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Inhalation
Kinds of Inhalation Terms modified by Inhalation Selected AbstractsInhalation of Amyl Nitrite and the Measurement of Left Ventricular Outflow Velocity: Studies in Normal, Young AdultsECHOCARDIOGRAPHY, Issue 2 2000BYRON F. VANDENBERG M.D. Amyl nitrite inhalation is useful in the identification of patients with provocable left ventricular (LV) outflow tract obstruction. However, there are no prospective studies that assess the normal change in LV outflow velocity during this intervention. Eighteen normal subjects (mean age, 34 ± 5 years; 9 men and 9 women) inhaled amyl nitrite during measurement of LV outflow velocity. Peak velocity increased from 109 ± 16 cm/s to 144 ± 24 cm/s (P < 0.001). There were no significant gender differences in velocity measurements at baseline or at peak. Our study provides prospective data that may be useful when evaluating young adults for LV outflow tract obstruction with Doppler echocardiography during amyl nitrite inhalation. [source] Cluster headache: aetiology, diagnosis and management.HEADACHE, Issue 3 2003K Ekbom Drugs. 2002;62(1):61-69 Cluster headache is characterised by repeated attacks of strictly unilateral pain in the orbital region associated with local autonomic symptoms or signs. The attacks are brief but of a very severe, almost excruciating intensity. For unknown reasons males are affected more often than females. Recent studies suggest that an autosomal dominant gene has a role in some families with cluster headache. Hormonal studies indicate a dysfunction in the central nervous system. Neuroimaging has revealed primary defects in the hypothalamic grey matter. Local homolateral dilatation in the intracranial segment of the internal carotid and ophthalmic arteries during attacks is the result of a generic neurovascular activation, probably mediated by trigeminal parasympathetic reflexes. Sumatriptan 6mg subcutaneously is the drug of choice in the treatment of acute attacks. Inhalation of 100% oxygen can also be recommended. In the prophylactic treatment, verapamil is the first option. Other drugs that can be considered are corticosteroids, which may induce a remission of frequent, severe attacks, and lithium. Oral ergotamine tartrate may be sufficient for patients with night attacks and/or short, rather mild to moderately severe cluster headache periods. Third line drugs are serotonin inhibitors (methysergide and pizotifen) and valproic acid. Patients should be encouraged to keep headache diaries and be carefully instructed about the nature and treatment of the headaches. Alcohol can bring on extra attacks and should not be consumed during active periods of cluster headache. Comment: A useful review of clinical options. Given the effectiveness of injectable sumatriptan and the prophylactic use of ergotamine mentioned, one might speculate that the new intranasal formulations of triptans (eg, zolmitriptan) and triptans with a longer half-life (eg, frovatriptan) may prove to be effective in the treatment of cluster headache. DSM [source] Suicidal Asphyxiation by Inhalation of Automobile Emission without Carbon Monoxide PoisoningJOURNAL OF FORENSIC SCIENCES, Issue 5 2006Stephen J. DeRoux M.D. ABSTRACT: Reported herein is the suicidal asphyxiation of a young man due to exhaustion of oxygen in the interior of a sealed automobile into which the exhaust emissions were diverted. His blood carboxyhemaglobin concentration was less than 5% saturation. The car was equipped with a catalytic converter and when tested, the exhaust carbon monoxide concentration was 0.01%. [source] Inhalation efficacy of RFI-641 in an African green monkey model of RSV infectionJOURNAL OF MEDICAL PRIMATOLOGY, Issue 2 2003W.J. Weiss Abstract: Human respiratory syncytial virus (RSV) is a major cause of acute upper and lower respiratory tract infections. RFI-641 is a novel RSV fusion inhibitor with potent in vitro activity. In vivo efficacy of RFI was determined in an African green monkey model of RSV infection involving prophylactic and therapeutic administration by inhalation exposure. Inhalation was with an RFI-641 nebulizer reservoir concentration of 15 mg/ml for 15 minutes (short exposure) or 2 hours (long exposure). Efficacy and RFI-641 exposure was determined by collection of throat swabs, nasal washes and bronchial alveolar lavage (BAL) on selected days. The short-exposure group (15 minutes) exhibited no effect on the nasal, throat or BAL samples. The throat and nasal samples for the long-exposure group failed to show a consistent reduction in viral titers. RFI-641 2 hours exposure-treated monkeys showed a statistically significantly log reduction for BAL samples of 0.73,1.34 PFU/ml (P -value 0.003) over all the sampling days. Analysis indicates that the long-exposure group titer was lower than the control titer on day 7 and when averaged across days. The results of this study demonstrate the ability of RFI-641 to reduce the viral load of RSV after inhalation exposure in the primate model of respiratory infection. [source] Arterial oxygen tension increase 2,3 h after hyperbaric oxygen therapy: a prospective observational studyACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2007B. Ratzenhofer-Komenda Background:, Inhalation of hyperbaric oxygen (HBO) has been reported to decrease arterial oxygen tension (PaO2) in the early period after exposure. The current investigation aimed at evaluating whether and to what extent arterial blood gases were affected in mechanically ventilated intensive care patients within 6 h after HBO treatment. Methods:, Arterial blood gases were measured in 11 ventilated subjects [nine males, two females, synchronized intermittent mandatory ventilation (SIMV) mode] undergoing HBO therapy for necrotizing soft tissue infection (seven patients), burn injury (two patients), crush injury (one patient) and major abdominal surgery (one patient). Blood gases were obtained with the patients in the supine position under continuous analgesia and sedation before the hyperbaric session (baseline), during isopression, after decompression, after each transport, and 1, 2, 3 and 6 h after exposure. Heart rates and blood pressures were recorded. Intensive care unit (ICU) ventilator settings remained unchanged. Transport and chamber ventilator settings were adjusted to baseline with maintenance of tidal volumes and positive end-expiratory pressure (PEEP) levels. The hyperbaric protocol consisted of 222.9 kPa (2.2 absolute atmospheres) and a 50-min isopression phase. The paired Wilcoxon's test was used. Results:, Major findings (median values, 25%/75% quantiles) as per cent change of baseline: PaO2 values decreased by 19.7% (7.0/31.7, P < 0.01) after 1 h and were elevated over baseline by 9.3% (1.5/13.7, P < 0.05) after 3 h. SaO2, alveolar-arterial oxygen tension difference and PaO2/FiO2 ratio behaved concomitantly. Acid-base status and carbon dioxide tension were unaffected. Conclusion:, Arterial oxygen tension declines transiently after HBO and subsequently improves over baseline in intensive care patients on volume-controlled mechanical ventilation. The effectiveness of other ventilation modes or a standardized recruitment manoeuvre has yet to be evaluated. [source] The science of aerosol delivery in cystic fibrosisPEDIATRIC PULMONOLOGY, Issue S9 2008David E. Geller MD Abstract Aerosolized drugs are universally used for treatment of cystic fibrosis airway disease. Inhalation can increase topical efficacy and reduce systemic exposure and toxicity of many drugs. A wide variety of inhaled drugs already exist with many more in the therapeutic pipeline. Understanding the principles of aerosol delivery and how aerosol devices function is important in designing the best therapeutic regimens for CF patients. The variables that determine where an aerosol deposits are numerous and complex. Important aerosol-related variables include particle-size distribution, hygroscopic properties, viscosity and surface tension of the drug. Patient-related variables include inspired flow rate, tidal volume, respiratory rate, breath-holding, upper airway anatomy, lower airways obstruction, and the cognitive and physical ability to use the device. These factors vary widely between patients of different age groups and disease severities, and cause the high variability in drug delivery seen with aerosol drugs. Classic aerosol delivery devices like metered dose inhalers and dry-powder inhalers are small, portable, and have short treatment times. However, they are limited by small drug payloads and user technique problems. Jet nebulizers are commonly used for CF drugs, are easy to operate, require no special breathing pattern, and can deliver very large quantities of drug. However, they require a power or air source, cleaning and sanitizing, and are relatively time consuming. Recently, novel aerosol delivery systems and formulations have been developed to improve delivery efficiency and reduce variability and delivery time. These new systems can ease the treatment burden and improve adherence and outcomes in cystic fibrosis. Pediatr Pulmonol. 2008; 43:S5,S17. © 2008 Wiley-Liss, Inc. [source] Cancer mortality among European asphalt workers: An international epidemiological study.AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 1 2003Abstract Background Inhalation of bitumen fumes is potentially carcinogenic to humans. Methods We conducted a study of 29,820 male workers exposed to bitumen in road paving, asphalt mixing and roofing, 32,245 ground and building construction workers unexposed to bitumen, and 17,757 workers not classifiable as bitumen workers, from Denmark, Finland, France, Germany, Israel, the Netherlands, Norway, and Sweden, with mortality follow-up during 1953,2000. We calculated standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) based on national mortality rates. Poisson regression analyses compared mortality of bitumen workers to that of building or ground construction workers. Results The overall mortality was below expectation in the total cohort (SMR 0.92, 95% CI 0.90,0.94) and in each group of workers. The SMR of lung cancer was higher among bitumen workers (1.17, 95% CI 1.04,1.30) than among workers in ground and building construction (SMR 1.01, 95% CI 0.89,1.15). In the internal comparison, the relative risk (RR) of lung cancer mortality among bitumen workers was 1.09 (95% CI 0.89,1.34). The results of cancer of the head and neck were similar to those of lung cancer, based on a smaller number of deaths. There was no suggestion of an association between employment in bitumen jobs and other cancers. Conclusions European workers employed in road paving, asphalt mixing and other jobs entailing exposure to bitumen fume might have experienced a small increase in lung cancer mortality risk, compared to workers in ground and building construction. However, exposure assessment was limited and confounding from exposure to carcinogens in other industries, tobacco smoking, and other lifestyle factors cannot be ruled out. Am. J. Ind. Med. 43:18,27, 2003. © 2003 Wiley-Liss, Inc. [source] Sensory neuropeptides are not involved in acetaldehyde-induced bronchoconstriction in guinea-pigsAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 3 2001S. Myou 1,Alcohol-induced asthma is characterized by worsening of asthmatic symptoms after alcohol ingestion. Acetaldehyde, a metabolite of ethanol, is thought to be a main factor of alcohol-induced asthma. Although airway sensory nerves are known to be activated in asthma, there have been no studies investigating the role of tachykinins in the airway response to acetaldehyde. The purpose of the present study was to evaluate the involvement of tachykinins on acetaldehyde-induced bronchoconstriction in guinea-pigs. 2,After capsaicin desensitization or intravenous administration of 10 mg kg,1 FK224, a NK1 and NK2 dual antagonist, airway responses to ascending doses (2.5,20 mg ml,1) of inhaled acetaldehyde was examined using a modified Konzett,Rössler method in guinea-pigs. 3,Inhalation of acetaldehyde induced bronchoconstriction in a dose-dependent manner. The FK224 failed to reduce the acetaldehyde-induced bronchoconstriction. Pretreatment with capsaicin did not alter the bronchoconstriction induced by acetaldehyde at a dose of 2.5,10 mg ml,1. Pretreatment with capsaicin slightly, but significantly, inhibited bronchoconstriction induced by 20 mg ml,1 of acetaldehyde. 4,The present results suggest that tachykinins are not involved in acetaldehyde-induced bronchoconstriction in guinea-pigs. [source] Retinal arterioles have impaired reactivity to hyperoxia in type 1 diabetesACTA OPHTHALMOLOGICA, Issue 4 2010Birgitte L. Justesen Abstract. Purpose:, Diabetes has adverse effects on the retinal microvasculature. The purpose of this study was to compare the effects of inhalation of hypoxic, hyperoxic and normoxic,hypercapnic gas mixtures on retinal vessel diameter in people with and without diabetes. Methods:, Sixty-one participants (aged 24,50 years) 29 with (male : female ratio 2.6 : 1) and 32 without (male : female ratio 0.7 : 1) diabetes, inhaled hypoxic, hyperoxic and normoxic,hypercapnic gas mixtures for 3,5 mins. The diameters of arterioles and venules were measured using digital retinal images taken before and after gas inhalation. Results:, There was no significant difference in the diameters of arterioles and venules prior to gas inhalation in people with and without diabetes. Inhalation of the hyperoxic gas mixture caused a statistically significant decrease in arteriolar and venular diameters without altering mean arterial pressure significantly. Arteriolar vasoconstriction in response to the hyperoxic gas mixture was significantly reduced in people with diabetes (3.95% versus 7.75%; p = 0.04), but venular vasoconstriction did not differ significantly. A hypoxic gas mixture caused increased arteriolar and venular diameter and a normoxic,hypercapnic gas mixture had no significant effect on vessel diameter. Responses to hypoxic and normoxic,hypercapnic gas did not differ significantly between diabetes and non-diabetes subjects. Conclusions:, Type 1 diabetes impairs retinal arteriolar responses to hyperoxia. Abnormalities in retinal arteriolar reactivity in response to oxygen may play a role in the development of diabetic retinopathy and this technique may represent a simple means of identifying early abnormalities in the reactivity of retinal arterioles in diabetes. [source] The Lung Is The Major Site That Produces Nitric Oxide To Induce Acute Pulmonary Oedema In Endotoxin ShockCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2001Ru Ping Lee SUMMARY 1. The present study was undertaken to determine the locus of nitric oxide (NO) production that is toxic to the lung and produces acute pulmonary oedema in endotoxin shock, to examine and compare the effects of changes in lung perfusate on endotoxin-induced pulmonary oedema (EPE) and to evaluate the involvement of constitutive and inducible NO synthase (cNOS and iNOS, respectively). 2. Experiments were designed to induce septic shock in anaesthetized rats with the administration of Escherichia coli lipopolysaccharide (LPS). Exhaled NO, lung weight (LW)/bodyweight (BW) ratio, LW gain (LWG) and lung histology were measured and observed to determine the degree of EPE 4 h following LPS. The EPE was compared between groups in which LPS had been injected either into the systemic circulation or into the isolated perfused lung. The lung perfusate was altered from whole blood to physiological saline solution (PSS) with 6% albumin to test whether different lung perfusions affected EPE. Pretreatment with various NOS inhibitors was undertaken 10 min before LPS to investigate the contribution of cNOS and iNOS to the observed effects. 3. Endotoxin caused profound systemic hypotension, but little change in pulmonary arterial pressure. The extent of EPE was not different between that induced by systemic injection and that following administration to isolated lungs preparations. Replacement of whole blood with PSS greatly attenuated (P < 0.05) EPE. In blood-perfused lungs, pretreatment with NOS inhibitors, such as N, -nitro- L -arginine methyl ester, aminoguanidine and dexamethasone, significantly prevented EPE (P < 0.05). 4. The major site of NO production through the whole blood is in the lung. The NO production mediated by the iNOS system is toxic to the endothelium in the pulmonary microvasculature. Inhalation of NO for patients with sepsis may be used with clinical caution. Therapeutic consideration of lung extracorporeal perfusion with PSS and pharmacological pretreatment with iNOS inhibitors may be warranted. [source] Budesonide delivered by dosimetric jet nebulization to preterm very low birthweight infants at high risk for development of chronic lung diseaseACTA PAEDIATRICA, Issue 12 2000B Jónsson We investigated the effect of an aerosolized corticosteroid (budesonide) on the oxygen requirement of infants at high risk for developing chronic lung disease (CLD) in a randomized, double-blind study. The study objective was to attain a 30% decrease in FiO2 levels in the budesonide treatment group after 14 d of therapy. Thirty very low birthweight (VLBW) infants (median (range)) gestational age 26 wk (23,29) and birthweight 805 g (525,1227) were randomized. Inclusion criteria were mechanical ventilation on day 6 of life, or if extubated on nasal continuous positive airway pressure with FiO2± 0.3. The budesonide (PulmicortÔ dose was 500 ,g bid, or placebo. The aerosol was delivered with a dosimetric jet nebulizer, with variable inspiratory time and breath sensitivity. Inhalations were started on day 7 of life. Twenty-seven patients completed the study. A significant lowering of the FiO2 levels at 21 d of life was not detected. Infants who received budesonide were more often extubated during the study period (7/8 vs 2/9) and had a greater relative change from baseline in their oxygenation index (budesonide decreased 26% vs placebo increased 60%). Subsequent use of intravenous dexamethasone or inhaled budesonide in the treatment group was significantly less. All patients required O2 supplementation on day 28 of life. At 36 wk postconceptual age, 61% of infants in the budesonide group needed supplemental O2 as opposed to 79% in the placebo group. No side effects on growth or adrenal function were observed Conclusion: We conclude that inhaled budesonide aerosol via dosimetric jet nebulizer started on day 7 of life for infants at high risk for developing CLD decreases the need for mechanical ventilation similar to intravenous dexamethasone, but without significant side effects. [source] Aerosols and gaseous contrast agents for magnetic resonance imaging of the lungCONTRAST MEDIA & MOLECULAR IMAGING, Issue 5 2008Karim Mosbah Abstract Magnetic resonance imaging of lungs and the investigation of pulmonary pathologies with this technique are limited by low proton spin density, degraded magnetic homogeneity and motion. Inhaled contrast agents (gases or aerosols) can improve the diagnostic value of MRI for lung. Paramagnetic contrast agents such as gadolinium chelates aerosol or dioxygen gas increase the relaxivity of proton in lung parenchyma and can be used to assess the ventilated fraction of the bronchoalveolar space. Similarly, inhalation of non proton-MRI nuclei such as perfluorinated gas or hyperpolarized gases (3He or 129Xe) can provide functional ventilation image. In this review paper, the principles, the practical implementation, the limitations and possible safety issues of these different techniques are summarized. The main pre-clinical and clinical applications of these approaches based on oral contrast agents are reviewed and illustrated with cutting-edge lung MRI studies. Copyright © 2008 John Wiley & Sons, Ltd. [source] Responses of the bronchial and pulmonary circulations to short-term nitric oxide inhalation before and after endotoxaemia in the pigACTA PHYSIOLOGICA, Issue 1 2002R. J. M. Middelveld ABSTRACT The physiological responses of the bronchial circulation to acute lung injury and endotoxin shock are largely unexplored territory. This study was carried out to study the responsiveness of the bronchial circulation to nitric oxide (NO) inhalation before and after endotoxaemia, in comparison with the pulmonary circulation, as well as to study changes in bronchial blood flow during endotoxaemia. Six anaesthetized pigs (pre-treated with the cortisol-synthesis inhibitor metyrapone) received an infusion of 10 µg/kg endotoxin during 2 h. Absolute bronchial blood flow was measured via an ultrasonic flow probe around the bronchial artery. The pigs received increasing doses of inhaled NO over 5 min each (0, 0.2, 2 and 20 ppm) before and after 4 h of endotoxaemia. The increase in bronchial vascular conductance during 5 min of inhalation of 20 ppm NO before endotoxin shock was significantly higher (area under curve (AUC) 474.2 ± 84.5% change) than after endotoxin shock (AUC 118.2 ± 40.4%, P < 0.05 Mann,Whitney U -test). The reduction of the pulmonary arterial pressure by 20 ppm NO was not different. A short rebound effect of the pulmonary arterial pressure occurred after discontinuation of inhaled NO before endotoxaemia (AUC values above baseline 54.4 ± 19.7% change), and was virtually abolished after endotoxaemia (AUC 6.1 ± 4.0%, P = 0.052, Mann,Whitney U -test). Our results indicate that the responsiveness of the bronchial circulation to inhalation of increasing doses of inhaled NO during endotoxin shock clearly differ from the responsiveness of the pulmonary circulation. The reduced responsiveness of the bronchial circulation is probably related to decreased driving pressure for the bronchial blood flow. The absence of the short rebound effect on pulmonary arterial pressure (PAP) after induction of shock could be related to maximum constriction of the pulmonary vessels at 4 h. [source] Behavioral and cardiovascular effects of 7.5% CO2 in human volunteersDEPRESSION AND ANXIETY, Issue 1 2005Jayne E. Bailey M.Sc. Abstract The study of carbon dioxide (CO2) inhalation in psychiatry has a long and varied history, with recent interest in using inhaled CO2 as an experimental tool to explore the neurobiology and treatment of panic disorder. As a consequence, many studies have examined the panic-like response to the gas either using the single or double breath 35% CO2 inhalation or 5,7% CO2 inhaled for 15,20 min, or rebreathing 5% CO2 for a shorter time. However, this lower dose regime produces little physiological or psychological effects in normal volunteers. For this reason we have studied the effects of a higher concentration of CO2, 7.5%, given over 20 min. Twenty healthy volunteers were recruited to a double blind, placebo-controlled study where air and 7.5% CO2 were inhaled for 20 min. Cardiovascular measures and subjective ratings were obtained. When compared to air, inhaling 7.5% CO2 for 20 min increases systolic blood pressure and heart rate, indicating increased autonomic arousal. It also increases ratings of anxiety and fear and other subjective symptoms associated with an anxiety state. The inhalation of 7.5% CO2 for 20 min is safe for use in healthy volunteers and produces robust subjective and objective effects. It seems promising as an anxiety provocation test that could be beneficial in the study of the effects of anxiety on sustained performance, the discovery of novel anxiolytic agents, and the study of brain circuits and mechanisms of anxiety. Depression and Anxiety 00:000,000, 2005. © 2005 Wiley-Liss, Inc. [source] The effects of acute exercise and high lactate levels on 35% CO2 challenge in healthy volunteersACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2002G. Esquivel Objective:, To test the possible antipanic effects of acute exercise in healthy volunteers exposed to an inhalation of 35% CO2 challenge. Method:, Twenty healthy subjects in a randomized separate group design, performed exercise in a bicycle ergometer reaching >6 mm of blood lactate and a control condition of minimal activity in the same fashion with no lactate elevation. Immediately afterwards an inhalation of a vital capacity using a mixture of 35% CO2/65% O2 through a mask was given on both conditions. Results:, Subjects under the exercise condition reported less panic symptoms than controls after a CO2 challenge on the diagnostic statistical manual-IV (DSM-IV) Panic Symptom List but no difference on the Visual Analogue Anxiety Scale. Conclusion:, Subjects under the exertion condition had lactate levels comparable with those of lactate infusions but an inhibitory rather than accumulative effect was seen when combined with a CO2 challenge. [source] Imaging studies of biodistribution and kinetics in drug developmentDRUG DEVELOPMENT RESEARCH, Issue 2 2003Marc S. Berridge Abstract Although the intravenous route of administration is rarely used for drugs, it is by far the most common route for PET and SPECT radiotracers. This article discusses the use of planar and tomographic nuclear medicine technologies to image and quantify the distribution of drugs after local administration. In principle, this would include topical dermatologic, otic, ophthalmic, rectal, and vaginal administration, as well as the intramuscular, oral, and inhalation routes, although precedents do not yet exist for all of these. The studies reviewed focus mainly on oral ingestion and oral and nasal inhalation. The use of nondrug tracers for formulations is discussed, principally with planar imaging or SPECT using radionuclides such as 99mTc, as well as PET imaging where the active ingredient of a formulation can be labeled with 11C or sometimes 18F. An example of the latter type is a study of the deposition and kinetics in the lungs and airways of triamcinolone acetonide, an antiinflammatory steroid used for topical treatment of allergic rhinitis and asthma, dispensed from an inhaler. PET has high potential for evaluation of different formulations and delivery devices in the development of topically applied drugs. Drug Dev. Res. 59:208,226, 2003. © 2003 Wiley-Liss, Inc. [source] Inhalation of Amyl Nitrite and the Measurement of Left Ventricular Outflow Velocity: Studies in Normal, Young AdultsECHOCARDIOGRAPHY, Issue 2 2000BYRON F. VANDENBERG M.D. Amyl nitrite inhalation is useful in the identification of patients with provocable left ventricular (LV) outflow tract obstruction. However, there are no prospective studies that assess the normal change in LV outflow velocity during this intervention. Eighteen normal subjects (mean age, 34 ± 5 years; 9 men and 9 women) inhaled amyl nitrite during measurement of LV outflow velocity. Peak velocity increased from 109 ± 16 cm/s to 144 ± 24 cm/s (P < 0.001). There were no significant gender differences in velocity measurements at baseline or at peak. Our study provides prospective data that may be useful when evaluating young adults for LV outflow tract obstruction with Doppler echocardiography during amyl nitrite inhalation. [source] Expression of caspase and apoptotic signal pathway induced by sulfur dioxideENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2010Juli Bai Abstract Sulfur dioxide (SO2) is a common air pollutant that is released in low concentrations into the atmosphere and in higher concentrations in some work places. In the present study, male Wistar rats were housed in exposure chambers and treated with 14.00 ± 1.01, 28.00 ± 1.77, and 56.00 ± 3.44 mg/m3 SO2 for 7 days (6 hr/day), while control rats were exposed to filtered air under the same conditions. The mRNA and protein levels of caspase-3, caspase-8, and caspase-9 were analyzed using a real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) assay and an immunohistochemistry method. Activities of caspases were detected using colorimetric and fluorescent assays. Chromatin degradation and cell morphological changes were investigated by TUNEL assay and H&E staining in livers and lungs, respectively. The results showed that mRNA levels, protein levels and activities of caspase-3, caspase-8, and caspase-9 were increased in a dose-dependent manner in livers and lungs of rats after SO2 inhalation. In addition, livers were infiltrated with lymphocytes, congestion and inflammation occurred in lungs, and eosinophil cells and apoptotic cells increased in both livers and lungs after SO2 inhalation. These results suggest that SO2 exposure increases the expression and activity of both initiator and and effector caspases, and may induce apoptosis in liver and lung of rats through both death receptor and mitochondrial pathways. Environ. Mol. Mutagen. 2010. © 2009 Wiley-Liss, Inc. [source] Tissue-specific metabolic activation and mutagenicity of 3-nitrobenzanthrone in MutaÔMouse,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 8 2008Guosheng Chen Abstract 3-Nitrobenzanthrone (3-NBA) is a mutagen and suspected human carcinogen detected in diesel exhaust, airborne particulate matter, and urban soil. We investigated the tissue specific mutagenicity of 3-NBA at the lacZ locus of transgenic MutaÔMouse following acute single dose or 28-day repeated-dose oral administration. In the acute high dose (50 mg/kg) exposure, increased lacZ mutant frequency was observed in bone marrow and colonic epithelium, but not in liver and bladder. In the repeated-dose study, a dose-dependent increase in lacZ mutant frequency was observed in bone marrow and liver (2- and 4-fold increase above control), but not in lung or intestinal epithelium. In addition, a concentration-dependent increase in mutant frequency (8.5-fold above control) was observed for MutaÔMouse FE1 lung epithelial cells exposed in vitro. 1-Nitropyrene reductase, 3-NBA reductase, and acetyltransferase activities were measured in a variety of MutaÔMouse specimens in an effort to link metabolic activation and mutagenicity. High 3-NBA nitroreductase activities were observed in lung, liver, colon and bladder, and detectable N -acetyltransferase activities were found in all tissues except bone marrow. The relatively high 3-NBA nitroreductase activity in MutaÔMouse tissues, as compared with those in Salmonella TA98 and TA100, suggests that 3-NBA is readily reduced and activated in vivo. High 3-NBA nitroreductase levels in liver and colon are consistent with the elevated lacZ mutant frequency values, and previously noted inductions of hepatic DNA adducts. Despite an absence of induced lacZ mutations, the highest 3-NBA reductase activity was detected in lung. Further studies are warranted, especially following inhalation or intratracheal exposures. Environ. Mol. Mutagen., 2008. Published 2008 Wiley-Liss, Inc. [source] DNA damage in mice treated with sulfur dioxide by inhalationENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 3 2005Ziqiang Meng Abstract Sulfur dioxide (SO2) is a ubiquitous air pollutant produced by the burning of fossil fuels. In this study, single-cell gel electrophoresis (the Comet assay) was used to evaluate the DNA damage produced by inhalation exposure of mice to SO2. Male and female mice were housed in exposure chambers and treated with 14.00 ± 1.25, 28.00 ± 1.98, 56.00 ± 3.11, and 112.00 ± 3.69 mg/m3 SO2 for 6 hr/day for 7 days, while control groups were exposed to filtered air. Comet assays were performed on blood lymphocytes and cells from the brain, lung, liver, spleen, kidney, intestine, and testicles of the animals. SO2 caused significant, dose-dependent increases in DNA damage, as measured by Olive tail moment, in all the cell types analyzed from both sexes of mice. The results indicate that inhalation exposure to SO2 damages the DNA of multiple organs in addition to the lung, and suggests that this damage could result in mutation, cancer, and other diseases related to DNA damage. Further work will be required to understand the ultimate toxicological significance of this damage. These data also suggest that detecting DNA damage in blood lymphocytes, using the Comet assay, may serve as a useful tool for evaluating the impact of pulmonary SO2 exposure in human biomonitoring studies. Environ. Mol. Mutagen., 2005. © 2005 Wiley-Liss, Inc. [source] Pulmonary responses of acute exposure to ultrafine iron particles in healthy adult ratsENVIRONMENTAL TOXICOLOGY, Issue 4 2003Ya-Mei Zhou Abstract As critical constituents of ambient particulate matter, transition metals such as iron may play an important role in health outcomes associated with air pollution. The purpose of this study was to determine the respiratory effects of inhaled ultrafine iron particles in rats. Sprague Dawley rats 10,12 weeks of age were exposed by inhalation to iron particles (57 and 90 ,g/m3, respectively) or filtered air (FA) for 6 h/day for 3 days. The median diameter of particles generated was 72 nm. Exposure to iron particles at a concentration of 90 ,g/m3 resulted in a significant decrease in total antioxidant power along with a significant induction in ferritin expression, GST activity, and IL-1, levels in lungs compared with lungs of the FA control or of animals exposed to iron particles at 57 ,g/m3. NF,B,DNA binding activity was elevated 1.3-fold compared with that of control animals following exposure to 90 ,g/m3 of iron, but this change was not statistically significant. We concluded that inhalation of iron particles leads to oxidative stress associated with a proinflammatory response in a dose-dependent manner. The activation of NF,B may be involved in iron-induced respiratory responses, but further studies are merited. © 2003 Wiley Periodicals, Inc. Environ Toxicol 18: 227,235, 2003. [source] Original Article: Pulmonary function, airway cytology and bronchoalveolar lavage fluid drug concentration after aerosol administration of cefquinome to horsesEQUINE VETERINARY EDUCATION, Issue 9 2010T. Art Summary The administration of antibiotics by aerosol to horses suffering from respiratory infections may partially circumvent the limitations of antimicrobial therapy, e.g. large injection volumes, low bioavailability and risk of diarrhoea. Only injectable formulations are available currently and usually contain other substances that could irritate the mucosa and induce coughing and bronchospasm. In addition, the quality of the aerosol, particularly in terms of the delivery of antibiotics to the deep parts of the lung, is unknown. Although used under field conditions, cefquinome delivered by aerosol has never been studied in horses. This study examined the safety of cefquinome injectable solution, administered by aerosol at a dose of 225 mg/inhalation to 7 healthy horses, by assessing (1) pulmonary function before and 15 min after a single inhalation, at the first day (Day 1) and the fifth day (Day 5) of a 5 day period treatment; and (2) the inflammatory status of the lung, i.e. percentage neutrophils and myeloperoxidase concentration, based on bronchoalveolar lavage (BAL) at D1 and D5. In addition, cefquinome concentrations were measured in bronchoalveolar lavage fluid after aerosol, intravenous (i.v.) and intramuscular (i.m.) administrations. A single aerosol of cefquinome injectable solution did not induce any immediate nor delayed pulmonary side effects in healthy horses and produced cefquinome concentrations in bronchoalveolar lavage (BAL) within 30 min that were higher than the minimal inhibitory concentration of the main equine respiratory pathogens. These results should stimulate further studies, especially in horses suffering from bronchial hyper-reactivity. Aerosol delivery of antibiotics may well have a role in equine therapeutics. [source] Development of equine upper airway fluid mechanics model for Thoroughbred racehorsesEQUINE VETERINARY JOURNAL, Issue 3 2008V. RAKESH Summary Reason for performing study: Computational fluid dynamics (CFD) models provide the means to evaluate airflow in the upper airways without requiring in vivo experiments. Hypothesis: The physiological conditions of a Thoroughbred racehorse's upper airway during exercise could be simulated. Methods: Computed tomography scanned images of a 3-year-old intact male Thoroughbred racehorse cadaver were used to simulate in vivo geometry. Airway pressure traces from a live Thoroughbred horse, during exercise was used to set the boundary condition. Fluid-flow equations were solved for turbulent flow in the airway during inspiratory and expiratory phases. The wall pressure turbulent kinetic energy and velocity distributions were studied at different cross-sections along the airway. This provided insight into the general flow pattern and helped identify regions susceptible to dynamic collapse. Results: The airflow velocity and static tracheal pressure were comparable to data of horses exercising on a high-speed treadmill reported in recent literature. The cross-sectional area of the fully dilated rima glottidis was 7% greater than the trachea. During inspiration, the area of highest turbulence (i.e. kinetic energy) was in the larynx, the rostral aspect of the nasopharynx was subjected to the most negative wall pressure and the highest airflow velocity is more caudal on the ventral aspect of the nasopharynx (i.e. the soft palate). During exhalation, the area of highest turbulence was in the rostral and mid-nasopharynx, the maximum positive pressure was observed at the caudal aspect of the soft palate and the highest airflow velocity at the front of the nasopharynx. Conclusions and clinical relevance: In the equine upper airway collapsible area, the floor of the rostral aspect of the nasopharynx is subjected to the most significant collapsing pressure with high average turbulent kinetic during inhalation, which may lead to palatal instability and explain the high prevalence of dorsal displacement of the soft palate (DDSP) in racehorses. Maximal abduction of the arytenoid cartilage may not be needed for optimal performance, since the trachea cross-sectional area is 7% smaller than the rima glottidis. [source] Effects of unilateral laser-assisted ventriculocordectomy in horses with laryngeal hemiplegiaEQUINE VETERINARY JOURNAL, Issue 6 2006P. ROBINSON Summary Reasons for performing study: Recent studies have evaluated surgical techniques aimed at reducing noise and improving airway function in horses with recurrent laryngeal neuropathy (RLN). These techniques require general anaesthesia and are invasive. A minimally invasive transnasal surgical technique for treatment of RLN that may be employed in the standing, sedated horse would be advantageous. Objective: To determine whether unilateral laser-assisted ventriculocordectomy (LVC) improves upper airway function and reduces noise during inhalation in exercising horses with laryngeal hemiplegia (LH). Methods: Six Standardbred horses were used; respiratory sound and inspiratory transupper airway pressure (Pui) measured before and after induction of LH, and 60, 90 and 120 days after LVC. Inspiratory sound level (SL) and the sound intensities of formants 1, 2 and 3 (F1, F2 and F3, respectively), were measured using computer-based sound analysis programmes. In addition, upper airway endoscopy was performed at each time interval, at rest and during treadmill exercise. Results: In LH-affected horses, Pui, SL and the sound intensity of F2 and F3 were increased significantly from baseline values. At 60 days after LVC, Pui and SL had returned to baseline, and F2 and F3 values had improved partially compared to LH values. At 90 and 120 days, however, SL increased again to LH levels. Conclusions: LVC decreases LH-associated airway obstruction by 60 days after surgery, and reduces inspiratory noise but not as effectively as bilateral ventriculocordectomy. Potential relevance: LVC may be recommended as a treatment of LH, where reduction of upper airway obstruction and respiratory noise is desired and the owner wishes to avoid risks associated with a laryngotomy incision or general anaesthesia. [source] Effects of inhalation of albuterol sulphate, ipratroprium bromide and frusemide on breathing mechanics and gas exchange in healthy exercising horsesEQUINE VETERINARY JOURNAL, Issue 3 2001W. M. BAYLY Summary The possibility that pre-exercise inhalation of a bronchodilator by healthy horses could improve their mechanics of breathing and enhance performance was investigated. Ipratropium bromide (0.35 ,g/kg bwt; n = 7) was administered by nebulisation 30 min before exercise and frusemide (1 mg/kg bwt; n = 6) was given in the same manner 2 h before exercise. Albuterol sulphate (360 and 720 ,g; n = 7) were administered with a metered dose inhaler 2 h before exercise. Each drug was investigated independently of the others using cross-over protocols. Horses completed incremental exercise tests and oxygen consumption, carbon dioxide production, arterial blood gases, heart rate and measures of breathing mechanics including total pulmonary resistance (RL) and nasopharyngeal resistance (RU) were determined for each exercise intensity. The resistance of the lower airways was calculated subsequently from the difference between RL and RU. None of the drugs tested had an effect on any of the variables measured, possibly because maximal bronchodilation is stimulated in healthy horses by the normal sympathoadrenergic response to exercise. Therefore, the pre-exercise inhalation of a bronchodilator by a healthy horse is unlikely to improve performance capacity. [source] ,-tocopherol improves impaired physiology of rat type II pneumocytes isolated from experimentally injured lungsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2000B. Müller Background Oxidant stress delivered by nitrogen dioxide (NO2) inhalation impairs the function of extracellular surfactant as well as surfactant phospholipid metabolism in type II pneumocytes. Because protection against oxidant stress is important to normal lung function, the lung contains a variety of antioxidants, including vitamin E. Whether administration of this antioxidant during NO2 inhalation attenuates NO2 -induced alterations in phospholipid metabolism in type II pneumocytes has not been studied. Methods We exposed rats to identical NO2 body doses (720 p.p.m. x h) using continuous, intermittent, or repetitive protocols. During exposure periods, the animals received daily intramuscular injections of vitamin E (25 mg kg,1). We isolated type II pneumocytes from NO2 -exposed rats and evaluated them for cell yield and viability, as well as for synthesis and secretion of phosphatidylcholine (PC) as measures of surfactant metabolism. Results The yield of type II pneumocytes was significantly elevated from animals that had been exposed continuously to NO2 whereas in intermittently and repeatedly exposed rats, cell yield was similar to yield from control animals. Viability of the isolated cells was similar in controls and all NO2 exposure protocols. Vitamin E treatment of the NO2 -exposed rats neither changed cell yield nor cell viability. Phospholipid de novo synthesis, as estimated by choline incorporation into PC, was increased most after continuous NO2 inhalation whereas in the other conditions there was only a slight increase. Vitamin E administration further increased phospholipid synthesis; this difference reached statistical significance only in the case of intermittent NO2 exposure. Secretion of phosphatidylcholine from type II cells was only reduced after continuous NO2 inhalation and administration of the antioxidant reduced the impairment. Conclusion Because vitamin E appears to preserve the ability of type II pneumocytes isolated from NO2 -exposed rats to synthesize and secrete surfactant lipid, we conclude that administration of vitamin E may mitigate NO2 -induced lung injury. [source] Diffusion-tensor MR imaging for evaluation of the efficacy of hyperbaric oxygen therapy in patients with delayed neuropsychiatric syndrome caused by carbon monoxide inhalationEUROPEAN JOURNAL OF NEUROLOGY, Issue 7 2007C.-P. Lo The purpose of this study is to assess the efficacy of hyperbaric oxygen therapy (HBOT) in patients with delayed neuropsychiatric syndrome (DNS) caused by carbon monoxide (CO) inhalation using diffusion tensor magnetic resonance (MR) imaging and neuropsychological test. Conventional and diffusion tensor brain MR imaging exams were performed in six patients with DNS immediately before and 3 months after the HBOT to obtain fractional anisotropy (FA) values. Six age- and sex-matched normal control subjects also received MR exams for comparison. Mini-Mental State Examination (MMSE) was also performed in patients immediately before and 3 months after the HBOT. A significantly higher mean FA value was found in control subjects as compared with the patients both before and 3 months after the HBOT (P < 0.001). The mean FA value 3 months after the HBOT was also significantly higher than that before the HBOT in the patient group (P < 0.001). All of the patients regained full scores in the MMSE 3 months after the HBOT. Diffusion tensor MR imaging can be a quantitative method for the assessment of the white matter change and monitor the treatment response in patients of CO-induced DNS with a good clinical correlation. HBO may be an effective therapy for DNS. [source] Synergistic regulation of neuropeptide levels by internal and external stimuliEXPERIMENTAL DERMATOLOGY, Issue 9 2004J. Hosoi The skin is the most peripheral organ confronting the external environment. We found that the level of substance P is regulated by both internal and external stimuli. Mock interview induced the acute stress in human assessed by the measurement of serum cortisol. The serum level of substance P increased within 1 h after the mock interview. Interestingly, the increase was suppressed by inhalation of 1,3-dimethoxy-5-methylbenzene. Similar regulation was observed in mice. Furthermore, restraint or the intravenous administration of substance P induced the activation of cutaneous mast cells. Housing under the condition of lower humidity (about 30%) for 24 h caused the increase in the substance P level both in peripheral blood and in the skin. Restraint for 2 h during the housing under the condition of lower humidity increased the substance P level further. The activation of cutaneous mast cells under the dry condition was reported. These data suggest that cutaneous neuropeptide level is regulated by both psychological and environmental mechanisms. The regulation may cause the downregulation of the threshold of the induction of itch and inflammation. [source] The effect of temperature and ventilation condition on the toxic product yields from burning polymersFIRE AND MATERIALS, Issue 1 2008A. A. Stec Abstract A major cause of death or permanent injury in fires is inhalation of toxic gases. Moreover, every fire is unique, and the range of products, highly dependant on fire conditions, produces a wide variety of toxic and irritant species responsible for the most fire fatalities. Therefore, to fully understand each contribution to the toxicity it is necessary to quantify the decomposition products of the material under the test. Fires can be divided into a number of stages from smouldering combustion to early well-ventilated flaming through to fully developed under-ventilated flaming. These stages can be replicated by certain bench-scale physical fire models using different fuel-to-oxygen ratios, controlled by the primary air flow, and expressed in terms of the equivalence ratio (the actual fuel/air ratio divided by the stoichiometric fuel/air ratio). This work presents combustion product yields generated using a small-scale fire model. The Purser Furnace apparatus (BS7990 and ISO TS 19700) enables different fire stages to be created. Identification and quantification of combustion gases and particularly their toxic components from different fire scenarios were undertaken by continuous Fourier transform infrared spectroscopy. The relationship between type of the fire particularly the temperature and ventilation conditions and the toxic product yields for four bulk polymers, low-density polyethylene, polystyrene (PS), Nylon 6.6 and polyvinyl chloride (PVC) is reported. For all the polymers tested, except PVC, there is a dramatic increase in the yield of products of incomplete combustion (CO and hydrocarbons) with increase in equivalence ratio, as might be expected. For PVC there is a consistently high level of products of incomplete combustion arising both from flame inhibition by HCl and oxygen depletion. There is a low sensitivity to furnace temperature over the range 650,850°C, except that at 650°C PS shows an unexpectedly high yield of CO under well-ventilated conditions and PVC shows a slightly higher hydrocarbon yield. This demonstrates the dependence of toxic product yields on the equivalence ratio, and the lack of dependence on furnace temperature, within this range. Copyright © 2007 John Wiley & Sons, Ltd. [source] Cough after inhalation of corticosteroids delivered from spacer devices in children with asthmaFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2003Jean-Christophe Dubus Abstract Children using a spacer device rather than another device for delivering inhaled corticosteroids (ICS) has been identified as a risk factor for cough immediately after inhalation. The aim of this study was to point out the different factors influencing the occurrence of such lateral side-effects. We studied this local side-effect in 402 asthmatic children (55.6 ± 34.9 months; 65.6% boys) treated for at least 1 month with beclomethasone dipropionate (n = 331), budesonide (n = 47) or fluticasone propionate (n = 24) delivered from pressurized metered-dose inhalers and small (75.1%) or large volume (24.8%) spacer devices mainly used with face mask (90.7%). A total of 219 patients (54.5%), treated with either high doses of ICS or ICS and long-acting ,2-agonist, were considered as having severe asthma. Cough was reported after each inhalation of corticosteroids in 216 patients (53.7%). Among them, about 30% also complained of cough with ,2-agonists. Despite different propellants and dispersants, all corticosteroids induced cough similarly. Cough was not linked with asthma severity, but was significantly related to therapy duration and use of long-acting ,2-agonist. Type and volume of the spacer device, use of a face mask or mouthpiece were not influencing factors. Cough after inhalation of corticosteroids delivered from spacer devices is a frequent local side-effect in children with asthma. This side effect can greatly alter compliance. A practitioner must be sought at each visit. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||