    Roche, Nicolas; Dekhuijzen, P N Richard

    2016-08-01

    Pressurized metered-dose inhalers (pMDIs) are sometimes viewed as old-fashioned and as having been superseded by dry powder inhalers (DPIs). Here, we review the technological advances that characterize modern pMDIs, and consider how they can influence the effectiveness of drug delivery for patients with asthma and chronic obstructive pulmonary disease. Compared with old chlorofluorocarbon (CFC)-based inhalers, many hydrofluoroalkane (HFA)-driven pMDIs have more favorable plume characteristics such as a reduced velocity and a higher fine particle fraction; together, these advances have resulted in the development of pMDIs with reduced oropharyngeal deposition and increased lung deposition. In addition, the plume from many HFA-pMDIs is warmer, which may facilitate their use by patients; moreover, devices are equipped with dose counters, which improves their reliability. As well as reviewing the technological advances of pMDIs, we also discuss the importance of individualizing inhaler therapies to each patient by accounting for their personal preferences and natural breathing patterns. Because pMDIs and DPIs differ considerably in their handling characteristics, matching the right inhaler to the right patient is key to ensuring effective therapy and good compliance. Finally, the majority of patients can be trained successfully in the correct use of their pMDI; training and regular monitoring of inhalation technique are essential prerequisites for effective therapy. While the 'ideal inhaler' may not exist, pMDIs are an effective device option suitable for many patients. pMDIs, together with other types of devices, offer opportunities for the effective individualization of treatments. PMID:26824873

  4. Reactive Oxygen Species and Nitric Oxide Control Early Steps of the Legume – Rhizobium Symbiotic Interaction

    PubMed Central

    Damiani, Isabelle; Pauly, Nicolas; Puppo, Alain; Brouquisse, Renaud; Boscari, Alexandre

    2016-01-01

    The symbiotic interaction between legumes and nitrogen-fixing rhizobium bacteria leads to the formation of a new organ, the nodule. Early steps of the interaction are characterized by the production of bacterial Nod factors, the reorientation of root-hair tip growth, the formation of an infection thread (IT) in the root hair, and the induction of cell division in inner cortical cells of the root, leading to a nodule primordium formation. Reactive oxygen species (ROS) and nitric oxide (NO) have been detected in early steps of the interaction. ROS/NO are determinant signals to arbitrate the specificity of this mutualistic association and modifications in their content impair the development of the symbiotic association. The decrease of ROS level prevents root hair curling and ITs formation, and that of NO conducts to delayed nodule formation. In root hairs, NADPH oxidases were shown to produce ROS which could be involved in the hair tip growth process. The use of enzyme inhibitors suggests that nitrate reductase and NO synthase-like enzymes are the main route for NO production during the early steps of the interaction. Transcriptomic analyses point to the involvement of ROS and NO in the success of the infection process, the induction of early nodulin gene expression, and the repression of plant defense, thereby favoring the establishment of the symbiosis. The occurrence of an interplay between ROS and NO was further supported by the finding of both S-sulfenylated and S-nitrosylated proteins during early symbiotic interaction, linking ROS/NO production to a redox-based regulation of the symbiotic process. PMID:27092165

  5. Reactive Oxygen Species and Nitric Oxide Control Early Steps of the Legume - Rhizobium Symbiotic Interaction.

    PubMed

    Damiani, Isabelle; Pauly, Nicolas; Puppo, Alain; Brouquisse, Renaud; Boscari, Alexandre

    2016-01-01

    The symbiotic interaction between legumes and nitrogen-fixing rhizobium bacteria leads to the formation of a new organ, the nodule. Early steps of the interaction are characterized by the production of bacterial Nod factors, the reorientation of root-hair tip growth, the formation of an infection thread (IT) in the root hair, and the induction of cell division in inner cortical cells of the root, leading to a nodule primordium formation. Reactive oxygen species (ROS) and nitric oxide (NO) have been detected in early steps of the interaction. ROS/NO are determinant signals to arbitrate the specificity of this mutualistic association and modifications in their content impair the development of the symbiotic association. The decrease of ROS level prevents root hair curling and ITs formation, and that of NO conducts to delayed nodule formation. In root hairs, NADPH oxidases were shown to produce ROS which could be involved in the hair tip growth process. The use of enzyme inhibitors suggests that nitrate reductase and NO synthase-like enzymes are the main route for NO production during the early steps of the interaction. Transcriptomic analyses point to the involvement of ROS and NO in the success of the infection process, the induction of early nodulin gene expression, and the repression of plant defense, thereby favoring the establishment of the symbiosis. The occurrence of an interplay between ROS and NO was further supported by the finding of both S-sulfenylated and S-nitrosylated proteins during early symbiotic interaction, linking ROS/NO production to a redox-based regulation of the symbiotic process. PMID:27092165

  6. Higher Activity of the Inducible Nitric Oxide Synthase Contributes to Very Early Onset Inflammatory Bowel Disease

    PubMed Central

    Dhillon, Sandeep S; Mastropaolo, Lucas A; Murchie, Ryan; Griffiths, Christopher; Thöni, Cornelia; Elkadri, Abdul; Xu, Wei; Mack, Amanda; Walters, Thomas; Guo, Conghui; Mack, David; Huynh, Hien; Baksh, Shairaz; Silverberg, Mark S; Brumell, John H; Snapper, Scott B; Muise, Aleixo M

    2014-01-01

    OBJECTIVES: The NOS2 gene encodes for the inducible nitric oxide synthase (iNOS), responsible for nitric oxide (NO) production, which contributes to antimicrobial and antipathogenic activities. Higher levels of both iNOS and NO-induced damage have been observed in inflammatory bowel disease (IBD) patients. NOS2 may have a role in a specific subset of IBD patients with severe and/or extensive colitis. Therefore, the aim of this study is to examine the role of NOS2 in such a subset, very early onset IBD (VEO-IBD). METHODS: Seventeen tag single nucleotide polymorphisms (SNPs) in the NOS2 gene were successfully genotyped in VEO-IBD patients. Genetic associations were replicated in an independent VEO-IBD cohort. Functional analysis for iNOS activity was performed on the most significantly associated functional variant. RESULTS: The NOS2 rs2297518 SNP was found to be associated in VEO-IBD in two independent cohorts. Upon combined analysis, a coding variant (S608L) showed the strongest association with VEO-IBD (Pcombined=1.13 × 10−6, OR (odds ratio)=3.398 (95% CI (confidence interval) 2.02–5.717)) as well as associations with VEO-Crohn's disease and VEO-ulcerative colitis (UC). This variant also showed an association with UC diagnosed between 11 and 17 years of age but not with adult-onset IBD (>17 years). B-cell lymphoblastoid cell lines genotyped for the risk variant as well as Henle-407 cells transfected with a plasmid construct with the risk variant showed higher NO production. Colonic biopsies of VEO-IBD patients showed higher immunohistochemical staining of nitrotyrosine, indicating more nitrosative stress and tissue damage. CONCLUSIONS: These studies suggest the importance of iNOS in genetic susceptibility to younger IBD presentation due to higher NO production. PMID:24430113

  7. Inducible nitric oxide synthase mediates early epithelial repair of porcine ileum.

    PubMed

    Gookin, Jody L; Rhoads, J Marc; Argenzio, Robert A

    2002-07-01

    Reports conflict regarding the effect of nitric oxide (NO) on intestinal epithelium. In chronic injury, NO appears detrimental by combining with reactive oxygen to form potent-free radicals. In contrast, inhibition of NO synthesis after acute injury exacerbates damage and inflammation. Recent studies have disclosed constitutive expression of inducible NO synthase (iNOS) by normal intestinal epithelia, yet little attention has been given to the role of iNOS in acute epithelial repair. We studied the local effects of iNOS on early epithelial repair of porcine ileal mucosa injured by deoxycholate within Ussing chambers. iNOS was constitutively expressed by the villous epithelium, and after deoxycholate injury, iNOS was expressed by injured and detaching enterocytes. Selective inhibition of iNOS abolished increases in NO synthesis and villous reepithelialization after injury. Exogenous L-arginine rescued baseline reepithelialization from NOS inhibitors but was only capable of stimulating additional repair in the presence of serum. These results demonstrate that iNOS-derived NO is a key mediator of early villous reepithelialization following acute mucosal injury. PMID:12065303

  8. Normobaric hyperoxia delays and attenuates early nitric oxide production in focal cerebral ischemic rats.

    PubMed

    Yuan, Zhongrui; Liu, Wenlan; Liu, Baoyi; Schnell, Aaron; Liu, Ke Jian

    2010-09-17

    Overproduction of neuronal nitric oxide synthase (nNOS)-derived NO is detrimental during cerebral ischemia. Normobaric hyperoxia (NBO) has been shown to be neuroprotective, extending the therapeutic time window for ischemic stroke, but the mechanism is not fully understood. In the present study, using a rat model of ischemic stroke, we investigated the effect of early NBO treatment on neuronal NO production. Male Sprague-Dawley rats were given normoxia (30% O(2)) or NBO (95% O(2)) during 10, 30, 60 or 90min filament occlusion of the middle cerebral artery. NO(x)(-) (nitrite plus nitrate) and 3-nitrotyrosine were measured in the ischemic cortex. Ischemia caused a rapid increase in the production of NO(x)(-), with a peak at 10min after ischemia onset, then gradually declining to the baseline level at 60min. NBO treatment delayed the NO(x)(-) production peak to 30min and attenuated the total amount of NO(x)(-). Ischemia also increased 3-nitrotyrosine formation, which was significantly reduced by NBO treatment. Inhibition of nNOS by pre-treatment with 7-nitroindazole had similar effect as NBO treatment on NO(x)(-) and 3-nitrotyrosine production, and when combined with NBO, no further reduction in NO production was observed. Furthermore, NBO treatment significantly decreased brain infarct volume. Taken together, our findings demonstrate that delaying and attenuating the early NO release from nNOS may be an important mechanism accounting for NBO's neuroprotection. PMID:20633543

  9. Comparison of early mortality in baboons and dogs after inhalation of /sup 239/PuO/sub 2/

    SciTech Connect

    Bair, W.J.; Metivier, H.; Park, J.F.; Masse, R.; Stevens, D.L.; Lafuma, J.; Watson, C.R.; Nolibe, D.

    1980-06-01

    Results from experiments with baboons were compared with those from experiments with dogs to determine the relative sensitivity of the two species to early mortality from inhaled /sup 239/PuO/sub 2/. To ensure a valid comparison of data developed at two laboratories, methodology differences were minimized by establishing a common pool of raw data, using the same computer programs to analyze the data, and standardizing assumptions regarding the calculation of plutonium concentration in lungs. Several comparison methods were used involving variations in estimating different parameters used in these calculations. Although nearly all comparisons suggested baboons were slightly more sensitive, none of the methods for comparing the relationship between dose and survival time showed consistently significant differences between baboons and dogs. Although the baboons were physiologically and morphologically immature when exposed to plutonium, whereas the dogs were mature, we concluded that adult baboons and dogs are similarly sensitive to the early effects of inhaled /sup 239/PuO/sub 2/. Since only early mortality was considered in this comparison, the results do not apply to possible late effects caused by much lower levels of plutonium than were used in these experiments.

  10. Nitric Oxide Chemical Donor Affects the Early Phases of In Vitro Wound Healing Process.

    PubMed

    La Torre, Cristina; Cinque, Benedetta; Lombardi, Francesca; Miconi, Gianfranca; Palumbo, Paola; Evtoski, Zoran; Placidi, Giuseppe; Fanini, Donatella; Cimini, Anna Maria; Benedetti, Elisabetta; Giuliani, Maurizio; Cifone, Maria Grazia

    2016-10-01

    An artificial wound in a confluent monolayer of human keratinocyte HaCaT cells or mouse embryo fibroblast Swiss NIH 3T3 cells was used to analyze the effects of the nitric oxide (NO) chemical donor, S-nitroso-N-acetylpenicillamine (SNAP). SNAP exposure promoted an enhanced rate of wound closure and accelerated motility of both keratinocytes and fibroblasts compared to control cells. The wounded monolayer cultures of HaCaT and NIH 3T3 cells, treated with or without SNAP, were monitored under a phase contrast microscope. Structural and ultrastructural modifications were analyzed by scanning electron microscopy (SEM). The images were captured by a digital camera at different time points (0-28 h) and the wound area was analyzed through software included in Matlab®. As early as 15 min, SNAP induced significant cytoskeletal remodeling, as shown by immunostaining (phalloidin-labelling), which in turn was associated with increased filopodium number and length rise. NO donor treatment also induced overexpression of Ki-67 protein, a typical marker of cell proliferation, as shown by immunostaining. Both SNAP-induced migration and proliferation were antagonized by the NO-sensitive GC inhibitor 1H-[1,2,4]oxadiazolo[-4,3-a]quinoxalin-1-one (ODQ), which suggests activation of the NO/cGMP signalling cascade in the observed SNAP-induced effects in the early stages of the healing process. Moreover, we provide evidence that PPAR-β antagonist (GSK0660) may interfere with NO-mediated wound healing process. J. Cell. Physiol. 231: 2185-2195, 2016. © 2016 Wiley Periodicals, Inc. PMID:26841260

  11. Nitric oxide-mediated vasodilation increases blood flow during the early stages of stress fracture healing.

    PubMed

    Tomlinson, Ryan E; Shoghi, Kooresh I; Silva, Matthew J

    2014-02-15

    Despite the strong connection between angiogenesis and osteogenesis in skeletal repair conditions such as fracture and distraction osteogenesis, little is known about the vascular requirements for bone formation after repetitive mechanical loading. Here, established protocols of damaging (stress fracture) and nondamaging (physiological) forelimb loading in the adult rat were used to stimulate either woven or lamellar bone formation, respectively. Positron emission tomography was used to evaluate blood flow and fluoride kinetics at the site of bone formation. In the group that received damaging mechanical loading leading to woven bone formation (WBF), (15)O water (blood) flow rate was significantly increased on day 0 and remained elevated 14 days after loading, whereas (18)F fluoride uptake peaked 7 days after loading. In the group that received nondamaging mechanical loading leading to lamellar bone formation (LBF), (15)O water and (18)F fluoride flow rates in loaded limbs were not significantly different from nonloaded limbs at any time point. The early increase in blood flow rate after WBF loading was associated with local vasodilation. In addition, Nos2 expression in mast cells was increased in WBF-, but not LBF-, loaded limbs. The nitric oxide (NO) synthase inhibitor N(ω)-nitro-l-arginine methyl ester was used to suppress NO generation, resulting in significant decreases in early blood flow rate and bone formation after WBF loading. These results demonstrate that NO-mediated vasodilation is a key feature of the normal response to stress fracture and precedes woven bone formation. Therefore, patients with impaired vascular function may heal stress fractures more slowly than expected. PMID:24356518

  12. Exogenous nitric oxide (NO) generated by NO-plasma treatment modulates osteoprogenitor cells early differentiation

    NASA Astrophysics Data System (ADS)

    Elsaadany, Mostafa; Subramanian, Gayathri; Ayan, Halim; Yildirim-Ayan, Eda

    2015-09-01

    In this study, we investigated whether nitric oxide (NO) generated using a non-thermal plasma system can mediate osteoblastic differentiation of osteoprogenitor cells without creating toxicity. Our objective was to create an NO delivery mechanism using NO-dielectric barrier discharge (DBD) plasma that can generate and transport NO with controlled concentration to the area of interest to regulate osteoprogenitor cell activity. We built a non-thermal atmospheric pressure DBD plasma nozzle system based on our previously published design and similar designs in the literature. The electrical and spectral analyses demonstrated that N2 dissociated into NO under typical DBD voltage-current characteristics. We treated osteoprogenitor cells (MC3T3-E1) using NO-plasma treatment system. Our results demonstrated that we could control NO concentration within cell culture media and could introduce NO into the intracellular space using NO-plasma treatment with various treatment times. We confirmed that NO-plasma treatment maintained cell viability and did not create any toxicity even with prolonged treatment durations. Finally, we demonstrated that NO-plasma treatment induced early osteogenic differentiation in the absence of pro-osteogenic growth factors/proteins. These findings suggest that through the NO-plasma treatment system we are able to generate and transport tissue-specific amounts of NO to an area of interest to mediate osteoprogenitor cell activity without subsequent toxicity. This opens up the possibility to develop DBD plasma-assisted tissue-specific NO delivery strategies for therapeutic intervention in the prevention and treatment of bone diseases.

  13. Adaptative nitric oxide overproduction in perivascular adipose tissue during early diet-induced obesity.

    PubMed

    Gil-Ortega, Marta; Stucchi, Paula; Guzmán-Ruiz, Rocío; Cano, Victoria; Arribas, Silvia; González, M Carmen; Ruiz-Gayo, Mariano; Fernández-Alfonso, Maria S; Somoza, Beatriz

    2010-07-01

    Perivascular adipose tissue (PVAT) plays a paracrine role in regulating vascular tone. We hypothesize that PVAT undergoes adaptative mechanisms during initial steps of diet-induced obesity (DIO) which contribute to preserve vascular function. Four-week-old male C57BL/6J mice were assigned either to a control [low-fat (LF); 10% kcal from fat] or to a high-fat diet (HF; 45% kcal from fat). After 8 wk of dietary treatment vascular function was analyzed in the whole perfused mesenteric bed (MB) and in isolated mesenteric arteries cleaned of PVAT. Relaxant responses to acetylcholine (10(-9)-10(-4) m) and sodium nitroprusside (10(-12)-10(-5) m) were significantly ameliorated in the whole MB from HF animals. However, there was no difference between HF and LF groups in isolated mesenteric arteries devoid of PVAT. The enhancement of relaxant responses detected in HF mice was not attributable to an increased release of nitric oxide (NO) from the endothelium nor to an increased sensitivity and/or activity of muscular guanilylcyclase. Mesenteric PVAT of HF animals showed an increased bioavailability of NO, detected by 4,5-diaminofluorescein diacetate (DAF2-DA) staining, which positively correlated with plasma leptin levels. DAF-2DA staining was absent in PVAT from ob/ob mice but was detected in these animals after 4-wk leptin replacement. The main finding in this study is that adaptative NO overproduction occurs in PVAT during early DIO which might be aimed at preserving vascular function. PMID:20410199

  14. Evaluation of salivary nitric oxide level in children with early childhood caries

    PubMed Central

    Senthil Eagappan, AR; Rao, V. Arun Prasad; Sujatha, S.; Senthil, D.; Sathiyajeeva, J.; Rajaraman, G.

    2016-01-01

    Background: Nitric oxide (NO), a highly reactive radical, participates in the nonspecific natural defense mechanism of the oral cavity. The present study was attempted to evaluate the salivary NO levels in 4–5 year-old children with early childhood caries (ECC). The objective of the present study was to assess the salivary NO concentration in children with different caries activity. Materials and Methods: The study included 120 healthy 4.5 year-old children and they were equally divided into three groups based on decayed, missing, filled surfaces (dmfs) score; forty caries-free children (control group), forty children with dmfs 1.5 (ECC group), and forty with dmfs ⩾6 (severe ECC group). Saliva collected was measured for NO concentration by Griess reaction method. The obtained data were analyzed by ANOVA and Pearson's correlation coefficient. Results: The mean level of NO in the saliva of the control group was 51.2 ± 8.3457 and that of ECC and severe ECC were 47.1 ± 5.2614 and 33.625 ± 4.6942, respectively. The mean salivary NO concentration was significantly higher in healthy controls when compared to children with ECC and severe ECC. Moreover, a negative correlation (r = −0.6658) was observed between the salivary NO level and the mean dmfs, suggesting that as the salivary NO level decreases, the caries incidence increases. Conclusion: The obtained results support the antimicrobial activity of salivary NO and also suggest that an increase in NO production might contribute to lower the caries occurrence in children. PMID:27605992

  15. Malignant alterations following early blockade of nitric oxide synthase in hypertensive rats.

    PubMed

    Hsu, Yung Hsiang; Hsu, Bang Gee; Chen, Hsing I

    2007-12-31

    Nitric oxide (NO) is important for the homeostasis of organ functions. We studied the structural and functional changes in the cardiovascular (CV) and renal systems following early NO deprivation by various nonspecific and specific NO synthase (NOS) inhibitors: N-nitro-L-arginine methyl ester (L-NAME), N-nitro-L-arginine (L-NA), S-methyl-isothiourea (SMT), and L-N6-(1-iminoethyl)-lysine (L-Nil). The aim is to elucidate the involvement of NO through endothelial or inducible NOS (eNOS and iNOS). Drugs were given to spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar Kyoto rats (WKY) from a young age (5-wk-old). Physiological, biochemical, and pathological examinations were performed. L-NAME and L-NA treatment caused a rapid increase in tail cuff pressure (TCP). The TCP of SHR reached a malignant level within 30 days with signs of stroke, proteinuria [corrected] severe glomerular sclerosis, and moderate ventricular hypertrophy (VH). The plasma nitrite/nitrate was reduced, while creatinine, urea nitrogen and uric acid were elevated. The renal tissue cyclic guanosine monophosphate (cGMP) was decreased with an elevated collagen content. The numbers of sclerotic glomeruli, arteriolar and glomerular injury scores were markedly increased, accompanied by reduction in renal blood flow, filtration rate, and fraction. Plasma endothelin-1 was increased following L,-NAME or L-NA treatment for 10 days. The expression of eNOS and iNOS mRNA was depressed by L-NAME and L-NA. The relevant iNOS inhibitors, SMT and L-Nil depressed the iNOS expression, but did not produce significant changes in CV and renal systems. The continuous release of NO via the eNOS system provides a compensatory mechanism to prevent the genetically hypertensive rats from rapid progression to malignant phase. Removal of this compensation results in VH, stroke, glomerular damage, renal function impairment, and sudden death. PMID:18442011

  16. Inhalation Injuries

    MedlinePlus

    ... you can inhale that can cause acute internal injuries. Particles in the air from fires and toxic ... and lung diseases worse. Symptoms of acute inhalation injuries may include Coughing and phlegm A scratchy throat ...

  17. Fluticasone Oral Inhalation

    MedlinePlus

    ... by mouth using an inhaler and as a powder to inhale by mouth using an inhaler. Fluticasone ... Flovent® HFA) is usually inhaled twice daily. Fluticasone powder for oral inhalation (Flovent® Diskus) is usually inhaled ...

  18. [Relationships between nitric oxide response signal and external factors during the early interaction between Pinus thunbergii and Bursaphelenchus xylophilus].

    PubMed

    Yu, Lu-Zhen; Wu, Xiao-Qin; Ye, Jian-Ren; Zhang, Sai-nan

    2013-03-01

    In the interaction between Pinus thunbergii and Bursaphelenchus xylophilus, nitric oxide (NO) is an important signaling molecule involving in the early response of P. thunbergii to the invasion of B. xylophilus. However, it is unclear that whether the NO production by P. thunbergii is triggered by the invaded B. xylophilus or its secreted metabolites. In the present study, the P. thunbergii was inoculated with living B. xylophilus, its secretion, and the suspension of grinded B. xylophilus, respectively, and the nitric oxide synthase (NOS) activity and NO content in the P. thunbergii were detected at the early stage. In all treatments, the inoculated P. thunbergii appeared disease symptoms, and the NOS activity and NO content in the P. thunbergii inoculated with B. xylophilus secretion and grinded B. xylophilus suspension increased, suggesting that besides living B. xylophilus, its contents or secretion could also trigger the expression of NO response signal in P. thunbergii, inducing the downstream response and causing the disease development of P. thunbergi. With the increasing temperature at 15-25 degrees C, both the NOS activity and the NO content in inoculated P. thunbergii increased, and the disease symptoms appeared earlier. The same patterns of NOS activity, NO content, and disease symptoms were also observed under increasing drought stress. It was suggested that within a definite range, increased. temperature and drought stress could enhance the NO signal expression in inoculated P. thunbergii and accelerate its disease development, and thus, the disease development of inoculated P. thunbergii under high temperature and drought condition could be related to the enhancement of the NO response signal in the host. PMID:23755476

  19. Development of a long-term ovine model of cutaneous burn and smoke inhalation injury and the effects of early excision and skin autografting

    PubMed Central

    Yamamoto, Yusuke; Enkhbaatar, Perenlei; Sakurai, Hiroyuki; Rehberg, Sebastian; Asmussen, Sven; Ito, Hiroshi; Sousse, Linda E.; Cox, Robert A.; Deyo, Donald J.; Traber, Lillian D.; Traber, Maret G.; Herndon, David N.; Traber, Daniel L.

    2013-01-01

    Smoke inhalation injury frequently increases the risk of pneumonia and mortality in burn patients. The pathophysiology of acute lung injury secondary to burn and smoke inhalation is well studied, but long-term pulmonary function, especially the process of lung tissue healing following burn and smoke inhalation, has not been fully investigated. By contrast, early burn excision has become the standard of care in the management of major burn injury. While many clinical studies and small-animal experiments support the concept of early burn wound excision, and show improved survival and infectious outcomes, we have developed a new chronic ovine model of burn and smoke inhalation injury with early excision and skin grafting that can be used to investigate lung pathophysiology over a period of 3 weeks. Materials and methods Eighteen female sheep were surgically prepared for this study under isoflurane anesthesia. The animals were divided into three groups: an Early Excision group (20% TBSA, third-degree cutaneous burn and 36 breaths of cotton smoke followed by early excision and skin autografting at 24 h after injury, n = 6), a Control group (20% TBSA, third-degree cutaneous burn and 36 breaths of cotton smoke without early excision, n = 6) and a Sham group (no injury, no early excision, n = 6). After induced injury, all sheep were placed on a ventilator and fluid-resuscitated with Lactated Ringers solution (4 mL/% TBS/kg). At 24 h post-injury, early excision was carried out to fascia, and skin grafting with meshed autografts (20/1000 in., 1:4 ratio) was performed under isoflurane anesthesia. At 48 h post-injury, weaning from ventilator was begun if PaO2/FiO2 was above 250 and sheep were monitored for 3 weeks. Results At 96 h post-injury, all animals were weaned from ventilator. There are no significant differences in PaO2/FiO2 between Early Excision and Control groups at any points. All animals were survived for 3 weeks without infectious complication in Early Excision

  20. Overview of inhalation toxicology.

    PubMed Central

    Dorato, M A

    1990-01-01

    The development of inhalation toxicology as a distinct discipline can be traced back well over one hundred years. The technology has advanced in terms of materials and designs used to construct inhalation chambers and the equipment used to generate controlled test atmospheres of a wide variety of gases, vapors, dusts, and droplets. Consideration of metered dose inhalers, a relatively recent concern, has led to the design of new equipment for administering this unique dosage form. The parameters used to evaluate inhalation toxicity are similar to those used for any other route of administration. In addition, there are some unique procedures for early screening of pulmonary toxicity, especially within a series of related chemicals. Images FIGURE 1. FIGURE 3. FIGURE 7. FIGURE 8. PMID:2200660

  1. Early life microbial exposure and fractional exhaled nitric oxide in school-age children: a prospective birth cohort study

    PubMed Central

    2013-01-01

    Background Inflammation is a key factor in the pathogenesis of respiratory diseases. Early life exposure to microbial agents may have an effect on the development of the immune system and on respiratory health later in life. In the present work we aimed to evaluate the associations between early life microbial exposures, and fractional exhaled nitric oxide (FeNO) at school age. Methods Endotoxin, extracellular polysaccharides (EPS) and β(1,3)-D-glucan were measured in living room dust collected at 2–3 months of age in homes of participants of three prospective European birth cohorts (LISA, n = 182; PIAMA, n = 244; and INMA, n = 355). Home dampness and pet ownership were periodically reported by the parents through questionnaires. FeNO was measured at age 8 for PIAMA and at age 10/11 for LISA and INMA. Cohort-specific associations between the indoor microbial exposures and FeNO were evaluated using multivariable regression analyses. Estimates were combined using random-effects meta-analyses. Results FeNO at school age was lower in children exposed to endotoxin at age 2–3 months (β -0.05, 95% confidence interval (CI) -0.10;-0.01) and in children with reported dog ownership during the first two years of life (GM ratio 0.82, CI 0.70-0.96). FeNO was not significantly associated with early life exposure to EPS, β(1,3)-D-glucan, indoor dampness and cat ownership. Conclusion Early life exposure to bacterial endotoxin and early life dog ownership are associated with lower FeNO at school age. Further studies are needed to confirm our results and to unravel the underlying mechanisms and possible clinical relevance of this finding. PMID:24295277

  2. Increased nitric oxide in exhaled air: an early marker of asthma in non-smoking aluminium potroom workers?

    PubMed Central

    Lund, M; Oksne, P; Hamre, R; Kongerud, J

    2000-01-01

    air may be an early marker of airway inflammation in aluminium potroom workers.


Keywords: nitric oxide; occupational asthma; potroom workers PMID:10810115

  3. Endothelial nitric oxide synthase immunoreactivity in early gestation and in trophoblastic disease.

    PubMed Central

    Ariel, I; Hochberg, A; Shochina, M

    1998-01-01

    AIMS: To study the localisation of the endothelial nitric oxide synthase (eNOS) in the normal placenta, with special emphasis on the implantation site in the first trimester of pregnancy, and in the different subtypes of trophoblastic cells in gestational trophoblastic disease. METHODS: The immunoperoxidase technique with an antibody directed against eNOS was applied to paraffin sections from first and second trimester placentas, placenta accreta, partial and complete hydatidiform moles, and choriocarcinoma. Immunoperoxidase staining for human placental lactogen (hPL) was performed on parallel sections. RESULTS: Prominent immunoreactivity for eNOS was found to be present in the intermediate trophoblastic cells of the cell columns of the anchoring villi and in trophoblastic cells at the implantation site. Staining was also present in the syncytiotrophoblast, most conspicuous at the apical cell border. In trophoblastic disease, proliferating large mononuclear cells, which were strongly positive for hPL, were found to be immunoreactive for eNOS. CONCLUSIONS: eNOS immunoreactivity is strongly positive in the extravillous trophoblastic cells and to a lesser extent in the syncytiotrophoblast. In the former it may play a role in implantation and vascular invasion. Cells with differentiation to intermediate trophoblast in complete hydatidiform mole and choriocarcinoma also show high levels of eNOS, which may be associated with the haematogenous mode of spread of trophoblastic disease. Images PMID:9771440

  4. Immunohistochemical detection of early myocardial damage in two sudden deaths due to intentional butane inhalation. Two case reports with review of literature.

    PubMed

    Novosel, Irena; Kovačić, Zdravko; Gusić, Stjepan; Batelja, Lovorka; Nestić, Marina; Seiwerth, Sven; Skavić, Josip

    2011-04-01

    The abuse of household and other commercially available products containing volatile organic solvents is underrecognized. Not infrequently intentional butane inhalation results in high morbidity and mortality. A fatal outcome of butane abuse can be caused by asphyxia, cardiac arrhythmia or trauma. The reported number of cases in which death was the consequence of pure butane inhalation is limited, and in most cases a mixture of propellants was involved. This report covers two cases of sudden death due to the sniffing of a cigarette lighter refill containing butane. Autopsy was followed by toxicological, pathohistological and immunohistochemical analysis. Butane gas was confirmed in samples of blood, urine, brain and lungs by the gas chromatography method - "headspace" technique. Histology showed almost identical changes in the lungs and heart in both cases. The morphology of heart damage on standard H/E stains was of special interest because it displayed all the characteristics of chronic and acute myocardial hypoxia found in the absence of atherosclerotic heart disease. In order to confirm early cardiac death caused by asphyxia due to butane inhalation a panel of immunohistochemical agents was used: Myoglobin, Desmin, Fibronectin, Fibrinogen and CC9. PMID:21420651

  5. Inhalant Abuse

    MedlinePlus

    ... risk of being hurt in a fall, a fire or a car crash (for example, if your child tries to drive while he or she is high on an inhalant). Inhalants block oxygen flow to the brain and every other organ ...

  6. Mometasone Oral Inhalation

    MedlinePlus

    ... powder to inhale by mouth and as an aerosol to inhale by mouth using an inhaler. Mometasone ... inhaler is not working properly.To use the aerosol inhaler, follow these steps: Remove the cap from ...

  7. Tiotropium Oral Inhalation

    MedlinePlus

    ... use the inhaler to breathe in the dry powder contained in the capsules. Tiotropium is usually inhaled ... the inhaler it comes with to inhale the powder in the capsules. Never try to inhale them ...

  8. Early generation of nitric oxide contributes to copper tolerance through reducing oxidative stress and cell death in hulless barley roots.

    PubMed

    Hu, Yanfeng

    2016-09-01

    The objective of this study was to investigate the specific role of nitric oxide (NO) in the early response of hulless barley roots to copper (Cu) stress. We used the fluorescent probe diaminofluorescein-FM diacetate to establish NO localization, and hydrogen peroxide (H2O2)-special labeling and histochemical procedures for the detection of reactive oxygen species (ROS) in the root apex. An early production of NO was observed in Cu-treated root tips of hulless barley, but the detection of NO levels was decreased by supplementation with a NO scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO). Application of sodium nitroprusside (a NO donor) relieved Cu-induced root inhibition, ROS accumulation and oxidative damage, while c-PTIO treatment had a synergistic effect with Cu and further enhanced ROS levels and oxidative stress. In addition, the Cu-dependent increase in activities of superoxide dismutase, peroxidase and ascorbate peroxidase were further enhanced by exogenous NO, but application of c-PTIO decreased the activities of catalase and ascorbate peroxidase in Cu-treated roots. Subsequently, cell death was observed in root tips and was identified as a type of programed cell death (PCD) by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The addition of NO prevented the increase of cell death in root tips, whereas inhibiting NO accumulation further increased the number of cells undergoing PCD. These results revealed that NO production is an early response of hulless barley roots to Cu stress and that NO contributes to Cu tolerance in hulless barley possibly by modulating antioxidant defense, subsequently reducing oxidative stress and PCD in root tips. PMID:27294966

  9. Asthma Inhalers

    MedlinePlus

    ... reduce the release of chlorofluorocarbons (CFCs) into the atmosphere when taking certain asthma medications. Until recently, most ... hydrofluoroalkane (HFA) inhalers, that do not rob the atmosphere of ozone. “The FDA [Food and Drug Administration] ...

  10. Mometasone Oral Inhalation

    MedlinePlus

    ... children 12 years of age and older. Mometasone powder for oral inhalation (Asmanex® Twisthaler) is used in ... Mometasone inhalation comes as a powder to inhale by mouth and as an aerosol to inhale by mouth using an inhaler. Mometasone oral inhalation is usually inhaled ...

  11. Endogenous oestrogens do not regulate endothelial nitric oxide production in early postnatal rats.

    PubMed

    Sofronova, Svetlana I; Gaynullina, Dina K; Martyanov, Andrey A; Tarasova, Olga S

    2015-10-15

    Previously we showed that endothelium of 1-2-weeks old rats exerts an anticontractile effect due to spontaneous NO production which correlates with a higher eNOS expression level compared to adult rats. Oestrogens are powerful regulators of eNOS expression and activity in arterial endothelium. This study tested the hypothesis that anticontractile influence of endothelium in young rats is regulated by endogenous oestrogens. Wistar rats were daily treated with ICI 182,780 or letrozole (oestrogen receptor antagonist and aromatase inhibitor, respectively; s.c., 1mg/kg/day) from the second postnatal day, control pups received vehicle injections. At the age of 10-12-days we studied contraction of saphenous arteries using wire myography. ELISA and qPCR were used to evaluate blood sex steroids levels and mRNA expression in arterial tissue, respectively. Ten-12 days old male rats compared to adult male rats demonstrated 78% higher serum 17β-oestradiol concentration and several-fold increase in mRNA contents of oestrogen receptors (ERα and GPER1). However, treatments with ICI 182,780 or letrozole did not affect arterial sensitivity to methoxamine (α1-adrenoceptor agonist) in 10-12-days old males. The blockade of NO-synthase with L-NNA caused tonic contraction and potentiated the response to methoxamine, these effects were similar in control and both treated groups. The sensitivity of endothelium-denuded saphenous arteries to NO-donor DEA/NO did not differ between control and treated groups as well. In addition, treatments with ICI 182,780 or letrozole did not change eNOS expression level in arterial tissue. Our results suggest that endogenous oestrogens do not regulate anticontractile effect of NO during early postnatal development in rats. PMID:26415981

  12. Perinatal Exogenous Nitric Oxide in Fawn-Hooded Hypertensive Rats Reduces Renal Ribosomal Biogenesis in Early Life

    PubMed Central

    Wesseling, Sebastiaan; Essers, Paul B.; Koeners, Maarten P.; Pereboom, Tamara C.; Braam, Branko; van Faassen, Ernst E.; MacInnes, Alyson W.; Joles, Jaap A.

    2011-01-01

    Nitric oxide (NO) is known to depress ribosome biogenesis in vitro. In this study we analyzed the influence of exogenous NO on ribosome biogenesis in vivo using a proven antihypertensive model of perinatal NO administration in genetically hypertensive rats. Fawn-hooded hypertensive rat (FHH) dams were supplied with the NO-donor molsidomine in drinking water from 2 weeks before to 4 weeks after birth, and the kidneys were subsequently collected from 2 day, 2 week, and 9 to 10-month-old adult offspring. Although the NO-donor increased maternal NO metabolite excretion, the NO status of juvenile renal (and liver) tissue was unchanged as assayed by EPR spectroscopy of NO trapped with iron-dithiocarbamate complexes. Nevertheless, microarray analysis revealed marked differential up-regulation of renal ribosomal protein genes at 2 days and down-regulation at 2 weeks and in adult males. Such differential regulation of renal ribosomal protein genes was not observed in females. These changes were confirmed in males at 2 weeks by expression analysis of renal ribosomal protein L36a and by polysome profiling, which also revealed a down-regulation of ribosomes in females at that age. However, renal polysome profiles returned to normal in adults after early exposure to molsidomine. No direct effects of molsidomine were observed on cellular proliferation in kidneys at any age, and the changes induced by molsidomine in renal polysome profiles at 2 weeks were absent in the livers of the same rats. Our results suggest that the previously found prolonged antihypertensive effects of perinatal NO administration may be due to epigenetically programmed alterations in renal ribosome biogenesis during a critical fetal period of renal development, and provide a salient example of a drug-induced reduction of ribosome biogenesis that is accompanied by a beneficial long-term health effect in both males and females. PMID:22303348

  13. Inhaled /sup 147/Pm and/or total-body gamma radiation: Early mortality and morbidity in rats

    SciTech Connect

    Filipy, R.E.; Lauhala, K.E.; McGee, D.R.; Cannon, W.C.; Buschbom, R.L.; Decker, J.R.; Kuffel, E.G.; Park, J.F.; Ragan, H.A.; Yaniv, S.S.; Scott, B.R.

    1989-05-01

    Rats were given doses of /sup 60/Co gamma radiation and/or lung burdens of /sup 147/Pm (in fused aluminosilicate particles) within lethal ranges in an experiment to determine and compare morbidity and mortality responses for the radiation insults within 1 year after exposure. Radiation-induced morbidity was assessed by measuring changes in body weights, hematologic parameters, and pulmonary-function parameters. Acute mortality and morbidity from inhaled promethium were caused primarily by radiation pneumonitis and pulmonary fibrosis that occurred more than 53 days after exposure. Acute mortality and morbidity from total-body gamma irradiation occurred within 30 days of exposure and resulted from the bone-marrow radiation syndrome. Gamma radiation caused transient morbidity, reflected by immediately depressed blood cell levels and by reduced body weight gain in animals that survived the acute gamma radiation syndrome. Inhaled promethium caused a loss of body weight and diminished pulmonary function, but its only effect on blood cell levels was lymphocytopenia. Combined gamma irradiation and promethium lung burdens were synergistic, in that animals receiving both radiation insults had higher morbidity and mortality rates than would be predicted based on the effect of either kind of radiation alone. Promethium lung burdens enhanced the effect of gamma radiation in rats within the first 30 days of exposure, and gamma radiation enhanced the later effect of promethium lung burdens. 70 refs., 68 figs., 21 tabs.

  14. Insulin Human Inhalation

    MedlinePlus

    ... inhalation comes as a powder to inhale by mouth using a special inhaler. It is usually used ... to your doctor.Before you use your insulin oral inhaler the first time, read the written instructions ...

  15. Inhaled Asthma Medications

    MedlinePlus

    ... metered – dose inhaler (MDI), which uses a chemical propellant to push the medication out of the inhaler. ... powder inhalers (DPIs) deliver medication without using chemical propellants, but they require a strong and fast inhalation. ...

  16. Only an early nitric oxide burst and the following wave of secondary nitric oxide generation enhanced effective defence responses of pelargonium to a necrotrophic pathogen.

    PubMed

    Floryszak-Wieczorek, Jolanta; Arasimowicz, Magdalena; Milczarek, Grzegorz; Jelen, Henryk; Jackowiak, Hanna

    2007-01-01

    Participation of nitric oxide (NO) in cross-talk between ivy pelargonium (Pelargonium peltatum) leaves and Botrytis cinerea was investigated using electrochemical and biochemical approaches. In response to the necrotroph, leaves initiated a near-immediate NO burst, but the specificity of its generation was dependent on the genetic makeup of the host plant. In the resistant cultivar, a strong NO burst was followed by a wave of secondary NO generation, shown by bio-imaging with DAF-2DA. The epicentre of NO synthesis was located in targeted cells, which exhibited a TUNEL-positive reaction. Soon after the challenge, an elevated concentration of hydrogen peroxide (H(2)O(2)) was correlated with a reversible inhibition of catalase (CAT), ascorbate peroxidase (APX), and suppression of ethylene synthesis. The induced NO generation initially expanded and then gradually disappeared on successive days, provoking noncell-death-associated resistance with an enhanced pool of antioxidants, which finally favoured the maintenance of homeostasis of surrounding cells. By contrast, in the susceptible pelargonium, a weak NO burst was recorded and further NO generation increased only as the disease progressed, which was accompanied by very intensive H(2)O(2) and ethylene synthesis. The pathogen colonizing susceptible cells also acquired the ability to produce considerable amounts of NO and enhanced nitrosative and oxidative stress in host tissues. PMID:17688587

  17. Experimental studies of the early effects of inhaled beta-emitting radionuclides for nuclear accident risk assessment: Phase 2 report

    SciTech Connect

    Scott, B.R.; Hahn, F.F.; Newton, G.J.; Snipes, M.B.; Damon, E.G.; Mauderly, J.L.; Boecker, B.B.; Gray, D.H.

    1987-11-01

    This report summarizes a series of experiments concerning the effect of linear energy transfer and temporal radiation dose pattern to the lung from inhaled beta-emitting radionuclides. The results were used to test the validity of a hazard-function mathematical model for predicting death from radiation pneumonitis. Both morbidity and mortality within 18 months after exposure were examined in rats exposed to beta-emitting radionuclides, giving brief or protracted irradiation of the lung or having weak or strong beta emissions. Protraction of the radiation dose to the lung from a half-time in the lung of less than three days to a half-time with a long-term component of about 150 days has a sparing effect. The median lethal dose for the protracted irradiation is about 1.7 times the median lethal dose for the brief irradiation. Low energy beta emissions from /sup 147/Pm have a similar effectiveness in producing lethal injury as high energy beta emissions from /sup 90/Sr. Changes in three parameters of morbidity were measured: body weight, hematology and pulmonary function; only changes in pulmonary function correlated well with pulmonary radiation injury. The doses of radiation required to produce impaired function, however, were not significantly different from those that produced death. The hazard-function model for predicting death from radiation pneumonitis, which was developed from previously obtained data for inhalation exposures of dogs to beta-emitting radionuclides, adequately predicted the median lethal doses for rats receiving one of several different beta dose rate patterns to the lung, thus strengthening the validity of the mathematical model. 23 refs., 41 figs., 12 tabs.

  18. Inhalation Injuries

    MedlinePlus

    ... increase mortality 30% to 40% when patients with cutaneous burns and inhalation injury are compared with patients ... nasal hairs • Facial burns • Burns around the mouth • Mineral spirits – 104º F – paint thinner, brush cleaner. • Redness, ...

  19. Bone mineral density in children treated with daily or periodical inhaled budesonide: the Helsinki Early Intervention Childhood Asthma study.

    PubMed

    Turpeinen, Markku; Pelkonen, Anna S; Nikander, Kurt; Sorva, Ritva; Selroos, Olof; Juntunen-Backman, Kaisu; Haahtela, Tari

    2010-08-01

    In a double-blind, randomized study, 136 children, 5-10-y-old, with newly detected persistent asthma received budesonide (BUD) 400 microg twice daily for 1 mo and thereafter 200 microg twice daily for 5 mo. Thereafter, 50 children were treated with BUD 100 microg twice daily, whereas 44 children used BUD as needed for 1 y; an additional 42 children received disodium cromoglycate (DSCG). Asthma exacerbations were treated with BUD for 2 wk in a dose of 400 microg twice daily in all groups. In this secondary analysis, bone mineral density (BMD) of the lumbar vertebrae was measured before and after the 18-mo treatment. Compared with DSCG, regular BUD treatment resulted in a significantly smaller increase in BMD (0.023 versus 0.034 g/cm; p = 0.023) and height (7.75 versus 8.80 cm; p = 0.001). Periodic treatment did not affect BMD. No intergroup differences were observed when BMD data were adjusted for changes in height. Daily BUD treatment in prepubertal children may slow down the increment in BMD and standing height. This was not observed in children receiving BUD periodically after the initial regular BUD treatment. The correlation between height and BMD suggests that following children's height might afford an estimation of inhaled corticosteroid effects on bone. PMID:20485203

  20. Inhibitory effects of inhaled complex traditional Chinese medicine on early and late asthmatic responses induced by ovalbumin in sensitized guinea pigs

    PubMed Central

    2011-01-01

    Background Many formulae of traditional Chinese medicines (TCMs) have been used for antiasthma treatment dating back many centuries. There is evidence to suggest that TCMs are effective as a cure for this allergenic disease administered via gastric tubes in animal studies; however, their efficacy, safety and side effects as an asthmatic therapy are still unclear. Methods In this study, guinea pigs sensitized with ovalbumin (OVA) were used as an animal model for asthma challenge, and the sensitization of animals by bronchial reactivity to methacholine (Mch) and the IgE concentration in the serum after OVA challenge were estimated. Complex traditional Chinese herbs (CTCM) were administered to the animals by nebulization, and the leukocytes were evaluated from bronchoalveolar lavage fluid (BALF). Results The results showed that inhalation of CTCM could abolish the increased lung resistance (13-fold increase) induced by challenge with OVA in the early asthmatic response (EAR), reducing to as low as baseline (1-fold). Moreover, our results indicated higher IgE levels (range, 78-83 ng/ml) in the serum of sensitized guinea pigs than in the unsensitized controls (0.9 ± 0.256 ng/ml). In addition, increased total leukocytes and higher levels of eosinophils and neutrophils were seen 6 hours after challenge, and the increased inflammatory cells were reduced by treatment with CTCM inhalation. The interleukin-5 (IL-5) level in BALF was also reduced by CTCM. Conclusion Our findings indicate a novel method of administering traditional Chinese medicines for asthma treatment in an animal model that may be more effective than traditional methods. PMID:21943157

  1. Daily versus as-needed inhaled corticosteroid for mild persistent asthma (The Helsinki early intervention childhood asthma study)

    PubMed Central

    Turpeinen, M; Nikander, K; Pelkonen, A S; Syvänen, P; Sorva, R; Raitio, H; Malmberg, P; Juntunen-Backman, K; Haahtela, T

    2008-01-01

    Objective: To compare the effect of inhaled budesonide given daily or as-needed on mild persistent childhood asthma. Patients, design and interventions: 176 children aged 5–10 years with newly detected asthma were randomly assigned to three treatment groups: (1) continuous budesonide (400 μg twice daily for 1 month, 200 μg twice daily for months 2–6, 100 μg twice daily for months 7–18); (2) budesonide, identical treatment to group 1 during months 1–6, then budesonide for exacerbations as needed for months 7–18; and (3) disodium cromoglycate (DSCG) 10 mg three times daily for months 1–18. Exacerbations were treated with budesonide 400 μg twice daily for 2 weeks. Main outcome measures: Lung function, the number of exacerbations and growth. Results: Compared with DSCG the initial regular budesonide treatment resulted in a significantly improved lung function, fewer exacerbations and a small but significant decline in growth velocity. After 18 months, however, the lung function improvements did not differ between the groups. During months 7–18, patients receiving continuous budesonide treatment had significantly fewer exacerbations (mean 0.97), compared with 1.69 in group 2 and 1.58 in group 3. The number of asthma-free days did not differ between regular and intermittent budesonide treatment. Growth velocity was normalised during continuous low-dose budesonide and budesonide therapy given as needed. The latter was associated with catch-up growth. Conclusions: Regular use of budesonide afforded better asthma control but had a more systemic effect than did use of budesonide as needed. The dose of ICS could be reduced as soon as asthma is controlled. Some children do not seem to need continuous ICS treatment. PMID:17634183

  2. Biotransformation of nitric oxide.

    PubMed Central

    Yoshida, K; Kasama, K

    1987-01-01

    Previous investigations into the health effects of nitrogen oxides (NOx) have mostly been conducted with special reference to nitrogen dioxide (NO2) and its direct effects on the respiratory system, while the study of nitric oxide (NO) has been disregarded. We carried out a study on NO by exposing rats and mice to 15NO or administering 15N-nitrite and 15N-nitrate to these animals by IP injection in order to elucidate the metabolic fate of NO. The results of our study and previous findings led us to assume that the major metabolic path of inhaled NO is as follows: inhaled NO reacts with hemoglobin, forming nitrosyl-hemoglobin (NOHb), and from NOHb, nitrite (NO2-) and nitrate (NO3-) are generated. Major quantities of NO3- are discharged into the urine and a certain amount is discharged into the oral cavity through the salivary glands and transformed to NO2-. Part of this NO2- is converted to N2 gas in the stomach. Nitrate in the intestine is partly reduced to ammonia (NH3) through NO2-, reabsorbed into the body, and converted to urea. Most of the metabolites of inhaled NO are excreted rapidly from the body within 48 hr. PMID:3665863

  3. Levalbuterol Oral Inhalation

    MedlinePlus

    ... by mouth using a nebulizer, and as an aerosol to inhale by mouth using an inhaler. The ... will come in canisters. Each canister of levalbuterol aerosol is designed to provide 200 inhalations. After the ...

  4. Albuterol Oral Inhalation

    MedlinePlus

    ... that affect the lungs and airways). Albuterol inhalation aerosol and powder for oral inhalation is also used to prevent breathing difficulties during exercise. Albuterol inhalation aerosol (Proair HFA, Proventil HFA, Ventolin HFA) is used ...

  5. Substance use - inhalants

    MedlinePlus

    ... in (inhaled). Common types of abused inhalants are: Aerosols, such as air freshener, deodorant, fabric protector, hair ... a gas from a balloon Dusting: Spraying an aerosol into the nose or mouth Glading: Inhaling air- ...

  6. Host-Mycobacterium avium subsp. paratuberculosis interactome reveals a novel iron assimilation mechanism linked to nitric oxide stress during early infection

    PubMed Central

    2013-01-01

    Background The initial interaction between host cell and pathogen sets the stage for the ensuing infection and ultimately determine the course of disease. However, there is limited knowledge of the transcripts utilized by host and pathogen and how they may impact one another during this critical step. The purpose of this study was to create a host-Mycobacterium avium subsp. paratuberculosis (MAP) interactome for early infection in an epithelium-macrophage co-culture system using RNA-seq. Results Establishment of the host-MAP interactome revealed a novel iron assimilation system for carboxymycobactin. Iron assimilation is linked to nitric oxide synthase-2 production by the host and subsequent nitric oxide buildup. Iron limitation as well as nitric oxide is a prompt for MAP to enter into an iron sequestration program. This new iron sequestration program provides an explanation for mycobactin independence in some MAP strains grown in vitro as well as during infection within the host cell. Utilization of such a pathway is likely to aid MAP establishment and long-term survival within the host. Conclusions The host-MAP interactome identified a number of metabolic, DNA repair and virulence genes worthy for consideration as novel drug targets as well as future pathogenesis studies. Reported interactome data may also be utilized to conduct focused, hypothesis-driven research. Co-culture of uninfected bovine epithelial cells (MAC-T) and primary bovine macrophages creates a tolerant genotype as demonstrated by downregulation of inflammatory pathways. This co-culture system may serve as a model to investigate other bovine enteric pathogens. PMID:24112552

  7. INTRAUTERINE EXPOSURE TO LEAD MAY ENHANCE SENSITIZATION TO COMMON INHALANT ALLERGENS IN EARLY CHILDHOOD. A PROSPECTIVE PREBIRTH COHORT STUDY

    PubMed Central

    Jedrychowski, Wieslaw; Perera, Frederica; Maugeri, Umberto; Miller, Rachel L.; Rembiasz, Maria; Flak, Elzbieta; Mroz, Elzbieta; Majewska, Renata; Zembala, Marek

    2010-01-01

    Background Several in vivo and in vitro studies have shown that metal-rich particles may enhance allergic responses to house dust mites and induce an increased release of allergy-related cytokines. Objectives The main goal of this analysis is to define the possible association of intrauterine exposure to lead and mercury with the occurrence of skin sensitization to common aeroallergens in early childhood. Material and Methods The present study refers to a sample of 224 women in the second trimester of pregnancy recruited from Krakow inner city area who had full term pregnancies and whose children underwent skin prick testing (SPT) at the age of 5. Lead and mercury levels were assessed in cord blood and retested in children at age of 5 years. Aeroallergen concentrations in house dust were measured at the age of 3 years. The main health outcome (atopic status) was defined as the positive SPT to at least one common aeroallergen (Der f1, Der p1, Can f1 and Fel d1) at the age of 5 years. In the statistical analysis of the association between atopic status of children and exposure to metals, the study considered a set of covariates such as maternal characteristics (age, education, atopy), child’s gender, number of older siblings, prenatal (measured via cord blood cotinine) and postnatal environmental tobacco smoke together with exposure to polycyclic aromatic hydrocarbons (PAH) as measured by PAH-DNA adducts. Results and conclusion In the binary regression analysis, which controlled for the confounders, the risk ratio (RR) estimate for atopic sensitization was significantly associated with the lead exposure (RR =2.25, 95%CI: 1.21–4.19). In conclusion, the data suggest that even very low-level of prenatal lead exposure may be implicated in enhancing sensitization to common aeroallergens in early childhood. PMID:21094490

  8. Ciclesonide Oral Inhalation

    MedlinePlus

    Ciclesonide comes as an aerosol to inhale by mouth using an inhaler. Ciclesonide is usually inhaled twice a day. Try to use ciclesonide at around ... than usual.The inhaler that comes with ciclesonide aerosol is designed for use only with a canister ...

  9. Zanamivir Oral Inhalation

    MedlinePlus

    Zanamivir comes as a powder to inhale (breathe in) by mouth. To treat influenza, it is usually inhaled twice daily for 5 days. You should ... plastic inhaler called a Diskhaler (device for inhaling powder) and five Rotadisks (circular foil blister packs each ...

  10. Fluticasone Oral Inhalation

    MedlinePlus

    ... fluticasone aerosol inhaler while you are near an open flame or a heat source. The inhaler may explode if it is exposed ... Do not store the inhaler near a heat source or an open flame. Protect the inhaler from freezing and direct ...

  11. Flunisolide Oral Inhalation

    MedlinePlus

    ... your flunisolide inhaler while you are near an open flame or a heat source. The inhaler may explode if it is exposed ... Do not store the inhaler near a heat source or an open flame. Protect the inhaler from freezing and direct ...

  12. Ciclesonide Oral Inhalation

    MedlinePlus

    ... your ciclesonide inhaler while you are near an open flame or a heat source. The inhaler may explode if it is exposed ... Do not store the inhaler near a heat source or an open flame. Protect the inhaler from freezing and direct ...

  13. Budesonide Oral Inhalation

    MedlinePlus

    ... tightness, wheezing, and coughing caused by asthma. Budesonide powder for oral inhalation (Pulmicort Flexhaler) is used in ... Budesonide comes as a powder to inhale by mouth using an inhaler and as a suspension to inhale by mouth using a special jet nebulizer ( ...

  14. Early response to inhaled bronchodilators and corticosteroids as a predictor of 12-month treatment responder status and COPD exacerbations

    PubMed Central

    Calverley, Peter M; Postma, Dirkje S; Anzueto, Antonio R; Make, Barry J; Eriksson, Göran; Peterson, Stefan; Jenkins, Christine R

    2016-01-01

    Background Early treatment response markers, for example, improvement in forced expiratory volume in 1 second (FEV1) and St George’s Respiratory Questionnaire (SGRQ) total score, may help clinicians to better manage patients with chronic obstructive pulmonary disease (COPD). We investigated the prevalence of clinically important improvements in FEV1 and SGRQ scores after 2-month budesonide/formoterol or formoterol treatment and whether such improvements predict subsequent improvements and exacerbation rates. Methods This post hoc analysis is based on data from three double-blind, randomized studies in patients with moderate-to-very-severe COPD receiving twice-daily budesonide/formoterol or formoterol alone for 6 or 12 months. Prebronchodilator FEV1 and SGRQ total score were measured before treatment and at 2 and 12 months; COPD exacerbation rates were measured during months 2–12. Responders were defined by ≥100 mL improvement in prebronchodilator FEV1 and ≥4-point decrease in SGRQ total score. Results Overall, 2,331 and 1,799 patients were included in the 0–2- and 0–12-month responder analyses, respectively, and 2,360 patients in the 2–12-month exacerbation rate analysis. At 2 months, 35.1% of patients were FEV1 responders and 44.3% were SGRQ responders. The probability of response was significantly greater with budesonide/formoterol than with formoterol or placebo for both parameters. Two-month responders had a greater chance of 12-month response than 2-month nonresponders for both FEV1 (odds ratio, 5.57; 95% confidence interval, 4.14–7.50) and SGRQ (odds ratio, 3.87; 95% confidence interval, 2.83–5.31). Two-month response in FEV1 (P<0.001), but not SGRQ (P=0.11), was associated with greater reductions in exacerbation risk. Conclusion Early FEV1 and SGRQ treatment responses relate to their changes at 12 months. FEV1 response, but not SGRQ response, at 2 months predicts the risk of a future COPD exacerbation in some, but not all patients. This is

  15. Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Hypertensive Patients With Primary Hyperaldosteronemia: Role of 5,6,7,8-Tetrahydrobiopterin Oxidation and Endothelial Nitric Oxide Synthase Uncoupling.

    PubMed

    Chen, Long; Ding, Mei-Lin; Wu, Fang; He, Wen; Li, Jin; Zhang, Xiao-Yu; Xie, Wen-Li; Duan, Sheng-Zhong; Xia, Wen-Hao; Tao, Jun

    2016-02-01

    Although hyperaldosteronemia exerts detrimental impacts on vascular endothelium in addition to elevating blood pressure, the effects and molecular mechanisms of hyperaldosteronemia on early endothelial progenitor cell (EPC)-mediated endothelial repair after arterial damage are yet to be determined. The aim of this study was to investigate the endothelial repair capacity of early EPCs from hypertensive patients with primary hyperaldosteronemia (PHA). In vivo endothelial repair capacity of early EPCs from PHAs (n=20), age- and blood pressure-matched essential hypertension patients (n=20), and age-matched healthy subjects (n=20) was evaluated by transplantation into a nude mouse carotid endothelial denudation model. Endothelial function was evaluated by flow-mediated dilation of brachial artery in human subjects. In vivo endothelial repair capacity of early EPCs and flow-mediated dilation were impaired both in PHAs and in essential hypertension patients when compared with age-matched healthy subjects; however, the early EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs were impaired more severely than essential hypertension patients. Oral spironolactone improved early EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs. Increased oxidative stress, oxidative 5,6,7,8-tetrahydrobiopterin degradation, endothelial nitric oxide synthase uncoupling and decreased nitric oxide production were found in early EPCs from PHAs. Nicotinamide adenine dinucleotide phosphate oxidase subunit p47(phox) knockdown or 5,6,7,8-tetrahydrobiopterin supplementation attenuated endothelial nitric oxide synthase uncoupling and enhanced in vivo endothelial repair capacity of early EPCs from PHAs. In conclusion, PHAs exhibited more impaired endothelial repair capacity of early EPCs than did essential hypertension patients independent of blood pressure, which was associated with mineralocorticoid receptor-dependent oxidative stress and subsequently 5

  16. Comparison of the Pulmonary Oxidative Stress Caused by Intratracheal Instillation and Inhalation of NiO Nanoparticles when Equivalent Amounts of NiO Are Retained in the Lung

    PubMed Central

    Horie, Masanori; Yoshiura, Yukiko; Izumi, Hiroto; Oyabu, Takako; Tomonaga, Taisuke; Okada, Takami; Lee, Byeong-Woo; Myojo, Toshihiko; Kubo, Masaru; Shimada, Manabu; Morimoto, Yasuo

    2016-01-01

    NiO nanoparticles were administered to rat lungs via intratracheal instillation or inhalation. During pulmonary toxicity caused by NiO nanoparticles, the induction of oxidative stress is a major factor. Both intratracheal instillation and inhalation of NiO nanoparticles induced pulmonary oxidative stress. The oxidative stress response protein, heme oxygenase-1 (HO-1), was induced by the administration of NiO nanoparticles at both the protein and gene expression level. Additionally, certain oxidative-stress markers in the lung, such as 8-iso-prostaglandin F2α, thioredoxin, and inducible nitric oxide synthase were increased. Furthermore, the concentration of myeloperoxidase (MPO) in the lung was also increased by the administration of NiO nanoparticles. When the amount of NiO in the lung is similar, the responses against pulmonary oxidative stress of intratracheal instillation and inhalation are also similar. However, the state of pulmonary oxidative stress in the early phase was different between intratracheal instillation and inhalation, even if the amount of NiO in the lung was similar. Inhalation causes milder oxidative stress than that caused by intratracheal instillation. On evaluation of the nanoparticle-induced pulmonary oxidative stress in the early phase, we should understand the different states of oxidative stress induced by intratracheal instillation and inhalation. PMID:26797643

  17. [Impact of inhaled NO on developing lung and brain].

    PubMed

    Baud, O; Olivier, P; Vottier, G; Pham, H; Mercier, J-C; Loron, G

    2009-09-01

    With the advent of prenatal steroids, postnatal exogenous surfactant and less aggressive respiratory support, premature infants can develop chronic lung disease without even acute respiratory distress. This "new bronchopulmonary dysplasia" could be the result of impaired postnatal growth. Several experimental studies have suggested a possible role of the vascular endothelial growth factor/nitric oxide (VEGF/NO) pathway in restoring pulmonary angiogenesis and enhancing distal lung growth. The results of the clinical studies are, however, inconclusive, and it is currently unclear which subsets of premature infants might benefit from inhaled nitric oxide. Besides, severe intracranial haemorrhage and/or cystic periventricular leukomalacia may affect the most immature babies, many of whom are spared from severe initial respiratory disease. Recently, inhaled nitric oxide was shown to significantly decrease the incidence of these neurological events, and to improve the long-term outcome in a few clinical trials. At times neuroprotective, at times neurotoxic, nitric oxide is capable of divergent effects depending upon the extent of cerebral damage, the redox state of the cell, and the experimental model used. Recently, inhaled nitric oxide had recognized to have dramatic remote effects including angiogenesis and maturation on the developing brain in rodent pups. Therefore, the developmental consequences of inhaled NO should be further investigated to ensure its safety on the developing brain and to test its potential neurprotective effect. PMID:19836663

  18. Inhaled Therapies for Pulmonary Hypertension.

    PubMed

    Hill, Nicholas S; Preston, Ioana R; Roberts, Kari E

    2015-06-01

    The inhaled route has a number of attractive features for treatment of pulmonary hypertension, including delivery of drug directly to the target organ, thus enhancing pulmonary specificity and reducing systemic adverse effects. It can also improve ventilation/perfusion matching by dilating vessels supplying ventilated regions, thus improving gas exchange. Furthermore, it can achieve higher local drug concentrations at a lower overall dose, potentially reducing drug cost. Accordingly, a number of inhaled agents have been developed to treat pulmonary hypertension. Most in current use are prostacyclins, including epoprostenol, which has been cleared for intravenous applications but is used off-label in acute care settings as a continuously nebulized medication. Aerosolized iloprost and treprostinil are both prostacyclins that have been cleared by the FDA to treat pulmonary arterial hypertension (PAH). Both require frequent administration (6 and 4 times daily, respectively), and both have a tendency to cause airway symptoms, including cough and wheeze, which can lead to intolerance. These agents cannot be used to substitute for the infused routes of prostacyclin because they do not permit delivery of medication at high doses. Inhaled nitric oxide (INO) is cleared for the treatment of primary pulmonary hypertension in newborns. It is also used off-label to test acute vasoreactivity in PAH during right-heart catheterization and to treat acute right-heart failure in hospitalized patients. In addition, some studies on long-term application of INO either have been recently completed with results pending or are under consideration. In the future, because of its inherent advantages in targeting the lung, the inhaled route is likely to be tested using a variety of small molecules that show promise as PAH therapies. PMID:26070575

  19. Nitric oxide

    Integrated Risk Information System (IRIS)

    Nitric oxide ; CASRN 10102 - 43 - 9 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Ef

  20. Indacaterol Oral Inhalation

    MedlinePlus

    ... a short-acting beta agonist inhaler such as albuterol (Proventil, Ventolin) to use during attacks. If you ... stop the pieces of capsule from reaching your mouth as you inhale the medication. Very tiny pieces ...

  1. Acute Pulmonary Vasodilator Testing With Inhaled Treprostinil in Children With Pulmonary Arterial Hypertension

    PubMed Central

    Takatsuki, Shinichi; Parker, Donna K.; Doran, Aimee K.; Friesen, Robert H.

    2012-01-01

    Acute pulmonary vasodilator testing (AVT) is essential to determining the initial therapy for children with pulmonary arterial hypertension (PAH). This study aimed to report the initial experience with inhaled treprostinil used for AVT in children with PAH and to evaluate the hemodynamic change after inhaled treprostinil compared with inhaled nitric oxide. This prospective cohort study was designed for 13 children who underwent AVT with inhaled treprostinil or oxygen plus inhaled nitric oxide (iNO) during catheterization. Inhaled treprostinil was delivered during cardiac catheterization by adapting the Optineb ultrasonic nebulizer via either a flow-inflating bag or the manual mode of the anesthesia system. The median age of the patients was 10 years (range 4–17 years). The etiologies of PAH included idiopathic PAH and associated PAH. All the patients tolerated inhaled treprostinil without marked clinical worsening and received six or nine breaths (36 or 54 µg) of treprostinil. The median of the total treprostinil doses was 1.53 µg/kg (range 0.71–2.89 µg/kg). Inhaled treprostinil was administrated via an endotracheal tube (n = 8), anesthesia mask (n = 3), or laryngeal mask airway (n = 2). Inhaled nitric oxide (iNO) and inhaled treprostinil significantly decreased the mean pulmonary artery pressure and the pulmonary vascular resistance index compared with baseline. Three adverse events were reported after inhaled treprostinil, including cough and mild to moderate hypotension with higher doses. All adverse events resolved without any intervention. This study report is the first to describe the use of inhaled treprostinil for AVT in children with PAH. In this small pediatric cohort, inhaled treprostinil was effectively delivered and well tolerated and may be useful for AVT. PMID:23184020

  2. Flunisolide Oral Inhalation

    MedlinePlus

    Flunisolide comes as an aerosol to inhale by mouth. It usually is inhaled twice daily. Try to use flunisolide at around the same times every ... acting medication than usual.Each canister of flunisolide aerosol is designed to provide 60 or 120 inhalations, ...

  3. Hydrazine inhalation hepatotoxicity.

    PubMed

    Kao, Yung Hsiang; Chong, C H; Ng, W T; Lim, D

    2007-10-01

    Abstract Hydrazine is a hazardous chemical commonly used as a reactant in rocket and jet fuel cells. Animal studies have demonstrated hepatic changes after hydrazine inhalation. Human case reports of hydrazine inhalation hepatotoxicity are rare. We report a case of mild hepatotoxicity following brief hydrazine vapour inhalation in a healthy young man, which resolved completely on expectant management. PMID:17761725

  4. Leishmania (Viannia) braziliensis amastigotes from patients with mucosal leishmaniasis have increased ability to disseminate and are controlled by nitric oxide at the early stage of murine infection.

    PubMed

    Gomes, Clayson M; Ávila, Lucilla R; Santos, Jéssica C; Oliveira, Pollyana G; Tomé, Fernanda D; Pereira, Ledice I A; Dorta, Miriam L; Lino, Ruy S; Ribeiro-Dias, Fátima; Oliveira, Milton A P

    2016-06-01

    Mucosal leishmaniasis (ML) caused by Leishmania (Vianna) braziliensis usually appears after the healing of the primary lesion when amastigotes disseminate from the infection site to the mucosal area. Here, we investigated murine infection with amastigotes obtained from patients with ML or localized cutaneous leishmaniasis (LCL). Amastigotes were used to infect wild type, IFN-γ KO and inducible nitric oxide synthase (iNOS) KO mice. Amastigotes from patients with LCL induced lesions that appeared earlier in IFN-γ KO than parasites from ML. The lesion after infection with ML appeared early in iNOS KO than in IFN-γ KO mice and in iNOS KO mice parasites from ML and LCL cause similar lesions at the initial phase of infection, while parasites from ML induced greater lesions than the ones from LCL at the late phase. A greater number of parasites were observed in spleen of IFN-γ KO and iNOS KO mice infected with amastigotes from patients with ML than those with LCL. Parasites from ML infect a lower percentage of macrophages and are killed independent on IFN-γ and dependent on NO. The data suggest that amastigotes responsible for mucosal lesion in humans develop slowly on the initial phase of infection due to high susceptibility to NO and they have an increased ability to disseminate. PMID:27073255

  5. A rapid response of beta-amylase to nitric oxide but not gibberellin in wheat seeds during the early stage of germination.

    PubMed

    Zhang, Hua; Shen, Wen-Biao; Zhang, Wei; Xu, Lang-Lai

    2005-03-01

    The effects of nitric oxide (NO) and gibberellic acid (GA(3)) on the responses of amylases in wheat (Triticum aestivum L.) seeds (caryopses) were investigated during the first 12 h of germination. GA(3) had no effects on the activities of alpha-amylase (EC 3.2.1.1) or beta-amylase (EC 3.2.1.2), either in intact seeds or embryoless halves within 12 h. In contrast, addition of sodium nitroprusside (SNP), an NO donor, was able to induce a rapid increase in beta-amylase activity without affecting alpha-amylase. Furthermore, the rapid response of beta-amylase to SNP in wheat seeds could be attributed to NO and was approximately dose-dependent. Some other aspects of SNP induction of amylase isozymes were also characterized. Further investigations showed that SNP might play an interesting role in the dissociation of free beta-amylase from small homopolymers or heteropolymers. Furthermore, SNP also directly induced the release of bound beta-amylase from glutenin and its crude enzyme preparation. However, the slight increase in protease also induced by SNP might not be responsible for this action. Interestingly, based on the fact that the rapid response of beta-amylase to NO also existed in seeds of other species, such as barley, soybean, rice and watermelon, it might be a universal event in early seed germination. PMID:15517355

  6. Chronic Running Exercise Alleviates Early Progression of Nephropathy with Upregulation of Nitric Oxide Synthases and Suppression of Glycation in Zucker Diabetic Rats

    PubMed Central

    Ito, Daisuke; Cao, Pengyu; Kakihana, Takaaki; Sato, Emiko; Suda, Chihiro; Muroya, Yoshikazu; Ogawa, Yoshiko; Hu, Gaizun; Ishii, Tadashi; Ito, Osamu; Kohzuki, Masahiro; Kiyomoto, Hideyasu

    2015-01-01

    Exercise training is known to exert multiple beneficial effects including renal protection in type 2 diabetes mellitus and obesity. However, the mechanisms regulating these actions remain unclear. The present study evaluated the effects of chronic running exercise on the early stage of diabetic nephropathy, focusing on nitric oxide synthase (NOS), oxidative stress and glycation in the kidneys of Zucker diabetic fatty (ZDF) rats. Male ZDF rats (6 weeks old) underwent forced treadmill exercise for 8 weeks (Ex-ZDF). Sedentary ZDF (Sed-ZDF) and Zucker lean (Sed-ZL) rats served as controls. Exercise attenuated hyperglycemia (plasma glucose; 242 ± 43 mg/dL in Sed-ZDF and 115 ± 5 mg/dL in Ex-ZDF) with increased insulin secretion (plasma insulin; 2.3 ± 0.7 and 5.3 ± 0.9 ng/mL), reduced albumin excretion (urine albumin; 492 ± 70 and 176 ± 11 mg/g creatinine) and normalized creatinine clearance (9.7 ± 1.4 and 4.5 ± 0.8 mL/min per body weight) in ZDF rats. Endothelial (e) and neuronal (n) NOS expression in kidneys of Sed-ZDF rats were lower compared with Sed-ZL rats (p<0.01), while both eNOS and nNOS expression were upregulated by exercise (p<0.01). Furthermore, exercise decreased NADPH oxidase activity, p47phox expression (p<0.01) and α-oxoaldehydes (the precursors for advanced glycation end products) (p<0.01) in the kidneys of ZDF rats. Additionally, morphometric evidence indicated renal damage was reduced in response to exercise. These data suggest that upregulation of NOS expression, suppression of NADPH oxidase and α-oxoaldehydes in the kidneys may, at least in part, contribute to the renal protective effects of exercise in the early progression of diabetic nephropathy in ZDF rats. Moreover, this study supports the theory that chronic aerobic exercise could be recommended as an effective non-pharmacological therapy for renoprotection in the early stages of type 2 diabetes mellitus and obesity. PMID:26379244

  7. A Nitric Oxide-Donor Furoxan Moiety Improves the Efficacy of Edaravone against Early Renal Dysfunction and Injury Evoked by Ischemia/Reperfusion

    PubMed Central

    Chiazza, Fausto; Chegaev, Konstantin; Rogazzo, Mara; Cutrin, Juan C.; Lazzarato, Loretta; Fruttero, Roberta

    2015-01-01

    Edaravone (5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, EDV) is a free-radical scavenger reduces organ ischemic injury. Here we investigated whether the protective effects of EDV in renal ischemia/reperfusion (I/R) injury may be enhanced by an EDV derivative bearing a nitric oxide- (NO-) donor furoxan moiety (NO-EDV). Male Wistar rats were subjected to renal ischemia (45 minutes), followed by reperfusion (6 hours). Administration of either EDV (1.2–6–30 µmol/kg, i.v.) or NO-EDV (0.3–1.2–6 µmol/kg, i.v.) dose-dependently attenuated markers of renal dysfunction (serum urea and creatinine, creatinine clearance, urine flow, urinary N-acetyl-β-D-glucosaminidase, and neutrophil gelatinase-associated lipocalin/lipocalin-2). NO-EDV exerted protective effects in the dose-range 1.2–6 µmol/kg, while a higher dose (30 µmol/kg) was needed to obtain protection by EDV. Both EDV and NO-EDV modulated tissue markers of oxidative stress and lipid peroxidation. NO-EDV, but not EDV, activated endothelial NO synthase (NOS) and blunted I/R-induced upregulation of inducible NOS, secondary to modulation of Akt and NF-κB activation, respectively. Besides NO-EDV administration inhibited I/R-induced IL-1β, IL-18, IL-6, and TNF-α overproduction. Overall, these findings demonstrate that the NO-donor moiety contributes to the protection against early renal I/R injury and suggest that NO-donor EDV codrugs are worthy of additional study as innovative pharmacological tools. PMID:25834700

  8. Inhaled medical gases: more to breathe than oxygen.

    PubMed

    Gentile, Michael A

    2011-09-01

    The mixture of oxygen and nitrogen is usually sufficient to achieve the therapeutic objective of supporting adequate gas exchange. Pediatric and neonatal patients have an assortment of physiologic conditions that may require adjunctive inhaled gases to treat the wide variety of diseases seen in this heterogeneous population. Inhaled nitric oxide, helium oxygen mixtures, inhaled anesthetics, hypercarbic mixtures, hypoxic mixtures, inhaled carbon monoxide, and hydrogen sulfide have been used to alter physiology in an attempt to improve patient outcomes. Balancing the therapeutic potential, possible adverse effects, and the complexity of the technical aspects of gas delivery, it is essential that clinicians thoroughly understand the application of medical gas therapy beyond the traditional nitrogen/oxygen mixture. PMID:21944684

  9. Inhaled therapy for the management of perioperative pulmonary hypertension

    PubMed Central

    Thunberg, C. A.; Morozowich, S. T.; Ramakrishna, Harish

    2015-01-01

    Patients with pulmonary hypertension (PH) are at high risk for complications in the perioperative setting and often receive vasodilators to control elevated pulmonary artery pressure (PAP). Administration of vasodilators via inhalation is an effective strategy for reducing PAP while avoiding systemic side effects, chiefly hypotension. The prototypical inhaled pulmonary-specific vasodilator, nitric oxide (NO), has a proven track record but is expensive and cumbersome to implement. Alternatives to NO, including prostanoids (such as epoprostenol, iloprost, and treprostinil), NO-donating drugs (sodium nitroprusside, nitroglycerin, and nitrite), and phosphodiesterase inhibitors (milrinone, sildenafil) may be given via inhalation for the purpose of treating elevated PAP. This review will focus on the perioperative therapy of PH using inhaled vasodilators. PMID:26139748

  10. [Inhaled therapy in asthma].

    PubMed

    Plaza Moral, Vicente; Giner Donaire, Jordi

    2016-04-01

    Because of its advantages, inhaled administration of aerosolized drugs is the administration route of choice for the treatment of asthma and COPD. Numerous technological advances in the devices used in inhaled therapy in recent decades have boosted the appearance of multiple inhalers and aerosolized drugs. However, this variety also requires that the prescribing physician is aware of their characteristics. The main objective of the present review is to summarize the current state of knowledge on inhalers and inhaled drugs commonly used in the treatment of asthma. The review ranges from theoretical aspects (fundamentals and available devices and drugs) to practical and relevant aspects for asthma care in the clinical setting (therapeutic strategies, education, and adherence to inhalers). PMID:26683076

  11. Inhalant Abuse and Dextromethorphan.

    PubMed

    Storck, Michael; Black, Laura; Liddell, Morgan

    2016-07-01

    Inhalant abuse is the intentional inhalation of a volatile substance for the purpose of achieving an altered mental state. As an important, yet underrecognized form of substance abuse, inhalant abuse crosses all demographic, ethnic, and socioeconomic boundaries, causing significant morbidity and mortality in school-aged and older children. This review presents current perspectives on epidemiology, detection, and clinical challenges of inhalant abuse and offers advice regarding the medical and mental health providers' roles in the prevention and management of this substance abuse problem. Also discussed is the misuse of a specific "over-the-counter" dissociative, dextromethorphan. PMID:27338970

  12. Modeling Deposition of Inhaled Particles

    EPA Science Inventory

    The mathematical modeling of the deposition and distribution of inhaled aerosols within human lungs is an invaluable tool in predicting both the health risks associated with inhaled environmental aerosols and the therapeutic dose delivered by inhaled pharmacological drugs. Howeve...

  13. Skin thickness in children treated with daily or periodical inhaled budesonide for mild persistent asthma. The Helsinki early intervention childhood asthma study.

    PubMed

    Turpeinen, Markku; Raitio, Hanna; Pelkonen, Anna S; Nikander, Kurt; Sorva, Ritva; Selroos, Olof; Juntunen-Backman, Kaisu; Haahtela, Tari

    2010-02-01

    In adults, asthma treatment with high doses of inhaled corticosteroids has resulted in dermal thinning. The aim of this study was to investigate the skin thickness in children with asthma during budesonide treatment. In a double-blind study, 113 children, 5-10 y old, with persistent asthma received budesonide 400 microg twice daily for 1 mo and thereafter 200 microg twice daily for 5 mo. Thereafter, 56 children received 100 microg twice daily for 1 y, whereas 57 other children used budesonide periodically for exacerbations. An additional 54 children were treated with disodium cromoglycate (DSCG) for 18 mo. Skin thickness was measured on each forearm before and after treatment for 6, 12, and 18 mo using a 20-MHz high-resolution ultrasonic device. The initial 6-mo budesonide treatment resulted in a greater reduction in mean skin thickness in the forearms compared with DSCG (right: -35.9 versus -5.9 microm; p = 0.004; left: -30.6 versus -7.3 microm; p = 0.03). At month 18, the inter-group differences were no longer significant. Budesonide inhalations in daily doses of 400-800 microg in prepubertal children with newly detected asthma may cause minor dermal thinning. The changes were reversible during low dose or periodic treatment with budesonide. PMID:19858777

  14. Nitric oxide inhibition strategies

    PubMed Central

    Wong, Vivian (Wai Chong); Lerner, Ethan

    2015-01-01

    Nitric oxide is involved in many physiologic processes. There are efforts, described elsewhere in this volume, to deliver nitric oxide to tissues as a therapy. Nitric oxide also contributes to pathophysiologic processes. Inhibiting nitric oxide or its production can thus also be of therapeutic benefit. This article addresses such inhibitory strategies. PMID:26634146

  15. Inhalation of chlorine gas.

    PubMed

    Williams, J G

    1997-11-01

    The clinical features of acute chlorine gas inhalation, and its management are reviewed. Current medical views on the chronic effects of an acute overwhelming exposure on lung function (reactive airways dysfunction syndrome), and the more controversial field of lung disease secondary to repeated inhalations of lower concentrations of chlorine gas are discussed. PMID:9519180

  16. Corpus callosum size and shape alterations in adolescent inhalant users.

    PubMed

    Takagi, Michael; Lubman, Dan I; Walterfang, Mark; Barton, Sarah; Reutens, David; Wood, Amanda; Yücel, Murat

    2013-09-01

    Inhalants, frequently abused during adolescence, are neurotoxic to white matter. We investigated the impact of inhalant misuse on the morphology of the corpus callosum (CC), the largest white matter bundle in the brain, in an adolescent sample of inhalant users [n = 14; mean age = 17.3; standard deviation (SD) = 1.7], cannabis users (n = 11; mean age = 19.7; SD = 1.7) and community controls (n = 9; mean age = 19.5; SD = 2.6). We identified significant morphological differences in the CC among inhalant users compared with community controls. There were no morphological differences between inhalant and cannabis users. Our findings may represent the early stages of neurobiological damage associated with chronic inhalant misuse. PMID:21955104

  17. Carboxyhemoglobin formation secondary to nitric oxide therapy in the setting of interstitial lung disease and pulmonary hypertension.

    PubMed

    Ruisi, Phillip; Ruisi, Michael

    2011-01-01

    Carbon monoxide (CO) has been widely recognized as an exogenous poison, although endogenous mechanisms for its formation involve heme-oxygenase (HO) isoforms, more specifically HO-1, in the setting of oxidative stress such as acute respiratory distress syndrome, sepsis, trauma, and nitric oxide use have been studied. In patients with refractory hypoxemia, inhaled nitric oxide (iNO) therapy is used to selectively vasodilate the pulmonary vasculature and improve ventilation-perfusion match. Inhaled nitric oxide is rapidly inactivated on binding to hemoglobin in the formation of nitrosyl- and methemoglobin in the pulmonary vasculature. Hence, inhaled nitric oxide has minimal systemic dissemination. Several experimental design studies involving lab rats have demonstrated increased levels of carboxyhemoglobin and exhaled CO as a result of nitric oxide HO-1 induction. PMID:21079530

  18. Extracellular killing of inhaled pneumococci in rats

    SciTech Connect

    Coonrod, J.D.; Marple, S.; Holmes, G.P.; Rehm, S.R.

    1987-12-01

    Early clearance of inhaled Staphylococcus aureus is believed to be caused by phagocytosis by alveolar macrophages. In murine models inhaled pneumococci are cleared even more rapidly than S. aureus. Conventional opsonins appear to play no role in this clearance, and recently it has been shown that murine alveolar lining material contains free fatty acids and other soluble factors that are directly bactericidal for pneumococci. To determine whether non-phagocytic factors are involved in pneumococcal clearance, we compared the site of killing of inhaled pneumococci and S. aureus in rats using histologic methods and bronchoalveolar lavage. Spontaneous lysis of pneumococci was prevented by use of autolysin-defective pneumococci or by substitution of ethanolamine for choline in the cell wall. Histologic studies showed that the percent of inhaled staphylococci associated with alveolar macrophages always exceeded the percent of staphylococci cleared, whereas there was little association of pneumococci with macrophages during clearance. Analysis of the intracellular or extracellular location of iron 59 in bronchoalveolar lavage fluid of rats that had inhaled aerosols of /sup 59/Fe-labeled bacteria suggested that staphylococci were killed predominantly in macrophages and pneumococci in the extracellular space. When /sup 59/Fe-labeled pneumococci or staphylococci were ingested and killed by macrophages in vitro, the /sup 59/Fe remained with the macrophages, suggesting that the extracellular location of /sup 59/Fe during pneumococcal killing in vivo was not caused by rapid turnover of /sup 59/Fe in macrophages. Studies of the site of killing of inhaled type 25 pneumococci labeled exclusively in the cell wall with carbon 14-ethanolamine confirmed the results obtained with /sup 59/Fe-labeled pneumococci. Thus, early killing of inhaled pneumococci, unlike staphylococci, appears to take place outside of macrophages.

  19. Inhalation treatment for asthma.

    PubMed Central

    Reiser, J; Warner, J O

    1986-01-01

    Inhaled medication has revolutionised the lives of many children with asthma. Despite this we see many children for whom appropriate inhaled medication has been prescribed but whose symptoms continue to be poorly controlled. In our experience this is often due to poor technique or inappropriately prescribed devices and an inadequate understanding of when and how to use the treatment. The prescribing physician must have a clear idea of the optimal inhalation technique. We have reviewed the standard devices available and our use of them in the treatment of childhood asthma. PMID:3082295

  20. Exhaled nitric oxide in children after accidental exposure to chlorine gas.

    PubMed

    Grasemann, Hartmut; Tschiedel, Eva; Groch, Manuela; Klepper, Jörg; Ratjen, Felix

    2007-08-01

    Chronic exposure to chlorine gas has been shown to cause occupational asthma. Acute inhalation of chlorine is known to cause airway inflammation and induce airway nitric oxide formation. Exhaled nitric oxide may therefore be a marker of airway damage after chlorine gas exposure. After accidental chlorine gas exposure in a swimming pool, exhaled nitric oxide and pulmonary function were repeatedly measured in 18 children over a 1-mo period. Symptomatic children with impaired pulmonary function had higher nitric oxide levels on the day after the exposure compared to day 8 and day 28. Differences in exhaled nitric oxide were more pronounced at a higher exhalation flow compared to lower flow, suggesting peripheral rather than central airway damage. This was in accordance with the observed changes in pulmonary function. No changes in exhaled nitric oxide were seen in asymptomatic children. These data suggest that acute chlorine gas exposure results in a mild increase of exhaled nitric oxide in symptomatic children. PMID:17687720

  1. Pirbuterol Acetate Oral Inhalation

    MedlinePlus

    ... used to prevent and treat wheezing, shortness of breath, coughing, and chest tightness caused by asthma, chronic ... the puff; continue to take a full, deep breath. Take the inhaler away from you mouth, hold ...

  2. Albuterol Oral Inhalation

    MedlinePlus

    ... in the dose counter go down. Do not waste doses by opening the inhaler unless you are ... refrigerator or at room temperature away from excess heat and moisture (not in the bathroom). Store the ...

  3. Umeclidinium Oral Inhalation

    MedlinePlus

    ... the inhaler without using your dose, you will waste the medication. The counter will count down by ... at room temperature and away from sunlight, excess heat and moisture (not in the bathroom). Throw away ...

  4. Cromolyn Oral Inhalation

    MedlinePlus

    ... difficulties (bronchospasm) caused by exercise, cold and dry air, or by inhaling substances such as pet dander, ... of substances that cause inflammation (swelling) in the air passages of the lungs.

  5. Insulin Human Inhalation

    MedlinePlus

    Insulin inhalation is used in combination with a long-acting insulin to treat type 1 diabetes (condition in which the body does not produce insulin and therefore cannot control the amount of sugar ...

  6. Olodaterol Oral Inhalation

    MedlinePlus

    ... of breath, coughing, and chest tightness caused by chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs ... Do not use olodaterol inhalation during a sudden COPD attack. Your doctor will prescribe a short-acting ( ...

  7. Arformoterol Oral Inhalation

    MedlinePlus

    ... a short acting beta agonist inhaler such as albuterol (Proventil, Ventolin) to use during attacks. If you ... Sit upright and place the mouthpiece in your mouth or put on the facemask. Turn on the ...

  8. Substance use - inhalants

    MedlinePlus

    ... it has been sprayed or put into a paper or plastic bag Ballooning: Inhaling a gas from ... empty soda cans, empty perfume bottles, and toilet paper tubes stuffed with rags or toilet paper soaked ...

  9. Inhaled /sup 239/PuO/sub 2/ and/or total-body gamma radiation: Early mortality and morbidity in rats and dogs

    SciTech Connect

    Filipy, R.E.; Decker, J.R.; Lai, Y.L.; Lauhala, K.E.; Buschbom, R.L.; Hiastala, M.P.; McGee, D.R.; Park, J.F.; Kuffel, E.G.; Ragan, H.A.; Cannon, W.C.; Yaniv, S.S.; Scott, B.R.

    1988-08-01

    Rats and beagle dogs were given doses of /sup 60/Co gamma radiation and/or body burdens of /sup 239/PuO/sub 2/ within lethal ranges in an experiment to determine and compare morbidity and mortality responses of both species within 1 year after exposure. Radiation-induced morbidity was assessed by measuring changes in body weights, hematologic parameters, and pulmonary-function parameters. Gamma radiation caused transient morbidity, reflected by immediately depressed blood cell concentrations and by long-term loss of body weight and diminished pulmonary function in animals of both species that survived the acute gamma radiation syndrome. Inhaled plutonium caused a loss of body weight and diminished pulmonary function in both species, but its only effect on blood cell concentrations was lymphocytopenia in dogs. Combined gamma irradiation and plutonium lung burdens were synergistic, in that animals receiving both radiation insults had higher morbidity and mortality rates than would be predicted based on the effect of either kind of radiation alone. Plutonium lung burdens enhanced the effect of gamma radiation in rats within the first 30 days of exposure, and gamma radiation enhanced the long-term effect of plutonium lung burdens in both species. Rats were less sensitive to both kinds of radiation, whether administered alone or in combination. 71 refs., 105 figs., 48 tabs.

  10. Treatment of ovalbumin-induced experimental allergic bronchitis in rats by inhaled inhibitor of secretory phospholipase A2

    PubMed Central

    Shoseyov, D; Bibi, H; Offer, S; Schwob, O; Krimsky, M; Kleiman, M; Yedgar, S

    2005-01-01

    Background: The pathophysiology of asthma involves the action of inflammatory/allergic lipid mediators formed following membrane phospholipid hydrolysis by phospholipase A2 (PLA2). Cysteinyl leukotrienes are considered potent inducers of bronchoconstriction and airway remodelling. Ovalbumin (OVA) induced bronchoconstriction in rats is associated with increased secretory PLA2 (sPLA2) activation and cysteinyl leukotriene production, together with suppression of cytosolic PLA2 and prostaglandin E2. These processes are reversed when the animals are pretreated systemically with an extracellular cell impermeable sPLA2 inhibitor which also suppresses the early allergic reaction to OVA challenge. In this study we examine the capacity of the sPLA2 inhibitor to ameliorate inflammatory and allergic manifestations (early and late bronchoconstriction) of OVA induced allergic bronchitis in rats when the inhibitor was administered by inhalation to confine it to the airways. Methods: Rats sensitised with OVA were treated with the sPLA2 inhibitor hyaluronic acid-linked phosphatidyl ethanolamine (HyPE). The rats were divided into four groups (n = 10 per group): (1) naïve controls (no sensitisation/no treatment); (2) positive controls (sensitisation + challenge with OVA inhalation and subcutaneous injection of 1 ml saline before each challenge; (3) sensitisation + challenge with OVA and HyPE inhalation before every challenge; and (4) sensitisation + challenge with OVA and treatment with subcutaneous dexamethasone (300 µg) before each challenge as a conventional reference. Another group received no treatment with HyPE during the sensitisation process but only before or after challenge of already sensitised rats. Pulmonary function was assessed and changes in the histology of the airways, levels of cysteinyl leukotrienes in BAL fluid, and the production of nitric oxide (No) and tumour necrosis factor α (TNFα) by BAL macrophages were determined. Results: Inhalation of HyPE markedly

  11. Acute Inhalation Injury

    PubMed Central

    Gorguner, Metin; Akgun, Metin

    2010-01-01

    Inhaled substances may cause injury in pulmonary epithelium at various levels of respiratory tract, leading from simple symptoms to severe disease. Acute inhalation injury (AII) is not uncommon condition. There are certain high risk groups but AII may occur at various places including home or workplace. Environmental exposure is also possible. In addition to individual susceptibility, the characteristics of inhaled substances such as water solubility, size of substances and chemical properties may affect disease severity as well as its location. Although AII cases may recover in a few days but AII may cause long-term complications, even death. We aimed to discuss the effects of short-term exposures (minutes to hours) to toxic substances on the lungs. PMID:25610115

  12. MODELING DEPOSITION OF INHALED PARTICLES

    EPA Science Inventory

    Modeling Deposition of Inhaled Particles: ABSTRACT

    The mathematical modeling of the deposition and distribution of inhaled aerosols within human lungs is an invaluable tool in predicting both the health risks associated with inhaled environmental aerosols and the therapeut...

  13. Fluticasone and Salmeterol Oral Inhalation

    MedlinePlus

    ... doctor about how you should take your other oral or inhaled medications for asthma during your treatment with salmeterol and fluticasone inhalation. If you were using a short-acting beta agonist inhaler such as albuterol (Proventil, Ventolin) on a regular basis, your doctor ...

  14. Isoetharine Oral Inhalation

    MedlinePlus

    Isoetharine comes as an aerosol and a solution to inhale by mouth. It is used as needed to relieve symptoms but usually should not be ... proper disposal of your medication. Avoid puncturing the aerosol container, and do not discard it in an ...

  15. Liposomal formulations for inhalation.

    PubMed

    Cipolla, David; Gonda, Igor; Chan, Hak-Kim

    2013-08-01

    No marketed inhaled products currently use sustained release formulations such as liposomes to enhance drug disposition in the lung, but that may soon change. This review focuses on the interaction between liposomal formulations and the inhalation technology used to deliver them as aerosols. There have been a number of dated reviews evaluating nebulization of liposomes. While the information they shared is still accurate, this paper incorporates data from more recent publications to review the factors that affect aerosol performance. Recent reviews have comprehensively covered the development of dry powder liposomes for aerosolization and only the key aspects of those technologies will be summarized. There are now at least two inhaled liposomal products in late-stage clinical development: ARIKACE(®) (Insmed, NJ, USA), a liposomal amikacin, and Pulmaquin™ (Aradigm Corp., CA, USA), a liposomal ciprofloxacin, both of which treat a variety of patient populations with lung infections. This review also highlights the safety of inhaled liposomes and summarizes the clinical experience with liposomal formulations for pulmonary application. PMID:23919478

  16. Inhalants. Specialized Information Service.

    ERIC Educational Resources Information Center

    Do It Now Foundation, Phoenix, AZ.

    The document presents a collection of articles about inhalant abuse. Article 1 presents findings on the psychophysiological effects related to the use of amyl or butyl nitrate as a "recreational drug." Article 2 suggests a strong association between chronic sniffing of the solvent toulene and irreversible brain damage. Article 3 warns about the…

  17. A rat model of smoke inhalation injury: influence of combustion smoke on gene expression in the brain.

    PubMed

    Lee, Heung M; Greeley, George H; Herndon, David N; Sinha, Mala; Luxon, Bruce A; Englander, Ella W

    2005-11-01

    Acute smoke inhalation causes death and injury in victims of home and industrial fires as well as victims of combat situations. The lethal factors in combustion smoke inhalation are toxic gases and oxygen deficiency, with carbon monoxide (CO) as a primary cause of death. In survivors, inhalation of smoke can result in severe immediate and delayed neuropathologies. To gain insight into the progression of molecular events contributing to smoke inhalation sequelae in the brain, we developed a smoke inhalation rat model and conducted a genome-wide analysis of gene expression. Microarray analysis revealed a modified brain transcriptome with changes peaking at 24 h and subsiding within 7 days post-smoke. Overall, smoke inhalation down regulated genes associated with synaptic function, neurotransmission, and neurotrophic support, and upregulated genes associated with stress responses, including nitric oxide synthesis, antioxidant defenses, proteolysis, inflammatory response, and glial activation. Notably, among the affected genes, many have been previously implicated in other types of brain injury, demonstrating the usefulness of microarrays for analysis of changes in gene expression in complex insults. In accord with previously described modulations of nitric oxide homeostasis in CO poisoning, microarray analysis revealed increased brain expression of nitric oxide synthase (NOS) and NOS ligand after inhalation of smoke. Furthermore, immunostaining showed significant elevations in perivascular NOS and in protein nitration, corroborating the involvement of nitric oxide perturbations in post-smoke sequelae in the brain. Thus, the new rat model, in combination with microarray analyses, affords insight into the complex molecular pathophysiology of smoke inhalation in the brain. PMID:15893353

  18. Nitric oxide function in atherosclerosis

    PubMed Central

    Matthys, K. E.

    1997-01-01

    Atherosclerosis is a chronic inflammatory process in the intima of conduit arteries, which disturbs the endothelium-dependent regulation of the vascular tone by the labile liposoluble radical nitric oxide (NO) formed by the constitutive endothelial nitric oxide synthase (eNOS). This defect predisposes to coronary vasospasm and cardiac ischaemia, with anginal pain as the typical clinical manifestation. It is now appreciated that endothelial dysfunction is an early event in atherogenesis and that it may also involve the microcirculation, in which atherosclerotic lesions do not develop. On the other hand, the inflammatory environment in atherosclerotic plaques may result in the expression of the inducible NO synthase (iNOS) isozyme. Whether the dysfunction in endothelial NO production is causal to, or the result of, atherosclerotic lesion formation is still highly debated. Most evidence supports the hypothesis that constitutive endothelial NO release protects against atherogenesis e.g. by preventing smooth muscle cell proliferation and leukocyte adhesion. Nitric oxide generated by the inducible isozyme may be beneficial by replacing the failing endothelial production but excessive release may damage the vascular wall cells, especially in combination with reactive oxygen intermediates. PMID:18472828

  19. Food hypersensitivity by inhalation

    PubMed Central

    Ramirez, Daniel A; Bahna, Sami L

    2009-01-01

    Though not widely recognized, food hypersensitivity by inhalation can cause major morbidity in affected individuals. The exposure is usually more obvious and often substantial in occupational environments but frequently occurs in non-occupational settings, such as homes, schools, restaurants, grocery stores, and commercial flights. The exposure can be trivial, as in mere smelling or being in the vicinity of the food. The clinical manifestations can vary from a benign respiratory or cutaneous reaction to a systemic one that can be life-threatening. In addition to strict avoidance, such highly-sensitive subjects should carry self-injectable epinephrine and wear MedicAlert® identification. Asthma is a strong predisposing factor and should be well-controlled. It is of great significance that food inhalation can cause de novo sensitization. PMID:19232116

  20. Nitric oxide and almitrine: the definitive answer for hypoxemia.

    PubMed

    Payen, D M; Muret, J

    1999-02-01

    Hypoxia-induced by acute lung injury results from abnormal ventilation/perfusion ratio distribution towards shunt or low ventilation/perfusion zones. Pharmacological modification of pulmonary blood flow distribution improving ventilation/perfusion ratio should correct hypoxia. The development of inhaled nitric oxide therapy had confirmed this concept, but with a relatively high proportion of 'non responders'. Then development of other drugs used alone or in association with nitric oxide may reinforce the benefit of nitric oxide. This has been tested with almitrine bismesylate, a lipophilic drug that reinforce hypoxic pulmonary vasoconstriction. Using inhaled nitric oxide in combination with almitrine, several studies in adult respiratory distress syndrome or acute lung injury patients have shown spectacular results in term of PaO2 and pulmonary shunt reduction. Moreover, the proportion of responders to this combination seems largely great than those observed for each drug alone. In conclusion, pulmonary blood flow manipulation improving ventilation/perfusion mismatching is one of the major strategies to correct severe hypoxia. PMID:17013295

  1. Molecular Steps in the Immune Signaling Pathway Evoked by Plant Elicitor Peptides: Ca2+-Dependent Protein Kinases, Nitric Oxide, and Reactive Oxygen Species Are Downstream from the Early Ca2+ Signal1[OPEN

    PubMed Central

    Ma, Yi; Zhao, Yichen; Walker, Robin K.; Berkowitz, Gerald A.

    2013-01-01

    Endogenous plant elicitor peptides (Peps) can act to facilitate immune signaling and pathogen defense responses. Binding of these peptides to the Arabidopsis (Arabidopsis thaliana) plasma membrane-localized Pep receptors (PEPRs) leads to cytosolic Ca2+ elevation, an early event in a signaling cascade that activates immune responses. This immune response includes the amplification of signaling evoked by direct perception of pathogen-associated molecular patterns by plant cells under assault. Work included in this report further characterizes the Pep immune response and identifies new molecular steps in the signal transduction cascade. The PEPR coreceptor BRASSINOSTEROID-INSENSITIVE1 Associated Kinase1 contributes to generation of the Pep-activated Ca2+ signal and leads to increased defense gene expression and resistance to a virulent bacterial pathogen. Ca2+-dependent protein kinases (CPKs) decode the Ca2+ signal, also facilitating defense gene expression and enhanced resistance to the pathogen. Nitric oxide and reduced nicotinamide adenine dinucleotide phosphate oxidase-dependent reactive oxygen species generation (due to the function of Respiratory Burst Oxidase Homolog proteins D and F) are also involved downstream from the Ca2+ signal in the Pep immune defense signal transduction cascade, as is the case with BRASSINOSTEROID-INSENSITIVE1 Associated Kinase1 and CPK5, CPK6, and CPK11. These steps of the pathogen defense response are required for maximal Pep immune activation that limits growth of a virulent bacterial pathogen in the plant. We find a synergism between function of the PEPR and Flagellin Sensing2 receptors in terms of both nitric oxide and reactive oxygen species generation. Presented results are also consistent with the involvement of the secondary messenger cyclic GMP and a cyclic GMP-activated Ca2+-conducting channel in the Pep immune signaling pathway. PMID:24019427

  2. Technosphere inhaled insulin (Afrezza).

    PubMed

    Rendell, M

    2014-12-01

    Technosphere® insulin uses a unique carrier -fumaryl diketopiperazine (FDKP)- which adsorbs insulin to form microparticles to permit delivery to the alveoli by inhalation. Toxicity studies have been entirely negative. The pulmonary absorption of insulin is very rapid, and the disappearance time is shorter than for subcutaneously delivered rapid-acting insulins. As a result, after inhalation, there is a rapid drop in glucose levels which subsequently return to normal in a shorter time than after subcutaneous insulin administration. Consequently, there is a lower incidence of hypoglycemic reactions. Pulmonary function studies have shown a small, reversible decrease in FEV1, and pulmonary imaging studies have shown no adverse effect. The inhalation of Technosphere insulin can produce a cough in up to 27% of patients. The cough has resulted in discontinuance in as many as 9% of users. Technosphere insulin has been approved for use in type 1 and type 2 diabetes. Long-term studies of pulmonary safety and surveillance for malignancy will be performed in the future. Studies to assess the optimal time dosing regimen are needed. PMID:25588086

  3. Nitric Oxide Nanoparticle Technology

    PubMed Central

    Englander, Laura

    2010-01-01

    Staphylococcus aureus infections account for the majority of skin and soft tissue infections in the United States. Staphylococcus aureus is rapidly evolving resistance to contemporary topical as well as systemic antibiotics. Alternatives to current treatment options for skin and soft tissue infections are needed for more effective treatment now and in the future. Nitric oxide's proven roles in both wound repair and as an antimicrobial agent make it an excellent candidate for the treatment of skin infections. Recent attempts at novel nitric oxide therapies, in the form of nitric oxide donors, have shown limited potential in treating cutaneous infection. However, more recent developments in nitric oxide delivery, using nitric oxide nanoparticle technology, demonstrate substantial promise in the promotion of wound repair and eradication of skin and soft tissue infections. PMID:20725551

  4. Observational Evidence Against Mountain-Wave Generation of Ice Nuclei as a Prerequisite for the Formation of Three Solid Nitric Acid Polar Stratospheric Clouds Observed in the Arctic in Early December 1999

    NASA Technical Reports Server (NTRS)

    Pagan, Kathy L.; Tabazadeh, Azadeh; Drdla, Katja; Hervig, Mark E.; Eckermann, Stephen D.; Browell, Edward V.; Legg, Marion J.; Foschi, Patricia G.

    2004-01-01

    A number of recently published papers suggest that mountain-wave activity in the stratosphere, producing ice particles when temperatures drop below the ice frost point, may be the primary source of large NAT particles. In this paper we use measurements from the Advanced Very High Resolution Radiometer (AVHRR) instruments on board the National Oceanic and Atmospheric Administration (NOAA) polar-orbiting satellites to map out regions of ice clouds produced by stratospheric mountain-wave activity inside the Arctic vortex. Lidar observations from three DC-8 flights in early December 1999 show the presence of solid nitric acid (Type Ia or NAT) polar stratospheric clouds (PSCs). By using back trajectories and superimposing the position maps on the AVHRR cloud imagery products, we show that these observed NAT clouds could not have originated at locations of high-amplitude mountain-wave activity. We also show that mountain-wave PSC climatology data and Mountain Wave Forecast Model 2.0 (MWFM-2) raw hemispheric ray and grid box averaged hemispheric wave temperature amplitude hindcast data from the same time period are in agreement with the AVHRR data. Our results show that ice cloud formation in mountain waves cannot explain how at least three large scale NAT clouds were formed in the stratosphere in early December 1999.

  5. Inhalant abuse among adolescents: neurobiological considerations.

    PubMed

    Lubman, D I; Yücel, M; Lawrence, A J

    2008-05-01

    Experimentation with volatile substances (inhalants) is common during early adolescence, yet limited work has been conducted examining the neurobiological impact of regular binge use during this key stage of development. Human studies consistently demonstrate that chronic use is associated with significant toxic effects, including neurological and neuropsychological impairment, as well as diffuse and subtle changes in white matter. However, most preclinical research has tended to focus on acute exposure, with limited work examining the neuropharmacological or toxicological mechanisms underpinning these changes or their potential reversibility with abstinence. Nevertheless, there is growing evidence that commonly abused inhalants share common cellular mechanisms, and have similar actions to other drugs of abuse. Indeed, the majority of acute behavioural effects appear to be underpinned by changes in receptor and/or ion channel activity (for example, GABA(A), glycine and 5HT(3) receptor activation, NMDA receptor inhibition), although nonspecific interactions can also arise at high concentrations. Recent studies examining the effects of toluene exposure during the early postnatal period are suggestive of long-term alterations in the function of NMDA and GABA(A) receptors, although limited work has been conducted investigating exposure during adolescence. Given the critical role of neurotransmitter systems in cognitive, emotional and brain development, future studies will need to take account of the substantial neuromaturational changes that are known to occur in the brain during childhood and adolescence, and to specifically investigate the neuropharmacological and toxicological profile of inhalant exposure during this period of development. PMID:18332858

  6. How to Use Metered-Dose Inhalers

    MedlinePlus

    ... methods really work, and people who use these methods may continue to use their inhalers after the inhalers are empty.Some inhalers come with a counter that shows the number of sprays that remain in the inhaler. If your inhaler ...

  7. Inhalation injury in severely burned children does not augment the systemic inflammatory response

    PubMed Central

    Finnerty, Celeste C; Herndon, David N; Jeschke, Marc G

    2007-01-01

    and IL-12p70. There were no increased levels of pro-inflammatory cytokines, indicating that an inhalation injury in addition to a burn injury does not augment the systemic inflammatory response early after burn. PMID:17306027

  8. Effects of nitric acid on carbachol reactivity of the airways in normal and allergic sheep

    SciTech Connect

    Abraham, W.M.; Kim, C.S.; King, M.M.; Oliver, W. Jr.; Yerger, L.

    1982-01-01

    The airway effects of a 4-hr exposure (via a Plexiglas hood) to 1.6 ppm nitric acid vapor were evaluated in seven normal and seven allergic sheep, i.e., animals that have a history of reacting with bronchospasm to inhalation challenge with Ascaris suum antigen. The nitric acid vapor was generated by ultrasonic nebulization of a 2% nitric acid solution. Airway effects were assessed by measuring the change in specific pulmonary flow resistance before and after a standard inhalation challenge with 2.5% carbachol aerosol. Nitric acid exposure did not produce bronchoconstriction in either group. Pre-exposure increases in specific pulmonary flow resistance after carbachol inhalation were 68% (SD+/- 13%) and 82% (SD+/- 35%) for the normal and allergic sheep, respectively. Within 24 hr, the largest post-exposure increases in specific pulmonary flow resistance for the normal and allergic sheep were 108% (SD+/- 51%(P<.06)) and 175% (SD+/- 87% (p<.02)), respectively. We conclude that a short-term exposure to nitric acid vapor at levels below the industrial threshold limit (2 ppm), produces airway hyperreactivity to aerosolized carbachol in allergic sheep.

  9. Carcinogenicity of inhaled nanoparticles.

    PubMed

    Roller, Markus

    2009-07-01

    Large epidemiological studies in the United States have shown a statistical association between air concentration of the fine dust fraction PM(2.5) in the general environment and increased risk of lung cancer. A quantitative risk assessment for lung cancer based on these studies corresponds to risk estimates based on studies at workplaces with exposure to diesel engine emissions; its magnitude cannot be explained by the known carcinogenicity of organic substances or metals adsorbed to the insoluble particle core. Carcinogenic effects of diesel particles were observed after inhalation in rats independently in several studies. The surprisingly strong effect of diesel particles was partially attributed to their small size. This hypothesis was corroborated by inhalation studies with synthetic nanoparticles virtually free of organic compounds. IARC found sufficient evidence for the carcinogenicity of carbon black and of titanium dioxide in experimental animals. Long-term studies by the method of intratracheal instillation confirmed the carcinogenic effects in rats for an even broader spectrum of synthetic nanoparticles. Non-positive studies with hamsters are not valid because hamsters did not develop lung tumors after inhalation of some known human carcinogens. In recent years, the number of publications reporting in vitro genotoxicity of TiO(2) and of carbon black nanomaterials has increased. Overall, there is clear positive evidence for carcinogenicity in rats, together with supporting evidence from human data of structurally related substances. Therefore, the European Union (EU) criteria for category 2 of carcinogenic substances appear to be fulfilled for bio-durable nanoparticles consisting of matter without known significant specific toxicity. PMID:19558247

  10. About Steroids (Inhaled and Oral Corticosteroids)

    MedlinePlus

    ... dose-inhalers ( inhaled steroids ), oral forms (pills or syrups) , injections (shots) and intravenous (IV) solutions. Healthcare providers ... slowly decreased. Inhaled steroids and steroid pills and syrups are often prescribed for people with a chronic ...

  11. Parent's Guide to Preventing Inhalant Abuse

    MedlinePlus

    ... conditioning coolants. How can you tell if a young person is an inhalant abuser? If someone is ... youths involved with inhalant abuse. How does a young person who abuses inhalants die? There are many ...

  12. Rethinking the paradigm for the development of inhaled drugs.

    PubMed

    Pritchard, John N

    2015-12-30

    Nebulized treatment is an important delivery option for the young, elderly, and those with severe chronic respiratory disease, but there is a lack of new nebulized drug products being produced for these patients, leading to the potential for under-treatment. This communication describes a new drug development paradigm as a timely solution to this issue. Often, drug development is initiated with nebulizers in the early stages, to provide cheaper and faster drug development, and then switched to inhaler devices in later clinical trials to address the majority of patients. However, the waste of resource on parallel development of the inhaler can be large due to the high early attrition rate of new drug development. The new paradigm uses the nebulizer to continue drug development through to market, and initiates inhaler development after completion of the riskier early phase studies. New drug safety and efficacy can be assessed faster and more efficiently by using a nebulized formulation rather than developing an inhaler. The results of calculations of expected net present value showed that the new paradigm produced higher expected net present values than the conventional model over a range of economic scenarios. This new paradigm could therefore provide improved returns on investments, as well as more modern drugs in nebulized form for those patients unable to use inhalers. PMID:26475968

  13. Accidental condom inhalation.

    PubMed

    Arya, C L; Gupta, Rajnish; Arora, V K

    2004-01-01

    A 27-year-old lady presented with persistent cough, sputum and fever for the preceding six months. Inspite of trials with antibiotics and anti-tuberculosis treatment for the preceeding four months, her symptoms did not improve. A subsequent chest radiograph showed non-homogeneous collapse-consolidation of right upper lobe. Videobronchoscopy revealed an inverted bag like structure in right upper lobe bronchus and rigid bronchoscopic removal with biopsy forceps confirmed the presence of a condom. Detailed retrospective history also confirmed accidental inhalation of the condom during fellatio. PMID:14870871

  14. Carbon Monoxide Inhalation Protects Rat Intestinal Grafts from Ischemia/Reperfusion Injury

    PubMed Central

    Nakao, Atsunori; Kimizuka, Kei; Stolz, Donna B.; Neto, Joao Seda; Kaizu, Takashi; Choi, Augustine M. K.; Uchiyama, Takashi; Zuckerbraun, Brian S.; Nalesnik, Michael A.; Otterbein, Leo E.; Murase, Noriko

    2003-01-01

    Carbon monoxide (CO), a byproduct of heme catalysis by heme oxygenases, has been shown to exert anti-inflammatory effects. This study examines the cytoprotective efficacy of inhaled CO during intestinal cold ischemia/reperfusion injury associated with small intestinal transplantation. Orthotopic syngenic intestinal transplantation was performed in Lewis rats after 6 hours of cold preservation in University of Wisconsin solution. Three groups were examined: normal untreated controls, control intestinal transplant recipients kept in room air, and recipients exposed to CO (250 ppm) for 1 hour before and 24 hours after surgery. In air grafts, mRNA levels for interleukin-6, cyclooxygenase-2, intracellular adhesion molecule (ICAM-1), and inducible nitric oxide synthase rapidly increased after intestinal transplant. Histopathological analysis revealed severe mucosal erosion, villous congestion, and inflammatory infiltrates. CO effectively blocked an early up-regulation of these mediators, showed less severe histopathological changes, and resulted in significantly improved animal survival of 92% from 58% in air-treated controls. CO also significantly reduced mRNA for proapoptotic Bax, while it up-regulated anti-apoptotic Bcl-2. These changes in CO-treated grafts correlated with well-preserved CD31+ vascular endothelial cells, less frequent apoptosis/necrosis in intestinal epithelial and capillary endothelial cells, and improved graft tissue blood circulation. Protective effects of CO in this study were mediated via soluble guanylyl cyclase, because 1H-(1,2,4)oxadiazole (4,3-α) quinoxaline-1-one (soluble guanylyl cyclase inhibitor) completely reversed the beneficial effect conferred by CO. Perioperative CO inhalation at a low concentration resulted in protection against ischemia/reperfusion injury to intestinal grafts with prolonged cold preservation. PMID:14507665

  15. Inhaled insulin--does it become reality?

    PubMed

    Siekmeier, R; Scheuch, G

    2008-12-01

    After more than 80 years of history the American and European Drug Agencies (FDA and EMEA) approved the first pulmonary delivered version of insulin (Exubera) from Pfizer/Nektar early 2006. However, in October 2007, Pfizer announced it would be taking Exubera off the market, citing that the drug had failed to gain market acceptance. Since 1924 various attempts have been made to get away from injectable insulin. Three alternative delivery methods where always discussed: Delivery to the upper nasal airways or the deep lungs, and through the stomach. From these, the delivery through the deep lungs is the most promising, because the physiological barriers for the uptake are the smallest, the inspired aerosol is deposited on a large area and the absorption into the blood happens through the extremely thin alveolar membrane. However, there is concern about the long-term effects of inhaling a growth protein into the lungs. It was assumed that the large surface area over which the insulin is spread out would minimize negative effects. But recent news indicates that, at least in smokers, the bronchial tumour rate under inhaled insulin seems to be increased. These findings, despite the fact that they are not yet statistical significant and in no case found in a non-smoker, give additional arguments to stop marketing this approach. Several companies worked on providing inhalable insulin and the insulin powder inhalation system Exubera was the most advanced technology. Treatment has been approved for adults only and patients with pulmonary diseases (e.g., asthma, emphysema, COPD) and smokers (current smokers and individuals who recently quitted smoking) were excluded from this therapy. Pharmacokinetics and pharmacodynamics of Exubera are similar to those found with short-acting subcutaneous human insulin or insulin analogs. It is thus possible to use Exubera as a substitute for short-acting human insulin or insulin analogs. Typical side effects of inhaled insulin were coughing

  16. Deposition and clearance of inhaled particles.

    PubMed Central

    Stuart, B O

    1984-01-01

    Theoretical models of respiratory tract deposition of inhaled particles are compared to experimental studies of deposition patterns in humans and animals, as governed principally by particle size, density, respiratory rate and flow parameters. Various models of inhaled particle deposition make use of approximations of the respiratory tract to predict fractional deposition caused by fundamental physical processes of particle impaction, sedimentation, and diffusion. These models for both total deposition and regional (nasopharyngeal, tracheobronchial, and pulmonary) deposition are compared with early and recent experimental studies. Reasonable correlation has been obtained between theoretical and experimental studies, but the behavior in the respiratory tract of very fine (less than 0.1 micron) particles requires further investigation. Properties of particle shape, charge and hygroscopicity as well as the degree of respiratory tract pathology also influence deposition patterns; definitive experimental work is needed in these areas. The influence upon deposition patterns of dynamic alterations in inspiratory flow profiles caused by a variety of breathing patterns also requires further study, and the use of differing ventilation techniques with selected inhaled particle sizes holds promise in diagnosis of respiratory tract diseases. Mechanisms of conducting airway and alveolar clearance processes involving the pulmonary macrophage, mucociliary clearance, dissolution, transport to systemic circulation, and translocation via regional lymphatic vessels are discussed. PMID:6376108

  17. Nitric oxide triggers a concentration-dependent differential modulation of superoxide dismutase (FeSOD and Cu/ZnSOD) activity in sunflower seedling roots and cotyledons as an early and long distance signaling response to NaCl stress

    PubMed Central

    Arora, Dhara; Bhatla, Satish C

    2015-01-01

    Dark-grown sunflower (Helianthus annuus L.) seedlings exhibit modulation of total superoxide dismutase (SOD;EC 1.15.1.1) activity in roots and cotyledons (10,000g supernatant) in response to salt stress (NaCl; 120 mM) through a differential, zymographically detectable, whole tissue activity of FeSOD and Cu/ZnSOD. Confocal laser scanning microscopic imaging (CLSM) has further shown that NaCl stress significantly influences differential spatial distribution of Cu/ZnSOD and MnSOD isoforms in an inverse manner. Dual action of nitric oxide (NO) is evident in its crosstalk with FeSOD and Cu/ZnSOD in seedling roots and cotyledons in control and NaCl− stress conditions. Cu/ZnSOD activity in the roots of 2 d old NaCl− stressed seedlings is enhanced in the presence of 125–1000 µM of NO donor (sodium nitroprusside; SNP) indicating salt sensitivity of the enzyme activity. Quenching of endogenous NO by cPTIO treatment (500, 1000 µM) lowers FeSOD activity in roots (-NaCl). Cotyledons from control seedlings show an upregulation of FeSOD activity with increasing availability of SNP (125–1000 µM) in the Hoagland irrigation medium. Quenching of NO by cPTIO provides evidence for an inverse correlation between NO availability and FeSOD activity in seedling cotyledons irrespective of NaCl stress. Variable response due to NO on SOD isoforms in sunflower seedlings reflects its concentration-dependent biphasic (pro- and antioxidant) nature of action. Differential induction of SOD isoforms by NO indicates separate intracellular signaling pathways (associated with their respective functional separation) operative in seedling roots as an early salt stress mechanism and in cotyledons as an early long-distance NaCl stress sensing mechanism. PMID:26339977

  18. Nitric oxide triggers a concentration-dependent differential modulation of superoxide dismutase (FeSOD and Cu/ZnSOD) activity in sunflower seedling roots and cotyledons as an early and long distance signaling response to NaCl stress.

    PubMed

    Arora, Dhara; Bhatla, Satish C

    2015-01-01

    Dark-grown sunflower (Helianthus annuus L.) seedlings exhibit modulation of total superoxide dismutase (SOD;EC 1.15.1.1) activity in roots and cotyledons (10,000g supernatant) in response to salt stress (NaCl; 120 mM) through a differential, zymographically detectable, whole tissue activity of FeSOD and Cu/ZnSOD. Confocal laser scanning microscopic imaging (CLSM) has further shown that NaCl stress significantly influences differential spatial distribution of Cu/ZnSOD and MnSOD isoforms in an inverse manner. Dual action of nitric oxide (NO) is evident in its crosstalk with FeSOD and Cu/ZnSOD in seedling roots and cotyledons in control and NaCl(-) stress conditions. Cu/ZnSOD activity in the roots of 2 d old NaCl(-) stressed seedlings is enhanced in the presence of 125-1000 µM of NO donor (sodium nitroprusside; SNP) indicating salt sensitivity of the enzyme activity. Quenching of endogenous NO by cPTIO treatment (500, 1000 µM) lowers FeSOD activity in roots (-NaCl). Cotyledons from control seedlings show an upregulation of FeSOD activity with increasing availability of SNP (125-1000 µM) in the Hoagland irrigation medium. Quenching of NO by cPTIO provides evidence for an inverse correlation between NO availability and FeSOD activity in seedling cotyledons irrespective of NaCl stress. Variable response due to NO on SOD isoforms in sunflower seedlings reflects its concentration-dependent biphasic (pro- and antioxidant) nature of action. Differential induction of SOD isoforms by NO indicates separate intracellular signaling pathways (associated with their respective functional separation) operative in seedling roots as an early salt stress mechanism and in cotyledons as an early long-distance NaCl stress sensing mechanism. PMID:26339977

  19. The Moderating Effects of Perceived Emotional Benefits on Inhalant Initiation Among American Indian and White Youth

    PubMed Central

    Swaim, Randall C.

    2015-01-01

    Background Inhalant use co-occurs with emotional distress. Inhalant use may be a means of self-medicating distress, but more recent study focuses on the cognitive appraisal of personal benefits of using substances. Objectives Objectives were to determine whether emotional distress variables predict early versus later initiation of inhalant use, whether such relationships differ between American Indian and white youth, and whether perceived emotional benefits of inhalant use moderates the relationship between emotional distress and stage of inhalant initiation. Methods Data were from a study of 7–12th grade American Indian youth who live on or near reservations. A total of 856 students from 32 schools surveyed from 2009 to 2012, who reported having used inhalants (American Indian = 683; white = 173), were surveyed about age first use of inhalants, levels of emotional distress, and perceived benefits of inhalant use. SEM models were used to assess study objectives. Results Depression and anger did not discriminate between early and later initiation. Lower self-esteem related to earlier initiation, but only among American Indian students. Perceived emotional benefits of inhalant use did not moderate the relationship between self-esteem and stage of initiation. Discussion and Conclusions Among middle school and high school American Indian and white youth living on or near American Indian reservations, emotional distress is not strongly related to stage of inhalant initiation. Scientific Significance These findings raise questions about the timing and strength of relationship between emotional distress and early inhalant initiation. Prospective studies are need to assess this relationship more fully. PMID:26246198

  20. Mephedrone inhalation causes pneumomediastinum

    PubMed Central

    Graham, Ruth; Bowen, Nia; Singh, Joy

    2014-01-01

    A 17-year-old male patient presented to A&E with swelling on the right side of his neck, extending to below the clavicle, associated with neck pain and dysphonia. On examination, subcutaneous supraclavicular and chest wall emphysema was noted. Clinical observations and bloods were normal. A chest X-ray and subsequent CT of the thorax showed evidence of pneumomediastinum and subcutaneous emphysema. The patient denied any history of trauma but admitted to inhalation of mephedrone 3 days previously. The patient was discussed with the regional cardiothoracic unit who advised conservative management. He was treated prophylactically with antibiotics and was initially kept nil by mouth, but diet was introduced 24 h later. He remained well, his dysphonia resolved and his subcutaneous emphysema improved. He was discharged after 3 days. He has not attended any formal follow-up but was well when contacted by phone. PMID:24614784

  1. Toxic inhalational exposures.

    PubMed

    Chen, Tze-Ming Benson; Malli, Harjoth; Maslove, David M; Wang, Helena; Kuschner, Ware G

    2013-01-01

    Respirable toxicants are a spectrum of irritant and nonirritant gases, vapors, fumes, and airborne particles that can be entrained into the body through the respiratory tract, resulting in exposures that cause pulmonary injury and/or systemic disease. Sources of respirable toxicants include structural fires, industrial accidents, domestic mishaps, and intentional releases of injurious agents on the battleground (warfare) or in civilian settings (acts of terrorism). Acute toxic inhalational exposures may result in respiratory failure, multisystem organ dysfunction, and death. Management of victims includes assessment and protection of the airway, monitoring and treatment of systemic toxicity, and delivery of exposure-specific and nonspecific therapies that improve outcomes. Treatments may include antidotes, hyperbaric oxygen, and other nonspecific life-supporting interventions. PMID:22232204

  2. Inhaled Hydrogen Sulfide

    PubMed Central

    Volpato, Gian Paolo; Searles, Robert; Yu, Binglan; Scherrer-Crosbie, Marielle; Bloch, Kenneth D.; Ichinose, Fumito; Zapol, Warren M.

    2010-01-01

    Background Breathing hydrogen sulfide (H2S) has been reported to induce a suspended animation–like state with hypothermia and a concomitant metabolic reduction in rodents. However, the impact of H2S breathing on cardiovascular function remains incompletely understood. In this study, the authors investigated the cardiovascular and metabolic effects of inhaled H2S in a murine model. Methods The impact of breathing H2S on cardiovascular function was examined using telemetry and echocardiography in awake mice. The effects of breathing H2S on carbon dioxide production and oxygen consumption were measured at room temperature and in a warmed environment. Results Breathing H2S at 80 parts per million by volume at 27°C ambient temperature for 6 h markedly reduced heart rate, core body temperature, respiratory rate, and physical activity, whereas blood pressure remained unchanged. Echocardiography demonstrated that H2S exposure decreased both heart rate and cardiac output but preserved stroke volume. Breathing H2S for 6 h at 35°C ambient temperature (to prevent hypothermia) decreased heart rate, physical activity, respiratory rate, and cardiac output without altering stroke volume or body temperature. H2S breathing seems to induce bradycardia by depressing sinus node activity. Breathing H2S for 30 min decreased whole body oxygen consumption and carbon dioxide production at either 27° or 35°C ambient temperature. Both parameters returned to baseline levels within 10 min after the cessation of H2S breathing. Conclusions Inhalation of H2S at either 27° or 35°C reversibly depresses cardiovascular function without changing blood pressure in mice. Breathing H2S also induces a rapidly reversible reduction of metabolic rate at either body temperature. PMID:18362598

  3. Inhaled matters of the heart

    PubMed Central

    Zaky, Ahmed; Ahmad, Aftab; Dell’Italia, Louis J; Jahromi, Leila; Reisenberg, Lee Ann; Matalon, Sadis; Ahmad, Shama

    2015-01-01

    Inhalations of atmospheric pollutants, especially particulate matters, are known to cause severe cardiac effects and to exacerbate preexisting heart disease. Heart failure is an important sequellae of gaseous inhalation such as that of carbon monoxide. Similarly, other gases such as sulphur dioxide are known to cause detrimental cardiovascular events. However, mechanisms of these cardiac toxicities are so far unknown. Increased susceptibility of the heart to oxidative stress may play a role. Low levels of antioxidants in the heart as compared to other organs and high levels of reactive oxygen species produced due to the high energetic demand and metabolic rate in cardiac muscle are important in rendering this susceptibility. Acute inhalation of high concentrations of halogen gases is often fatal. Severe respiratory injury and distress occurs upon inhalation of halogens gases, such as chlorine and bromine; however, studies on their cardiac effects are scant. We have demonstrated that inhalation of high concentrations of halogen gases cause significant cardiac injury, dysfunction, and failure that can be critical in causing mortalities following exposures. Our studies also demonstrated that cardiac dysfunction occurs as a result of a direct insult independent of coexisting hypoxia, since it is not fully reversed by oxygen supplementation. Therefore, studies on offsite organ effects of inhaled toxic gases can impact development of treatment strategies upon accidental or deliberate exposures to these agents. Here we summarize the knowledge of cardiovascular effects of common inhaled toxic gases with the intent to highlight the importance of consideration of cardiac symptoms while treating the victims. PMID:26665179

  4. Inhaled antibiotics: dry or wet?

    PubMed

    Tiddens, Harm A W M; Bos, Aukje C; Mouton, Johan W; Devadason, Sunalene; Janssens, Hettie M

    2014-11-01

    Dry powder inhalers (DPIs) delivering antibiotics for the suppressive treatment of Pseudomonas aeruginosa in cystic fibrosis patients were developed recently and are now increasingly replacing time-consuming nebuliser therapy. Noninferiority studies have shown that the efficacy of inhaled tobramycin delivered by DPI was similar to that of wet nebulisation. However, there are many differences between inhaled antibiotic therapy delivered by DPI and by nebuliser. The question is whether and to what extent inhalation technique and other patient-related factors affect the efficacy of antibiotics delivered by DPI compared with nebulisers. Health professionals should be aware of the differences between dry and wet aerosols, and of patient-related factors that can influence efficacy, in order to personalise treatment, to give appropriate instructions to patients and to better understand the response to the treatment after switching. In this review, key issues of aerosol therapy are discussed in relation to inhaled antibiotic therapy with the aim of optimising the use of both nebulised and DPI antibiotics by patients. An example of these issues is the relationship between airway generation, structural lung changes and local concentrations of the inhaled antibiotics. The pros and cons of dry and wet modes of delivery for inhaled antibiotics are discussed. PMID:25323242

  5. Infant with Altered Consciousness after Cannabis Passive Inhalation

    ERIC Educational Resources Information Center

    Zarfin, Yehoshua; Yefet, Enav; Abozaid, Said; Nasser, Wael; Mor, Tamer; Finkelstein, Yoram

    2012-01-01

    We report on an infant who was admitted to hospital with severe neurological symptoms following passive inhalation of cannabis. To date, cannabis abuse has been described almost entirely in adolescents and adults. In early childhood, however, cannabis effects were almost exclusively discussed in the context of maternal prenatal exposure, and the…

  6. Endotoxin Inhalation Alters Lung Development in Neonatal Mice

    PubMed Central

    Kulhankova, Katarina; George, Caroline L.S.; Kline, Joel N.; Darling, Melissa; Thorne, Peter S.

    2012-01-01

    Background Childhood asthma is a significant public health problem. Epidemiologic evidence suggests an association between childhood asthma exacerbations and early life exposure to environmental endotoxin. Although the pathogenesis of endotoxin-induced adult asthma is well studied, questions remain about the impact of environmental endotoxin on pulmonary responsiveness in early life. Methods We developed a murine model of neonatal/juvenile endotoxin exposures approximating those in young children and evaluated the lungs inflammatory and remodeling responses. Results Persistent lung inflammation induced by the inhalation of endotoxin in early life was demonstrated by the influx of inflammatory cells and pro-inflammatory mediators to the airways and resulted in abnormal alveolarization. Conclusions Results of this study advance the understanding of the impact early life endotoxin inhalation has on the lower airways, and demonstrates the importance of an experimental design that approximates environmental exposures as they occur in young children. PMID:22576659

  7. A mathematical model for predicting the probability of acute mortality in a human population exposed to accidentally released airborne radionuclides. Final report for Phase I of the project: early effects of inhaled radionuclides

    SciTech Connect

    Filipy, R.E.; Borst, F.J.; Cross, F.T.; Park, J.F.; Moss, O.R.

    1980-06-01

    The report presents a mathematical model for the purpose of predicting the fraction of human population which would die within 1 year of an accidental exposure to airborne radionuclides. The model is based on data from laboratory experiments with rats, dogs and baboons, and from human epidemiological data. Doses from external, whole-body irradiation and from inhaled, alpha- and beta-emitting radionuclides are calculated for several organs. The probabilities of death from radiation pneumonitis and from bone marrow irradiation are predicted from doses accumulated within 30 days of exposure to the radioactive aerosol. The model is compared with existing similar models under hypothetical exposure conditions. Suggestions for further experiments with inhaled radionuclides are included.

  8. Nitric oxide and cardiovascular disease.

    PubMed Central

    McIntyre, M.; Dominiczak, A. F.

    1997-01-01

    Endothelium-derived nitric oxide is an important regulatory molecule in cardiovascular function. Reduced availability of nitric oxide has been implicated in the pathogenesis of hypertension and atherosclerosis. PMID:9497971

  9. Fluticasone and Vilanterol Oral Inhalation

    MedlinePlus

    ... the inhaler without using your dose, you will waste the medication. The counter will count down by ... at room temperature and away from sunlight, excess heat and moisture (not in the bathroom). Throw away ...

  10. Fluticasone and Salmeterol Oral Inhalation

    MedlinePlus

    ... in the dose counter go down. Do not waste doses by closing or tilting the inhaler, playing ... at room temperature and away from sunlight, excess heat and moisture (not in the bathroom). Throw away ...

  11. Umeclidinium and Vilanterol Oral Inhalation

    MedlinePlus

    ... the inhaler without using your dose, you will waste the medication. The counter will count down by ... at room temperature and away from sunlight, excess heat and moisture (not in the bathroom). Throw away ...

  12. Foreign object - inhaled or swallowed

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/000036.htm Foreign object - inhaled or swallowed To use the sharing features ... please enable JavaScript. If you breathe a foreign object into your nose, mouth, or respiratory tract, it ...

  13. Inhaled chemotherapy in lung cancer: future concept of nanomedicine

    PubMed Central

    Zarogoulidis, Paul; Chatzaki, Ekaterini; Porpodis, Konstantinos; Domvri, Kalliopi; Hohenforst-Schmidt, Wolfgang; Goldberg, Eugene P; Karamanos, Nikos; Zarogoulidis, Konstantinos

    2012-01-01

    Regional chemotherapy was first used for lung cancer 30 years ago. Since then, new methods of drug delivery and pharmaceuticals have been investigated in vitro, and in animals and humans. An extensive review of drug delivery systems, pharmaceuticals, patient monitoring, methods of enhancing inhaled drug deposition, safety and efficacy, and also additional applications of inhaled chemotherapy and its advantages and disadvantages are presented. Regional chemotherapy to the lung parenchyma for lung cancer is feasible and efficient. Safety depends on the chemotherapy agent delivered to the lungs and is dose-dependent and time-dependent. Further evaluation is needed to provide data regarding early lung cancer stages, and whether regional chemotherapy can be used as neoadjuvant or adjuvant treatment. Finally, inhaled chemotherapy could one day be administered at home with fewer systemic adverse effects. PMID:22619512

  14. High-flow oxygen therapy and other inhaled therapies in intensive care units.

    PubMed

    Levy, Sean D; Alladina, Jehan W; Hibbert, Kathryn A; Harris, R Scott; Bajwa, Ednan K; Hess, Dean R

    2016-04-30

    In this Series paper, we review the current evidence for the use of high-flow oxygen therapy, inhaled gases, and aerosols in the care of critically ill patients. The available evidence supports the use of high-flow nasal cannulae for selected patients with acute hypoxaemic respiratory failure. Heliox might prevent intubation or improve gas flow in mechanically ventilated patients with severe asthma. Additionally, it might improve the delivery of aerosolised bronchodilators in obstructive lung disease in general. Inhaled nitric oxide might improve outcomes in a subset of patients with postoperative pulmonary hypertension who had cardiac surgery; however, it has not been shown to provide long-term benefit in patients with acute respiratory distress syndrome (ARDS). Inhaled prostacyclins, similar to inhaled nitric oxide, are not recommended for routine use in patients with ARDS, but can be used to improve oxygenation in patients who are not adequately stabilised with traditional therapies. Aerosolised bronchodilators are useful in mechanically ventilated patients with asthma and chronic obstructive pulmonary disease, but are not recommended for those with ARDS. Use of aerosolised antibiotics for ventilator-associated pneumonia and ventilator-associated tracheobronchitis shows promise, but the delivered dose can be highly variable if proper attention is not paid to the delivery method. PMID:27203510

  15. Nanoparticle inhalation impairs endothelium-dependent vasodilation in subepicardial arterioles

    PubMed Central

    LeBlanc, AJ; Cumpston, JL; Chen, BT; Frazer, D; Castranova, V; Nurkiewicz, TR

    2009-01-01

    Exposure to fine particulate matter (PM, mean aerodynamic diameter ≤ 2.5 μm) has been shown to be a risk factor for cardiovascular disease mortality and may contribute to acute coronary events such as myocardial infarction (MI). There is sufficient reason to believe that smaller particles, such as nanoparticles, might be even more detrimental than larger-sized particles due to their increased surface area and higher pulmonary deposition. Our lab showed that nanoparticle inhalation impairs endothelium-dependent arteriolar vasodilation in skeletal muscle. However, it is not known if coronary microvascular endothelial function is affected in a similar manner. Rats were exposed to filtered air (control) or TiO2 nanoparticles (primary particle diameter, ~21 nm) via inhalation at concentrations that produced measured depositions (10 μg) relevant to ambient air pollution. Subepicardial arterioles (~150 μm in diameter) were isolated and responses to transmural pressure, flow-induced dilation (FID), acetylcholine, the Ca2+ ionophore A23187, and sodium nitroprusside (SNP) assessed. Myogenic responsiveness was preserved between groups. In addition, there was no difference in the vasodilation to SNP, signifying that smooth muscle sensitivity to nitric oxide (NO) is unaffected by nano-TiO2 exposure. However, inhalation of nano-TiO2 produced an increase in spontaneous tone in coronary arterioles and also impaired endothelium-dependent FID. In addition, ACh- and A23187-induced vasodilation was also blunted in arterioles after inhalation of nano-TiO2. Data showed that nanoparticle exposure significantly impairs endothelium-dependent vasodilation in subepicardial arterioles. Such disturbances in coronary microvascular function are consistent with the cardiac events associated with particle pollution exposure. PMID:20077232

  16. Pneumoconiosis after sericite inhalation

    PubMed Central

    Algranti, E; Handar, A; Dumortier, P; Mendonca, E; Rodrigues, G; Santos, A; Mauad, T; Dolhnikoff, M; De Vuyst, P; Saldiva, P; Bussacos, M

    2005-01-01

    Aims: To investigate and describe the radiological, clinical, and pathological changes in miners and millers exposed to sericite dust with mineralogical characteristics of inhaled dust. Methods: The working premises were visited to examine the sericite processing and to classify the jobs according to make qualitative evaluation. Respirable dust was collected and the amount of crystalline silica and particle size distribution were measured. Forty four workers were examined by a standard questionnaire for respiratory symptoms, spirometry, and chest x ray. Material from an open lung biopsy was reviewed for histopathological and mineralogical analysis, together with sericite samples from the work site to compare the mineral characteristics in lung lesions and work area. Results: Respirable dust contained 4.5–10.0% crystalline silica. Particle size distribution showed a heavy burden of very fine particles (23–55%) with a mean diameter of <0.5 µm. Mean age of sericite miners was 41.0 (11.9) and mean number of years of exposure was 13.5 (10.1). In 52.3% of workers (23/44), chest radiographs presented a median category of 1/0 or above, and 18.2% (8/44) had a reduced FEV1. There was a significant association between exposure indices and x ray category. Histological studies of the lung biopsy showed lesions compatible with mixed dust fibrosis with no silicotic nodules. x Ray diffraction analysis of the lung dust residue and the bulk samples collected from work area showed similar mineralogical characteristics. Muscovite and kaolinite were the major mineral particle inclusions in the lung. Conclusion: Exposure to fine sericite particles is associated with the development of functional and radiological changes in workers inducing mixed dust lesions, which are distinct histologically from silicosis. PMID:15723874

  17. [A new spacer, Babyhaler, for BDP inhalation therapy in severe infantile asthma].

    PubMed

    Yamada, Y; Yoshihara, S; Abe, T; Fukuda, N; Watanabe, M; Ono, M; Arisaka, O

    2000-11-01

    Recently, it has been recognized that airway inflammation is the most important pathogenesis of bronchial asthma, and inhaled corticosteroids therapy is effective for childhood asthma. However, using metered dose inhalers (MDI) of beclomethasone dipropionate (BDP) is difficult for infants. In this study, we administered BDP inhalation therapy with a new spacer, Babyhaler, for five cases of early childhood with severe infantile asthma that we could not control even by combination of theophylline round the clock (RTC) therapy and disodium cromoglycate (DSCG) + beta 2 stimulant (beta 2) regular use. We compared symptom score of asthma attack between the pre-treatment period (prior 2 weeks) and post-treatment period (following 8 weeks) of BDP inhalation therapy with Babyhaler. As a result, symptom score decreased significantly within 4 weeks after treatment of BDP with Babyhaler as compared with the score before treatment of BDP. These findings suggest that Babyhaler is useful for BDP inhalation therapy in infantile asthma. PMID:11193463

  18. Inhaled NO prevents hyperoxia-induced white matter damage in neonatal rats.

    PubMed

    Pham, Hoa; Vottier, Gaelle; Pansiot, Julien; Duong-Quy, Sy; Bollen, Bieke; Dalous, Jérémie; Gallego, Jorge; Mercier, Jean-Christophe; Dinh-Xuan, Anh Tuan; Bonnin, Philippe; Charriaut-Marlangue, Christiane; Baud, Olivier

    2014-02-01

    White matter damage (WMD) and bronchopulmonary dysplasia (BPD) are the two main complications occurring in very preterm infants. Inhaled nitric oxide (iNO) has been proposed to promote alveolarization in the developing lung, and we have reported that iNO promotes myelination and induces neuroprotection in neonatal rats with excitotoxic brain damage. Our hypothesis is that, in addition to its pulmonary effects, iNO may be neuroprotective in rat pups exposed to hyperoxia. To test this hypothesis, we exposed rat pups to hyperoxia, and we assessed the impact of iNO on WMD and BPD. Rat pups were exposed to either hyperoxia (80% FiO2) or to normoxia for 8 days. Both groups received iNO (5 ppm) or air. We assessed the neurological and pulmonary effects of iNO in hyperoxia-injured rat pups using histological, molecular and behavioral approaches. iNO significantly attenuated the severity of hyperoxia-induced WMD induced in neonatal rats. Specifically, iNO decreased white matter inflammation, cell death, and enhanced the density of proliferating oligodendrocytes and oligodendroglial maturation. Furthermore, iNO triggered an early upregulation of P27kip1 and brain-derived growth factor (BDNF). Whereas hyperoxia disrupted early associative abilities, iNO treatment maintained learning scores to a level similar to that of control pups. In contrast to its marked neuroprotective effects, iNO induced only small and transient improvements of BPD. These findings suggest that iNO exposure at low doses is specifically neuroprotective in an animal model combining injuries of the developing lung and brain that mimicked BPD and WMD in preterm infants. PMID:24322053

  19. Air contamination with nitric oxide: effect on exhaled nitric oxide response.

    PubMed

    Therminarias, A; Flore, P; Favre-Juvin, A; Oddou, M F; Delaire, M; Grimbert, F

    1998-03-01

    This study examines the response of exhaled nitric oxide (NO) concentration (ECNO) and quantity of exhaled NO over time (EVNO) in 10 healthy subjects breathing into five polyethylene bags, one in which synthetic air was free of NO and four in which NO was diluted to concentrations of 20 +/- 0.6, 49 +/- 0.8, 98 +/- 2, and 148 +/- 2 ppb, respectively. Each subject was connected to each bag for 10 min at random. Minute ventilation and ECNO were measured continuously, and EVNO was calculated continuously. ECNO and EVNO values were significantly higher for an inhaled NO concentration of 20 ppb than for NO-free air. Above 20 ppb, ECNO and EVNO increased linearly with inhaled NO concentration. It is reasonable to assume that a share of the quantity of inspired NO over time (InspVNO) because of air contamination by pollution is rejected by the ventilatory pathway. Insofar as InspVNO does not affect endogenous production or the metabolic fate of NO in the airway, this share may be estimated as being approximately one third of InspVNO, the remainder being taken by the endogenous pathway. Thus, air contamination by the NO resulting from pollution greatly increases the NO response in exhaled air. PMID:9517592

  20. Zinc toxicology following particulate inhalation.

    PubMed

    Cooper, Ross G

    2008-04-01

    The current mini-review describes the toxic effects of zinc inhalation principally in the workplace and associated complications with breathing and respiration. The International Classification of Functioning, Disability and Health Criteria were used to specifically select articles. Most of the commercial production of zinc involves the galvanizing of iron and the manufacture of brass. The recommended daily allowance for adults is 15 mg zinc/day. Metal fume fever associated with inhalation of fumes of ZnO is characterized by fatigue, chills, fever, myalgias, cough, dyspnea, leukocytosis, thirst, metallic taste and salivation. ZnCl(2) inhalation results in edema in the alveolar surface and the protein therein the lavage fluid is elevated. Particular pathological changes associated with zinc intoxication include: pale mucous membranes; jaundice; numerous Heinz bodies; and marked anemia. Adequate ambient air monitors for permissible exposure limits, excellent ventilation and extraction systems, and approved respirators are all important in providing adequate protection. PMID:20040991

  1. Extrapulmonary organ distribution of plutonium in healthy workers exposed by chronic inhalation at the Mayak production association.

    PubMed

    Suslova, K G; Khokhryakov, V F; Tokarskaya, Z B; Nifatov, A P; Krahenbuhl, M P; Miller, S C

    2002-04-01

    The systemic distribution of plutonium was determined for "healthy" workers who chronically inhaled plutonium at the radiochemical plants of the Mayak Production Association. The data were obtained by radiochemical analysis of soft tissues and bones samples collected upon autopsy of 120 workers who died from acute coronary diseases and accidents. The soft tissue samples were wet-ashed using nitric acid and hydrogen peroxide. Bone samples were ashed in a muffle furnace at 500 degrees C. Plutonium was extracted on anionite and coprecipitated with bismuth phosphate. The precipitation was blended with ZnS powder, and the alpha-activity was measured by ZnS solid scintillation counting in a low-background alpha radiometer. Twenty-five years after the beginning of inhalation exposures, the average percentage of plutonium in the skeleton and liver was 50% and 42% of systemic burden, respectively. A multivariate regression was used to quantify the effects of exposure time, "transportability" of the various compounds, plutonium body content, and age on systemic plutonium distribution. The early retention of plutonium in the liver is assumed to be greater than that in the skeleton. The initial distribution of plutonium between the liver and the skeleton, immediately after entering the circulatory system, was 50:38%, respectively. With time, the fraction of plutonium found in the liver decreased, while the fraction in the skeleton increased at a rate of 0.5% y(-1) of systemic deposition. Exposure time had a greater effect on the relative retention of plutonium in the main organs when compared to age. The statistical estimates that characterized the relative plutonium distribution were less stable for the liver than for the skeleton, likely due to the slower turnover of skeletal tissues and the retention of plutonium in bone. PMID:11906132

  2. Novel insights into phosgene-induced acute lung injury in rats: role of dysregulated cardiopulmonary reflexes and nitric oxide in lung edema pathogenesis.

    PubMed

    Li, Wenli; Liu, Fangfang; Wang, Chen; Truebel, Hubert; Pauluhn, Juergen

    2013-02-01

    Phosgene gas is a lower respiratory tract irritant. As such, it stimulates nociceptive vagal C-fiber-related reflexes in a dose-rate and concentration × exposure duration (C × t)-dependent manner. In rats, this reflex is characterized by extended apnea time periods, bradycardia, and hypothermia. Although inhalation exposures at nonlethal C × t products show rapid reversibility of reflexively induced changes in respiratory patterns, lethal C × t products seem to cause prolonged stimulation after discontinued exposure to phosgene. This observation has been taken as indirect evidence that phosgene-induced lethal lung edema is likely to be associated with a dysfunctional neurogenic control of cardiopulmonary and microvascular physiology. In order to verify this hypothesis, data from respiratory function measurements during and after the inhalation exposure to phosgene gas were compared with time-course measurements of cardiac function over 20 h post-phosgene exposure. These data were complemented by time-course analyses of nitric oxide (NO(e)) and carbon dioxide in exhaled breath, including time-dependent changes of extravasated protein in bronchoalveolar lavage fluid and hemoglobin in blood. The nitric oxidase synthetase inhibitors L-NAME and L-NIL were used to further elucidate the role of NO(e) in this type of acute lung injury and whether its analysis can serve as an early biomarker of pulmonary injury. Collectively, the sequence and time course of pathological events in phosgene-induced lung edema appear to suggest that overstimulated, continued sensorimotor vagal reflexes affect cardiopulmonary hemodynamics. A continued parasympathetic tone appears to be involved in this etiopathology. PMID:23143928

  3. Anaphylaxis induced by lentil inhalation.

    PubMed

    Ayşenur, Kaya; Akan, Ayşegül; Mustafa, Erkoçoğlu; Müge, Toyran; Kocabaş, Can Naci

    2012-06-01

    Anaphylaxis is a rapid onset serious allergic reaction which may be fatal. Foods are the most common allergens leading to anaphylaxis especially for childhood. Most of the food-induced anaphylactic reactions take place after ingestion of the allergic food and only a few cases exist with anaphylactic reactions induced by inhalation of foods such as peanut, soybean and lupine. The case we present is unusual in that an 8 1/2-year-old boy developed anaphylaxis with the inhalation of steam from boiling lentils. PMID:22830298

  4. Comparison of combination inhalers vs inhaled corticosteroids alone in moderate persistent asthma

    PubMed Central

    Lee, Daniel K C; Jackson, Catherine M; Currie, Graeme P; Cockburn, Wendy J; Lipworth, Brian J

    2003-01-01

    Aims Inhalers combining long acting β2-adrenoceptor agonists (LABA) and corticosteroids (ICS) are indicated at Step 3 of current asthma guidelines. We evaluated the relative effects of LABA + ICS combination vs ICS alone on pulmonary function, bronchoprotection, acute salbutamol recovery following methacholine bronchial challenge, and surrogate inflammatory markers in patients with moderate persistent asthma. Methods Twenty-nine patients with mean FEV1 (± SEM) of 78 ± 3% predicted completed a randomized, double-blind, double-dummy, cross-over study. Patients received either 4 weeks of budesonide 400 µg + formoterol 12 µg (BUD + FM) combination twice daily followed by 1 week of BUD 400 µg alone twice daily, or 4 weeks of fluticasone propionate 250 µg + salmeterol 50 µg (FP + SM) combination twice daily followed by 1 week of FP 250 µg alone twice daily. Measurements were made at baseline and following each randomized treatment. Results FEV1 increase from pretreatment baseline as mean (± SEM) % predicted was significantly higher (P < 0.05) for BUD + FM (8 ± 1%) vs BUD (2 ± 1%), and for FP + SM (8 ± 1%) vs FP (2 ± 1%). The fall in FEV1 following methacholine challenge as percentage change from prechallenge baseline FEV1 was not significantly different in all four groups; BUD + FM (22 ± 1%), BUD (24 ± 1%), FP + SM (23 ± 1%) and FP (23 ± 1%). Salbutamol recovery over 30 min following methacholine challenge as area under curve (AUC %.min) was significantly blunted (P < 0.05) with BUD + FM (486.7 ± 35.5) vs BUD (281.1 ± 52.8), and with FP + SM (553.1 ± 34.1) vs FP (368.3 ± 46.7). There were no significant differences between respective combination inhalers or between respective ICS alone. Decreases in exhaled nitric oxide (NO) and serum eosinophilic cationic protein (ECP) from baseline were not significantly different between treatments. Conclusions Combination inhalers improve pulmonary function without potentiating anti-inflammatory effects on

  5. Aloe vera affects changes induced in pulmonary tissue of mice caused by cigarette smoke inhalation.

    PubMed

    Koul, Ashwani; Bala, Shashi; Yasmeen; Arora, Neha

    2015-09-01

    This study was undertaken to determine the influence of Aloe vera (AV) on changes induced in pulmonary tissue of cigarette smoke (CS) inhaling mice. CS inhalation for 4 weeks caused pulmonary damage as evident by histoarchitectural alterations and enhanced serum and tissue lactate dehydrogenase (LDH) activities. CS inhalation also led to increased mucin production as revealed by mucicarmine and Alcian Blue-Periodic Acid Schiff (AB-PAS) staining. Studies on bronchoalveolar lavage fluid (balf) of CS exposed animals revealed structural changes in phospholipids and increase in surface tension when compared with control counterparts. These changes were accompanied by enhanced nitric oxide (NO) levels, citrulline levels, peroxidative damage, and differential modulation of antioxidant defense system. AV administration (seven weeks, 500 mg/kg b.w. daily) to CS inhaling mice led to modulation of CS induced pulmonary changes as revealed by lesser degree of histoarchitectural alterations, lesser mucin production, decreased NO levels, citrulline levels, peroxidative damage, and serum LDH activity. AV treatment to CS inhaling mice was associated with varying response to antioxidant defense system, however balf of CS + AV treated animals did not exhibit appreciable changes when compared with that of CS exposed animals. These observations suggest that AV has the potential to modulate CS induced changes in the pulmonary tissue which could have implications in management of CS associated pulmonary diseases, however, further investigations are required to explore its complete mechanism of action. PMID:24615921

  6. Beneficial effects of inhaled NO on apoptotic pneumocytes in pulmonary thromboembolism model

    PubMed Central

    2014-01-01

    Background Lung ischemia–reperfusion injury (LIRI) may occur in the region of the affected lung after reperfusion therapy. Inhaled NO may be useful in treating acute and chronic pulmonary thromboembolism (PTE) due to the biological effect property of NO. Methods A PTE canine model was established through selectively embolizing blood clots to an intended right lower lobar pulmonary artery. PaO2/FiO2, the mPAP and PVR were investigated at the time points of 2, 4, 6 hours after inhaled NO. Masson’s trichrome stain, apoptotic pneumocytes and lung sample ultrastructure were also investigated among different groups. Results The PaO2/FiO2 in the Inhaled NO group increased significantly when compared with the Reperfusion group at time points of 4 and 6 hours after reperfusion, mPAP decreased significantly at point of 2 hours and the PVR decreased significantly at point of 6 hours after reperfusion. The amounts of apoptotic type II pneumocytes in the lower lobar lung have negative correlation trend with the arterial blood PaO2/FiO2 in Reperfusion group and Inhaled NO group. Inhaled nitric oxide given at 20 ppm for 6 hours can significantly alleviate the LIRI in the model. Conclusions Dramatic physiological improvements are seen during the therapeutic use of inhaled NO in pulmonary thromboembolism canine model. Inhaled NO may be useful in treating LIRI in acute or chronic PTE by alleviating apoptotic type II pneumocytes. This potential application warrants further investigation. PMID:25109474

  7. TARGETED DELIVERY OF INHALED PROTEINS

    EPA Science Inventory

    ETD-02-047 (Martonen) GPRA # 10108

    TARGETED DELIVERY OF INHALED PROTEINS
    T. B. Martonen1, J. Schroeter2, Z. Zhang3, D. Hwang4, and J. S. Fleming5
    1Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Research Triangle Park...

  8. Inhalant Use in Florida Youth

    ERIC Educational Resources Information Center

    Siqueira, Lorena; Crandall, Lee A.

    2006-01-01

    Purpose: To determine (1) the prevalence of use, (2) risk and protective factors for use of inhalants in Florida youth. Methods: The Florida Youth Substance Abuse Survey 2004 is a comprehensive assessment of youth substance abuse attitudes and practices obtained by sampling youth from sixty-five counties. Results: The sample consisted of 60,345…

  9. INHALATION EXPOSURE-RESPONSE METHODOLOGY

    EPA Science Inventory

    The Inhalation Exposure-Response Analysis Methodology Document is expected to provide guidance on the development of the basic toxicological foundations for deriving reference values for human health effects, focusing on the hazard identification and dose-response aspects of the ...

  10. Parental Influence on Inhalant Use

    ERIC Educational Resources Information Center

    Baltazar, Alina; Hopkins, Gary; McBride, Duane; Vanderwaal, Curt; Pepper, Sara; Mackey, Sarah

    2013-01-01

    The purpose of this article is to examine the dynamics of the relationship between parents and their adolescent children and their association with lifetime and past-month inhalant usage. The population studied was seventh- through ninth-grade students in rural Idaho (N = 570). The authors found a small, but consistent, significant inverse…

  11. NITRIC ACID PICKLING PROCESS

    DOEpatents

    Boller, E.R.; Eubank, L.D.

    1958-08-19

    An improved process is described for the treatment of metallic uranium surfaces preparatory to being given hot dip coatings. The process consists in first pickling the uraniunn surInce with aqueous 50% to 70% nitric acid, at 60 to 70 deg C, for about 5 minutes, rinsing the acid solution from the uranium article, promptly drying and then passing it through a molten alkali-metal halide flux consisting of 42% LiCl, 53% KCla and 5% NaCl into a molten metal bath consisting of 85 parts by weight of zinc and 15 parts by weight of aluminum

  12. Impact of inhalation therapy on oral health

    PubMed Central

    Godara, Navneet; Godara, Ramya; Khullar, Megha

    2011-01-01

    Inhalation therapy has been employed as the mainstay of the treatment in chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Beta-2 agonists, anticholinergic bronchodilators, inhaled corticosteroids, and sodium cromoglycate are often used alone or in combination in an inhaled form. Studies have shown that inhaled drugs used in the treatment have some adverse effects on the oral health based on their dosage, frequency, and duration of use. Several oral conditions such as xerostomia, dental caries, candidiasis, ulceration, gingivitis, periodontitis, and taste changes have been associated with inhalation therapy. Since the prevalence of chronic respiratory diseases is rising, it is important to provide optimal oral care to the individuals receiving inhalation therapy. This article will review the influence of inhaled drugs on the oral health of individuals and adequate management and prevention of the same. PMID:22084541

  13. Tropospheric nitric oxide measurements

    NASA Technical Reports Server (NTRS)

    Torres, A. L.

    1988-01-01

    Nitric oxide (NO) plays a key role in tropospheric photo-chemistry. The photochemical oxidation of hydrocarbons, for example, can serve as either a source or a sink for ozone, depending on the local abundance of NO. Nitric oxide also helps govern atmospheric concentrations of the hydroxyl (OH) radical. The OH radical is the single most important player in photochemical transformations because it controls the atmospheric lifetimes of so many chemical species. Although NO serves as a very effective catalyst in many important chemical processes, its concentration is low enough to normally be expressed in units of parts per trillion by volume (pptv). Consequently, commercially available detectors for NO (with detection limits of about one part per billion) have proven to be unsuitable for use anywhere except in urban areas and near other local pollution sources. Under the sponsorship of NASA's Global Tropospheric Experiment (GTE), Wallops has developed an extremely sensitive detector with a detection limit of a few pptv. The system was specifically designed for aircraft use, with the objective of applying it in global aircraft studies of tropospheric chemistry. Studies with the detector are examined.

  14. [Effects of Instruction on Inhalation Techniques Using iPads - Web Application "Inhalation Lessons"].

    PubMed

    Kogawa, Noriko; Ito, Reiko; Gon, Yasuhiro; Maruoka, Shuichiro; Hashimoto, Shu

    2015-12-01

    Instruction on inhalation techniques for chronic obstructive pulmonary disease(COPD)and asthma patients being treated with inhalants have sufficient therapeutic effects and are important to maintain adherence. However, problems continue to exist, including time constraints of medical staff that have a large number of patients and a lack of knowledge on inhalation instruction methods. A web application,"Inhalation Lessons,'for the iPad has been developed. It explains inhalation methods, and consists of videos and review tests. Instruction on inhalation techniques was performed using this application for patients that use Diskus, and the effects were examined. As a result, there are significant improvements in the inhalation techniques of patients after viewing the"Inhalation Lessons'application. Uniform instruction on inhalation techniques can be performed even in the field of homecare. PMID:26809400

  15. Moderating Effects of Perceived Social Benefits on Inhalant Initiation Among American Indian and White Youth

    PubMed Central

    Swaim, Randall C.

    2016-01-01

    This study examined whether perceived social benefits moderated the relationship between social influence variables (school attachment, peer inhalant use, perceived family caring, parental monitoring) and stage of inhalant initiation (Study 1), and lifetime inhalant use (Study 2). Participants were 7th–12th grade students attending schools on or near American Indian reservations with comparisons made between American Indian and White students. A total of 3498 American Indian and 1596 White students were surveyed. Differences in mean levels of social influence variables were found across ethnicity and stage of inhalant initiation and lifetime inhalant use. SEM models were evaluated to examine variable relationships for the two studies. For Study 1, social influence variables did not clearly differentiate early versus later inhalant initiators, and perceived social benefits failed to serve as a moderator. More differences were observed between users and non-users across measures of social influence (Study 2). Perceived social benefits generally did not moderate the relationships with two exceptions. Low perceived social benefits provided greater protection against the influence of peers on lifetime inhalant use among White students, while high perceived social benefits increased risk of peer influence among American Indian students. PMID:26962974

  16. Inhaled allergen bronchoprovocation tests.

    PubMed

    Diamant, Zuzana; Gauvreau, Gail M; Cockcroft, Don W; Boulet, Louis-Philippe; Sterk, Peter J; de Jongh, Frans H C; Dahlén, Barbro; O'Byrne, Paul M

    2013-11-01

    The allergen bronchoprovocation test is a long-standing exacerbation model of allergic asthma that can induce several clinical and pathophysiologic features of asthma in sensitized subjects. Standardized allergen challenge is primarily a research tool, and when properly conducted by qualified and experienced investigators, it is safe and highly reproducible. In combination with validated airway sampling and sensitive detection techniques, allergen challenge allows the study of several features of the physiology of mainly TH2 cell-driven asthma in relation to the kinetics of the underlying airway pathology occurring during the allergen-induced late response. Furthermore, given the small within-subject variability in allergen-induced airway responses, allergen challenge offers an adequate disease model for the evaluation of new (targeted) controller therapies for asthma in a limited number of subjects. In proof-of-efficacy studies thus far, allergen challenge showed a fair positive predicted value and an excellent negative predictive value for the actual clinical efficacy of new antiasthma therapies, underscoring its important role in early drug development. In this review we provide recommendations on challenge methods, response measurements, sample size, safety, and harmonization for future applications. PMID:24119772

  17. Inhalation therapy in mechanical ventilation

    PubMed Central

    Maccari, Juçara Gasparetto; Teixeira, Cassiano; Gazzana, Marcelo Basso; Savi, Augusto; Dexheimer-Neto, Felippe Leopoldo; Knorst, Marli Maria

    2015-01-01

    Patients with obstructive lung disease often require ventilatory support via invasive or noninvasive mechanical ventilation, depending on the severity of the exacerbation. The use of inhaled bronchodilators can significantly reduce airway resistance, contributing to the improvement of respiratory mechanics and patient-ventilator synchrony. Although various studies have been published on this topic, little is known about the effectiveness of the bronchodilators routinely prescribed for patients on mechanical ventilation or about the deposition of those drugs throughout the lungs. The inhaled bronchodilators most commonly used in ICUs are beta adrenergic agonists and anticholinergics. Various factors might influence the effect of bronchodilators, including ventilation mode, position of the spacer in the circuit, tube size, formulation, drug dose, severity of the disease, and patient-ventilator synchrony. Knowledge of the pharmacological properties of bronchodilators and the appropriate techniques for their administration is fundamental to optimizing the treatment of these patients. PMID:26578139

  18. Recognition and prevention of inhalant abuse.

    PubMed

    Anderson, Carrie E; Loomis, Glenn A

    2003-09-01

    Inhalant abuse is a prevalent and often overlooked form of substance abuse in adolescents. Survey results consistently show that nearly 20 percent of children in middle school and high school have experimented with inhaled substances. The method of delivery is inhalation of a solvent from its container, a soaked rag, or a bag. Solvents include almost any household cleaning agent or propellant, paint thinner, glue, and lighter fluid. Inhalant abuse typically can cause a euphoric feeling and can become addictive. Acute effects include sudden sniffing death syndrome, asphyxia, and serious injuries (e.g., falls, burns, frostbite). Chronic inhalant abuse can damage cardiac, renal, hepatic, and neurologic systems. Inhalant abuse during pregnancy can cause fetal abnormalities. Diagnosis of inhalant abuse is difficult and relies almost entirely on a thorough history and a high index of suspicion. No specific laboratory tests confirm solvent inhalation. Treatment is generally supportive, because there are no reversal agents for inhalant intoxication. Education of young persons and their parents is essential to decrease experimentation with inhalants. PMID:13678134

  19. [Significance of inhaled environmental allergens].

    PubMed

    Zochert, J

    1983-01-01

    Whereas the importance of pollen as inhalative allergens has been largely investigated and is generally known, the experience in the frequency and the role of the sensibilization with air-borne fungi is relatively limited. In 720 patients with Asthma bronchiale the degree of sensitization has been tested with various extracts of air-borne fungi of SSW Dresden (mould mixture, aspergillin, mucor, cladosporium and penicillium and alternaria). The most frequent and also the strongest reactions were found with alternaria and the smallest part of positive skin reactions with penicillium. An isolated sensitization with mould has been demonstrated in 20 per cent of the cases. In 60 per cent of the tested patients a manifest mould allergy was shown by means of the Inhalative Allergen Test, the most favourable correlation between Intracutaneous Test (ICT) and Inhalative Test (IAT) was found with alternaria (76%). A conformance between ICT and basophils degranulation test (BDT) was stated in 69% of the cases. The aim should be comparable tests with allergen extracts without irritative effects and qualitative measurements of air-borne fungi. PMID:6649704

  20. Demystified … Nitric oxide

    PubMed Central

    Stuart-Smith, K

    2002-01-01

    The discovery of nitric oxide (NO) demonstrated that cells could communicate via the manufacture and local diffusion of an unstable lipid soluble molecule. Since the original demonstration of the vascular relaxant properties of endothelium derived NO, this fascinating molecule has been shown to have multiple, complex roles within many biological systems. This review cannot hope to cover all of the recent advances in NO biology, but seeks to place the discovery of NO in its historical context, and show how far our understanding has come in the past 20 years. The role of NO in mitochondrial respiration, and consequently in oxidative stress, is described in detail because these processes probably underline the importance of NO in the development of disease. PMID:12456772

  1. Synthetic vitreous fibers--inhalation studies.

    PubMed

    McConnell, E E

    1994-12-01

    Synthetic vitreous fibers (SVFs), often referred to as "man-made vitreous fibers," are a class of materials that have their major uses for insulation against heat and sound. The original fibers are produced by melting various types of rock, clay, etc. and then blowing or extruding them into fibers of particular properties. During production and use small fractions of airborne fibers can be generated. Because of this a series of state-of-the-art inhalation studies was initiated to study the possible health hazards presented by the four major types of vitreous materials [two types of insulation glass wool, rock wool, slag wool, and four types of refractory ceramic fibers (RCF)] found in the workplace or to which the general public may be exposed. Rats and hamsters (30 mg/m3 kaolin-based RCF only) were exposed by nose-only inhalation to 3, 16, or 30 mg/m3 for 6 hr/day, 5 days/week, for 18 (hamsters) or 24 (rats) months and were held for lifetime observation (until approximately 20% survival) to study the chronic toxicity and potential carcinogenic activity of these classes of SVFs. Chrysotile or crocidolite asbestos served as positive controls. All of the fibers stimulated an inflammatory response characterized by an increase in the number of pulmonary macrophages at the level of the terminal bronchioles and proximal alveoli. RCF produced interstitial fibrosis in the walls of the proximal alveoli as early as 3 months and rock wool by 12 months. The only fiber which showed carcinogenic activity was RCF which produced a dose-related increase in both primary lung neoplasms (rats only) and mesotheliomas (rats and hamsters). PMID:7724853

  2. The Skeletal Effects of Inhaled Glucocorticoids.

    PubMed

    Sutter, Stephanie A; Stein, Emily M

    2016-06-01

    The skeletal effects of inhaled glucocorticoids are poorly understood. Children with asthma treated with inhaled glucocorticoids have lower growth velocity, bone density, and adult height. Studies of adults with asthma have reported variable effects on BMD, although prospective studies have demonstrated bone loss after initiation of inhaled glucocorticoids in premenopausal women. There is a dose-response relationship between inhaled glucocorticoids and fracture risk in asthmatics; the risk of vertebral and non-vertebral fractures is greater in subjects treated with the highest doses in the majority of studies. Patients with COPD have lower BMD and higher fracture rates compared to controls, however, the majority of studies have not found an additional detrimental effect of inhaled glucocorticoids on bone. While the evidence is not conclusive, it supports using the lowest possible dose of inhaled glucocorticoids to treat patients with asthma and COPD and highlights the need for further research on this topic. PMID:27091558

  3. Misuse of xylometazoline nasal drops by inhalation.

    PubMed

    Anand, Jacek Sein; Salamon, Marek; Habrat, Boguslaw; Scinska, Anna; Bienkowski, Przemyslaw

    2008-12-01

    Six male prisoners who misused xylometazoline nasal drops by inhalation were interviewed by a prison physician in 2006. The prisoners received xylometazoline drops during regular visits in the prison ambulatory service. In order to get the medication, the subjects reported false symptoms of rhinosinusitis and allergic reactions. Psychoactive effects of inhaled xylometazoline were described as "stimulation," "excitation," and "feeling of strength." Although preliminary, our findings suggest that topical adrenergic decongestants can produce rewarding effects when administered by inhalation. PMID:19085441

  4. Augmentation of pulmonary reactions to quartz inhalation by trace amounts of iron-containing particles.

    PubMed Central

    Castranova, V; Vallyathan, V; Ramsey, D M; McLaurin, J L; Pack, D; Leonard, S; Barger, M W; Ma, J Y; Dalal, N S; Teass, A

    1997-01-01

    Fracturing quartz produces silica-based radicals on the fracture planes and generates hydroxyl radicals (.OH) in aqueous media. .OH production has been shown to be directly associated with quartz-induced cell damage and phagocyte activation in vitro. This .OH production in vitro is inhibited by desferrioxamine mesylate, an Fe chelator, indicating involvement of a Fenton-like reaction. Our objective was to determine if Fe contamination increased the ability of inhaled quartz to cause inflammation and lung injury. Male Fischer 344 rats were exposed 5 hr/day for 10 days to filtered air, 20 mg/m3 freshly milled quartz (57 ppm Fe), or 20 mg/m3 freshly milled quartz contaminated with Fe (430 ppm Fe). High Fe contamination of quartz produced approximately 57% more reactive species in water than quartz with low Fe contamination. Compared to inhalation of quartz with low Fe contamination, high Fe contamination of quartz resulted in increases in the following responses: leukocyte recruitment (537%), lavageable red blood cells (157%), macrophage production of oxygen radicals measured by electron spin resonance or chemiluminescence (32 or 90%, respectively), nitric oxide production by macrophages (71%), and lipid peroxidation of lung tissue (38%). These results suggest that inhalation of freshly fractured quartz contaminated with trace levels of Fe may be more pathogenic than inhalation of quartz alone. PMID:9400745

  5. Nanoparticle inhalation alters systemic arteriolar vasoreactivity through sympathetic and cyclooxygenase-mediated pathways

    PubMed Central

    Knuckles, Travis L.; Yi, Jinghai; Frazer, David G.; Leonard, Howard D.; Chen, Bean T.; Castranova, Vince; Nurkiewicz, Timothy R.

    2016-01-01

    The widespread increase in the production and use of nanomaterials has increased the potential for nanoparticle exposure; however, the biological effects of nanoparticle inhalation are poorly understood. Rats were exposed to nanosized titanium dioxide aerosols (10 µg lung burden); at 24 h post-exposure, the spinotrapezius muscle was prepared for intravital microscopy. Nanoparticle exposure did not alter perivascular nerve stimulation (PVNS)-induced arteriolar constriction under normal conditions; however, adrenergic receptor inhibition revealed a more robust effect. Nanoparticle inhalation reduced arteriolar dilation in response to active hyperaemia (AH). In both PVNS and AH experiments, nitric oxide synthase (NOS) inhibition affected only controls. Whereas cyclooxygenase (COX) inhibition only attenuated AH-induced arteriolar dilation in nanoparticle-exposed animals. This group displayed an enhanced U46619 constriction and attenuated iloprost-induced dilation. Collectively, these studies indicate that nanoparticle exposure reduces microvascular NO bioavailability and alters COX-mediated vasoreactivity. Furthermore, the enhanced adrenergic receptor sensitivity suggests an augmented sympathetic responsiveness. PMID:21830860

  6. Inhalant abuse: youth at risk.

    PubMed

    Ahern, Nancy R; Falsafi, Nasrin

    2013-08-01

    Inhalant abuse is a significant problem affecting many people, particularly youth. The easy availability of products containing volatile substances (e.g., aerosol sprays, cleaning products, paint) provides opportunity for mind-altering experiences. Unfortunately, serious complications such as brain, cardiovascular, liver, and renal damage or even death may ensue. Adolescents perceive the risk as low, and parents may be unaware of the risks. Health care providers, particularly psychiatric nurses, should undertake strategies of prevention, assessment, and treatment of this challenging problem. PMID:23786241

  7. Chemiluminescence of nitric oxide

    NASA Technical Reports Server (NTRS)

    Sharp, W. E.; Rusch, D. W.

    1981-01-01

    Measurements of the intensities of the delta and gamma bands of nitric oxide in the nighttime terrestrial thermosphere are presented and used to infer the rate coefficient for the transition from the C 2 Pi to the A 2 Sigma + states. The nightglow spectrum was observed between 1900 and 2300 A at a resolution of 15 A by a rocket-borne scanning 1/4-m spectrometer pointing north at an apogee of 150 km. Progressions of the delta, gamma and epsilon bands are identified on the spectra by the construction of synthetic spectra, and the contributions of resonance fluorescence to the total band intensities are calculated. Finally, the ratio of the sum of the gamma bands for v-prime = 0 to the sum of the delta bands for v-prime = 0 is used to derive a branching ratio of 0.21 + or - 0.04 to the A 2 Sigma + state, which yields a probability for the C-A transition of 5.6 + or - 1.5 x to the 6th/sec.

  8. [The use of nitric oxide during transport of newborns with critical respiratory insufficiency: own experience, preliminary report].

    PubMed

    Ziebiński, Marek; Walas, Wojciech

    2002-01-01

    This preliminary report presents author's experience with inhaled nitric oxide during transport of newborns with critical respiratory insufficiency. The theoretical basis, indications and contraindications as well as principles of administration during transport are described. The required equipment and some technical aspects are discussed. A short preview of performed transportations is given. Preliminary data show, that use of NO during transport is very helpful in children with critical respiratory insufficiency. PMID:12108077

  9. How to use an inhaler - with spacer

    MedlinePlus

    ... out through your mouth. After using your inhaler, rinse your mouth with water, gargle, and spit. This helps reduce side effects from your medicine. Keep your inhaler clean Look at the ... mouthpiece. Rinse only the mouthpiece and cap in warm water. ...

  10. Tips for Teens: The Truth about Inhalants

    MedlinePlus

    ... site at www. whitehousedrugpolicy. gov. No.Even though household products like glue and air freshener have legal,useful ... A. A. Q.Since inhalants are found in household products,aren’t they safe? Q.Can inhalants make ...

  11. 40 CFR 798.2450 - Inhalation toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 33 2013-07-01 2013-07-01 false Inhalation toxicity. 798.2450 Section 798.2450 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Subchronic Exposure § 798.2450 Inhalation toxicity. (a) Purpose. In the assessment...

  12. Inhaled antimicrobial therapy - barriers to effective treatment.

    PubMed

    Weers, Jeffry

    2015-05-01

    Inhaled antibiotics dramatically improve targeting of drug to the site of respiratory infections, while simultaneously minimizing systemic exposure and associated toxicity. The high local concentrations of antibiotic may enable more effective treatment of multi-drug resistant pathogens. This review explores barriers to effective treatment with inhaled antibiotics. In addition, potential opportunities for improvements in treatment are reviewed. PMID:25193067

  13. Nanotechnology and pharmaceutical inhalation aerosols.

    PubMed

    Patel, A R; Vavia, P R

    2007-02-01

    Pharmaceutical inhalation aerosols have been playing a crucial role in the health and well being of millions of people throughout the world for many years. The technology's continual advancement, the ease of use and the more desirable pulmonary-rather-than-needle delivery for systemic drugs has increased the attraction for the pharmaceutical aerosol in recent years. But administration of drugs by the pulmonary route is technically challenging because oral deposition can be high, and variations in inhalation technique can affect the quantity of drug delivered to the lungs. Recent advances in nanotechnology, particularly drug delivery field have encouraged formulation scientists to expand their reach in solving tricky problems related to drug delivery. Moreover, application of nanotechnology to aerosol science has opened up a new category of pharmaceutical aerosols (collectively known as nanoenabled-aerosols) with added advantages and effectiveness. In this review, some of the latest approaches of nano-enabled aerosol drug delivery system (including nano-suspension, trojan particles, bioadhesive nanoparticles and smart particle aerosols) that can be employed successfully to overcome problems of conventional aerosol systems have been introduced. PMID:17375556

  14. Toxicological Assessment of Noxious Inhalants

    PubMed Central

    Kleinsasser, N. H.; Sassen, A. W.; Wallner, B. W.; Staudenmaier, R.; Harréus, U. A.; Richter, E.

    2004-01-01

    In the past centuries mankind has been exposed to various forms of air pollution not only at his occupational but also in his social environment. He mainly gets exposed with these pollutants through the respiratory organs and partially absorbs them into the body. Many of these airborne substances can be harmful for humans and some of them may account for tumorigenic effects. The following essay describes the main features of toxicological assessment of inhalative environmental and workplace xenobiotics. The essay also explains relevant characteristics and limit values of noxious compounds and gases and depicts modern testing methods. To this end, emphasis is given on methods characterizing the different stages of tumorigenic processes. Various test systems have been developed which can be used in vivo, ex vivo or in vitro. They are to a great part based on the evidence of changes in DNA or particular genes of cells. Among others they have highlighted the impact of interindividual variability on enzymatic activation of xenobiotics and on susceptibility of the host to tumor diseases. Unfortunately, for many inhalative environmental noxious agents no sufficient risk profiles have been developed. The completion of these profiles should be the goal of toxicological assessment in order to allow reasonable socioeconomic or individual-based risk reduction. PMID:22073045

  15. Inhalants

    MedlinePlus

    ... for the wide variety of substances—including solvents, aerosols, gases, and nitrites—that are rarely, if ever, ... a glue bottle or a marking pen), spray aerosols (such as computer cleaning dusters) directly into their ...

  16. Inhalants

    MedlinePlus

    ... that your kids will use drugs such as marijuana or LSD. But you may not realize the dangers of substances in your own home. Household products such as glues, hair sprays, paints and lighter fluid can be drugs ...

  17. Inhalants

    MedlinePlus

    ... electronic contact cleaner Aerosols are sprays that contain propellants and solvents. They include: Spray paint, hair spray, ... burn injuries Freon (difluoroethane substitutes) Refrigerant and aerosol propellant Sudden sniffing death Breathing problems and death (from ...

  18. Impairment of Coronary Arteriolar Endothelium-Dependent Dilation after Multi-Walled Carbon Nanotube Inhalation: A Time-Course Study

    PubMed Central

    Stapleton, Phoebe A.; Minarchick, Valerie C.; Cumpston, Amy M.; McKinney, Walter; Chen, Bean T.; Sager, Tina M.; Frazer, David G.; Mercer, Robert R.; Scabilloni, James; Andrew, Michael E.; Castranova, Vincent; Nurkiewicz, Timothy R.

    2012-01-01

    Engineered nanomaterials have been developed for widespread applications due to many highly unique and desirable characteristics. The purpose of this study was to assess pulmonary inflammation and subepicardial arteriolar reactivity in response to multi-walled carbon nanotube (MWCNT) inhalation and evaluate the time course of vascular alterations. Rats were exposed to MWCNT aerosols producing pulmonary deposition. Pulmonary inflammation via bronchoalveolar lavage and MWCNT translocation from the lungs to systemic organs was evident 24 h post-inhalation. Coronary arterioles were evaluated 24–168 h post-exposure to determine microvascular response to changes in transmural pressure, endothelium-dependent and -independent reactivity. Myogenic responsiveness, vascular smooth muscle reactivity to nitric oxide, and α-adrenergic responses all remained intact. However, a severe impact on endothelium-dependent dilation was observed within 24 h after MWCNT inhalation, a condition which improved, but did not fully return to control after 168 h. In conclusion, results indicate that MWCNT inhalation not only leads to pulmonary inflammation and cytotoxicity at low lung burdens, but also a low level of particle translocation to systemic organs. MWCNT inhalation also leads to impairments of endothelium-dependent dilation in the coronary microcirculation within 24 h, a condition which does not fully dissipate within 168 h. The innovations within the field of nanotechnology, while exciting and novel, can only reach their full potential if toxicity is first properly assessed. PMID:23203034

  19. Inhalation of Polychlorinated Biphenyls (PCB) Produces Hyperactivity in Rats.

    PubMed

    Lombardo, John P; Berger, David F; Hunt, Anne; Carpenter, David O

    2015-01-01

    Attention deficit hyperactivity disorder (ADHD) is a serious behavioral syndrome seen in children, and more common in males than females. There is increasing evidence that prenatal and/or early life exposure to persistent organic pollutants (POP) such as polychlorinated biphenyls (PCB) is associated with increased risk of ADHD occurrence. While PCB exposure is usually attributed to ingestion of contaminated food, recent reports of elevated PCB concentrations in indoor air, especially in schools, raised concern regarding inhalation as an important route of exposure to PCB with consequent effects on neurobehavior. The effects of exposure to air contaminated with Aroclor 1248 or contaminated sediment (SED) from the St. Lawrence River were examined on operant behavior of male and female Sprague-Dawley rats. Data showed that relative to controls, vapor-phase inhalation of PCB, whether from blowing air over Aroclor 1248 or from blowing air over sediment contaminated with PCB, resulted in hyperactivity and impatience in rats, more pronounced in males than females. These results are consistent with the hypothesis that inhalation of PCB may contribute to behavioral abnormalities in children. PMID:26398098

  20. Stimulation of Oxytocin Receptor during Early Reperfusion Period Protects the Heart against Ischemia/Reperfusion Injury: the Role of Mitochondrial ATP-Sensitive Potassium Channel, Nitric Oxide, and Prostaglandins.

    PubMed

    Imani, Alireza; Khansari, Maryam; Azizi, Yaser; Rakhshan, Kamran; Faghihi, Mahdieh

    2015-08-01

    Postconditioning is a simple and safe strategy for cardioprotection and infarct size limitation. Our previous study showed that oxytocin (OT) exerts postconditioning effect on ischemic/reperfused isolated rat heart. The aim of this study was to investigate the involvement of OT receptor, mitochondrial ATP-sensitive potassium channel (mKATP), nitric oxide (NO) and cyclooxygenase (COX) pathways in OT postconditioning. Isolated rat hearts were divided into10 groups and underwent 30 min of regional ischemia followed by 120 min of reperfusion (n =6). In I/R (ischemia/reperfusion) group, ischemia and reperfusion were induced without any treatment. In OT group, oxytocin was perfused 5 min prior to beginning of reperfusion for 25 min. In groups 3-6, atosiban (oxytocin receptor blocker), L-NAME (N-Nitro-L-Arginine Methyl Ester, non-specific nitric oxide synthase inhibitor), 5-HD (5-hydroxydecanoate, mKATP inhibitor) and indomethacin (cyclooxygenase inhibitor) were infused prior to oxytocin administration. In others, the mentioned inhibitors were perfused prior to ischemia without oxytocin infusion. Infarct size, ventricular hemodynamic, coronary effluent, malondialdehyde (MDA) and lactate dehydrogenase (LDH) were measured at the end of reperfusion. OT perfusion significantly reduced infarct size, MDA and LDH in comparison with IR group. Atosiban, 5HD, L-NAME and indomethacin abolished the postconditioning effect of OT. Perfusion of the inhibitors alone prior to ischemia had no effect on infarct size, hemodynamic parameters, coronary effluent and biochemical markers as compared with I/R group. In conclusion, this study indicates that postconditioning effects of OT are mediated by activation of mKATP and production of NO and Prostaglandins (PGs). PMID:26545994

  1. Inhaled Corticosteroids and Secondary Adrenal Insufficiency

    PubMed Central

    Sannarangappa, Vishnu; Jalleh, Ryan

    2014-01-01

    Inhaled corticosteroids (ICS) have been used as first line treatment of asthma for many decades. ICS are a form of exogenous glucocorticosteroids that can suppress the endogenous production of glucocorticosteroids, a condition known as adrenal suppression (AS). As a result, cessation, decreasing the dose or changing the type of ICS may trigger features of adrenal insufficiency (AI). AI may cause a spectrum of presentations varying from vague symptoms of fatigue to potentially life threatening acute adrenal crises. This article reviews the current literature on ICS and AI particularly in adults (although majority of data available is from the paediatric population). It aims to increase awareness of the potential risk of AI associated with ICS use, delineate the pathogenesis of AI and to provide recommendations on screening and management. From our literature review, we have found numerous case reports that have shown an association between ICS and AI particularly in children and patients using high doses. However, there have also been reports of AI in adults as well as in patients using low to moderate doses of ICS. To conclude, we recommend screening for AI in select patient groups with an initial early morning serum cortisol. If results are abnormal, more definitive testing such as the low dose corticotropin stimulation test may be done to confirm the diagnosis. PMID:25674179

  2. Pharmacologic strategies in neonatal pulmonary hypertension other than nitric oxide.

    PubMed

    Lakshminrusimha, Satyan; Mathew, Bobby; Leach, Corinne L

    2016-04-01

    Inhaled nitric oxide (iNO) is approved for use in persistent pulmonary hypertension of the newborn (PPHN) but does not lead to sustained improvement in oxygenation in one-third of patients with PPHN. Inhaled NO is less effective in the management of PPHN secondary to congenital diaphragmatic hernia (CDH), extreme prematurity, and bronchopulmonary dysplasia (BPD). Intravenous pulmonary vasodilators such as prostacyclin, alprostadil, sildenafil, and milrinone have been successfully used in PPHN resistant to iNO. Oral pulmonary vasodilators such as endothelin receptor antagonist bosentan and phosphodiesterase-5 inhibitors such as sildenafil and tadalafil are used both during acute and chronic phases of PPHN. In the absence of infection, glucocorticoids may also be effective in PPHN. Many of these pharmacologic agents are not approved for use in PPHN and our knowledge is based on case reports and small trials. Large multicenter randomized controlled trials with long-term follow-up are required to evaluate alternate pharmacologic strategies in PPHN. PMID:26778236

  3. Determination of the atherogenic potential of inhaled carbon monoxide

    SciTech Connect

    Penn, A. )

    1993-05-01

    he effects of chronic exposure to moderate levels of carbon monoxide upon the augmentation of arteriosclerotic plaque development were investigated in a series of in vivo studies in the cockerel (young rooster). This animal model has been well characterized, especially regarding the role of environmental agents in exacerbating early stages of plaque development. Cockerels injected with subtumorigenic doses of carcinogens exhibit markedly accelerated development of aortic arteriosclerotic plaques. Inhalation of mainstream smoke from two packs of cigarettes (100 minutes/day for 16 weeks) causes small but statistically significant increases in plaque size. As is the case with many animal models of plaque development, raised fat-proliferative plaques also appear in these animals following cholesterol feeding. Carbon monoxide is a ubiquitous pollutant in urban environments, where it is derived largely from mobile sources and cigarette smoke. Exposure to chronically elevated carbon monoxide levels has been implicated in a number of health-related problems. Whether such exposure plays a role in the development of arteriosclerosis has not been determined conclusively. In the present study, three questions were posed: 1. Will inhaled carbon monoxide at levels of 50 to 200 parts per million (ppm)* (two hours/day for 16 weeks) be sufficient to augment arteriosclerotic plaque development in cockerels, in the absence of other plaque-promoting agents 2. Will the inhalation of 100 ppm carbon monoxide (two hours/day for 16 weeks), concomitant with the feeding of low levels (0.1%) of cholesterol, yield larger plaques than those obtained with either of these agents administered alone 3. Will inhalation of 100 ppm carbon monoxide (two hours/day for 11 or 22 weeks), by cockerels in whom plaques have already appeared, further augment plaque development Cockerels were exposed to carefully regulated levels of carbon monoxide in stainless-steel and Plexiglas dynamic exposure chambers.

  4. Nitric oxide as an antioxidant

    SciTech Connect

    Kanner, J.; Harel, S.; Granit, R. )

    1991-08-15

    Benzoate monohydroxy compounds, and in particular salicylate, were produced during interaction of ferrous complexes with hydrogen peroxide (Fenton reaction) in a N2 environment. These reactions were inhibited when Fe complexes were flushed, prior to the addition in the model system, by nitric oxide. Methionine oxidation to ethylene by Fenton reagents was also inhibited by nitric oxide. Myoglobin in several forms such as metmyoglobin, oxymyoglobin, and nitric oxide-myoglobin were interacted with an equimolar concentration of hydrogen peroxide. Spectra changes in the visible region and the changes in membrane (microsomes) lipid peroxidation by the accumulation of thiobarbituric acid-reactive substances (TBA-RS) were determined. The results showed that metmyoglobin and oxymyoglobin were activated by H2O2 to ferryl myoglobin, which initiates membrane lipid peroxidation; but not nitric oxide-myoglobin, which, during interaction with H2O2, did not form ferryl but metmyoglobin which only poorly affected lipid peroxidation. It is assumed that nitric oxide, liganded to ferrous complexes, acts to prevent the prooxidative reaction of these complexes with H2O2.

  5. In vivo characterization of GSK256066, a high-affinity inhaled phosphodiesterase 4 inhibitor.

    PubMed

    Nials, Anthony T; Tralau-Stewart, Cathy J; Gascoigne, Michele H; Ball, Douglas I; Ranshaw, Lisa E; Knowles, Richard G

    2011-04-01

    Oral phosphodiesterase (PDE) 4 inhibitors have demonstrated clinical efficacy in chronic obstructive pulmonary disease and asthma. Preclinical and clinical investigation of inhaled PDE4 inhibitors is ongoing. 6-({3-[(Dimethylamino)carbonyl]phenyl}sulfonyl)-8-methyl-4-{[3-methyloxy)phenyl]amino}-3-quinolinecarboxamide (GSK256066) is an exceptionally high-affinity and selective inhibitor of PDE4 designed for inhaled delivery. The aim of these studies was to investigate the potency, duration of action, and therapeutic index of GSK256066 in animal models of pulmonary inflammation. The effects of intratracheally administered GSK256066 were investigated in rat lipopolysaccharide (LPS)- and ovalbumin (OVA)-induced models of acute pulmonary inflammation. In some studies, fluticasone propionate (FP) was included as a comparator. The therapeutic index (anti-inflammatory effect versus emesis) of GSK256066 was studied in ferrets where acute pulmonary inflammation was induced with inhaled LPS. In rats, GSK256066 and FP caused significant (p < 0.05) inhibition of LPS-induced pulmonary neutrophilia. The duration of action of GSK256066 at 10 × ED(50) dose (10 μg/kg) was 12 h. GSK256066 and FP also inhibited LPS-induced increases in exhaled nitric oxide (ED(50) 35 and 92 μg/kg, respectively). In addition, GSK256066 inhibited pulmonary eosinophilia in rats exposed to OVA (ED(50) 0.4 μg/kg). In ferrets, inhaled GSK256066 inhibited LPS-induced pulmonary neutrophilia (ED(50) 18 μg/kg), and no emetic episodes were observed. Thus, GSK256066 may have an improved therapeutic index compared with oral PDE4 inhibitors, e.g., cilomilast and roflumilast. In summary, GSK256066 demonstrates potent and long-lasting anti-inflammatory effects in animal models of pulmonary inflammation and does not induce emetic episodes in ferrets. GSK256066 has potential as an inhaled therapeutic for the treatment of asthma and chronic obstructive pulmonary disease. PMID:21205924

  6. Inhalation injury: epidemiology, pathology, treatment strategies

    PubMed Central

    2013-01-01

    Lung injury resulting from inhalation of smoke or chemical products of combustion continues to be associated with significant morbidity and mortality. Combined with cutaneous burns, inhalation injury increases fluid resuscitation requirements, incidence of pulmonary complications and overall mortality of thermal injury. While many products and techniques have been developed to manage cutaneous thermal trauma, relatively few diagnosis-specific therapeutic options have been identified for patients with inhalation injury. Several factors explain slower progress for improvement in management of patients with inhalation injury. Inhalation injury is a more complex clinical problem. Burned cutaneous tissue may be excised and replaced with skin grafts. Injured pulmonary tissue must be protected from secondary injury due to resuscitation, mechanical ventilation and infection while host repair mechanisms receive appropriate support. Many of the consequences of smoke inhalation result from an inflammatory response involving mediators whose number and role remain incompletely understood despite improved tools for processing of clinical material. Improvements in mortality from inhalation injury are mostly due to widespread improvements in critical care rather than focused interventions for smoke inhalation. Morbidity associated with inhalation injury is produced by heat exposure and inhaled toxins. Management of toxin exposure in smoke inhalation remains controversial, particularly as related to carbon monoxide and cyanide. Hyperbaric oxygen treatment has been evaluated in multiple trials to manage neurologic sequelae of carbon monoxide exposure. Unfortunately, data to date do not support application of hyperbaric oxygen in this population outside the context of clinical trials. Cyanide is another toxin produced by combustion of natural or synthetic materials. A number of antidote strategies have been evaluated to address tissue hypoxia associated with cyanide exposure. Data

  7. Inflammatory effects of inhaled sulfur mustard in rat lung

    SciTech Connect

    Malaviya, Rama; Sunil, Vasanthi R.; Cervelli, Jessica; Anderson, Dana R.; Holmes, Wesley W.; Conti, Michele L.; Gordon, Ronald E.; Laskin, Jeffrey D.; Laskin, Debra L.

    2010-10-15

    Inhalation of sulfur mustard (SM), a bifunctional alkylating agent that causes severe lung damage, is a significant threat to both military and civilian populations. The mechanisms mediating its cytotoxic effects are unknown and were investigated in the present studies. Male rats Crl:CD(SD) were anesthetized, and then intratracheally intubated and exposed to 0.7-1.4 mg/kg SM by vapor inhalation. Animals were euthanized 6, 24, 48 h or 7 days post-exposure and bronchoalveolar lavage fluid (BAL) and lung tissue collected. Exposure of rats to SM resulted in rapid pulmonary toxicity, including focal ulceration and detachment of the trachea and bronchial epithelia from underlying mucosa, thickening of alveolar septal walls and increased numbers of inflammatory cells in the tissue. There was also evidence of autophagy and apoptosis in the tissue. This was correlated with increased BAL protein content, a marker of injury to the alveolar epithelial lining. SM exposure also resulted in increased expression of markers of inflammation including cyclooxygenase-2 (COX-2), tumor necrosis factor-{alpha} (TNF{alpha}), inducible nitric oxide synthase (iNOS), and matrix metalloproteinase-9 (MMP-9), each of which has been implicated in pulmonary toxicity. Whereas COX-2, TNF{alpha} and iNOS were mainly localized in alveolar regions, MMP-9 was prominent in bronchial epithelium. In contrast, expression of the anti-oxidant hemeoxygenase, and the anti-inflammatory collectin, surfactant protein-D, decreased in the lung after SM exposure. These data demonstrate that SM-induced oxidative stress and injury are associated with the generation of cytotoxic inflammatory proteins which may contribute to the pathogenic response to this vesicant.

  8. [Influence of inhaler and fine particle on efficacy of inhalation therapy in COPD].

    PubMed

    Sliwiński, Paweł; Chazan, Ryszarda; Dąbrowiecki, Piotr; Jahnz-Różyk, Karina; Mróz, Robert; Pirożyński, Michał

    2014-01-01

    Orally inhaled products delivered via inhalation exert their effect directly to the target organ. This allows to administer a very low dose of a drug compared with an oral route with similar clinical effect and significantly reduced toxicity. However inhalation therapy is also limited by several factors. Delivery of the desired dose of the drug to the airways depends on a type of the inhaler - pressurised metered-dose inhaler (pMDI) or dry powder inhaler (DPI), inhaler characteristics (low or high internal resistance, diameter of particles and distribution of the generated aerosol fine particles), thermal conditions of air, and ability of patient to generate sufficient inspiratory flow (for DPI) or to coordinate actuation with inhalation (for pMDI). Unlike pMDIs, DPIs are breath- -actuated, hence avoiding the need for the patient to coordinate actuation with inspiration. Furthermore, DPIs are propellant-free and do not produce the cold sensation on inhalation. Currently available DPIs vary widely in design, operating characteristics and performance. And poor inhalation technique may compromise treatment efficacy. Hence, there is a clear need for a careful selection of DPIs for different patient groups, including children, elderly patients and those with severe airway obstruction. PMID:24793155

  9. A hypothesis about cellular signaling with nitric oxide in the earliest life forms in evolution.

    PubMed

    Murad, Ferid; Barber, Roger

    2009-11-01

    We propose that nitric oxide participated as an extracellular and intracellular messenger in the early evolution of life. From a toxic and noxious substance it evolved into an important material for cellular communication and regulation with unique chemistry and properties. The presence of some nitric oxide complexes in extraterrestrial samples may support evidence for life forms in the past or present. Although nitric oxide probably participated in the evolution and maintenance of life, if pollution continues at an ever-increasing rate, it could also end life on the planet as we know it today. PMID:19439177

  10. Dynamics of airflow in a short inhalation

    PubMed Central

    Bates, A. J.; Doorly, D. J.; Cetto, R.; Calmet, H.; Gambaruto, A. M.; Tolley, N. S.; Houzeaux, G.; Schroter, R. C.

    2015-01-01

    During a rapid inhalation, such as a sniff, the flow in the airways accelerates and decays quickly. The consequences for flow development and convective transport of an inhaled gas were investigated in a subject geometry extending from the nose to the bronchi. The progress of flow transition and the advance of an inhaled non-absorbed gas were determined using highly resolved simulations of a sniff 0.5 s long, 1 l s−1 peak flow, 364 ml inhaled volume. In the nose, the distribution of airflow evolved through three phases: (i) an initial transient of about 50 ms, roughly the filling time for a nasal volume, (ii) quasi-equilibrium over the majority of the inhalation, and (iii) a terminating phase. Flow transition commenced in the supraglottic region within 20 ms, resulting in large-amplitude fluctuations persisting throughout the inhalation; in the nose, fluctuations that arose nearer peak flow were of much reduced intensity and diminished in the flow decay phase. Measures of gas concentration showed non-uniform build-up and wash-out of the inhaled gas in the nose. At the carina, the form of the temporal concentration profile reflected both shear dispersion and airway filling defects owing to recirculation regions. PMID:25551147