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Sample records for early inhaled nitric

  1. 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.

  2. Inhaled Nitric Oxide in Acute Lung Disease.

    DTIC Science & Technology

    1995-01-01

    seems likely ECMO extracorporeal membrane oxygenation EDRF endothelial-derived relaxing factor that the potent dose-related selective pulmonary GBS... ECMO ). To evaluate the dose response and time inhaled NO. (Fig. 7). The significant decrease in oxy- course of the pulmonary effects of NO., inspiratory...effects (39, 40). In many of these chil- dren, ECMO has been avoided. Similar improvement _0 has been noted in adult patients undergoing cardio- LPS NO

  3. Use of inhaled nitric oxide in preterm infants.

    PubMed

    Kumar, Praveen

    2014-01-01

    Nitric oxide, an important signaling molecule with multiple regulatory effects throughout the body, is an important tool for the treatment of full-term and late-preterm infants with persistent pulmonary hypertension of the newborn and hypoxemic respiratory failure. Several randomized controlled trials have evaluated its role in the management of preterm infants ≤ 34 weeks' gestational age with varying results. The purpose of this clinical report is to summarize the existing evidence for the use of inhaled nitric oxide in preterm infants and provide guidance regarding its use in this population.

  4. Efficacy of inhaled nitric oxide in preterm neonates.

    PubMed

    Love, Lauren E; Bradshaw, Wanda T

    2012-02-01

    Over the past 20 years, the recognition of nitric oxide (NO) as an endothelial-derived vasodilator has led to remarkable advances in vascular biology awareness. The signaling molecule NO, produced by NO synthase, is a molecule that is widespread in the body and important in multiple organ systems. Soon after its discovery, investigators found NO to be a potent pulmonary vasodilator in term neonates. Nitric oxide has come to perform a key function in neonatal therapy and management since its identification, especially in those with respiratory failure. It is conventionally used in the neonatal population for the treatment of persistent pulmonary hypertension, resulting in hypoxic respiratory failure of the term or near-term newborn. Inhaled NO has been successful in acutely improving oxygenation and in reducing the need for extracorporeal membrane oxygenation treatment. In recent years, the efficacy of inhaled NO for the prevention of pulmonary disability as well as its neuroprotective capabilities in preterm infants has been explored.

  5. [Recommendations for inhaled nitric oxide treatment in the newborn diseases].

    PubMed

    2001-09-01

    The recommendations in this document highlight current indications for inhaled nitric oxide (iNO) treatment in the newborn by clearly differentiating between those that are supported by scientific evidence and those for which evidence is still lacking. However, the use of this treatment in preterm infants and in those with congenital heart disease has not yet been scientifically approved. We discuss the methodology, dosage and adverse effects of iNO administration, as well as the reasons for its ineffectiveness.

  6. [Recommendations for inhaled nitric oxide treatment in the newborn].

    PubMed

    Figueras Aloy, J; Castillo Salinas, F; Elorza Fernández, D; Sánchez-Luna, M; Pérez Rodríguez, J

    2006-03-01

    The recommendations in this document describe the current indications for inhaled nitric oxide (iNO) treatment in the newborn and clearly distinguish between those supported by scientific evidence and those for which evidence is still lacking, such as its use in preterm infants. The methodology for iNO administration, its dosage and the main secondary effects are discussed, and the reasons for lack of response to this treatment are analyzed.

  7. Bronchodilator action of inhaled nitric oxide in guinea pigs.

    PubMed Central

    Dupuy, P M; Shore, S A; Drazen, J M; Frostell, C; Hill, W A; Zapol, W M

    1992-01-01

    The effects of inhaling nitric oxide (NO) on airway mechanics were studied in anesthetized and mechanically ventilated guinea pigs. In animals without induced bronchoconstriction, breathing 300 ppm NO decreased baseline pulmonary resistance (RL) from 0.138 +/- 0.004 (mean +/- SE) to 0.125 +/- 0.002 cmH2O/ml.s (P less than 0.05). When an intravenous infusion of methacholine (3.5-12 micrograms/kg.min) was used to increase RL from 0.143 +/- 0.008 to 0.474 +/- 0.041 cmH2O/ml.s (P less than 0.05), inhalation of 5-300 ppm NO-containing gas mixtures produced a dose-related, rapid, consistent, and reversible reduction of RL and an increase of dynamic lung compliance. The onset of bronchodilation was rapid, beginning within 30 s after commencing inhalation. An inhaled NO concentration of 15.0 +/- 2.1 ppm was required to reduce RL by 50% of the induced bronchoconstriction. Inhalation of 100 ppm NO for 1 h did not produce tolerance to its bronchodilator effect nor did it induce substantial methemoglobinemia (less than 2%). The bronchodilating effects of NO were additive with the effects of inhaled terbutaline, irrespective of the sequence of NO and terbutaline administration. Inhaling aerosol generated from S-nitroso-N-acetylpenicillamine also induced a rapid and profound decrease of RL from 0.453 +/- 0.022 to 0.287 +/- 0.022 cmH2O/ml.s, which lasted for over 15 min in guinea pigs broncho-constricted with methacholine. Our results indicate that low levels of inhaled gaseous NO, or an aerosolized NO-releasing compound are potent bronchodilators in guinea pigs. PMID:1644915

  8. Acute lung injury after inhalation of nitric acid.

    PubMed

    Kao, Shih Ling; Yap, Eng Soo; Khoo, See Meng; Lim, Tow Keang; Mukhopadhyay, Amartya; Teo, Sylvia Tzu Li

    2008-12-01

    We report two cases of acute lung injury after the inhalation of nitric acid fumes in an industrial accident. The first patient, who was not using a respirator and standing in close proximity to the site of spillage of concentrated nitric acid, presented within 12 h with worsening dyspnea and required noninvasive ventilation for type 1 respiratory failure. The second case presented 1 day later with similar symptoms, but only required supportive treatment with high-flow oxygen. Both patients' chest radiographs showed widespread bilateral airspace shadows consistent with acute lung injury. Both received treatment with systemic steroids. They were discharged from hospital 5 days postexposure. Initial lung function test showed a restrictive pattern that normalized by 3 weeks postexposure. This case series describes the natural history after acute inhalation of nitric acid fumes, and demonstrates that the severity of lung injury is directly dependent on the exposure level. It also highlights the use of noninvasive ventilatory support in the management of such patients.

  9. Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxidedelivery

    PubMed Central

    Cannon, Richard O.; Schechter, Alan N.; Panza, Julio A.; Ognibene, Frederick P.; Pease-Fye, Margaret E.; Waclawiw, Myron A.; Shelhamer, James H.; Gladwin, Mark T.

    2001-01-01

    Nitric oxide (NO) may be stabilized by binding to hemoglobin, by nitrosating thiol-containing plasma molecules, or by conversion to nitrite, all reactions potentially preserving its bioactivity in blood. Here we examined the contribution of blood-transported NO to regional vascular tone in humans before and during NO inhalation. While breathing room air and then room air with NO at 80 parts per million, forearm blood flow was measured in 16 subjects at rest and after blockade of forearm NO synthesis with NG-monomethyl-L-arginine (L-NMMA) followed by forearm exercise stress. L-NMMA reduced blood flow by 25% and increased resistance by 50%, an effect that was blocked by NO inhalation. With NO inhalation, resistance was significantly lower during L-NMMA infusion, both at rest and during repetitive hand-grip exercise. S-nitrosohemoglobin and plasma S-nitrosothiols did not change with NO inhalation. Arterial nitrite levels increased by 11% and arterial nitrosyl(heme)hemoglobin levels increased tenfold to the micromolar range, and both measures were consistently higher in the arterial than in venous blood. S-nitrosohemoglobin levels were in the nanomolar range, with no significant artery-to-vein gradients. These results indicate that inhaled NO during blockade of regional NO synthesis can supply intravascular NO to maintain normal vascular function. This effect may have application for the treatment of diseases characterized by endothelial dysfunction. PMID:11457881

  10. Use of inhaled nitric oxide in the new born period: results from the European Inhaled Nitric Oxide Registry.

    PubMed

    Dewhurst, Chris; Ibrahim, Hafis; Göthberg, Sylvia; Jónsson, Baldvin; Subhedar, Nimish

    2010-06-01

    The aim of this study was to present data relating to the use of inhaled nitric oxide (iNO) in newborn infants included in the European Inhaled Nitric Oxide Registry. Demographic, clinical and therapeutic data from seven European centres are reported. Univariate analyses were performed to identify factors associated with acute response to iNO and survival without extra corporeal membrane oxygenation (ECMO). A total of 112 newborn infants received iNO, with 40% being less than 34 weeks gestational age. The commonest indication for iNO was secondary pulmonary hypertension. Acute response to iNO was more common in infants with a higher oxygenation index (median OI 32.7 vs 22.6, p = 0.040), although acute response did not predict survival without ECMO. Infants who survived without ECMO had a lower OI prior to therapy (median OI 24 vs 43, p = 0.009), were commenced on a higher starting dose (median dose 20 ppm vs 10 ppm p = 0.013) and received a lower maintenance dose (median dose 10 vs 17 ppm, p = 0.027) than those who died or received ECMO. Collating and reporting data about iNO therapy in neonates across a number of European centres using a web-based system is feasible. These data may be used to monitor the clinical use of iNO, identify adverse effects, generate research hypotheses and promote high standards in the clinical use of iNO.

  11. Inhaled nitric oxide aggravates phosgene model of acute lung injury.

    PubMed

    Li, Wen-Li; Hai, Chun-Xu; Pauluhn, Jürgen

    2011-11-01

    The principal acute mode of action of inhaled phosgene gas is related to an increase alveolar fluid exudation under pathologic conditions. This paper considers some aspects in modeling phosgene-induced acute lung injury (ALI) in an acute rat bioassay and whether edema formation can be modulated by inhaled nitric oxide (iNO). Protein analysis in bronchoalveolar lavage (BAL) fluid is amongst the most sensitive method to quantify the phosgene-induced non-cardiogenic, pulmonary high-permeability edema following acute inhalation exposure. Maximum concentrations in BAL-protein occur within one day postexposure, typically within a latency period up to about 15 h as a consequence of an increasingly exhausted lymphatic drainage. An almost similar sensitivity was given by the functional endpoint 'enhanced pause (Penh)' when measured by non-invasive whole-body barometric plethysmography over a time period of 20 h. The magnitude of edema formation follows a concentration x time (C¹xt) relationship, although animal model-specific deviations may occur at very short exposure durations (1-20 min) due to a rodent-specific, reflexively induced transient decreased ventilation. This has to be accounted for when simulating accidental exposure scenarios to study the mechanisms involved in pharmacological modulation of fluid transport in this type of ALI. Therefore, a special focus has to be given to the dosimetry of inhaled phosgene, otherwise any change in effect magnitude, as a result of under-dosing of phosgene, may be misconceived as promising therapy. This study demonstrates that accidental exposures can be modeled best in rats by exposure durations of at least 20-30 min. Lung function measurements (Penh) show that pathophysiological effects appear to occur concomitant with the exposure to phosgene; however, its full clinical manifestation requires a gross imbalance of pulmonary fluid clearance. When applying this concept, post-phosgene exposure iNO at 1.5 ppm × 6 h or

  12. Inhaled nitric oxide induces cerebrovascular effects in anesthetized pigs.

    PubMed

    Kuebler, W M; Kisch-Wedel, H; Kemming, G I; Meisner, F; Bruhn, S; Koehler, C; Flondor, M; Messmer, K; Zwissler, B

    2003-09-11

    Although inhaled nitric oxide (NO(i)) is considered to act selectively on pulmonary vessels, EEG abnormalities and even occasional neurotoxic effects of NO(i) have been proposed. Here, we investigated cerebrovascular effects of increasing concentrations of 5, 10 and 50 ppm NO(i) in seven anesthetized pigs. Cerebral hemodynamics were assessed non-invasively by use of near-infared spectroscopy and indicator dilution techniques. NO(i) increased cerebral blood volume significantly and reversibly. This effect was not attributable to changes of macrohemodynamic parameters or arterial blood gases. Simultaneously, cerebral transit time increased while cerebral blood flow remained unchanged. These data demonstrate a vasodilatory action of NO(i) in the cerebral vasculature, which may occur preferentially in the venous compartment.

  13. Inhaled nitric oxide augments nitric oxide transport on sickle cell hemoglobin without affecting oxygen affinity

    PubMed Central

    Gladwin, Mark T.; Schechter, Alan N.; Shelhamer, James H.; Pannell, Lewis K.; Conway, Deirdre A.; Hrinczenko, Borys W.; Nichols, James S.; Pease-Fye, Margaret E.; Noguchi, Constance T.; Rodgers, Griffin P.; Ognibene, Frederick P.

    1999-01-01

    Nitric oxide (NO) inhalation has been reported to increase the oxygen affinity of sickle cell erythrocytes. Also, proposed allosteric mechanisms for hemoglobin, based on S-nitrosation of β-chain cysteine 93, raise the possibilty of altering the pathophysiology of sickle cell disease by inhibiting polymerization or by increasing NO delivery to the tissue. We studied the effects of a 2-hour treatment, using varying concentrations of inhaled NO. Oxygen affinity, as measured by P50, did not respond to inhaled NO, either in controls or in individuals with sickle cell disease. At baseline, the arterial and venous levels of nitrosylated hemoglobin were not significantly different, but NO inhalation led to a dose-dependent increase in mean nitrosylated hemoglobin, and at the highest dosage, a significant arterial-venous difference emerged. The levels of nitrosylated hemoglobin are too low to affect overall hemoglobin oxygen affinity, but augmented NO transport to the microvasculature seems a promising strategy for improving microvascular perfusion. PMID:10510334

  14. Effects of nitric oxide inhalation on pulmonary serial vascular resistances in ARDS.

    PubMed

    Rossetti, M; Guénard, H; Gabinski, C

    1996-11-01

    The pulmonary vasculature site of action of nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS) is still unknown. Seven patients were studied during the early stage of ARDS. The bedside pulmonary artery single-occlusion technique, which allows estimation of the pulmonary capillary pressure (Pcap) and segmental pulmonary vascular resistance, was used without NO or with increasing inhaled NO concentrations (15 and 25 parts per million [ppm]). Systemic circulatory parameters remained unaltered during 15 ppm NO inhalation, whereas 25 ppm NO inhalation slightly decreased mean systemic arterial pressure from 76.7 +/- 5.1 (mean +/- SEM) to 69 +/- 5.2 mm Hg (p < 0.01). Mean pulmonary arterial pressure (Ppam) and mean pulmonary capillary pressure (Pcapm) fell during 25 ppm NO inhalation from 27.4 +/- 3.5 to 21 +/- 2.2 mm Hg (p < 0.001) and from 14.8 +/- 1.5 to 10.7 +/- 1.4 mm Hg (p < 0.001) respectively, the total pulmonary resistance decreased by 28% (p < 0.01). The resistance of the capillary-venous compartment fell during 25 ppm NO inhalation from 100 +/- 16 to 47 +/- 16 dyn x s x m(2) x cm(-5) (p < 0.01), whereas the pulmonary arterial resistance was unchanged. In these patients NO inhalation during the early stage of ARDS reduces selectively Ppam and Pcapm by decreasing the pulmonary capillary-venous resistance. This latter effect may reduce the filtration through the capillary bed and hence alveolar edema during ARDS.

  15. Therapeutic application of inhaled nitric oxide in adult cardiac surgical patients.

    PubMed

    Makker, Robina; Mehta, Yatin; Trehan, Naresh; Bapna, Rk

    2006-01-01

    Increased pulmonary vascular resistance can be detrimental to the cardiac output in post-operative cardiac surgical patients. Pulmonary vasodilator therapy by systemic pharmacologic agents is non-selective. Inhaled nitric oxide is a selective pulmonary vasodilator and does not cause systemic hypotension. In this prospective study, 14 adult post-operative cardiac surgical patients with pulmonary hypertension underwent inhaled nitric oxide therapy and their hemodynamic changes were evaluated. Inhaled nitric oxide was administered in doses of 5 ppm-25 ppm. The result was a decrease in pulmonary vascular resistance from 456.57 +/- 137.13 to 357.64 +/- 119.80 dynes-sec- Continued. - See Free Full Text.

  16. Use of nitric oxide inhalation in chronic obstructive pulmonary disease

    PubMed Central

    Ashutosh, K.; Phadke, K.; Jackson, J. F.; Steele, D.

    2000-01-01

    BACKGROUND—Inhalation of nitric oxide with oxygen could be a promising treatment in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension. However, the current methods of delivery of NO are cumbersome and unsuitable for long term use. The present study was undertaken to investigate the safety and efficacy of a mixture of nitric oxide (NO) and oxygen administered via a nasal cannula for 24 hours in patients with oxygen dependent COPD.
METHODS—Twenty five parts per million (ppm) of NO was administered by inhalation combined with supplemental oxygen at a flow rate of 2 l/min via a nasal cannula for 24 hours to 11 ambulatory men with stable, oxygen dependent COPD. Room air with supplemental oxygen at 2 l/min was administered in an identical manner for another 24 hours as control therapy in a randomised, double blind, crossover fashion to all patients. Pulmonary function tests, exercise tolerance, dyspnoea grade, and lung volumes were measured at baseline, 24, and 48 hours. Pulmonary artery pressure (PAP), cardiac output (CO), pulmonary vascular resistance (PVR), arterial blood gas tensions, and minute ventilation were measured at baseline, after 30 minutes and 24 hours of breathing NO and oxygen. Venous admixture ratio (Qs/Qt) and dead space ratio (Vd/Vt) were also calculated. Concentrations of nitrogen dioxide (NO2) and NO in the inhaled and ambient air were monitored continuously. Differences in pulmonary function, arterial blood gas tensions, pulmonary haemodynamics, exercise tolerance, and dyspnoea between oxygen and NO breathing periods were analysed for significance using paired t tests.
RESULTS—A significant (p<0.05) fall was observed in PVR (183.1 (116.05) and 137.2 (108.4) dynes.s.cm-3 before and after breathing NO for 24 hours, respectively) with NO administration without significant changes in symptoms, pulmonary function, arterial oxygen tension, or exercise tolerance.
CONCLUSIONS—NO at a concentration of 25 ppm

  17. 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.

  18. 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

    ... HUMAN SERVICES National Institutes of Health NIH Consensus Development Conference on Inhaled Nitric..., brain development, and brain function. Nitric oxide is a chemical compound in gas form that is sometimes..., thereby reducing progression to bronchopulmonary dysplasia and improving long-term lung health and...

  19. Nasal and oral contribution to inhaled and exhaled nitric oxide: a study in tracheotomized patients.

    PubMed

    Törnberg, D C F; Marteus, H; Schedin, U; Alving, K; Lundberg, J O N; Weitzberg, E

    2002-05-01

    Nitric oxide (NO) is produced at different sites in the human airways and may have several physiological effects. Orally-produced NO seems to contribute to the levels found in exhaled air. Autoinhalation of nasal NO increases oxygenation and reduces pulmonary artery pressure in humans. The aim of this study was to measure the concentration and output of NO during nasal, oral and tracheal controlled exhalation and inhalation. Ten tracheotomized patients and seven healthy subjects were studied. The mean+/-SEM fraction of exhaled NO from the nose, mouth and trachea was 56+/-8, 14+/-4 and 6+/-1 parts per billion (ppb), respectively. During single-breath nasal, oral and tracheal inhalation the fraction of inhaled NO was 64+/-14, 11+/-3 and 4+/-1, respectively. There was a marked flow dependency on nasal NO output in the healthy subjects, which was four-fold greater at the higher flow rates, during inhalation when compared to exhalation. There is a substantial contribution of nasal and oral nitric oxide during both inhalation and exhalation. Nasal nitric oxide output is markedly higher during inhalation, reaching levels similar to those that are found to have clinical effects in the trachea. These findings have implications for the measurement of nitric oxide in exhaled air and the physiological effects of autoinhaled endogenous nitric oxide.

  20. Economic evaluation of inhaled nitric oxide in preterm infants undergoing mechanical ventilation.

    PubMed

    Zupancic, John A F; Hibbs, Anna Maria; Palermo, Lisa; Truog, William E; Cnaan, Avital; Black, Dennis M; Ballard, Philip L; Wadlinger, Sandra R; Ballard, Roberta A

    2009-11-01

    In the previously reported Nitric Oxide for Chronic Lung Disease (NO CLD) trial, ventilated preterm infants who received a course of inhaled nitric oxide (iNO) between 7 and 21 days of life had a significant improvement in survival without bronchopulmonary dysplasia (BPD), as well as a shorter duration of admission and ventilation. However, the price for the drug may be a barrier to widespread use. We sought to estimate the incremental cost-effectiveness of iNO therapy to prevent BPD in infants of <1250 g birth weight. We used patient-level data from the NO CLD randomized trial. The study took a third-party payer perspective and measured costs and effects through hospital discharge. We applied previously reported hospital per-diem costs stratified according to intensity of ventilatory support, nitric oxide costs from standard market prices, and professional (physician) fees from the Medicare fee schedule. We compared log transformed costs by using multivariable modeling and performed incremental cost-effectiveness analysis with estimation of uncertainty through nonparametric bootstrapping. The mean cost per infant was $193125 in the placebo group and $194702 in the iNO group (adjusted P = .17). The point estimate for the incremental cost per additional survivor without BPD was $21297. For infants in whom iNO was initiated between 7 and 14 days of life, the mean cost per infant was $187407 in the placebo group and $181525 in the iNO group (adjusted P = .46). In this group of early treated infants, there was a 71% probability that iNO actually decreased costs while improving outcomes. Despite its higher price relative to many other neonatal therapies, iNO in this trial was not associated with higher costs of care, an effect that is likely due to its impact on length of stay and ventilation. Indeed, for infants who receive nitric oxide between 7 and 14 days of life, the therapy seemed to lower costs while improving outcomes.

  1. Inhaled nitric oxide in premature infants: effect on tracheal aspirate and plasma nitric oxide metabolites

    PubMed Central

    Posencheg, M A; Gow, A J; Truog, W E; Ballard, R A; Cnaan, A; Golombek, S G; Ballard, P L

    2010-01-01

    Objective: Inhaled nitric oxide (iNO) is a potential new therapy for prevention of bronchopulmonary dysplasia and brain injury in premature infants. This study examined dose-related effects of iNO on NO metabolites as evidence of NO delivery. Study Design: A subset of 102 premature infants in the NO CLD trial, receiving 24 days of iNO (20 p.p.m. decreasing to 2 p.p.m.) or placebo, were analyzed. Tracheal aspirate (TA) and plasma samples collected at enrollment and at intervals during study gas were analyzed for NO metabolites. Result: iNO treatment increased NO metabolites in TA at 20 and 10 p.p.m. (1.7- to 2.3-fold vs control) and in plasma at 20, 10, and 5 p.p.m. (1.6- to 2.3-fold). In post hoc analysis, treated infants with lower metabolite levels at entry had an improved clinical outcome. Conclusion: iNO causes dose-related increases in NO metabolites in the circulation as well as lung fluid, as evidenced by TA analysis, showing NO delivery to these compartments. PMID:19812581

  2. [Application of inhaled nitric oxide in extreme preterm neonates with with BPD].

    PubMed

    Radulova, P; Slancheva, B

    2014-01-01

    Prolonged inhaled nitric oxide (iNO) from birth in preterm neonates with BPD improves endogenous surfactant function as well as lung growth, angiogenesis, and alveologenesis. As a result there is a reduction in the frequency of the "new" form of BPD in neonates under 28 weeks of gestation and birth weight under 1000 gr. Delivery of inhaled nitric oxide is a new method of prevention of chronic lung disease. According to a large number of randomized trials iNO in premature neonates reduces pulmonary morbidity and leads to a reduction of the mortality in this population of patients. This new therapy does not have serious side effects.

  3. Inhaled nitric oxide decreases pulmonary endothelial nitric oxide synthase expression and activity in normal newborn rat lungs.

    PubMed

    Hua-Huy, Thông; Duong-Quy, Sy; Pham, Hoa; Pansiot, Julien; Mercier, Jean-Christophe; Baud, Olivier; Dinh-Xuan, Anh Tuan

    2016-01-01

    Inhaled nitric oxide (iNO) is commonly used in the treatment of very ill pre-term newborns. Previous studies showed that exogenous NO could affect endothelial NO synthase (eNOS) activity and expression in vascular endothelial cell cultures or adult rat models, but this has never been fully described in newborn rat lungs. We therefore aimed to assess the effects of iNO on eNOS expression and activity in newborn rats. Rat pups, post-natal day (P) 0 to P7, and their dams were placed in a chamber containing NO at 5 ppm (iNO-5 ppm group) or 20 ppm (iNO-20 ppm group), or in room air (control group). Rat pups were sacrificed at P7 and P14 for evaluation of lung eNOS expression and activity. At P7, eNOS protein expression in total lung lysates, in bronchial and arterial sections, was significantly decreased in the iNO-20 ppm versus control group. At P14, eNOS expression was comparable among all three groups. The amounts of eNOS mRNA significantly differed at P7 between the iNO-20 ppm and control groups. NOS activity decreased in the iNO-20 ppm group at P7 and returned to normal levels at P14. There was an imbalance between superoxide dismutase and NOS activities in the iNO-20 ppm group at P7. Inhalation of NO at 20 ppm early after birth decreases eNOS gene transcription, protein expression and enzyme activity. This decrease might account for the rebound phenomenon observed in patients treated with iNO.

  4. Two-Year Neurodevelopmental Outcomes of Ventilated Preterm Infants Treated with Inhaled Nitric Oxide

    PubMed Central

    Walsh, Michele C.; Hibbs, Anna Maria; Martin, Camilia R.; Cnaan, Avital; Keller, Roberta L.; Vittinghoff, Eric; Martin, Richard J.; Truog, William E.; Ballard, Philip L.; Zadell, Arlene; Wadlinger, Sandra R.; Coburn, Christine E.; Ballard, Roberta A.

    2009-01-01

    Objective In a randomized multi-center trial, we demonstrated that inhaled nitric oxide begun between 7 and 21 days and treated for 24 days significantly increased survival without bronchopulmonary dysplasia (BPD) in ventilated premature infants weighing < 1250 g. Since some preventative BPD treatments are associated with neurodevelopmental impairment, we designed a follow-up study to assess the safety of nitric oxide. Study design Our hypothesis was that inhaled nitric oxide will not increase neurodevelopmental impairment compared with placebo. We prospectively evaluated neurodevelopmental and growth outcomes at 24 months PMA in 477 (89%) of 535 surviving infants enrolled in the trial. Results In the treated group, 109 of 243 children (45%) had neurodevelopmental impairment (moderate or severe cerebral palsy, bilateral blindness, bilateral hearing loss or score of less than 70 on the Bayley Scales II), compared with 114 of 234 (49%) in the placebo group (Relative Risk 0.92; 95% confidence interval, 0.75 to 1.12; p = 0.39). No differences on any subcomponent of neurodevelopmental impairment or growth variables were found between inhaled nitric oxide or placebo. Conclusions Inhaled nitric oxide improved survival free of bronchopulmonary dysplasia with no adverse neurodevelopmental effects at 2 years of age. PMID:20138299

  5. Fatal pulmonary edema due to nitric acid fume inhalation in three pulp-mill workers.

    PubMed

    Hajela, R; Janigan, D T; Landrigan, P L; Boudreau, S F; Sebastian, S

    1990-02-01

    Three young men died of rapidly progressive pulmonary edema of delayed onset after inhalation of fumes from an accidental nitric acid explosion. Electron microscopy revealed altered neutrophils and necrotic endothelial cells in alveolar capillaries. Immunohistochemistry showed small and large serum proteins, including immunoglobulin M, in the edema fluid and hyaline membranes. Increased permeability is a consequence of direct microvascular injury by inhaled nitrogen dioxide. However, our findings, implicating neutrophils and serum-derived mediators in the pathogenesis of the pulmonary edema, are consistent with recent proposals on their roles in the maintenance and/or progression of edema initiated by toxic inhalations.

  6. Extrapulmonary effects of inhaled nitric oxide: role of reversible S-nitrosylation of erythrocytic hemoglobin.

    PubMed

    McMahon, Timothy J; Doctor, Allan

    2006-04-01

    Early applications of inhaled nitric oxide (iNO), typically in the treatment of diseases marked by acute pulmonary hypertension, were met by great enthusiasm regarding the purported specificity of iNO: vasodilation by iNO was specific to the lung (without a change in systemic vascular resistance), and within the lung, NO activity was said to be confined spatially and temporally by Hb within the vascular lumen. Underlying these claims were classical views of NO as a short-lived paracrine hormone that acts largely through the heme groups of soluble guanylate cyclase, and whose potential activity is terminated on encountering the hemes of red blood cell (RBC) Hb. These classical views are yielding to a broader paradigm, in which NO-related signaling is achieved through redox-related NO adducts that endow NO synthase products with the ability to act at a distance in space and time from NO synthase itself. Evidence supporting the biological importance of such stable NO adducts is probably strongest for S-nitrosothiols (SNOs), in which NO binds to critical cysteine residues in proteins or peptides. The circulating RBC is a major SNO reservoir, and RBC Hb releases SNO-related bioactivity peripherally on O2 desaturation. These new paradigms describing NO transport also provide a plausible mechanistic understanding of the increasingly recognized peripheral effects of inhaled NO. An explanation for the peripheral actions of inhaled NO is discussed here, and the rationale and results of attempts to exploit the "NO delivery" function of the RBC are reviewed.

  7. Inhaled nitric oxide in preterm infants with prolonged preterm rupture of the membranes: a case series.

    PubMed

    Semberova, J; O'Donnell, S M; Franta, J; Miletin, J

    2015-04-01

    The available evidence does not support the routine use of inhaled nitric oxide (iNO) in the care of premature infants. We present a case series of 22 preterm infants born after prolonged preterm premature rupture of membranes and oligohydramnios with respiratory failure. Oxygenation index decreased significantly after commencement of iNO.

  8. Comparison of inhaled milrinone, nitric oxide and prostacyclin in acute respiratory distress syndrome

    PubMed Central

    Albert, Martin; Corsilli, Daniel; Williamson, David R; Brosseau, Marc; Bellemare, Patrick; Delisle, Stéphane; Nguyen, Anne QN; Varin, France

    2017-01-01

    AIM To evaluate the safety and efficacy of inhaled milrinone in acute respiratory distress syndrome (ARDS). METHODS Open-label prospective cross-over pilot study where fifteen adult patients with hypoxemic failure meeting standard ARDS criteria and monitored with a pulmonary artery catheter were recruited in an academic 24-bed medico-surgical intensive care unit. Random sequential administration of iNO (20 ppm) or nebulized epoprostenol (10 μg/mL) was done in all patients. Thereafter, inhaled milrinone (1 mg/mL) alone followed by inhaled milrinone in association with inhaled nitric oxide (iNO) was administered. A jet nebulization device synchronized with the mechanical ventilation was use to administrate the epoprostenol and the milrinone. Hemodynamic measurements and partial pressure of arterial oxygen (PaO2) were recorded before and after each inhaled therapy administration. RESULTS The majority of ARDS were of pulmonary cause (n = 13) and pneumonia (n = 7) was the leading underlying initial disease. Other pulmonary causes of ARDS were: Post cardiopulmonary bypass (n = 2), smoke inhalation injury (n = 1), thoracic trauma and pulmonary contusions (n = 2) and aspiration (n = 1). Two patients had an extra pulmonary cause of ARDS: A polytrauma patient and an intra-abdominal abscess Inhaled nitric oxide, epoprostenol, inhaled milrinone and the combination of inhaled milrinone and iNO had no impact on systemic hemodynamics. No significant adverse events related to study medications were observed. The median increase of PaO2 from baseline was 8.8 mmHg [interquartile range (IQR) = 16.3], 6.0 mmHg (IQR = 18.4), 6 mmHg (IQR = 15.8) and 9.2 mmHg (IQR = 20.2) respectively with iNO, epoprostenol, inhaled milrinone, and iNO added to milrinone. Only iNO and the combination of inhaled milrinone and iNO had a statistically significant effect on PaO2. CONCLUSION When comparing the effects of inhaled NO, milrinone and epoprostenol, only NO significantly improved oxygenation

  9. [A preliminary observation on the effects of inhaled nitric oxide on bronchial asthma].

    PubMed

    Zhang, H; Yang, Y; Weng, X

    1995-12-01

    Nitric oxide (NO) is a vasodilator as well as a bronchodilator. In order to estimate the therapeutic effects of NO on bronchial asthma, 10 patients in acute exacerbation stage were selected for this study. 40 ppm NO was inhaled for 20 minutes. The clinical stage and pulmonary function were evaluated instantly. The results showed that subjective symptoms were relieved and wheezing rales decreased to a different extent, FEV1 and PEF improved significantly (P < 0.05). It is suggested that low concentration NO inhalation can be used as a therapeutic measure for bronchial asthma.

  10. 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.

  11. Organ Dysfunction among Piglets Treated with Inhaled Nitric Oxide and Intravenous Hydrocortisone during Prolonged Endotoxin Infusion

    PubMed Central

    Göranson, Sofie Paues; Goździk, Waldemar; Harbut, Piotr; Ryniak, Stanisław; Zielinski, Stanisław; Haegerstrand, Caroline Gillis; Kübler, Andrzej; Hedenstierna, Göran; Frostell, Claes; Albert, Johanna

    2014-01-01

    Objective It has previously been shown that a combination of inhaled nitric oxide (iNO) and intravenous (IV) steroid attenuates endotoxin-induced organ damage in a 6-hour porcine endotoxemia model. We aimed to further explore these effects in a 30-hour model with attention to clinically important variables. Design Randomized controlled trial. Setting University animal laboratory. Subjects Domestic piglets (n = 30). Interventions Animals were randomized into 5 groups (n = 6 each): 1) Controls, 2) LPS-only (endotoxin/lipopolysaccharide (LPS) infusion), 3) LPS + iNO, 4) LPS + IV steroid, 5) LPS + iNO + IV steroid. Measurements and Main Results Exposure to LPS temporarily increased pulmonary artery mean pressure and impeded renal function with elevated serum creatinine and acidosis compared to a control group over the 30-hour study period. Double treatment with both iNO and IV steroid tended to blunt the deterioration in renal function, although the only significant effect was on Base Excess (p = 0.045). None of the LPS + iNO + IV steroid treated animals died during the study period, whereas one animal died in each of the other LPS-infused groups. Conclusions This study suggests that combined early therapy with iNO and IV steroid is associated with partial protection of kidney function after 30 hours of experimental LPS infusion. PMID:24827456

  12. Role of inhaled nitric oxide in ischaemia-reperfusion injury in the perfused rabbit lung.

    PubMed

    Ishibe, Y; Liu, R; Ueda, M; Mori, K; Miura, N

    1999-09-01

    We have tested if inhaled nitric oxide (NO) is beneficial in ischaemia-reperfusion (IR) lung injury using an isolated perfused rabbit lung model. Ischaemia for 60 min was followed by reperfusion and ventilation with nitric oxide 40 ppm (n = 6) or without nitric oxide ventilation (n = 6) for 60 min. In the control group (n = 6), the lungs were perfused continuously for 120 min. Permeability coefficient (Kfc) and vascular resistance (PVR) were measured serially for 60 min after reperfusion. We also determined the left lung W/D ratio and measured nitric oxide metabolites (NOx) and cGMP concentrations in bronchoalveolar lavage (BAL) fluid from the right lung. IR increased Kfc, PVR and W/D followed by decreased cGMP. Ventilation with nitric oxide restored these changes by preventing the decrease in cGMP. Differences in NOx concentrations in BAL fluid between the control and IR groups were not statistically significant. Our results indicate that IR impaired pulmonary vascular function and resulted in microvascular constriction and leakage. Ventilation with nitric oxide from the beginning of the reperfusion period improved pulmonary dysfunction such as vasoconstriction and capillary leak by restoring cGMP concentrations.

  13. Evaluation of nitrogen dioxide scavengers during delivery of inhaled nitric oxide.

    PubMed

    Lindberg, L; Rydgren, G

    1998-09-01

    We have analysed the ability of three nitrogen dioxide absorbing materials (soda lime, noXon and zeolite) to act as nitrogen dioxide scavengers during delivery of inhaled nitric oxide. Different mixtures of gas were produced in a ventilator (Servo Ventilator 300) and passed through an inspiratory tube. Concentrations of nitrogen dioxide and nitric oxide were measured in the distal part of the tube, with and without the gas having passed through a canister containing the different filter materials. Our findings indicated that nitrogen dioxide was absorbed effectively by all filter materials but that there was re-formation of nitrogen dioxide from nitric oxide and oxygen in or immediately after the canister. This initial production of nitrogen dioxide was very rapid and could not be prevented by the use of scavengers. Thus soda lime and zeolite had no practical effect as scavengers in this delivery system, and the effect of noXon was very slight.

  14. [Effect of acute phosgene inhalation on antioxidant enzymes, nitric oxide and nitric-oxide synthase in rats].

    PubMed

    Qin, Xu-jun; Hai, Chun-xu; Liang, Xin; Wang, Peng; Chen, Hong-li; Liu, Rui

    2004-06-01

    To study the effect of acute phosgene inhalation on the antioxidant enzymes, nitric oxide (NO) and nitric oxide synthase (NOS) in rats. Phosgene was produced by decomposing bis (trichdomethyl) carbonate in the presence of N,N-dimethyl formamide. SD rats were randomly divided into two groups: control and phosgene exposure groups. In a special experimental device with equipment modulating the gas flow, phosgene exposed rats inhaled phosgene quantitatively for five minutes. Two hours later, all the rats were sacrificed and the ratio of wet weight to dried weight of lung (WW/DW) was calculated. Peripheral blood, serum and liver were collected to examine the activities of antioxidant enzymes including glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), NOS, and NO level. The total content of proteins were also determined. The WW/DW ratio of lung in phosgene exposure group was much higher than that in control group (P < 0.01). The activities of GST in serum and liver of phosgene exposure group increased significantly (P < 0.05). The activities of SOD, CAT, GSHPx and NOS in serum or blood and liver of phosgene exposure group were also increased significantly (P < 0.05). But the content of NO was significantly decreased (P < 0.01). Acute phosgene inhalation may cause a dramatically changes of several antioxidant enzyme activities, and acute injury of liver to some extent in rats. The latter is related to reactive oxygen species. But the elevation of antioxidant enzyme activities suggests that antioxidative treatment for acute phosgene poisoning should not be considered first.

  15. 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

  16. The biological chemistry of nitric oxide as it pertains to the extrapulmonary effects of inhaled nitric oxide.

    PubMed

    Gow, Andrew J

    2006-04-01

    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.

  17. 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.

  18. 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

  19. The Effect of Inhaled Nitric Oxide on Smoke Inhalation Injury in an Ovine Model.

    DTIC Science & Technology

    1994-08-01

    maceuticals, West Orange, NJ), and bronchoalveolar lavage (1.5 mL/kg/ h ). (BAL) was performed under mechanical ventilation. Twenty milliliters of 0.9...carboxyhemoglobin levels, and platelet counts. Methe- moglobin in group 2 was significantly higher than in 10 group 1 at 3 hours and for the duration of the study...decreases free cytosolic calcium lev- moglobin with production of nitrite and nitrate, which es.4 - 6’ 27 Nitric oxide also appears to inhibit the are then

  20. Effects of nitric oxide inhalation on pulmonary gas exchange during exercise in highly trained athletes.

    PubMed

    Durand, F; Mucci, P; Safont, L; Prefaut, C

    1999-02-01

    The pathophysiology of exercise-induced hypoxaemia in elite athletes is still unclear but several studies indicate that a diffusion limitation, which could be explained by an interstitial pulmonary oedema, is a major contributing factor. Stress failure would induce a haemodynamical interstitial oedema with inflammatory reaction and release of mediators like histamine. Histamine release was found to be correlated with the hypoxaemia in elite athletes. If stress failure is involved, inhalation of pulmonary vasodilatators such as nitric oxide during exercise in athletes should induce an inhibition of the histamine release and a reversal of the hypoxaemia. Nine male endurance-trained young athletes performed two randomized exercise tests: one without and the other with 15 p.p.m. of inhaled NO. Measurements of histamine release and arterial blood gas analysis were performed at rest and at 50, 75 and 100% VO2max. At rest, inhaled NO induced a decrease in PaO2 and an increase in (Ai-a)DO2 suggesting increased perfusion of units with low V(A)/Q. During exercise, NO inhalation suppressed the histamine release observed without NO and induced a moderation in the decrease in PaO2 and the increase in (Ai-a)DO2 observed between 75 and 100% of VO2max (P < 0.005). In conclusion, this study showed that NO inhalation inhibited exercise-induced histamine release in highly trained athletes, but we were unable to confirm the suppression of exercise-induced hypoxaemia (EIH). An unexpected result was that inhaled NO seemed to have a marked effect on arterial oxygenation in highly trained-athletes, by disturbing gas exchanges.

  1. Greater nasal nitric oxide output during inhalation: Effects on air temperature and water content

    PubMed Central

    Holden, William E.; Sippel, Jeffrey M.; Nelson, Bella; Giraud, George D.

    2010-01-01

    The nose conditions the temperature and humidity of nasal air, and the nasal mucosal vasculature supplies heat and water for these processes. We hypothesize that nitric oxide (NO) modulates these processes through vasoactive effects on nasal mucosal vasculature. We measured the temperature, humidity and NO concentrations of nasal air during inhalation and exhalation across the nose and calculated net heat, water and NO output before (controls, n = 7) and after inhibition of NO synthase by topical L-NAME (N=5) in healthy humans. We found that calculated NO output across the nasal passages is approximately three-fold greater during inhalation (503 ± 105 nL/min) compared with exhalation (162 ± 56 nL/min). Moreover, topical administration of L-NAME decreased nasal air temperature and humidity conditioning and NO output, but these effects were limited to inhalation. We conclude that nasal NO output is greater during inhalation than exhalation in humans. Our findings also support a role of nasal NO in temperature and humidity conditioning of nasal air. PMID:18952009

  2. Greater nasal nitric oxide output during inhalation: effects on air temperature and water content.

    PubMed

    Holden, William E; Sippel, Jeffrey M; Nelson, Bella; Giraud, George D

    2009-01-01

    The nose conditions the temperature and humidity of nasal air, and the nasal mucosal vasculature supplies heat and water for these processes. We hypothesize that nitric oxide (NO) modulates these processes through vasoactive effects on nasal mucosal vasculature. We measured the temperature, humidity and NO concentrations of nasal air during inhalation and exhalation across the nose and calculated net heat, water and NO output before (controls, n=7) and after inhibition of NO synthase by topical l-NAME (N=5) in healthy humans. We found that calculated NO output across the nasal passages is approximately three-fold greater during inhalation (503+/-105 nL/min) compared with exhalation (162+/-56 nL/min). Moreover, topical administration of l-NAME decreased nasal air temperature and humidity conditioning and NO output, but these effects were limited to inhalation. We conclude that nasal NO output is greater during inhalation than exhalation in humans. Our findings also support a role of nasal NO in temperature and humidity conditioning of nasal air.

  3. Inhaled nitric oxide as an adjunct to suction thrombectomy for pulmonary embolism.

    PubMed

    Faintuch, Salomão; Lang, Elvira V; Cohen, Robert I; Pinto, Duane S

    2004-11-01

    Pulmonary suction thrombectomy can be a successful interventional tool in the treatment of pulmonary thromboembolism. Removal of clot burden typically results in prompt recovery of hemodynamic stability and improved oxygenation. However, in rare cases, clot removal does not sufficiently improve the clinical situation. Herein, two patients with massive pulmonary thromboembolism are presented whose condition improved only after they received nitric oxide as an adjunct to pulmonary suction thrombectomy. The treatment with this inhalable vasodilator was based on the hypothesis that prolonged ischemia had induced microcirculatory vasospasm, persistent after removal of the central clot.

  4. Inhaled Nitric Oxide in preterm infants: a systematic review and individual patient data meta-analysis

    PubMed Central

    2010-01-01

    Background Preterm infants requiring assisted ventilation are at significant risk of both pulmonary and cerebral injury. Inhaled Nitric Oxide, an effective therapy for pulmonary hypertension and hypoxic respiratory failure in the full term infant, has also been studied in preterm infants. The most recent Cochrane review of preterm infants includes 11 studies and 3,370 participants. The results show a statistically significant reduction in the combined outcome of death or chronic lung disease (CLD) in two studies with routine use of iNO in intubated preterm infants. However, uncertainty remains as a larger study (Kinsella 2006) showed no significant benefit for iNO for this combined outcome. Also, trials that included very ill infants do not demonstrate significant benefit. One trial of iNO treatment at a later postnatal age reported a decrease in the incidence of CLD. The aim of this individual patient meta-analysis is to confirm or refute these potentially conflicting results and to determine the extent to which patient or treatment characteristics may explain the results and/or may predict benefit from inhaled Nitric Oxide in preterm infants. Methods/Design The Meta-Analysis of Preterm Patients on inhaled Nitric Oxide (MAPPiNO) Collaboration will perform an individual patient data meta-analysis to answer these important clinical questions. Studies will be included if preterm infants receiving assisted ventilation are randomized to receive inhaled Nitric Oxide or to a control group. The individual patient data provided by the Collaborators will be analyzed on an intention-to-treat basis where possible. Binary outcomes will be analyzed using log-binomial regression models and continuous outcomes will be analyzed using linear fixed effects models. Adjustments for trial differences will be made by including the trial variable in the model specification. Discussion Thirteen (13) trials, with a total of 3567 infants are eligible for inclusion in the MAPPiNO systematic

  5. Combined exogenous surfactant and inhaled nitric oxide therapy for lung ischemia-reperfusion injury in minipigs.

    PubMed

    Warnecke, G; Strüber, M; Fraud, S; Hohlfeld, J M; Haverich, A

    2001-05-15

    The combined application of exogenous surfactant and inhaled nitric oxide was evaluated for prevention of ischemia-reperfusion injury of the lung. Left lungs were selectively perfused in 18 minipigs in situ with cold preservation solution. After 90 min of warm ischemia, the lungs were reperfused and the right pulmonary artery and bronchus were ligated (control group, n=6). Exogenous surfactant was instilled via bronchoscopy during ischemia (surfactant group, n=6). In a third group, surfactant was applied, followed by administration of inhaled nitric oxide (surfactant+NO group, n=6). Hemodynamic and respiratory parameters were recorded for 7 hr, and bronchoalveolar lavage fluid (BALF) was obtained before and after reperfusion for measurement of surface tension, small aggregate/large aggregate ratio, protein and phospholipid contents, and a differential cell count. Control group animals survived for 3.7+/-1.4 hr. In both surfactant-treated groups, five out of six animals survived the observation period (P<0.001). Dynamic compliance of the lung was decreased in control animals (P<0.001). In the surfactant+NO group, arterial PO2 was higher than in both other groups (P<0.001). BALF cell count and histology showed reduced neutrophil infiltration in surfactant+NO-treated lungs. Surface tension assessed in BALF with a pulsating bubble surfactometer was severely impaired in control animals (gammamin, 14.82+/-9.95 mN/m), but maintained in surfactant-treated (gammamin, 1.11+/-0.56 mN/m) and surfactant+NO-treated animals (gammamin, 3.90+/-2.35 mN/m, P=0.02). Administration of exogenous surfactant in lung reperfusion injury results in improved lung compliance. The addition of inhaled NO improves arterial oxygenation and reduces neutrophil extravasation compared with surfactant treatment alone.

  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. 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…

  8. Inhaled nitric oxide for the adjunctive therapy of severe malaria: Protocol for a randomized controlled trial

    PubMed Central

    2011-01-01

    Background Severe malaria remains a major cause of global morbidity and mortality. Despite the use of potent anti-parasitic agents, the mortality rate in severe malaria remains high. Adjunctive therapies that target the underlying pathophysiology of severe malaria may further reduce morbidity and mortality. Endothelial activation plays a central role in the pathogenesis of severe malaria, of which angiopoietin-2 (Ang-2) has recently been shown to function as a key regulator. Nitric oxide (NO) is a major inhibitor of Ang-2 release from endothelium and has been shown to decrease endothelial inflammation and reduce the adhesion of parasitized erythrocytes. Low-flow inhaled nitric oxide (iNO) gas is a US FDA-approved treatment for hypoxic respiratory failure in neonates. Methods/Design This prospective, parallel arm, randomized, placebo-controlled, blinded clinical trial compares adjunctive continuous inhaled nitric oxide at 80 ppm to placebo (both arms receiving standard anti-malarial therapy), among Ugandan children aged 1-10 years of age with severe malaria. The primary endpoint is the longitudinal change in Ang-2, an objective and quantitative biomarker of malaria severity, which will be analysed using a mixed-effects linear model. Secondary endpoints include mortality, recovery time, parasite clearance and neurocognitive sequelae. Discussion Noteworthy aspects of this trial design include its efficient sample size supported by a computer simulation study to evaluate statistical power, meticulous attention to complex ethical issues in a cross-cultural setting, and innovative strategies for safety monitoring and blinding to treatment allocation in a resource-constrained setting in sub-Saharan Africa. Trial Registration ClinicalTrials.gov Identifier: NCT01255215 PMID:21752262

  9. Inhaled Nitric Oxide Improves Outcomes After Successful Cardiopulmonary Resuscitation in Mice

    PubMed Central

    Minamishima, Shizuka; Kida, Kotaro; Tokuda, Kentaro; Wang, Huifang; Sips, Patrick Y.; Kosugi, Shizuko; Mandeville, Joseph B.; Buys, Emmanuel S.; Brouckaert, Peter; Liu, Philip K.; Liu, Christina H.; Bloch, Kenneth D.; Ichinose, Fumito

    2011-01-01

    Introduction Sudden cardiac arrest (CA) is a leading cause of death worldwide. Breathing nitric oxide (NO) reduces ischemia-reperfusion (IR) injury in animal models and in patients. The objective of this study was to learn whether inhaled NO improves outcomes after CA and cardiopulmonary resuscitation (CPR). Methods and Results Adult male mice were subjected to potassium-induced CA for 7.5 min whereupon CPR was performed with chest compression and mechanical ventilation. One hour after CPR, mice were extubated and breathed air alone or air supplemented with 40 parts per million (ppm) NO for 23h. Mice that were subjected to CA/CPR and breathed air exhibited a poor 10-day survival rate (4/13), depressed neurological and left ventricular (LV) function, and increased caspase-3 activation and inflammatory cytokine induction in the brain. Magnetic resonance imaging revealed brain regions with marked water diffusion abnormality 24h after CA/CPR in mice that breathed air. Breathing air supplemented with NO for 23h starting 1h after CPR attenuated neurological and LV dysfunction 4 days after CA/CPR and markedly improved 10-day survival rate (11/13, P=0.003 vs Air). The protective effects of inhaled NO on the outcome after CA/CPR were associated with reduced water diffusion abnormality, caspase-3 activation, and cytokine induction in the brain and increased serum NOx levels. Deficiency of the α1 subunit of soluble guanylate cyclase (sGC), a primary target of NO, abrogated the ability of inhaled NO to improve outcomes after CA/CPR. Conclusions These results suggest that NO inhalation after CA and successful CPR improves outcome via sGC-dependent mechanisms. PMID:21931083

  10. Inhaled nitric oxide reduces endothelial activation and parasite accumulation in the brain, and enhances survival in experimental cerebral malaria.

    PubMed

    Serghides, Lena; Kim, Hani; Lu, Ziyue; Kain, Dylan C; Miller, Chris; Francis, Roland C; Liles, W Conrad; Zapol, Warren M; Kain, Kevin C

    2011-01-01

    The host immune response contributes to the onset and progression of severe malaria syndromes, such as cerebral malaria. Adjunctive immunomodulatory strategies for severe malaria may improve clinical outcome beyond that achievable with artemisinin-based therapy alone. Here, we report that prophylaxis with inhaled nitric oxide significantly reduced systemic inflammation (lower TNF, IFNγ and MCP-1 in peripheral blood) and endothelial activation (decreased sICAM-1 and vWF, and increased angiopoeitin-1 levels in peripheral blood) in an experimental cerebral malaria model. Mice that received inhaled nitric oxide starting prior to infection had reduced parasitized erythrocyte accumulation in the brain, decreased brain expression of ICAM-1, and preserved vascular integrity compared to control mice.Inhaled nitric oxide administered in combination with artesunate, starting as late as 5.5 days post-infection, improved survival over treatment with artesunate alone (70% survival in the artesunate only vs. 100% survival in the artesunate plus iNO group, p = 0.03). These data support the clinical investigation of inhaled nitric oxide as a novel adjunctive therapy in patients with severe malaria.

  11. Inhaled nitric oxide for preterm premature rupture of membranes, oligohydramnios, and pulmonary hypoplasia.

    PubMed

    Chock, Valerie Y; Van Meurs, Krisa P; Hintz, Susan R; Ehrenkranz, Richard A; Lemons, James A; Kendrick, Douglas E; Stevenson, David K

    2009-04-01

    We sought to determine if inhaled nitric oxide (iNO) administered to preterm infants with premature rupture of membranes (PPROM), oligohydramnios, and pulmonary hypoplasia improved oxygenation, survival, or other clinical outcomes. Data were analyzed from infants with suspected pulmonary hypoplasia, oligohydramnios, and PPROM enrolled in the National Institute of Child Health and Development Neonatal Research Network Preemie Inhaled Nitric Oxide (PiNO) trial, where patients were randomized to receive placebo (oxygen) or iNO at 5 to 10 ppm. Outcome variables assessed were PaO (2) response, mortality, bronchopulmonary dysplasia (BPD), and severe intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL). Twelve of 449 infants in the PiNO trial met criteria. Six infants received iNO and six received placebo. The iNO group had a mean increase in PaO (2) of 39 +/- 50 mm Hg versus a mean decrease of 11 +/- 15 mm Hg in the control group. Mortality was 33% versus 67%, BPD (2/5) 40% versus (2/2) 100%, and severe IVH or PVL (1/5) 20% versus (1/2) 50% in the iNO and control groups, respectively. None of these changes were statistically significant. Review of a limited number of cases from a large multicenter trial suggests that iNO use in the setting of PPROM, oligohydramnios, and suspected pulmonary hypoplasia improves oxygenation and may decrease the rate of BPD and death without increasing severe IVH or PVL. However, the small sample size precludes definitive conclusions. Further studies are required to determine if iNO is of benefit in this specific patient population.

  12. Prevention of ischemia-reperfusion lung injury by inhaled nitric oxide in neonatal piglets.

    PubMed

    Barbotin-Larrieu, F; Mazmanian, M; Baudet, B; Détruit, H; Chapelier, A; Libert, J M; Dartevelle, P; Hervé, P

    1996-03-01

    Lung ischemia-reperfusion results in a decrease in the release of nitric oxide (NO) by the pulmonary endothelium. NO may have lung-protective effects by decreasing neutrophil accumulation in the lung. We tested whether NO inhalation would attenuate reperfusion-induced endothelial dysfunction and increases in microvascular permeability and total pulmonary vascular resistance (RT) by preventing neutrophil lung accumulation. After baseline determinations of RT, coefficient of filtration (Kfc), and circulating neutrophil counts, isolated neonatal piglet lungs were subjected to a 1-h period of ischemia followed by a 1-h period of blood reperfusion and reventilation with or without addition of NO (10 ppm). NO prevented reperfusion-induced increases in RT and Kfc, as well as the decrease in circulating neutrophils. After reperfusion, increases in Kfc were correlated with decreases in circulating neutrophils. NO prevented reperfusion-induced decrease in endothelium-dependent relaxation in precontracted pulmonary arterial rings. This demonstrates that inhaled NO prevents microvascular injury, endothelial dysfunction, and pulmonary neutrophil accumulation in a neonatal piglet model of lung ischemia-reperfusion.

  13. 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

  14. Inhaled nitric oxide pretreatment but not posttreatment attenuates ischemia-reperfusion-induced pulmonary microvascular leak.

    PubMed

    Chetham, P M; Sefton, W D; Bridges, J P; Stevens, T; McMurtry, I F

    1997-04-01

    Ischemia-reperfusion (I/R) pulmonary edema probably reflects a leukocyte-dependent, oxidant-mediated mechanism. Nitric oxide (NO) attenuates leukocyte-endothelial cell interactions and I/R-induced microvascular leak. Cyclic adenosine monophosphate (cAMP) agonists reverse and prevent I/R-induced microvascular leak, but reversal by inhaled NO (INO) has not been tested. In addition, the role of soluble guanylyl cyclase (sGC) activation in the NO protection effect is unknown. Rat lungs perfused with salt solution were grouped as either I/R, I/R with INO (10 or 50 ppm) on reperfusion, or time control. Capillary filtration coefficients (Kfc) were estimated 25 min before ischemia (baseline) and after 30 and 75 min of reperfusion. Perfusate cell counts and lung homogenate myeloperoxidase activity were determined in selected groups. Additional groups were treated with either INO (50 ppm) or isoproterenol (ISO-10 microM) after 30 min of reperfusion. Guanylyl cyclase was inhibited with 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ-15 microM), and Kfc was estimated at baseline and after 30 min of reperfusion. (1) Inhaled NO attenuated I/R-induced increases in Kfc. (2) Cell counts were similar at baseline. After 75 min of reperfusion, lung neutrophil retention (myeloperoxidase activity) and decreased perfusate neutrophil counts were similar in all groups. (3) In contrast to ISO, INO did not reverse microvascular leak. (4) 8-bromoguanosine 3',5'-cyclic monophosphate (8-br-cGMP) prevented I/R-induced microvascular leak in ODQ-treated lungs, but INO was no longer effective. Inhaled NO attenuates I/R-induced pulmonary microvascular leak, which requires sGC activation and may involve a mechanism independent of inhibition of leukocyte-endothelial cell interactions. In addition, INO is ineffective in reversing I/R-induced microvascular leak.

  15. [Inhaled nitric oxide: a physiologic treatment of persistent pulmonary arterial hypertension in the newborn].

    PubMed

    Thébaud, B; Mercier, J C

    1997-10-01

    Fetal pulmonary circulation is characterized by high resistance and low pulmonary blood flow. Right-to-left shunting through the foramen ovale and/or patent ductus arteriosus is necessary to perfuse the placenta and insure fetal life. At birth, pulmonary arterial blood flow increases immediately by 8- to 10-fold, and allows pulmonary gas exchange and postnatal life. In some circumstances, this adaptation to extra-uterine life is inadequate, because of persistent high pulmonary resistance (PPHN). Due to the lack of a selective pulmonary vasodilator, the treatment of this syndrome remained purely symptomatic using high oxygen levels and barotraumatic mechanical hyperventilation. When this medical treatment failed, the only alternative was extracorporeal membrane oxygenation (ECMO). The discovery of the major role of various endothelium-derived factors including nitric oxide (NO) in the control of vascular reactivity led to dramatic switches in the concepts of severe neonatal respiratory failure and the therapeutic approach of PPHN. It was shown, first in experimental animals then in a few infants with hypoxemic respiratory failure, that NO inhalation selectively vasodilated the vasoconstricted pulmonary vessels, and reversed right-to-left shunting and refractory hypoxemia. Whether inhaled NO also reduces mortality and/or morbidity in hypoxic infants remains to be proven by appropriate randomized clinical trials. However, not only PPHN is associated with pulmonary diseases of various etiologies and underlying pathophysiologic mechanisms, but also inhaled NO is used in conjunction with other validated therapeutic strategies including ante- or postnatal steroids, exogenous surfactants, and high-frequency oscillatory ventilation. Thus, the relevant primary endpoint might be not only crude survival but the most physiological and economical way of obtaining it.

  16. Pulmonary expression of nitric oxide synthase isoforms in sheep with smoke inhalation and burn injury.

    PubMed

    Cox, Robert A; Jacob, Sam; Oliveras, Gloria; Murakami, Kazunori; Enkhbaatar, Perenlei; Traber, Lillian; Schmalstieg, Frank C; Herndon, David N; Traber, Daniel L; Hawkins, Hal K

    2009-03-01

    Previous studies have indicated increased plasma levels of inducible nitric oxide synthase in lung. This study further examines the pulmonary expression of nitric oxide synthase (NOS) isoforms in an ovine model of acute lung injury induced by smoke inhalation and burn injury (S+B injury). Female range bred sheep (4 per group) were sacrificed at 4, 8, 12, 24, and 48 hours after injury and immunohistochemistry was performed in tissues for various NOS isoforms. The study indicates that in uninjured sheep lung, endothelial (eNOS) is constitutively expressed in the endothelial cells associated with the airways and parenchyma, and in macrophages. Similarly, neuronal (nNOS) is constitutively present in the mucous cells of the epithelium and in neurons of airway ganglia. In uninjured lung, inducible (iNOS) was present in bronchial secretory cells and macrophages. In tissue after S+B injury, new expression of iNOS was evident in bronchial ciliated cells, basal cells, and mucus gland cells. In the parenchyma, a slight increase in iNOS immunostaining was seen in type I cells at 12 and 24 hours after injury only. Virtually no change in eNOS or nNOS was seen after injury.

  17. Inhaled nitric oxide and arterial oxygen tension in patients with chronic obstructive pulmonary disease and severe pulmonary hypertension

    PubMed Central

    Katayama, Y.; Higenbottam, T. W.; d Diaz; Cremona, G.; Akamine, S.; Barbera, J. A.; Rodriguez-Roisin, R.

    1997-01-01

    BACKGROUND: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator which can improve gas exchange in acute lung injury. However, it is uncertain that this effect on arterial oxygenation can be generalised to all lung diseases. METHODS: The effects of inhaled NO on gas exchange were studied in nine patients with chronic obstructive pulmonary disease (COPD), 11 patients with severe pulmonary hypertension, and 14 healthy volunteers. A randomized sequence of 40 ppm of NO or air was inhaled for 20 minutes through an orofacial mask. RESULTS: Inhaled NO reduced mean (SE) transcutaneous arterial oxygen tension (TcPO2) from 9.6 (0.3) to 8.9 (0.4) kPa in healthy volunteers and from 7.4 (0.6) to 7.0 (0.5) kPa in patients with COPD. There was no change in TcPO2 in patients with severe pulmonary hypertension. During inhalation of NO and air no change occurred in transcutaneous arterial carbon dioxide tension (TcPCO2), arterial oxygen saturation (SaO2) measured by pulse oximeter, or cardiac output determined by the transthoracic impedance method. CONCLUSIONS: Inhaled NO does not improve TcPO2 nor increase cardiac output in normal subjects and patients with COPD, suggesting that inhaled NO worsens gas exchange. This could represent inhaled NO overriding hypoxic pulmonary vasoconstriction in COPD. The finding that TcPO2 also fell when normal subjects inhaled NO suggests that a similar mechanism normally contributes to optimal gas exchange. Whilst inhaled NO can improve oxygenation, this effect should not be considered to be a general response but is dependent on the type of lung disease. 


 PMID:9059470

  18. Inflammatory Mediators in Tracheal Aspirates of Preterm Infants Participating in a Randomized Trial of Inhaled Nitric Oxide

    PubMed Central

    Amann, Elena; Uhlig, Ulrike; Yang, Yang; Fuchs, Hans W.; Zemlin, Michael; Mercier, Jean-Christophe; Maier, Rolf F.; Hummler, Helmut D.; Uhlig, Stefan; Thome, Ulrich H.

    2017-01-01

    Background Ventilated preterm infants frequently develop bronchopulmonary dysplasia (BPD) which is associated with elevated inflammatory mediators in their tracheal aspirates (TA). In animal models of BPD, inhaled nitric oxide (iNO) has been shown to reduce lung inflammation, but data for human preterm infants is missing. Methods Within a European multicenter trial of NO inhalation for preterm infants to prevent BPD (EUNO), TA was collected to determine the effects of iNO on pulmonary inflammation. TA was collected from 43 premature infants randomly assigned to receive either iNO or placebo gas (birth weight 530–1230 g, median 800 g, gestational age 24 to 28 2/7 weeks, median 26 weeks). Interleukin (IL)-1β, IL-6, IL-8, transforming growth factor (TGF)-β1, interferon γ-induced protein 10 (IP-10), macrophage inflammatory protein (MIP)-1α, acid sphingomyelinase (ASM), neuropeptide Y and leukotriene B4 were measured in serial TA samples from postnatal day 2 to 14. Furthermore, TA levels of nitrotyrosine and nitrite were determined under iNO therapy. Results The TA levels of IP-10, IL-6, IL-8, MIP-1α, IL-1β, ASM and albumin increased with advancing postnatal age in critically ill preterm infants, whereas nitrotyrosine TA levels declined in both, iNO-treated and placebo-treated infants. The iNO treatment generally increased nitrite TA levels, whereas nitrotyrosine TA levels were not affected by iNO treatment. Furthermore, iNO treatment transiently reduced early inflammatory and fibrotic markers associated with BPD development including TGF-β1, IP-10 and IL-8, but induced a delayed increase of ASM TA levels. Conclusion Treatment with iNO may have played a role in reducing several inflammatory and fibrotic mediators in TA of preterm infants compared to placebo-treated infants. However, survival without BPD was not affected in the main EUNO trial. Trial registration NCT00551642 PMID:28046032

  19. Inhalants

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  20. Inhalants

    MedlinePlus

    ... place a chemical- soaked rag in their mouth. Abusers may also inhale fumes from a balloon or ... by inhalants usually lasts just a few minutes, abusers often try to prolong it by continuing to ...

  1. 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 ...

  2. Anti-inflammatory effects of inhaled nitric oxide are optimized at lower oxygen concentration in experimental Klebsiella pneumoniae pneumonia.

    PubMed

    Sun, Z; Sun, B; Wang, X; Wang, W; Zhu, L

    2006-10-01

    To evaluate whether antiinflammatory effects of inhaled nitric oxide (NO) in experimental Klebsiella pneumoniae pneumonia may be affected by oxygen levels in association with cytokine response and NO synthase (NOS) activity. Healthy adult rats were intratracheally instilled with live Klebsiella pneumoniae to induce pneumonia (P) or with sterile saline as a control (C) group. Group C was allocated to room air (CA) and inhaled NO (CNO, NO = 20 parts per million) groups. Group P was divided into 6 groups (n = 8 - 10) exposed to room air (PA), inhaled NO (PNO), low oxygen (40%, PLO), inhaled NO and low oxygen (PLONO), high oxygen (100%, PHO), and inhaled NO and high oxygen (98%, PHONO). After 24 h exposure, intraalveolar cells, expression of proinflammatory cytokines, nuclear transcription factor (NF-kappaB), myeloperoxidase (MPO) and NOS activities, characteristic of lung inflammatory mechanisms, were measured. All the pneumonia groups had pneumonia whereas CA and CNO had no or mild lung inflammation. Compared to the PA, significantly decreased recruitment of alveolar neutrophils was found in the PNO, along with lower NF-kappaB and MPO activity, tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecule-1 (ICAM-1). Similar trends were found between the PLONO and PLO in alleviation of lung inflammation. However, PHONO significantly enhanced recruitment of alveolar neutrophils and pulmonary MPO activity associated with increased TNF-alpha. Inhaled NO improved bacterial clearance, reduced total proteins in alveoli, and ICAM-1 expression irrespective of oxygen levels. Inhaled NO and/or low and high oxygen partially restored constitutive NOS activity whereas high oxygen or together with inhaled NO depressed inducible NOS activity. The overall beneficial effects of inhaled NO in anti-inflammation in the mature lungs with K. pneumoniae pneumonia are in favor of a combination with lower level of oxygen, which warrants clinical verification in the treatment of

  3. One-Year Respiratory Outcomes of Preterm Infants Enrolled in the Nitric Oxide[H1] (to Prevent) Chronic Lung Disease Trial of Inhaled Nitric Oxide

    PubMed Central

    Hibbs, Anna Maria; Walsh, Michele C.; Martin, Richard J.; Truog, William E.; Lorch, Scott A.; Alessandrini, Evaline; Cnaan, Avital; Palermo, Lisa; Wadlinger, Sandra R.; Coburn, Christine E.; Ballard, Philip L.; Ballard, Roberta A.

    2009-01-01

    Objective To identify whether inhaled nitric oxide treatment decreased indicators of long-term pulmonary morbidities after discharge from the NICU. Study design The NO CLD trial enrolled preterm infants (<1250g) between 7–21 days of age who were ventilated and at high risk for BPD. Follow-up occurred at 12 ± 3 months of age adjusted for prematurity; long-term pulmonary morbidities and other outcomes were reported by parents during structured blinded interviews. Results 456 infants (85%) were seen at 1 yr. Compared with control infants, infants randomized to inhaled nitric oxide received significantly less bronchodilators [odds ratio (OR) 0.53 (95% confidence interval 0.36–0.78)], inhaled steroids [OR 0.50 (0.32–0.77)], systemic steroids [OR 0.56 (0.32–0.97)], diuretics [OR 0.54 (0.34–0.85)], and supplemental oxygen [OR 0.65 (0.44–0.95)] after discharge from neonatal intensive care. There were no significant differences between parental report of re-hospitalizations [OR 0.83 (0.57–1.21)] or wheezing or whistling in the chest [OR 0.70 (0.48–1.03)]. Conclusions Infants treated with inhaled nitric oxide received fewer outpatient respiratory medications than the control group. However, any decision to institute routine use of this dosing regimen should also take into account the results of the 24 month neurodevelopmental assessment. PMID:18534620

  4. 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.

  5. Modified INOvent for delivery of inhaled nitric oxide during cardiac MRI.

    PubMed

    Devendra, Ganesh P; Hart, Stephen A; Kim, Yuli Y; Setser, Randy M; Flamm, Scott D; Krasuski, Richard A

    2011-10-01

    The aim of this study was to assess the feasibility of delivering NO through a modified system to allow clearance of the magnetic field and thus compatibility with cardiac magnetic resonance (CMR). Nitric oxide (NO) is an inhalational, selective pulmonary vasodilator with a wide range of applications in a variety of disease states, including diseases that affect the right ventricle. Accurate assessment of dynamic changes in right ventricular function necessitates CMR; however, delivery of NO is only possible using equipment that is not magnetic resonance imaging (MRI) compatible (INOvent delivery system, Ohmeda, Inc., Madison, WI, USA). The INOvent delivery system was modified by using 35 ft. of standard oxygen tubing to allow NO delivery through an electrical conduit and into the MRI suite. The concentrations of oxygen (O(2)), nitrogen dioxide (a harmful byproduct, NO(2)) and NO were measured in triplicate using the built-in electrochemical analyzer on the INOvent. After confirmation of safety, the system was used to administer drug to a patient x, and dynamic MRI measurements were performed. When the standard INOvent was set to administer 40 ppm of NO, the mean/standard deviation of gas delivered was as follows: NO: 42/0 ppm; NO(2): 0.3/0.1 ppm; and O(2): 93/0 ppm. In comparison, the gas delivery of the modified INOvent was follows: NO: 41/0 ppm; NO(2): 0.5/0 ppm; and O(2): 93.7/0.6 ppm. During administration to an index patient with severe pulmonic insufficiency (PI), a measurable reduction in PI was observed by CMR. Nitric oxide can be administered through 35 ft. of standard oxygen tubing without significantly affecting dose delivery. This technique has potential application in patients with right-sided structural heart disease for determination of dynamic physiological changes. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Inhaled Nitric Oxide Decreases Leukocyte Trafficking in the Neonatal Mouse Lung During Exposure to >95% Oxygen

    PubMed Central

    Rose, Melissa J.; Stenger, Michael R.; Joshi, Mandar S.; Welty, Stephen E.; Bauer, John Anthony; Nelin, Leif D.

    2010-01-01

    Chronic lung injury in the neonate is termed bronchopulmonary dysplasia (BPD). These patients generally require supplemental oxygen therapy, and hyperoxia has been implicated in the pathogenesis of BPD. The concomitant use of oxygen and inhaled nitric oxide (iNO) may result in the generation of reactive nitrogen species, or may have an anti-inflammatory effect in the neonatal lung. We tested the hypothesis that exposure to >95% O2 in neonatal mice would increase trafficking of leukocytes into the lung, and that the addition of iNO to >95% O2 would decrease this leukocyte trafficking. Hyperoxia resulted in fewer alveoli, increased presence of neutrophils and macrophages, and decreased number of mast cells within the lung parenchyma. Adding iNO to hyperoxia prevented the hyperoxia-induced changes and resulted in the numbers of alveoli, neutrophils, macrophages, and mast cells approximating those found in controls (room air exposure). Intercellular adhesion molecule (ICAM) and monocyte chemotactic protein-1 (MCP-1), two factors responsible for leukocyte recruitment, were upregulated by hyperoxic exposure, but the addition of iNO to the hyperoxic exposure prevented the hyperoxia-induced upregulation of ICAM and MCP-1. These data demonstrate that iNO alters the hyperoxia-induced recruitment of leukocytes into the lung. PMID:19915514

  7. Effect of inhaled nitric oxide on cerebrospinal fluid and blood nitrite concentrations in newborn lambs

    PubMed Central

    Conahey, George R.; Power, Gordon G.; Hopper, Andrew O.; Terry, Michael H.; Kirby, Laura S.; Blood, Arlin B.

    2009-01-01

    Inhaled nitric oxide (iNO) has many extrapulmonary effects. As the half-life of NO in blood is orders of magnitude less than the circulation time from lungs to the brain, the mediator of systemic effects of iNO is unknown. We hypothesized that concentrations of nitrite, a circulating byproduct of NO with demonstrated NO bioactivity, would increase in blood and cerebrospinal fluid (CSF) during iNO therapy. iNO (80ppm) was given to six newborn lambs and results compared to six control lambs. Blood and CSF nitrite concentrations increased two-fold in response to iNO. cGMP increased in blood but not CSF suggesting brain guanylate cyclase activity was not increased. When sodium nitrite was infused intravenously blood and CSF nitrite levels increased within 10 min and reached similar levels of 14.6±1.5 µM after 40 min. The reactivity of nitrite in hemoglobin-free brain homogenates was investigated, with the findings that nitrite did not disappear nor did measurable amounts of s-nitroso, n-nitroso, or iron-nitrosyl-species appear. We conclude that although nitrite diffuses freely between blood and CSF, due to its lack of reactivity in the brain, nitrite’s putative role as the mediator of the systemic effects of iNO is limited to intravascular reactions. PMID:18535482

  8. Inhaled nitric oxide in adult patients with acute respiratory distress syndrome.

    PubMed

    Monsalve-Naharro, José Ángel; Domingo-Chiva, Esther; García Castillo, Sergio; Cuesta-Montero, Pablo; Jiménez-Vizuete, José María

    2017-03-01

    In some patients, acute respiratory distress syndrome (ARDS) leads to life-threatening refractory hypoxemia developing. Physicians may consider hypoxemic rescue therapies in an attempt to improve oxygenation in these patients while on conventional mechanical ventilation support. Use of inhaled nitric oxide (iNO) in ARDS is one of the most widely-studied pharmacological interventions over the past two decades. Its efficacy was examined in several randomized clinical trials and has undergone meta-analyses. Although iNO treatment was associated with improved oxygenation, researchers unfortunately never demonstrated a concomitant decrease in mortality or any improved outcome. Hence the current evidence suggests that iNO should not be routinely used in patients with ARDS however may be considered as adjunct therapy to tentatively improve oxygenation while other therapies are being considered in patients with severely hypoxemic ARDS.This review focuses on the therapeutic use of iNO in adult ARDS patients. We set out some recommendations for its use as rescue therapy against refractory hypoxemia.

  9. Inhaled Nitric Oxide Use in Preterm Infants in California Neonatal Intensive Care Units

    PubMed Central

    Handley, Sara C.; Steinhorn, Robin H.; Hopper, Andrew O.; Govindaswami, Balaji; Bhatt, Dilip R.; Van Meurs, Krisa P.; Ariagno, Ronald L.; Gould, Jeffrey B.; Lee, Henry C.

    2016-01-01

    Objective To describe inhaled nitric oxide (iNO) exposure in preterm infants and variation in Neonatal Intensive Care Unit (NICU) use. Study Design This was a retrospective cohort study of infants, 22–33+6/7 weeks gestational age (GA), during 2005–2013. Analyses were stratified by GA and included population characteristics, iNO use over time and hospital variation. Result Of 65 824 infants, 1 718 (2.61%) received iNO. Infants, 22–24+6/7 weeks GA, had the highest incidence of iNO exposure (6.54%). Community NICUs (n = 77, median hospital use rate 0.7%) used less iNO than regional NICUs (n = 23, median hospital use rate 5.8%). In 22–24+6/7 week GA infants the median rate in regional centers was 10.6% (hospital IQR 3.8%–22.6%). Conclusion iNO exposure varied with GA and hospital level, with the most use in extremely premature infants and regional centers. Variation reflects a lack of consensus regarding the appropriate use of iNO for preterm infants. PMID:27031320

  10. Beneficial Effects of Concomitant Neuronal and Inducible Nitric Oxide Synthase Inhibition in Ovine Burn and Inhalation Injury

    PubMed Central

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

    2013-01-01

    Different isoforms of nitric oxide 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 nitric oxide synthase effectively prevents the pulmonary lesions in an ovine model of acute respiratory distress syndrome (ARDS) 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 nitric oxide synthase inhibitors (n = 5). The injury was induced by 48 breath of cotton smoke and a 3rd 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 nitric oxide synthase exerts beneficial pulmonary effects in an ovine model of ARDS 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

  11. Inhaled nitric oxide in term/late preterm neonates with hypoxic respiratory failure: estimating the financial impact of earlier use.

    PubMed

    Konduri, G Ganesh; Menzin, Joseph; Frean, Molly; Lee, Terry; Potenziano, Jim; Singer, Joel

    2015-01-01

    We reported recently that early use of inhaled nitric oxide therapy (iNO) for term and late preterm infants with hypoxic respiratory failure (HRF) at an oxygenation index (OI) of ≥15 and <20 is associated with earlier discharge from the hospital, relative to babies treated at OI ≥25. The objective of the present analysis is to determine whether earlier use of iNO in this cohort leads to lower cost of medical care. We used a decision-analytic model, which was developed to compare hospital resource use and costs associated with early versus standard use of iNO in HRF. The model population included infants with moderate HRF caused by primary pulmonary hypertension with an OI ≥15 and <20. A hypothetical case population of 1000 patients was assumed and probabilistic sensitivity analyses were completed where all the clinical inputs into the model were varied. Two deterministic sensitivity analyses were also completed, one surrounding the hospital cost inputs and another surrounding the cost of iNO. Early iNO was associated with fewer hospital days, fewer days of ventilation and fewer hours on extracorporeal membrane oxygenation (ECMO). In probabilistic sensitivity analyses, total costs per patient were $88,518 ± $7574 and $92,581 ± $9664 for early iNO and standard iNO, respectively. The probability of early iNO being cost-effective was approximately 72%, based on a willingness to pay $100,000 or less to prevent ECMO therapy and/or death. In both deterministic sensitivity analyses, early iNO was cost-saving. Our analysis shows that early use of iNO at an OI of ≥15 and <20 may be associated with shorter hospitalizations and a decreased cost of care for term/late preterm infants with HRF associated with pulmonary hypertension. Our results are based on clinical data from a single trial; future research using data from real-world practice is warranted.

  12. Use of inhaled nitric oxide in pediatric cardiac intensive care unit.

    PubMed

    Öztürk, Erkut; Haydin, Sertaç; Tanıdır, İbrahim Cansaran; Özyılmaz, İsa; Ergül, Yakup; Erek, Ersin; Güzeltaş, Alper; Ödemiş, Ender; Bakır, İhsan

    2016-04-01

    Experience with administration of inhaled nitric oxide (iNO) in pediatric cardiac intensive care unit was retrospectively reviewed. Data from 32 pediatric patients treated with iNO between 2011 and 2012 were collected. Patients were divided into 3 groups: Group I comprised postoperative patients, Group II comprised newborns with persistent pulmonary hypertension (PPH), and Group III comprised patients with primary pulmonary hypertension (PH) or Eisenmenger's syndrome. Age, sex, weight, primary diagnosis, arterial blood sample, pulmonary artery pressure (PAP), systemic arterial pressure (SAP), and oxygen saturation levels were analyzed. Groups I, II, and III included 25, 3, and 4 patients, respectively. Median weight was 8 kg (range: 3-40 kg), and median age was 7 months (range: 2 days-10 years). On average, iNO treatment was initiated at the 12th hour after admission to the unit (range: 1-48 hours) and continued for a median duration of 24 hours (range: 12-168 hours). Systolic PAP was 40±15 mmHg, mean SAP was 57±18 mmHg, PAP/SAP ratio was 0.69, and oxygen saturation levels were 88% prior to iNO treatment. Following iNO treatment, PAP decreased to 24±9 mmHg (p<0.05), PAP/SAP ratio decreased to 0.4 (p<0.05), SAP showed no change (60±12 mmHg), and saturation levels increased to 98% (p<0.05). Seven patients died during follow-up (Group I, n=5; Group II, n=1; Group III, n=1). iNO seems to effectively reduce PAP, and can be used effectively and safely to prevent pulmonary hypertensive crises in pediatric cardiac intensive care units.

  13. Impact of Stewardship on Inhaled Nitric Oxide Utilization in a Neonatal ICU.

    PubMed

    Elmekkawi, Amir; More, Kiran; Shea, Jennifer; Sperling, Christina; Da Silva, Zelia; Finelli, Michael; Rolnitsky, Asaph; Jankov, Robert P

    2016-10-01

    Inhaled nitric oxide (iNO) remains the "gold standard" therapy for hypoxemic respiratory failure in newborns. Despite good quality evidence to guide iNO use in this population, we observed considerable practice variation, particularly in timing and rate of weaning. To promote evidence-based practice, we launched an iNO stewardship program in April 2013. Our objective was to determine whether iNO stewardship led to changes in iNO utilization and weaning. We conducted a quality improvement project in an outborn quaternary NICU, targeting improved iNO guideline compliance. We compared patterns of iNO utilization between 2 cohorts: prestewardship (April 2011-March 2013; retrospective data collection) and poststewardship (April 2013-March 2015; prospective data collection). Eighty-seven neonates received 88 courses of iNO in the 2 years prestewardship, and 64 neonates received 64 courses of iNO in the 2 years poststewardship. There were no significant differences (P > .05) in patient demographics, in the proportion of patients receiving iNO "off-label," in proportion initiated at the referring hospital, or in outcomes (death or extracorporeal membrane oxygenation). There were significant (P < .05) reductions in median total hours on iNO per patient (47 vs 20; P < .001), in iNO hours per patient from maximum dose to initial wean (28 vs 9; P < .01), and in hours from initial wean to discontinuation (14 vs 8; P < .05). The introduction of iNO stewardship was associated with improved adherence to evidence-based guidelines and an overall reduction in total and per-patient iNO use. Copyright © 2016 by the American Academy of Pediatrics.

  14. Transpulmonary flux of S-nitrosothiols and pulmonary vasodilation during nitric oxide inhalation: role of transport.

    PubMed

    Torok, Jordan A; Brahmajothi, Mulugu V; Zhu, Hongmei; Tinch, Brian T; Auten, Richard L; McMahon, Timothy J

    2012-07-01

    Inhaled nitric oxide (iNO) is used to treat pulmonary hypertension and is being investigated for prevention of bronchopulmonary dysplasia in neonates. Extrapulmonary effects of iNO are widely recognized, but the underlying chemistry and pharmacology are poorly understood. Growing evidence suggests that, in addition to acting via diffusion, NO can be converted into nitrosants capable of reacting with endogenous L-cysteine (L-Cys) in the alveolar lining fluid, forming S-nitrosothiol (SNO)-L-cysteine (CSNO). CSNO can then enter cells via the type L amino acid transporter (LAT). To determine the influence of LAT and supplemental L-Cys on the functional activity of iNO and transpulmonary movement of SNOs or other related species, we exposed C57Bl6 mice to nebulized L-Cys or D-cysteine (D-Cys) and/or LAT competitors. Isolated lungs were then perfused with physiologic buffer while effluent was collected to assay perfusate SNOs. Nebulized L-Cys, but not D-Cys, augmented the iNO-induced increase in circulating SNOs in the effluent without altering iNO-induced pulmonary vasodilation. Addition to the perfusate of either L-leucine (L-Leu) or 2-amino-2-norborane carboxylic acid, two distinct LAT competitors, inhibited appearance in the perfusate of SNOs in L-Cys-exposed lungs; a higher concentration of L-Leu significantly inhibited the iNO-induced pulmonary vasodilation as well as SNO accumulation. We conclude that iNO-induced pulmonary vasodilation and the transpulmonary movement of iNO-derived SNOs are mediated in part by formation of extracellular CSNO, uptake by alveolar epithelial LAT, and/or export by LAT from the pulmonary endothelium into the circulation. Therapies that exploit and optimize LAT-dependent SNO transport might improve the efficacy of and clinical outcomes with NO-based therapy by improving systemic SNO delivery.

  15. Inhalants

    MedlinePlus

    ... lack of coordination, euphoria (a feeling of intense happiness), and dizziness. Some users also experience lightheadedness, hallucinations ( ... on the type of inhalant used, the harmful health effects will differ. The table below lists some ...

  16. 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 ...

  17. Inhaled nitric oxide for the brain dead donor with neurogenic pulmonary edema during anesthesia for organ donation: a case report

    PubMed Central

    Park, Eun Sun; Lee, A-Ran; Lee, Sang Hyun; Kim, An Suk; Park, Soon Eun; Cho, Young Woo

    2014-01-01

    Neurogenic pulmonary edema (NPE) in brain dead organ donors occurring after an acute central nervous system insult threatens organ preservation of potential organ donors and the outcome of organ donation. Hence the active and immediate management of NPE is critical. In this case, a 50-year-old male was admitted to the intensive care unit (ICU) for organ donation. He was hypoxic due to NPE induced by spontaneous intracerebral hemorrhage and intraventricular hemorrhage. Protective ventilatory management, intermittent recruitment maneuvers, and supportive treatment were maintained in the ICU and the operating room (OR). Despite this management, the hypoxemia worsened after the OR admission. So inhaled nitric oxide (NO) therapy was performed during the operation, and the hypoxic phenomena showed remarkable improvement. The organ retrieval was successfully completed. Therefore, NO inhalation can be helpful in the improvement of hypoxemia caused by NPE in brain dead organ donors during anesthesia for the organ donation. PMID:25237451

  18. Fractional Exhaled Nitric Oxide (FeNO) and Spirometry as Indicators of Inhalation Exposure to Chemical Agents in Pathology Workers.

    PubMed

    Suzuki, Ritsuko Arakawa; Irokawa, Toshiya; Ogawa, Hiromasa; Ohkouchi, Shinya; Tabata, Masao; Togashi, Susumu; Nakamura, Takeshi; Ohisa, Noriko; Nikkuni, Etsuhiro; Miura, Emiri; Yoshida, Kaoru; Inomata, Hiroshi; Kurosawa, Hajime

    2017-05-01

    The objective of this study was to examine whether fractional exhaled nitric oxide (FeNO) and spirometry can be used as indices to evaluate adverse health effects of low-concentrated chemical inhalation exposure, mainly to formaldehyde. Thirty-three subjects (pathology technicians) and 30 controls (workers without handling any chemicals in the same hospitals) participated in this study. All participants underwent FeNO measurement and spirometry before and after 5 days of work. FeNO significantly increased in the subjects with a history of asthma (P < 0.05), whereas forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) decreased in the subjects (P < 0.05). Furthermore, work duration and pre-work levels of FEV1 in the subjects had a significant association. The results suggest that FeNO, FVC, and FEV1 represent effective health-effect indices of low-concentrated chemical inhalation exposure.

  19. Concomitant Phosphodiesterase 5 Inhibition Enhances Myocardial Protection by Inhaled Nitric Oxide in Ischemia-Reperfusion Injury.

    PubMed

    Lux, Arpad; Pokreisz, Peter; Swinnen, Melissa; Caluwe, Ellen; Gillijns, Hilde; Szelid, Zsolt; Merkely, Bela; Janssens, Stefan P

    2016-02-01

    Enhanced cyclic guanosine monophosphate (cGMP) signaling may attenuate myocardial ischemia-reperfusion injury (I/R) and improve left ventricular (LV) functional recovery after myocardial infarction (MI). We investigated the cardioprotection afforded by inhaled NO (iNO), the phosphodiesterase 5 (PDE5)-specific inhibitor tadalafil (TAD), or their combination (iNO+TAD) in C57Bl6J mice subjected to 6-minute left anterior descending artery ligation followed by reperfusion. We measured plasma and cardiac concentrations of cGMP during early reperfusion, quantified myocardial necrosis and inflammation by serial troponin-I (TnI) and myeloperoxidase-positive cell infiltration at day 3, and evaluated LV function and remodeling after 4 weeks using echocardiography and pressure-conductance catheterization. Administration of iNO, TAD, or both during I/R was safe and hemodynamically well tolerated. Compared with untreated mice (CON), only iNO+TAD increased plasma and cardiac-cGMP levels during early reperfusion (80 ± 12 versus 36 ± 6 pmol/ml and 0.15 ± 0.02 versus 0.05 ± 0.01 pmol/mg protein, P < 0.05 for both). Moreover, iNO+TAD reduced TnI at 4 hours to a greater extent (P < 0.001 versus CON) than either alone (P < 0.05 versus CON) and was associated with significantly less myocardial inflammatory cell infiltration at day 3. After 4 weeks and compared with CON, iNO+TAD was associated with increased fractional shortening (43 ± 1 versus 33 ± 2%, P < 0.01), larger stroke volumes (14.9 ± 1.2 versus 10.2 ± 0.9 μl, P < 0.05), enhanced septal and posterior wall thickening (P < 0.05 and P < 0.001, respectively), and attenuated LV dilatation (P < 0.001), whereas iNO or TAD alone conferred less benefit. Thus, iNO+TAD has superior efficacy to limit early reperfusion injury and attenuate adverse LV remodeling. Combination of inhaled NO with a long-acting PDE5 inhibitor may represent a promising strategy to reduce ischemic damage following reperfusion and better preserve LV

  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.

  1. Inhaled corticosteroid dose response using domiciliary exhaled nitric oxide in persistent asthma: the FENOtype trial.

    PubMed

    Anderson, William J; Short, Philip M; Williamson, Peter A; Lipworth, Brian J

    2012-12-01

    International guidelines advocate a standard approach to asthma management for all, despite its heterogeneity. "Personalized" treatment of inflammatory asthma phenotypes confers superior benefits. We wished to evaluate dose response to inhaled corticosteroids (ICSs) in patients with asthma with an elevated fractional exhaled nitric oxide (Feno) phenotype using domiciliary measurements. We performed a randomized, crossover trial in 21 patients with mild to moderate persistent asthma receiving ICSs with elevated Feno (>30 parts per billion [ppb]) that increased further (>10 ppb) after ICS washout. Patients were randomized to 2 weeks of either fluticasone propionate 50 μg bid (FP100) or 250 μg bid (FP500). The primary outcome was response in diurnal domiciliary Feno levels. Secondary outcomes included mannitol challenge, serum eosinophilic cationic protein (ECP), blood eosinophil count, and asthma control questionnaire. We found significant dose-related reductions of diurnal Feno compared with baseline - morning Feno: baseline = 71 ppb (95% CI, 61-83 ppb); FP100 = 34 ppb (95% CI, 29-40 ppb), P < .001; FP500 = 27 ppb (95% CI, 22-33 ppb), P < .001; and significant dose separation for morning, P < .05, and evening, P < .001. Time-series Feno displayed exponential decay: FP100 R² = 0.913, half-life = 69 h (95% CI, 50-114 h); FP500 R² = 0.966, half-life = 55 h (95% CI, 45-69 h), as well as diurnal variation. The Asthma Control Questionnaire showed significant improvements exceeding the minimal important difference (>0.5) with values in keeping with controlled asthma (<0.75) after each dose: FP100 = 0.48 (95% CI, 0.24-0.71), P = .004; FP500 = 0.37 (95% CI, 0.18-0.57), P = .001. All other secondary inflammatory related outcomes (mannitol, ECP, and eosinophils) showed significant improvements from baseline but no dose separation. There is a significant dose response of diurnal Feno to ICS in patients with asthma with an elevated Feno phenotype, which translates into well

  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. Effects of various timings and concentrations of inhaled nitric oxide in lung ischemia-reperfusion. The Paris-Sud University Lung Transplantation Group.

    PubMed

    Murakami, S; Bacha, E A; Mazmanian, G M; Détruit, H; Chapelier, A; Dartevelle, P; Hervé, P

    1997-08-01

    Experimental studies reveal that inhaled nitric oxide (NO) can prevent, worsen, or have no effect on lung injury in the setting of ischemia-reperfusion (I-R). We tested the hypothesis that these disparate effects could be related to differences in the timing of administration and/or concentration of inhaled NO during I-R. Isolated rat lungs were subjected to 1-h periods of ischemia followed by 1-h periods of blood reperfusion. We investigated the effects of NO (30 ppm) given during ischemia, NO (30 or 80 ppm) begun immediately at reperfusion, or NO (30 ppm) given 15 min after the beginning of reperfusion, on total pulmonary vascular resistance (PVR), the coefficient of filtration (Kfc), the lung wet/dry weight ratio (W/D) of lung tissue, and lung myeloperoxidase activity (MPO). A control group did not receive NO. NO given during ischemia had no effect on Kfc or MPO, but decreased PVR. NO (30 ppm) during reperfusion (early or delayed) decreased PVR, W/D, Kfc and MPO. NO at 80 ppm decreased PVR and MPO but not W/D or Kfc. In conclusion, NO at 30 ppm, given immediately or in a delayed fashion during reperfusion, attenuates I-R-induced lung injury. NO at 30 ppm given during ischemia or at 80 ppm during reperfusion is not protective.

  4. Inhaled nitric oxide plus iloprost in the setting of post-left assist device right heart dysfunction.

    PubMed

    Antoniou, Theofani; Prokakis, Christos; Athanasopoulos, Georgios; Thanopoulos, Apostolos; Rellia, Panagiota; Zarkalis, Dimitrios; Kogerakis, Nektarios; Koletsis, Efstratios N; Bairaktaris, Andreas

    2012-09-01

    Pulmonary hypertension and right ventricular (RV) dysfunction may complicate the implantation of a left ventricular assist device (LVAD). We examined whether inhaled vasodilators can sufficiently reduce RV afterload, avoiding the need for temporary RV mechanical support. The study includes 7 patients with RV dysfunction after LVAD insertion. Treatment consisted of inotropes, inhaled nitric oxide (10 ppm), and iloprost (10 μg) in repeated doses. Full hemodynamic profile was obtained before inhalation, during administration of inhaled NO alone (before and after iloprost), as well as after the first two doses of inhaled iloprost. Tricuspid annular velocity was estimated at baseline and before and after adding iloprost. There was a statistically significant reduction in pulmonary vascular resistance (PVR), mean pulmonary artery pressure (MPAP), RV systolic pressure, and pulmonary capillary wedge pressure, and a considerable increase in LVAD flow, LV flow rate index, and tricuspid annular velocity at all points of evaluation versus baseline. By the end of the protocol, MPAP/mean systemic arterial pressure, and PVR/systemic vascular resistance ratios were reduced by 0.17±0.03 (95% confidence interval, 0.10 to 0.25, p=0.001) and 0.12±0.025 (95% confidence interval, 0.06 to 0.18; p=0.003), respectively. The tricuspid annular velocity increased by 2.3±0.18 cm/s (95% confidence interval, 1.83 to 2.73 cm/s; p<0.001). Pairwise comparisons before and after iloprost showed an important decrease in PVR (p=0.022), MPAP (p=0.001), pulmonary capillary wedge pressure (p=0.002), and RV systolic pressure (p<0.001), and a rise in tricuspid annular velocity (p=0.008). Inhaled vasodilators mainly affected the pulmonary vasculature. Combination treatment with inhaled NO and iloprost sufficiently decreased PVR and MPAP on the basis of an additive effect, improved RV function, and avoided the need for RV assist device. Copyright © 2012 The Society of Thoracic Surgeons. Published by

  5. 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.

  6. Early Inhaled Budesonide for the Prevention of Bronchopulmonary Dysplasia.

    PubMed

    Bassler, Dirk; Plavka, Richard; Shinwell, Eric S; Hallman, Mikko; Jarreau, Pierre-Henri; Carnielli, Virgilio; Van den Anker, Johannes N; Meisner, Christoph; Engel, Corinna; Schwab, Matthias; Halliday, Henry L; Poets, Christian F

    2015-10-15

    Systemic glucocorticoids reduce the incidence of bronchopulmonary dysplasia among extremely preterm infants, but they may compromise brain development. The effects of inhaled glucocorticoids on outcomes in these infants are unclear. We randomly assigned 863 infants (gestational age, 23 weeks 0 days to 27 weeks 6 days) to early (within 24 hours after birth) inhaled budesonide or placebo until they no longer required oxygen and positive-pressure support or until they reached a postmenstrual age of 32 weeks 0 days. The primary outcome was death or bronchopulmonary dysplasia, confirmed by means of standardized oxygen-saturation monitoring, at a postmenstrual age of 36 weeks. A total of 175 of 437 infants assigned to budesonide for whom adequate data were available (40.0%), as compared with 194 of 419 infants assigned to placebo for whom adequate data were available (46.3%), died or had bronchopulmonary dysplasia (relative risk, stratified according to gestational age, 0.86; 95% confidence interval [CI], 0.75 to 1.00; P=0.05). The incidence of bronchopulmonary dysplasia was 27.8% in the budesonide group versus 38.0% in the placebo group (relative risk, stratified according to gestational age, 0.74; 95% CI, 0.60 to 0.91; P=0.004); death occurred in 16.9% and 13.6% of the patients, respectively (relative risk, stratified according to gestational age, 1.24; 95% CI, 0.91 to 1.69; P=0.17). The proportion of infants who required surgical closure of a patent ductus arteriosus was lower in the budesonide group than in the placebo group (relative risk, stratified according to gestational age, 0.55; 95% CI, 0.36 to 0.83; P=0.004), as was the proportion of infants who required reintubation (relative risk, stratified according to gestational age, 0.58; 95% CI, 0.35 to 0.96; P=0.03). Rates of other neonatal illnesses and adverse events were similar in the two groups. Among extremely preterm infants, the incidence of bronchopulmonary dysplasia was lower among those who received early

  7. [Cost effectiveness and budget impact analysis of inhaled nitric oxide in a neonatal unit from the perspective of the public health system].

    PubMed

    Kilchemmann Fuentes, Carlos; Vallejos Vallejos, Carlos; Román Navarro, Andrés

    Inhaled nitric oxide (iNO) is currently the first-line therapy in severe hypoxaemic respiratory failure of the newborn. Most of regional neonatal centres in Chile do not have this therapeutic alternative. To determine the cost effectiveness of inhaled nitric oxide in the treatment of respiratory failure associated with pulmonary hypertension of the newborn compared to the usual care, including the transfer to a more complex unit. A clinical decision tree was designed from the perspective of Chilean Public Health Service. Incremental cost effectiveness rates (ICER) were calculated, deterministic sensitivity analysis was performed, and probabilistic budget impact was estimated using: TreeAge Pro Healthcare 2014 software. The iNO option leads to an increase in mean cost of $ 11.7 million Chilean pesos (€15,000) per patient treated, with an ICER compared with the usual care of $23 million pesos (€30,000) in case of death or ECMO avoided. By sensitising the results by incidence, it was found that from 7 cases and upwards treated annually, inhaled nitric oxide is less costly than the transfer to a more complex unit. From the perspective of a Chilean regional hospital, incorporating inhaled nitric oxide into the management of neonatal respiratory failure is the optimal alternative in most scenarios. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Successful treatment of acute respiratory distress syndrome after hysterectomy for life-threatening atonic bleeding by inhaled nitric oxide.

    PubMed

    Fujita, Ayaka; Hashiba, Eiji; Otomo, Noriaki; Muraoka, Masatoshi; Kimura, Futoshi; Hirota, Kazuyoshi

    2011-10-01

    We report a case of a 33-year-old female who developed severe acute respiratory distress syndrome (ARDS) after emergency hysterectomy for life-threatening atonic bleeding. A marked decline in pulmonary oxygenation was observed during the surgery, which led to a diagnosis of ARDS. Following admission to the intensive care unit, hypoxia became critical, with a PaO(2)/F(I)O(2) value of 52 even after recruitment maneuvers. Inhaled nitric oxide (NO 10 ppm) was administered to the patient as a rescue treatment, resulting in a gradual but dramatic improvement in pulmonary oxygenation. Although several randomized trials have failed to confirm the beneficial effects of NO on morbidity in patients with ARDS, NO administration is worth consideration as treatment prior to invasive treatments, such as extracorporeal membrane oxygenation, for patients with acute lung injury/ARDS.

  9. Regulation of caveolin-1 expression, nitric oxide production and tissue injury by tumor necrosis factor-alpha following ozone inhalation.

    PubMed

    Fakhrzadeh, Ladan; Laskin, Jeffrey D; Laskin, Debra L

    2008-03-15

    Alveolar macrophages (AM) and inflammatory mediators including nitric oxide and peroxynitrite contribute to ozone-induced lung injury. The generation of these mediators is regulated, in part, by the transcription factor NF-kappaB. We previously demonstrated a critical role for NF-kappaB p50 in ozone-induced injury. In the present studies mechanisms regulating NF-kappaB activation in the lung after ozone inhalation were analyzed. Treatment of wild type (WT) mice with ozone (0.8 ppm, 3 h) resulted in a rapid increase in NF-kappaB binding activity in AM, which persisted for at least 12 h. This was not evident in mice lacking TNFalpha which are protected from ozone-induced injury; there was also no evidence of nitric oxide or peroxynitrite production in lungs from these animals. These data demonstrate that TNFalpha plays a role in NF-kappaB activation and toxicity. TNFalpha signaling involves PI-3-kinase (PI3K)/protein kinase B (PKB), and p44/42 MAP kinase (MAPK) which are important in NF-kappaB activation. Ozone Inhalation resulted in rapid and transient increases in p44/42 MAPK and PI3K/PKB in AM from WT mice, which was evident immediately after exposure. Caveolin-1, a transmembrane protein that negatively regulates PI3K/PKB and p44/42 MAPK signaling, was downregulated in AM from WT mice after ozone exposure. In contrast, ozone had no effect on caveolin-1, PI3K/PKB or p44/42 MAPK expression in AM from TNFalpha knockout mice. These data, together with our findings that TNFalpha suppressed caveolin-1 expression in cultured AM, suggest that TNFalpha and downstream signaling mediate activation of NF-kappaB and the regulation of inflammatory genes important in ozone toxicity, and that this process is linked to caveolin-1.

  10. Effects of early intervention with inhaled sodium cromoglycate in childhood asthma.

    PubMed

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

    2006-01-01

    International and Japanese guidelines classify childhood asthma as mild, moderate, or severe, and recommend treatment with "as needed" bronchodilators, inhaled sodium cromoglycate, and inhaled corticosteroids, respectively. Alternatively, some investigators proposed inhaled corticosteroids as first-line therapy to prevent airway inflammatory obstruction. This article describes a clinical study assessing the effect of early intervention with inhaled sodium cromoglycate in childhood asthma. This was a retrospective study of 189 asthmatic children treated with inhaled sodium cromoglycate for five years and whose age of onset of asthma was six year of age or younger. An end-of-study questionnaire completed the examination. Children administered oral or inhaled corticosteroids simultaneously with sodium cromoglycate, were excluded. Asthma scores as defined by the Japanese Pediatric Allergic Committee, were reduced continuously during the five years after the start of sodium cromoglycate treatment. The frequency of emergency department visits and hospitalizations also decreased. Significant between-period intervention differences showed improvement of clinical outcomes for children with severe asthma during the five years of sodium cromoglycate inhalation. The early intervention regime of starting sodium cromoglycate inhalation within two years of the onset of asthma shows a large improvement in the long-term prognosis of childhood asthma, especially for children with severe asthma. It is possible that starting inhaled sodium cromoglycate earlier than the present recommendation of corticosteroids could further improve clinical outcomes, but a prospective study should be performed to verify our results.

  11. The Association Between Heroin Inhalation and Early Onset Emphysema.

    PubMed

    Walker, Paul P; Thwaite, Erica; Amin, Suzanne; Curtis, John M; Calverley, Peter M A

    2015-11-01

    Inhalation/smoking has become the most common method of recreational opiate consumption in the United Kingdom and other countries. Although some heroin smokers appear to develop COPD, little is known about the association. We present data from a cohort of 73 heroin smokers with clinician-diagnosed and spirometrically confirmed COPD, seen within our clinical service, where symptoms developed before the age of 40 years. The whole group mean age at diagnosis was 41 years, subjects had smoked heroin for 14 years, and mean FEV1 was 1.08 L (31.5% predicted), with mean FEV1/FVC of 0.4. No subject was found to have severe α1-antitrypsin deficiency. Forty-four subjects had either a high-resolution CT (HRCT) scan (32) or measurement of lung diffusion (12). Overall HRCT scan emphysema score averaged across the upper, middle, and lower part of the lung was 2.3 (5%-25% emphysema), with 47% subjects having an upper lobe emphysema score ≥ 3 (25%-50% emphysema). Median diffusing capacity of the lung for carbon monoxide was 48% of predicted value. Recreational smoking of heroin appears to lead to early onset COPD with a predominant emphysema phenotype. This message is important to both clinicians and the public, and targeted screening and education of this high-risk population may be justified.

  12. Hemodynamic effects of combination therapy with inhaled nitric oxide and iloprost in patients with pulmonary hypertension and right ventricular dysfunction after high-risk cardiac surgery.

    PubMed

    Antoniou, Theofani; Koletsis, Efstratios N; Prokakis, Christos; Rellia, Panagiota; Thanopoulos, Apostolos; Theodoraki, Kassiani; Zarkalis, Dimitrios; Sfyrakis, Petros

    2013-06-01

    The purpose of this study was to evaluate the hemodynamic effects of inhaled nitric oxide (NO) plus aerosolized iloprost in patients with pulmonary hypertension/right ventricular dysfunction after cardiac surgery. A retrospective study. A single center. Eight consecutive patients with valve disease and postextracorporeal circulation (ECC) pulmonary hypertension/right ventricular dysfunction. The continuous inhalation of nitric oxide (10 ppm) and iloprost, 10 μg, in repeated doses. The hemodynamic profile was obtained before inhalation, during the administration of inhaled NO alone (prior and after iloprost), and after the first 2 doses of iloprost. Tricuspid annular velocity and tricuspid annular plane systolic excursion were estimated at baseline and before and after adding iloprost. At the end of the protocol, there were significant decreases in pulmonary vascular resistance (p < 0.001), the mean pulmonary arterial pressure (p < 0.001), and the mean pulmonary artery pressure/mean arterial pressure ratio (p = 0.006). Both tricuspid annular velocity (p < 0.001) and tricuspid annular plane systolic excursion (p < 0.001) increased. The cardiac index (p < 0.001) and venous blood oxygen saturation (p = 0.001) increased throughout the evaluation period. Each iloprost dose was associated with further decreases in pulmonary vascular resistances/pressure. By comparing data at the beginning of inhaled NO with those after the second dose of iloprost, the authors noticed decreases in pulmonary vascular resistances (p = 0.004) and the mean pulmonary artery pressure (p = 0.017) and rises in tricuspid annular velocity (p < 0.001) and tricuspid annular systolic plane systolic excursion (p < 0.001). Inhaled NO and iloprost significantly reduced pulmonary hypertension and contributed to the improvement in right ventricular function. Inhaled NO and iloprost have additive effects on pulmonary vasculature. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Inhaled nitric oxide therapy increases blood nitrite, nitrate, and s-nitrosohemoglobin concentrations in infants with pulmonary hypertension.

    PubMed

    Ibrahim, Yomna I; Ninnis, Janet R; Hopper, Andrew O; Deming, Douglas D; Zhang, Amy X; Herring, Jason L; Sowers, Lawrence C; McMahon, Timothy J; Power, Gordon G; Blood, Arlin B

    2012-02-01

    To measure the circulating concentrations of nitric oxide (NO) adducts with NO bioactivity after inhaled NO (iNO) therapy in infants with pulmonary hypertension. In this single center study, 5 sequential blood samples were collected from infants with pulmonary hypertension before, during, and after therapy with iNO (n = 17). Samples were collected from a control group of hospitalized infants without pulmonary hypertension (n = 16) and from healthy adults for comparison (n = 12). After beginning iNO (20 ppm) whole blood nitrite levels increased approximately two-fold within 2 hours (P<.01). Whole blood nitrate levels increased to 4-fold higher than baseline during treatment with 20 ppm iNO (P<.01). S-nitrosohemoglobin increased measurably after beginning iNO (P<.01), whereas iron nitrosyl hemoglobin and total hemoglobin-bound NO-species compounds did not change. Treatment of pulmonary hypertensive infants with iNO results in increases in levels of nitrite, nitrate, and S-nitrosohemoglobin in circulating blood. We speculate that these compounds may be carriers of NO bioactivity throughout the body and account for peripheral effects of iNO in the brain, heart, and other organs. Copyright © 2012 Mosby, Inc. All rights reserved.

  14. Nitric oxide (NO) and phytohormones crosstalk during early plant development.

    PubMed

    Sanz, Luis; Albertos, Pablo; Mateos, Isabel; Sánchez-Vicente, Inmaculada; Lechón, Tamara; Fernández-Marcos, María; Lorenzo, Oscar

    2015-05-01

    During the past two decades, nitric oxide (NO) has evolved from a mere gaseous free radical to become a new messenger in plant biology with an important role in a plethora of physiological processes. This molecule is involved in the regulation of plant growth and development, pathogen defence and abiotic stress responses, and in most cases this is achieved through its interaction with phytohormones. Understanding the role of plant growth regulators is essential to elucidate how plants activate the appropriate set of responses to a particular developmental stage or a particular stress. The first task to achieve this goal is the identification of molecular targets, especially those involved in the regulation of the crosstalk. The nature of NO targets in these growth and development processes and stress responses remains poorly described. Currently, the molecular mechanisms underlying the effects of NO in these processes and their interaction with other plant hormones are beginning to unravel. In this review, we made a compilation of the described interactions between NO and phytohormones during early plant developmental processes (i.e. seed dormancy and germination, hypocotyl elongation and root development).

  15. An evaluation of a new analyser for inhaled nitric oxide administration.

    PubMed

    Carter, B; Holt, M; Tibballs, J; Hochmann, M; Osborne, A

    1998-02-01

    We examined the ability of a new combined nitric oxide (NO)/nitrogen dioxide (NO2) electrochemical analyser (PrinterNOx, Micro Medical Limited, Chatham, Kent, England) to measure NO and NO2 concentrations. The PrinterNOx was compared to a chemiluminescence analyser (42H, Thermo Environmental Instruments Inc, Franklin MA, U.S.A.). NO and NO2 were generated in a standard ventilator circuit using a paediatric ventilator (900C, Siemens Elema, Sweden) connected to an artificial lung (260li, TTL Test Lung, Michigan Instruments, MI, U.S.A.). Forty-four paired NO measurements ranging from 2.56 ppm to 74.6 ppm and 50 paired NO2 measurements ranging from 0.0 ppm to 5.39 ppm were obtained. For the measurement of NO the PrinterNOx showed a tendency to overestimate the chemiluminescence analyser. Regression analysis showed a close relationship between the two analysers with r2 = 0.9981 and a regression equation of y = 1.1658 x +0.0197. In the more clinically important range of 0-25 ppm, r2 increased to 0.9996 with a regression equation of y = 1.1984 x -0.4657. Conversely the PrinterNOx underestimated the chemiluminescence analyser for the measurement of NO2. The regression equation describing this relationship was y = 0.879 x -0.0447 (r2 = 0.9993). We conclude that the PrinterNOx is of sufficient accuracy to be of clinical use in the administration of NO.

  16. Pulmonary vasodilator therapy in the NICU: inhaled nitric oxide, sildenafil, and other pulmonary vasodilating agents.

    PubMed

    Porta, Nicolas F M; Steinhorn, Robin H

    2012-03-01

    The perinatal transition from fetal to extrauterine life requires a dramatic change in the circulatory pattern as the organ of gas exchange switches from the placenta to the lungs. Pulmonary hypertension can occur during early newborn life, and present as early respiratory failure or as a complication of more chronic diseases, such as bronchopulmonary dysplasia. The most effective pharmacotherapeutic strategies for infants with persistent pulmonary hypertension of the newborn are directed at selective reduction of pulmonary vascular resistance. This article discusses currently available therapies for pulmonary hypertension, their biologic rationales, and evidence for their clinical effectiveness.

  17. Adverse Effects of Hemorrhagic Shock Resuscitation with Stored Blood are Ameliorated by Inhaled Nitric Oxide in Lambs

    PubMed Central

    Baron, David M.; Beloiartsev, Arkadi; Nakagawa, Akito; Martyn, Trejeeve; Stowell, Christopher P.; Malhotra, Rajeev; Mayeur, Claire; Bloch, Kenneth D.; Zapol, Warren M.

    2013-01-01

    Objectives Transfusion of stored red blood cells (RBCs) is associated with increased morbidity and mortality in trauma patients. Plasma hemoglobin scavenges nitric oxide (NO), which can cause vasoconstriction, induce inflammation and activate platelets. We hypothesized that transfusion of RBCs stored for prolonged periods would induce adverse effects (pulmonary vasoconstriction, tissue injury, inflammation, and platelet activation) in lambs subjected to severe hemorrhagic shock, and that concurrent inhalation of NO would prevent these adverse effects. Design Animal study. Setting Research laboratory at the Massachusetts General Hospital, Boston, MA. Subjects Seventeen awake Polypay-breed lambs. Interventions Lambs were subjected to 2 h of hemorrhagic shock by acutely withdrawing 50% of their blood volume. Lambs were resuscitated with autologous RBCs stored for 2 h or less (fresh) or 39±2 (mean±SD) days (stored). Stored RBCs were administered with or without breathing NO (80 ppm) during resuscitation and for 21 h thereafter. Measurements and Main Results We measured hemodynamic and oxygenation parameters, markers of tissue injury and inflammation, plasma hemoglobin concentrations, and platelet activation. Peak pulmonary arterial pressure was higher after resuscitation with stored than with fresh RBCs (24±4 vs. 14±2 mmHg, p<0.001) and correlated with peak plasma hemoglobin concentrations (R2=0.56, p=0.003). At 21 h after resuscitation, pulmonary myeloperoxidase activity was higher in lambs resuscitated with stored than with fresh RBCs (11±2 vs. 4±1 U/g, p=0.007). Furthermore, transfusion of stored RBCs increased plasma markers of tissue injury and sensitized platelets to adenosine diphosphate activation. Breathing NO prevented the pulmonary hypertension, and attenuated the pulmonary myeloperoxidase activity, as well as tissue injury and sensitization of platelets to adenosine diphosphate. Conclusions Our data suggest that resuscitation of lambs from hemorrhagic

  18. Association between inflammatory mediators and response to inhaled nitric oxide in a model of endotoxin-induced lung injury

    PubMed Central

    Trachsel, Sebastien; Deby-Dupont, Ginette; Maurenbrecher, Edwige; Nys, Monique; Lamy, Maurice; Hedenstierna, Göran

    2008-01-01

    Introduction Inhaled nitric oxide (INO) allows selective pulmonary vasodilation in acute respiratory distress syndrome and improves PaO2 by redistribution of pulmonary blood flow towards better ventilated parenchyma. One-third of patients are nonresponders to INO, however, and it is difficult to predict who will respond. The aim of the present study was to identify, within a panel of inflammatory mediators released during endotoxin-induced lung injury, specific mediators that are associated with a PaO2 response to INO. Methods After animal ethics committee approval, pigs were anesthetized and exposed to 2 hours of endotoxin infusion. Levels of cytokines, prostanoid, leucotriene and endothelin-1 (ET-1) were sampled prior to endotoxin exposure and hourly thereafter. All animals were exposed to 40 ppm INO: 28 animals were exposed at either 4 hours or 6 hours and a subgroup of nine animals was exposed both at 4 hours and 6 hours after onset of endotoxin infusion. Results Based on the response to INO, the animals were retrospectively placed into a responder group (increase in PaO2 ≥ 20%) or a nonresponder group. All mediators increased with endotoxin infusion although no significant differences were seen between responders and nonresponders. There was a mean difference in ET-1, however, with lower levels in the nonresponder group than in the responder group, 0.1 pg/ml versus 3.0 pg/ml. Moreover, five animals in the group exposed twice to INO switched from responder to nonresponder and had decreased ET-1 levels (3.0 (2.5 to 7.5) pg/ml versus 0.1 (0.1 to 2.1) pg/ml, P < 0.05). The pulmonary artery pressure and ET-1 level were higher in future responders to INO. Conclusions ET-1 may therefore be involved in mediating the response to INO. PMID:18954441

  19. Inhaled nitric oxide alleviates hyperoxia suppressed phosphatidylcholine synthesis in endotoxin-induced injury in mature rat lungs

    PubMed Central

    Gong, Xiaohui; Guo, Chunbao; Huang, Shibing; Sun, Bo

    2006-01-01

    Background We investigated efficacy of inhaled nitric oxide (NO) in modulation of metabolism of phosphatidylcholine (PC) of pulmonary surfactant and in anti-inflammatory mechanism of mature lungs with inflammatory injury. Methods Healthy adult rats were divided into a group of lung inflammation induced by i.v. lipopolysaccharides (LPS) or a normal control (C) for 24 h, and then exposed to: room air (Air), 95% oxygen (O), NO (20 parts per million, NO), both O and NO (ONO) as subgroups, whereas [3H]-choline was injected i.v. for incorporation into PC of the lungs which were processed subsequently at 10 min, 4, 8, 12 and 24 h, respectively, for measurement of PC synthesis and proinflammatory cytokine production. Results LPS-NO subgroup had the lowest level of labeled PC in total phospholipids and disaturated PC in bronchoalveolar lavage fluid and lung tissue (decreased by 46–59%), along with the lowest activity of cytidine triphosphate: phosphocholine cytidylyltransferase (-14–18%) in the lungs, compared to all other subgroups at 4 h (p < 0.01), but not at 8 and 12 h. After 24-h, all LPS-subgroups had lower labeled PC than the corresponding C-subgroups (p < 0.05). LPS-ONO had higher labeled PC in total phospholipids and disaturated PC, activity of cytidylyltransferase, and lower activity of nuclear transcription factor-κB and expression of proinflammatory cytokine mRNA, than that in the LPS-O subgroup (p < 0.05). Conclusion In LPS-induced lung inflammation in association with hyperoxia, depressed PC synthesis and enhanced proinflammatory cytokine production may be alleviated by iNO. NO alone only transiently suppressed the PC synthesis as a result of lower activity of cytidylyltransferase. PMID:16403237

  20. Comparison of inhaled nitric oxide with aerosolized iloprost for treatment of pulmonary hypertension in children after cardiopulmonary bypass surgery.

    PubMed

    Loukanov, Tsvetomir; Bucsenez, Dietrich; Springer, Wolfgang; Sebening, Christian; Rauch, Helmut; Roesch, Eva; Karck, Matthias; Gorenflo, Matthias

    2011-07-01

    Pilot study to compare the effect of inhaled nitric oxide (iNO) and aerosolized iloprost in preventing perioperative pulmonary hypertensive crises (PHTCs). Guidelines recommend the use of iNO to treat PHTCs, but treatment with iNO is not an ideal vasodilator. Aerosolized iloprost may be a possible alternative to iNO in this setting. Investigator-initiated, open-label, randomized clinical trial in 15 infants (age range 77-257 days) with left-to-right shunt (11 out of 15 with additional trisomy 21), and pulmonary hypertension (i.e. mean pulmonary artery pressure [PAP] >25 mmHg) after weaning from cardiopulmonary bypass. Patients were randomized to treatment with iNO at 10 ppm or aerosolized iloprost at 0.5 µg/kg (every 2 h). The observation period was 72 h after weaning from cardiopulmonary bypass. The primary endpoint was the occurrence of PHTCs; the secondary endpoints were mean PAP, duration of mechanical ventilation, safety of administration, and in-hospital mortality. Seven patients received iNO and eight patients received iloprost. During the observation period, 13 of the 15 patients had at least one major or minor PHTC. There was no difference between the groups with regard to the frequency of PHTCs, mean PAP and duration of mechanical ventilation (p > 0.05). In this pilot study, aerosolized iloprost had a favorable safety profile. Larger trials are needed to compare its efficacy to iNO for the treatment of perioperative pulmonary hypertension. However, neither treatment alone abolished the occurrence of PHTCs.

  1. Comparison of acute hemodynamic effects of aerosolized iloprost and inhaled nitric oxide in adult congenital heart disease with severe pulmonary arterial hypertension.

    PubMed

    Caojin, Zhang; Yigao, Huang; Tao, Huang; Wenhui, Huang; Chunli, Xia; Xinsheng, Huang

    2012-01-01

    To compare the acute hemodynamic effects of aerosolized iloprost and inhaled nitric oxide (NO) in adult congenital heart disease (CHD) patients with severe pulmonary arterial hypertension (PAH). One hundred and eighty five adult CHDs with severe PAH were nonrandomized into two groups (iloprost, n=127; NO, n=58). Various hemodynamic parameters were measured before and after iloprost or NO inhalation. Iloprost and NO inhalation resulted in significant reductions in pulmonary arterial pressure (from 110.6±21.8 mmHg to 105.5±22.3 mmHg, p<0.05; from 113.1±18.7 mmHg to 107.2±19.9 mmHg, p<0.05, respectively) and pulmonary vascular resistance (PVR) (from 13.4±8.3 Wood units to 9.6±6.4 Wood units, p<0.01; from 13.7±7.1 Wood units to 9.3±4.9 Wood units, p<0.01, respectively) and increases in pulmonary blood flow (from 6.7±3.3 L/min to 9.4±5.8 L/min, p<0.05; from 6.6±3.1 L/min to 9.6±5.9 L/min, p<0.01, respectively) and the Qp/Qs ratio (from 1.5±0.8 to 2.1±1.4, p<0.01; from 1.5±0.8 to 2.0±1.3, p<0.01, respectively). When the effects of inhaled iloprost and NO were compared, similar reductions in pulmonary arterial pressure and pulmonary vascular resistance were observed. Aerosolized iloprost and inhaled nitric oxide (iNO) were generally well tolerated and no patient experienced any side effects during inhalation. Aerosolized iloprost can be effectively and safely used and might be an alternative to NO for testing pulmonary vascular reactivity and treating severe PAH in adult CHD patients.

  2. The effects of inhaled nitric oxide, gabexate mesilate, and retrograde flush in the lung graft from non-heart beating minipig donors.

    PubMed

    Luh, S P; Tsai, C C; Shau, W Y; Chen, J S; Kuo, S H; Lin-Shiau, S Y; Lee, Y C

    2000-05-27

    The use of lung grafts from non-heart-beating donors (NHBD) is one way of solving the donor organ shortage problem. In this experiment, we studied the effect of retrograde flush (RF) from the left atrium before harvest, inhaled nitric oxide (NO), and gabexate mesilate (FOY), a protease inhibitor, in the lung grafts from NHBD. Forty-eight Lee-Sung, small-ear, miniature pigs (15-20 kg) were divided into 24 pairs (donor and recipient) and four groups. The donor lungs were flushed and harvested 90 min after cardiac arrest. No i.v. heparin was administered until the time before flush and harvest. Left single lung transplantation was undertaken, and the recipients were observed for 18 hr. The grafts warm and cold ischemia times were 90 (controlled) and 183+/-23.4 min. Group 1 (untreated control, UC, n=6) had core perfusion through a Swan-Ganz catheter followed by a single, antegrade flush with modified Euro-Collin's solution containing heparin, urokinase, and PGE1. Group 2 (RF group, n=6) had the same as group 1, except that one additive retrograde flush through the left atrium was administered. Group 3 (NO group, n=6) had the same as group 1, except that 20 parts per million (ppm) inhaled NO was administered for the cadaver donors before the graft harvest, and for the recipients after the grafts reperfusion. Group 4 (FOY group, n=6) had the same as group 1, except that the recipients received FOY i.v. infusion from the beginning of the recipient's operation and continuously throughout the experiments. Compared with the group 1 (control), group 2 (RF) had significantly (P<0.05) lower mean pulmonary artery pressure, pulmonary vascular resistance (PVR), lung wet/dry ratio, histological lung injury score, and higher PaO2/FiO2 and pulmonary dynamic compliance. Group 3 (NO) had significantly lower mean pulmonary arterial pressure, PVR, lung injury score, degree of tissue neutrophils infiltration (histological and myeloperoxidase assay), bronchoalveolar lavage fluid protein

  3. Early treatment with inhaled antibiotics postpones next occurrence of Achromobacter in cystic fibrosis.

    PubMed

    Wang, M; Ridderberg, W; Hansen, C R; Høiby, N; Jensen-Fangel, S; Olesen, H V; Skov, M; Lemming, L E; Pressler, T; Johansen, H K; Nørskov-Lauritsen, N

    2013-12-01

    In this nationwide retrospective study, we analysed species distribution, antimicrobial susceptibility and time to next occurrence of Achromobacter in Danish cystic fibrosis (CF) patients from 2000 to 2011. Thirty-four primary isolates were identified to species level and subjected to antimicrobial susceptibility testing. Effectiveness of early antimicrobial treatment was assessed by a Kaplan-Meier estimation of time to recurrence. Achromobacter xylosoxidans accounted for 13 (38%) of the isolates, and an unnamed species accounted for 11 (32%) of the isolates. Meropenem, piperacillin-tazobactam and trimethoprim-sulfamethoxazole were highly active against chemotherapy-naïve Achromobacter, while ceftazidime, colistin and tobramycin were judged adequate for inhalation therapy. Fifty-five percent of 25 patients treated with inhaled ceftazidime, colistin, or tobramycin remained free of Achromobacter three years after acquisition, in contrast to 17% of 22 patients who did not receive inhaled antibiotics (P<0.01). Early treatment with inhaled antibiotics may prevent or postpone chronic infection with Achromobacter in CF patients. Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  4. Effects of pulse-delivered inhaled nitric oxide administration on pulmonary perfusion and arterial oxygenation in dorsally recumbent isoflurane-anesthetized horses.

    PubMed

    Grubb, Tamara L; Lord, Peter F; Berger, Mieth; Larsson, Christina; Rydén, Anneli; Frendin, Jan; Funkquist, Pia; Edner, Anna; Nyman, Görel

    2014-11-01

    To image the spatial distribution of pulmonary blood flow by means of scintigraphy, evaluate ventilation-perfusion (VA/Q) matching and pulmonary blood shunting (Qs/Qt) by means of the multiple inert gas elimination technique (MIGET), and measure arterial oxygenation and plasma endothelin-1 concentrations before, during, and after pulse-delivered inhaled nitric oxide (PiNO) administration to isoflurane-anesthetized horses in dorsal recumbency. 3 healthy adult Standardbreds. Nitric oxide was pulsed into the inspired gases in dorsally recumbent isoflurane-anesthetized horses. Assessment of VA/Q matching, Qs/Qt, and Pao2 content was performed by use of the MIGET, and spatial distribution of pulmonary blood flow was measured by perfusion scintigraphy following IV injection of technetium Tc 99m-labeled macroaggregated human albumin before, during, and 30 minutes after cessation of PiNO administration. During PiNO administration, significant redistribution of blood flow from the dependent regions to the nondependent regions of the lungs was found and was reflected by improvements in VA/Q matching, decreases in Qs/Qt, and increases in Pao2 content, all of which reverted to baseline values at 30 minutes after PiNO administration. Administration of PiNO in anesthetized dorsally recumbent horses resulted in redistribution of pulmonary blood flow from dependent atelectatic lung regions to nondependent aerated lung regions. Because hypoxemia is commonly the result of atelectasis in anesthetized dorsally recumbent horses, the addition of nitric oxide to inhaled gases could be used clinically to alleviate hypoxemia in horses during anesthesia.

  5. Effects of early intervention with inhaled budesonide on lung function in newly diagnosed asthma.

    PubMed

    O'Byrne, Paul M; Pedersen, Søren; Busse, William W; Tan, Wan C; Chen, Yu-Zhi; Ohlsson, Stefan V; Ullman, Anders; Lamm, Carl Johan; Pauwels, Romain A

    2006-06-01

    Asthmatic patients lose lung function faster than normal subjects. The effectiveness of early intervention with inhaled corticosteroids on this decline in lung function is not established in recent-onset disease. The Inhaled Steroid Treatment as Regular Therapy in Early Asthma study was a randomized, double-blind study in 7,165 patients (5 to 66 years old), with persistent asthma for < 2 years to determine whether early intervention with low-dose inhaled budesonide prevents severe asthma-related events and the decline in lung function. Patients received budesonide (200 mug qd for children < 11 years old and 400 mug qd for others) or placebo for 3 years in addition to usual asthma medications. Treatment with budesonide significantly improved prebronchodilator and postbronchodilator FEV(1) percentage of predicted and reduced the mean declines from baseline for postbronchodilator FEV(1) at 1 year and 3 years: - 0.62% and - 1.79% for budesonide and - 2.11% and - 2.68% for placebo, respectively (p < 0.001). The decline was more marked for male patients, active smokers, and patients > 18 years old, and the smallest treatment effects were in adolescents. Long-term, once-daily treatment with low-dose budesonide improved both prebronchodilator and postbronchodilator FEV(1) in patients with recent-onset, persistent asthma, and reduced the loss of lung function over time.

  6. [Effect of nebulised iloprost combined with inhaled nitric oxide and oral sildenafil on lung transplant patients. Therapeutic efficacy in pulmonary hypertension during surgery].

    PubMed

    Rabanal Llevot, J M; Cimadevilla Calvo, B; Cifrian Martinez, J M; Ruisanchez Villar, C; Mons Lera, R

    2012-03-01

    There is a high incidence of pulmonary hypertension during the lung transplant peri-operative period, and could lead to a haemodynamic deterioration that may require the need of extracorporeal circulation. Our aim was to study the haemodynamic effects on the pulmonary and systemic circulation of the combination of inhaled nitric oxide and iloprost and oral sildenafil in patients with severe pulmonary hypertension during lung transplant surgery. Seventeen patients received 10μg of nebulised iloprost during the peri-operative period of the lung transplant when their mean pulmonary pressure exceeded 50mmHg. AU the patients received 50mg of oral sildenafil 30min before anaesthetic induction, 20ppm of inhaled nitric oxide after tracheal intubation. The haemodynamic and respiratory variables were recorded at baseline (after anaesthetic induction), prior to the administering of iloprost, and at 5 and 30min after it was given. The administering of iloprost significantly reduced the pulmonary arterial pressure and significantly increases the cardiac Índex and the right ventrícular ejection fractíon. There were no signíficant changes occurred in the systemic arterial pressure. The triple combination significantly reduces the pulmonary pressures in the lung transplant peri-operative and should be considered when there is severe pulmonary hypertension during the surgery or during the immediate post-operative period of lung transplantation. Copyright © 2010 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España.. All rights reserved.

  7. Inhaled nitric oxide alters the distribution of blood flow in the healthy human lung, suggesting active hypoxic pulmonary vasoconstriction in normoxia.

    PubMed

    Asadi, Amran K; Sá, Rui Carlos; Kim, Nick H; Theilmann, Rebecca J; Hopkins, Susan R; Buxton, Richard B; Prisk, G Kim

    2015-02-01

    Hypoxic pulmonary vasoconstriction (HPV) is thought to actively regulate ventilation-perfusion (V̇a/Q̇) matching, reducing perfusion in regions of alveolar hypoxia. We assessed the extent of HPV in the healthy human lung using inhaled nitric oxide (iNO) under inspired oxygen fractions (FiO2 ) of 0.125, 0.21, and 0.30 (a hyperoxic stimulus designed to abolish HPV without the development of atelectasis). Dynamic measures of blood flow were made in a single sagittal slice of the right lung of five healthy male subjects using an arterial spin labeling (ASL) MRI sequence, following a block stimulus pattern (3 × 60 breaths) with 40 ppm iNO administered in the central block. The overall spatial heterogeneity, spatiotemporal variability, and regional pattern of pulmonary blood flow was quantified as a function of condition (FiO2 × iNO state). While spatial heterogeneity did not change significantly with iNO administration or FiO2 , there were statistically significant increases in Global Fluctuation Dispersion, (a marker of spatiotemporal flow variability) when iNO was administered during hypoxia (5.4 percentage point increase, P = 0.003). iNO had an effect on regional blood flow that was FiO2 dependent (P = 0.02), with regional changes in the pattern of blood flow occurring in hypoxia (P = 0.007) and normoxia (P = 0.008) tending to increase flow to dependent lung at the expense of nondependent lung. These findings indicate that inhaled nitric oxide significantly alters the distribution of blood flow in both hypoxic and normoxic healthy subjects, and suggests that some baseline HPV may indeed be present in the normoxic lung. Copyright © 2015 the American Physiological Society.

  8. A pilot study of inhaled nitric oxide in preterm infants treated with nasal continuous positive airway pressure for respiratory distress syndrome.

    PubMed

    Lindwall, Robert; Blennow, Mats; Svensson, Mats; Jonsson, Baldvin; Berggren-Boström, Eva; Flanby, Martino; Lönnqvist, Per-Arne; Frostell, Claes; Norman, Mikael

    2005-07-01

    To explore the acute effects of inhaled nitric oxide (iNO) on oxygenation, respiratory rate, and CO2 levels in spontaneously breathing preterm infants treated with nasal continuous positive airway pressure (nCPAP) for moderate respiratory distress syndrome (RDS). Randomized, prospective, double-blind, cross-over study in the neonatal intensive care units of a university hospital. 15 infants treated for RDS, with a median gestational age of 32 weeks (27-36), birth weight 1940 g (1100-4125), and postnatal age at the beginning of study 23 h (3-91). nCPAP pressure was kept constant at 4.3 cmH2O (3.4-5.1). We examined effects on gas exchange and vital signs during a 30-min exposure to 10 ppm iNO or placebo gas (nitrogen). Before administering test gases the baseline arterial to alveolar oxygen tension ratio (aAPO2) was 0.19+/-0.06. aAPO2 remained unchanged during placebo but increased to 0.22+/-0.05 (+20%) during iNO exposure. Respiratory rate and arterial carbon dioxide tension remained unchanged, as did heart rate, blood pressure, and methemoglobin. Follow-up at 30 days of age showed no deaths, delayed morbidity, or need for supplemental oxygen. Adding 10 ppm nitric oxide to nasal CPAP treatment in preterm infants suffering from RDS results in a moderate but statistically significant improvement in oxygenation, with no effect on respiratory drive or systemic circulatory parameters.

  9. [Nitric oxide].

    PubMed

    Rovira, I

    1995-01-01

    Nitric oxide was identified as the relaxing factor derived from the endothelium in 1987. Nitric oxide synthesis allows the vascular system to maintain a state of vasodilation, thereby regulating arterial pressure. Nitric oxide is also found in platelets, where it inhibits adhesion and aggregation; in the immune system, where it is responsible for the cytotoxic action of macrophages; and in the nervous system, where it acts as neurotransmitter. A deficit in endogenous synthesis of nitric oxide contributes to such conditions as essential arterial hypertension, pulmonary hypertension and heart disease. An excess of nitrous oxide induced by endotoxins and cytokinins, meanwhile, is believed to be responsible for hypotension in septic shock and for hyperdynamic circulatory state in cirrhosis of the liver. Nitric oxide has also been implicated in the rejection of transplanted organs and in cell damage after reperfusion. Inhaled nitrous oxide gas reduces pulmonary hypertension without triggering systemic hypotension in both experimental and clinical conditions. It also produces selective vasodilation when used to ventilate specific pulmonary areas, thereby improving the ventilation/perfusion ratio and, hence, oxygenation. Nitric oxide inhalation is effective in pulmonary hypertension-coincident with chronic obstructive lung disease, in persistent neonatal pulmonary hypertension and in pulmonary hypertension with congenital or acquired heart disease. Likewise, it reduces intrapulmonary shunt in acute respiratory failure and improves gas exchange. Under experimental conditions nitric oxide acts as a bronchodilator, although it seems to be less effective for this purpose in clinical use.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Inhalant abuse

    PubMed Central

    Baydala, L

    2010-01-01

    Inhalant abuse – also known as volatile substance abuse, solvent abuse, sniffing, huffing and bagging – is the deliberate inhalation of a volatile substance to achieve an altered mental state. Inhalant abuse is a worldwide problem that is especially common in individuals from minority and marginalized populations, and is strongly correlated with the social determinants of health. It often affects younger children, compared with other forms of substance abuse, and crosses social and ethnic boundaries. Inhalants are pharmacologically diverse products that are selected for their low price, legal and widespread availability, and ability to rapidly induce euphoria. Chronic abuse is associated with serious and often irreversible effects. Widespread screening and early referrals to treatment programs have resulted in significant improvements in the mental, physical and social conditions of those affected. The present statement reviews critical aspects of inhalant abuse, highlighting new information and data that pertain to Aboriginal children and youth, and provides recommendations for treatment and prevention. PMID:21886449

  11. The Inhaled Steroid Treatment As Regular Therapy in Early Asthma (START) study 5-year follow-up: effectiveness of early intervention with budesonide in mild persistent asthma.

    PubMed

    Busse, William W; Pedersen, Søren; Pauwels, Romain A; Tan, Wan C; Chen, Yu-Zhi; Lamm, Carl Johan; O'Byrne, Paul M

    2008-05-01

    The Inhaled Steroid Treatment as Regular Therapy in Early Asthma (START) study enrolled 7241 patients aged 5 to 66 years with recent-onset, mild persistent asthma to assess early intervention with the inhaled corticosteroid budesonide on long-term asthma control. The open-label phase of the START study was included to determine the effect on lung function and asthma control of adding budesonide to the reference group patients who had not initially received inhaled corticosteroids. Patients were randomized to double-blind treatment with budesonide, 200 mug (those aged < 11 years) or 400 mug once daily, or placebo plus the usual asthma therapy for 3 years, after which all patients received 2 years of open-label treatment with budesonide once daily. During the full 5-year study period, postbronchodilator FEV(1) percent predicted decreased, irrespective of randomized treatment during the double-blind phase, by an average of 2.22% (SE, 0.15%). However, patients with inhaled budesonide in the double-blind phase had a significantly lower risk (odds ratio, 0.61; P < .001) of a severe asthma-related event during the full 5-year study period than those in the reference group. Moreover, patients in the reference group used more additional asthma medications during both the open-label and double-blind phases. In mild persistent asthma early intervention with inhaled budesonide was associated with improved asthma control and less additional asthma medication use.

  12. 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

  13. 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

  14. Combined early fluid resuscitation and hydrogen inhalation attenuates lung and intestine injury

    PubMed Central

    Liu, Wei; Shan, Li-Ping; Dong, Xue-Song; Liu, Xiao-Wei; Ma, Tao; Liu, Zhi

    2013-01-01

    AIM: To study the effects of combined early fluid resuscitation and hydrogen inhalation on septic shock-induced lung and intestine injuries. METHODS: Wistar male rats were randomly divided into four groups: control group (Group A, n = 15); septic shock group (Group B, n = 15); early fluid resuscitation-treated septic shock group (Group C, n = 15); and early fluid resuscitation and inhalation of 2% hydrogen-treated septic shock group (Group D, n = 15). The activity of hydroxyl radicals, myeloperoxidase (MPO), superoxide dismutase (SOD), diamine oxidase (DAO), and the concentration of malonaldehyde (MDA) in the lung and intestinal tissue were assessed according to the corresponding kits. Hematoxylin and eosin staining was carried out to detect the pathology of the lung and intestine. The expression levels of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α in lung and intestine tissue were detected by enzyme-linked immunosorbent assay method. The expression levels of Fas and Bcl2 in lung tissues were determined by immunohistochemistry and Western blotting. RESULTS: Septic shock elicited a significant increase in the levels of MDA (10.17 ± 1.12 nmol/mg protein vs 2.98 ± 0.64 nmol/mg protein) and MPO (6.79 ± 1.02 U/g wet tissue vs 1.69 ± 0.14 U/g wet tissue) in lung tissues. These effects were not significantly decreased by Group C pretreatment, but were significantly reduced by Group D pretreatment (MDA: 4.45 ± 1.13 nmol/mg protein vs 9.56 ± 1.37 nmol/mg protein; MPO: 2.58 ± 0.21 U/g wet tissue vs 6.02 ± 1.16 U/g wet tissue). The activity of SOD (250.32 ± 8.56 U/mg protein vs 365.78 ± 10.26 U/mg protein) in lung tissues was decreased after septic shock, and was not significantly increased by Group C pretreatment, but was significantly enhanced by Group D pretreatment (331.15 ± 9.64 U/mg protein vs 262.98 ± 5.47 U/mg protein). Histological evidence of lung hemorrhage, neutrophil infiltration and overexpression of IL-6, IL-8, and TNF-α was

  15. Combined early fluid resuscitation and hydrogen inhalation attenuates lung and intestine injury.

    PubMed

    Liu, Wei; Shan, Li-Ping; Dong, Xue-Song; Liu, Xiao-Wei; Ma, Tao; Liu, Zhi

    2013-01-28

    To study the effects of combined early fluid resuscitation and hydrogen inhalation on septic shock-induced lung and intestine injuries. Wistar male rats were randomly divided into four groups: control group (Group A, n = 15); septic shock group (Group B, n = 15); early fluid resuscitation-treated septic shock group (Group C, n = 15); and early fluid resuscitation and inhalation of 2% hydrogen-treated septic shock group (Group D, n = 15). The activity of hydroxyl radicals, myeloperoxidase (MPO), superoxide dismutase (SOD), diamine oxidase (DAO), and the concentration of malonaldehyde (MDA) in the lung and intestinal tissue were assessed according to the corresponding kits. Hematoxylin and eosin staining was carried out to detect the pathology of the lung and intestine. The expression levels of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α in lung and intestine tissue were detected by enzyme-linked immunosorbent assay method. The expression levels of Fas and Bcl2 in lung tissues were determined by immunohistochemistry and Western blotting. Septic shock elicited a significant increase in the levels of MDA (10.17 ± 1.12 nmol/mg protein vs 2.98 ± 0.64 nmol/mg protein) and MPO (6.79 ± 1.02 U/g wet tissue vs 1.69 ± 0.14 U/g wet tissue) in lung tissues. These effects were not significantly decreased by Group C pretreatment, but were significantly reduced by Group D pretreatment (MDA: 4.45 ± 1.13 nmol/mg protein vs 9.56 ± 1.37 nmol/mg protein; MPO: 2.58 ± 0.21 U/g wet tissue vs 6.02 ± 1.16 U/g wet tissue). The activity of SOD (250.32 ± 8.56 U/mg protein vs 365.78 ± 10.26 U/mg protein) in lung tissues was decreased after septic shock, and was not significantly increased by Group C pretreatment, but was significantly enhanced by Group D pretreatment (331.15 ± 9.64 U/mg protein vs 262.98 ± 5.47 U/mg protein). Histological evidence of lung hemorrhage, neutrophil infiltration and overexpression of IL-6, IL-8, and TNF-α was observed in lung tissues

  16. Exhaled nitric oxide, systemic inflammation, and the spirometric response to inhaled fluticasone propionate in severe chronic obstructive pulmonary disease: a prospective study.

    PubMed

    Kunisaki, Ken M; Rice, Kathryn L; Janoff, Edward N; Rector, Thomas S; Niewoehner, Dennis E

    2008-04-01

    A subset of patients with chronic obstructive pulmonary disease (COPD) may respond more favorably to inhaled corticosteroids (ICS), but no simple method is currently utilized to predict the presence or absence of ICS responses in patients with COPD.We evaluated the ability of exhaled nitric oxide (FENO) and serum inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6], and interleukin-8 [IL-8]) to independently predict spirometric responses to ICS in patients with COPD. Among 60 ex-smokers with severe COPD (mean FEV1 1.07 L, 36% of predicted), we conducted a single-arm, open-label study. Participants spent four weeks free of any ICS, followed by four weeks of ICS use (fluticasone propionate 500 mcg twice daily). FENO, CRP, IL-6, IL-8, and pre-bronchodilator spirometry were measured immediately before and after the four weeks of ICS use. Baseline FENO, CRP, IL-6, and IL-8 showed no correlations to FEV1 responses to ICS. ICS responders (increase in FEV1 > or = 200 mL after four weeks of ICS) did have significantly higher baseline FENO levels compared with non-responders (46.5 parts per billion [ppb] vs. 25 ppb, p = 0.028). The receiver operating characteristic curve for FENO to discriminate responders from non-responders had an area under curve of 0.72. Baseline serum inflammatory markers did not differ between responders and non-responders. In ex-smokers with severe COPD, a measure of local pulmonary inflammation, FENO, may be more closely associated with FEV1 responses to four weeks of ICS than are standard markers of systemic inflammation, serum CRP, IL-6, and IL-8.

  17. Relationship between Fractional Exhaled Nitric Oxide Level and Efficacy of Inhaled Corticosteroid in Asthma-COPD Overlap Syndrome Patients with Different Disease Severity

    PubMed Central

    2017-01-01

    This study explored the relationship between the fractional exhaled nitric oxide (FeNO) level and the efficacy of inhaled corticosteroid (ICS) in asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) patients with different disease severity. A total of 127 ACOS patients with ACOS (case group) and 131 healthy people (control group) were enrolled in this study. Based on the severity of COPD, the ACOS patients were divided into: mild ACOS; moderate ACOS; severe ACOS; and extremely severe ACOS groups. We compared FeNO levels, pulmonary function parameters including percentage of forced expiratory volume in 1 second (FEV1) to predicted value (FEV1%pred), ratio of FEV1 to forced vital capacity (FEV1/FVC), inspiratory capacity to total lung capacity (IC/TLC) and residual volume to total lung capacity (RV/TLC), arterial blood gas parameters, including PH, arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2), total serum immunoglobulin E (IgE), induced sputum eosinophil (EOS), plasma surfactant protein A (SP-A), plasma soluble receptor for advanced glycation end products (sRAGE), sputum myeloperoxidase (MPO), sputum neutrophil gelatinase-associated lipocalin (NGAL) and Asthma Control Test (ACT) scores, and COPD Assessment Test (CAT) scores. Compared with pre-treatment parameters, the FeNO levels, RV/TLC, PaCO2, total serum IgE, induced sputum EOS, plasma SP-A, sputum MPO, sputum NGAL, and CAT scores were significantly decreased after 6 months of ICS treatment, while FEV1%pred, FEV1/FVC, IC/TLC, PH, PaO2, plasma sRAGE, and ACT scores were significantly increased in ACOS patients with different disease severity after 6 months of ICS treatment. This finding suggests that the FeNO level may accurately predict the efficacy of ICS in the treatment of ACOS patients. PMID:28145647

  18. Acute right heart failure after hemorrhagic shock and trauma pneumonectomy-a management approach: A blinded randomized controlled animal trial using inhaled nitric oxide.

    PubMed

    Lubitz, Andrea L; Sjoholm, Lars O; Goldberg, Amy; Pathak, Abhijit; Santora, Thomas; Sharp, Thomas E; Wallner, Markus; Berretta, Remus M; Poole, Lauren A; Wu, Jichuan; Wolfson, Marla R

    2017-02-01

    Hemorrhagic shock and pneumonectomy causes an acute increase in pulmonary vascular resistance (PVR). The increase in PVR and right ventricular (RV) afterload leads to acute RV failure, thus reducing left ventricular (LV) preload and output. Inhaled nitric oxide (iNO) lowers PVR by relaxing pulmonary arterial smooth muscle without remarkable systemic vascular effects. We hypothesized that with hemorrhagic shock and pneumonectomy, iNO can be used to decrease PVR and mitigate right heart failure. A hemorrhagic shock and pneumonectomy model was developed using sheep. Sheep received lung protective ventilatory support and were instrumented to serially obtain measurements of hemodynamics, gas exchange, and blood chemistry. Heart function was assessed with echocardiography. After randomization to study gas of iNO 20 ppm (n = 9) or nitrogen as placebo (n = 9), baseline measurements were obtained. Hemorrhagic shock was initiated by exsanguination to a target of 50% of the baseline mean arterial pressure. The resuscitation phase was initiated, consisting of simultaneous left pulmonary hilum ligation, via median sternotomy, infusion of autologous blood and initiation of study gas. Animals were monitored for 4 hours. All animals had an initial increase in PVR. PVR remained elevated with placebo; with iNO, PVR decreased to baseline. Echo showed improved RV function in the iNO group while it remained impaired in the placebo group. After an initial increase in shunt and lactate and decrease in SvO2, all returned toward baseline in the iNO group but remained abnormal in the placebo group. These data indicate that by decreasing PVR, iNO decreased RV afterload, preserved RV and LV function, and tissue oxygenation in this hemorrhagic shock and pneumonectomy model. This suggests that iNO may be a useful clinical adjunct to mitigate right heart failure and improve survival when trauma pneumonectomy is required.

  19. Inhaled nitric oxide improves short term memory and reduces the inflammatory reaction in a mouse model of mild traumatic brain injury.

    PubMed

    Liu, Ping; Li, Yong-Sheng; Quartermain, David; Boutajangout, Allal; Ji, Yong

    2013-07-19

    Although the mechanisms underlying mild traumatic brain injury (mTBI) are becoming well understood, treatment options are still limited. In the present study, mTBI was induced by a weight drop model to produce a closed head injury to mice and the effect of inhaled nitric oxide (INO) was evaluated by a short term memory task (object recognition task) and immunohistochemical staining of glial fibrillary acidic protein (GFAP) and CD45 for the detection of reactive astrocytes and microglia. Results showed that mTBI model did not produce brain edema, skull fracture or sensorimotor coordination dysfunctions. Mice did however exhibit a significant deficit in short term memory (STM) and strong inflammatory reaction in the ipsilateral cortex and hippocampus compared to sham-injured controls 24h after mTBI. Additional groups of untreated mice tested 3 and 7 days later, demonstrated that recognition memory had recovered to normal levels by Day 3. Mice treated with 10ppm INO for 4 or 8h, beginning immediately after TBI demonstrated significantly improved STM at 24h when compared with room air controls (p<0.05). Whereas mice treated with 10ppm INO for 24h showed no improvement in STM. Mice treated with INO 10ppm for 8h exhibited significantly reduced microglia and astrocyte activation compared with room air controls. These data demonstrate that mTBI produces a disruption of STM which is evident 24h after injury and persists for 2-3 days. Treatment with low concentration or short durations of INO prevents this memory loss and also attenuates the inflammatory response. These findings may have relevance for the treatment of patients diagnosed with concussion. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Analgesic Effects of Inhalation of Nitric Oxide (Entonox) and Parenteral Morphine Sulfate in Patients with Renal Colic; A Randomized Clinical Trial

    PubMed Central

    Kariman, Hamid; Majidi, Alireza; Taheri, Sara; Shahrami, Ali; Hatamabadi, Hamid Reza

    2015-01-01

    Objective: To compare the analgesiceffects of Nitrous oxide and morphine sulfate in patients with acute renal colic due to urolithiasis. Methods: This was randomized clinical trial being performed in Imam Hossein hospital affiliated with Shahid Beheshti University of Medical Sciences during a 1-year period from May2013 to May2014.  A total of number of 100 patients, with an age range of 20-50 years, who presented with renal colic secondary to urolithiasis confirmed by ultrasonography were randomly assigned to receive morphine sulfate injection (0.1 mg/kg) with 100 mg diclofenac suppository (n=50) or Entonox exhalation (50% nitric oxide and 50% oxygen) for 30-minutes with 100 mg diclofenac suppository (n=50). Quantitative measurement was of pain was performed according to a visual analogue scale (VAS), before, 3, 5, 10 and 30-minute after the intervention. The pain severity and side effects were measured between two study groups. Results: The baseline characteristics of the patients in two study groups were comparable. The frequencies of pain persistence (at least 50%) at 3-, 5-, 10- and 30-minute intervals in morphine sulfategroup were 96%, 80%, 50% and 8%, respectively; these frequencies in Entonex  were 82%, 42%, 12% and 2%, respectively (p<0.001). Cox regression modeling showed that use of Entonox was the only effective agent in the success of treatment, compared to the use of morphine, i.e. use of Entonox increased the success of treatment up to 2.1 folds compared to the use of morphine (HR=2.1; 95% CI: 1.2-3.6; p=0.006). Conclusion: The results of the present study demonstrate that inhalation of Entonox is an effective and safe analgesic regimen for acute renal colic. It acts more rapidly and is more potent in relieving renal colic when compared to morphine sulfate.Entonox can be regarded as an appropriate alternative to analgesics like opioids in this ground. PMID:27162902

  1. Effect of modulators of hypoxic pulmonary vasoconstriction on the response to inhaled nitric oxide in a neonatal model of severe pulmonary atelectasis.

    PubMed

    Eyal, F G; Hachey, W E; Curtet-Eyal, N L; Kellum, F E; Alpan, G

    1996-06-01

    Hypoxic pulmonary vasoconstriction (HPV) is an intrinsic mechanism that facilitates ventilation to perfusion matching and preservation of oxygenation. We investigated the neonatal HPV response from extensive atelectasis and tested the hypothesis that (I) the resulting hypoxemia is corrected by inhaled nitric oxide (NO); (2) the "pulmonary steal" of blood away from hypoxic area is further improved by modulators of the HPV. Intratracheal injection of steel beads in 32 piglets (7 to 20 days) resulted in atelectasis of 50% to 75% of the lungs. The piglets were then randomized to receive saline (control), indomethacin (IND) 2 mg/kg, doxapram (DOX) 0.5 mg/kg/h or almitrine (ALM) 4 micrograms/kg/min. After 30 minutes, all animals were subjected to NO at 40 ppm. Atelectasis resulted in severe impairment in oxygenation (PaO2 - 105 +/- 6 mm Hg, AaDO2 = 536 +/- 9 mm Hg; shunt fraction = 31% +/- 2%) and moderate pulmonary hypertension. Mean pulmonary artery pressure (PAP) increased to 35 +/- 0.8 mm Hg. NO reduced pulmonary vascular resistance (PVR) from 128 +/- 14 mm Hg/kg/mL/min to 74 +/- 9 mm Hg/kg/mL/min and improved gas exchange (PaO2 = 180 +/- 50 and AaDO2 = 438 +/- 50 mm Hg). Following the development of atelectasis, the peripheral chemoreceptor agonists (ALM and DOX) did not modify gas exchange and had no significant cardiovascular effect. ALM and DOX failed to enhance the response to NO. IND did not alter HPV, but prevented the improvement in gas exchange associated with NO-induced pulmonary vasodilation.

  2. A pilot study to assess effects of long-term inhalation of airborne particulate matter on early Alzheimer-like changes in the mouse brain.

    PubMed

    Bhatt, Dhaval P; Puig, Kendra L; Gorr, Matthew W; Wold, Loren E; Combs, Colin K

    2015-01-01

    Exposure to air pollutants, including particulate matter, results in activation of the brain inflammatory response and Alzheimer disease (AD)-like pathology in dogs and humans. However, the length of time required for inhalation of ambient particulate matter to influence brain inflammation and AD pathology is less clear. Here, we studied the effect of 3 and 9 months of air particulate matter (<2.5 μm diameter, PM2.5) exposure on brain inflammatory phenotype and pathological hallmarks of AD in C57BL/6 mice. Using western blot, ELISA, and cytokine array analysis we quantified brain APP, beta-site APP cleaving enzyme (BACE), oligomeric protein, total Aβ 1-40 and Aβ 1-42 levels, inducible nitric oxide synthase (iNOS), nitrotyrosine-modified proteins, HNE-Michael adducts, vascular cell adhesion molecule 1 (VCAM-1), glial markers (GFAP, Iba-1), pre- and post- synaptic markers (synaptophysin and PSD-95), cyclooxygenase (COX-1, COX-2) levels, and the cytokine profile in PM2.5 exposed and filtered air control mice. Only 9 month PM2.5 exposure increased BACE protein levels, APP processing, and Aβ 1-40 levels. This correlated with a concomitant increase in COX-1 and COX-2 protein levels and a modest alteration in the cytokine profile. These data support the hypothesis that prolonged exposure to airborne particulate matter has the potential to alter brain inflammatory phenotype and promote development of early AD-like pathology.

  3. Enhancing Prediction of Inhalant Abuse Risk in Samples of Early Adolescents: A Secondary Analysis

    PubMed Central

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

    2008-01-01

    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

  4. 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.

  5. [Early effects of ulinastatin by aerosol inhalation on rabbits with lipopolysaccharide-induced acute lung injury].

    PubMed

    Zhang, Yangyang; Qiu, Xiaochen; Zhou, Guoyong; Liu, Zhen; Chang, Na; Jia, Chiyu

    2014-06-01

    To study the early effects of ulinastatin (UTI) by aerosol inhalation on rabbits with acute lung injury induced by LPS, and to observe the early diagnostic value of 320-slice CT. According to the random number table, 18 specific pathogen free New Zealand white rabbits were divided into normal control group, group LPS, and group UTI, with 6 rabbits in each group. Rabbits in group LPS and group UTI were given 15 mL lipopolysaccharide (0.16 mg/mL, in the dose of 0.8 mg/kg) to reproduce acute lung injury model. Rabbits in normal control group were given equal volume of normal saline. Rabbits in UTI group were treated with UTI by aerosol inhalation for 10 min from 30 min after injury, while those in the other two groups received normal saline by aerosol inhalation. Rabbits in group LPS and group UTI were scanned by 320-slice CT at post injury hour (PIH) 6 and 24. After anesthesia, heart blood of rabbits in group LPS and group UTI was collected for determination of serum levels of TNF-α, IL-1β, and IL-6 by ELISA at PBH 24. At PBH 24, lung tissue samples were harvested for gross observation and histomorphological observation, measurement of wet to dry weight ratio, and detection of mRNA expressions of TNF-α, IL-1β, and IL-6 with RT-PCR. Above-mentioned indexes were detected in rabbits of normal control group at the same time point. Data were processed with one-way analysis of variance and LSD test. (1) CT perfusion (CTP) image. The difference in CTP image of rabbits in group LPS between PBH 6 and PBH 24 was obvious, while that of rabbits in group UTI and normal control group was slight and not obvious respectively. (2) There were statistically significant differences in the serum levels of TNF-α, IL-1β, and IL-6 of rabbits among the three groups (with F values from 843.896 to 2 564.336, P values below 0.001). The serum levels of TNF-α, IL-1β, and IL-6 in group UTI were respectively (225 ± 9), (190 ± 8), (227 ± 6) pg/mL, and they were significantly lower than

  6. Clinical Utility of Fractional exhaled Nitric Oxide (FeNO) as a Biomarker to Predict Severity of Disease and Response to Inhaled Corticosteroid (ICS) in Asthma Patients.

    PubMed

    Neelamegan, Revathy; Saka, Vinodkumar; Tamilarasu, Kadhiravan; Rajaram, Manju; Selvarajan, Sandhiya; Chandrasekaran, Adithan

    2016-12-01

    Bronchial asthma is a common chronic inflammatory airway disease diagnosed and is based on symptomatic history and Pulmonary Function Tests (PFT). Fractional exhaled Nitric Oxide (FeNO) is exclusively a non-invasive biomarker of on-going eosinophilic airway inflammation which remains unpredictable only with PFTs. FeNO measurement is recommended in predicting asthma severity and Inhaled Corticosteroid (ICS) response but further research is required to understand its clinical utility and agreement with current recommendations in a specific population. To estimate FeNO levels in Tamilian patients with mild-to-moderate persistent asthma and to correlate with disease severity and ICS response. The study was a prospective cohort with a single group of 102 persistent asthma patients under standard ICS regimen for 8 weeks (follow-up period). PFT and FeNO were measured using portable spirometry and chemiluminescence based exhaled breath analyser, at baseline and during follow-up visits. Based on PFT and FeNO parameters, the study population was sub-grouped with respect to asthma severity (as mild, moderate and moderately severe), FeNO cut-off (> or < 50ppb) and ICS response classification (good vs poor ICS responders). Significant decrease in mean FeNO levels were found in mild, moderate and moderately severe asthmatic groups following ICS treatment (90.15±27.36, 75.74±31.98 and 77.18±32.79 ppb) compared to similar baseline FeNO levels (103.03±34.08, 91.38±37.60 and 97.90±43.84 ppb) in all the above groups. Similarly, significant decrease in mean FeNO levels was found - FeNO>50ppb, good and poor ICS responders groups, in post- ICS treatment (89.63±24.04, 77.90±31.12 and 86.49±32.57 ppb) compared to baseline levels (110.183±1.23, 97.12±42.04 and 99.68±34.71 ppb). The observed baseline FeNO values in all groups as stated above did not show significant difference to differentiate asthma severity or ICS responders groups. The present study results do not support the

  7. Clinical Utility of Fractional exhaled Nitric Oxide (FeNO) as a Biomarker to Predict Severity of Disease and Response to Inhaled Corticosteroid (ICS) in Asthma Patients

    PubMed Central

    Saka, Vinodkumar; Tamilarasu, Kadhiravan; Rajaram, Manju; Selvarajan, Sandhiya; Chandrasekaran, Adithan

    2016-01-01

    Introduction Bronchial asthma is a common chronic inflammatory airway disease diagnosed and is based on symptomatic history and Pulmonary Function Tests (PFT). Fractional exhaled Nitric Oxide (FeNO) is exclusively a non-invasive biomarker of on-going eosinophilic airway inflammation which remains unpredictable only with PFTs. FeNO measurement is recommended in predicting asthma severity and Inhaled Corticosteroid (ICS) response but further research is required to understand its clinical utility and agreement with current recommendations in a specific population. Aim To estimate FeNO levels in Tamilian patients with mild-to-moderate persistent asthma and to correlate with disease severity and ICS response. Materials and Methods The study was a prospective cohort with a single group of 102 persistent asthma patients under standard ICS regimen for 8 weeks (follow-up period). PFT and FeNO were measured using portable spirometry and chemiluminescence based exhaled breath analyser, at baseline and during follow-up visits. Based on PFT and FeNO parameters, the study population was sub-grouped with respect to asthma severity (as mild, moderate and moderately severe), FeNO cut-off (> or < 50ppb) and ICS response classification (good vs poor ICS responders). Results Significant decrease in mean FeNO levels were found in mild, moderate and moderately severe asthmatic groups following ICS treatment (90.15±27.36, 75.74±31.98 and 77.18±32.79 ppb) compared to similar baseline FeNO levels (103.03±34.08, 91.38±37.60 and 97.90±43.84 ppb) in all the above groups. Similarly, significant decrease in mean FeNO levels was found - FeNO>50ppb, good and poor ICS responders groups, in post- ICS treatment (89.63±24.04, 77.90±31.12 and 86.49±32.57 ppb) compared to baseline levels (110.183±1.23, 97.12±42.04 and 99.68±34.71 ppb). Conclusion The observed baseline FeNO values in all groups as stated above did not show significant difference to differentiate asthma severity or ICS

  8. Lung [18F]fluorodeoxyglucose uptake and ventilation-perfusion mismatch in the early stage of experimental acute smoke inhalation

    PubMed Central

    Musch, Guido; Winkler, Tilo; Harris, R. Scott; Vidal Melo, Marcos F.; Wellman, Tyler J.; de Prost, Nicolas; Kradin, Richard L.; Venegas, Jose G.

    2014-01-01

    Background Acute lung injury (ALI) occurs in a third of patients with smoke inhalation injury. Its clinical manifestations usually do not appear until 48 to 72 h after inhalation. Identifying inflammatory changes that occur in pulmonary parenchyma earlier than that could provide insight into the pathogenesis of smoke-induced ALI. Furthermore, noninvasive measurement of such changes might lead to earlier diagnosis and treatment. Because glucose is the main source of energy for pulmonary inflammatory cells, we hypothesized that its pulmonary metabolism is increased shortly after smoke inhalation, when classic manifestations of ALI are not yet expected. Methods In five sheep we induced unilateral injury with 48 breaths of cotton smoke while the contralateral lung served as control. We used positron emission tomography with: 1) [18F]fluorodeoxyglucose to measure pulmonary inflammatory cell metabolic activity; and 2) [13N]nitrogen in saline to measure shunt and ventilation-perfusion distributions separately in the smoke-exposed and control lungs. Results The pulmonary [18F]fluorodeoxyglucose uptake rate was increased at 4 h after smoke inhalation (mean ± SD: 0.0031 ± 0.0013 vs. 0.0026 ± 0.0010 min−1, P < 0.05) mainly as a result of increased glucose phosphorylation. At this stage there was no worsening in lung aeration or shunt. However, there was a shift of perfusion toward units with lower ventilation-to-perfusion ratio (mean ratio ± SD: 0.82 ± 0.10 vs. 1.12 ± 0.02, P < 0.05) and increased heterogeneity of the ventilation-perfusion distribution (mean ± SD: 0.21 ± 0.07 vs. 0.13 ± 0.01, P < 0.05). Conclusion Using noninvasive imaging we demonstrated that increased pulmonary [18F]fluorodeoxyglucose uptake and ventilation-perfusion mismatch occur early after smoke inhalation. PMID:24051392

  9. Lung [(18)F]fluorodeoxyglucose uptake and ventilation-perfusion mismatch in the early stage of experimental acute smoke inhalation.

    PubMed

    Musch, Guido; Winkler, Tilo; Harris, R Scott; Vidal Melo, Marcos F; Wellman, Tyler J; de Prost, Nicolas; Kradin, Richard L; Venegas, Jose G

    2014-03-01

    Acute lung injury occurs in a third of patients with smoke inhalation injury. Its clinical manifestations usually do not appear until 48-72 h after inhalation. Identifying inflammatory changes that occur in pulmonary parenchyma earlier than that could provide insight into the pathogenesis of smoke-induced acute lung injury. Furthermore, noninvasive measurement of such changes might lead to earlier diagnosis and treatment. Because glucose is the main source of energy for pulmonary inflammatory cells, the authors hypothesized that its pulmonary metabolism is increased shortly after smoke inhalation, when classic manifestations of acute lung injury are not yet expected. In five sheep, the authors induced unilateral injury with 48 breaths of cotton smoke while the contralateral lung served as control. The authors used positron emission tomography with: (1) [F]fluorodeoxyglucose to measure metabolic activity of pulmonary inflammatory cells; and (2) [N]nitrogen in saline to measure shunt and ventilation-perfusion distributions separately in the smoke-exposed and control lungs. The pulmonary [F]fluorodeoxyglucose uptake rate was increased at 4 h after smoke inhalation (mean ± SD: 0.0031 ± 0.0013 vs. 0.0026 ± 0.0010 min; P < 0.05) mainly as a result of increased glucose phosphorylation. At this stage, there was no worsening in lung aeration or shunt. However, there was a shift of perfusion toward units with lower ventilation-to-perfusion ratio (mean ratio ± SD: 0.82 ± 0.10 vs. 1.12 ± 0.02; P < 0.05) and increased heterogeneity of the ventilation-perfusion distribution (mean ± SD: 0.21 ± 0.07 vs. 0.13 ± 0.01; P < 0 .05). Using noninvasive imaging, the authors demonstrated that increased pulmonary [F]fluorodeoxyglucose uptake and ventilation-perfusion mismatch occur early after smoke inhalation.

  10. 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

  11. Role of Heat Shock Protein 90 and Endothelial Nitric Oxide Synthase during Early Anesthetic and Ischemic Preconditioning

    PubMed Central

    Amour, Julien; Brzezinska, Anna K.; Weihrauch, Dorothee; Billstrom, Amie R.; Zielonka, Jacek; Krolikowski, John G.; Bienengraeber, Martin W.; Warltier, David C.; Pratt, Philip F.; Kersten, Judy R.

    2009-01-01

    Background Nitric oxide is known to be essential for early anesthetic (APC) and ischemic (IPC) preconditioning of myocardium. Heat shock protein 90 (Hsp90) regulates endothelial nitric oxide synthase (eNOS) activity. In this study, we tested the hypothesis that Hsp90-eNOS interactions modulate APC and IPC. Methods Myocardial infarct size was measured in rabbits after coronary occlusion and reperfusion in the absence or presence of preconditioning with 30 min of isoflurane (APC) or 5 min of coronary artery occlusion (IPC), and with or without pre-treatment with geldanamycin or radicicol, two chemically distinct Hsp90 inhibitors, or NG-nitro-L-arginine methylester, a non-specific NOS inhibitor. Isoflurane-dependent nitric oxide production was measured (ozone chemiluminescence) in human coronary artery endothelial cells or mouse cardiomyocytes, in the absence or presence of Hsp90 inhibitors or NG-nitro-L-arginine methylester. Interactions between Hsp90 and eNOS, and eNOS activation were assessed with immunoprecipitation, immunoblotting, and confocal microscopy. Results APC and IPC decreased infarct size (50% and 59%, respectively) and this action was abolished by Hsp90 inhibitors. NG-nitro-L-arginine methylester blocked APC but not IPC. Isoflurane increased nitric oxide production in human coronary artery endothelial cells, concomitantly with an increase in Hsp90-eNOS interaction (immunoprecipitation, immunoblotting, and immunohistochemistry). Pretreatment with Hsp90 inhibitors abolished isoflurane-dependent nitric oxide production and decreased Hsp90-eNOS interactions. Isoflurane did not increase nitric oxide production in mouse cardiomyocytes and eNOS was below the level of detection. Conclusion The results indicate that Hsp90 plays a critical role in mediating APC and IPC through protein-protein interactions, and suggest that endothelial cells are important contributors to nitric oxide-mediated signalling during APC. PMID:19194158

  12. Computational Models of Inhalation Therapy in Early Childhood: Therapeutic Aerosols in the Developing Acinus.

    PubMed

    Katan, Janna Tenenbaum; Hofemeier, Philipp; Sznitman, Josué

    2016-06-01

    Inhalation therapy targeted to the deep alveolated regions holds great promise, specifically in pediatric populations. Yet, inhalation devices and medical protocols are overwhelmingly derived from adult guidelines, with very low therapeutic efficiency in young children. During the first years of life, airway remodeling and changing ventilation patterns are anticipated to alter aerosol deposition with underachieving outcomes in infants. As past research is still overwhelmingly focused on adults or limited to models of upper airways, a fundamental understanding of inhaled therapeutic transport and deposition in the acinar regions is needed to shed light on delivering medication to the developing alveoli. Using computational fluid dynamics (CFD), we simulated inhalation maneuvers in anatomically-inspired models of developing acinar airways, covering the distinct phases of lung development, from underdeveloped, saccular pulmonary architectures in infants, to structural changes in toddlers, ultimately mimicking space-filling morphologies of a young child, representing scaled-down adult lungs. We model aerosols whose diameters span the range of sizes acknowledged to reach the alveolar regions and examine the coupling between morphological changes, varying ventilation patterns and particle characteristics on deposition outcomes. Spatial distributions of deposited particles point to noticeable changes in the patterns of aerosol deposition with age, in particular in the youngest age group examined (3 month). Total deposition efficiency, as well as deposition dispersion, vary not only with the phases of lung development but also and critically with aerosol diameter. Given the various challenges when prescribing inhalation therapy to a young infant, our findings underline some mechanistic aspects to consider when targeting medication to the developing alveoli. Not only does the intricate coupling between acinar morphology and ventilation patterns need to be considered, but

  13. The selective pulmonary vasodilatory effect of inhaled DETA/NO, a novel nitric oxide donor, in ARDS-a pilot human trial.

    PubMed

    Lam, Chen-Fuh; Van Heerden, P Vernon; Blott, John; Roberts, Brigit; Ilett, Kenneth F

    2004-03-01

    To examine the effects of inhaled NONOates in patients with acute respiratory distress syndrome (ARDS). Case-series, phase I clinical trial. A multidisciplinary intensive care unit in a tertiary teaching hospital. Five consecutive patients with ARDS (men; age range, 47-76 years). DETA/NO (150 micromol) was aerosolized into the lungs of patients on mechanical ventilation via the endotracheal tube over 20 minutes. Hemodynamic parameters were measured and blood samples were taken before, during, and after inhalation. Compared to baseline values, pulmonary vascular resistance decreased until the end of the study period (180 minutes) while intrapulmonary shunting decreased significantly up to 45 min after DETA/NO aerosol administration. Inhaled DETA/NO had no effect on the systemic circulation (systemic blood pressure or cardiac output). Inhaled DETA/NO is a selective pulmonary vasodilator in patients with ARDS. However, a larger number of patients is required to confirm the findings of this pilot study.

  14. Brisk production of nitric oxide and associated formation of S-nitrosothiols in early hemorrhage.

    PubMed

    Atkins, James L; Day, Billy W; Handrigan, Michael T; Zhang, Zhe; Pamnani, Motilal B; Gorbunov, Nikolai V

    2006-04-01

    The results of previous inhibitor studies suggest that there is some increase in nitric oxide (NO) production from constitutive NO synthase in early hemorrhage (H), but the magnitude of NO production early after H has not been previously assessed. It is generally believed that only modest production rates are possible from the constitutively expressed NO synthases. To study this, anesthetized male Sprague-Dawley rats were subjected to 90 min of isobaric (40 mmHg) H. During this period of time, the dynamics of accumulation of NO intermediates in the arterial blood was assessed using electron paramagnetic resonance spectroscopy, chemiluminescence, fluorescence imaging, and mass spectrometry. Electron paramagnetic resonance-detectable NO adducts were also measured with spin traps in blood plasma and red blood cells. H led to an increase in the concentration of hemoglobin-NO from 0.9 +/- 0.2 to 4.8 +/- 0.7 microM. This accumulation was attenuated by a nonselective inhibitor of NO synthase, NG-nitro-L-argininemethyl ester (L-NAME), but not by NG-nitro-D-argininemethyl ester (D-NAME) or 1400W. Administration of L-NAME (but not 1400W or D-NAME) during H produced a short-term increase in mean arterial pressure ( approximately 90%). In H, the level of N oxides in red blood cells increased sevenfold. S-nitrosylation of plasma proteins was revealed with "biotin switch" techniques. The results provide compelling evidence that there is brisk production of NO in early H. The results indicate that the initial compensatory response to H is more complicated than previously realized, and it involves an orchestrated balance between intense vasoconstrictor and vasodilatory components.

  15. 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.

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

    PubMed Central

    Shoghi, Kooresh I.; Silva, Matthew J.

    2013-01-01

    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), 15O water (blood) flow rate was significantly increased on day 0 and remained elevated 14 days after loading, whereas 18F fluoride uptake peaked 7 days after loading. In the group that received nondamaging mechanical loading leading to lamellar bone formation (LBF), 15O water and 18F 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 Nω-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

  17. 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. © 2016 Wiley Periodicals, Inc.

  18. 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.

  19. Nasal nitric oxide for early diagnosis of primary ciliary dyskinesia: practical issues in children.

    PubMed

    Piacentini, Giorgio L; Bodini, Alessandro; Peroni, Diego; Rigotti, Erika; Pigozzi, Roberta; Pradal, Ugo; Boner, Attilio L

    2008-04-01

    Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormally beating cilia. In these patients, levels of nasal nitric oxide (nNO) are lower than those observed in healthy subjects. We identify the nNO levels in healthy pre-school uncooperative children and in PCD patients, in order the application of nNO measurement in the early identification of young children with PCD. We measured nNO in 77 healthy children (50 uncooperative and 27 cooperative) and in 10 PCD patients. Fifteen cooperative healthy children were also asked to perform an uncooperative test. PCD patients presented low nNO levels (29.7+/-5.7 ppb) compared to those observed in healthy children (358.8+/-35.2 ppb; p<0.05). nNO levels were increased in healthy cooperative children (650+/-60.6 ppb; p<0.05) as compared to those uncooperative aging more than 6 month (309.1+/-45.9 ppb; p<0.05) or less (128.1+/-16.2 ppb; p<0.05). Twenty-four uncooperative children with nNO values < or = 200 ppb performed a second evaluation at least 6 months later and mean levels increased from 104.7+/-10.5 ppb to 169.9+/-19.6 ppb (p<0.05). In the 15 collaborative children nNO levels were higher during the breath holding manoeuvre (687.7+/-96.9 ppb) than during the tidal breathing manoeuvre (335.9+/-57.9 ppb; p<0.05). Healthy children have higher nNO levels than PCD patients. In 15% of uncooperative healthy children can be found low nNO levels, similar to PCD patients, but those values increased some months later, in successive evaluations. Nasal NO may be used for PCD screening even though repeated evaluations may be necessary in young children.

  20. 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.

  1. Treatment satisfaction in cystic fibrosis: early patient experience with tobramycin inhalation powder

    PubMed Central

    Greenberg, Jonathan; Palmer, Jacqueline B; Chan, Wing W; Correia, Catherine E; Whalley, Diane; Shannon, Paul; Sawicki, Gregory S

    2016-01-01

    Background This study assessed treatment satisfaction of cystic fibrosis (CF) patients in a routine clinical setting for tobramycin inhalation powder (TIP), the first dry powder–inhaled antibiotic for Pseudomonas aeruginosa infection. Methods CF patients aged 6 years or older treated with at least one cycle of TIP completed a web survey on experience with TIP, including the Treatment Satisfaction Questionnaire for Medication (TSQM). Regression analysis determined the factors associated with TSQM global satisfaction. Results Eighty patients (mean age ± standard deviation: 24.4±9.4 years; 57.5% female; mean forced expiratory volume in 1 second ± standard deviation: 67.1%±27.3% predicted) completed the survey. The majority expressed satisfaction with TIP’s administration time (100%), time to clean (97.1%), portability (97.1%), and ease of use (94.3%). Effectiveness was significantly associated with TSQM global satisfaction (regression R-squared: 0.54). Conclusion Patient preferences for TIP were based on administration time and ease of use. Global satisfaction was related to greater patient-perceived effectiveness. PMID:27822017

  2. Early pulmonary response is critical for extra-pulmonary carbon nanoparticle mediated effects: comparison of inhalation versus intra-arterial infusion exposures in mice.

    PubMed

    Ganguly, Koustav; Ettehadieh, Dariusch; Upadhyay, Swapna; Takenaka, Shinji; Adler, Thure; Karg, Erwin; Krombach, Fritz; Kreyling, Wolfgang G; Schulz, Holger; Schmid, Otmar; Stoeger, Tobias

    2017-06-20

    inhalation are dominated by indirect effects (particle-cell interactions in the lung) rather than direct effects (translocated CNPs) within the first hours after exposure. Hence, CNP translocation may not be the key event inducing early cardiovascular impairment following air pollution episodes. The considerable response detected in the aorta after CNP inhalation warrants more emphasis on this tissue in future studies.

  3. Neuronal nitric oxide synthase immunoreactivity in ependymal cells during early postnatal development.

    PubMed

    Soygüder, Zafer; Karadağ, Hüseyin; Nazli, Mümtaz

    2004-03-01

    Neuronal nitric oxide synthase (nNOS) immunoreactivity was observed in ependymal cell layer of the central canal of spinal cord of neonatal rats (2-20 days old). Neuronal nitric oxide synthase immunoreactivity was present in postnatal day 2 and this immunoreactivity gradually disappeared by postnatal day 16. The progressive decrease in nNOS staining with the increasing postnatal age may suggest that nNOS staining paralleled the maturation of the central canal and may also suggest that nNOS activity plays a role in the development of the ependymal cells.

  4. Glutathione improves early somatic embryogenesis in Araucaria angustifolia (Bert) O. Kuntze by alteration in nitric oxide emission.

    PubMed

    Vieira, Leila do Nascimento; Santa-Catarina, Claudete; de Freitas Fraga, Hugo Pacheco; Dos Santos, André Luis Wendt; Steinmacher, Douglas André; Schlogl, Paulo Sérgio; Silveira, Vanildo; Steiner, Neusa; Floh, Eny Iochevet Segal; Guerra, Miguel Pedro

    2012-10-01

    In this work, it was observed a straight relationship between the manipulation of the reduced glutathione (GSH)/glutathione disulfide (GSSG) ratio, nitric oxide emission and quality and number of early somatic embryos in Araucaria angustifolia, a Brazilian endangered native conifer. In low concentrations GSH (0.01 and 0.1mM) is a potential NO scavenger in the culture medium. Furthermore, it can increase the number of early SE formed in cell suspension culture media in a few days. However, the maintenance in this low redox state lead to a loss of early somatic embryos polarization. In gelled culture medium, high levels of GSH (5mM) allows the development of globular embryos presenting a high NO emission on embryo apex, stressing its importance in the differentiation and cell division. Taken together these results indicate that the modification of the embryogenic cultures redox state might be an effective strategy to develop more efficient embryogenic systems in A. angustifolia.

  5. Iloprost inhalation in mild asthma.

    PubMed

    Majeski, Elizabeth; Hoskins, Aimee; Dworski, Ryszard; Sheller, James R

    2012-11-01

    To determine the feasibility of administering iloprost by inhalation in patients with mild atopic asthma. Volunteers underwent supervised inhalation of iloprost in the clinic with measurement of spirometry and blood pressure for 2 hours. The volunteers then inhaled iloprost four times daily at a dose of 2.5 or 5 μg for 14 days. Spirometry, asthma questionnaires, peak flow diaries, measurement of methacholine responsiveness, and exhaled nitric oxide concentrations were obtained prior to and after the treatment period. Chronic inhalation of iloprost (2.5-5 μg) did not alter spirometry or methacholine responsiveness. Inhaled iloprost in carefully selected volunteers with mild asthma appears to be a suitable intervention to explore the effects of prostacyclin in human asthma.

  6. [Asthma therapy by the general practitioner--new approaches and progress. Why inhaled steroids and delayed action beta-2 adrenergic drugs should be combined early on].

    PubMed

    Petro, W

    1999-08-26

    Early treatment with high-dose inhaled steroids can significantly improve the prognosis of asthma. Inhaled steroids used to treat inflammation of the mucosa, and hyperreactivity may be reduced only under careful surveillance. Hig-dose initial treatment must be followed by low-dose maintenance therapy. The best therapeutic results are obtained with a combination of inhaled steroids and long-acting beta-2-adrenergic agents. Careful titration of the dose and therapeutic effects is a major task for the family doctor. Bronchial inflammation and reactivity are dependent on external factors, and are rarely stable. The most important therapeutic basis is, therefore, continuous management involving both the patient and the family doctor. The patient should be provided with relevant information on his/her disease and its treatment. A prerequisite for the effective management of asthma is the provision of individual peak-flow-adjusted and emergency plans.

  7. Early administration of inhaled corticosteroids for preventing chronic lung disease in very low birth weight preterm neonates.

    PubMed

    Shah, Vibhuti S; Ohlsson, Arne; Halliday, Henry L; Dunn, Michael

    2017-01-04

    an additional beneficial outcome (NNTB) was calculated. We used the GRADE approach to assess the quality of evidence. According to GRADE the quality of the studies was moderate. Three additional trials are included in this update. The present review includes data analyses based on 10 qualifying trials that enrolled 1644 neonates. There was no significant difference in the incidence of CLD at 36 weeks' PMA in the inhaled steroid versus the placebo group (5 trials, 429 neonates) among all randomised (typical RR 0.97, 95% CI 0.62 to 1.52; typical RD -0.00, 95% CI -0.07 to 0.06). There was no heterogeneity for this outcome (typical RR I² = 11%; typical RD I² = 0%). There was a significant reduction in the incidence of CLD at 36 weeks' PMA among survivors (6 trials, 1088 neonates) (typical RR 0.76, 95% CI 0.63 to 0.93; typical RD -0.07, 95% CI -0.13 to -0.02; NNTB 14, 95% CI 8 to 50). There was a significant reduction in the combined outcome of death or CLD at 36 weeks' PMA among all randomised neonates (6 trials, 1285 neonates) (typical RR 0.86, 95% CI 0.75 to 0.99; typical RD -0.06, 95% CI -0.11 to -0.00) (P = 0.04); NNTB 17, 95% CI 9 to infinity). There was no significant heterogeneity for any of these analyses (I² = 0%). A lower rate of reintubation was noted in the inhaled steroid group compared with the control group in one study. There were no statistically significant differences in short-term complications between groups and no differences in adverse events at long-term follow-up reported. Long-term follow-up of infants enrolled in the study by Bassler 2015 is ongoing. Based on this updated review, there is increasing evidence from the trials reviewed that early administration of inhaled steroids to VLBW neonates is effective in reducing the incidence of death or CLD at 36 weeks' PMA among either all randomised infants or among survivors. Even though there is statistical significance, the clinical relevance is of question as the upper CI limit for the outcome

  8. 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 ...

  9. Inhalant abuse.

    PubMed

    Williams, Janet F; Storck, Michael

    2007-05-01

    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 clinical report reviews key aspects of inhalant abuse, emphasizes the need for greater awareness, and offers advice regarding the pediatrician's role in the prevention and management of this substance abuse problem.

  10. Inhalant Abuse

    MedlinePlus

    ... to every organ over time.Also, if your child abuses inhalants, he or she is likely to try ... How can I start a discussion about inhalant abuse with my child? Other organizationsNational Inhalant Prevention Coalition (NIPC)National Institute ...

  11. Lifetime use of cigarettes, alcohol, marijuana and inhalants in Latino early adolescents.

    PubMed

    Kouyoumdjian, Claudia; Guzmán, Bianca L; Leon, Nancy

    2015-01-01

    A growing population in the US is Latinos, an ethnic group defined by people of origin from Latin America. By 2050, Hispanics will be at least one quarter of the United States population (U.S. Census Bureau, 2006 ) with a substantial proportion under the age of 25 (Vaughan, Kratz, & D'argent, 2011 ). Yet, the literature on substance use among Latino adolescents is not advancing parallel to the growth of the population (Szapocznik, Lopez, Prado, Schwartz, & Pantin, 2006 ). Health concerns during early adolescence can have a lasting impact on the Latino community and society at large, as early substance initiation can lead to addiction during adulthood (Behrendt, Wittchen, Höfler, Lieb, & Beesdo, 2009 ). Therefore, research that aims to identify psychosocial determinants that serve as risk and protective factors specific to Latino early adolescents is needed as a critical first step in the development of culturally specific prevention initiatives (Vaughan et al., 2011 ).

  12. Uncertainties in doses calculated according to ICRP recommendations after inhalation of 239PUO2 and early chest monitoring.

    PubMed

    Fritsch, P

    2007-01-01

    This study estimates uncertainties in Pu biokinetics and effective doses calculated after an acute inhalation exposure to 239PuO2 according to ICRP recommendations (default values for aerosols size and PuO2 dissolution parameters). This was performed using the most recently reported variations in model parameters and simulations after a Monte Carlo approach. Without chest monitoring, uncertainties in thoracic retention and plutonium excretion was 8-10 (95% confidence interval as the ratio between 97.5 and 2.5 percentiles of the lognormal distributions) up to 900 d after exposure. Early chest monitoring reduces significantly the uncertainties in plutonium biokinetics and doses which remain within a 95% confidence interval of 2.3 as compared with 6.6, without monitoring. Analysis of bioassay data previously reported shows that the dose delivered to some individuals can be out of the confidence interval, which was mostly due to an inhibition of the late mechanical clearance of the alveolar interstitium.

  13. Increase in non-specific bronchial hyperresponsiveness as an early marker of bronchial response to occupational agents during specific inhalation challenges.

    PubMed Central

    Vandenplas, O.; Delwiche, J. P.; Jamart, J.; Van de Weyer, R.

    1996-01-01

    BACKGROUND: Specific bronchial reactivity to occupational agents may decline after exposure in the workplace ceases leading to falsely negative specific inhalation challenges. A study was carried out to assess prospectively whether increases in nonspecific bronchial hyperresponsiveness could be useful in detecting the bronchial response to occupational agents during specific inhalation challenges. METHODS: Specific inhalation challenges were performed in 66 subjects with possible occupational asthma due to various agents. After a control day the subjects were challenged with the suspected agent for up to two hours on the first test day. Those subjects who did not show an asthmatic reaction were rechallenged on the next day for 2-3 hours. The provocative concentration of histamine causing a 20% fall (PC20) in the forced expiratory volume in one second (FEV1) was assessed at the end of the control day as well as six hours after each challenge that did not cause a > or = 20% fall in FEV1. The subjects who had a significant (> or = 3.1-fold) reduction in PC20 value at the end of the second challenge day were requested to perform additional specific inhalation challenges. RESULTS: The first test day elicited an asthmatic reaction in 25 subjects. Of the other 41 subjects five (12%, 95% confidence interval (CI) 4% to 26%) exhibited a > or = 3.1-fold fall in the PC20 value after the inhalation challenge and developed an asthmatic reaction during the second (n = 3) or third (n = 2) challenge exposure. The offending agents included persulphate (n = 1), wood dust (n = 2), isocyanate (n = 1), or amoxycillin (n = 1). These five subjects had left their workplace for a longer period (mean (SD) 21 (14) months) than those who reacted after the first specific inhalation challenge (8 (11) months). CONCLUSIONS: The increase in non-specific bronchial hyperresponsiveness after a specific inhalation challenge can be an early and sensitive marker of bronchial response to occupational

  14. Effects of helium and air inhalation on the innate and early adaptive immune system in healthy volunteers ex vivo.

    PubMed

    Oei, Gezina T M L; Smit, Kirsten F; vd Vondervoort, Djai; Brevoord, Daniel; Hoogendijk, Arjan; Wieland, Catharina W; Hollmann, Markus W; Preckel, Benedikt; Weber, Nina C

    2012-09-24

    Helium inhalation protects myocardium, brain and endothelium against ischemia/reperfusion injury in animals and humans, when applied according to specific "conditioning" protocols. Before widespread use of this "conditioning" agent in clinical practice, negative side effects have to be ruled out. We investigated the effect of prolonged helium inhalation on the responsiveness of the human immune response in whole blood ex vivo. Male healthy volunteers inhaled 30 minutes heliox (79%He/21%O(2)) or air in a cross over design, with two weeks between measurements. Blood was withdrawn at T0 (baseline), T1 (25 min inhalation) and T2-T5 (1, 2, 6, 24 h after inhalation) and incubated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), T-cell stimuli anti-CD3/ anti-CD28 (TCS) or RPMI (as control) for 2, 4 and 24 hours or not incubated (0 h). An additional group of six volunteers inhaled 60 minutes of heliox or air, followed by blood incubation with LPS and RPMI. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interferon-γ (IFN-γ) and interleukin-2 (IL-2) was analyzed by cytometric bead array. Statistical analysis was performed by the Wilcoxon test for matched samples. Incubation with LPS, LTA or TCS significantly increased TNF-α, IL-1β, IL-6, IL-8, IFN-γ and IL-2 in comparison to incubation with RPMI alone. Thirty min of helium inhalation did not influence the amounts of TNF-α, IL-1β, IL-6, IL-8, IFN-γ and IL-2 in comparison to air. Sixty min of helium inhalation did not affect cytokine production after LPS stimulation. We conclude that 79% helium inhalation does not affect the responsiveness of the human immune system in healthy volunteers. Dutch Trial Register: http://www.trialregister.nl/ NTR2152.

  15. Effects of helium and air inhalation on the innate and early adaptive immune system in healthy volunteers ex vivo

    PubMed Central

    2012-01-01

    Background Helium inhalation protects myocardium, brain and endothelium against ischemia/reperfusion injury in animals and humans, when applied according to specific “conditioning” protocols. Before widespread use of this “conditioning” agent in clinical practice, negative side effects have to be ruled out. We investigated the effect of prolonged helium inhalation on the responsiveness of the human immune response in whole blood ex vivo. Methods Male healthy volunteers inhaled 30 minutes heliox (79%He/21%O2) or air in a cross over design, with two weeks between measurements. Blood was withdrawn at T0 (baseline), T1 (25 min inhalation) and T2-T5 (1, 2, 6, 24 h after inhalation) and incubated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), T-cell stimuli anti-CD3/ anti-CD28 (TCS) or RPMI (as control) for 2, 4 and 24 hours or not incubated (0 h). An additional group of six volunteers inhaled 60 minutes of heliox or air, followed by blood incubation with LPS and RPMI. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interferon-γ (IFN-γ) and interleukin-2 (IL-2) was analyzed by cytometric bead array. Statistical analysis was performed by the Wilcoxon test for matched samples. Results Incubation with LPS, LTA or TCS significantly increased TNF-α, IL-1β, IL-6, IL-8, IFN-γ and IL-2 in comparison to incubation with RPMI alone. Thirty min of helium inhalation did not influence the amounts of TNF-α, IL-1β, IL-6, IL-8, IFN-γ and IL-2 in comparison to air. Sixty min of helium inhalation did not affect cytokine production after LPS stimulation. Conclusions We conclude that 79% helium inhalation does not affect the responsiveness of the human immune system in healthy volunteers. Trial registration Dutch Trial Register: http://www.trialregister.nl/ NTR2152 PMID:23006534

  16. Substance use - inhalants

    MedlinePlus

    Substance abuse - inhalants; Drug abuse - inhalants; Drug use - inhalants; Glue - inhalants ... symptoms and may include: Strong cravings for the drug Having mood swings from feeling depressed to agitated ...

  17. Combined effect of low-dose nitric oxide gas inhalation with partial liquid ventilation on hemodynamics, pulmonary function, and gas exchange in acute lung injury of newborn piglets.

    PubMed Central

    Choi, Chang Won; Hwang, Jong Hee; Chang, Yun Sil; Park, Won Soon

    2003-01-01

    We conducted a randomized animal study to determine whether there is a cumulative effect on hemodynamics, pulmonary function, and gas exchange when low-dose nitric oxide (NO) is added to partial liquid ventilation (PLV) in acute lung injury. Eighteen newborn piglets were saline-lavaged repeatedly, and randomly divided into two groups: PLV with perfluorocarbon group (n=8) and lavage only (control) group (n=10). Perfluorodecalin (30 mL/kg) was instilled into the endotracheal tube for 30 min, followed by 5-10 mL/kg/hr. Fifteen minutes after the completion of perfluorodecalin dosing, NO (10 ppm) was added to the inspiratory gas in an "on/off" manner. Perfluorodecalin instillation produced a significant improvement in gas exchange, pulmonary mechanics, shunt, and pulmonary arterial pressure (PAP). The addition of NO produced a further significant improvement in PaO2 and PAP. The "on/off" response to NO was seen apparently in PAP, PaO2, dynamic compliance, and shunt. All the variables in control group were remained at near the after-lavage levels without significant improvements until the end of the experiment. We concluded that NO might have a cumulative effect on gas exchange when combined with PLV, and this might be attributable to deceased PAP and V/Q mismatching. PMID:14676437

  18. 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

  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

    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

    2012-09-01

    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. 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 24h 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 24h 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 PaO(2)/FiO(2) was above 250 and sheep were monitored for 3 weeks. At 96 h post-injury, all animals were weaned from ventilator. There are no significant differences in PaO(2)/FiO(2) between Early Excision and Control groups at any points. All animals were survived for 3 weeks without infectious complication in Early Excision and Sham groups, whereas two

  20. 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

  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. Hemodynamic effect of iloprost inhalation and oral sildenafil during acute vasoreactivity test in pulmonary arterial hypertension.

    PubMed

    Sompradeekul, Suree; Wattanasiriphakdee, Siriphan

    2015-02-01

    The vasoreactivity test is usually performed to identify pulmonary arterial hypertension (PAH) patients who may benefit from long-term calcium channel blocker (CCB). The first and most commonly used agent is intravenous epoprostenol. A few other agents such as intravenous adenosine and inhaled nitric oxide are also used. In Thailand, epoprostenol is not available and the others are costly. Therefore, inhaled iloprost or oral sildenafil may be alternatives to test vasoreactivity. To evaluate the hemodynamic effect and response rate of inhaled iloprost and oral sildenafil during acute vasoreactivity test in PAH patients. In this retrospective descriptive study, the authors recruited patients with idiopathic PAH (IPAH) or PAHassociated with connective tissue disease (PAH-CNT) seen at the Medicine department Siriraj Hospital between January 2005 and December 2011 for whom acute vasoreactivity test was indicated. All patients used 20 microgram of inhaled iloprost via Delphinus® nebulizer for the test. Hemodynamic parameters were recorded before and after iloprost administration. Eight of those patients subsequently had a repeated test using 100 mg of oral sildenafil. Fifteen patients had acute vasoreactivity testing. Eleven patients were IPAH and four were PAH-CNT Using ESC/ERS guidelines criteria for responsiveness to vasoreactivity test, the response rate was 13% (2 out of 15 patients) using inhaled iloprost. Hemodynamic change was seen as early as five minutes after the inhalation and the effect lasted up to 35 minutes. The response rate was 25% (2 out of 8 patients) using oral sildenafil. Hemodynamic change was seen as early as 30 minutes after sildenafil ingestion and lasted up to 480 minutes. Inhaled iloprost can be used for acute vasoreactivity test in Thailand. The hemodynamic parameters should be recorded immediately after iloprost inhalation. Oral sildenafil, however, is not a suitable agent for acute vasoreactivity test due to its extended effect.

  4. Interannual variations of early winter Antarctic polar stratospheric cloud formation and nitric acid observed by CALIOP and MLS

    NASA Astrophysics Data System (ADS)

    Lambert, Alyn; Santee, Michelle L.; Livesey, Nathaniel J.

    2016-12-01

    We use satellite-borne measurements collected over the last decade (2006-2015) from the Aura Microwave Limb Sounder (MLS) and the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) to investigate the nitric acid distribution and the properties of polar stratospheric clouds (PSCs) in the early winter Antarctic vortex. Frequently, at the very start of the winter, we find that synoptic-scale depletion of HNO3 can be detected in the inner vortex before the first lidar detection of geophysically associated PSCs. The generation of "sub-visible" PSCs can be explained as arising from the development of a solid particle population with low number densities and large particle sizes. Assumed to be composed of nitric acid trihydrate (NAT), the sub-visible PSCs form at ambient temperatures well above the ice frost point, but also above the temperature at which supercooled ternary solution (STS) grows out of the background supercooled binary solution (SBS) distribution. The temperature regime of their formation, inferred from the simultaneous uptake of ambient HNO3 into NAT and their Lagrangian temperature histories, is at a depression of a few kelvin with respect to the NAT existence threshold, TNAT. Therefore, their nucleation requires a considerable supersaturation of HNO3 over NAT, and is consistent with a recently described heterogeneous nucleation process on solid foreign nuclei immersed in liquid aerosol. We make a detailed investigation of the comparative limits of detection of PSCs and the resulting sequestration of HNO3 imposed by lidar, mid-infrared, and microwave techniques. We find that the temperature history of air parcels, in addition to the local ambient temperature, is an important factor in the relative frequency of formation of liquid/solid PSCs. We conclude that the initiation of NAT nucleation and the subsequent development of large NAT particles capable of sedimentation and denitrification in the early winter do not emanate from an ice

  5. 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.

  6. Major surgery diminishes systemic arginine availability and suppresses nitric oxide response to feeding in patients with early stage breast cancer.

    PubMed

    Engelen, Mariëlle P K J; Klimberg, V Suzanne; Allasia, Arianna; Deutz, Nicolaas E P

    2017-08-05

    Plasma arginine (ARG) levels are reduced in breast cancer, suggesting diminished systemic ARG availability. ARG and its product nitric oxide (NO) are important in early postoperative recovery due to its roles in immune function and wound healing. It remains unclear whether major surgery further diminishes systemic ARG availability due to enhanced ARG catabolism and/or insufficient endogenous ARG synthesis negatively affecting NO synthesis in patients with early stage breast cancer. In 9 women with early stage breast malignancy and 9 healthy women with genetic predisposition to breast cancer, whole body ARG and citrulline (CIT) rates of appearances were measured to determine their production rates prior to and within 24 h after major breast surgery by stable isotope methodology in the postabsorptive and postprandial state. The conversions of CIT > ARG, ARG > CIT, and ARG > Urea (markers of de novo ARG and NO synthesis, arginase activity, respectively), and ARG clearance (reflecting ARG disposal capacity) were calculated. Prior to surgery, plasma ARG, CIT and glutamine concentrations were lower in cancer (P < 0.05) but no differences were found in the rate of appearances of ARG, CIT and their conversions. Surgery increased ARG clearance and reduced CIT rate of appearance, conversion of CIT > ARG (P < 0.001), and plasma ARG, CIT, ornithine concentrations (P < 0.001). Furthermore, postprandial increase in ARG > CIT conversion (P < 0.05), plasma ARG (P < 0.001) and CIT (P = 0.06) concentrations were lower after surgery. The cancer group had lower values for postprandial increase in ARG > CIT conversion, plasma CIT (P < 0.05) and glutamine concentrations (P = 0.08). Major surgery in early stage breast cancer further reduces systemic ARG availability in the early phase of recovery due to a combined process of increased ARG catabolism and impaired endogenous ARG synthesis. The suppressed postprandial NO increase in early stage cancer suggests

  7. Nitric oxide synthase during early embryonic development in silkworm Bombyx mori: Gene expression, enzyme activity, and tissue distribution.

    PubMed

    Kitta, Ryo; Kuwamoto, Marina; Yamahama, Yumi; Mase, Keisuke; Sawada, Hiroshi

    2016-12-01

    To elucidate the mechanism for embryonic diapause or the breakdown of diapause in Bombyx mori, we biochemically analyzed nitric oxide synthase (NOS) during the embryogenesis of B. mori. The gene expression and enzyme activity of B. mori NOS (BmNOS) were examined in diapause, non-diapause, and HCl-treated diapause eggs. In the case of HCl-treated diapause eggs, the gene expression and enzyme activity of BmNOS were induced by HCl treatment. However, in the case of diapause and non-diapause eggs during embryogenesis, changes in the BmNOS activity and gene expressions did not coincide except 48-60 h after oviposition in diapause eggs. The results imply that changes in BmNOS activity during the embryogenesis of diapause and non-diapause eggs are regulated not only at the level of transcription but also post-transcription. The distribution and localization of BmNOS were also investigated with an immunohistochemical technique using antibodies against the universal NOS; the localization of BmNOS was observed mainly in the cytoplasm of yolk cells in diapause eggs and HCl-treated diapause eggs. These data suggest that BmNOS has an important role in the early embryonic development of the B. mori.

  8. Early signaling components in ultraviolet-B responses: distinct roles for different reactive oxygen species and nitric oxide.

    PubMed

    A -H -Mackerness, S; John, C F; Jordan, B; Thomas, B

    2001-02-02

    The nature and origin of the reactive oxygen species (ROS) involved in the early part of Ultraviolet-B (UV-B)-induced signaling pathways were investigated in Arabidopsis thaliana using a range of enzyme inhibitors and free radical scavengers. The increase in PR-1 transcript and decrease in Lhcb transcript in response to UV-B exposure was shown to be mediated through pathways involving hydrogen peroxide (H(2)O(2)) derived from superoxide (O(2)(&z.rad;-)). In contrast, the up-regulation of PDF1.2 transcript was mediated through a pathway involving O(2)(&z.rad;-) directly. The origins of the ROS were also shown to be distinct and to involve NADPH oxidase and peroxidase(s). The up-regulation of Chs by UV-B was not affected by ROS scavengers, but was reduced by inhibitors of nitric oxide synthase (NOS) or NO scavengers. Together these results suggest that UV-B exposure leads to the generation of ROS, from multiple sources, and NO, through increased NOS activity, giving rise to parallel signaling pathways mediating responses of specific genes to UV-B radiation.

  9. Unusually strong nitric oxide descent in the Arctic middle atmosphere in early 2013 as observed by Odin/SMR

    NASA Astrophysics Data System (ADS)

    Pérot, K.; Urban, J.; Murtagh, D. P.

    2014-08-01

    The middle atmosphere was affected by an exceptionally strong midwinter stratospheric sudden warming (SSW) during the Arctic winter 2012/2013. These unusual meteorological conditions led to a breakdown of the polar vortex, followed by the reformation of a strong upper stratospheric vortex associated with particularly efficient descent of air. Measurements by the submillimetre radiometer (SMR), on board the Odin satellite, show that very large amounts of nitric oxide (NO), produced by energetic particle precipitation (EPP) in the mesosphere/lower thermosphere (MLT), could thus enter the polar stratosphere in early 2013. The mechanism referring to the downward transport of EPP-generated NOx during winter is generally called the EPP indirect effect. SMR observed up to 20 times more NO in the upper stratosphere than the average NO measured at the same latitude, pressure and time during three previous winters where no mixing between mesospheric and stratospheric air was noticeable. This event turned out to be the strongest in the aeronomy-only period of SMR (2007-present). Our study is based on a comparison with the Arctic winter 2008/2009, when a similar situation was observed. This outstanding situation is the result of the combination of a relatively high geomagnetic activity and an unusually high dynamical activity, which makes this case a prime example to study the EPP impacts on the atmospheric composition.

  10. 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] ...

  11. Inhaled Steroids

    MedlinePlus

    ... side effects with inhaled steroids are thrush (a yeast infection of the mouth or throat that causes ... There have been concerns regarding the possibility of growth suppression in children. Recent studies have not shown ...

  12. Crucial Role for Neuronal Nitric Oxide Synthase in Early Microcirculatory Derangement and Recipient Survival following Murine Pancreas Transplantation

    PubMed Central

    Cardini, Benno; Watschinger, Katrin; Hermann, Martin; Obrist, Peter; Oberhuber, Rupert; Brandacher, Gerald; Chuaiphichai, Surawee; Channon, Keith M.; Pratschke, Johann; Maglione, Manuel; Werner, Ernst R.

    2014-01-01

    Objective Aim of this study was to identify the nitric oxide synthase (NOS) isoform involved in early microcirculatory derangements following solid organ transplantation. Background Tetrahydrobiopterin donor treatment has been shown to specifically attenuate these derangements following pancreas transplantation, and tetrahydrobiopterin-mediated protective effects to rely on its NOS-cofactor activity, rather than on its antioxidant capacity. However, the NOS-isoform mainly involved in this process has still to be defined. Methods Using a murine pancreas transplantation model, grafts lacking one of the three NOS-isoforms were compared to grafts from wild-type controls. Donors were treated with either tetrahydrobiopterin or remained untreated. All grafts were subjected to 16 h cold ischemia time and transplanted into wild-type recipients. Following 4 h graft reperfusion, microcirculation was analysed by confocal intravital fluorescence microscopy. Recipient survival was monitored for 50 days. Results Transplantation of the pancreas from untreated wild-type donor mice resulted in microcirculatory damage of the transplanted graft and no recipient survived more than 72 h. Transplanting grafts from untreated donor mice lacking either endothelial or inducible NOS led to similar outcomes. In contrast, donor treatment with tetrahydrobiopterin prevented microcirculatory breakdown enabling long-term survival. Sole exception was transplantation of grafts from untreated donor mice lacking neuronal NOS. It resulted in intact microvascular structure and long-term recipient survival, either if donor mice were untreated or treated with tetrahydrobiopterin. Conclusion We demonstrate for the first time the crucial involvement of neuronal NOS in early microcirculatory derangements following solid organ transplantation. In this model, protective effects of tetrahydrobiopterin are mediated by targeting this isoform. PMID:25389974

  13. Role of nitric oxide synthases in early blood-brain barrier disruption following transient focal cerebral ischemia.

    PubMed

    Jiang, Zheng; Li, Chun; Arrick, Denise M; Yang, Shu; Baluna, Alexandra E; Sun, Hong

    2014-01-01

    The role of nitric oxide synthases (NOSs) in early blood-brain barrier (BBB) disruption was determined using a new mouse model of transient focal cerebral ischemia. Ischemia was induced by ligating the middle cerebral artery (MCA) at its M2 segment and reperfusion was induced by releasing the ligation. The diameter alteration of the MCA, arterial anastomoses and collateral arteries were imaged and measured in real time. BBB disruption was assessed by Evans Blue (EB) and sodium fluorescein (Na-F) extravasation at 3 hours of reperfusion. The reperfusion produced an extensive vasodilation and a sustained hyperemia. Although expression of NOSs was not altered at 3 hours of reperfusion, L-NAME (a non-specific NOS inhibitor) abolished reperfusion-induced vasodilation/hyperemia and significantly reduced EB and Na-F extravasation. L-NIO (an endothelial NOS (eNOS) inhibitor) significantly attenuated cerebral vasodilation but not BBB disruption, whereas L-NPA and 7-NI (neuronal NOS (nNOS) inhibitors) significantly reduced BBB disruption but not cerebral vasodilation. In contrast, aminoguanidine (AG) (an inducible NOS (iNOS) inhibitor) had less effect on either cerebral vasodilation or BBB disruption. On the other hand, papaverine (PV) not only increased the vasodilation/hyperemia but also significantly reduced BBB disruption. Combined treatment with L-NAME and PV preserved the vasodilation/hyperemia and significantly reduced BBB disruption. Our findings suggest that nNOS may play a major role in early BBB disruption following transient focal cerebral ischemia via a hyperemia-independent mechanism.

  14. Intrauterine growth retardation in endothelial nitric oxide synthase-deficient mice is established from early stages of pregnancy.

    PubMed

    Pallares, Pilar; Gonzalez-Bulnes, Antonio

    2008-06-01

    The current study aimed to determine effects of deficiencies in nitric oxide synthase (NOS) 3 on embryo and fetal development by in vivo, noninvasive, real-time ultrasonographic assessment of phenotypic changes in Nos3-knockout pregnant mice and their wild-type counterparts. From Day 4.5 of pregnancy onwards, embryonic vesicle diameters, crown-rump lengths, and trunk diameters were obtained by serial scanning of seven adult pregnant female mice, strain B6.129P2-Nos3(tm1Unc)/J, N9 generation backcrossing with C57BL/6J mice, homozygous for the disruption of the endothelial NOS gene (group Nos3(-/-)), and 12 pregnant, wild-type C57BL/6J mice (group Nos3(+/+)). All the measurements increased in both genotypes throughout gestation. However, embryo length and width were significantly larger in Nos3(+/+) than in Nos3(-/-) mice from Day 8.5, and both longitudinal and transverse diameters of the entire gestational sacs were larger in Nos3(+/+) mice from Day 10.5. Assessment of the relative growth of embryos/fetuses and gestational annexes showed different patterns among Nos3(-/-) and Nos3(+/+) mice. Throughout pregnancy, the distance between the external limit of the gestational sac and the embryo in Nos3(+/+) mice diminished in longitudinal sections, or remained unaffected in transverse sections. In Nos3(-/-) mice, there were significant increases (P < 0.005) in the differences between embryo and gestational vesicle measurements in both longitudinal and transversal curves from Days 5.5 to 14.5, but from Day 14.5 of pregnancy onward, the changes were not significant. The results demonstrate that the processes of fetal growth retardation in the Nos3(-/-) mice are established from early pregnancy stages.

  15. Hydrodynamics of viscous inhalant flows

    NASA Astrophysics Data System (ADS)

    True, Aaron C.; Crimaldi, John P.

    2017-05-01

    Inhalant flows draw fluid into an orifice from a reservoir and are ubiquitous in engineering and biology. Surprisingly, there is a lack of quantitative information on viscous inhalant flows. We consider here laminar flows (Reynolds number Re≤100 ) developing after impulsive inhalation begins. We implement finite element simulations of flows with varying Re and extraction height h (orifice height above a bottom bed). Numerical results are experimentally validated using particle image velocimetry measurements in a physical model for a representative flow case in the middle of the Re-h parameter space. We use two metrics to characterize the flow in space and time: regions of influence (ROIs), which describe the spatial extent of the flow field, and inhalation volumes, which describe the initial distribution of inhaled fluid. The transient response for all Re features an inviscid sinklike component at early times followed by a viscous diffusive component. At lower Re, diffusion entrains an increasing volume of fluid over time, enlarging the ROI indefinitely. In some geometries, these flows spatially bifurcate, with some fluid being inhaled through the orifice and some bypassing into recirculation. At higher Re, inward advection dominates outward viscous diffusion and the flow remains trapped in a sinklike state. Both ROIs and inhalation volumes are strongly dependent on Re and extraction height, suggesting that organisms or engineers could tune these parameters to achieve specific inhalation criteria.

  16. The effects of perioperative inhaled iloprost on pulmonary hypertension with congenital heart disease.

    PubMed

    Sung, Ki Won; Jeon, Yang Bin; Kim, Na Yeon; Park, Kook Yang; Park, Chul Hyun; Choi, Chang Hyu; Choi, Deok Young

    2013-01-01

    The treatment of choice for congenital heart disease (CHD) with pulmonary arterial hypertension (PAH) is still controversial. We assessed the efficacy and safety of perioperative inhaled iloprost therapy in CHD with PAH. Among 45 patients with a ventricular septal defect and/or an atrial septal defect with PAH, 28 patients were treated with inhaled iloprost before and after surgery. Perioperative clinical parameters and plasma B-type natriuretic peptide (BNP) were evaluated. No statistical difference in the estimated right ventricular systolic pressure (e-RVP), the e-RVP-to-systemic pressure ratio, and preoperative BNP levels between the iloprost group and the control group were found. Among the iloprost group, oxygen saturation was increased significantly after iloprost inhalation therapy (p = 0.0052). The iloprost group was also significantly correlated with less use of inhaled nitric oxide in the immediate postoperative period compared to the control group (p = 0.021). The durations of mechanical ventilation (p = 0.018), ICU stay (p = 0.005), and chest tube use (p = 0.039) were significantly shorter in the iloprost group compared to the control group. The plasma BNP, checked on 7th day of postoperatively, was lower in the iloprost group than in the control group (p = 0.008). Perioperative inhaled iloprost therapy showed the benefit of cardiac functional improvement and early weaning of postoperative supportive care in the management of CHD with PAH.

  17. Nitric oxide: a key mediator in the early and late phase of carrageenan-induced rat paw inflammation.

    PubMed Central

    Salvemini, D.; Wang, Z. Q.; Wyatt, P. S.; Bourdon, D. M.; Marino, M. H.; Manning, P. T.; Currie, M. G.

    1996-01-01

    1 The role of nitric oxide (NO) derived from constitutive and inducible nitric oxide synthase (cNOS and iNOS) and its relationship to oxygen-derived free radicals and prostaglandins (PG) was investigated in a carrageenan-induced model of acute hindpaw inflammation. 2 The intraplantar injection of carrageenan elicited an inflammatory response that was characterized by a time-dependent increase in paw oedema, neutrophil infiltration, and increased levels of nitrite/nitrate (NO2-/NO3-) and prostaglandin E2(PGE2) in the paw exudate. 3 Paw oedema was maximal by 6 h and remained elevated for 10 h following carrageenan administration. The non-selective cNOS/iNOS inhibitors, NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME) given intravenously (30-300 mg kg-1) 1 h before or after carrageenan administration, inhibited paw oedema at all time points. 4 The selective iNOS inhibitors, N-iminoethyl-L-lysine (L-NIL) or aminoguanidine (AG), failed to inhibit carrageenan-induced paw oedema during the first 4 h following carrageenan administration, but inhibited paw oedema at subsequent time points (from 5-10 h). iNOS mRNA was detected between 3 to 10 h following carrageenan administration using ribonuclease protection assays. iNOS protein was first detected 6 h and was maximal 10 h following carrageenan administration as shown by Western blot analysis. Administration of the iNOS inhibitors 5 h after carrageenan (a time point where iNOS was expressed) inhibited paw oedema at all subsequent time points. Infiltrating neutrophils were not the source of iNOS since pretreatment with colchicine (2 mg kg-1) suppressed neutrophil infiltration, but did not inhibit the iNOS mRNA expression or the elevated NO2-/NO3- levels in the paw exudate. 5 Inhibition of paw oedema by the NOS inhibitors was associated with attenuation of both the NO2-/NO3- and PGE2 levels in the paw exudate. These inhibitors also reduced the neutrophil infiltration at the site of inflammation

  18. Early bronchodilatory effects of budesonide/formoterol pMDI compared with fluticasone/salmeterol DPI and albuterol pMDI: 2 randomized controlled trials in adults with persistent asthma previously treated with inhaled corticosteroids.

    PubMed

    Hampel, Frank C; Martin, Paula; Mezzanotte, William S

    2008-05-01

    Two identically designed, randomized, multicenter, single-dose, crossover studies were conducted in patients aged > or = 18 years with mild to moderate asthma previously treated with inhaled corticosteroids. After 2 weeks on twice-daily budesonide pressurized metered-dose inhaler (pMDI) 160 microg, patients received a randomized sequence of budesonide/formoterol pMDI 80/4.5 microg x 2 inhalations (160/9 microg), fluticasone/salmeterol dry powder inhaler (DPI) 250/50 microg x 1 inhalation, albuterol pMDI 90 microg x 2 inhalations (180 microg), and placebo pMDI (3-to 14-day washout periods). Improvements in forced expiratory volume in 1 second (FEV(1)) at 3 minutes were significantly (p < 0.001) greater after treatment with budesonide/formoterol pMDI compared with fluticasone/salmeterol DPI and similar to that of albuterol pMDI. In addition, significantly (p < 0.001) more patients treated with budesonide/formoterol pMDI achieved a 15% improvement in FEV(1) within 15 minutes compared with patients treated with fluticasone/salmeterol DPI and placebo. Thus, the early bronchodilatory effects of budesonide/formoterol pMDI were greater than with fluticasone/salmeterol DPI.

  19. 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.

  20. Inhalation Injury.

    DTIC Science & Technology

    1994-01-01

    alpha,-antitrypsin resulting cur most often as the result of tracheal in prolonged action of proteases such as or laryngeal damage from the endotra... curs is determined by physicochemical Turbulent airflow, such as at bifurca- properties of the inhaled substance, its tions of the airway, separates

  1. 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.

  2. Effects of chronic nitric oxide activation or inhibition on early hepatic fibrosis in rats with bile duct ligation.

    PubMed

    Mayoral, P; Criado, M; Hidalgo, F; Flores, O; Arévalo, M A; Eleno, N; Sánchez-Rodríguez, A; López-Novoa, J M; Esteller, A

    1999-03-01

    Hepatic fibrosis or increased liver collagen contents drive functional abnormalities that, when extensive, may be life threatening. The purpose of this study was to assess the effects of the chronic stimulation or inhibition of nitric oxide synthesis in rats with hepatic fibrosis induced by permanent common bile duct ligation (3 weeks) and the role of expression of the different nitric oxide synthase isoforms. Bile duct ligation led to an important accumulation of collagen in the hepatic parenchyma, as shown both histologically and by the hydroxyproline contents of livers. Bilirubin and serum enzyme activities (measured as markers of cholestasis) increased several-fold after bile duct ligation. The area of fibrotic tissue, liver hydroxyproline content and serum markers of cholestasis were clearly related in obstructed rats. The absence of modifications in haemodynamic parameters excludes circulatory changes from being responsible for the development of liver alterations. In animals treated with NG-nitro-L-arginine methyl ester (L-NAME) the area of fibrosis was similar to that of untreated animals, the signs of cholestasis and cellular injury being more evident. In rats treated with L-arginine the area of fibrosis was almost three times larger than that found in bile duct ligated rats and in L-NAME-treated bile duct ligated rats, although the observed biochemical changes were similar to those seen in rats treated with L-NAME. Our results with inducible nitric oxide synthase, obtained by Western blots and immunohistochemistry, indicate a greater expression of the inducible enzyme in bile duct ligated and L-arginine-treated animals and a lower expression in the L-NAME and control groups. Constitutive nitric oxide synthase expression, obtained by Western blots, was very similar in all groups, except for the L-arginine-treated rats in which it was lower. These results suggest that nitric oxide production may be a key factor in the development of fibrosis in bile duct

  3. Ipratropium Oral Inhalation

    MedlinePlus

    ... not use your ipratropium inhaler when you are near a flame or source of heat. The inhaler may explode if it is exposed to very high temperatures.Before you use ipratropium inhalation for the first ...

  4. Beclomethasone Oral Inhalation

    MedlinePlus

    ... not use your beclomethasone inhaler when you are near a flame or source of heat. The inhaler may explode if it is exposed to very high temperatures.Each beclomethasone inhaler is designed to provide 50, ...

  5. Nicotine Oral Inhalation

    MedlinePlus

    Nicotine oral inhalation is used to help people stop smoking. Nicotine oral inhalation should be used together with a ... support groups, counseling, or specific behavioral change techniques. Nicotine inhalation is in a class of medications called ...

  6. Albuterol Oral Inhalation

    MedlinePlus

    ... and airways). Albuterol inhalation aerosol and powder for oral inhalation is also used to prevent breathing difficulties ... years of age and older. Albuterol powder for oral inhalation (Proair Respiclick) is used in children 12 ...

  7. 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

  8. 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

  9. Inhalation toxicology.

    PubMed

    MacFarland, H N

    1975-07-01

    Two kinds of problems associated with developing standardized procedures for the safety evaluation of new compounds are identified. The first of these is the question of the desirability of using such standard methods. It is concluded that a basic set of procedures is to be recommended, but this should be supplemented with special tests as may be indicated. The second problem is connected with the technical difficulties of any given type of assay and is normally dealt with in terms of the state of the art at the time. Assays by the inhalation route tend to be custom designed and do not follow standard protocols. One of the causes of this situation is the propensity of individual investigators to design de novo the equipment used to effect exposure of animals to airborne substances. Second, some confusion exists because investigators do not always appreciate that the concentration-time product is not the same as the true dose received by the exposed subjects and this may lead to anomalies when dose-response relationships are being characterized. It is suggested that interlaboratory studies be undertaken to ascertain the variability that might be expected in independent assays of inhalation toxicity.

  10. Chlorine Gas Inhalation

    PubMed Central

    White, Carl W.; Martin, James G.

    2010-01-01

    inhalation have demonstrated evidence of oxidative injury and inflammation. Early epithelial injury, airways hyperresponsiveness, and airway remodeling, likely diminishing over time, have been shown. As in humans, ALI/ARDS can occur, becoming more likely when the upper airways are bypassed. Inhalation models of chlorine toxicity provide unique opportunities for testing potential pharmacologic rescue agents. PMID:20601629

  11. Prevalence, timing, and predictors of transitions from inhalant use to inhalant use disorders.

    PubMed

    Perron, Brian E; Howard, Matthew O; Maitra, Samopriyo; Vaughn, Michael G

    2009-03-01

    Few studies of the natural history of DSM-IV inhalant substance use disorders (I-SUDs) have been conducted. This investigation examined the prevalence, timing, and predictors of transitions from inhalant use to formal I-SUDs among inhalant users within a nationally representative sample. Participants were 664 U.S. residents participating in the 2000-2001 National Epidemiologic Survey on Alcohol and Related Conditions who reported lifetime inhalant use. Respondents completed structured interviews assessing DSM-IV psychiatric/substance use disorders. Bivariate and Cox regression analyses were conducted to identify risk factors for transitions from inhalant use to I-SUDs. Nearly one in five (19.4%) persons initiating inhalant use developed an I-SUD. Most I-SUD transitions were to inhalant abuse rather than inhalant dependence. Risk for development of I-SUDs was greatest in the first year following initiation of inhalant use and low thereafter. Multivariate proportional hazards models indicated that presence of a mood/anxiety disorder (HR=7.7, CI=3.1-18.9) or alcohol use disorder (HR=11.9, CI=5.46-26.00) antedating initiation of inhalant use predicted significantly elevated risk for I-SUDs, whereas being married conferred a lower risk for onset of I-SUDs. I-SUDs were relatively common among inhalant users, generally occurred in the year following initiation of inhalant use, and were associated with early-onset mood/anxiety and alcohol use disorders. Given the young average age at onset of inhalant use and the rapidity with which most I-SUDs developed, interventions directed to adolescents who have initiated inhalant use might be effective in reducing the proportion of inhalant users who develop I-SUDs.

  12. Nitrate reductase-mediated early nitric oxide burst alleviates oxidative damage induced by aluminum through enhancement of antioxidant defenses in roots of wheat (Triticum aestivum).

    PubMed

    Sun, Chengliang; Lu, Lingli; Liu, Lijuan; Liu, Wenjing; Yu, Yan; Liu, Xiaoxia; Hu, Yan; Jin, Chongwei; Lin, Xianyong

    2014-03-01

    Nitric oxide (NO) is an important signaling molecule involved in the physiological processes of plants. The role of NO release in the tolerance strategies of roots of wheat (Triticum aestivum) under aluminum (Al) stress was investigated using two genotypes with different Al resistances. • An early NO burst at 3 h was observed in the root tips of the Al-tolerant genotype Jian-864, whereas the Al-sensitive genotype Yang-5 showed no NO accumulation at 3 h but an extremely high NO concentration after 12 h. Stimulating NO production at 3 h in the root tips of Yang-5 with the NO donor relieved Al-induced root inhibition and callose production, as well as oxidative damage and ROS accumulation, while elimination of the early NO burst by NO scavenger aggravated root inhibition in Jian-864. • Synthesis of early NO in roots of Jian-864 was mediated through nitrate reductase (NR) but not through NO synthase. Elevated antioxidant enzyme activities were induced by Al stress in both wheat genotypes and significantly enhanced by NO donor, but suppressed by NO scavenger or NR inhibitor. • These results suggest that an NR-mediated early NO burst plays an important role in Al resistance of wheat through modulating enhanced antioxidant defense to adapt to Al stress.

  13. Theoretical evaluation of burns to the human respiratory tract due to inhalation of hot gas in the early stage of fires.

    PubMed

    Lv, Yong-Gang; Liu, Jing; Zhang, Jun

    2006-06-01

    A transient two-dimensional mathematical model for heat and water vapor transport across the respiratory tract of human body was established and applied to predict the thermal impact of inhaled hot gas to the nasal tissues during the early stage of fires. Influences of individual's physiological status and environment variables were comprehensively investigated through numerical calculations. Burn evaluation was performed using the classical Henriques model to predict the time for thermal injury to occur. It was shown that decreasing the air velocity and increasing the respiratory rate is helpful to minimize the burn over the respiratory tract. The effect of relative humidity of surrounding dry hot air could be ignored in predicting burns for short duration exposures. Due to evaporation cooling on the mucousal membrane, the burn often occurs at certain positions underneath the skin of the tract near the inlet of the respiratory tract. Most of the tissues near the surface suffer injury immediately after exposure to fire, while in the deeper tissues, serious damage occurs after a relatively longer time period. The method presented in this paper may suggest a valuable approach to theoretically evaluate the injury of hot air to the human respiratory tract under various fire situations.

  14. 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 ...

  15. 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 ...

  16. 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 ...

  17. 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

  18. The effect of exposure to sulphuric acid on the early asthmatic response to inhaled grass pollen allergen.

    PubMed

    Tunnicliffe, W S; Evans, D E; Mark, D; Harrison, R M; Ayres, J G

    2001-10-01

    Particulate sulphates, including sulphuric acid (H2SO4), are important components of the ambient aerosol in some areas and are regarded as air pollutants with potentially important human health effects. Challenge studies suggest little or no effect of H2SO4 exposure on lung function in asthmatic adults, although some epidemiological studies demonstrate an effect of acid species on symptoms in subjects with asthma. To date, the effect of H2SO4 on allergen responsiveness has not been studied. The effect of exposure to particulate H2SO4 on the early asthmatic response to grass pollen allergen has been investigated in 13 adults with mild asthma. After establishment of the provocative dose of allergen producing a 15% fall in forced expiratory volume in one second (FEVI) (PD15) for each subject, they were exposed to air, 100 microg m(-3) or 1,000 g x m(-3) H2SO4 for 1 h, double-blind in random order > or =2 weeks apart, through a head dome delivery system 14 h after each exposure subject underwent a fixed-dose allergen challenge (PD15). Ten subjects completed the study. The mean early asthmatic responses (maximum percentage change in FEV1 during the first 2 h after challenge) following air, 100 microg x m(-3) H2SO4, and 1,000 microg m(-3) H2SO4, were -14.1%, -16.7%, and -18.4%, respectively. The difference between 1,000 microg x m(-3) H2SO4 and air was significant (mean difference: -4.3%, 95% confidence interval (CI: -1.2-7.4%, p=0.013). The difference between air and 100 microg m(-3) H2SO4 approached significance (mean difference: -2.6%, 95% CI: 0.0-5.3%, p = 0.051). These results suggest that, at least at high mass concentration, sulphuric acid can potentiate the early asthmatic response of mild asthmatic subjects to grass pollen allergen, although the effect is limited.

  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. 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

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

    PubMed

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

    2016-01-01

    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. 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. 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. 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 potentially useful in clinical practice, although

  2. Nitric oxide and airway reactivity.

    PubMed

    Strapkova, A; Nosalova, G

    2001-01-01

    Nitric oxide is a neurotransmitter of the inhibitory nonadrenergic noncholinergic mediation in the respiratory system. Its participation in the regulation of airways functions is determined by its level in the organism. We examined participation of nitric oxide in the changes of the airway reactivity evoked by toluene exposure as the source of the free radicals. The changes of nitric oxide level in the organism were evoked by administration of its indirect donor isosorbide dinitrate. Thiol groups were provided by administration of antioxidative mucolytic N-acetylcysteine. Used drugs--isosorbide dinitrate (5 mg/kg b.w.) and N-acetylcysteine (300 mg/kg b.w.) were administered intraperitoneally or by inhalation 30 minutes before each exposure to the toluene vapours. The control group was not treated with drugs. After toluene exposure (2 hours in each of 3 consecutive days) tracheal and lung strips smooth muscle reactivity to histamine was observed under in "in vitro" conditions. The administration of isosorbide dinitrate decreased especially the lung strip smooth muscle reactivity to histamine. We revealed more expressive effect of the pretreatment with intraperitoneally administered isosorbide dinitrate in the comparison with inhalation. Simultaneous pretreatment with N-acetylcysteine intensified beneficial effect of isosorbide dinitrate probably by increasing of the intracellullary level of thiols. In our experimental conditions possible participation of nitric oxide in changes of airways smooth muscle reactivity after exposure to the toluene follows from results, as well as the importance of thiol groups for the activity of its indirect donors. (Fig. 6, Tab. 3, Ref. 35.)

  3. 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.

  4. A novel lignan composition from Cedrus deodara induces apoptosis and early nitric oxide generation in human leukemia Molt-4 and HL-60 cells.

    PubMed

    Shashi, Bhushan; Jaswant, Singh; Madhusudana, Rao J; Kumar, Saxena A; Nabi, Qazi G

    2006-02-01

    AP9-cd, a standardized lignan composition from Cedrus deodara consisting of (-)-wikstromal, (-)-matairesinol, and dibenzyl butyrolactol, showed cytotoxicity in several human cancer cell lines reported earlier. An attempt was made in this study to investigate the mechanism of cell death in human leukemia Molt-4 and HL-60 cells. It inhibited Molt-4 cell proliferation with 48-h IC(50) of approximately 15 microg/ml, increased sub-G0 cell fraction with no mitotic block, produced apoptotic bodies and induced DNA ladder formation. Flow cytometric analysis of annexinV-FITC/PI-stained cells showed time-related increase in apoptosis and post-apoptotic necrosis. All these biological end-points indicated cell death by apoptosis. Further, initial events involved massive nitric oxide (NO) formation within 4 h with subsequent late appearance of peroxides in cells; measured by flow cytometry using specific fluorescent probes. Persistently high levels of NO and peroxide appeared to decrease mitochondrial membrane potential (Psi(mt)) which was recovered by cyclosporin A in Molt-4 cells. AP9-cd caused 2-fold activation of caspase-3 in Molt-4 and 5-fold activation in HL-60 cells. Also caspases-8 and -9 were activated in HL-60 cells. Ascorbate suppressed the enhanced caspases activities indicating a pro-oxidant effect of AP9-cd. Further, caspase-3 activation correlated with NO generation that was partially impaired by nitric oxide synthase (NOS) inhibitors and ascorbate suggesting a role of pro-oxidant species in caspase-3 activation. AP9-cd produced no cytotoxicity in primary rat hepatocyte culture at the concentrations used. The studies indicated that AP9-cd mediated early NO formation leads to caspases activation, peroxide generation, and mitochondrial depolarization which may be responsible for mitochondrial-dependent and -independent apoptotic pathways involved in the killing of leukemia cells by AP9-cd.

  5. [Inhalant-related disorder].

    PubMed

    Mizuhara, Yuki; Tsuchida, Hideto; Fukui, Kenji

    2010-08-01

    Inhalant abuse and dependence are prevalent in adolescent population because inhalants are inexpensive, legal and accessible substance for youth. In Japan, the prevalence of inhalant abuse and dependence is gradually declining in these days, although inhalants can still become a "gateway drug" to other dependent substances such as cocaine and cannabinoids. Inhalant abuse causes show serious mental and somatic symptoms, and mortality in acute and chronic phases, while the abusers are ignorant about it. This paper reviews recent studies that investigate the symptoms and the treatments of inhalant abuse and dependence.

  6. Inhalation Therapy in Horses.

    PubMed

    Cha, Mandy L; Costa, Lais R R

    2017-04-01

    This article discusses the benefits and limitations of inhalation therapy in horses. Inhalation drug therapy delivers the drug directly to the airways, thereby achieving maximal drug concentrations at the target site. Inhalation therapy has the additional advantage of decreasing systemic side effects. Inhalation therapy in horses is delivered by the use of nebulizers or pressured metered dose inhalers. It also requires the use of a muzzle or nasal mask in horses. Drugs most commonly delivered through inhalation drug therapy in horses include bronchodilators, antiinflammatories, and antimicrobials.

  7. Early inflammatory response to asbestos exposure in rat and hamster lungs: role of inducible nitric oxide synthase.

    PubMed

    Dörger, Martina; Allmeling, Anne-Marie; Kiefmann, Rainer; Münzing, Silvia; Messmer, Konrad; Krombach, Fritz

    2002-06-01

    Recent studies have suggested that inducible nitric oxide synthase (iNOS) plays a role in the development of asbestos-related pulmonary disorders. The pulmonary reactions of rats and hamsters upon exposure to asbestos fibers are well known to be disparate. In addition, in vitro experiments have indicated that mononuclear phagocytes from hamsters, in contrast to those from rats, lack the iNOS pathway. Therefore, the purpose of this study was to investigate whether rats and hamsters differ in lung iNOS expression in vivo upon exposure to asbestos fibers and whether differences in iNOS induction are associated with differences in the acute pulmonary inflammatory reaction. Body weight, alveolar-arterial oxygen difference, differential cell count in bronchoalveolar lavage fluid, total protein leakage, lung myeloperoxidase activity and lipidperoxidation, wet/dry ratio, iNOS mRNA and protein expression, and nitrotyrosine staining of lung tissue were determined 1 and 7 days after intratracheal instillation of asbestos fibers in CD rats and Syrian golden hamsters. Exposure of rats to asbestos fibers resulted in enhanced pulmonary iNOS expression and nitrotyrosine staining together with an acute inflammation that was characterized by an influx of neutrophils, enhanced myeloperoxidase activity and lipid peroxidation, damage of the alveolar-capillary membrane, edema formation, and impairment of gas exchange. In comparison, instillation of asbestos fibers in hamsters resulted in a significantly milder inflammatory reaction of the lung with no induction of iNOS in pulmonary cells. The data obtained provide important information to understand the underlying mechanisms of species differences in the pulmonary response upon exposure to asbestos fibers.

  8. Smoke inhalation injury

    NASA Astrophysics Data System (ADS)

    Birky, M.

    The cause of death by fires was studied. The present results and information are, however, not enough to reduce loss of life or inhalation injury. The magnitude and type of inhalation injury for civilians and firefighters represents the most inadequately defined human element of accidental fires. Little information is available on compounds other than carbon monoxide, which are responsible for respiration injury or toxicological syndrome. Effective treatment methods for inhalation victims and studies on fatalities, inhalation injury and animals are suggested.

  9. Interplay between GST and nitric oxide in the early response of soybean (Glycine max L.) plants to salinity stress.

    PubMed

    Dinler, Burcu Seckin; Antoniou, Chrystalla; Fotopoulos, Vasileios

    2014-11-15

    Glutathione-s-transferases (GSTs) and nitric oxide (NO) have both been implicated in the response of plants to salinity stress. However, their interplay and underlying mechanisms are relatively unknown. The present study attempts to provide new insight into the time course effects of NO application on GST biosynthesis regulation in Glycine max L. leaves under salt stress. A 150μM concentration of sodium nitroprusside (SNP), a widely used NO donor, was sprayed on soybean seedlings for two days at 24h intervals, followed by application of 200mM NaCl. The relative water content (RWC), total chlorophyll content (CHL), stomatal conductance (gs), ABA content, malondialdehyde (MDA), hydrogen peroxide content (H2O2), along with GST enzyme and isoenzyme activities and GST1 and GST4 transcript levels were determined at 0h, 6h and 12h after stress imposition. The results indicated that salt treatment alone did not alter MDA, H2O2 or ABA content and stomatal conductance in soybean leaves, most likely due to short-term (6h and 12h) application, although lower RWC and CHL were recorded. SNP treatment alone increased ABA content and reduced stomatal conductance, but did not change RWC, CHL, MDA (except at 12h) and H2O2. However, exogenous SNP application protected soybean leaves from salt stress by increasing RWC, CHL and ABA content, as well as by lowering stomatal conductance in order to maintain water balance. A significant increase in GST activity was recorded under salt stress alone at 6h. Conversely, SNP application lowered GST activity in soybean leaves at 0h and 12h, while it increased at 6h, supported by GST isoenzyme activities. Thus, it could be suggested that exogenous NO application induced GST activity in an ABA-dependent manner, while GST activity could also be induced by salt stress independent of ABA. In addition, SNP pre-treatment in salt-stressed seedlings lowered GST activity at 6h and 12h, in line with the GST isoenzyme expression profile. Finally, GST1 and

  10. Focus on Inhalants.

    ERIC Educational Resources Information Center

    Challenge: Safe, Disciplines, and Drug-Free Schools, 1994

    1994-01-01

    The use of inhalants is a major health concern among the school-age population. Information presented in this publication dispels the myths about inhalant use and presents common warning signs that alert teachers to a student's use. The short- and long-term effects of inhalant use are described to shed light on the health risks involved. Lesson…

  11. CBOs Helping Inhalant Abusers.

    ERIC Educational Resources Information Center

    Rubio, Gloria

    1980-01-01

    Noting the high barrio use of inhalants, the environment often surrounding inhaling, and various treatment approaches, the article describes the programs of several Hispanic community-based organizations in Mexico, Arizona, and California which have been developed to assist inhalant abusers and their families in overcoming the habit. (SB)

  12. 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.

  13. Inhalant abuse and dependence among adolescents in the United States.

    PubMed

    Wu, Li-Tzy; Pilowsky, Daniel J; Schlenger, William E

    2004-10-01

    To examine the patterns of inhalant use and correlates of the progression from inhalant use to abuse and dependence among adolescents aged 12 to 17. Study data were drawn from the 2000 and 2001 National Household Surveys on Drug Abuse. Multinominal logistic regression was used to identify the characteristics associated with progression to inhalant abuse and dependence. Inhalant use was common among the studied adolescents. Among adolescents aged 12 to 17, 0.4% met DSM-IV inhalant abuse or dependence criteria in the past year. Inhalant abuse and dependence affected adolescents regardless of gender, age, race/ethnicity, and family income. The progression from inhalant use to abuse or dependence was related to early first use, use of multiple inhalants, and weekly inhalant use. Adolescents with inhalant use disorders reported coexisting multiple drug abuse and dependence, mental health treatment, and delinquent behaviors. Adolescents with an inhalant use disorder may represent a subgroup of highly troubled youths with multiple vulnerabilities. Because early use is associated with progression to abuse and dependence, prevention programs should target elementary school-age children.

  14. Inhalant Abuse and Dependence Among Adolescents in the United States

    PubMed Central

    WU, LI-TZY; PILOWSKY, DANIEL J.; SCHLENGER, WILLIAM E.

    2005-01-01

    Objective To examine the patterns of inhalant use and correlates of the progression from inhalant use to abuse and dependence among adolescents aged 12 to 17. Method Study data were drawn from the 2000 and 2001 National Household Surveys on Drug Abuse. Multinominal logistic regression was used to identify the characteristics associated with progression to inhalant abuse and dependence. Results Inhalant use was common among the studied adolescents. Among adolescents aged 12 to 17, 0.4% met DSM-IV inhalant abuse or dependence criteria in the past year. Inhalant abuse and dependence affected adolescents regardless of gender, age, race/ethnicity, and family income. The progression from inhalant use to abuse or dependence was related to early first use, use of multiple inhalants, and weekly inhalant use. Adolescents with inhalant use disorders reported coexisting multiple drug abuse and dependence, mental health treatment, and delinquent behaviors. Conclusions Adolescents with an inhalant use disorder may represent a subgroup of highly troubled youths with multiple vulnerabilities. Because early use is associated with progression to abuse and dependence, prevention programs should target elementary school–age children. PMID:15381887

  15. Comparison of maternal and umbilical cord blood HIF-1α and nitric oxide levels in early and late onset preeclamptic pregnancies.

    PubMed

    Demircan Sezer, Selda; Küçük, Mert; Nergiz Avcıoğlu, Sümeyra; Zafer, Emre; Altınkaya, Sunduz Özlem; Bıçakçı, Burcu; Yenisey, Çiğdem; Yüksel, Hasan; Kurt Ömürlü, İmran

    2015-01-01

    Despite the absence of a complete physiologic-pathologic understanding, common accepted theory for development of preeclampsia is incomplete trophoblastic invasion leading to failed uterine and spiral arteriolar remodeling, causing maternal vascular endothelial dysfunction by secreted molecules in response to decreased placental perfusion, placental hypoxia, and ischemia. Placental angiogenesis is especially ineffective in early onset preeclampsia and fetal morbidity/mortality rates are higher because of further decreased blood flow. In this study, we aim to compare the maternal and umbilical cord blood levels of hypoxia-inducible transcription factor-1α (HIF-1α), which is believed to regulate hypoxia-related transcriptional responses, to play role in activating genes for initial phases of placental development and angiogenesis and a physiologic vasodilator molecule nitric oxide (NO) in normal, early and late onset preeclamptic pregnant women. Pregnant women who were diagnosed with preeclampsia (early onset ≤34 weeks; late onset >34 weeks) and delivered in our clinic were enrolled for this prospective case-controlled study. Pregnant women without preeclampsia were recruited as control group. HIF-1α and NO levels in maternal and umbilical cord blood measured and compared among groups. A total of 46 cases were enrolled for this study, including 25 preeclamptic (13 in the early onset group and 12 in the late onset group) and 21 normal pregnant women in the control group. Comparison of preeclampsia group to controls revealed higher maternal blood HIF-1α levels in the control group, however higher umbilical cord NO levels in the preeclampsia group (p < 0.05 and p < 0.001, respectively). In a second analysis, when compared to control group, both early and late onset preeclampsia subgroups were found to have higher umbilical cord blood NO levels (p < 0.001). In this study, we observed lower maternal blood HIF-1α levels and higher umbilical cord NO

  16. Early systemic inflammatory response in mice after a single oral gavage with live Escherichia coli is evidenced by increased TNF-alpha and nitric oxide production.

    PubMed

    Nemec, Ana; Jerin, Aleš; Zdovc, Irena; Budefeld, Tomaž; Verstraete, Frank J M; Eržen, Damijan; Sentjurc, Marjeta; Petelin, Milan; Hitti, Tina; Pavlica, Zlatko

    2012-06-01

    Twenty-four female BALB/c mice were orally inoculated with 10(8) CFU Escherichia coli ATCC 25922 and euthanized 2.5, 7, 13 and 25 h post-inoculation. The levels of organ nitric oxide (NO) and plasma endotoxin, TNF-alpha and nitrite/nitrate (NO(x)) were compared to those found in sham-inoculated mice, to evaluate systemic host-response to a low-level oral exposure to Gram-negative bacteria. Organ bacterial culture and immunohistochemistry for iNOS were performed on lungs, liver, kidneys and brain from all mice. Organ NO and plasma TNF-alpha levels were higher in E. coli-inoculated animals, but no differences were detected in plasma endotoxin levels, NO(x) or iNOS immunostaining for any of the animal groups. Single oral gavage with live E. coli stimulates an early systemic immune response in clinically healthy mice as evidenced by increased plasma TNF-alpha and organ NO levels, but bacteremia and endotoxemia are not related to this inflammatory response.

  17. 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.

  18. Inhalant Use and Delinquent Behaviors among Young Adolescents. The NSDUH Report

    ERIC Educational Resources Information Center

    US Department of Health and Human Services, 2005

    2005-01-01

    This report presents the prevalence of inhalant use among young adolescents aged 12 or 13, the association between inhalant use and delinquent behaviors within this age group, and the association between early onset of inhalant use and problems later in life. Early onset of substance use has been linked to substance use disorders, delinquent…

  19. Inhalant Use and Delinquent Behaviors among Young Adolescents. The NSDUH Report

    ERIC Educational Resources Information Center

    US Department of Health and Human Services, 2005

    2005-01-01

    This report presents the prevalence of inhalant use among young adolescents aged 12 or 13, the association between inhalant use and delinquent behaviors within this age group, and the association between early onset of inhalant use and problems later in life. Early onset of substance use has been linked to substance use disorders, delinquent…

  20. Iloprost inhalation for the treatment of severe persistent pulmonary hypertension of the newborn, experience at QSNICH.

    PubMed

    Chotigeat, Uraiwan; Champrasert, Maneewan; Khorana, Meera; Sangtaweesin, Varaporn; Kanjanapattanakul, Wiboon

    2014-06-01

    Persistent pulmonary hypertension of the newborn (PPHN) is the most serious condition that causes high mortality in term and post term infants. The authors have an experience of using high frequency oscillatory ventilation (HFOV) and inhaled nitric oxide (iNO) for treatment of this condition with a good result. However, due to high cost of iNo, other pulmonary vasodilators have been use. Sildenafil had some side effects of systemic hypotension. Thus, inhaled iloprost was introduced for treatment of PPHN at our institute. To evaluate the outcome of inhaled iloprost for the treatment of PPHN. This was a retrospective study. The data from medical records of newborns, diagnosed as persistent pulmonary hypertension of the newborn and had received inhaled iloprost from October 1st, 2008-October 31st, 2012, were reviewed. Nineteen cases of PPHN treated with inhaled iloprost were reviewed. Male to female ratio was 1.3 7:1 (11:8). Mean birth weight and gestational age of these patients were 2,997 ± 531.63 grams and 37.9 ± 2.51 weeks, respectively. Meconium aspiration syndrome was the leading underlying cause of this condition. The mortality rate in this study was 21% (4 from 19 cases). After the addition of inhaled iloprost, the oxygen index (OI) in the survivor group decreased significantly at one hour after treatment (from 32.89 to 22.06, 18.76, 13. 76 at 1, 6, 12 hours, respectively). Oxygen saturation (SpO2) continued increasing after treatment in the survivor group (from 82.40% to 92.20%, 95.00%, 95.80% at 1, 6, 12 hours, respectively) with significant difference at one hour. There was a significant difference of OI and SpO2 between the survivor and non-survivor groups after treatment. Low Apgar score at 5 minutes and early diagnosis of PPHN were found statistically significant different in the non-survivor compared to the survivor groups. Inhaled iloprost could be used as an alternative treatment of PPHN without side effects of systemic hypotension.

  1. 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

  2. Angiotensin II type 2 receptors and nitric oxide sustain oxygenation in the clipped kidney of early Goldblatt hypertensive rats.

    PubMed

    Palm, Fredrik; Connors, Stephanie G; Mendonca, Margarida; Welch, William J; Wilcox, Christopher S

    2008-02-01

    Angiotensin-converting enzyme inhibitors (ACEIs) decrease the glomerular filtration rate and renal blood flow in the clipped kidneys of early 2-kidney, 1-clip Goldblatt hypertensive rats, but the consequences for oxygenation are unclear. We investigated the hypothesis that angiotensin II type 1 or angiotensin II type 2 receptors or NO synthase mediate renal oxygenation responses to ACEI. Three weeks after left renal artery clipping, kidney function, oxygen (O(2)) use, renal blood flow, renal cortical blood flow, and renal cortical oxygen tension (Po(2)) were measured after acute administration of an ACEI (enalaprilat) and after acute administration of ACEI following acute administration of an angiotensin II type 1 or angiotensin II type 2 receptor blocker (candesartan or PD-123,319) or an NO synthase blocker (N(G)-nitro-L-arginine methyl ester with control of renal perfusion pressure) and compared with mechanical reduction in renal perfusion pressure to the levels after ACEI. The basal renal cortical Po(2) of clipped kidneys was significantly lower than contralateral kidneys (35+/-1 versus 51+/-1 mm Hg; n=40 each). ACEI lowered renal venous Po(2), cortical Po(2), renal blood flow, glomerular filtration rate, and cortical blood flow and increased the renal vascular resistance in the clipped kidney, whereas mechanical reduction in renal perfusion pressure was ineffective. PD-123,319 and N(G)-nitro-L-arginine methyl ester, but not candesartan, reduced the Po(2) of clipped kidneys and blocked the fall in Po(2) with acute ACEI administration. In conclusion, oxygen availability in the clipped kidney is maintained by angiotensin II generation, angiotensin II type 2 receptors, and NO synthase. This discloses a novel mechanism whereby angiotensin can prevent hypoxia in a kidney challenged with a reduced perfusion pressure.

  3. Inhalant abuse by adolescents.

    PubMed

    Kurtzman, T L; Otsuka, K N; Wahl, R A

    2001-03-01

    The deliberate misuse of volatile substances poses a poorly recognized risk for considerable morbidity and mortality in adolescent populations worldwide. The abuse of inhalants continues to be a significant problem among our country's youth. While many household and industrial chemicals can be inhaled, glues, paints, and aerosol propellants are among the most commonly abused. Adolescents are often unaware of the health threats posed by inhalation of solvents. Inhalation can result in serious organ system dysfunction or even sudden death. This review discusses the prevalence of inhalant abuse in the United States, summarizes the various types of substances used, highlights the major physiologic effects of inhalants, and briefly discusses associated risk behaviors, prevention and medical management.

  4. [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).

  5. Relationship of Progesterone, Bovine Pregnancy-Associated Glycoprotein-1 and Nitric Oxide with Late Embryonic and Early Fetal Mortalities in Dairy Cows

    PubMed Central

    KAREN, Aly; BAJCSY, Árpád Csaba; MINOIA, Rosa; KOVÁCS, Rezső; DE SOUSA, Noelita Melo; BECKERS, Jean-François; TIBOLD, János; MÁDL, István; SZENCI, Ottó

    2014-01-01

    The aim of the present study was to determine the relationship of progesterone (P4), bovine pregnancy-associated glycoprotein-1 (bPAG-1) and nitric oxide (NO) levels with late embryonic (LEM; day 28 to day 42) and early fetal mortalities (EFM; > day 42 to day 56) in dairy cows. Transrectal ultrasonography (6–8 MHz) was performed in 100 Holstein-Friesian cows at days 28, 42 and 56 after artificial insemination (AI; day 0) to diagnose pregnancy and to monitor the fate of the embryo. After ultrasound scanning of each cow, a milk sample was collected for assessment of P4 by an ELISA test and a blood sample was collected for assessment of bPAG-1, by using a double-antibody radioimmunoassay, and serum NO metabolites (nitrate + nitrite). Based on ultrasonographic examinations and bPAG-1-RIA, 41 of 100 inseminated cows were confirmed pregnant at day 28 after AI. Nine cows suffered of LEM, and 6 cows suffered of EFM and the overall pregnancy loss rate was 36.6% (15/41) between days 28 and 56 of pregnancy. By logistic regression analysis, there were no significant relationships between the level of P4 and bPAG-1 at day 28 after AI and the occurrence of LEM and EFM. Also, there were no significant relationships between the levels of P4 and bPAG-1 at day 42 and the occurrence of EFM. On the other hand, a significant relationship (P<0.05) was found between NO level at day 28 and the occurrence of LEM. In conclusion, measurement of the serum NO concentration at day 28 of pregnancy might help to predict the outcome of pregnancy by day 42 in dairy cows but further studies are needed to confirm this. PMID:24531657

  6. Neptunium-237 inhalation in rats.

    PubMed

    Sullivan, M F; Ruemmler, P S; Buschbom, R L

    1986-12-01

    Groups of rats were exposed to aerosols of 237Np nitrate to determine clearance rates, retention and distribution at various intervals after inhalation. Initial lung burdens (ILB) after 237Np inhalation by three treatment groups were 0.12, 0.19 and 0.37 mu Ci/kg, respectively. Radiochemical analyses of animals killed at 4, 8, 14, 28 and 90 d, as well as data for others maintained until they became moribund, showed that their lung clearance followed a three-compartment model, clearance half-times for which were 1, 35, and 10,000 d, respectively. Only 3% of the ILB was retained after 90 d; 12% of that burden had translocated to the skeleton at 750 d; the half-time for skeletal retention was 2500 d. A single tumor was the only malignancy detected in the lungs of the 35 animals allowed to survive the early phase of the study.

  7. 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.

  8. Inhalant allergies in children.

    PubMed

    Mims, James W; Veling, Maria C

    2011-06-01

    Children with chronic or recurrent upper respiratory inflammatory disease (rhinitis) should be considered for inhalant allergies. Risk factors for inhalant allergies in children include a first-degree relative with allergies, food allergy in infancy, and atopic dermatitis. Although inhalant allergies are rare in infancy, inhalant allergies are common in older children and impair quality of life and productivity. Differentiating between viral and allergic rhinitis can be challenging in children, but the child's age, history, and risk factors can provide helpful information. Allergic rhinitis is a risk factor for asthma, and if one is present, medical consideration of the other is warranted. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Protective effects of hydrogen sulfide inhalation on oxidative stress in rats with cotton smoke inhalation-induced lung injury

    PubMed Central

    HAN, ZHI-HAI; JIANG, YI; DUAN, YUN-YOU; WANG, XIAO-YANG; HUANG, YAN; FANG, TING-ZHENG

    2015-01-01

    The aim of the present study was to investigate the mechanism by which hydrogen sulfide (H2S) inhalation protects against oxidative stress in rats with cotton smoke inhalation-induced lung injury. A total of 24 male Sprague-Dawley rats were separated randomly into four groups, which included the control, H2S, smoke and smoke + H2S groups. A rat model of cotton smoke inhalation-induced lung injury was established following inhalation of 30% oxygen for 6 h. In addition, H2S (80 ppm) was inhaled by the rats in the H2S and smoke + H2S groups for 6 h following smoke or sham-smoke inhalation. Enzyme-linked immunosorbent assays were performed to measure various indices in the rat lung homogenate, while the levels of nuclear factor (NF)-κBp65 in the lung tissue of the rats were determined and semiquantitatively analyzed using immunohistochemistry. In addition, quantitative fluorescence polymerase chain reaction was employed to detect the mRNA expression of inducible nitric oxide synthase (iNOS) in the rat lung tissue. The concentrations of malondialdehyde (MDA), nitric oxide (NO), inducible iNOS and NF-κBp65, as well as the sum-integrated optical density of NF-κBp65 and the relative mRNA expression of iNOS, in the rat lung tissue from the smoke + H2S group were significantly lower when compared with the smoke group. The concentrations of MDA, NO, iNOS and NF-κBp65 in the H2S group were comparable to that of the control group. Therefore, inhalation of 80 ppm H2S may reduce iNOS mRNA transcription and the production of iNOS and NO in rats by inhibiting NF-κBp65 activation, subsequently decreasing oxidative stress and cotton smoke inhalation-induced lung injury. PMID:26170929

  10. 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...

  11. 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...

  12. Inhalant misuse in youth: time for a coordinated response.

    PubMed

    Lubman, Dan I; Hides, Leanne; Yücel, Murat

    2006-09-18

    Early adolescence is associated with high rates of experimental inhalant misuse, but only a minority continue to inhale on a regular basis. Inhalant misuse is associated with a range of adverse outcomes, including reports of increased morbidity and mortality. Research into inhalant use among adolescents is lacking, with limited data available on long-term outcomes or evidence-based approaches to treatment. Legislative and supply-reduction strategies have been introduced by a number of states and territories over recent years, but direct funding for specific targeted interventions is lacking. Investment and commitment to a national research framework, as well as coordination of local services, is urgently required.

  13. Inhalation of chlorine gas.

    PubMed Central

    Williams, J. G.

    1997-01-01

    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. Images Figure PMID:9519180

  14. Reasons for Inhalant Use.

    ERIC Educational Resources Information Center

    Joe, George W.; Simpson, D. Dwayne

    1991-01-01

    Among 110 Mexican-American adolescents in a Texas drug abuse program, initial use of toxicant inhalants was related to availability and sensation-seeking, followed by psychological problems, parental and home problems, and peer influence. Quitting inhalant use was related to social pressures, attitude change, and perceived health risks. (Author/SV)

  15. Nonthermal Inhalation Injury.

    DTIC Science & Technology

    1992-01-01

    understand the effects of the various byproducts of combustion on the human body. A thorough knowledge of the physiological mechanisms , relevant...as soon as possible. Overview of Smoke Inhalation Physiology The physiologic mechanisms of injury from smoke inhalation are multiple and complex...to breathe Lower airway obstruction Dyspnea, tachypnea, wheezing, rhonchi, carbonaceous sputum Parenchymal injury Dyspnea, tachypnea, rales Table 1

  16. Inhalants in Peru.

    PubMed

    Lerner, R; Ferrando, D

    1995-01-01

    In Peru, the prevalence and consequences of inhalant abuse appear to be low in the general population and high among marginalized children. Inhalant use ranks third in lifetime prevalence after alcohol and tobacco. Most of the use appears to be infrequent. Among marginalized children, that is, children working in the streets but living at home or children living in the street, the problem of inhalant abuse is a serious problem. Among children working in the streets but living at home, the lifetime prevalence rate for inhalant abuse is high, ranging from 15 to 45 percent depending on the study being cited. For children living in the streets, the use of inhalant is even more severe. As mentioned earlier in this chapter, most of these street children use inhalants on a daily basis. The lack of research on the problem of inhalant abuse is a serious impediment to development of intervention programs and strategies to address this problem in Peru. Epidemiologic and ethnographic research on the nature and extent of inhalant abuse are obvious prerequisites to targeted treatment and preventive intervention programs. The urgent need for current and valid data is underscored by the unique vulnerability of the youthful population at risk and the undisputed harm that results from chronic abuse of inhalants. Nonetheless, it is important to mention several programs that work with street children. Some, such as the Information and Education Center for the Prevention of Drug Abuse, Generation, and Centro Integracion de Menores en Abandono have shelters where street children are offered transition to a less marginal lifestyle. Teams of street educators provide the children with practical solutions and gain their confidence, as well as offer them alternative socialization experiences to help them survive the streets and avoid the often repressive and counterproductive environments typical of many institutions. Most of the children who go through these programs tend to abandon

  17. 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.

  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. Albuterol and Ipratropium Oral Inhalation

    MedlinePlus

    ... out of the box and insert the narrow end into the inhaler. You can press the inhaler against a hard surface to be sure it is inserted correctly. Replace the clear plastic base on the inhaler. Hold the inhaler upright with ...

  20. Huffing: What Parents Should Know about Inhalant Abuse.

    ERIC Educational Resources Information Center

    Dewey, Stephen L.

    2002-01-01

    Inhalant abuse, or "huffing," is disturbingly common among children and adolescents. This article outlines some alarming facts about this form of drug abuse, which often begins at an early age. (Author)

  1. Nitric oxide and hyperoxic acute lung injury

    PubMed Central

    Liu, Wen-wu; Han, Cui-hong; Zhang, Pei-xi; Zheng, Juan; Liu, Kan; Sun, Xue-jun

    2016-01-01

    Hyperoxic acute lung injury (HALI) refers to the damage to the lungs secondary to exposure to elevated oxygen partial pressure. HALI has been a concern in clinical practice with the development of deep diving and the use of normobaric as well as hyperbaric oxygen in clinical practice. Although the pathogenesis of HALI has been extensively studied, the findings are still controversial. Nitric oxide (NO) is an intercellular messenger and has been considered as a signaling molecule involved in many physiological and pathological processes. Although the role of NO in the occurrence and development of pulmonary diseases including HALI has been extensively studied, the findings on the role of NO in HALI are conflicting. Moreover, inhalation of NO has been approved as a therapeutic strategy for several diseases. In this paper, we briefly summarize the role of NO in the pathogenesis of HALI and the therapeutic potential of inhaled NO in HALI. PMID:27867474

  2. Cromolyn Oral Inhalation

    MedlinePlus

    ... dry air, or by inhaling substances such as pet dander, pollen, dust mites, or chemicals, such as ... disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, ...

  3. 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 ...

  4. Pirbuterol Acetate Oral Inhalation

    MedlinePlus

    ... bronchodilators. It works by relaxing and opening air passages in the lungs, making it easier to breathe. ... and stays up. Hold the inhaler around the middle and shake gently several times. Continue to hold ...

  5. Zanamivir Oral Inhalation

    MedlinePlus

    ... you use an inhaled medication to treat asthma, emphysema, or other breathing problems and you are scheduled ... the air passages that lead to the lungs); emphysema (damage to air sacs in the lungs); or ...

  6. Indacaterol Oral Inhalation

    MedlinePlus

    ... LABAs). It works by relaxing and opening air passages in the lungs, making it easier to breathe. ... use extra doses of indacaterol. Call your doctor right away.Indacaterol inhalation controls the symptoms of COPD ...

  7. Budesonide Oral Inhalation

    MedlinePlus

    Budesonide is used to prevent difficulty breathing, chest tightness, wheezing, and coughing caused by asthma. Budesonide powder for oral inhalation (Pulmicort Flexhaler) is used in adults and children 6 ...

  8. Acetylcysteine Oral Inhalation

    MedlinePlus

    Acetylcysteine inhalation is used along with other treatments to relieve chest congestion due to thick or abnormal ... that causes problems with breathing, digestion, and reproduction). Acetylcysteine is in a class of medications called mucolytic ...

  9. Umeclidinium Oral Inhalation

    MedlinePlus

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

  10. Olodaterol Oral Inhalation

    MedlinePlus

    ... 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 ( ...

  11. Nitric oxide in the pulmonary vasculature.

    PubMed

    Coggins, Matthew P; Bloch, Kenneth D

    2007-09-01

    Homeostasis in the pulmonary vasculature is maintained by the actions of vasoactive compounds, including nitric oxide (NO). NO is critical for normal development of the pulmonary vasculature and continues to mediate normal vasoregulation in adulthood. Loss of NO bioavailability is one component of the endothelial dysfunction and vascular pathology found in pulmonary hypertension (PH). A broad research effort continues to expand our understanding of the control of NO production and NO signaling and has generated novel theories on the importance of pulmonary NO production in the control of the systemic vasculature. This understanding has led to exciting developments in our ability to treat PH, including inhaled NO and phosphodiesterase inhibitors, and to several promising directions for future therapies using nitric oxide-donor compounds, stimulators of soluble guanylate cyclase, progenitor cells expressing NO synthase (NOS), and NOS gene manipulation.

  12. Epidemiology of inhalant use.

    PubMed

    Medina-Mora, María Elena; Real, Tania

    2008-05-01

    The aim of the present article is to review recent research on the prevalence and correlates of inhalant use. During the review period more prevalence studies have been conducted in the developing world, adding information to the ongoing studies that are periodically undertaken in the more developed countries. These studies suggest that inhalant use is widespread among children and adolescents and is increasing among females in the developing and developed world. Not all surveys report inhalants as a separate group from other illegal substances; data by type of inhalants are even rarer, and few studies address abuse or dependence. New evidence suggests lower reliability rates for the diagnostic criteria of dependence as compared with other substances, suggesting the need for a review including the evidence of withdrawal. Studies conducted in the period identify vulnerable groups and suggest an increased risk of injecting drug use, HIV, suicidality and psychiatric disorders among inhalant users. The extension of inhalant abuse and its adverse consequences argues for greater efforts to advance classification and to increase knowledge through research, including the evaluation of prevention and treatment models.

  13. Inhalant Use and Inhalant Use Disorders in the United States

    PubMed Central

    Howard, Matthew O.; Bowen, Scott E.; Garland, Eric L.; Perron, Brian E.; Vaughn, Michael G.

    2011-01-01

    More than 22 million Americans age 12 and older have used inhalants, and every year more than 750,000 use inhalants for the first time. Despite the substantial prevalence and serious toxicities of inhalant use, it has been termed “the forgotten epidemic.” Inhalant abuse remains the least-studied form of substance abuse, although research on its epidemiology, neurobiology, treatment, and prevention has accelerated in recent years. This review examines current findings in these areas, identifies gaps in the research and clinical literatures pertaining to inhalant use, and discusses future directions for inhalant-related research and practice efforts. PMID:22003419

  14. Inhaled human insulin.

    PubMed

    Strack, Thomas R

    2006-04-01

    The benefit of subcutaneous insulin therapy in patients with diabetes is frequently limited due to difficulty in convincing patients of the importance of multiple daily insulin injections to cope effectively with meal-associated glycemic changes. Thus, the aim of achieving tight glycemic control, which is critical for reducing the risk of long-term diabetes-related complications, frequently remains elusive. The successful development of an inhalable insulin as a noninvasive alternative promises to change the management of diabetes. The first product to become available to patients is inhaled human insulin, a dry-powder formulation packaged into discrete blisters containing 1 or 3 mg of dry-powder human insulin and administered via a unique pulmonary inhaler device. It has recently been approved in both the United States and the European Union for the control of hyperglycemia in adult patients with type 1 or type 2 diabetes. The pharmacokinetic profile of inhaled human insulin closely mimics the natural pattern of insulin secretion, and resembles that of rapid-acting subcutaneous analogs. Similarly to rapid-acting subcutaneous analogs, inhaled human insulin has a more rapid onset of glucose-lowering activity compared to subcutaneous regular insulin, allowing it to be administered shortly before meals. It has a duration of glucose-lowering activity comparable to subcutaneous regular insulin and longer than rapid-acting insulin analogs. Inhaled human insulin effectively controls postprandial glucose concentrations in patients with type 1 or type 2 diabetes without increasing the risk of hypoglycemia, and even improves fasting glucose levels compared to subcutaneous insulin. Inhaled human insulin has an overall favorable safety profile. There are small reductions in lung function (1-1.5% of total lung forced expiratory volume in the first second [FEV1] capacity) after onset of treatment that are reversible in most patients if treatment is discontinued. Inhaled human

  15. Effectiveness of Inhalant Abuse Legislation.

    PubMed

    Batis, Jeffery C

    2017-01-28

    Since peaking in the 1990s, inhalant abuse has steadily decreased over the past two decades. Concurrently, nearly every state has passed legislation aimed at minimizing inhalant abuse. While males have historically been more likely to abuse inhalants than females, there is no longer a sex effect in self-reported rates of inhalant abuse. The objective of the present study is to evaluate the effect of anti-inhalant abuse legislation on self-reported rates of inhalant abuse, in high school age males and females. Beginning in 1993, the CDC's biannual Youth Risk Behavior Surveillance Survey asked respondents if they have ever used inhalants to get high. Data from these surveys were collected, along with the date of passage of anti-inhalant abuse legislation in 46 of 50 states. ANOVAs were conducted to assess the effect of legislation on self-reported inhalant abuse rates. There were no significant main effects or interactions that demonstrated that inhalant abuse rates decreased in males or females following passage of legislation aimed at decreasing inhalant abuse. Conclusion/Importance: To date, 46 of 50 states have passed laws aimed at minimizing inhalant abuse, and while inhalant abuse rates have been decreasing for the past two decades, there is no evidence that this decline is related to enactment of these laws. Further research is needed to determine the cause of the decrease in inhalant abuse. The laws may benefit from amendments to include options for treatment.

  16. 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.

  17. Review of inhaled iloprost for the control of pulmonary artery hypertension in children

    PubMed Central

    Tissot, Cecile; Beghetti, Maurice

    2009-01-01

    In the pediatric population, pulmonary hypertension may present as an acute event in the setting of lung or cardiac pathology or as a chronic disease, mainly as idiopathic pulmonary hypertension or associated with congenital heart disease. Recently, new pharmacologic approaches have demonstrated significant efficacy in the management of adults with pulmonary arterial hypertension; these include intravenous epoprostenol, prostacyclin analogs, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors. The same treatment strategies are currently used in children. There are only few reports of the use of inhaled iloprost in pediatrics, only one of which reported the use of chronic inhaled iloprost in a significant number of children. This report showed that 1) the acute pulmonary vasodilator response to inhaled iloprost is equivalent to that of inhaled nitric oxide; 2) acute inhalation of iloprost can induce bronchoconstriction 3) the addition of inhaled iloprost can reduce the need for intravenous prostanoid therapy in some patients; 4) most children tolerated the combination of inhaled iloprost and endothelin receptor antagonist or phosphodiesterase inhibitors; 5) Several patients had clinical deterioration during chronic inhaled iloprost therapy and required rescue therapy with intravenous prostanoids. In this review we will discuss the role of inhaled iloprost in acute and chronic pulmonary hypertension in children. PMID:19436672

  18. 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

  19. 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

  20. Inhalation exposure methodology.

    PubMed Central

    Phalen, R F; Mannix, R C; Drew, R T

    1984-01-01

    Modern man is being confronted with an ever-increasing inventory of potentially toxic airborne substances. Exposures to these atmospheric contaminants occur in residential and commercial settings, as well as in the workplace. In order to study the toxicity of such materials, a special technology relating to inhalation exposure systems has evolved. The purpose of this paper is to provide a description of the techniques which are used in exposing laboratory subjects to airborne particles and gases. The various modes of inhalation exposure (whole body, head only, nose or mouth only, etc.) are described at length, including the advantages and disadvantages inherent to each mode. Numerous literature citations are included for further reading. Among the topics briefly discussed are the selection of appropriate animal species for toxicological testing, and the types of inhalation studies performed (acute, chronic, etc.). PMID:6383799

  1. Bronchiolitis obliterans organizing pneumonia following nitric acid fume exposure.

    PubMed

    Lee, L T; Ho, C H B; Putti, T C

    2014-03-01

    We describe a patient with clinical, radiological and pathological features of bronchiolitis obliterans organizing pneumonia. Investigation showed that this was likely to have been a delayed consequence of inhalation of nitric acid fumes (containing nitrogen dioxide) after a fire. This case shows that thorough investigation of the aetiology is important not only in clinical management but also in ensuring patients benefit from appropriate work injury compensation.

  2. 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...

  3. 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...

  4. Who Can Use an Inhaler?

    MedlinePlus

    ... it can help stop breathing problems related to asthma. Inhalers are small and easily fit into your pocket or backpack. Research shows that even young kids can use inhalers, especially when they're used with a spacer . There are two types of inhalers: Metered (say: ...

  5. Nitrite inhalants: history, epidemiology, and possible links to AIDS.

    PubMed Central

    Haverkos, H W; Kopstein, A N; Wilson, H; Drotman, P

    1994-01-01

    Nitrite inhalants have been commonly abused substances in the United States. Nitrite inhalants and AIDS was a popular topic in the early 1980s, when the cause of AIDS was not known. With the discovery of HIV, concern about nitrite use in the USA waned. However, nitrite inhalant use is associated with behavioral relapse and HIV transmission among gay men, with decreased lymphocyte counts and natural killer cell activity in a few laboratory studies, and it remains a candidate cofactor in the pathogenesis of AIDS-related Kaposi's sarcoma. Discouraging nitrite use continues to be a worthwhile public health goal. PMID:9644194

  6. Psychiatric disorders in inhalant users: results from The National Epidemiologic Survey on Alcohol and Related Conditions.

    PubMed

    Wu, Li-Tzy; Howard, Matthew Owen

    2007-05-11

    To examine the prevalence and correlates of mood, anxiety, and personality disorders among lifetime inhalant users. Statistical analyses were based on data from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative survey of adults in the United States. Inhalant users (N=664) had high lifetime prevalences of DSM-IV mood (48%), anxiety (36%), and personality (45%) disorders. Of all inhalant users, 70% met criteria for at least one lifetime mood, anxiety, or personality disorder and 38% experienced a mood or anxiety disorder in the past year. Prevalences of comorbid psychiatric disorders varied by gender. Compared with male inhalant users, female inhalant users had higher prevalences of lifetime dysthymia (24% versus 16%), any anxiety disorder (53% versus 30%), panic disorder without agoraphobia (25% versus 11%), and specific phobia (28% versus 14%), but a lower prevalence of antisocial personality disorder (22% versus 36%). Female inhalant users also were more likely than male inhalant users to meet criteria for three or more mood or anxiety disorders (15% versus 8%) in the past year. Among inhalant users with comorbid disorders, those who developed social or specific phobia typically experienced onset of these disorders prior to initiation of inhalant use; all other mood and anxiety disorders usually developed following the onset of inhalant use. Inhalant users who were women, poor, less educated, with early onset of inhalant use, family histories of psychopathology, and personal histories of substance abuse treatment had increased odds of psychiatric disorders. Psychiatric disorders are highly prevalent among inhalant users nationally and female inhalant users are more likely than male inhalant users to experience multiple psychiatric disorders. Inhalant use and its consequences among females warrant greater research attention.

  7. Psychiatric Disorders in Inhalant Users: Results from The National Epidemiologic Survey on Alcohol and Related Conditions

    PubMed Central

    Wu, Li-Tzy; Howard, Matthew Owen

    2007-01-01

    Objective To examine the prevalence and correlates of mood, anxiety, and personality disorders among lifetime inhalant users. Methods Statistical analyses were based on data from the 2001─2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative survey of adults in the United States. Results Inhalant users (N = 664) had high lifetime prevalences of DSM-IV mood (48%), anxiety (36%), and personality (45%) disorders. Of all inhalant users, 70% met criteria for at least one lifetime mood, anxiety, or personality disorder and 38% experienced a mood or anxiety disorder in the past year. Prevalences of comorbid psychiatric disorders varied by gender. Compared with male inhalant users, female inhalant users had higher prevalences of lifetime dysthymia (24% vs. 16%), any anxiety disorder (53% vs. 30%), panic disorder without agoraphobia (25% vs. 11%), and specific phobia (28% vs. 14%), but a lower prevalence of antisocial personality disorder (22% vs.36%). Female inhalant users also were more likely than male inhalant users to meet criteria for three or more mood or anxiety disorders (15% vs. 8%) in the past year. Among inhalant users with comorbid disorders, those who developed social or specific phobia typically experienced onset of these disorders prior to initiation of inhalant use; all other mood and anxiety disorders usually developed following the onset of inhalant use. Inhalant users who were women, poor, less educated, with early onset of inhalant use, family histories of psychopathology, and personal histories of substance abuse treatment had increased odds of psychiatric disorders. Conclusions Psychiatric disorders are highly prevalent among inhalant users nationally and female inhalant users are more likely than male inhalant users to experience multiple psychiatric disorders. Inhalant use and its consequences among females warrant greater research attention. PMID:17129683

  8. Inhaled surfactant in the treatment of accidental talc powder inhalation: a new case report.

    PubMed

    Matina, Federico; Collura, Mirella; Maggio, Maria Cristina; Vitulo, Patrizio; Lo Piparo, Caterina; Corsello, Giovanni

    2011-09-27

    The use of talcum powder is incorrectly part of the traditional care of infants. Its acute aspiration is a very dangerous condition in childhood. Although the use of baby powder has been discouraged from many authors and the reports of its accidental inhalation have been ever more rare, sometimes new cases with several fatalities have been reported. We report on a patient in which accidental inhalation of baby powder induced severe respiratory difficulties. We also point out the benefits of surfactant administration. Surfactant contributed to the rapid improvement of the medical and radiological condition, preventing severe early and late complications and avoiding invasive approaches.

  9. 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…

  10. 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…

  11. 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.

  12. Two-week inhalation toxicity of polymeric diphenylmethane-4, 4'-diisocyanate (PMDI) in rats: analysis of biochemical and morphological markers of early pulmonary response.

    PubMed

    Pauluhn, J; Emura, M; Mohr, U; Popp, A; Rosenbruch, M

    1999-12-01

    The pulmonary response of Wistar rats to respirable polymeric diphenylmethane-4,4'-diisocyanate (PMDI) aerosol was examined in a 2-wk repeated nose-only inhalation exposure study. Exposure concentrations were 1.1, 3.3, and 13.7 mg PMDI/m(3) (6 h/day, 15 exposures). The level of 13.7 mg/m(3) was actually a combination of an initial target concentration of 10 mg/m(3) in wk 1, which was raised to 16 mg/m(3) in wk 2, due to a lack of signs suggestive of pulmonary irritation. An acute sensory irritation study on rats served as basis for selection of these concentrations. Shortly after the 2-wk exposure period, rats were subjected to pulmonary function and arterial blood gas measurements. Lungs were examined by light and transmission electron microscopy, and labeling indices in terminal bronchioles were measured. Bronchoalveolar lavage (BAL) was performed to assess various indicators of pulmonary inflammation, including neutrophil and macrophage numbers, protein, lactate dehydrogenase (LDH), gamma-glutamyltranspeptidase (gamma-GT), alkaline phosphatase (APh), acid phosphatase (ACPh), and beta-N-acetylglucosaminidase (beta-NAG). Phosphatidylcholine in BAL fluid and BAL cells was determined as aggregated endpoint suggestive of changes in pulmonary surfactant. Rats exposed to 3.3 and 13.7 mg/m(3) experienced concentration-dependent signs of respiratory tract irritation. Determination of arterial blood gases, lung mechanics, and carbon monoxide diffusing capacity did not demonstrate specific effects. Analysis of BAL fluid and BAL cells revealed changes indicative of marked inflammatory response and/or cytotoxicity in rats exposed to 13.7 mg/m(3), and the changes were characterized by statistically significantly increased activities of LDH, beta-NAG, and protein. Phospholipid concentrations were increased in rats exposed to 1.1 mg/m(3) and above (elevated levels of lipid material in alveolar macrophages demonstrated by polychrome stain) and 3.3 mg/m(3) and above (increased

  13. [Ventricular fibrillation following deodorant spray inhalation].

    PubMed

    Girard, F; Le Tacon, S; Maria, M; Pierrard, O; Monin, P

    2008-01-01

    We report one case of out-of-hospital cardiac arrest with ventricular fibrillation following butane poisoning after inhalation of antiperspiration aerosol. An early management using semi-automatic defibrillator explained the success of the resuscitation. The mechanism of butane toxicity could be an increased sensitivity of cardiac receptors to circulating catecholamines, responsible for cardiac arrest during exercise and for resuscitation difficulties. The indication of epinephrine is discussed.

  14. Short- and Long-Term Effects of Inhaled Iloprost Therapy in Children With Pulmonary Arterial Hypertension

    PubMed Central

    Ivy, D. Dunbar; Doran, Aimee K.; Smith, Kelly J.; Mallory, George B.; Beghetti, Maurice; Barst, Robyn J.; Brady, Daniela; Law, Yuk; Parker, Donna; Claussen, Lori; Abman, Steven H.

    2011-01-01

    Objectives This study investigated the short- and long-term outcome of children with pulmonary arterial hypertension (PAH) treated with inhaled iloprost. Background Inhaled iloprost has been approved for the treatment of adults with PAH, but little is known about the effects in children with PAH. Methods We evaluated the acute effects of inhaled iloprost on hemodynamic status and lung function and the response to long-term therapy in 22 children (range 4.5 to 17.7 years) with PAH (idiopathic, n = 12; congenital heart disease, n = 10). Cardiac catheterization, standard lung function testing before and after iloprost inhalation, 6-min walk test, World Health Organization functional class, and hemodynamic parameters were monitored. Results Acute administration of inhaled iloprost lowered mean pulmonary artery pressure equivalent to the response to inhaled nitric oxide with oxygen. Acute iloprost inhalation reduced forced expiratory volume in 1 s and mid-volume forced expiratory flow by 5% and 10%, respectively, consistent with acute bronchoconstriction. At 6 months, functional class improved in 35%, decreased in 15%, and remained unchanged in 50% of children. Sixty-four percent of patients continued receiving long-term iloprost therapy, 36% stopped iloprost, due to lower airway reactivity, clinical deterioration, or death. In 9 patients on chronic intravenous prostanoids, 8 transitioned from intravenous prostanoids to inhaled iloprost, which continued during follow-up. Conclusions Inhaled iloprost caused sustained functional improvement in some children with PAH, although inhaled iloprost occasionally induced bronchoconstriction. Most patients tolerated the transition from intravenous to inhaled prostanoid therapy. Clinical deterioration, side effects, and poor compliance, owing to the frequency of treatments, could limit chronic treatment in children. PMID:18191742

  15. 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

  16. Treatment of Inhalation Injury

    DTIC Science & Technology

    1983-01-21

    injuries not visible with endoscopy. . Thermal and especially chemical inhalation injuries. Direct damage to the surfactant is probably implicated. o...exists a set of indirect alveolar lesions, subordinated to the skin burn itself, which is common in patients with extensive burns. This we call the...normo or hypocapnia. Very likely, a 5th lesional level exists which is the capillary itself(Venus et al). By primary or secondary damage , it affects the

  17. 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+ signal.

    PubMed

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

    2013-11-01

    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 Ca(2+) 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 Ca(2+) signal and leads to increased defense gene expression and resistance to a virulent bacterial pathogen. Ca(2+)-dependent protein kinases (CPKs) decode the Ca(2+) 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 Ca(2+) 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 Ca(2+)-conducting channel in the Pep immune signaling pathway.

  18. 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.

  19. [Acute respiratory insufficiency in burn patients from smoke inhalation].

    PubMed

    Gartner, R; Griffe, O; Captier, G; Selloumi, D; Otman, S; Brabet, M; Baro, B

    2002-03-01

    Respiratory injuries by smoke inhalation are one of the most frequent reasons for acute respiratory failure in burn victims. They are most often of chemical origin and are responsible of a 20 to 70% increase of the mortality compared to the mortality of patients with similar burn injuries, but without inhalation lesions. They are often associated to a certain degree to other factors of acute respiratory failure: superior air way obstruction by oedema in face and neck burns, thoracic expansion hindrance due to thoracic burns, lung trauma lesions by blast injury. The generalized inflammatory reaction due to the extent of burns and an initial inadequate resuscitation are worsening factors. The inflammatory process may be responsible of lung injuries similar to those induced by smoke inhalation, even when there is no inhalation. The treatment remains symptomatic and based on the oxygen therapy, mechanical ventilation, prevention of infections and maintain of homeostasis by hydroelectrolytic adequate resuscitation. The nitric oxyde associated to the almitrin allows in a certain number of cases to minimize intra pulmonary shunting and to normalize the VA/O ratio. The development of treatments allowing to modulate inflammatory mediators may lead to news therapies in the future.

  20. Inhaled iloprost for the control of acute pulmonary hypertension in children: a systematic review.

    PubMed

    Mulligan, Claire; Beghetti, Maurice

    2012-07-01

    Inhaled iloprost is attracting growing interest as a potential alternative and/or adjuvant to inhaled nitric oxide in the management of pediatric pulmonary hypertension in the acute and intensive care settings. However, there are currently no formal evidence-based guidelines regarding the use of inhaled iloprost in children with pulmonary hypertension. The aim of this systematic review is to assess the literature concerning the use of inhaled iloprost in children with pulmonary hypertension in the acute setting. Studies were identified from PubMed and Embase. Internal literature databases and recent congress abstracts (2009 onward) were also searched for relevant publications. Studies were included if they examined the use of inhaled iloprost in children with pulmonary hypertension in an acute or intensive care setting. Twenty-eight studies were included in the review. The majority were case studies or case series (n = 17), and in total, the 28 studies represented the treatment of 195 children with iloprost. Iloprost was most frequently studied in children undergoing cardiac surgery (as a bridge to surgery and postoperatively), in children undergoing acute pulmonary vasoreactivity testing, and in neonates with persistent pulmonary hypertension of the newborn. The results of the included studies suggested that inhaled iloprost may have a diverse role in the acute treatment of pediatric pulmonary hypertension and that its acute effects are similar to those of inhaled nitric oxide. However, the iloprost dose was not consistently reported and varied greatly between studies, and several different administration devices were used. Inhaled iloprost may be useful in the acute treatment of children and neonates with pulmonary hypertension, but clinical data are scarce, and the appropriate dosing of iloprost in different scenarios is uncertain. Well-designed prospective clinical trials are needed.

  1. How to match the optimal currently available inhaler device to an individual child with asthma or recurrent wheeze

    PubMed Central

    van Aalderen, Wim M; Garcia-Marcos, Luis; Gappa, Monika; Lenney, Warren; Pedersen, Søren; Dekhuijzen, Richard; Price, David

    2015-01-01

    Inhaled medications are the cornerstone of treatment in early childhood wheezing and paediatric asthma. A match between patient and device and a correct inhalation technique are crucial for good asthma control. The aim of this paper is to propose an inhaler strategy that will facilitate an inhaler choice most likely to benefit different groups of children. The main focus will be on pressurised metered dose inhalers and dry powder inhalers. In this paper we will discuss (1) practical difficulties with the devices and with inhaled therapy and (2) the optimal location for deposition of medicines in the lungs, and (3) we will propose a practical and easy way to make the best match between the inhaler device and the individual patient. We hope that this paper will contribute to an increased likelihood of treatment success and improved adherence to therapy. PMID:25568979

  2. Inhalant abuse among adolescents: neurobiological considerations

    PubMed Central

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

    2008-01-01

    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, GABAA, glycine and 5HT3 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 GABAA 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

  3. 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.

  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. 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.

  6. Blood Gases as an Indicator of Inhalation Injury and Prognosis in Burn Patients

    PubMed Central

    Megahed, M.A.; Ghareeb, F.; Kishk, T.; El-Barah, A.; Abou-Gereda, H.; El-Fol, H.; El-Sisy, A.; Omran, A.M.

    2008-01-01

    Summary Inhalation injury greatly increases the incidence of respiratory failure and the acute respiratory distress syndrome. It is also the cause of most early deaths in burn victims. The aim of our research was to study the incidence, early diagnosis, complications, and management of inhalation injury and to discuss the relation between inhalation injury and death in burn patients.This study included 130 burn patients with inhalation injury admitted to Menoufiya University Hospital Burn Center, Egypt, from January 2004 to April 2008 (61 males and 69 females). We found that the presence of inhalation injury, increasing burn size, and advancing age were all associated with increased mortality (p < 0.01). The incidence of inhalation injury in our study was 46.3% (130 patients were identified as having inhalation injury out of 281). The overall mortality for patients with inhalation injury was 41.5% (54 patients out of 130) compared with 7.2% (11 patients out of 151) for patients without inhalation injury. These statistical data make it clear that inhalation injury is an important factor for the prediction of mortality in burn patients. Approximately 80% of fire-related deaths are due not to the burn injury to the airway but to the inhalation of toxic products, especially carbon monoxide and hydrogen cyanide gases. Inhalation injury is generally caused by thermal burns, mostly confined to the upper airways.Major airway, pulmonary, and systemic complications may occur in cases of inhalation injury and thus increase the incidence of burn patient mortality PMID:21991136

  7. Inhaled nitrite reverses hemolysis-induced pulmonary vasoconstriction in newborn lambs without blood participation

    PubMed Central

    Blood, Arlin B.; Schroeder, Hobe J.; Terry, Michael H.; Merrill-Henry, Jeanette; Bragg, Shannon L.; Vrancken, Kurt; Liu, Taiming; Herring, Jason L.; Sowers, Lawrence C.; Wilson, Sean M.; Power, Gordon G.

    2011-01-01

    Background Nitrite can be converted to nitric oxide (NO) by a number of different biochemical pathways. In newborn lambs an aerosol of inhaled nitrite has been found to reduce pulmonary blood pressure, possibly acting via conversion to NO by reaction with intraerythrocytic deoxyhemoglobin. If so, the vasodilating effects of nitrite would be attenuated by free hemoglobin in plasma that would rapidly scavenge NO. Methods and Results Pulmonary vascular pressures and resistances to flow were measured in anesthetized newborn lambs. Plasma hemoglobin concentrations were then elevated, resulting in marked pulmonary hypertension. This effect was attenuated if infused hemoglobin was first oxidized to methemoglobin which does not scavenge NO. These results further implicate NO as a tonic pulmonary vasodilator. Next, while free hemoglobin continued to be infused, the lambs were given inhaled NO gas (20 ppm), inhaled sodium nitrite aerosol (0.87 M), or an intravascular nitrite infusion (3 mg·hr−1 bolus, 5 mg·kg−1·hr−1 infusion). Inhaled NO and inhaled nitrite aerosol both resulted in pulmonary vasodilation. Intravascular infusion of nitrite, however, did not. Increases in exhaled NO gas were observed while breathing the nitrite aerosol (~20 ppb NO) but not during intravascular infusion of nitrite. Conclusions We conclude that the pulmonary vasodilating effect of inhaled nitrite results from its conversion to NO in airway and parenchymal lung tissue and is not dependent on reactions with deoxyhemoglobin in the pulmonary circulation. Inhaled nitrite aerosol remains a promising candidate to reduce pulmonary hypertension in clinical application. PMID:21282501

  8. How to Use Metered-Dose Inhalers

    MedlinePlus

    ... inhaler the right way so that the full dose of medication reaches your lungs. You can use ... inhaler.These directions explain how to use metered-dose inhalers. If you are using a different type ...

  9. An interesting case of characteristic methanol toxicity through inhalational exposure

    PubMed Central

    Kumar, Pratyush; Gogia, Atul; Kakar, Atul; Miglani, Pratyush

    2015-01-01

    Methanol poisoning is rare but carries high risk of morbidity and mortality. Most of the cases witnessed in emergency are due to consumption of adulterated alcohol. Here we are reporting a very rare case of methanol poisoning through inhalational exposure leading to putamen necrosis and decreased visual acuity. He had dyselectrolytemia and metabolic acidosis which was successfully managed with early intervention. Its importance lies in the fact that inhalational methanol poisoning is an entity which if picked up early can prevent long-term neurological sequelae. PMID:26285665

  10. Inhalation exposure of animals.

    PubMed Central

    Phalen, R F

    1976-01-01

    Relative advantages and disadvantages and important design criteria for various exposure methods are presented. Five types of exposures are discussed: whole-body chambers, head-only exposures, nose or mouth-only methods, lung-only exposures, and partial-lung exposures. Design considerations covered include: air cleaning and conditioning; construction materials; losses of exposure materials; evenness of exposure; sampling biases; animal observation and care; noise and vibration control, safe exhausts, chamber loading, reliability, pressure fluctuations; neck seals, masks, animal restraint methods; and animal comfort. Ethical considerations in use of animals in inhalation experiments are also discussed. PMID:1017420

  11. 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.

  12. Inhaled technosphere regular insulin powder.

    PubMed

    Anderson, Zachary L; Clements, Jennifer N

    2015-11-01

    The lungs are an effective way to deliver insulin for patients with diabetes, but an initial inhaled insulin product was withdrawn from the market because of high cost and inconsistent dosing. This article describes a recently approved inhaled insulin that appears to control blood glucose as well as rapid-acting injectable insulin.

  13. American Indian Adolescent Inhalant Use.

    ERIC Educational Resources Information Center

    Thurman, Pamela Jumper; Green, Vicki A.

    1997-01-01

    A study of inhalant use among 87 American Indian boarding school students aged 10-18 found that inhalant use was negatively related to participation in traditional tribal activities for both males and females and was also related to measures of cognitive ability and cognitive egocentrism for males. (Contains 43 references.) (SV)

  14. Inhalation delivery of protein therapeutics.

    PubMed

    Kane, Colleen; O'Neil, Karyn; Conk, Michelle; Picha, Kristen

    2013-04-01

    Inhaled therapeutics are used routinely to treat a variety of pulmonary diseases including asthma, COPD and cystic fibrosis. In addition, biological therapies represent the fastest growing segment of approved pharmaceuticals. However, despite the increased availability of biological therapies, nearly all inhaled therapeutics are small molecule drugs with only a single inhaled protein therapeutic approved. There remains a significant unmet need for therapeutics in pulmonary diseases, and biological therapies with potential to alter disease progression represent a significant opportunity to treat these challenging diseases. This review provides a background into efforts to develop inhaled biological therapies and highlights some of the associated challenges. In addition, we speculate on the ideal properties of a biologic therapy for inhaled delivery.

  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. Smoke Inhalation Lung Injury: An Update

    PubMed Central

    Demling, Robert H.

    2008-01-01

    Objectives: The purpose of this study is to present a multifaceted, definitive review of the past and current status of smoke inhalation injury. History along with current understanding of anatomical, physiology, and biologic components will be discussed. Methods: The literature has been reviewed from the early onset of the concept of smoke inhalation in the 1920s to our current understanding as of 2007. Results: The results indicate that the current pathophysiologic concept is of a disease process that leads to immediate and delayed pulmonary injury best managed by aggressive physiologic support. Management approaches for the biochemical changes have not kept up with current knowledge. The lung injury process is activated by toxins in the smoke's gas and particle components and perpetuated by a resulting lung inflammation. This inflammatory process becomes self-perpetuating through the activation of a large number of inflammatory cascades. In addition, smoke injury leads to significant systemic abnormalities injuring other organs and accentuating the burn injury process and subsequently leading to mediator-induced cellular injury leading potentially to multisystem organ failure. Conclusions: Smoke inhalation injury results in the anatomic finding of denuded and sometimes sloughed airways mucosa. Physiologic findings include small airways containing fibrin casts of mucosa and neutrophils. Airway hyper-reactivity results as well, leading to further decreased collapse, causing obstruction. PMID:18552974

  17. 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

  18. Exubera. Inhale therapeutic systems.

    PubMed

    Bindra, Sanjit; Cefalu, William T

    2002-05-01

    Inhale, in colaboration with Pfizer and Aventis Pharma (formerly Hoechst Marion Roussel; HMR), is developing an insulin formulation utilizing its pulmonary delivery technology for macromolecules for the potential treatment of type I and II diabetes. By July 2001, the phase III program had been completed and the companies had begun to assemble data for MAA and NDA filings; however, it was already clear at this time that additional data might be required for filing. By December 2001, it had been decided that the NDA should include an increased level of controlled, long-term pulmonary safety data in diabetic patients and a major study was planned to be completed in 2002, with the NDA filed thereafter (during 2002). US-05997848 was issued to Inhale Therapeutic Systems in December 1999, and corresponds to WO-09524183, filed in February 1995. Equivalent applications have appeared to date in Australia, Brazil, Canada, China, Czech Republic, Europe, Finland, Hungary, Japan, Norway, New Zealand, Poland and South Africa. This family of applications is specific to pulmonary delivery of insulin. In February 1999, Lehman Brothers gave this inhaled insulin a 60% probability of reaching market, with a possible launch date of 2001. The analysts estimated peak sales at $3 billion in 2011. In May 2000, Aventis predicted that estimated peak sales would be in excess of $1 billion. In February 2000, Merrill Lynch expected product launch in 2002 and predicted that it would be a multibillion-dollar product. Analysts Merril Lynch predicted, in September and November 2000, that the product would be launched by 2002, with sales in that year of e75 million, rising to euro 500 million in 2004. In April 2001, Merrill Lynch predicted that filing for this drug would occur in 2001. Following the report of the potential delay in regulatory filing, issued in July 2001, Deutsche Banc Alex Brown predicted a filing would take place in the fourth quarter of 2002 and launch would take place in the first

  19. Nitric oxide in the airways.

    PubMed

    Scadding, Glenis

    2007-08-01

    This review briefly explains the basic facts about nitric oxide, which is entering clinical practice as a measure of lower airways inflammation and is likely also to be employed in otorhinolaryngological practice. These include the validity of nasal nitric oxide in diagnosing primary ciliary dyskinesia and in monitoring the response to chronic rhinosinusitis therapy. The nasal nitric oxide value combined with a humming manoeuvre, which increases the passage of nitric oxide from the sinuses to the nose if the ostiomeatal complex is patent, could reduce the need for computed tomography scans. The link between nitric oxide production and ciliary beating requires further exploration. Therapeutic adjustments to nitric oxide production are under investigation. Nitric oxide is likely to prove highly relevant to airways defence, as well as being an inflammatory mediator. Nasal nitric oxide probably explains some of the benefit of nasal rather than mouth breathing.

  20. Inhalant abuse in New Zealand.

    PubMed

    Beasley, Michael; Frampton, Laura; Fountain, John

    2006-05-05

    To describe patterns of inhalant abuse in New Zealand and discuss management. Calls to the National Poisons Centre (NPC) from January 1 2003 to December 31 2004 were analysed. In addition, deaths following inhalational abuse were identified from the Institute of Environmental Science and Research Limited (ESR) database for 2001 and 2002 and available data for 2003. Seventy calls were classified as relating to inhalational abuse incidents. In abusers whose age was known, 83% were between 11 and 20 years, and 61% were male. Over half (44/70) of the calls involved abuse of propane or butane, either alone or in combination with a synthetic pyrethroid. ESR coronial data identified 11 inhalant abuse related deaths, most commonly attributed to cardiac effects. 73% of deaths were in teenagers and all but one fatality involved propane and/or butane. Inhalant abuse is a persisting problem in New Zealand. NPC and ESR data demonstrate that teenagers are more likely to abuse inhalants than other age groups and butane and propane are the inhalants of choice. Acute management can be difficult, with significant mortality and morbidity. Continued education and other preventive measures are essential to help curb an extremely dangerous practice.

  1. 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

  2. Concurrent use of metered dose inhalers without spacer and dry powder inhalers by asthmatic children adversely affect proper inhalation technique

    PubMed Central

    Alotaibi, Saad; Hassan, Walid M; Alhashimi, Hashim

    2011-01-01

    Asthma is a common chronic disease of children. A good control of symptoms will improve quality of patient life. Inhalation technique is an important aspect in the management of asthma. The better the inhalation technique the better the lung deposition of asthma therapy especially inhaled corticosteroids. This will lead to better control of symptoms and improve adherence to treatment. In the following study the inhalation technique of asthma devices were compared using inhalation technique score system. The asthma devices studied were metered dose inhalers (pressurized MDI) without spacers and dry powder inhalers (DPI). The hypothesis studied was that the inhalation technique score of dry powder inhalers will be adversely affected with concurrent use of metered dose inhalers without spacers. PMID:21760757

  3. Concurrent use of metered dose inhalers without spacer and dry powder inhalers by asthmatic children adversely affect proper inhalation technique.

    PubMed

    Alotaibi, Saad; Hassan, Walid M; Alhashimi, Hashim

    2011-06-14

    Asthma is a common chronic disease of children. A good control of symptoms will improve quality of patient life. Inhalation technique is an important aspect in the management of asthma. The better the inhalation technique the better the lung deposition of asthma therapy especially inhaled corticosteroids. This will lead to better control of symptoms and improve adherence to treatment. In the following study the inhalation technique of asthma devices were compared using inhalation technique score system. The asthma devices studied were metered dose inhalers (pressurized MDI) without spacers and dry powder inhalers (DPI). The hypothesis studied was that the inhalation technique score of dry powder inhalers will be adversely affected with concurrent use of metered dose inhalers without spacers.

  4. 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.

  5. Beneficial effects of nitric oxide breathing in adult patients with sickle cell crisis.

    PubMed

    Head, C Alvin; Swerdlow, Paul; McDade, William A; Joshi, Ratan Mani; Ikuta, Tohru; Cooper, Melanie L; Eckman, James R

    2010-10-01

    Pain from vaso-occlusive crisis (VOC) is the major cause of hospitalization in patients with sickle cell disease (SCD). The beneficial therapeutic effects of inhaled nitric oxide (NO) on the pathophysiology of SCD have been reported. A double-blind, randomized, placebo-controlled clinical trial was conducted to determine whether NO breathing reduces acute VOC pain in adult patients and to study the safety of inhaled NO. Twenty-three patients experiencing acute VOC were enrolled. After randomization but before treatment, five were found to not meet final eligibility criteria. Nine patients were assigned to inhaled NO (80 ppm) and nine to placebo (21% O2). Primary outcome was the mean change in pain scores after 4 hr of inhalation, measured on a 10-cm visual analog scale (VAS). Both groups had similar baseline VAS pain scores but inhaled NO significantly reduced pain scores compared with placebo (P 5 0.02) at the end of NO inhalation. Secondary outcome was parenteral morphine use at baseline, 4, and 6 hr. Parenteral morphine use was lower in the inhaled NO group, but the difference was not statistically significant.Safety assessments included systolic blood pressure measurements,pulse oximetry readings, concentration of delivered nitrogen dioxide, and concentration of methemoglobin (metHb). None of these NO toxicities was observed.

  6. 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…

  7. Trends in the Use of Inhalants among American Indian Adolescents.

    ERIC Educational Resources Information Center

    Beauvais, Fred; And Others

    1985-01-01

    A survey of four large samples of Native American adolescents, conducted since 1975, shows that inhalant use is much higher for Indian than for non-Indian youth, is increasing, begins at an early age, is often associated with use of other drugs, and is influenced by peer and family attitudes. (JHZ)

  8. 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…

  9. Nitric oxide-sensitive pulmonary hypertension in congenital rubella syndrome.

    PubMed

    Raimondi, Francesco; Migliaro, Fiorella; Di Pietro, Elisa; Borgia, Francesco; Rapacciuolo, Antonio; Capasso, Letizia

    2015-01-01

    Persistent pulmonary hypertension is a very rare presentation of congenital virus infection. We discuss the case of complete congenital rubella syndrome presenting at echocardiography with pulmonary hypertension that worsened after ductus ligation. Cardiac catheterization showed a normal pulmonary valve and vascular tree but a PAP = 40 mmHg. The infant promptly responded to inhaled nitric oxide while on mechanical ventilation and was later shifted to oral sildenafil. It is not clear whether our observation may be due to direct viral damage to the endothelium or to the rubella virus increasing the vascular tone via a metabolic derangement.

  10. Umeclidinium and Vilanterol Oral Inhalation

    MedlinePlus

    ... chest tightness caused by chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs ... use umeclidinium and vilanterol inhalation during a sudden COPD attack. Your doctor will prescribe a short-acting ( ...

  11. Fluticasone and Vilanterol Oral Inhalation

    MedlinePlus

    ... and chest tightness caused by chronic obstructive pulmonary (COPD; a group of diseases that affect the lungs ... use fluticasone and vilanterol inhalation during a sudden COPD attack. Your doctor will prescribe a short acting ( ...

  12. Fluticasone and Salmeterol Oral Inhalation

    MedlinePlus

    ... caused by asthma and chronic obstructive pulmonary disease (COPD; a group of lung diseases that includes chronic ... and salmeterol during an attack of asthma or COPD. Your doctor will prescribe a short-acting inhaler ...

  13. Assessing Inhalation Exposures Associated with ...

    EPA Pesticide Factsheets

    Journal Article This paper presents a simulation-based approach for assessing short-term, water-distribution-system-wide inhalation exposures that could result from showering and the use of humidifiers during contamination events.

  14. Inhaled fluticasone propionate impairs pulmonary clearance of Klebsiella Pneumoniae in mice

    PubMed Central

    2012-01-01

    Background Recent trials demonstrate increased pneumonia risk in chronic obstructive pulmonary disease patients treated with the inhaled corticosteroid (ICS) fluticasone propionate (FP). There is limited work describing FP effects on host defenses against bacterial pneumonia. Methods C57BL/6 mice received daily, nose-only exposure to nebulized FP or vehicle for 8 days, followed by pulmonary challenge with Klebsiella pneumoniae. Bacterial burden, phagocytosis, leukocyte recruitment, cytokine expression, nitric oxide release, and survival were measured. Results Inhaled FP increased bacterial burden in lungs and blood 48 h after infection but affected neither in vivo phagocytosis of bacteria by alveolar macrophages (AM) nor alveolar neutrophil recruitment. AM from FP-treated mice showed impaired expression of infection induced TNF-alpha, IP-10 (CXCL-10), and interleukin 6 (IL-6), and AM also showed a trend towards impaired intracellular pathogen control following in vivo infection. In vitro FP treatment resulted in a dose-dependent impairment of cytokine expression by AM. Furthermore, infection-induced nitric oxide (but not hydrogen peroxide) production was impaired by FP in vivo and in vitro. FP decreased survival in this model. Conclusions Exposure to inhaled FP impairs pulmonary clearance of K. pneumoniae in mice, an effect associated with greater systemic bacteremia and death. Decreased AM cytokine and nitric oxide expression parallel the failure to control infection. These results support the study of ICS effects on human pulmonary host defenses. PMID:22651370

  15. 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

  16. Pulmonary Hypertension in Lambs Transfused with Stored Blood is Prevented by Breathing Nitric Oxide

    PubMed Central

    Baron, David M.; Yu, Binglan; Lei, Chong; Bagchi, Aranya; Beloiartsev, Arkadi; Stowell, Christopher P.; Steinbicker, Andrea U.; Malhotra, Rajeev; Bloch, Kenneth D.; Zapol, Warren M.

    2012-01-01

    Background During extended storage, erythrocytes undergo functional changes. These changes reduce the viability of erythrocytes leading to release of oxyhemoglobin, a potent scavenger of nitric oxide. We hypothesized that transfusion of ovine packed erythrocytes (PRBC) stored for prolonged periods would induce pulmonary vasoconstriction in lambs, and that reduced vascular nitric oxide concentrations would increase this vasoconstrictor effect. Methods We developed a model of autologous stored blood transfusion in lambs (n=36). Leukoreduced blood was stored for either 2 days (fresh PRBC) or 40 days (stored PRBC). Fresh or stored PRBC were transfused into donors instrumented for awake hemodynamic measurements. Hemodynamic effects of PRBC transfusion were also studied after infusion of NG-nitro-L-arginine methyl-ester (25 mg/kg) or during inhalation of nitric oxide (80 ppm). Results Cell-free hemoglobin levels were higher in the supernatant of stored PRBC than in supernatant of fresh PRBC (Mean±SD, 148±20 versus 41±13 mg/dl, respectively, P<0.001). Pulmonary artery pressure during transfusion of stored PRBC transiently increased from 13±1 to 18±1 mmHg (P<0.001) and was associated with increased plasma hemoglobin concentrations. NG-nitro-L-arginine methyl-ester potentiated the increase in pulmonary arterial pressure induced by transfusing stored PRBC, whereas inhalation of nitric oxide prevented the vasoconstrictor response. Conclusions Our results suggest that patients with reduced vascular nitric oxide levels due to endothelial dysfunction may be more susceptible to adverse effects of transfusing blood stored for prolonged periods. These patients might benefit from transfusion of fresh PRBC, when available, or inhaled nitric oxide supplementation to prevent the pulmonary hypertension associated with transfusion of stored PRBC. PMID:22293717

  17. Potent Inhalational Anesthetics for Dentistry

    PubMed Central

    Satuito, Mary; Tom, James

    2016-01-01

    Nitrous oxide and the volatile inhalational anesthetics have defined anxiety and pain control in both dentistry and medicine for over a century. From curious experimentation to spectacular public demonstrations, the initial work of 2 dentists, Horace Wells and William T. G. Morton, persists to this day in modern surgery and anesthesia. This article reviews the history, similarities, differences, and clinical applications of the most popular inhalational agents used in contemporary dental surgical settings. PMID:26866411

  18. Potent Inhalational Anesthetics for Dentistry.

    PubMed

    Satuito, Mary; Tom, James

    2016-01-01

    Nitrous oxide and the volatile inhalational anesthetics have defined anxiety and pain control in both dentistry and medicine for over a century. From curious experimentation to spectacular public demonstrations, the initial work of 2 dentists, Horace Wells and William T. G. Morton, persists to this day in modern surgery and anesthesia. This article reviews the history, similarities, differences, and clinical applications of the most popular inhalational agents used in contemporary dental surgical settings.

  19. Inhaler Technique in Asthma: How Does It Relate to Patients' Preferences and Attitudes Toward Their Inhalers?

    PubMed Central

    Jahedi, Lia; Downie, Sue R.; Saini, Bandana; Chan, Hak-Kim

    2017-01-01

    Abstract Background: Correct inhaler technique can increase medication efficacy, reducing both dose and side effects. Patient preference for inhaler device has not been fully explored, and we hypothesized that if patients have a preference and can choose their inhaler, they might be more likely to use it correctly. Our aim was to determine the preferences, attitudes, and perceptions of patients with asthma toward their inhalers, and to evaluate whether any of these factors were related to inhalation technique. Methods: Twenty-five patients with asthma (mean age 43.1 years) participated. Qualitative semi-structured interviews and quantitative patient satisfaction and preference questionnaires (PASAPQ) were used to explore patients' preferences, attitudes, and perceptions about their inhalers. Objective inhalation technique assessment was performed. Data were triangulated to identify characteristics that could indicate a relationship between inhaler technique, satisfaction, preference, and decision making. Results: Themes from qualitative interviews were as follows: asthma inhalers and expectations; inhaler preference; characteristics of an ideal inhaler; perceived effectiveness of inhalers; and inhalers and patient decision making. PASAPQ scores indicated that all patients were at least “somewhat satisfied” with their inhalers, regardless of technique. Only 12% of inhalers were used correctly, despite pilot PASAPQ data suggesting that most patients were confident with their technique. The inhaler technique was unlikely to be related to satisfaction, perception of inhaler devices, or choice in device selection. Patients with correct inhaler technique were more aware of their asthma and expressed motivation to achieve optimal asthma control. Conclusions: The majority of the asthmatic patients did not use their inhaler(s) correctly, despite most having confidence in their technique. Patients attributed confidence in their inhaler technique to their belief that

  20. Inhaler Technique in Asthma: How Does It Relate to Patients' Preferences and Attitudes Toward Their Inhalers?

    PubMed

    Jahedi, Lia; Downie, Sue R; Saini, Bandana; Chan, Hak-Kim; Bosnic-Anticevich, Sinthia

    2017-02-01

    Correct inhaler technique can increase medication efficacy, reducing both dose and side effects. Patient preference for inhaler device has not been fully explored, and we hypothesized that if patients have a preference and can choose their inhaler, they might be more likely to use it correctly. Our aim was to determine the preferences, attitudes, and perceptions of patients with asthma toward their inhalers, and to evaluate whether any of these factors were related to inhalation technique. Twenty-five patients with asthma (mean age 43.1 years) participated. Qualitative semi-structured interviews and quantitative patient satisfaction and preference questionnaires (PASAPQ) were used to explore patients' preferences, attitudes, and perceptions about their inhalers. Objective inhalation technique assessment was performed. Data were triangulated to identify characteristics that could indicate a relationship between inhaler technique, satisfaction, preference, and decision making. Themes from qualitative interviews were as follows: asthma inhalers and expectations; inhaler preference; characteristics of an ideal inhaler; perceived effectiveness of inhalers; and inhalers and patient decision making. PASAPQ scores indicated that all patients were at least "somewhat satisfied" with their inhalers, regardless of technique. Only 12% of inhalers were used correctly, despite pilot PASAPQ data suggesting that most patients were confident with their technique. The inhaler technique was unlikely to be related to satisfaction, perception of inhaler devices, or choice in device selection. Patients with correct inhaler technique were more aware of their asthma and expressed motivation to achieve optimal asthma control. The majority of the asthmatic patients did not use their inhaler(s) correctly, despite most having confidence in their technique. Patients attributed confidence in their inhaler technique to their belief that their inhaler was effective. Most patients had not been

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

    PubMed

    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.

  2. 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

  3. [New inhalation anesthetics].

    PubMed

    Conzen, P; Nuscheler, M

    1996-08-01

    Recently, two new halogenated volatile anaesthetics, sevoflurane and desflurane, have been approved for clinical use in Germany. Their low solubility in blood is the most important common property, and this represents the most obvious difference from the inhalational anaesthetics currently used. Extensive clinical and experimental evaluations have confirmed the superior pharmacokinetic properties predicted. Both sevoflurane and desflurane provide more rapid emergence from anaesthesia, permit easier titration of the anaesthetic dose during maintenance and offer more rapid recovery from anaesthesia. For sevoflurane, there are additional advantages: a pleasant odor, negligible airway irritation, and excellent pharmacodynamic characteristics that even provide cardiovascular stability comparable to isoflurane. A certain disadvantage and source of potential nephrotoxicity result from the metabolism of sevoflurane (2-5%) to anorganic fluoride and degradation to compound A in carbon dioxide absorbents. The extensive clinical data reported to date have revealed no evidence that sevoflurane has adverse renal effects. New insight into the pathomechanism of nephrotoxicity associated with either production of fluoride or compound A may well support clinical experience. Desflurane strongly resists in vivo metabolism and because of this it appears to be devoid of toxicity. Nevertheless, potential side-effects may result from degradation in dry absorbents and subsequent release of CO, from its extreme pungency and irritating airway effects. Thus, desflurane is not recommended for induction of anaesthesia, especially in children. The tendency for desflurane transiently to stimulate sympathetic activity, especially at concentrations above 1.0 MAC, limits its application in patients with cardiac disease.

  4. 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.

  5. Safety of an alkalinizing buffer designed for inhaled medications in humans.

    PubMed

    Davis, Michael D; Walsh, Brian K; Dwyer, Scott T; Combs, Casey; Vehse, Nico; Paget-Brown, Alix; Pajewski, Thomas; Hunt, John F

    2013-07-01

    Airway acidification plays a role in disorders of the pulmonary tract. We hypothesized that the inhalation of alkalinized glycine buffer would measurably alkalinize the airways without compromising lung function or causing adverse events. We evaluated the safety of an inhaled alkaline glycine buffer in both healthy subjects and in subjects with stable obstructive airway disease. This work includes 2 open-label safety studies. The healthy controls were part of a phase 1 safety study of multiple inhalations of low-dose alkaline glycine buffer; nebulized saline was used as a comparator in 8 of the healthy controls. Subsequently, a phase 2 study in subjects with stable obstructive airway disease was completed using a single nebulized higher-dose strategy of the alkaline inhalation. We studied 20 non-smoking adults (10 healthy controls and 10 subjects with obstructive airway disease), both at baseline and after inhalation of alkaline buffer. We used spirometry and vital signs as markers of clinical safety. We used changes in fraction of exhaled nitric oxide (NO) and exhaled breath condensate (EBC) pH as surrogate markers of airway pH modification. Alkaline glycine inhalation was tolerated by all subjects in both studies, with no adverse effects on spirometric parameters or vital signs. Airway alkalinization was confirmed by a median increase in EBC pH of 0.235 pH units (IQR 0.56-0.03, P = .03) in subjects after inhalation of the higher-dose alkaline buffer (2.5 mL of 100 mmol/L glycine). Alkalinization of airway lining fluid is accomplished with inhalation of alkaline glycine buffer and causes no adverse effects on pulmonary function or vital signs.

  6. Inhalant Withdrawal as a Clinically Significant Feature of Inhalant Dependence Disorder

    PubMed Central

    Perron, Brian E.; Howard, Matthew O.; Vaughn, Michael G.; Jarman, Christopher N.

    2009-01-01

    Inhalant use is the intentional inhalation of vapors from commercial products or specific chemical agents for the purpose of achieving intoxication. Inhalants are among the most common and pernicious forms of substance use and the least studied of the major drugs. Diagnosis of inhalant dependence, according to the DSM-IV [1] excludes inhalant withdrawal symptoms, as expert opinion has suggested that an inhalant withdrawal syndrome is neither common nor clinically significant. This article draws from multiple sources of data to suggest that withdrawal symptoms can be part of inhalant dependence and are clinically significant. This hypothesis needs rigorous evaluation to ensure the diagnostic validity of inhalant use disorders. PMID:19632058

  7. Adverse consequences of acute inhalant intoxication.

    PubMed

    Garland, Eric L; Howard, Matthew O

    2011-04-01

    Inhalants are widely misused by adolescents and are among the most toxic of psychoactive substances. This investigation examined the prevalence and correlates of adverse consequences of acute inhalant intoxication. Adolescent inhalant users (n = 279) in residential care completed structured interviews including assessments of the characteristics of their inhalant use. Multivariate logistic and linear regression and path analyses identified correlates of adverse inhalant intoxication-related experiences. Results of this study indicated that high-risk behaviors and adverse outcomes experienced during episodes of inhalant intoxication were common in this sample. High-frequency inhalant users were significantly more likely than moderate- and low-frequency users to experience adverse consequences of inhalant intoxication. Certain risky behaviors and consequences, such as engaging in unprotected sex or acts of physical violence while high on inhalants, were dramatically more common among high-frequency users than low-frequency users. Prior traumatic experiences, trait impulsivity, self-medication use of inhalants, and polydrug use were significant correlates of adverse inhalant-intoxication-related consequences. Adverse events and high-risk behaviors commonly occurred during episodes of inhalant intoxication in this sample of adolescents. High-frequency inhalant users and youth who used inhalants to medicate negative affective states were at elevated risk for such events.

  8. [Inhaled medication and inhalation devices for lung disease].

    PubMed

    Solé, Amparo; Girón, Rosa Ma

    2015-09-01

    Nebulized antibiotic therapy is an attractive therapeutic option given the high concentration obtained from the drug at the site of infection, minimizing the adverse effects and possible drug interactions. Inhalation of drugs as treatment of cystic fibrosis (CF) related lung disease has been proven to be highly effective. Consequently, an increasing number of drugs and devices have been developed for CF lung disease or are currently under development. Other limited areas of experience in this field are lung transplant recipients, immunosuppressed patients, bronchiectasis and ventilated patients. In this review document we analyse the current status of the inhaled medications, their modes of administration and indications and their results as well as side effects. Specifically we address antibiotics, and additionally, we review the current knowledge on devices for inhalation therapy with regard to optimal particle sizes and characteristics of wet nebulisers, dry powder and metered dose inhalers. Several factors contribute to a highly variable pulmonary drug deposition as the devices, the physical properties of the administered antimicrobial agent, the type of respiratory disease and the inhalation technique. Despite many clinicians have obtained a valuable experience from the aerosolized administration of antimicrobials and persuaded of their efficacy and safety. However, RCTs out of CF are needed to answer important clinical questions, such as what is the appropriate dose, the optimal delivery device, the optimal way of drug administration, as well as the exact therapeutic role and pharmacokinetic profile of aerosolized drug.

  9. Evaluation of serum concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-10, and nitric oxide (NO) during the estrous cycle, early pregnancy and abortion in goats.

    PubMed

    Chen, Youwang; Lv, Wenting; Jia, Jingliang; Wang, Jiantao; Yang, Jianhui

    2016-11-01

    The aim of this study was to establish the serum concentrations, ranges, and trends of Th1 type cytokine (tumor necrosis factor (TNF)-α and interleukin (IL)-2), Th2 type cytokine (IL-10), and nitric oxide (NO) during the estrous cycle, early pregnancy and abortion in goats. Boer goats (n=25) having symptoms of normal estrous cycles were selected, 20 were mated and 15 conceived a pregnancy, and the remaining five were not mated and served as estrous controls. On the Day 60 of pregnancy, all 15 pregnant goats were induced to abort the pregnancy by intramuscular injection of prostaglandin (PG). Serum samples were collected on Days 1, 7, 14, and 19 of the estrous cycle, at Days 0, 10, 20, 30, 40, 50, and 60 of pregnancy, and at Days 1, 3, 8, 10 over the period when abortion were occurring. Results of the present study indicated that during the estrous cycle the balance between Th1 and Th2 cytokines slightly shifted toward Th1 cytokine production (TNF-α and IL-2). The NO may have a direct positive role in inducing a Th1 response. During early pregnancy, TNF-α and IL-2 serum concentrations markedly increased from Days 0 to 10, and gradually decreased from Days 10 to 60, while IL-10 and NO serum concentrations remained elevated from Days 0 to 60. The increased concentrations of IL-10 and decreased concentrations of TNF-α and IL-2 are characteristic of a Th2-enhanced response, which may be related to increased concentrations of NO. These changes may be essential to maintain a normal pregnancy. In addition, the serum concentrations of TNF-α, IL-2 and NO at Days 1, 3, 8 and 10 of the period of induced abortion were markedly greater than that on Day 60 of pregnancy. Conversely, IL-10 concentrations at these four time points of abortion were markedly less than that on Day 60 of pregnancy. After abortion, the Th2 response shifted to a Th1-enhanced response. Thus, NO concentrations increase and the Th1-enhanced response may function synergistically to be involved in

  10. 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.

  11. Reduced upper airway nitric oxide in cystic fibrosis.

    PubMed Central

    Balfour-Lynn, I M; Laverty, A; Dinwiddie, R

    1996-01-01

    Nitric oxide (NO) produced within the respiratory tract is detectable in exhaled and nasal air. Its synthesis may be induced by inflammatory cytokines and reduced by glucocorticoids. Increased concentrations have been found in asthma and bronchiectasis. In this study, NO concentrations were determined in 63 children with cystic fibrosis, of whom 13 were on inhaled steroids (mean age 13.3 years) and 50 were not (mean age 12.3 years); 57 normal children (mean age 12.2 years) were also studied. NO was measured by chemiluminescence analyser, exhaled NO following a relaxed vital capacity manoeuvre, and nasal NO with the breath held following a full inspiration. Mean concentration of exhaled NO in cystic fibrosis patients (no steroids) was 4.7 parts per billion (ppb) (95% confidence interval (CI) 4.0 to 5.3); this did not differ from values in normal children (mean 4.8 ppb, 95% CI 3.8 to 5.8) or in cystic fibrosis patients on inhaled steroids (mean 3.6 ppb, 95% CI 2.5 to 4.8). Nasal concentrations were significantly lower in cystic fibrosis patients, with or without inhaled steroids, than in normal children (cystic fibrosis, no inhaled steroids: 460 ppb, 95% CI 399 to 520; cystic fibrosis, inhaled steroids: 522 ppb, 95% CI 313 to 730, v normal children: 1024 ppb, 95% CI 896 to 1152, p < 0.0001). Considering the inflammatory nature of cystic fibrosis, it is surprising exhaled NO levels were not increased, but this may have been due to alteration in NO diffusion through thick mucus. The low nasal NO concentrations, which are probably the result of impaired flow from the paranasal sinuses, may contribute to the recurrent respiratory infections typical of cystic fibrosis. PMID:8984918

  12. 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

  13. Fluticasone furoate, a novel inhaled corticosteroid, demonstrates prolonged lung absorption kinetics in man compared with inhaled fluticasone propionate.

    PubMed

    Allen, Ann; Bareille, Philippe J; Rousell, Vicki M

    2013-01-01

    Fluticasone furoate (FF; GW685698) is a novel inhaled corticosteroid that is active at 24 h and under development for once-daily administration in combination with the long-acting β(2)-adrenoceptor agonist vilanterol (GW642444) for chronic obstructive pulmonary disease and asthma. In vitro studies examining the respiratory tissue-binding properties of corticosteroids showed FF to have the largest cellular accumulation and slowest rate of efflux compared with other clinically used inhaled corticosteroids, consistent with greater tissue retention. The enhanced affinity of the glucocorticoid receptor binding of FF, coupled with its extended tissue association, may be expected to lead to greater and more prolonged anti-inflammatory effects and should provide relevant once-daily efficacy. The aim of this study was to assess the rate and extent of systemic absorption of FF from the lung following inhaled administration of FF from three exploratory dry powder formulations (via DISKHALER(®)) compared with inhaled fluticasone propionate (FP) [via DISKHALER(®)] using deconvolution analysis. This open-label, part-randomized, six-way crossover study evaluated three early development dry powder inhaled formulations of FF administered as single doses via DISKHALER(®). Healthy male subjects (n = 24) each received FF (2,000 μg; three formulations), inhaled FP (1,000 μg; via DISKHALER(®)) and 250 μg of each molecule by intravenous infusion. The bioavailability of both inhaled FF and FP represents absorption from the lung as the oral bioavailability from the swallowed portion of the inhaled dose is negligible (<1.5 %). To investigate the absorption kinetics from the lung, the inhaled concentration-time data were subjected to deconvolution analysis using derived pharmacokinetic parameters from fitting of the intravenous concentration-time data. The terminal elimination half-life (t(½β)) for inhaled FF was considerably longer (range 17-24 h) than the t(½β) estimated for

  14. Beneficial effects of nitric oxide on outcomes after cardiac arrest and cardiopulmonary resuscitation in hypothermia-treated mice

    PubMed Central

    Kida, Kotaro; Shirozu, Kazuhiro; Yu, Binglan; Mandeville, Joseph B.; Bloch, Kenneth D.; Ichinose, Fumito

    2015-01-01

    Background Therapeutic hypothermia (TH) improves neurological outcomes after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Although nitric oxide prevents organ injury induced by ischemia and reperfusion, role of nitric oxide during TH after CPR remains unclear. Here, we examined the impact of endogenous nitric oxide synthesis on the beneficial effects of hypothermia after CA/CPR. We also examined whether or not inhaled nitric oxide during hypothermia further improves outcomes after CA/CPR in mice treated with TH. Methods Wild-type (WT) mice and mice deficient for nitric oxide synthase 3 (NOS3−/−) were subjected to CA at 37°C and then resuscitated with chest compression. Body temperature was maintained at 37°C (normothermia) or reduced to 33°C (TH) for 24 hours after resuscitation. Mice breathed air or air mixed with nitric oxide at 10, 20, 40, 60, or 80 ppm during hypothermia. To evaluate brain injury and cerebral blood flow, magnetic resonance imaging was performed in WT mice after CA/CPR. Results Hypothermia up-regulated the NOS3-dependent signaling in the brain (n=6–7). Deficiency of NOS3 abolished the beneficial effects of hypothermia after CA/CPR (n=5–6). Breathing nitric oxide at 40 ppm improved survival rate in hypothermia-treated NOS3−/− mice (n=6) after CA/CPR compared to NOS3−/− mice that were treated with hypothermia alone (n=6, P<0.05). Breathing nitric oxide at 40 (n=9) or 60 (n=9) ppm markedly improved survival rates in TH-treated WT mice (n=51) (both P<0.05 vs TH-treated WT mice). Inhaled nitric oxide during TH (n=7) prevented brain injury compared to TH alone (n=7) without affecting cerebral blood flow after CA/CPR (n=6). Conclusions NOS3 is required for the beneficial effects of TH. Inhaled nitric oxide during TH remains beneficial and further improves outcomes after CA/CPR. Nitric oxide breathing exerts protective effects after CA/CPR even when TH is ineffective due to impaired endogenous nitric oxide production

  15. 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.

  16. Nitric oxide and the paranasal sinuses.

    PubMed

    Lundberg, Jon O

    2008-11-01

    The discovery within the paranasal sinuses for the production of nitric oxide (NO) has altered the traditional explanations of sinus physiology. This review article reports the ongoing investigation of sinus physiology beginning with the discovery of NO gas production in the paranasal sinuses that occurred in 1995, and the impact that finding has had both in the basic science and clinical arenas. It was shown that healthy paranasal sinus epithelium expresses an inducible NO synthase that continuously generates large amounts of NO, a pluripotent gaseous messenger with potent vasodilating, and antimicrobial activity. This NO can be measured noninvasively in nasally exhaled breath. The role of NO in the sinuses is likely to enhance local host defense mechanisms via direct inhibition of pathogen growth and stimulation of mucociliary activity. The NO concentration in a healthy sinus exceeds those that are needed for antibacterial effects in vitro. In patients with primary ciliary dyskinesia (PCD) and in cystic fibrosis, nasal NO is extremely low. This defect NO generation likely contributes to the great susceptibility to chronic sinusitis in these patients. In addition, the low-nasal NO is of diagnostic value especially in PCD, where nasal NO is very low or absent. Intriguingly, NO gas from the nose and sinuses is inhaled with every breath and reaches the lungs in a more diluted form to enhance pulmonary oxygen uptake via local vasodilation. In this sense NO may be regarded as an "aerocrine" hormone that is produced in the nose and sinuses and transported to a distal site of action with every inhalation. Copyright 2008 Wiley-Liss, Inc.

  17. [Ciclesonide -- a new inhaled corticosteroid].

    PubMed

    Ukena, D

    2005-10-01

    Ciclesonide is a novel inhaled corticosteroid delivered as inactive prodrug via a hydrofluoroalkane metered-dose inhaler with a deposition rate of 50 - 60 %. At its target sites, the lungs, ciclesonide is converted to an active metabolite, desisobutyryl-ciclesonide (des-CIC) [so-called on-site activation]. High lipophilicity and formation of local depot prolong pulmonary duration of action, explaining once-daily administration of ciclesonide. High protein binding and rapid clearance reduce systemic interactions. In long-term studies, ciclesonide at doses as high as 1280-1600 microg/d did not suppress biochemical markers of adrenal function. Since ciclesonide is not being activated in the oropharynx, the incidence of local adverse effects is comparable to that of placebo. Compared to other ICS, ciclesonide shows a improved therapeutic index and can, therefore, be regarded as prototype of a new, third generation of inhaled corticosteroids.

  18. Comparison of Physician-, Biomarker-, and Symptom-Based Strategies for Adjustment of Inhaled Corticosteroid Therapy in Adults With Asthma

    PubMed Central

    Calhoun, William J.; Ameredes, Bill T.; King, Tonya S.; Icitovic, Nikolina; Bleecker, Eugene R.; Castro, Mario; Cherniack, Reuben M.; Chinchilli, Vernon M.; Craig, Timothy; Denlinger, Loren; DiMango, Emily A.; Engle, Linda L.; Fahy, John V.; Grant, J. Andrew; Israel, Elliot; Jarjour, Nizar; Kazani, Shamsah D.; Kraft, Monica; Kunselman, Susan J.; Lazarus, Stephen C.; Lemanske, Robert F.; Lugogo, Njira; Martin, Richard J.; Meyers, Deborah A.; Moore, Wendy C.; Pascual, Rodolfo; Peters, Stephen P.; Ramsdell, Joe; Sorkness, Christine A.; Sutherland, E. Rand; Szefler, Stanley J.; Wasserman, Stephen I.; Walter, Michael J.; Wechsler, Michael E.; Boushey, Homer A.

    2013-01-01

    Context No consensus exists for adjusting inhaled corticosteroid therapy in patients with asthma. Approaches include adjustment at outpatient visits guided by physician assessment of asthma control (symptoms, rescue therapy, pulmonary function), based on exhaled nitric oxide, or on a day-to-day basis guided by symptoms. Objective To determine if adjustment of inhaled corticosteroid therapy based on exhaled nitric oxide or day-to-day symptoms is superior to guideline-informed, physician assessment–based adjustment in preventing treatment failure in adults with mild to moderate asthma. Design, Setting, and Participants A randomized, parallel, 3-group, placebo-controlled, multiply-blinded trial of 342 adults with mild to moderate asthma controlled by low-dose inhaled corticosteroid therapy (n=114 assigned to physician assessment–based adjustment [101 completed], n=115 to biomarker-based [exhaled nitric oxide] adjustment [92 completed], and n=113 to symptom-based adjustment [97 completed]), the Best Adjustment Strategy for Asthma in the Long Term (BASALT) trial was conducted by the Asthma Clinical Research Network at 10 academic medical centers in the United States for 9 months between June 2007 and July 2010. Interventions For physician assessment–based adjustment and biomarker-based (exhaled nitric oxide) adjustment, the dose of inhaled corticosteroids was adjusted every 6 weeks; for symptom-based adjustment, inhaled corticosteroids were taken with each albuterol rescue use. Main Outcome Measure The primary outcome was time to treatment failure. Results There were no significant differences in time to treatment failure. The 9-month Kaplan-Meier failure rates were 22% (97.5% CI, 14%-33%; 24 events) for physician assessment–based adjustment, 20% (97.5% CI, 13%-30%; 21 events) for biomarker-based adjustment, and 15% (97.5% CI, 9%-25%; 16 events) for symptom-based adjustment. The hazard ratio for physician assessment–based adjustment vs biomarker

  19. 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. © 2014 Wiley Periodicals, Inc.

  20. Inhalant Abuse: Is Your Child at Risk?

    MedlinePlus

    ... can be valuable as well. With help, your child can end inhalant abuse and learn how to make healthy choices for a lifetime. References Baydala L. Inhalant abuse. Paediatrics and Child Health. 2010;15:443. Results from the 2013 ...

  1. Asthma Inhalers: Which One's Right for You?

    MedlinePlus

    ... medication in these inhalers by breathing in a deep, fast breath. There are multiple-dose devices, which ... and convenient to carry. Doesn't require a deep, fast, inhaled breath. Doesn't require a deep, ...

  2. Huffing: prehospital identification & treatment of inhalant abuse.

    PubMed

    Criss, Liz

    2009-05-01

    Sniffing. Huffing. Bagging. These street terms describe methods of inhaling toxic chemicals to achieve mind-altering states of intoxication or euphoria. Just about anything in the house that comes in spray form can be used as an inhalant.

  3. Substance use disorders among inhalant users: results from the National Epidemiologic Survey on alcohol and related conditions.

    PubMed

    Wu, Li-Tzy; Howard, Matthew Owen; Pilowsky, Daniel J

    2008-07-01

    To assess the prevalence, correlates, and age of onset of DSM-IV substance use disorders (SUDs) among adult inhalant users. Analyses were based on structured psychiatric interviews of a nationally representative sample of 43,093 US adults. The lifetime prevalence of SUDs among adult inhalant users was 96%. Alcohol (87%), marijuana (68%), nicotine (58%), cocaine (35%), hallucinogen (31%), and stimulant (28%) use disorders were more prevalent than inhalant use disorders (19%). An estimated 62% of inhalant users met criteria for a past-year SUD. Less education, residence in non-metropolitan areas, early onset of inhalant use, and a history of substance abuse treatment were associated with increased odds of having an inhalant use disorder. Inhalant users who were under age 30 or who were members of families with low incomes had increased odds of having nicotine dependence and an alcohol or drug use disorder in the past year. Compared with substance users without a history of inhalant use, inhalant users, on average, initiated use of cigarettes, alcohol, and almost all other drugs at younger ages, and had a higher lifetime prevalence of nicotine, alcohol, and any drug use disorder. Lifetime and past-year SUDs are prevalent among adults with a history of inhalant use.

  4. Substance use disorders among inhalant users: Results from the National Epidemiologic Survey on Alcohol and Related Conditions

    PubMed Central

    Wu, Li-Tzy; Howard, Matthew Owen; Pilowsky, Daniel J.

    2008-01-01

    Objective To assess the prevalence, correlates, and age of onset of DSM-IV substance use disorders (SUDs) among adult inhalant users. Methods Analyses were based on structured psychiatric interviews of a nationally representative sample of 43,093 U.S. adults. Results The lifetime prevalence of SUDs among adult inhalant users was 96%. Alcohol (87%), marijuana (68%), nicotine (58%), cocaine (35%), hallucinogen (31%), and stimulant (28%) use disorders were more prevalent than inhalant use disorders (19%). An estimated 62% of inhalant users met criteria for a past-year SUD. Less education, residence in non-metropolitan areas, early onset of inhalant use, and a history of substance abuse treatment were associated with increased odds of having an inhalant use disorder. Inhalant users who were under age 30 or who were members of families with low incomes had increased odds of having nicotine dependence and an alcohol or drug use disorder in the past year. Compared with substance users without a history of inhalant use, inhalant users, on average, initiated use of cigarettes, alcohol, and almost all other drugs at younger ages, and had a higher lifetime prevalence of nicotine, alcohol, and any drug use disorder. Conclusions Lifetime and past-year SUDs are prevalent among adults with a history of inhalant use. PMID:18403132

  5. Perceived Risk of Harm and Intentions of Future Inhalant Use among Adolescent Inhalant Users

    PubMed Central

    Perron, Brian E.; Howard, Matthew O.

    2008-01-01

    Objective To identify predictors of perceived a) risk of harm associated with inhalant use and b) intention to use inhalants among adolescent inhalant users. Method Participants were 279 lifetime inhalant users (Mage = 15.5, 84 % male) identified in a statewide survey of 723 adolescents in Missouri Division of Youth Services’ residential care for antisocial conduct. Youth completed interviews assessing inhalant and other drug use, psychiatric symptoms, and antisocial traits/behavior. Results More than one-third (37%) of youth perceived experimental inhalant use as of slight or no risk; one-in-eight (11.9 %) youth perceived regular inhalant use as of slight or no risk. Risk perceptions of experimental and regular inhalant use were not associated with intentions to use. Youth with friends/sibling inhalant who use inhalants were less likely to perceive risks associated with experimental and regular inhalant use compared to youth without friends/sibling users. Adolescents who were younger and those with more extensive substance abuse problems, prior problems with inhalants, greater current psychiatric distress, friends/sibling who use inhalants were significantly more likely to report intentions of future inhalant use than their counterparts. Conclusions Assessment of substance use among youth, particularly those in the criminal justice system, should include an assessment of inhalants. Intervention efforts should include addressing misperceptions of risk associated with inhalants and developing strategies for managing social network influences. PMID:18524500

  6. 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

  7. Inhalant Use by Canadian Aboriginal Youth.

    ERIC Educational Resources Information Center

    Coleman, Heather; Charles, Grant; Collins, Jennifer

    2001-01-01

    Study followed youth who received treatment for inhalant abuse. Many came from backgrounds marked by isolation, poverty, family violence, and substance abuse. Average age the youths first used inhalants was 9.72 years. Model predicted those who abused inhalants immediately before admission, were described as unmotivated in treatment, and were…

  8. Airway function, oedema, cell infiltration and nitric oxide generation in conscious ozone-exposed guinea-pigs: effects of dexamethasone and rolipram.

    PubMed

    Toward, Toby J; Broadley, Kenneth J

    2002-07-01

    1. The effects of ozone inhalation (90 min, 2.15+/-0.05 p.p.m.) and their modification by dexamethasone (20 mg kg(-1)) or the phosphodiesterase-4 inhibitor, rolipram (1 mg kg(-1)), administered (i.p.) 24 and 0.5 h before and 24 h after ozone exposure were examined in conscious guinea-pigs. 2. Ozone caused an early-phase bronchoconstriction (EPB) as a fall in specific airways conductance (sG(aw)) measured by whole body plethysmography, followed at 5 h by a late-phase bronchoconstriction (LPB) and increased respiratory rate. Rolipram did not alter this profile but dexamethasone inhibited the EPB. 3. Airway hyperreactivity to inhaled histamine (1 mM, 20 s) occurred at 0.5, 2, 12, 24 and 48 h after ozone inhalation, the 2 h change being abolished by rolipram and dexamethasone. 4. Bronchoalveolar lavage fluid (BALF) macrophages, eosinophils and neutrophils were significantly (P<0.05) elevated at 12, 24 and 48 h after ozone exposure, the 48 h influx being significantly attenuated (P<0.05) by rolipram and dexamethasone. 5. BALF nitric oxide (NO) metabolites decreased 0.5 h after ozone exposure by 52%, recovered at 2 h and significantly increased at 12 (101%) and 24 h (127%). The elevated NO was unaffected by rolipram or dexamethasone. 6. Lung oedema, measured from wet/dry weight differences, was significant 12, 24 and 48 h after ozone exposure, the latter being significantly attenuated (P<0.05) by rolipram and dexamethasone. 7. Ozone exposure of guinea-pigs produced features common to COPD. Although rolipram and dexamethasone did not affect the airway function changes, they inhibited the inflammation, airway hyperreactivity and oedema.

  9. Inhalational Anesthetics as Preconditioning Agents in Ischemic Brain

    PubMed Central

    Wang, Lan; Traystman, Richard J.; Murphy, Stephanie J.

    2008-01-01

    SUMMARY While many pharmacological agents have been shown to protect the brain from cerebral ischemia in animal models, none have translated successfully to human patients. One potential clinical neuroprotective strategy in humans may involve increasing the brain’s tolerance to ischemia by pre-ischemic conditioning (preconditioning). There are many methods to induce tolerance via preconditioning such as: ischemia itself, pharmacological, hypoxia, endotoxin, and others. Inhalational anesthetic agents have also been shown to result in brain preconditioning. Mechanisms responsible for brain preconditioning are many, complex, and unclear and may involve Akt activation, ATP-sensitive potassium channels, and nitric oxide, amongst many others. Anesthetics, however, may play an important and unique role as preconditioning agents, particularly during the perioperative period. PMID:17962069

  10. Detection of nitric oxide pollution

    NASA Technical Reports Server (NTRS)

    Chackerian, C., Jr.; Weisbach, M. F.

    1973-01-01

    Studies of absorption spectra enhancement of certain atomic and molecular species inserter in dye-laser cavities have indicated that nitric oxide can be determined at low concentrations. Absorption coefficient of small amounts of nitric oxide in intra-laser-cavity absorption cell containing helium is enhanced by more than two orders of magnitude.

  11. Bacterial nitric oxide synthases.

    PubMed

    Crane, Brian R; Sudhamsu, Jawahar; Patel, Bhumit A

    2010-01-01

    Nitric oxide synthases (NOSs) are multidomain metalloproteins first identified in mammals as being responsible for the synthesis of the wide-spread signaling and protective agent nitric oxide (NO). Over the past 10 years, prokaryotic proteins that are homologous to animal NOSs have been identified and characterized, both in terms of enzymology and biological function. Despite some interesting differences in cofactor utilization and redox partners, the bacterial enzymes are in many ways similar to their mammalian NOS (mNOS) counterparts and, as such, have provided insight into the structural and catalytic properties of the NOS family. In particular, spectroscopic studies of thermostable bacterial NOSs have revealed key oxyheme intermediates involved in the oxidation of substrate L-arginine (Arg) to product NO. The biological functions of some bacterial NOSs have only more recently come to light. These studies disclose new roles for NO in biology, such as taking part in toxin biosynthesis, protection against oxidative stress, and regulation of recovery from radiation damage.

  12. Nitric oxide neurotoxicity.

    PubMed

    Dawson, V L; Dawson, T M

    1996-06-01

    Derangements in glutamate neurotransmission have been implicated in several neurodegenerative disorders including, stroke, epilepsy, Huntington's disease, Alzheimer's disease, and amyotrophic lateral sclerosis (ALS). Activation of the N-methyl-D-aspartate (NMDA) receptor subtype of glutamate receptors results in the influx of calcium which binds calmodulin and activates neuronal nitric oxide synthase (nNOS), to convent L-arginine to citrulline and nitric oxide (NO). NO has many roles in the central nervous system as a messenger molecule, however, when generated in excess NO can be neurotoxic. Excess NO is in part responsible for glutamate neurotoxicity in primary neuronal cell culture and in animal models of stroke. It is likely that most of the neurotoxic actions of NO are mediated by peroxynitrite (ONOO-), the reaction product from NO and superoxide anion. In pathologic conditions, peroxynitrite and oxygen free radicals can be generated in excess of a cell antioxidant capacity resulting in severe damage to cellular constituents including proteins, DNA and lipids. The inherent biochemical and physiological characteristics of the brain, including high lipid concentrations and energy requirements, make it particularly susceptible to free radical and oxidant mediated insult. Increasing evidence indicates that many neurologic disorders may have components of free radical and oxidative stress induced injury.

  13. 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…

  14. 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...

  15. Acculturation Influences on Inhalant Use.

    ERIC Educational Resources Information Center

    Barrett, Mark E.; And Others

    1991-01-01

    Analyses of data on 110 Mexican-American adolescent inhalant users and 78 of their mothers indicate that level of acculturation, cultural factors, and socioeconomic factors did not directly affect youth's drug use and criminality but may have had indirect effects through socialization and psychological factors. Contains 22 references. (Author/SV)

  16. 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…

  17. 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...

  18. 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…

  19. 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…

  20. 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 ...

  1. 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 ...

  2. A nebulizer chronolog to monitor compliance with inhaler use.

    PubMed

    Tashkin, D P; Rand, C; Nides, M; Simmons, M; Wise, R; Coulson, A H; Li, V; Gong, H

    1991-10-21

    The Lung Health Study is a 10-center 5-year clinical trial sponsored by the National Heart, Lung, and Blood Institute to evaluate the effectiveness of early intervention in chronic obstructive pulmonary disease (COPD). The specific objectives of the trial are to determine whether the accelerated decline in lung function characteristic of COPD and morbidity due to COPD can be reduced by special intervention at a relatively early stage in the evolution of the disease. Special intervention consists of a smoking-cessation program and the use of an inhaled bronchodilator to suppress airway hyperreactivity. The use of the inhaler canister is monitored every 4 months by canister weighing and, at two of the 10 centers, by an electronic recording device, the Nebulizer Chronolog. Among trial participants assigned the latter device, results from the first 4 months of the study indicate that only 52% of trial participants who were uninformed as to the nature of the chronolog used their inhaler at least twice daily as measured by the chronolog, compared with 87% as determined by self-report. Satisfactory or good compliance was achieved by 52% of these subjects as measured by the chronolog compared with 85% as assessed by canister weighing. Eighteen percent of uninformed participants "dumped" their inhalers within a 3-hour time period, contributing to the inaccuracy of canister weights as an indicator of compliance. Feedback of information to the participants from the chronolog improved the level of compliance and eliminated the "dumping" phenomenon. We conclude that, when accurate determinations of compliance are important, as in a drug trial, objective medication monitors should be considered. Electronic monitoring of inhaler use can provide valuable feedback, which encourages improved compliance.

  3. Acute Lung Injury after Phosgene Inhalation

    PubMed Central

    Lim, Sung-Chul; Yang, Ju-Yeoul; Jang, An-Soo; Park, Yong-Uk; Kim, Young-Chul; Choi, In-Seon; Park, Kyung-Ok

    1996-01-01

    Phosgene (COCl2) is a colorless oxidant gas which is heavier than air and the lethal exposure dose (LC50) in humans is 500 ppm/min. This gas was originally manufactured as an agent for chemical warfare during World War I and there had been a great deal of studies on phosgene poisoning during the early years of industrial use. It is still widely used in the synthesis of chemicals and plastics. In the modern era, however, phosgene poisoning is relatively uncommon except in accidental exposures. In Korea, there has been no report about lung injury from phosgene inhalation. We present a clinical experience with six patients accidentally exposed to phosgene. PMID:8882481

  4. Effects of nitric oxide in mucociliary transport.

    PubMed

    Blanco, Eleonora Elisia Abra; Pinge, Marli Cardoso Martins; Andrade Neto, Otavio André; Pessoa, Nathália Gardin

    2009-01-01

    The airways are made up of ciliated epithelium which secretes mucous, protecting the respiratory tract from particles inhaled during breathing. Its is paramount to understand the physiology and the mechanisms involved in mucociliary activity. Literature suggests that Nitric oxide (NO), especially the one produced by iNOS expression, maintains the mucociliary function and the immune defense of the nasal cavity. to assess NO participation and the enzymatic pathways in the production of NO and mucociliary transport, using constructive and inductive NO synthetase inhibitors, L-NAME and aminoguanidine, respectively. frog palates were prepared and immersed in ringer (control), L-NAME or aminoguanidine solutions. The palates were immersed in these solutions for four periods of 15 minutes. Mucociliary transport measures were carried out before and after each exposure. control palates maintained stable their transportation speed. L-NAME increased, while aminoguanidine reduced mucous transportation velocity. unspecific cNOS block with L-NAME and relatively specific iNOS block with aminoguanidine results leads us to propose that depending on the pathway, the NO can increase or reduce mucociliary transport in frog palates.

  5. Evaluation and Management of Patients with Inhalation Injury

    DTIC Science & Technology

    1990-12-01

    and wheezing, are often ( de- effect f early atelectasis consequent to occlusion of the layed onset (2). Conversely, the presence of carbonaceous small...least in part the atelectasis that tation, may produce a falsely negative scan if the scan is occurs in patients with inhalation injury. The adminis...injury makes the maintenance of form the more sophisticated tests and the essentiality of ventilation and prevention of atelectasis a primary din

  6. Dry-powder inhalers in acute asthma.

    PubMed

    Selroos, Olof

    2014-01-01

    An updated literature search was performed to evaluate the efficacy of rapid-acting β2-agonists delivered via dry powder inhalers in the treatment of moderate-to-severe acute asthma. Databases were searched from 1985 up to December 2012. A total of 23 randomized, double-blind or open clinical studies in acute asthma comparing the efficacy of a dry powder inhaler with a pressurized metered-dose inhaler or a nebulizer, and performed under controlled hospital conditions, were identified. This review found that administration of β2-agonist bronchodilators via dry powder inhalers (formoterol, salbutamol, terbutaline and budesonide/formoterol) was effective during severe asthma worsening and acute asthma attacks, and was as effective as established therapies with a pressurized metered-dose inhaler with or without a spacer, or nebulization. These results ensure that patients can rely upon dry powder inhalers equally well as other inhaler devices during episodes of asthma worsening.

  7. Energy Efficient Monitoring of Metered Dose Inhaler Usage.

    PubMed

    Lalos, Aris S; Lakoumentas, John; Dimas, Anastasios; Moustakas, Konstantinos

    2016-12-01

    Life-long chronic inflammatory diseases of the airways, such as asthma and Chronic Obstructive Pulmonary Disease, are very common worldwide, affecting people of all ages, race and gender. One of the most important aspects for the effective management of asthma is medication adherence which is defined as the extent to which patients follow their prescribed action plan and use their inhaler correctly. Wireless telemonitoring of the medication adherence can facilitate early diagnosis and management of these diseases through the use of an accurate and energy efficient mHealth system. Therefore, low complexity audio compression schemes need to be integrated with high accuracy classification approaches for the assessment of adherence of patients that use of pressurized Metered Dose Inhalers (pMDIs). To this end, we propose a novel solution that enables the energy efficient monitoring of metered dose inhaler usage, by exploiting the specific characteristics of the reconstructed audio features at the receiver. Simulation studies, carried out with a large dataset of indoor & outdoor measurements have led to high levels of accuracy (98 %) utilizing only 2 % of the recorded audio samples at the receiver, demonstrating the potential of this method for the development of novel energy efficient inhalers and medical devices in the area of respiratory medicine.

  8. [Experience in the management of severe inhalation injury].

    PubMed

    Chen, B; Jia, C; Su, Y

    1999-11-01

    To summarize our clinical experiences in the treatment of severe inhalation injury accompanying extensive burn. Retrospective analysis of 30 cases of inhalation injury (1980-1996) was done, the cure rate, mortality, effective treatments and lessons of failure were summarized. As soon as the diagnosis was defined, tracheostomy should be done immediately, followed by oxygen therapy, tracheo-bronchial lavage, aspiration, and clearance of airway secretion. If there was pulmonary edema or severe bronchospasm, cortical hormone was used for a short time, in addition, the patients were encouraged to cough, breathe deeply, and change postures, as well as patted on the back and also positioned to facilitate posture drainage, etc. These measures were effective. In this series, there were thirty cases of severe inhalation injury. Fourteen patients(46.6%) were cured, sixteen patients died(53.3%). The result was basically satisfactory. It is possible to increase the cure rate of severe inhalation injury, and the treatment should be carried out conscientiously as early as possible, and great attention should be paid to prevent various complications.

  9. [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.

  10. 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

  11. Nitric oxide enhancement strategies.

    PubMed

    Bryan, Nathan S

    2015-08-01

    It is becoming increasingly clear that many diseases are characterized or associated with perturbations in nitric oxide (NO) production/signaling. Therapeutics or strategies designed to restore normal NO homeostasis will likely have broad application and utility. This highly complex and multistep pathway for NO production and subsequent target activation provides many steps in the endogenous pathway that may be useful targets for drug development for cardiovascular disease, antimicrobial, cancer, wound healing, etc. This article will summarize known strategies that are currently available or in development for enhancing NO production or availability in the human body. Each strategy will be discussed including exogenous sources of NO, use of precursors to promote NO production and downstream pathways affected by NO production with advantages and disadvantages highlighted for each. Development of NO-based therapeutics is and will continue to be a major focus of biotech, academia as well as pharmaceutical companies. Application of safe and effective strategies will certainly transform health and disease.

  12. Perceived risk of harm and intentions of future inhalant use among adolescent inhalant users.

    PubMed

    Perron, Brian E; Howard, Matthew O

    2008-09-01

    To identify predictors of perceived (a) risk of harm associated with inhalant use and (b) intention to use inhalants among adolescent inhalant users. Participants were 279 lifetime inhalant users (M(age)=15.5, 84% male) identified in a statewide survey of 723 adolescents in Missouri Division of Youth Services' residential care for antisocial conduct. Youth completed interviews assessing inhalant and other drug use, psychiatric symptoms, and antisocial traits/behavior. More than one-third (37%) of youth perceived experimental inhalant use as of slight or no risk; one-in-eight (11.9%) youth perceived regular inhalant use as of slight or no risk. Risk perceptions of experimental and regular inhalant use were not associated with intentions to use. Youth with friends/siblings who use inhalants were less likely to perceive risks associated with experimental and regular inhalant use compared to youth without friends/sibling users. Adolescents who were younger and those with more extensive substance abuse problems, prior problems with inhalants, greater current psychiatric distress, and friends/siblings who use inhalants were significantly more likely to report intentions of future inhalant use than their counterparts. Assessments of substance use among youth, particularly those in the criminal justice system, should include an assessment of inhalant use. Intervention efforts should focus on developing strategies for managing social network influences.

  13. Nitric oxide signaling in plants.

    PubMed

    Shapiro, Allan D

    2005-01-01

    Plants have four nitric oxide synthase (NOS) enzymes. NOS1 appears mitochondrial, and inducible nitric oxide synthase (iNOS) chloroplastic. Distinct peroxisomal and apoplastic NOS enzymes are predicted. Nitrite-dependent NO synthesis is catalyzed by cytoplasmic nitrate reductase or a root plasma membrane enzyme, or occurs nonenzymatically. Nitric oxide undergoes both catalyzed and uncatalyzed oxidation. However, there is no evidence of reaction with superoxide, and S-nitrosylation reactions are unlikely except during hypoxia. The only proven direct targets of NO in plants are metalloenzymes and one metal complex. Nitric oxide inhibits apoplastic catalases/ascorbate peroxidases in some species but may stimulate these enzymes in others. Plants also have the NO response pathway involving cGMP, cADPR, and release of calcium from internal stores. Other known targets include chloroplast and mitochondrial electron transport. Nitric oxide suppresses Fenton chemistry by interacting with ferryl ion, preventing generation of hydroxyl radicals. Functions of NO in plant development, response to biotic and abiotic stressors, iron homeostasis, and regulation of respiration and photosynthesis may all be ascribed to interaction with one of these targets. Nitric oxide function in drought/abscisic acid (ABA)-induction of stomatal closure requires nitrate reductase and NOS1. Nitric oxide synthasel likely functions to produce sufficient NO to inhibit photosynthetic electron transport, allowing nitrite accumulation. Nitric oxide is produced during the hypersensitive response outside cells undergoing programmed cell death immediately prior to loss of plasma membrane integrity. A plasma membrane lipid-derived signal likely activates apoplastic NOS. Nitric oxide diffuses within the apoplast and signals neighboring cells via hydrogen peroxide (H2O2)-dependent induction of salicylic acid biosynthesis. Response to wounding appears to involve the same NOS and direct targets.

  14. [Inhalant abusers and psychiatric symptoms].

    PubMed

    Okudaira, K; Yabana, T; Takahashi, H; Iizuka, H; Nakajima, K; Saito, A

    1996-01-01

    There are different opinions about the cause of chronic psychiatric symptoms observed in drug abusers between Japanese and foreign psychiatrists. The Japanese seem to recognize the chronic psychosis as the result of drug abuse. In the other hand, foreigners diagnose these cases as dual diagnosis of drug abuse and psychosis. Authors studied the problem in this research. One of the authors has examined 120 inhalant abusers of all, in- and out-patients in Kanagawa Prefectural Center of Psychiatry, Serigaya Hospital from 1991 to 1995. These patients were classified into three groups: psychosis group (23 patients), dependence group (51 patients) and abuse group (46 patients) according to their clinical courses and psychiatric symptoms. The psychosis group consists of patients who showed psychiatric symptoms such as hallucination, delusion and thought disturbance for long time after detoxification. The dependence group contains patients whose inhalant dependence was severe and met DSM-4 Diagnostic Criteria for Substance Dependence, but manifested no chronic psychiatric symptoms after detoxification. The patients belonging to abuse group were at the earlier stages of inhalant abuse and had no chronic psychiatric symptoms. The average age of the first inhalant abuse was 14.7 years old in the psychosis group, 14.8 years in the dependence group and 14.7 years in the abuse group. The average years of abuse was 9.0 years in the psychosis group, and 8.5 years in the dependence group. There was little difference between these two groups. The psychosis patients manifested chronic symptoms 5.7 years on average after the first abuse of inhalants. About one forth (26.1%) of the psychosis patients and only 5.9% of the dependence patients had family history of schizophrenia. The difference was statistically significant. These results suggest that chronic psychiatric symptoms are caused not only by inhalant abuse, but also by the genetic factors of psychosis of each patient. There have

  15. Nitric oxide and cardiovascular system.

    PubMed

    Cengel, Atiye; Sahinarslan, Asife

    2006-12-01

    Endothelium has many important functions including the control of blood-tissue permeability and vascular tonus, regulation of vascular surface properties for homeostasis and inflammation. Nitric oxide is the chief molecule in regulation of endothelial functions. Nitric oxide deficiency, which is also known as endothelial dysfunction, is the first step for the occurrence of many disease states in cardiovascular system including heart failure, hypertension, dyslipidemia, insulin resistance, diabetes mellitus, hyperhomocysteinemia and smoking. This review deals with the importance of nitric oxide for cardiovascular system. It also includes the latest improvements in the diagnosis and treatment of endothelial dysfunction.

  16. 49 CFR 173.337 - Nitric oxide.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Nitric oxide. 173.337 Section 173.337... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.337 Nitric oxide. (a) Nitric oxide must be... valve and valve seat that will not deteriorate in contact with nitric oxide. Cylinders or valves may...

  17. 49 CFR 173.337 - Nitric oxide.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false Nitric oxide. 173.337 Section 173.337... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.337 Nitric oxide. (a) Nitric oxide must be... valve and valve seat that will not deteriorate in contact with nitric oxide. Cylinders or valves may...

  18. 49 CFR 173.337 - Nitric oxide.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false Nitric oxide. 173.337 Section 173.337... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.337 Nitric oxide. (a) Nitric oxide must be... valve and valve seat that will not deteriorate in contact with nitric oxide. Cylinders or valves may...

  19. 49 CFR 173.337 - Nitric oxide.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 2 2012-10-01 2012-10-01 false Nitric oxide. 173.337 Section 173.337... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.337 Nitric oxide. (a) Nitric oxide must be... valve and valve seat that will not deteriorate in contact with nitric oxide. Cylinders or valves may...

  20. 49 CFR 173.158 - Nitric acid.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 2 2012-10-01 2012-10-01 false Nitric acid. 173.158 Section 173.158... Nitric acid. (a) Nitric acid exceeding 40 percent concentration may not be packaged with any other material. (b) Nitric acid in any concentration which does not contain sulfuric acid or hydrochloric acid as...

  1. 49 CFR 173.158 - Nitric acid.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Nitric acid. 173.158 Section 173.158... Nitric acid. (a) Nitric acid exceeding 40 percent concentration may not be packaged with any other material. (b) Nitric acid in any concentration which does not contain sulfuric acid or hydrochloric acid as...

  2. 49 CFR 173.158 - Nitric acid.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false Nitric acid. 173.158 Section 173.158... Nitric acid. (a) Nitric acid exceeding 40 percent concentration may not be packaged with any other material. (b) Nitric acid in any concentration which does not contain sulfuric acid or hydrochloric acid as...

  3. 49 CFR 173.158 - Nitric acid.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Nitric acid. 173.158 Section 173.158... Nitric acid. (a) Nitric acid exceeding 40 percent concentration may not be packaged with any other material. (b) Nitric acid in any concentration which does not contain sulfuric acid or hydrochloric acid as...

  4. 49 CFR 173.158 - Nitric acid.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false Nitric acid. 173.158 Section 173.158... Nitric acid. (a) Nitric acid exceeding 40 percent concentration may not be packaged with any other material. (b) Nitric acid in any concentration which does not contain sulfuric acid or hydrochloric acid as...

  5. 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

  6. Inhaled anesthetics: an historical overview.

    PubMed

    Whalen, Francis X; Bacon, Douglas R; Smith, Hugh M

    2005-09-01

    Inhalational agents have played a pivotal role in anesthesia history. The first publicly demonstrated anesthetic of the modern era, diethyl ether, was an inhalational anesthetic. The attributes of a good agent, ability to rapidly induce anesthesia, with limited side effects has led research efforts for over a hundred and fifty years. The explosion hazard was largely conquered with the development of the halogenated agents in the 1950s. Rapid emergence, with limited nausea and vomiting continue to drive discovery efforts, yet the 'modern' agents continue to improve upon those in the past. The future holds promise, but perhaps the most interesting contrast over time is the ability to rapidly introduce new agents into practice. From James Young Simpson's dinner table one evening to the operating suite the next day, modern agents take decades from first synthesis to clinical introduction.

  7. 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

  8. 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.

  9. Hazard identification of inhaled nanomaterials: making use of short-term inhalation studies.

    PubMed

    Klein, Christoph L; Wiench, Karin; Wiemann, Martin; Ma-Hock, Lan; van Ravenzwaay, Ben; Landsiedel, Robert

    2012-07-01

    A major health concern for nanomaterials is their potential toxic effect after inhalation of dusts. Correspondingly, the core element of tier 1 in the currently proposed integrated testing strategy (ITS) is a short-term rat inhalation study (STIS) for this route of exposure. STIS comprises a comprehensive scheme of biological effects and marker determination in order to generate appropriate information on early key elements of pathogenesis, such as inflammatory reactions in the lung and indications of effects in other organs. Within the STIS information on the persistence, progression and/or regression of effects is obtained. The STIS also addresses organ burden in the lung and potential translocation to other tissues. Up to now, STIS was performed in research projects and routine testing of nanomaterials. Meanwhile, rat STIS results for more than 20 nanomaterials are available including the representative nanomaterials listed by the Organization for Economic Cooperation and Development (OECD) working party on manufactured nanomaterials (WPMN), which has endorsed a list of representative manufactured nanomaterials (MN) as well as a set of relevant endpoints to be addressed. Here, results of STIS carried out with different nanomaterials are discussed as case studies. The ranking of different nanomaterials potential to induce adverse effects and the ranking of the respective NOAEC are the same among the STIS and the corresponding subchronic and chronic studies. In another case study, a translocation of a coated silica nanomaterial was judged critical for its safety assessment. Thus, STIS enables application of the proposed ITS, as long as reliable and relevant in vitro methods for the tier 1 testing are still missing. Compared to traditional subacute and subchronic inhalation testing (according to OECD test guidelines 412 and 413), STIS uses less animals and resources and offers additional information on organ burden and progression or regression of potential effects.

  10. Brain permeability of inhaled corticosteroids.

    PubMed

    Arya, Vikram; Issar, Manish; Wang, Yaning; Talton, James D; Hochhaus, Guenther

    2005-09-01

    The aim of this study was to evaluate if the permeability of inhaled corticosteroids entering the brain is reduced and if P-glycoprotein (P-gp) transporters are involved. Currently employed inhaled corticosteroids were given intravenously and intratracheally to rats at a dose of 100 microg kg-1. An ex-vivo receptor binding assay was used to monitor over 12 h the glucocorticoid receptor occupancy in the brain and a systemic reference organ (kidney). The involvement of P-gp in the brain permeability of triamcinolone acetonide was assessed in wild-type mice and mdr1a(-/-) knockout mice (mice lacking the gene for expressing P-gp). After both forms of administration, the average brain receptor occupancies were 20-56% of those of the reference organ, with the more lipophilic drugs showing a more pronounced receptor occupation. While the receptor occupancies in the liver of wild-type and mdr1a(-/-) mice were similar after administration of triamcinolone acetonide, brain receptor occupancies in mdr1a(-/-) mice were significantly greater (mdr1a(-/-): 47.6%, 40.2-55.0%, n=14; 2; wild-type: 11.5+/-33.0%, n=14; 3). Penetration into the brain for inhaled corticosteroids (especially those of lower lipophilicity) is reduced. Experiments in mdr1a(-/-) mice confirmed the involvement of P-gp transporters. Further studies are needed to assess whether potential drug interactions at the transporter level are of pharmacological significance.

  11. Dynamics of Structural Parameters and Accumulation of Collagen Fibrils in Rat Lung after Inhalations of Surfactant-BL at Various Terms of Bleomycin-Induced Alveolitis.

    PubMed

    Volchkov, V A; Dubrovskaya, V F; Valkovich, A A; Klestova, O V; Serzhanina, V A; Zhuikov, A G; Seiliev, A A; Rosenberg, O A

    2016-08-01

    Rats were subjected to surfactant-BL inhalations at the early and late phases of bleomycininduced alveolitis. In both regimens, the drug reduced the severity of inflammation. In the acute phase of alveolitis, the therapeutic effect of inhalation was accompanied by activation of the synthesis of fine lose collagen fibrils. In the late phase of alveolitis, inhalation of surfactant-BL thickened the fibrils and diminished their population in alveolar walls.

  12. 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).

  13. Smoke inhalation increases intensive care requirements and morbidity in paediatric burns.

    PubMed

    Tan, Alethea; Smailes, Sarah; Friebel, Thessa; Magdum, Ashish; Frew, Quentin; El-Muttardi, Naguib; Dziewulski, Peter

    2016-08-01

    Burn survival has improved with advancements in fluid resuscitation, surgical wound management, wound dressings, access to antibiotics and nutritional support for burn patients. Despite these advancements, the presence of smoke inhalation injury in addition to a cutaneous burn still significantly increases morbidity and mortality. The pathophysiology of smoke inhalation has been well studied in animal models. Translation of this knowledge into effectiveness of clinical management and correlation with patient outcomes including the paediatric population, is still limited. We retrospectively reviewed our experience of 13 years of paediatric burns admitted to a regional burn's intensive care unit. We compared critical care requirements and patient outcomes between those with cutaneous burns only and those with concurrent smoke inhalation injury. Smoke inhalation increases critical care requirements and mortality in the paediatric burn population. Therefore, early critical care input in the management of these patients is advised.

  14. Tobramycin inhalation powder for P. aeruginosa infection in cystic fibrosis: the EVOLVE trial

    PubMed Central

    Konstan, Michael W; Geller, David E; Minić, Predrag; Brockhaus, Florian; Zhang, Jie; Angyalosi, Gerhild

    2014-01-01

    Tobramycin inhalation solution is used to treat chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients. We evaluated the efficacy and safety of a novel, light-porous-particle, dry-powder formulation of tobramycin, which was developed to improve delivery efficiency to the airways and substantially reduce the delivery time. In this randomized, double-blind study, patients with cystic fibrosis (age 6–21 years) received tobramycin inhalation powder (112 mg tobramycin) twice daily (n = 46) or placebo (n = 49) via the T-326 Inhaler for one cycle, followed by two open-label cycles (all patients). Cycles were 28 days on, 28 days off treatment. The primary endpoint was change in FEV1 % predicted from baseline to Day 28 of Cycle 1. The study was terminated early based on positive results in the interim analysis. Tobramycin inhalation powder significantly improved FEV1 % predicted versus placebo at Day 28 (difference 13.3, 95% CI 5.31, 21.28; P = 0.0016). Similar changes in FEV1 were seen in patients switching from placebo to tobramycin inhalation powder in Cycle 2; improvements were maintained over time. Tobramycin inhalation powder also reduced sputum Pseudomonas aeruginosa density, respiratory-related hospitalization and antipseudomonal antibiotic use versus placebo. The most common adverse event was cough; the frequency of cough was higher in patients receiving placebo (26.5%) versus tobramycin inhalation powder (13.0%) in Cycle 1. Tobramycin inhalation powder was not associated with ototoxicity or nephrotoxicity. Administration time was between 4 and 6 minutes. In conclusion, tobramycin inhalation powder was effective and well tolerated in cystic fibrosis patients, and may offer an important treatment option to decrease the treatment burden of cystic fibrosis pseudomonas lung infections. PMID:20963831

  15. Reconstruction of the inhalation dose in the 30-km zone after the Chernobyl accident.

    PubMed

    Mück, Konrad; Pröhl, Gerhard; Likhtarev, Ilya; Kovgan, Lina; Golikov, Vladislav; Zeger, Johann

    2002-02-01

    Due to lack of measurements of activity concentrations in air, the assessment of the inhalation dose of the population evacuated from the 30-km zone after the Chernobyl accident is not possible from continuous filter measurements. Since the evaluation of the inhalation dose in each settlement of the zone is of great interest for epidemiological purposes, an approach was chosen that utilizes the available data on ground deposition of 137Cs, a recently performed best estimate of the radionuclide vector and its spatial distribution as well as the radionuclide dependent deposition velocity. The derived inhalation dose values in the 30-km zone range between 3 mSv to 150 mSv effective dose for adults depending on the distance to the reactor site and the day of evacuation. For 1-y-old infants the values range between 10 to 700 mSv. In Chernobyl town, an effective inhalation dose of 25 mSv until evacuation day was assessed. Thyroid doses due to inhalation ranged from 0.02 to 1 Sv for adults, for 1-y-old infants from 0.02 to 6 Sv. The inhalation dose in each settlement of the 30-km zone is approximately 8-13 times higher than the external exposure in each settlement if evacuation of the settlement occurred at an early stage. For settlements with evacuation at a later stage (day 10 or later) the inhalation dose was about 50-70% higher than the external dose. The dominant contribution to the effective inhalation dose comes from 131I (about 40%) and tellurium and rubidium isotopes (about 20-30%). Despite high zirconium and cerium ground depositions, zirconium and cerium isotopes contribute rather little to the inhalation dose which is mainly due to the great particle sizes to which they are attached. The relative contribution of short-lived radionuclides is, despite higher activities than at greater distances, less than 5%.

  16. 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

  17. Enhanced S-nitroso-albumin formation from inhaled NO during ischemia/reperfusion.

    PubMed

    Ng, Ella S M; Jourd'heuil, David; McCord, Joe M; Hernandez, Daniel; Yasui, Mitsukuni; Knight, Derrice; Kubes, Paul

    2004-03-05

    In the present study, we investigated whether inhaled nitric oxide (NO) was transported by plasma proteins, such as S-nitroso-albumin (SNO-Alb), in the feline circulation and whether this molecule delivers NO to the periphery under conditions of stress, specifically ischemia/reperfusion (I/R). A flow probe was interposed between the femoral and superior mesenteric artery for blood flow measurements, and a branch of the superior mesenteric vein was cannulated for arterial-venous sampling. In animals breathing room air, SNO-Alb was below detection level in arterial or venous blood. NO inhalation resulted in a significant arterial-venous gradient for SNO-Alb. Concomitant with this loss of SNO-Alb across the intestinal vasculature was an increase in nitrite (NO2-). However, this release of NO was not sufficient to alter intestinal blood flow. I/R during NO inhalation caused a very large increase in arterial SNO-Alb that permitted a 5-fold increase in SNO-Alb consumption and significant generation of NO2- within the postischemic intestinal vasculature. The increased SNO-Alb consumption was sufficient to dramatically improve intestinal blood flow. The very large burst of arterial SNO-Alb during I/R was completely blocked by the administration of superoxide dismutase, suggesting that oxidative stress contributed to the increased SNO-Alb formation. Our data suggest that inhaled NO can increase nitrosothiol production and these molecules may be a functional NO delivery system during cardiovascular disease.

  18. [Inhalation therapy: inhaled generics, inhaled antidotes, the future of anti-infectives and the indications of inhaled pentamidine. GAT aerosolstorming, Paris 2012].

    PubMed

    Peron, N; Le Guen, P; Andrieu, V; Bardot, S; Ravilly, S; Oudyi, M; Dubus, J-C

    2013-12-01

    The working group on aerosol therapy (GAT) of the Société de pneumologie de langue française (SPLF) organized its third "Aerosolstorming" in 2012. During the course of one day, different aspects of inhaled therapy were discussed, and these will be treated separately in two articles, this one being the first. Inhaled products represent a large volume of prescriptions both in the community and in hospital settings and they involve various specialties particularly ENT and respiratory care. Technical aspects of the development of these products, their mode of administration and compliance with their indications are key elements for the effective therapeutic use of inhaled treatments. In this first article, we will review issues concerning generic inhaled products, the existence of inhaled antidotes, new anti-infective agents and indications for inhaled pentamidine.

  19. Inhaled corticosteroid metered-dose inhalers: how do variations in technique for solutions versus suspensions affect drug distribution?

    PubMed

    Robinson, Christie A; Tsourounis, Candy

    2013-03-01

    To assess the literature that evaluates how variations in metered-dose inhaler (MDI) technique affect lung distribution for inhaled corticosteroids (ICSs) formulated as MDI suspensions and solutions. PubMed (up to November 2012) and Cochrane Library (up to November 2012) were searched using the terms metered-dose inhalers, HFA 134a, Asthma/*drug therapy, and inhaled corticosteroids. In addition, reference citations from publications identified were reviewed. All articles in English from the data sources that assessed MDI technique comparing total lung distribution (TLD) of MDI solutions or suspensions formulated with ICSs were included in the review. Five relevant studies were identified. Five controlled studies compared how variations in MDI technique affect TLD for ICS MDI solutions with suspensions. MDI solutions resulted in greater TLD compared with larger particle MDI suspensions. Delayed or early inspiration upon device actuation of MDI solutions resulted in less TLD than coordinated actuation, but with a 3- to 4-times greater TLD than MDI suspensions inhaled using a standard technique. A sixth study evaluated inspiratory flow rates (IFR) for small, medium, and large particles. Rapid and slow IFRs resulted in similar TLD for small particles, while far fewer particles reached the airways with medium and large particles at rapid, rather than slow, IFRs. Based on the literature evaluated, standard MDI technique should be used for ICS suspensions. ICS MDI solutions can provide a higher average TLD than larger-particle ICS suspensions using standard technique, discoordinated inspiration and medication actuation timing, or rapid and slow IFRs. ICS MDI solutions allow for a more forgiving technique, which makes them uniquely suitable options for patients with asthma who have difficultly with MDI technique.

  20. Methods for Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry

    EPA Pesticide Factsheets

    EPA's methodology for estimation of inhalation reference concentrations (RfCs) as benchmark estimates of the quantitative dose-response assessment of chronic noncancer toxicity for individual inhaled chemicals.

  1. Inhalant withdrawal as a clinically significant feature of inhalant dependence disorder.

    PubMed

    Perron, Brian E; Howard, Matthew O; Vaughn, Michael G; Jarman, Christopher N

    2009-12-01

    Inhalant use is the intentional inhalation of vapors from commercial products or specific chemical agents for the purpose of achieving intoxication. Inhalants are among the most common and pernicious forms of substance use and the least studied of the major drugs. Diagnosis of inhalant dependence, according to the DSM-IV [Weintraub E, Gandhi D, Robinson C. Medical complications due to mothball abuse. South Med J 2000;93:427-9] excludes inhalant withdrawal symptoms, as expert opinion has suggested that an inhalant withdrawal syndrome is neither common nor clinically significant. This article draws from multiple sources of data to suggest that withdrawal symptoms can be part of inhalant dependence and are clinically significant. This hypothesis needs rigorous evaluation to ensure the diagnostic validity of inhalant use disorders.

  2. Nitric oxide and cancer

    PubMed Central

    Muntané, Jordi; la Mata, Manuel De

    2010-01-01

    Nitric oxide (NO) is a lipophilic, highly diffusible and short-lived physiological messenger which regulates a variety of important physiological responses including vasodilation, respiration, cell migration, immune response and apoptosis. NO is synthesized by three differentially gene-encoded NO synthase (NOS) in mammals: neuronal NOS (nNOS or NOS-1), inducible NOS (iNOS or NOS-2) and endothelial NOS (eNOS or NOS-3). All isoforms of NOS catalyze the reaction of L-arginine, NADPH and oxygen to NO, L-citrulline and NADP. NO may exert its cellular action by cGMP-dependent as well as by cGMP-independent pathways including postranslational modifications in cysteine (S-nitrosylation or S-nitrosation) and tyrosine (nitration) residues, mixed disulfide formation (S-nitrosoglutathione or GSNO) or promoting further oxidation protein stages which have been related to altered protein function and gene transcription, genotoxic lesions, alteration of cell-cycle check points, apoptosis and DNA repair. NO sensitizes tumor cells to chemotherapeutic compounds. The expression of NOS-2 and NOS-3 has been found to be increased in a variety of human cancers. The multiple actions of NO in the tumor environment is related to heterogeneous cell responses with particular attention in the regulation of the stress response mediated by the hypoxia inducible factor-1 and p53 generally leading to growth arrest, apoptosis or adaptation. PMID:21161018

  3. Nitric oxide in shock.

    PubMed

    Cauwels, A

    2007-09-01

    Refractory hypotension with end-organ hypoperfusion and failure is an ominous feature of shock. Distributive shock is caused by severe infections (septic shock) or severe systemic allergic reactions (anaphylactic shock). In 1986, it was concluded that nitric oxide (NO) is the endothelium-derived relaxing factor that had been discovered 6 years earlier. Since then, NO has been shown to be important for the physiological and pathological control of vascular tone. Nevertheless, although inhibition of NO synthesis restores blood pressure, NO synthase (NOS) inhibition cannot improve outcome, on the contrary. This implies that NO acts as a double-edged sword during septic shock. Consequently, the focus has shifted towards selective inducible NOS (iNOS) inhibitors. The contribution of NO to anaphylactic shock seems to be more straightforward, as NOS inhibition abrogates shock in conscious mice. Surprisingly, however, this shock-inducing NO is not produced by the inducible iNOS, but by the so-called constitutive enzyme endothelial NOS. This review summarizes the contribution of NO to septic and anaphylactic shock. Although NOS inhibition may be promising for the treatment of anaphylactic shock, the failure of a phase III trial indicates that other approaches are required for the successful treatment of septic shock. Amongst these, high hopes are set for selective iNOS inhibitors. But it might also be necessary to shift gears and focus on downstream cardiovascular targets of NO or on other vasodilating phenomena.

  4. 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.

  5. Nitric oxide enhancement strategies

    PubMed Central

    Bryan, Nathan S

    2015-01-01

    It is becoming increasingly clear that many diseases are characterized or associated with perturbations in nitric oxide (NO) production/signaling. Therapeutics or strategies designed to restore normal NO homeostasis will likely have broad application and utility. This highly complex and multistep pathway for NO production and subsequent target activation provides many steps in the endogenous pathway that may be useful targets for drug development for cardiovascular disease, antimicrobial, cancer, wound healing, etc. This article will summarize known strategies that are currently available or in development for enhancing NO production or availability in the human body. Each strategy will be discussed including exogenous sources of NO, use of precursors to promote NO production and downstream pathways affected by NO production with advantages and disadvantages highlighted for each. Development of NO-based therapeutics is and will continue to be a major focus of biotech, academia as well as pharmaceutical companies. Application of safe and effective strategies will certainly transform health and disease. PMID:28031863

  6. Telephonic Monitoring and Optimization of Inhaler Technique

    PubMed Central

    Nelson, Philip; Young, Henry N.; Knobloch, Mary Jo

    2011-01-01

    Abstract Introduction Improper inhaler technique is a common problem affecting asthma control and healthcare costs. Telephonic asthma management can increase access to care while reducing costs and hospitalizations. However, no reliable method has been established for telephonically evaluating and correcting inhaler technique. Objective The purpose of this study was to pilot test a method for assessing and correcting patient inhaler technique via telephone. Methods Participants (n=30) were adults with asthma using metered-dose inhalers (MDIs) and diskus inhalers. A pharmacist was located in one room and communicated via telephone with a participant in another room. The pharmacist telephonically assessed and taught inhaler technique. Participants were video-recorded, and videos were later examined by a second pharmacist to visually evaluate inhaler technique. Participants were assigned pre- and posteducation inhaler technique scores for the telephonic and video assessments. Scores were based on summated scales for MDI (0–9) and diskus (0–11) inhalers. Paired samples t-tests were used to compare telephone and video assessments. Results Findings indicated a significant difference between the telephone and video assessments of MDI technique (p<0.05); however, no difference was found for the diskus inhaler. Comparing pre- and posteducation inhaler technique for MDI and diskus, mean scores significantly improved from 5.7 to 7.8 (p<0.05) and from 8.5 to 10.4 (p<0.05), respectively. Conclusions The telephonic method was able to improve and detect some deficiencies in patients' inhaler technique. However, modifications and further investigation will more clearly determine the role and value of such a telephonic intervention. PMID:21943162

  7. The Toxicity of Inhaled Sulphur Mustard

    DTIC Science & Technology

    2012-03-01

    acetyl -L- cysteine (Mucomyst™; NAC ), in ameliorating inhaled HD-induced lung injury was then assessed in the established model. This work was conducted...J and Sciuto AM. N- acetyl -L- cysteine ( NAC ) Protects Against Inhaled Sulfur Mustard (HD) Poisoning in the Large Swine. Clinical Toxicology, 2012...2012. N- acetyl -L- cysteine ( NAC ) Protects against inhaled sulfur mustard (HD) poisoning in the large swine. Clinical Toxicology; in preparation

  8. The Toxicity of Inhaled Sulphur Mustard

    DTIC Science & Technology

    2012-10-01

    model. The thiol compound, N- acetyl -L- cysteine ( NAC - Mucomyst™) was chosen due to its anti-oxidant and mucolytic effects, administered via the inhaled...other beneficial therapies. Sulfur mustard, pig, inhalation, toxicology, pathology, physiology, N- acetyl -L- cysteine ( NAC ) 347 bjjugg@dstl.gov.uk 4...Finally, the efficacy of the commercial off the shelf (COTS) drug, N- acetyl -L- cysteine (Mucomyst™; NAC ), in ameliorating inhaled HD-induced lung

  9. Inhalant use and suicidality among incarcerated youth.

    PubMed

    Freedenthal, Stacey; Vaughn, Michael G; Jenson, Jeffrey M; Howard, Matthew O

    2007-09-06

    Studies consistently indicate that inhalant use is associated with increased mental health problems in adolescents, but few investigations have focused on the potential relationship of inhalant use to suicidality (ideation or attempt). This study examined how different levels of volatile solvent use relate to suicidal ideation and attempted suicide among 723 incarcerated youth (mean age=15.5, S.D.=1.2; 87% male) in Missouri, and whether any associations between solvent use and suicidality differ by gender. In bivariate analyses, severity of inhalant use was positively associated with histories of suicidal ideation and suicide attempt for both boys and girls. In multivariate analyses, inhalant use disorders remained significantly associated with suicidal ideation and suicide attempt histories even after adjusting for general level of psychiatric symptoms, prior trauma, other substance use, gender, and additional potential confounders. Inhalant use without abuse or dependence also significantly related to suicidal ideation in multivariate analyses, but an interaction between gender and inhalant use signified this relationship was stronger for girls. Inhalant use disorders in incarcerated youth, as well as inhalant use without abuse or dependence (particularly in girls), may signal elevated suicide risk. Suicide risk assessments should, therefore, include questions about inhalation of volatile solvents such as paint, gasoline, and household cleaners.

  10. Inhalant use and suicidality among incarcerated youth

    PubMed Central

    Freedenthal, Stacey; Vaughn, Michael G.; Jenson, Jeffrey M.; Howard, Matthew O.

    2007-01-01

    Studies consistently indicate that inhalant use is associated with increased mental health problems in adolescents, but few investigations have focused on the potential relationship of inhalant use to suicidality (ideation or attempt). This study examined how different levels of volatile solvent use relate to suicidal ideation and attempted suicide among 723 incarcerated youth (mean age = 15.5, S.D. = 1.2; 87% male) in Missouri, and whether any associations between solvent use and suicidality differ by gender. In bivariate analyses, severity of inhalant use was positively associated with histories of suicidal ideation and suicide attempt for both boys and girls. In multivariate analyses, inhalant use disorders remained significantly associated with suicidal ideation and suicide attempt histories even after adjusting for general level of psychiatric symptoms, prior trauma, other substance use, gender, and additional potential confounders. Inhalant use without abuse or dependence also significantly related to suicidal ideation in multivariate analyses, but an interaction between gender and inhalant use signified this relationship was stronger for girls. Inhalant use disorders in incarcerated youth, as well as inhalant use without abuse or dependence (particularly in girls), may signal elevated suicide risk. Suicide risk assessments should, therefore, include questions about inhalation of volatile solvents such as paint, gasoline, and household cleaners. PMID:17433572

  11. Apoptotic Cell Death in Rat Lung Following Mustard Gas Inhalation.

    PubMed

    Andres, Devon Katherine; Keyser, Brian M; Melber, Ashley A; Benton, Betty Jean; Hamilton, Tracey A; Kniffin, Denise M; Martens, Magaret E; Ray, Radharaman

    2017-03-30

    To investigate apoptosis as a mechanism of sulfur mustard (SM) inhalation injury in animals, we studied different caspases (caspase-8, -9, -3 and -6) in the lungs from a ventilated rat SM aerosol inhalation model. SM activated all four caspases in cells obtained from bronchoalveolar lavage fluid (BALF) as early as 6 hr after exposure. Caspase-8, which is known to initiate the extrinsic Fas-mediated pathway of apoptosis, was increased 5-fold between 6 to 24 hr, decreasing to the unexposed-control level at 48 hr. The initiator, caspase-9, in the intrinsic mitochondrial pathway of apoptosis as well as the executioner caspases, caspase-3 and -6, all peaked (p<0.01) at 24 hr; caspase-3 and -6 remained elevated, but caspase-9 decreased to unexposed-control level at 48 hr. To study further the Fas pathway, we examined soluble as well as membrane-bound Fas ligand (sFas-L, mFas-L, respectively) and Fas receptor (Fas-R) in both BALF cells and BALF. SFas-L increased significantly at 24 hr after SM exposure in both BALF cells (p<0.01) and BALF (p<0.05). However, mFas-L increased only in BALF cells between 24 to 48 hr (p<0.1, <0.001, respectively). Fas-R increased only in BALF cells by 6 hr (p<0.01) after SM exposure. Apoptosis in SM-inhaled rat lung specimens was also confirmed by both immunohistochemical staining using cleaved caspse-3 and -9 antibodies and TUNEL staining as early as 6 hr in the proximal trachea and bronchi, but not before 48 hr in distal airways. These findings suggest pathogenic mechanisms at the cellular and molecular levels and logical therapeutic target(s) for SM inhalation injury in animals.

  12. Peri-operative trans-oesophageal echocardiography and nitric oxide during general anaesthesia in a patient with Eisenmenger's syndrome.

    PubMed

    Bouch, D C; Allsager, C M; Moore, N

    2006-10-01

    We describe the peri-operative care of a patient with Eisenmenger's syndrome presenting for laparotomy. These patients require techniques to prevent the potential increase in intracardiac shunt caused by anaesthesia, by minimising increases in pulmonary artery pressure and reductions in systemic vascular resistance. The successful use of combined epidural and general anaesthesia with elective use of inhaled nitric oxide as a pulmonary vasodilator, and intra-operative trans-oesophageal echocardiography is described.

  13. [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.

  14. Successful resuscitation from cardiopulmonary arrest following deliberate inhalation of Freon refrigerant gas.

    PubMed

    Brilliant, L C; Grillo, A

    1993-06-01

    Presented is a case of successful resuscitation of cardiopulmonary arrest following inhalation of a fluorinated hydrocarbon. Fluorinated hydrocarbons have a direct cardiotoxic effect. We found no previous reports describing resuscitation with good neurologic outcome of a patient in cardiopulmonary arrest subsequent to inhalation of a fluorinated hydrocarbon. Early bystander cardiopulmonary resuscitation and ACLS provider intervention help to contribute to improved patient survival. We present a case illustrating the utility of basic life support and early advanced life support, followed by a review of the pertinent literature.

  15. Inhaled hyperosmolar agents for bronchiectasis.

    PubMed

    Hart, Anna; Sugumar, Karnam; Milan, Stephen J; Fowler, Stephen J; Crossingham, Iain

    2014-05-12

    Mucus retention in the lungs is a prominent feature of bronchiectasis. The stagnant mucus becomes chronically colonised with bacteria, which elicit a host neutrophilic response. This fails to eliminate the bacteria, and the large concentration of host-derived protease may contribute to the airway damage. The sensation of retained mucus is itself a cause of suffering, and the failure to maintain airway sterility probably contributes to the frequent respiratory infections experienced by many patients.Hypertonic saline inhalation is known to accelerate tracheobronchial clearance in many conditions, probably by inducing a liquid flux into the airway surface, which alters mucus rheology in a way favourable to mucociliary clearance. Inhaled dry powder mannitol has a similar effect. Such agents are an attractive approach to the problem of mucostasis, and deserve further clinical evaluation. To determine whether inhaled hyperosmolar substances are effective in the treatment of bronchiectasis. We searched the Cochrane Airways Group Specialised Register, trials registries, and the reference lists of included studies and review articles. Searches are current up to April 2014. Any randomised controlled trial (RCT) using hyperosmolar inhalation in patients with bronchiectasis not caused by cystic fibrosis. Two review authors assessed studies for suitability. We used standard methods recommended by The Cochrane Collaboration. Eleven studies met the inclusion criteria of the review (1021 participants).Five studies on 833 participants compared inhaled mannitol with placebo but poor outcome reporting meant we could pool very little data and most outcomes were reported by only one study. One 12-month trial on 461 participants provided results for exacerbations and demonstrated an advantage for mannitol in terms of time to first exacerbation (median time to exacerbation 165 versus 124 days for mannitol and placebo respectively (hazard ratio (HR) 0.78, 95% confidence interval (CI) 0

  16. Adolescent inhalant use, abuse and dependence.

    PubMed

    Perron, Brian E; Howard, Matthew O

    2009-07-01

    To compare adolescent inhalant users without DSM-IV inhalant use disorders (IUDs) to youth with IUDs (i.e. abuse or dependence) across demographic, psychosocial and clinical measures. Cross-sectional survey with structured psychiatric interviews. Facilities (n = 32) comprising the Missouri Division of Youth Services (MDYS) residential treatment system for juvenile offenders. Participants Current MDYS residents (n = 723); 97.7% of residents participated. Most youth were male (87%) and in mid-adolescence (mean = 15.5 years, standard deviation = 1.2, range = 11-20); more than one-third (38.6%, n = 279) reported life-time inhalant use. Antisocial behavior, temperament, trauma-exposure, suicidality, psychiatric symptoms and substance-related problems. Among life-time inhalant users, 46.9% met criteria for a life-time DSM-IV IUD (inhalant abuse = 18.6%, inhalant dependence = 28.3%). Bivariate analyses showed that, in comparison to non-users, inhalant users with and without an IUD were more likely to be Caucasian, live in rural or small towns, have higher levels of anxiety and depressive symptoms, evidence more impulsive and fearless temperaments and report more past-year antisocial behavior and life-time suicidality, traumatic experiences and global substance use problems. A monotonic relationship between inhalant use, abuse and dependence and adverse outcomes was observed, with comparatively high rates of dysfunction observed among inhalant-dependent youth. Multivariate regression analyses showed that inhalant users with and without an IUD had greater levels of suicidal ideation and substance use problems than non-users. Youth with IUDs have personal histories characterized by high levels of trauma, suicidality, psychiatric distress, antisocial behavior and substance-related problems. A monotonic relationship between inhalant use, abuse and dependence and serious adverse outcomes was observed.

  17. 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. Copyright 2013, SLACK Incorporated.

  18. Comparison of physician-, biomarker-, and symptom-based strategies for adjustment of inhaled corticosteroid therapy in adults with asthma: the BASALT randomized controlled trial.

    PubMed

    Calhoun, William J; Ameredes, Bill T; King, Tonya S; Icitovic, Nikolina; Bleecker, Eugene R; Castro, Mario; Cherniack, Reuben M; Chinchilli, Vernon M; Craig, Timothy; Denlinger, Loren; DiMango, Emily A; Engle, Linda L; Fahy, John V; Grant, J Andrew; Israel, Elliot; Jarjour, Nizar; Kazani, Shamsah D; Kraft, Monica; Kunselman, Susan J; Lazarus, Stephen C; Lemanske, Robert F; Lugogo, Njira; Martin, Richard J; Meyers, Deborah A; Moore, Wendy C; Pascual, Rodolfo; Peters, Stephen P; Ramsdell, Joe; Sorkness, Christine A; Sutherland, E Rand; Szefler, Stanley J; Wasserman, Stephen I; Walter, Michael J; Wechsler, Michael E; Boushey, Homer A

    2012-09-12

    No consensus exists for adjusting inhaled corticosteroid therapy in patients with asthma. Approaches include adjustment at outpatient visits guided by physician assessment of asthma control (symptoms, rescue therapy, pulmonary function), based on exhaled nitric oxide, or on a day-to-day basis guided by symptoms. To determine if adjustment of inhaled corticosteroid therapy based on exhaled nitric oxide or day-to-day symptoms is superior to guideline-informed, physician assessment-based adjustment in preventing treatment failure in adults with mild to moderate asthma. A randomized, parallel, 3-group, placebo-controlled, multiply-blinded trial of 342 adults with mild to moderate asthma controlled by low-dose inhaled corticosteroid therapy (n = 114 assigned to physician assessment-based adjustment [101 completed], n = 115 to biomarker-based [exhaled nitric oxide] adjustment [92 completed], and n = 113 to symptom-based adjustment [97 completed]), the Best Adjustment Strategy for Asthma in the Long Term (BASALT) trial was conducted by the Asthma Clinical Research Network at 10 academic medical centers in the United States for 9 months between June 2007 and July 2010. For physician assessment-based adjustment and biomarker-based (exhaled nitric oxide) adjustment, the dose of inhaled corticosteroids was adjusted every 6 weeks; for symptom-based adjustment, inhaled corticosteroids were taken with each albuterol rescue use. The primary outcome was time to treatment failure. There were no significant differences in time to treatment failure. The 9-month Kaplan-Meier failure rates were 22% (97.5% CI, 14%-33%; 24 events) for physician assessment-based adjustment, 20% (97.5% CI, 13%-30%; 21 events) for biomarker-based adjustment, and 15% (97.5% CI, 9%-25%; 16 events) for symptom-based adjustment. The hazard ratio for physician assessment-based adjustment vs biomarker-based adjustment was 1.2 (97.5% CI, 0.6-2.3). The hazard ratio for physician assessment-based adjustment vs

  19. 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

  20. Inhalant Abuse: A Call for Attention.

    ERIC Educational Resources Information Center

    Ballard, Mary B.

    1998-01-01

    The percentage of youth inhaling volatile substances is on the rise in the United States. Professional literature has been critical of the helping professions for not doing enough to address this problem adequately. This article attempts to heighten the awareness of the mental health profession by defining inhalant abuse, its consequences, and…

  1. Investigation of inhalation anthrax case, United States.

    PubMed

    Griffith, Jayne; Blaney, David; Shadomy, Sean; Lehman, Mark; Pesik, Nicki; Tostenson, Samantha; Delaney, Lisa; Tiller, Rebekah; DeVries, Aaron; Gomez, Thomas; Sullivan, Maureen; Blackmore, Carina; Stanek, Danielle; Lynfield, Ruth

    2014-02-01

    Inhalation anthrax occurred in a man who vacationed in 4 US states where anthrax is enzootic. Despite an extensive multi-agency investigation, the specific source was not detected, and no additional related human or animal cases were found. Although rare, inhalation anthrax can occur naturally in the United States.

  2. Investigation of Inhalation Anthrax Case, United States

    PubMed Central

    Blaney, David; Shadomy, Sean; Lehman, Mark; Pesik, Nicki; Tostenson, Samantha; Delaney, Lisa; Tiller, Rebekah; DeVries, Aaron; Gomez, Thomas; Sullivan, Maureen; Blackmore, Carina; Stanek, Danielle; Lynfield, Ruth

    2014-01-01

    Inhalation anthrax occurred in a man who vacationed in 4 US states where anthrax is enzootic. Despite an extensive multi-agency investigation, the specific source was not detected, and no additional related human or animal cases were found. Although rare, inhalation anthrax can occur naturally in the United States. PMID:24447835

  3. Inhalant initiation and the relationship of inhalant use to the use of other substances.

    PubMed

    Shamblen, Stephen R; Miller, Ted

    2012-01-01

    Conventional wisdom suggests that inhalant use is primarily isolated to youthful experimentation; however, a growing body of evidence suggests that inhalant use (a) occurs after use of common substances of experimentation (e.g., alcohol, marijuana), (b) can persist into later life, and (c) is associated with severe consequences. The current study examined the sequencing of substances relative to inhalants and the post-initiation correlates of inhalant use between youth and young adulthood in nationally representative Add Health data. Analyses examined the relationship of substance of initiation to use of other substances, as well as an examination of the relationship between substance use and consequences. The analyses suggest that (a) those initiating their substance use careers with inhalants often go on to use hard drugs, (b) inhalant use likely occurs after alcohol and marijuana use, and (c) inhalant use during adolescence was associated with health and criminal consequences in both adolescence and young adulthood.

  4. 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

  5. Dissociation constant of nitric acid

    NASA Astrophysics Data System (ADS)

    Levanov, A. V.; Isaikina, O. Ya.; Lunin, V. V.

    2017-07-01

    The composition of nitric acid solutions is investigated by means Raman spectroscopy (RS). The results are compared to critically selected data from other authors. The value of the thermodynamic dissociation constant in an aqueous nitric acid solution at 25°C ( K a = [ {{H^ + }} ]{[ {NO_3^ - } ]_{γ '}}_ ± ^2/[ {HN{O_3}} ]{γ '_{HN{O_3}}} = 35.5 ± 1.5M) is determined by analyzing an extensive set of reliable and consistent literature and original data. Expressions for the dependences of the activity coefficient of undissociated HNO3 molecules ({γ '_{HN{O_3}}} ) and the mean ionic coefficient ({γ '_ ± } = √ {{{γ '}_H} + {{γ '}_{NO_3^ - }}} ) on the stoichiometric concentration of nitric acid in the range of 0-18 M are found.

  6. The sepsis model: an emerging hypothesis for the lethality of inhalation anthrax

    PubMed Central

    Coggeshall, Kenneth Mark; Lupu, Florea; Ballard, Jimmy; Metcalf, Jordan P; James, Judith A; Farris, Darise; Kurosawa, Shinichiro

    2013-01-01

    Inhalation anthrax is often described as a toxin-mediated disease. However, the toxaemia model does not account for the high mortality of inhalation anthrax relative to other forms of the disease or for the pathology present in inhalation anthrax. Patients with inhalation anthrax consistently show extreme bacteraemia and, in contrast to animals challenged with toxin, signs of sepsis. Rather than toxaemia, we propose that death in inhalation anthrax results from an overwhelming bacteraemia that leads to severe sepsis. According to our model, the central role of anthrax toxin is to permit the vegetative bacteria to escape immune detection. Other forms of B. anthracis infection have lower mortality because their overt symptoms early in the course of disease cause patients to seek medical care at a time when the infection and its sequelae can still be reversed by antibiotics. Thus, the sepsis model explains key features of inhalation anthrax and may offer a more complete understanding of disease pathology for researchers as well as those involved in the care of patients. PMID:23742651

  7. The sepsis model: an emerging hypothesis for the lethality of inhalation anthrax.

    PubMed

    Coggeshall, Kenneth Mark; Lupu, Florea; Ballard, Jimmy; Metcalf, Jordan P; James, Judith A; Farris, Darise; Kurosawa, Shinichiro

    2013-07-01

    Inhalation anthrax is often described as a toxin-mediated disease. However, the toxaemia model does not account for the high mortality of inhalation anthrax relative to other forms of the disease or for the pathology present in inhalation anthrax. Patients with inhalation anthrax consistently show extreme bacteraemia and, in contrast to animals challenged with toxin, signs of sepsis. Rather than toxaemia, we propose that death in inhalation anthrax results from an overwhelming bacteraemia that leads to severe sepsis. According to our model, the central role of anthrax toxin is to permit the vegetative bacteria to escape immune detection. Other forms of B. anthracis infection have lower mortality because their overt symptoms early in the course of disease cause patients to seek medical care at a time when the infection and its sequelae can still be reversed by antibiotics. Thus, the sepsis model explains key features of inhalation anthrax and may offer a more complete understanding of disease pathology for researchers as well as those involved in the care of patients.

  8. Experimental inhalation injury in the goat.

    PubMed

    Walker, H L; McLeod, C G; McManus, W F

    1981-11-01

    Inhalation injuries are usually produced by inhalation of gaseous or particulate products of incomplete combustion and are rarely due to heat per se unless steam is inhaled. The clinical and anatomic characteristics of an appropriate animal model should mimic the disease encountered clinically. A model of inhalation injury has been produced in anesthetized goats through the use of a modified bee smoker. The smoke is delivered at a low temperature and contains byproducts of incomplete combustion. This reproducible injury produces necrotic tracheobronchitis and bronchiolitis with pseudomembrane and cast formation in association with mild multifocal atelectasis and bronchopneumonia. These lesions spontaneously resolve within 3 weeks without supportive therapy. The upper trachea, protected from smoke injury by the inflated cuff of the endotracheal tube, showed no evidence of injury. This nonlethal injury is proposed as an appropriate model for evaluation of the pathophysiology and treatment of inhalation injury.

  9. Nitric oxide for respiratory failure in infants born at or near term.

    PubMed

    Barrington, Keith J; Finer, Neil; Pennaforte, Thomas; Altit, Gabriel

    2017-01-05

    received iNO early satisfied late treatment criteria, showing that earlier iNO reduced progression of the disease but did not further decrease mortality nor the need for ECMO (moderate-quality evidence). Incidence of disability, incidence of deafness and infant development scores were all similar between tested survivors who received iNO and those who did not. Inhaled nitric oxide is effective at an initial concentration of 20 ppm for term and near-term infants with hypoxic respiratory failure who do not have a diaphragmatic hernia.

  10. [Indication and effect of inhaled DSCG for the treatment of adult asthmatics].

    PubMed

    Arai, Y

    1996-11-01

    International guidelines have recommended the early use of anti-inflammatory therapy in the treatment of asthma. Currently available anti-inflammatory agents include the corticosteroid hormones and the non-steroid drugs, nedocromil sodium (currently not available in Japan) and disodium cromoglycate (DSCG). In general, DSCG has shown clinical activity in atopic young patients with mild asthma who do not require inhaled corticosteroids as maintenance therapy. However, nebulised DSCG showed early, significant improvements in symptoms and peak expiratory flow rate in non-atopic as well as atopic asthmatics with severe asthma who require high doses of inhaled and oral corticosteroids as maintenance therapy. In adult asthmatics, it is important that the choice of mode of administration of DSCG is made according to asthma severity, such as using metered dose inhaler (MDI) for mild asthma and the nebulised formulation for more severe asthma.

  11. Pharmacokinetics of fluticasone propionate multidose, inhalation-driven, novel, dry powder inhaler versus a prevailing dry powder inhaler and a metered-dose inhaler.

    PubMed

    Gillespie, Michael; Song, Sharon; Steinfeld, Jonathan

    2015-01-01

    A novel inhalation-driven multidose dry powder inhaler (MDPI) that eliminates the need for the patient to coordinate device actuation with inhalation has been developed for delivery of inhaled asthma medications. To characterize the pharmacokinetics of single-dose fluticasone propionate (Fp) MDPI compared with single doses of Fp dry powder inhaler (DPI) and a metered-dose inhaler (MDI) in healthy subjects. This was a single-center, open-label, randomized, three-period crossover, single-dose pilot study in healthy adults ages 18 to 45 years. Eligible subjects (N = 18) were randomized to one of six treatment sequences that contained three treatment arms: Fp MDPI 400 μg/inhalation × two inhalations (800 μg total dose); Fp DPI 250 μg/inhalation × four (1000 μg total dose); and Fp MDI 220 μg/inhalation × four (880 μg total dose). Pharmacokinetics (area under concentration-versus-time curve [AUC], maximum plasma concentration [Cmax], time to Cmax [tmax], and elimination half-life [t½]), safety, and tolerability were assessed for each treatment. Plasma Fp concentration-versus-time curves were comparable across treatments. Geometric mean AUC0-t and Cmax for Fp MDPI 800 μg were 19% and 18% higher, respectively, compared with Fp DPI 1000 μg, and 47% and 82% higher, respectively, compared with Fp MDI 880 μg. Median tmax (60.0-60.6 minutes) and median t1/2 (9.1-9.8 hours) were comparable across the three treatments. Single-dose Fp was well tolerated, with no new safety issues noted. Single-dose administration of Fp MDPI 800 μg produced systemic exposure comparable with those for Fp DPI 1000 μg and Fp MDI 880 μg.

  12. 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.

  13. Airway response to chlorine inhalation (bleach) among cleaning workers with and without bronchial hyperresponsiveness.

    PubMed

    Sastre, Joaquín; Madero, Mauro F; Fernández-Nieto, Mar; Sastre, Beatriz; del Pozo, Victoria; Potro, Manuela García-del; Quirce, Santiago

    2011-04-01

    Symptoms of obstructive lung disease in domestic cleaning staff have been related to the use of bleach and other irritant cleaning products. Included in the study were thirteen cleaning employees with work-related asthma-like symptoms, three asthmatic controls and three atopic subjects without bronchial hyperresponsiveness (BHR) who had no exposure to cleaning products. The study protocol consisted of a methacholine test, sputum induction and fraction of exhaled nitric oxide measurement (FENO) both at baseline and 24 hr after a 1-hr inhalation challenge with either placebo or bleach at a concentration of 0.4 ppm of chlorine. The inhalation of the placebo caused no bronchial reactions. Mean maximum fall in FEV(1) during challenge testing with bleach was significantly higher than the values obtained during the placebo challenge. Inhalation challenge with bleach elicited two isolated late asthmatic reactions and one dual asthmatic reaction. Of all the patients who underwent challenge testing with bleach, only one had a ≥2-fold decrease in methacholine PC(20) 24 hr after the challenge. No significant correlation was found between maximum fall in FEV(1) and PC(20) methacholine. Following challenge testing with bleach, no clinically significant changes in sputum cell counts or FENO were detected. These results suggest that bleach inhalation at a concentration of 0.4 ppm-a concentration below 8-hr permissible occupational exposure level-brings about a substantial decrease in FEV1 in subjects with and without BHR. Some subjects have a positive challenge response to bleach inhalation. Copyright © 2010 Wiley-Liss, Inc.

  14. 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).

  15. [Evaluation of a new nitric oxide delivery system during mechanical ventilation].

    PubMed

    Noguchi, T; Miyakawa, H; Mori, M; Kitano, T; Iwasaka, H; Oda, S; Taniguchi, K; Honda, N

    1994-07-01

    A new nitric oxide delivery and continuous monitoring system is described. During mechanical ventilation, this new system connected with Siemens Servo 900C ventilator was shown to be able to provide a constant inspired NO concentration (10-100 ppm) using chemiluminescence technique for NO analysis. Gas was analysed at the mixing chamber in front of the ventilator inlet and inspiratory tube connected with the soda-lime carbon-dioxide absorber. Both NO concentrations showed a good correlation (r = 0.99). The actual NO concentration from the NO supply cylinder was 1154 ppm and NO2 concentration was 14 ppm. In mongrel dogs, after 20 minutes of NO inhalation (10-100 ppm), the blood methemoglobin level reached a peak value of 2.2% starting from the pre-inhalation level of 0%. To optimize the safety of the clinical application of NO, its concentration should be measured continuously with chemiluminescence technique.

  16. 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.

  17. 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

  18. 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.

  19. Efficacy of environmental controls for inhalant allergies.

    PubMed

    Mims, James W; Biddy, Ashley C

    2013-06-01

    This review examines the efficacy of environmental controls as part of the management for inhalant allergic disease (allergic rhinitis and allergic asthma). Evidence of efficacy of environmental controls for allergic disease can be categorized into two types of studies: environmental controls reducing measured allergen levels and environmental controls affecting clinical outcomes (e.g., symptom scores, medication use, or measured lung function). Multiple environmental control strategies have demonstrated efficacy in reducing allergen levels; however, clinical benefit secondary to allergen reduction has been variable. Clinical benefit is seen more consistently in studies that remove the allergic patient from a high allergen environment, than in studies that attempt to reduce the allergen level within the home. Prevention of sensitization using environmental controls in the prenatal and infant periods has been studied, but it has been difficult to demonstrate a consistent reduction in the development of allergic disease or decrease symptom severity. Allergen exposure early in life may paradoxically promote tolerance in some populations and sensitizations in others. Although many studies evaluating a single environmental control strategy fail to show an improvement in clinical outcomes, comprehensive environmental controls may provide some benefit. Additionally, studies that relocate patients to low allergen environments tend to demonstrate clinical improvement.

  20. Nitric oxide generating/releasing materials

    PubMed Central

    Liang, Hongying; Nacharaju, Parimala; Friedman, Adam; Friedman, Joel M

    2015-01-01

    Harnessing the impressive therapeutic potential of Nitric oxide (NO) remains an ongoing challenge. This paper describes several of the current strategies both with respect to the underlying chemistry and physics and to the applications where they have shown promise. Included in this overview are molecular systems such as NONOates that release NO through chemical reactions and delivery vehicles such as nanoparticles that can generate, store, transport and deliver NO and related bioactive forms of NO such as nitrosothiols. Although there has been much positive movement, it is clear that we are only at the early stages of knowing how to precisely produce, transport and deliver to targeted sites therapeutic levels of NO and related molecules. PMID:26855790

  1. Particle inhalability at low wind speeds.

    PubMed

    Brown, James S

    2005-12-15

    Accurate quantification of the dose delivered by aerosol exposures is essential for estimating the risk of potential adverse health effects. The fraction of airborne particles that can enter the nose or mouth during inhalation is referred to as the inspirable particulate mass fraction. This inhalable fraction is equivalent to delivered dose for particles greater than approximately 25 microm (aerodynamic particle diameter, d(ae)), which deposit completely and almost exclusively in the extrathoracic airways. Particle inhalability at high wind speeds (1-9 m/s) has been well characterized. However, there is a paucity of data describing the inhalability of particles at low wind speeds (< or =0.3 m/s), which are typical of indoor environments. High-wind-speed criteria poorly describe inhalability at low wind speeds. Based on the aspiration efficiencies of blunt and sharp-edged inlets, a function was developed for oral inhalability, P(I(O)), of particles at low wind speeds. This function predicts a slow decline in P(I(O)) from 0.95 at d(ae)= 8 microm, to 0.5 at d(ae) = 74 microm, and 0.1 at d(ae)= 175 microm. Data available from the literature for inhalability at relatively low wind speeds during oral breathing are well described by this logistic function (r(2)= 0.69).

  2. 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

  3. Inhaled Corticosteroids and Bone Health

    PubMed Central

    Chee, Carolyn; Sellahewa, Luckni; Pappachan, Joseph M

    2014-01-01

    Inhaled corticosteroids (ICS) are the cornerstones in the management of bronchial asthma and some cases of chronic obstructive pulmonary disease. Although ICS are claimed to have low side effect profiles, at high doses they can cause systemic adverse effects including bone diseases such as osteopenia, osteoporosis and osteonecrosis. Corticosteroids have detrimental effects on function and survival of osteoblasts and osteocytes, and with the prolongation of osteoclast survival, induce metabolic bone disease. Glucocorticoid-induced osteoporosis (GIO) can be associated with major complications such as vertebral and neck of femur fractures. The American College of Rheumatology (ACR) published criteria in 2010 for the management of GIO. ACR recommends bisphosphonates along with calcium and vitamin D supplements as the first-line agents for GIO management. ACR recommendations can be applied to manage patients on ICS with a high risk of developing metabolic bone disease. This review outlines the mechanisms and management of ICS-induced bone disease. PMID:25674178

  4. Inhalation challenge in humidifier fever.

    PubMed

    Edwards, J H; Cockcroft, A

    1981-05-01

    When exposed to an amount of contaminated humidifier water roughly equivalent to that inhaled over an 8-hour period at their work place, four out of six subjects developed symptoms of humidifier fever. Two non-exposed subjects failed to react to the same challenge. Characteristic lung function, temperature and leucocyte changes were recorded; however, a fall in gas transfer previously reported was not seen. That the reaction was immunologically mediated and not due to endotoxin activity was shown by a negative pyrogen response in rabbits inoculated intravenously with concentrated humidifier water. The nature of the immune response has not as yet been evaluated but it does not reside with the ability of humidifier fever antigens to activate complement. Skin testing produced an immediate weal and flare in the four subjects with precipitins and may reflect the presence of short-term anaphylactic IgG antibody.

  5. Inhalant use and disorders among adults in the United States.

    PubMed

    Wu, Li-Tzy; Ringwalt, Christopher L

    2006-10-15

    To examine the patterns of adult inhalant use and correlates of inhalant use disorder. We drew study data from the 2002 and 2003 National Surveys on Drug Use and Health (NSDUH). We used logistic regression to identify the characteristics associated both with inhalant use and inhalant use disorder. One in 10 of all adults had used an inhalant at least once in their lives, and 0.5% used one in the past year. Among all past year inhalant users, 8% met the criteria for an inhalant use disorder (i.e., 6.6% for abuse and 1.1% for dependence) within that period. We found an increased prevalence of past year inhalant use among young adults aged 18-25 years, Asians, past year alcohol abusers and dependents, lifetime drug users, white women, and men reporting symptoms of serious mental illness. Inhalant-using adults who met the criteria for an inhalant use disorder were predominantly adults aged 35-49 years and were less educated, had received recent professional treatment for emotional or psychological problems, used inhalants weekly, and had a coexisting alcohol use disorder. The patterns and consequences of adult inhalant use differ from those of adolescents. Compared with adolescent inhalant users, adult users tend not to initiate inhalant use until adulthood, use inhalants less frequently, use fewer inhalants, and are less likely to engage in criminal activities.

  6. Inhalant Use and Disorders among Adults in the United States

    PubMed Central

    Wu, Li-Tzy; Ringwalt, Christopher L.

    2006-01-01

    Objective To examine the patterns of adult inhalant use and correlates of inhalant use disorder. Method We drew study data from the 2002 and 2003 National Surveys on Drug Use and Health (NSDUH). We used logistic regression to identify the characteristics associated both with inhalant use and inhalant use disorder. Results One in ten of all adults had used an inhalant at least once in their lives, and 0.5% used one in the past year. Among all past year inhalant users, 8% met the criteria for an inhalant use disorder (i.e., 6.6% for abuse and 1.1% for dependence) within that period. We found an increased prevalence of past year inhalant use among young adults aged 18–25, Asians, past year alcohol abusers and dependents, lifetime drug users, white women, and men reporting symptoms of serious mental illness. Inhalant-using adults who met the criteria for an inhalant use disorder were predominantly adults aged 35–49 and were less educated, had received recent professional treatment for emotional or psychological problems, used inhalants weekly, and had a coexisting alcohol use disorder. Conclusion The patterns and consequences of adult inhalant use differ from those of adolescents. Compared with adolescent inhalant users, adult users tend not to initiate inhalant use until adulthood, use inhalants less frequently, use fewer inhalants, and are less likely to engage in criminal activities. PMID:16581202

  7. 42 CFR 84.90 - Breathing resistance test; inhalation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Breathing resistance test; inhalation. 84.90...-Contained Breathing Apparatus § 84.90 Breathing resistance test; inhalation. (a) Resistance to inhalation... machine as described in § 84.88. (b) The inhalation resistance of open-circuit apparatus shall not...

  8. 42 CFR 84.90 - Breathing resistance test; inhalation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Breathing resistance test; inhalation. 84.90...-Contained Breathing Apparatus § 84.90 Breathing resistance test; inhalation. (a) Resistance to inhalation... machine as described in § 84.88. (b) The inhalation resistance of open-circuit apparatus shall not...

  9. A Community Prevention Model to Prevent Children from Inhaling and Ingesting Harmful Legal Products

    ERIC Educational Resources Information Center

    Johnson, K. W.; Grube, J. W.; Ogilvie, K. A.; Collins, D.; Courser, M.; Dirks, L. G.; Ogilvie, D.; Driscoll, D.

    2012-01-01

    Children's misuse of harmful legal products (HLPs), including inhaling or ingesting everyday household products, prescription drugs, and over-the-counter drugs, constitutes a serious health problem for American society. This article presents a community prevention model (CPM) focusing on this problem among pre and early adolescents. The model,…

  10. A Community Prevention Model to Prevent Children from Inhaling and Ingesting Harmful Legal Products

    ERIC Educational Resources Information Center

    Johnson, K. W.; Grube, J. W.; Ogilvie, K. A.; Collins, D.; Courser, M.; Dirks, L. G.; Ogilvie, D.; Driscoll, D.

    2012-01-01

    Children's misuse of harmful legal products (HLPs), including inhaling or ingesting everyday household products, prescription drugs, and over-the-counter drugs, constitutes a serious health problem for American society. This article presents a community prevention model (CPM) focusing on this problem among pre and early adolescents. The model,…

  11. Animal model of sensitization by inhalation.

    PubMed Central

    Barboriak, J J; Knoblock, H W; Hensley, G T; Gombas, O F; Fink, J N

    1976-01-01

    Groups of rats exposed to daily inhalation challenge with aerosolized pigeon serum developed precipitating antibody within 2 weeks and definitive granulomatous inflammatory changes in the lung after 7 weeks of exposure. The dissociation of the two responses to an inhalation challenge indicate that the rat model may serve for screening of the various inhalant antigens for their sensitizing potential, and for investigation of the contributory role of some of the factors involved in the pathogenesis of hypersensitivity pneumonitis. Images FIG. 1 FIG. 2 PMID:939055

  12. The potential of Angeli’s salt to decrease nitric oxide scavenging by plasma hemoglobin

    PubMed Central

    He, Xiaojun; Azarov, Ivan; Jeffers, Anne; Presley, Tennille; Richardson, Jodi; King, S. Bruce; Gladwin, Mark T.; Kim-Shapiro, Daniel B.

    2008-01-01

    Release of hemoglobin from the erythrocyte during intravascular hemolysis contributes to the pathology of a variety of diseased states. This effect is partially due to the enhanced ability of cell-free plasma hemoglobin, which is primarily found in the ferrous, oxygenated state, to scavenge nitric oxide. Oxidation of the cell-free hemoglobin to methemoglobin, which does not effectively scavenge nitric oxide, using inhaled nitric oxide has been shown to be effective in limiting pulmonary and systemic vasoconstriction. However, the ferric heme species may be reduced back to ferrous hemoglobin in plasma and has the potential to drive injurious redox chemistry. We propose that compounds that selectively convert cell-free hemoglobin to ferric, and ideally iron-nitrosylated heme species that do not actively scavenge nitric oxide would effectively treat intravascular hemolysis. We show here that nitroxyl, generated by Angeli’s salt (Sodium α-oxyhyponitrite, Na2N2O3), preferentially reacts with cell-free hemoglobin compared to that encapsulated in the red blood cell under physiologically relevant conditions. Nitroxyl oxidizes oxygenated ferrous hemoglobin to methemoglobin and can convert the methemoglobin to a more stable, less toxic species, iron-nitrosyl hemoglobin. These results support the notion that Angeli’s salt or a similar compound could be used to effectively treat conditions associated with intravascular hemolysis. PMID:18243145

  13. Inhalant use, inhalant-use disorders, and antisocial behavior: findings from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).

    PubMed

    Howard, Matthew O; Perron, Brian E; Vaughn, Michael G; Bender, Kimberly A; Garland, Eric

    2010-03-01

    , IUD+ respondents differed significantly from their IUD- counterparts primarily across measures of interpersonal violence. Among persons with antisocial personality disorder, inhalant use and IUDs were associated with greater antisocial behavior, albeit with fewer and weaker effects. Respondents with IUDs had pervasively elevated levels of antisocial conduct, including diverse forms of early-onset and interpersonally violent behavior.

  14. Inhalant Use, Inhalant-Use Disorders, and Antisocial Behavior: Findings From the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC)*

    PubMed Central

    Howard, Matthew O.; Perron, Brian E.; Vaughn, Michael G.; Bender, Kimberly A.; Garland, Eric

    2010-01-01

    , and physical cruelty to people. Similarly, IUD+ respondents differed significantly from their IUD− counterparts primarily across measures of interpersonal violence. Among persons with antisocial personality disorder, inhalant use and IUDs were associated with greater antisocial behavior, albeit with fewer and weaker effects. Conclusions: Respondents with IUDs had pervasively elevated levels of antisocial conduct, including diverse forms of early-onset and inter-personally violent behavior. PMID:20230717

  15. Use of ultra pure nitric oxide generated by the reduction of nitrogen dioxide to reverse pulmonary hypertension in hypoxemic swine.

    PubMed

    Lovich, Mark A; Bruno, Natalie K; Plant, Charles P; Wei, Abraham E; Vasquez, Gregory B; Johnson, Bryan J; Fine, David H; Gilbert, Richard J

    2011-05-31

    Inhaled nitric oxide (NO) has the capacity to selectively dilate pulmonary blood vessels, and thus enhance the matching of ventilation and perfusion, improve oxygenation and decrease pulmonary hypertension. However, existing approaches for the administration of inhaled NO are associated with the co-delivery of potentially toxic concentrations of nitrogen dioxide (NO2) due to the oxidation of NO in oxygen rich environments. We tested the ability of a novel methodology for generating highly purified NO through the reduction of NO2 by ascorbic acid to reverse pulmonary hypertension. In vitro testing demonstrated that the NO output of the novel device is ultrapure and free of NO2. An in vivo hypoxemic swine model of pulmonary hypertension was used to examine the dose response to NO in terms of pulmonary pressures and pulmonary vascular resistance. Pulmonary hypertension was induced by lowering inspired oxygen to 15% prior to treatment with inhaled ultra purified NO (1, 5, 20, and 80PPM). Hypoxemia increased mean pulmonary artery pressures and pulmonary vascular resistance. Inhaled ultra purified NO doses (down to 1PPM) show a marked reduction of hypoxemia-induced pulmonary vascular resistance. These experiments demonstrate a simple and robust method to generate purified inhaled NO that is devoid of NO2 and capable of reversing hypoxemia induced pulmonary hypertension.

  16. A randomised controlled trial of small particle inhaled steroids in refractory eosinophilic asthma (SPIRA)

    PubMed Central

    Hodgson, David; Anderson, John; Reynolds, Catherine; Meakin, Garry; Bailey, Helen; Pavord, Ian; Shaw, Dominick; Harrison, Tim

    2015-01-01

    Background Some patients with refractory asthma have evidence of uncontrolled eosinophilic inflammation in the distal airways. While traditional formulations of inhaled steroids settle predominantly in the large airways, newer formulations with an extra-fine particle size have a more peripheral pattern of deposition. Specifically treating distal airway inflammation may improve asthma control. Methods 30 patients with refractory asthma despite high dose inhaled corticosteroids were identified as having persistent airway eosinophilia. Following 2 weeks of prednisolone 30 mg, patients demonstrating an improvement in asthma control were randomised to receive either ciclesonide 320 µg twice daily or placebo in addition to usual maintenance therapy for 8 weeks. The primary outcome measure was sputum eosinophil count at week 8. Alveolar nitric oxide was measured as a marker of distal airway inflammation. Results There was continued suppression of differential sputum eosinophil counts with ciclesonide (median 2.3%) but not placebo (median 4.5%) though the between-group difference was not significant. When patients who had changed their maintenance prednisolone dose during the trial were excluded the difference between groups was significant (1.4% vs 4.5%, p=0.028). Though alveolar nitric oxide decreased with ciclesonide the value did not reach statistical significance. Conclusions These data demonstrate that patients with ongoing eosinophilic inflammation are not truly refractory, and that suppression of airway eosinophilia may be maintained with additional inhaled corticosteroid. Further work is needed with a focus on patient-orientated outcome measures such as exacerbation rate, with additional tests of small airway function. Trial registration number NCT01171365. Protocol available at http://www.clinicaltrials.gov. PMID:25858909

  17. Myocardial damage after inhalation of chloramines.

    PubMed

    Gonzalez-Castro, Alejandro; Holanda, Maria Soledad; Canas, Borja S; Morlote, Jesús G; Minambres, Eduardo; Prieto Solis, José A

    2006-04-01

    The objective of this case report was to document a rare case of myocardial damage, in the context of an accidental inhalation of chloramines, demonstrated by electrocardiogram and myocardium-specific enzymes.

  18. Analysis of uncertainties in CRAC2 calculations: the inhalation pathway

    SciTech Connect

    Killough, G.G.; Dunning, D.E. Jr.

    1984-01-01

    CRAC2 is a computer code for estimating the health effects and economic costs that might result from a release of radioactivity from a nuclear reactor to the environment. This paper describes tests of sensitivity of the predicted health effects to uncertainties in parameters associated with inhalation of the released radionuclides. These parameters are the particle size of the carrier aerosol and, for each element in the release, the clearance parameters for the lung model on which the code's dose conversion factors for inhalation are based. CRAC2 uses hourly meteorological data and a straight-line Gaussian plume model to predict the transport of airborne radioactivity; it includes models for plume depletion and population evacuation, and data for the distributions of population and land use. The code can compute results for single weather sequences, or it can perform random sampling of weather sequences from the meteorological data file and compute results for each weather sequence in the sample. For the work described in this paper, we concentrated on three fixed weather sequences that represent a range of conditions. For each fixed weather sequence, we applied random sampling to joint distributions of the inhalation parameters in order to estimate the sensitivity of the predicted health effects. All sampling runs produced coefficients of variation that were less than 50%, but some differences of means between weather sequences were substantial, as were some differences between means and the corresponding CRAC2 results without random sampling. Early injuries showed differences of as much as 1 to 2 orders of magnitude, while the differences in early fatalities were less than a factor of 2. Latent cancer fatalities varied by less than 10%. 19 references, 6 figures, 3 tables.

  19. ARDS following inhalation of hydrochloric acid.

    PubMed

    Bansal, D P; Ambegaonkar, Rahul; Radhika, P; Sharma, Manish

    2011-02-01

    The clinical spectrum of Inhalation injury can range from mild cough to a devastating ARDS. We herewith present a patient who is a goldsmith by occupation and his work consists of dissolving gold in Hydrochloric acid. He had accidentally inhaled fumes of Hydrochloric acid and presented with cough and breathlessness, later on required mechanical ventilation for ARDS and improved. This highlights the importance of not to neglect mild symptoms like cough and dyspnea in such a scenario which may have some hidden catastrophe.

  20. Olfactory deposition of inhaled nanoparticles in humans.

    PubMed

    Garcia, Guilherme J M; Schroeter, Jeffry D; Kimbell, Julia S

    2015-01-01

    Inhaled nanoparticles can migrate to the brain via the olfactory bulb, as demonstrated in experiments in several animal species. This route of exposure may be the mechanism behind the correlation between air pollution and human neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. This article aims to (i) estimate the dose of inhaled nanoparticles that deposit in the human olfactory epithelium during nasal breathing at rest and (ii) compare the olfactory dose in humans with our earlier dose estimates for rats. An anatomically-accurate model of the human nasal cavity was developed based on computed tomography scans. The deposition of 1-100 nm particles in the whole nasal cavity and its olfactory region were estimated via computational fluid dynamics (CFD) simulations. Our CFD methods were validated by comparing our numerical predictions for whole-nose deposition with experimental data and previous CFD studies in the literature. In humans, olfactory dose of inhaled nanoparticles is highest for 1-2 nm particles with ∼1% of inhaled particles depositing in the olfactory region. As particle size grows to 100 nm, olfactory deposition decreases to 0.01% of inhaled particles. Our results suggest that the percentage of inhaled particles that deposit in the olfactory region is lower in humans than in rats. However, olfactory dose per unit surface area is estimated to be higher in humans in the 1--7 nm size range due to the larger inhalation rate in humans. These dose estimates are important for risk assessment and dose-response studies investigating the neurotoxicity of inhaled nanoparticles.

  1. Inhalation gases or gaseous mediators as neuroprotectants for cerebral ischaemia.

    PubMed

    Sutherland, Brad A; Harrison, Joanne C; Nair, Shiva M; Sammut, Ivan A

    2013-01-01

    Ischaemic stroke is one of the leading causes of morbidity and mortality worldwide. While recombinant tissue plasminogen activator can be administered to produce thrombolysis and restore blood flow to the ischaemic brain, therapeutic benefit is only achieved in a fraction of the subset of patients eligible for fibrinolytic intervention. Neuroprotective therapies attempting to restrict the extent of brain injury following cerebral ischaemia have not been successfully translated into the clinic despite overwhelming pre-clinical evidence of neuroprotection. Therefore, an adequate treatment for the majority of acute ischaemic stroke patients remains elusive. In the stroke literature, the use of therapeutic gases has received relatively little attention. Gases such as hyperbaric and normobaric oxygen, xenon, hydrogen, helium and argon all possess biological effects that have shown to be neuroprotective in pre-clinical models of ischaemic stroke. There are significant advantages to using gases including their relative abundance, low cost and feasibility for administration, all of which make them ideal candidates for a translational therapy for stroke. In addition, modulating cellular gaseous mediators including nitric oxide, carbon monoxide, and hydrogen sulphide may be an attractive option for ischaemic stroke therapy. Inhalation of these gaseous mediators can also produce neuroprotection, but this strategy remains to be confirmed as a viable therapy for ischaemic stroke. This review highlights the neuroprotective potential of therapeutic gas therapy and modulation of gaseous mediators for ischaemic stroke. The therapeutic advantages of gaseous therapy offer new promising directions in breaking the translational barrier for ischaemic stroke.

  2. Systemic disposition of inhaled nitric oxide, a significant somponent of vehicular emissions

    EPA Science Inventory

    Epidemiological studies have associated airborne pollution with adverse cardiovascular outcomes. Furthermore, air pollution-associated gases, primarily from mobile source emissions (e.g. NOx), have been linked to increased cardiovascular death. A mechanism for these effects has...

  3. Nanoparticle Inhalation Increases Microvascular Oxidative Stress and Compromises Nitric Oxide Bioavailability

    EPA Science Inventory

    We have shown that pulmonary nanoparticle exposure impairs endothelium dependent dilation in systemic arterioles. However, the mechanism(s) through which this effect occurs are unclear. The purpose of this study was to identify alterations in the production of oxidative stress an...

  4. Systemic disposition of inhaled nitric oxide, a significant somponent of vehicular emissions

    EPA Science Inventory

    Epidemiological studies have associated airborne pollution with adverse cardiovascular outcomes. Furthermore, air pollution-associated gases, primarily from mobile source emissions (e.g. NOx), have been linked to increased cardiovascular death. A mechanism for these effects has...

  5. Effect of Inhaled Nitric Oxide on Pulmonary Function After Sepsis in a Swine Model.

    DTIC Science & Technology

    1994-08-01

    exact mechanism by which sepsis affects the pul- disease, adult respiratory distress syndrome ( ARDS ), monary system is unknown. Activation of both lcuko...the areas to normal V.\\/Q areas. These changes attenuated adult respiratory distress syndrome . (tin Infect l)is 1992;14: 1213-28.the incrcase in V/Q...in patients with does not improve Vx/Q mismatching to the same degree adult respiratory distress syndrome . Anesthesiology 1989:70: when low V.\\/Q

  6. Automated Inhaled Nitric Oxide Alerts for Adult Extracorporeal Membrane Oxygenation Patient Identification

    DTIC Science & Technology

    2014-09-01

    26 26 Alive 3 33 Female Cystic fibrosis ARDS 9 13 Alive/died* 4 33 Male Fall with polytrauma ARDS 112 180 Alive 5 35 Female Sepsis/ MRSA bacteremia...17 days later. MRSA , methicillin-resistant Staphylococcus aureus; TEN, toxic epidermal necrolysis. TABLE 2. Patient Characteristics at the Time of

  7. Nanoparticle Inhalation Increases Microvascular Oxidative Stress and Compromises Nitric Oxide Bioavailability

    EPA Science Inventory

    We have shown that pulmonary nanoparticle exposure impairs endothelium dependent dilation in systemic arterioles. However, the mechanism(s) through which this effect occurs are unclear. The purpose of this study was to identify alterations in the production of oxidative stress an...

  8. Assessing inhalation injury in the emergency room

    PubMed Central

    Tanizaki, Shinsuke

    2015-01-01

    Respiratory tract injuries caused by inhalation of smoke or chemical products are related to significant morbidity and mortality. While many strategies have been built up to manage cutaneous burn injuries, few logical diagnostic strategies for patients with inhalation injuries exist and almost all treatment is supportive. The goals of initial management are to ensure that the airway allows adequate oxygenation and ventilation and to avoid ventilator-induced lung injury and substances that may complicate subsequent care. Intubation should be considered if any of the following signs exist: respiratory distress, stridor, hypoventilation, use of accessory respiratory muscles, blistering or edema of the oropharynx, or deep burns to the face or neck. Any patients suspected to have inhalation injuries should receive a high concentration of supplemental oxygen to quickly reverse hypoxia and to displace carbon monoxide from protein binding sites. Management of carbon monoxide and cyanide exposure in smoke inhalation patients remains controversial. Absolute indications for hyperbaric oxygen therapy do not exist because there is a low correlation between carboxyhemoglobin levels and the severity of the clinical state. A cyanide antidote should be administered when cyanide poisoning is clinically suspected. Although an ideal approach for respiratory support of patients with inhalation injuries do not exist, it is important that they are supported using techniques that do not further exacerbate respiratory failure. A well-organized strategy for patients with inhalation injury is critical to reduce morbidity and mortality. PMID:27147888

  9. Predictive value of bronchoscopy in assessing the severity of inhalation injury.

    PubMed

    Mosier, Michael J; Pham, Tam N; Park, David R; Simmons, Jill; Klein, Matthew B; Gibran, Nicole S

    2012-01-01

    Inhalation injury is associated with severe pulmonary complications as inhaled products of combustion cause lung inflammation and loss of natural defenses. A bronchoscopic grading for inhalation injury has been proposed but has not yet been validated in burn patients. In this study, the authors evaluated whether bronchoscopic grading of injury clinically correlated with indices of gas exchange over the first 72 hours or predicted differences in hospitalization outcomes. They conducted a single-center retrospective review of all mechanically ventilated adults with suspected inhalation injury and thermal injury over an 18-month period. All recorded bronchoscopy examinations were reviewed and categorized injury according to the published abbreviated injury score (AIS 0: no injury, 1: mild, 2: moderate, 3: severe, and 4: massive injury). They also compared changes in oxygenation, airway pressures, chest radiograph findings, fluid administration, and early development of pneumonia and organ failure, by severity of inhalation injury according to the AIS. Thirty-two adult patients met inclusion criteria over the study period. This cohort was 69% male with a mean age of 44.5 ± 14 years and a mean % TBSA burn of 33.9 ± 17%. Of these 32 patients, 11 patients (34%) were classified as grade 0, 9 patients (28%) were classified as grade 1, 7 patients (22%) were classified as grade 2, and 5 patients (16%) were classified as grade 3. Measured carboxyhemoglobin levels increased significantly with higher AIS grade. Oxygenation indices were worse as grade worsened by 24, 48, and 72 hours. The incidence of acute respiratory distress syndrome increased by grade of injury: 0, 22, 57, and 80%, respectively, at 24 hours (P < .01), and remained statistically different at 48 and 72 hours. After adjustment for age, % TBSA burn, and full-thickness component, severe inhalation injury (grades 2 and 3) was associated with an increased risk of acute respiratory distress syndrome at 24 and 72

  10. [Nitric oxide production in plants].

    PubMed

    Małolepsza, Urszula

    2007-01-01

    There are still many controversial observations and opinions on the cellular/subcellular localization and sources of endogenous nitric oxide synthesis in plant cells. NO can be produced in plants by non-enzymatic and enzymatic systems depending on plant species, organ or tissue as well as on physiological state of the plant and changing environmental conditions. The best documented reactions in plant that contribute to NO production are NO production from nitrite as a substrate by cytosolic (cNR) and membrane bound (PM-NR) nitrate reductases (NR), and NO production by several arginine-dependent nitric oxide synthase-like activities (NOS). The latest papers indicate that mitochondria are an important source of arginine- and nitrite-dependent NO production in plants. There are other potential enzymatic sources of NO in plants including xanthine oxidoreductase, peroxidase, cytochrome P450.

  11. Nitric oxide and the common cold.

    PubMed

    Proud, David

    2005-02-01

    The common cold is a clinical syndrome triggered by a variety of viral pathogens, but rhinoviruses are the most frequent cause. Complications of such infections include sinusitis, otitis media, and exacerbations of asthma and chronic obstructive lung disease. There is growing interest in host innate defence responses that may regulate the severity of viral responses. We will review recent evidence that nitric oxide is an important contributor to the host response during colds. Infection of human airway epithelial cells with human rhinovirus has been shown to lead to the increased expression of inducible nitric oxide synthase both in vitro and in vivo. This increase in epithelial inducible nitric oxide synthase correlates with increased levels of nitric oxide in exhaled air. Importantly, nitric oxide can inhibit human rhinovirus-induced epithelial expression of several pro-inflammatory cytokines and can inhibit viral replication in epithelial cells in vitro. Moreover, nitric oxide can modulate several signal transduction pathways that are associated with cytokine generation. Nitric oxide can also nitrosylate viral proteases and can interact with the immune system. Consistent with these observations, pilot studies have indicated that the increased generation of nitric oxide during rhinovirus infections is associated with fewer symptoms and more rapid viral clearance. Further studies are warranted to evaluate the role of nitric oxide in colds and to determine whether the administration of nitric oxide donor compounds could be a viable therapeutic approach for viral exacerbations of airway diseases.

  12. Nitric oxide reburning with methane

    SciTech Connect

    Kumpaty, S.K.; Subramanian, K.

    1996-12-31

    This paper deals with initial findings from the ongoing, three-year DOE program that began on 02/01/1995. The program involves computer simulation studies to aid in planning and conducting a series of experiments that will extend the knowledge of reburning process. The objective of this work is to find nitric oxide reduction effectiveness for various reburning fuels and identify both homogeneous and heterogeneous reaction mechanisms characterizing NO reduction.

  13. Alternative to Nitric Acid Passivation

    NASA Technical Reports Server (NTRS)

    Kessel, Kurt R.

    2016-01-01

    Corrosion is an extensive problem that affects the National Aeronautics and Space Administration (NASA) and European Space Agency (ESA). The deleterious effects of corrosion result in steep costs, asset downtime affecting mission readiness, and safety risks to personnel. It is vital to reduce corrosion costs and risks in a sustainable manner. The primary objective of this effort is to qualify citric acid as an environmentally-preferable alternative to nitric acid for passivation of stainless steel alloys.

  14. Nitric Oxide Production in Plants

    PubMed Central

    Planchet, Elisabeth

    2006-01-01

    There is now general agreement that nitric oxide (NO) is an important and almost universal signal in plants. Nevertheless, there are still many controversial observations and opinions on the importance and function of NO in plants. Partly, this may be due to the difficulties in detecting and even more in quantifying NO. Here, we summarize major pathways of NO production in plants, and briefly discuss some methodical problems. PMID:19521475

  15. Toxic Inhalational Injury-Associated Interstitial Lung Disease in Children

    PubMed Central

    Lee, Eun; Seo, Ju-Hee; Kim, Hyung Young; Yu, Jinho; Jhang, Won-Kyoung; Park, Seong-Jong; Kwon, Ji-Won; Kim, Byoung-Ju; Do, Kyung-Hyun; Cho, Young Ah; Kim, Sun-A; Jang, Se Jin

    2013-01-01

    Interstitial lung disease in children (chILD) is a group of disorders characterized by lung inflammation and interstitial fibrosis. In the past recent years, we noted an outbreak of child in Korea, which is possibly associated with inhalation toxicity. Here, we report a series of cases involving toxic inhalational injury-associated chILD with bronchiolitis obliterans pattern in Korean children. This study included 16 pediatric patients confirmed by lung biopsy and chest computed tomography, between February 2006 and May 2011 at Asan Medical Center Children's Hospital. The most common presenting symptoms were cough and dyspnea. The median age at presentation was 26 months (range: 12-47 months), with high mortality (44%). Histopathological analysis showed bronchiolar destruction and centrilobular distribution of alveolar destruction by inflammatory and fibroproliferative process with subpleural sparing. Chest computed tomography showed ground-glass opacities and consolidation in the early phase and diffuse centrilobular nodular opacity in the late phase. Air leak with severe respiratory difficulty was associated with poor prognosis. Although respiratory chemicals such as humidifier disinfectants were strongly considered as a cause of this disease, further studies are needed to understand the etiology and pathophysiology of the disease to improve the prognosis and allow early diagnosis and treatment. PMID:23772158

  16. Inhaling to mitigate exhaled bioaerosols

    PubMed Central

    Edwards, David A.; Man, Jonathan C.; Brand, Peter; Katstra, Jeffrey P.; Sommerer, K.; Stone, Howard A.; Nardell, Edward; Scheuch, Gerhard

    2004-01-01

    Humans commonly exhale aerosols comprised of small droplets of airway-lining fluid during normal breathing. These “exhaled bioaerosols” may carry airborne pathogens and thereby magnify the spread of certain infectious diseases, such as influenza, tuberculosis, and severe acute respiratory syndrome. We hypothesize that, by altering lung airway surface properties through an inhaled nontoxic aerosol, we might substantially diminish the number of exhaled bioaerosol droplets and thereby provide a simple means to potentially mitigate the spread of airborne infectious disease independently of the identity of the airborne pathogen or the nature of any specific therapy. We find that some normal human subjects expire many more bioaerosol particles than other individuals during quiet breathing and therefore bear the burden of production of exhaled bioaerosols. Administering nebulized isotonic saline to these “high-producer” individuals diminishes the number of exhaled bioaerosol particles expired by 72.10 ± 8.19% for up to 6 h. In vitro and in vivo experiments with saline and surfactants suggest that the mechanism of action of the nebulized saline relates to modification of the physical properties of the airway-lining fluid, notably surface tension. PMID:15583121

  17. Inhaling to mitigate exhaled bioaerosols.

    PubMed

    Edwards, David A; Man, Jonathan C; Brand, Peter; Katstra, Jeffrey P; Sommerer, K; Stone, Howard A; Nardell, Edward; Scheuch, Gerhard

    2004-12-14

    Humans commonly exhale aerosols comprised of small droplets of airway-lining fluid during normal breathing. These "exhaled bioaerosols" may carry airborne pathogens and thereby magnify the spread of certain infectious diseases, such as influenza, tuberculosis, and severe acute respiratory syndrome. We hypothesize that, by altering lung airway surface properties through an inhaled nontoxic aerosol, we might substantially diminish the number of exhaled bioaerosol droplets and thereby provide a simple means to potentially mitigate the spread of airborne infectious disease independently of the identity of the airborne pathogen or the nature of any specific therapy. We find that some normal human subjects expire many more bioaerosol particles than other individuals during quiet breathing and therefore bear the burden of production of exhaled bioaerosols. Administering nebulized isotonic saline to these "high-producer" individuals diminishes the number of exhaled bioaerosol particles expired by 72.10 +/- 8.19% for up to 6 h. In vitro and in vivo experiments with saline and surfactants suggest that the mechanism of action of the nebulized saline relates to modification of the physical properties of the airway-lining fluid, notably surface tension.

  18. Intestinal circulation during inhalation anesthesia

    SciTech Connect

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-04-01

    This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of /sub 86/Rb and 9-microns spheres labeled with /sup 141/Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia were accompanied by a much lower arteriovenous oxygen content difference (AVDO/sub 2/) and oxygen uptake than pentobarbital or nitrous oxide. Compared with pentobarbital, enflurane anesthesia was not accompanied by marked differences in VR, F, Cl-Rb, and Cl-Sph; halothane at 2 MAC decreased VR and increased F and Cl-Rb while isoflurane increased VR and decreased F. alpha-Adrenoceptor blockade with phentolamine (1 mg . kg-1) abolished isoflurane-induced vasoconstriction, suggesting that the increase in VR was mediated via circulating catecholamines.

  19. Systems Pharmacology Approach Toward the Design of Inhaled Formulations of Rifampicin and Isoniazid for Treatment of Tuberculosis

    PubMed Central

    Cilfone, NA; Pienaar, E; Thurber, GM; Kirschner, DE; Linderman, JJ

    2015-01-01

    Conventional oral therapies for the treatment of tuberculosis are limited by poor antibiotic distribution in granulomas, which contributes to lengthy treatment regimens and inadequate bacterial sterilization. Inhaled formulations are a promising strategy to increase antibiotic efficacy and reduce dose frequency. We develop a multiscale computational approach that accounts for simultaneous dynamics of a lung granuloma, carrier release kinetics, pharmacokinetics, and pharmacodynamics. Using this computational platform, we predict that a rationally designed inhaled formulation of isoniazid given at a significantly reduced dose frequency has better sterilizing capabilities and reduced toxicity than the current oral regimen. Furthermore, we predict that inhaled formulations of rifampicin require unrealistic carrier antibiotic loadings that lead to early toxicity concerns. Lastly, we predict that targeting carriers to macrophages has limited effects on treatment efficacy. Our platform can be extended to account for additional antibiotics and provides a new tool for rapidly prototyping the efficacy of inhaled formulations. PMID:26225241

  20. Optimizing the Entrainment Geometry of a Dry Powder Inhaler: Methodology and Preliminary Results.

    PubMed

    Kopsch, Thomas; Murnane, Darragh; Symons, Digby

    2016-11-01

    For passive dry powder inhalers (DPIs) entrainment and emission of the aerosolized drug dose depends strongly on device geometry and the patient's inhalation manoeuvre. We propose a computational method for optimizing the entrainment part of a DPI. The approach assumes that the pulmonary delivery location of aerosol can be determined by the timing of dose emission into the tidal airstream. An optimization algorithm was used to iteratively perform computational fluid dynamic (CFD) simulations of the drug emission of a DPI. The algorithm seeks to improve performance by changing the device geometry. Objectives were to achieve drug emission that was: A) independent of inhalation manoeuvre; B) similar to a target profile. The simulations used complete inhalation flow-rate profiles generated dependent on the device resistance. The CFD solver was OpenFOAM with drug/air flow simulated by the Eulerian-Eulerian method. To demonstrate the method, a 2D geometry was optimized for inhalation independence (comparing two breath profiles) and an early-bolus delivery. Entrainment was both shear-driven and gas-assisted. Optimization for a delay in the bolus delivery was not possible with the chosen geometry. Computational optimization of a DPI geometry for most similar drug delivery has been accomplished for an example entrainment geometry.

  1. Airway Obstruction Due to Bronchial Vascular Injury after Sulfur Mustard Analog Inhalation

    PubMed Central

    Veress, Livia A.; O'Neill, Heidi C.; Hendry-Hofer, Tara B.; Loader, Joan E.; Rancourt, Raymond C.; White, Carl W.

    2010-01-01

    Rationale: Sulfur mustard (SM) is a frequently used chemical warfare agent, even in modern history. SM inhalation causes significant respiratory tract injury, with early complications due to airway obstructive bronchial casts, akin to those seen after smoke inhalation and in single-ventricle physiology. This process with SM is poorly understood because animal models are unavailable. Objectives: To develop a rat inhalation model for airway obstruction with the SM analog 2-chloroethyl ethyl sulfide (CEES), and to investigate the pathogenesis of bronchial cast formation. Methods: Adult rats were exposed to 0, 5, or 7.5% CEES in ethanol via nose-only aerosol inhalation (15 min). Airway microdissection and confocal microscopy were used to assess cast formation (4 and 18 h after exposure). Bronchoalveolar lavage fluid (BALF) retrieval and intravascular dye injection were done to evaluate vascular permeability. Measurements and Main Results: Bronchial casts, composed of abundant fibrin and lacking mucus, occluded dependent lobar bronchi within 18 hours of CEES exposure. BALF contained elevated concentrations of IgM, protein, and fibrin. Accumulation of fibrin-rich fluid in peribronchovascular regions (4 h) preceded cast formation. Monastral blue dye leakage identified bronchial vessels as the site of leakage. Conclusions: After CEES inhalation, increased permeability from damaged bronchial vessels underlying damaged airway epithelium leads to the appearance of plasma proteins in both peribronchovascular regions and BALF. The subsequent formation of fibrin-rich casts within the airways then leads to airways obstruction, causing significant morbidity and mortality acutely after exposure. PMID:20639443

  2. [Inhalation therapy by dose-inhalers: analysis of patients performance and possibilities for improvement].

    PubMed

    Petro, W; Schuppenies, A

    2005-05-01

    Inhalation therapy in chronic obstructive airways disease requires an efficient inhalation technique. This study analyses step by step the mistakes made in the usage of different MDIs, relates these to patient information prior to the testing and examines several teaching procedures for improvement of knowledge and performance of the inhalation technique. 125 patients suffering from COPD were assigned to six different groups according to their background knowledge in the inhalation technique. The performance was assessed in standardized single steps and as overall performance. Furthermore the efficacy of an interactive pc-based-training program was evaluated. The worst performance was seen in patients who only used the suppliers medication leaflet as a guide. Patients trained in outpatient clinics as well as patients trained in small groups during an inpatient stay showed a better performance. A high improvement rate was seen in prior MDI naive patients after they had undergone the interactive pc-based training program. Most problems were detected in the application step "exhalation before inhalation" and in the actuation-inhalation step. Besides the classical and the pc-based training the use of MDI phantoms showed very good results. The practical conclusion of this study is that the ability of patients to use inhalation pharmacotherapy efficiently needs improvement. Training programs of different intensity lead to a different outcome in performance and knowledge depending on prior knowledge. Inhalation pharmacotherapy without adequate training is insufficient.

  3. Automatic identification and accurate temporal detection of inhalations in asthma inhaler recordings.

    PubMed

    Holmes, Martin S; Le Menn, Marine; D'Arcy, Shona; Rapcan, Viliam; MacHale, Elaine; Costello, Richard W; Reilly, Richard B

    2012-01-01

    Asthma is chronic airways disease characterized by recurrent attacks of breathlessness and wheezing. Adherence to medication regimes is a common failing for asthmatic patients and there exists a requirement to monitor such patients' adherence. The detection of inhalations from recordings of inhaler use can provide empirical evidence about patients' adherence to their asthma medication regime. Manually listening to recordings of inhaler use is a tedious and time consuming process and thus an algorithm which can automatically and accurately carry out this task would be of great value. This study employs a recording device attached to a commonly used dry powder inhaler to record the acoustic signals of patients taking their prescribed medication. An algorithm was developed to automatically detect and accurately demarcate inhalations from the acoustic signals. This algorithm was tested on a dataset of 255 separate recordings of inhaler use in real world environments. The dataset was obtained from 12 asthma outpatients who attended a respiratory clinic over a three month period. Evaluation of the algorithm on this dataset achieved sensitivity of 95%, specificity of 94% and an accuracy of 89% in detecting inhalations compared to manual inhalation detection.

  4. Inhalant Initiation and the Relationship of Inhalant Use to the Use of Other Substances

    ERIC Educational Resources Information Center

    Shamblen, Stephen R.; Miller, Ted

    2012-01-01

    Conventional wisdom suggests that inhalant use is primarily isolated to youthful experimentation; however, a growing body of evidence suggests that inhalant use (a) occurs after use of common substances of experimentation (e.g., alcohol, marijuana), (b) can persist into later life, and (c) is associated with severe consequences. The current study…

  5. Inhalant Initiation and the Relationship of Inhalant Use to the Use of Other Substances

    ERIC Educational Resources Information Center

    Shamblen, Stephen R.; Miller, Ted

    2012-01-01

    Conventional wisdom suggests that inhalant use is primarily isolated to youthful experimentation; however, a growing body of evidence suggests that inhalant use (a) occurs after use of common substances of experimentation (e.g., alcohol, marijuana), (b) can persist into later life, and (c) is associated with severe consequences. The current study…

  6. Checklists for the Assessment of Correct Inhalation Therapy.

    PubMed

    Knipel, V; Schwarz, S; Magnet, F S; Storre, J H; Criée, C P; Windisch, W

    2017-02-01

    Introduction For the long-term treatment of obstructive lung diseases inhalation therapy with drugs being delivered directly to the lungs as an aerosol has become the method of choice. However, patient-related mistakes in inhalation techniques are frequent and recognized to be associated with reduced disease control. Since the assessment of patient-mistakes in inhalation has yet not been standardized, the present study was aimed at developing checklists for the assessment of correct inhalation. Methods Checklists were developed in German by an expert panel of pneumologists and professionally translated into English following back-translation procedures. The checklists comparably assessed three major steps of inhalation: 1) inhalation preparation, 2) inhalation routine, and 3) closure of inhalation. Results Checklists for eight frequently used inhalers were developed: Aerolizer, Breezhaler, Diskus (Accuhaler), metered-dose inhaler, Handihaler, Novolizer, Respimat, Turbohaler. Each checklist consists of ten items: three for inhalation preparation, six for inhalation routine, and one for closure of inhalation. Discussion Standardized checklists for frequently used inhalers are available in German and English. These checklists can be used for clinical routines or for clinical trials. All checklists can be downloaded free of charge for non-profit application from the homepage of the German Airway League (Deutsche Atemwegsliga e. V.): www.atemwegsliga.de.

  7. Nitric oxide: a challenge to chiropractic

    PubMed Central

    Morgan, Lon

    2000-01-01

    The 1998 Nobel Prize in Physiology or Medicine recognized the biological significance of nitric oxide. Nitric oxide is derived from the amino acid arginine. It is intimately involved with circulatory vessel dilation where, for example, it protects against heart attacks, and is the basis for new medications such as Sildenafil (Viagra). Nitric oxide acts as a neurotransmitter and can modulate many neurological reactions. The immune system uses nitric oxide to destroy pathogens by interfering with key enzymes. Nitric oxide is responsible for both osteoclastic and osteoblastic responses in bone and is a key player in the degenerative aspects of arthritis. The process of apoptosis employs nitric oxide in the orderly removal of unneeded cells. There is clear evidence that major signaling and control mechanisms exist in the body apart from the nervous system. Chiropractic is thus faced with the challenge of how to incorporate this new knowledge which conflicts with traditional chiropractic concepts.

  8. Temperature and Nitric Oxide Generation in a Pulsed Arc Discharge Plasma

    NASA Astrophysics Data System (ADS)

    Namihira, T.; Sakai, S.; Matsuda, M.; D., Wang; Kiyan, T.; Akiyama, H.; Okamoto, K.; Toda, K.

    2007-12-01

    Nitric oxide (NO) is increasingly being used in medical treatments of high blood pressure, acute respiratory distress syndrome and other illnesses related to the lungs. Currently a NO inhalation system consists of a gas cylinder of N2 mixed with a high concentration of NO. This arrangement is potentially risky due to the possibility of an accidental leak of NO from the cylinder. The presence of NO in the air leads to the formation of nitric dioxide (NO2), which is toxic to the lungs. Therefore, an on-site generator of NO would be highly desirable for medical doctors to use with patients with lung disease. To develop the NO inhalation system without a gas cylinder, which would include a high concentration of NO, NAMIHIRA et al have recently reported on the production of NO from room air using a pulsed arc discharge. In the present work, the temperature of the pulsed arc discharge plasma used to generate NO was measured to optimize the discharge condition. The results of the temperature measurements showed the temperature of the pulsed arc discharge plasma reached about 10,000 K immediately after discharge initiation and gradually decreased over tens of microseconds. In addition, it was found that NO was formed in a discharge plasma having temperatures higher than 9,000 K and a smaller input energy into the discharge plasma generates NO more efficiently than a larger one.

  9. Effect of Disease Severity in Asthma and Chronic Obstructive Pulmonary Disease on Inhaler-Specific Inhalation Profiles Through the ELLIPTA® Dry Powder Inhaler.

    PubMed

    Prime, David; de Backer, Wilfried; Hamilton, Melanie; Cahn, Anthony; Preece, Andrew; Kelleher, Dennis; Baines, Amanda; Moore, Alison; Brealey, Noushin; Moynihan, Jackie

    2015-12-01

    Two studies were undertaken to characterize the maximal effort inhalation profiles of healthy subjects and patients with asthma or chronic obstructive pulmonary disease (COPD) through a moderate-resistance dry powder inhaler (DPI). Correlations between inhaler-specific inhalation characteristics and inhaler-independent lung function parameters were investigated. Healthy subjects (n = 15), patients with mild, moderate, or severe asthma (n = 45), and patients with mild, moderate, severe, or very-severe COPD (n = 60) were included in the studies. Inhalation pressure drop versus time profiles were recorded using an instrumented ELLIPTA® DPI or bespoke resistor component with equivalent resistivity. Inhaler-independent lung function assessments included pharyngometry, spirometry, plethysmography, and diffusion. For the inhaler-specific inhalation profiles, the mean maximal effort peak inspiratory flow rates (PIFRs) varied across the subgroups from 65.8-110.6 L/min (range: 41.6-142.9). Peak pressure drop, PIFR, inhaled volume, and average inhalation flow rate (primary endpoints) did not differ markedly between healthy subjects and patients with asthma or mild COPD. Moderate, severe, and very-severe COPD patients demonstrated lower mean peak pressure drops, PIFRs and inhaled volumes, which tended to decrease with increasing COPD severity. Severe and very-severe COPD patients demonstrated shorter mean inhalation times compared with all other participants. Inhaler-independent lung function parameters were consistent with disease severity, and statistically significant (p < 0.05) strong correlations (R > 0.7) with components of the inhaler-specific inhalation profiles were observed in the COPD cohort; correlations in the asthma cohort tended to be weaker. All participants achieved a maximal effort PIFR ≥ 41.6 L/min through the moderate resistance of the ELLIPTA inhaler. Patients with asthma achieved similar inhalation profiles to healthy subjects

  10. Effect of Disease Severity in Asthma and Chronic Obstructive Pulmonary Disease on Inhaler-Specific Inhalation Profiles Through the ELLIPTA® Dry Powder Inhaler

    PubMed Central

    de Backer, Wilfried; Hamilton, Melanie; Cahn, Anthony; Preece, Andrew; Kelleher, Dennis; Baines, Amanda; Moore, Alison; Brealey, Noushin; Moynihan, Jackie

    2015-01-01

    Abstract Background: Two studies were undertaken to characterize the maximal effort inhalation profiles of healthy subjects and patients with asthma or chronic obstructive pulmonary disease (COPD) through a moderate-resistance dry powder inhaler (DPI). Correlations between inhaler-specific inhalation characteristics and inhaler-independent lung function parameters were investigated. Methods: Healthy subjects (n = 15), patients with mild, moderate, or severe asthma (n = 45), and patients with mild, moderate, severe, or very-severe COPD (n = 60) were included in the studies. Inhalation pressure drop versus time profiles were recorded using an instrumented ELLIPTA® DPI or bespoke resistor component with equivalent resistivity. Inhaler-independent lung function assessments included pharyngometry, spirometry, plethysmography, and diffusion. Results: For the inhaler-specific inhalation profiles, the mean maximal effort peak inspiratory flow rates (PIFRs) varied across the subgroups from 65.8–110.6 L/min (range: 41.6–142.9). Peak pressure drop, PIFR, inhaled volume, and average inhalation flow rate (primary endpoints) did not differ markedly between healthy subjects and patients with asthma or mild COPD. Moderate, severe, and very-severe COPD patients demonstrated lower mean peak pressure drops, PIFRs and inhaled volumes, which tended to decrease with increasing COPD severity. Severe and very-severe COPD patients demonstrated shorter mean inhalation times compared with all other participants. Inhaler-independent lung function parameters were consistent with disease severity, and statistically significant (p < 0.05) strong correlations (R > 0.7) with components of the inhaler-specific inhalation profiles were observed in the COPD cohort; correlations in the asthma cohort tended to be weaker. Conclusions: All participants achieved a maximal effort PIFR ≥ 41.6 L/min through the moderate resistance of the ELLIPTA inhaler. Patients with asthma

  11. Inhalation devices, delivery systems, and patient technique.

    PubMed

    Nelson, Harold S

    2016-12-01

    In real-life clinical settings, physicians often consider the properties of various inhaled corticosteroids (ICSs), but typically little consideration is given to the properties of different inhalers and formulations. To discuss the effects of inhalation devices and user technique on efficacy, safety, and adherence with the aim of improving asthma management. Relevant publications were selected to augment discussion. There are many types of devices available, each with advantages, disadvantages, ease of use, and rate of misuse. Aerosol particle size influences the deposition pattern of a drug in the lungs, and the optimal particle size range is 1 to 5 μm. Retrospective reviews suggest that smaller particles (1-2 μm) could provide improved asthma control, but randomized, prospective studies are needed. Multiple studies have demonstrated high misuse rates in patients for pressurized metered-dose inhalers and dry powder inhalers. Because of this, repeated education should include physical demonstrations of using the device, checking the patient's technique, correcting the technique, and rechecking the technique. This also means that dedicated, trained staff and placebo devices should be available for instructing patients. Furthermore, the device should be selected to be cost effective and to fit the patient's preference and ability to use it correctly to enhance compliance. Asthma management guidelines and algorithms are available to guide the clinician. The choice of inhaler device should depend on cost effectiveness and the patient's preference and ability to use it correctly. Patient inhaler technique should be checked and, if necessary, corrected and rechecked, with retraining if needed, at every opportunity. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  12. Olfactory deposition of inhaled nanoparticles in humans

    PubMed Central

    Garcia, Guilherme J. M.; Schroeter, Jeffry D.; Kimbell, Julia S.

    2016-01-01

    Context Inhaled nanoparticles can migrate to the brain via the olfactory bulb, as demonstrated in experiments in several animal species. This route of exposure may be the mechanism behind the correlation between air pollution and human neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Objectives This manuscript aims to (1) estimate the dose of inhaled nanoparticles that deposit in the human olfactory epithelium during nasal breathing at rest and (2) compare the olfactory dose in humans with our earlier dose estimates for rats. Materials and methods An anatomically-accurate model of the human nasal cavity was developed based on computed tomography scans. The deposition of 1–100 nm particles in the whole nasal cavity and its olfactory region were estimated via computational fluid dynamics (CFD) simulations. Our CFD methods were validated by comparing our numerical predictions for whole-nose deposition with experimental data and previous CFD studies in the literature. Results In humans, olfactory dose of inhaled nanoparticles is highest for 1–2 nm particles with approximately 1% of inhaled particles depositing in the olfactory region. As particle size grows to 100 nm, olfactory deposition decreases to 0.01% of inhaled particles. Discussion and conclusion Our results suggest that the percentage of inhaled particles that deposit in the olfactory region is lower in humans than in rats. However, olfactory dose per unit surface area is estimated to be higher in humans due to their larger minute volume. These dose estimates are important for risk assessment and dose-response studies investigating the neurotoxicity of inhaled nanoparticles. PMID:26194036

  13. Nitric oxide in marine photosynthetic organisms.

    PubMed

    Kumar, Amit; Castellano, Immacolata; Patti, Francesco Paolo; Palumbo, Anna; Buia, Maria Cristina

    2015-05-01

    Nitric oxide is a versatile and powerful signaling molecule in plants. However, most of our understanding stems from studies on terrestrial plants and very little is known about marine autotrophs. This review summarizes current knowledge about the source of nitric oxide synthesis in marine photosynthetic organisms and its role in various physiological processes under normal and stress conditions. The interactions of nitric oxide with other stress signals and cross talk among secondary messengers are also highlighted.

  14. NITRIC ACID RECPVERY FROM WASTE COLUTIONS

    DOEpatents

    Wilson, A.S.

    1959-04-14

    The recovery of nitric acid from aqueous nitrate solutions containing fission products as impurities is described. It is desirable to subject such solutions to concentration by evaporation since nitric acid is regenerated thereby. A difficulty, however, is that the highly radioactive fission product ruthenium is volatilized together with the nitric acid. It has been found that by adding nitrous acids ruthenium volatilization is suppressed and reduced to a negligible degree so that the distillate obtained is practically free of rutheniuim.

  15. Nitric acid recovery from waste solutions

    DOEpatents

    Wilson, A. S.

    1959-04-14

    The recovery of nitric acid from aqueous nitrate solutions containing fission products as impurities is described. It is desirable to subject such solutions to concentration by evaporation since nitric acid is regenerated thereby. A difficulty, however, is that the highly radioactive fission product ruthenium is volatilized together with the nitric acid. It has been found that by adding nitrous acid, ruthenium volatilization is suppressed and reduced to a negligible degree so that the distillate obtained is practically free of ruthenium.

  16. The Oxidation of Hydrazine by Nitric Acid

    SciTech Connect

    Karraker, D.G.

    2001-07-02

    Hydrazine nitrate-nitric acid solutions are used in the ion exchange process for separating Pu-238 and Np-237 and have been found to dissolve plutonium metal in a manner advantageous to SRP metal recovery operations. Laboratory tests on the stability of hydrazine in nitric acid solutions were performed to obtain accurate data, and the results of these tests are reported here. These tests provide sufficient information to specify temperature control for hydrazine-nitric acid solutions in plant processes.

  17. [Health significance of inhaled particles].

    PubMed

    Gillissen, A; Gessner, C; Hammerschmidt, S; Hoheisel, G; Wirtz, H

    2006-03-24

    Particulates refer to particles, dust, dirt, soot and aerosol mists that has suspended in the surrounding air. They may consist of solids of various forms including fibres or liquids. Long term exposure to silicon dioxide containing dusts (crystalline silica: quartz, tridymite, cristobalite, coesite, stishovite) may cause pneumoconiosis in the form of acute or/either chronic silicosis. Asbestos refers to a divers family of crystalline hydrated fibrous siliates typically exhibiting a greater tha 3:1 length ot diameter ratio. It is subdivided into serpentine (Chrysotile) and amphibole (crocidolite, amosite, anthophyllite, tremolite, actinolite). Exposure to asbestos fibres may cause lung fibrosis and promote cancer of the lung or the pleura. Besides the induction of malignant diseases dust exposure may result in obstructive as well as restrictive lung diseases which may be compensate in case of the recognition as a occupational diseases. Other occupational exposures leading to pneumoconiosis are caused be talc, or metals including aluminium containing dusts. Also the group of man-made mineral (MMMFs) or vitreous fibres (MMVFs), including glass wool, rock wool, slag wool, glass filaments, microfibres, refractory ceramic fibres are bioactive under certain experimental conditions. Although it has been shown that MMMFs may cause malignancies when injected intraperitoneally in high quantities in rodents, inhalation trials and human studies could not reproduce these results in the same precision. Fine particles (particulate matter = PM) comprise one of the most widespread and harmful air pollutants in the industrialized world. PM may cause worsening of asthma and other respiratory diseases, reduce lung function development in children, potentially increased the risk of premature death in the elderly and enhance mortality from cardiac diseases. Because of the small size PM2.5 is seen to be even more hazardous than PM10.

  18. Recent advances in inhalation anesthesia.

    PubMed

    Steffey, Eugene P

    2002-04-01

    Both desflurane and sevoflurane offer theoretical and practical advantages over other inhalation anesthetics for horses. The lower solubility of both agents provides improved control of delivery and helps to counteract the confounding influence of the voluminous patient breathing circuit commonly used for anesthetizing horses. The lower solubility should account for faster rates of recovery compared with the older agents; whether or not the quality of recovery differs remains to be objectively evaluated in a broad range of circumstances. The pharmacodynamic effects are, in large part, similar to those of isoflurane (e.g., low arrhythmogenicity) but with some differences. For example, desflurane may be overall more sparing to cardiovascular function (especially during controlled ventilation) compared with isoflurane and sevoflurane, which are roughly similar. Respiratory depression with both new agents is equal to or more depressing than isoflurane, suggesting the use of mechanical ventilation, especially in circumstances of prolonged management (i.e., hours of anesthesia). Both new anesthetics, not surprisingly, are expensive. From this point there are some agent-unique considerations. The anesthetic potency of both agents is less than that of isoflurane, which influences the cost of anesthesia, but also places an upper limit on inspired oxygen concentration (of particular concern with desflurane). Both agents require new vaporizers, but because of the high boiling point and steep vapor-pressure curve of desflurane, new technology was required. This translates into more costly equipment, adding to the cost of desflurane use. In addition, electricity is necessary for the new desflurane vaporizer to function, which limits its portability and adds additional practical considerations in its clinical use. On the other hand, desflurane strongly resists degradation both in vitro and in vivo, but in vitro degradation of sevoflurane by CO2 absorbents may produce renal

  19. Effect of terbutaline on mucociliary clearance in asthmatic and healthy subjects after inhalation from a pressurised inhaler and a dry powder inhaler.

    PubMed Central

    Mortensen, J; Groth, S; Lange, P; Hermansen, F

    1991-01-01

    BACKGROUND: beta Agonists have been shown to increase mucociliary clearance in some studies but not all. Whether the formulation of beta agonists affects mucociliary clearance is not known but may be important as the use of dry powder inhalers increases. METHODS: The effect of different methods of administration of inhaled terbutaline on mucociliary clearance and forced expiratory volume in one second (FEV1) was assessed in 10 patients with asthma and 10 healthy subjects. Terbutaline (1 mg) was administered through a metered dose inhaler with a spacer (Nebuhaler) or a dry powder inhaler (Turbuhaler), or both treatments were given, in a four way double blind, double dummy trial. Mucociliary clearance was measured by bronchoscintigraphy. RESULTS: Clearance of radioactivity from the lobar bronchi increased in the asthmatic patients by a median of 32% after terbutaline was given by metered dose inhaler and 55% after a combined dose of 2 mg from both inhalers (1 mg from each) compared with placebo but by only 9% after 1 mg of terbutaline was given by a dry powder inhaler. In the healthy subjects mucociliary clearance increased by 51% when terbutaline was given by a dry powder inhaler, by 66% when given by a metered dose inhaler, and by 66% when given by both inhalers combined. The effect of terbutaline on FEV1 was the same with each of the inhalers. CONCLUSION: Despite similar changes in FEV1 with the two formulations terbutaline increased mucociliary clearance significantly in asthmatic and healthy subjects when inhaled from a metered dose inhaler whereas when it was inhaled from a dry powder inhaler its effect was significant only in healthy subjects. The reason for the difference in asthmatic subjects is unclear, but may be associated with differences in the deposition of terbutaline. Images PMID:1771605

  20. IRIS Toxicological Review of Formaldehyde (Inhalation) ...

    EPA Pesticide Factsheets

    UPDATE EPA is currently revising its Integrated Risk Information System (IRIS) assessment of formaldehyde to address the 2011 NAS peer review recommendations. This assessment addresses both noncancer and cancer human health effects that are relevant to assessing the risks from chronic inhalation exposure to formaldehyde. To facilitate discussion of several scientific issues pertinent to the assessment, EPA convened a state-of-the-science workshop on April 30 and May 1, 2014. This workshop focused on the following three themes: Evidence pertaining to the influence of formaldehyde that is produced endogenously (by the body during normal biological processes) on the toxicity of inhaled formaldehyde, and implications for the health assessment; Mechanistic evidence relevant to formaldehyde inhalation exposure and lymphohematopoietic cancers (leukemia and lymphomas); and Epidemiological research examining the potential association between formaldehyde exposure and lymphohematopoietic cancers (leukemia and lymphomas). June 2010: EPA is conducting an independent expert peer review by the National Academy of Sciences and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Formaldehyde-Inhalation that when finalized will appear on the Integrated Risk Information System (IRIS) database. This draft IRIS health assessment addresses both noncancer and cancer human health effects that may result from chronic inhal