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Sample records for carbogen inhalation increases

  1. Carbogen inhalation increases oxygen transport to hypoperfused brain tissue in patients with occlusive carotid artery disease: increased oxygen transport to hypoperfused brain

    DEFF Research Database (Denmark)

    Ashkanian, Mahmoud; Gjedde, Albert; Mouridsen, Kim;

    2009-01-01

    Sa(O2) are readily obtained with carbogen, while oxygen increases only Sa(O2). Thus, carbogen improves oxygen transport to brain tissue more efficiently than oxygen alone. Further studies with more subjects are, however, needed to investigate the applicability of carbogen for long-term inhalation and...

  2. Improvement of Brain Tissue Oxygenation by Inhalation of Carbogen

    DEFF Research Database (Denmark)

    Ashkanian, M.; Borghammer, P.; Gjedde, A.; Ostergaard, L.; Vafaee, M.

    2008-01-01

    confirmed by statistical cluster analysis. Oxygen and carbogen were equally potent in increasing oxygen saturation of arterial blood (Sa(O2)). The present data demonstrate that inhalation of carbogen increases both CBF and Sa(O2) in healthy adults. In conclusion we speculate that carbogen inhalation is...... sufficient for optimal oxygenation of healthy brain tissue, whereas carbogen induces concomitant increases of CBF and Sa(O2).......Hyperoxic therapy for cerebral ischemia is suspected to reduce cerebral blood flow (CBF), due to the vasoconstrictive effect of oxygen on cerebral arterioles. We hypothesized that vasodilation predominates when 5% CO(2) is added to the inhaled oxygen (carbogen). Therefore, we used positron emission...

  3. Effects of carbogen plus fractionated irradiation on KHT tumor oxygenation

    International Nuclear Information System (INIS)

    Background and purpose: Numerous studies have demonstrated improvements in the oxygenation of tumor cells following both irradiation and carbogen breathing. The current studies were initiated to measure the combined effects of carbogen inhalation plus single and multi-dose irradiation on tumor oxygen availability, to better define the underlying physiological relationships. Materials and methods: Using KHT murine sarcomas, radiation was delivered to the tumor-bearing legs of non-anesthetized mice. Tumors were quick-frozen prior to or following single or multifraction irradiation and carbogen breathing, and intravascular HbO2 saturation profiles were determined cryospectrophotometrically. Results: HbO2 levels for blood vessels located near the tumor surface initially decreased following 10 Gy irradiation, then increased and remained elevated. Interior HbO2 levels remained unchanged. Following 2.5 Gy, HbO2 changes were minimal. At 24 h following 10 Gy, HbO2 levels were significantly increased compared to non-irradiated controls, and carbogen breathing produced no additional benefit. At 24 h following five fractions of 2 Gy, HbO2 levels throughout the tumor volume were significantly higher in carbogen breathing animals than in air breathing controls. Conclusions: Although peripheral blood vessels demonstrated substantial improvements in oxygenation following irradiation, oxygen availability nearer the tumor center remained at very low levels. The utility of carbogen in enhancing tumor oxygen availability was maintained following five clinically relevant fractions. At higher doses, radiation-induced enhancements in HbO2 levels overshadowed the carbogen effect. For either air or carbogen breathing, a decrease in the percentage of vessels with very low oxygen content did not appear to be a major factor in the reoxygenation of the KHT tumor

  4. Mild hyperthermia alone or in combination with carbogen is effective in increasing tumor pO2

    International Nuclear Information System (INIS)

    Purpose/Objective: We have studied the effect of mild temperature hyperthermia (MTH) on pO2 with or without carbogen breathing and the radio response in three different rodent tumors. Materials and Methods: SCK mammary carcinoma of A/J mice, FSall fibrosarcoma of C3H mice, and R3230 AC mammary carcinoma of Fischer rats were used. The changes in pO2 in these tumors by MTH alone or in combination with carbogen (95% O2 + 5% CO2) breathing were studied. The MTH was done by immersing the legs bearing s.c. tumors into a water bath and the pO2 was measured using an Eppendorf pO2 Histograph machine. The influence of MTH on the effect of X-irradiation (250 kVp) on tumors was investigated with tumor growth delay and the in vivo-in vitro excision assay for hypoxic cell fraction. Results: The pO2 in all three tumor types was increased significantly by MTH. The most effective heating conditions were 60 min at 41.5 deg. C for SCK and FSall, and 30 min at 42.5 deg. C for R3230 AC. Carbogen breathing alone increased the pO2, but the effect of carbogen was dramatically enhanced when combined with heating. FSall tumors heated at 41.5 deg. C for 60 min before receiving a dose of 20 Gy took an average of 3 days longer than tumors receiving heat after irradiation to grow to four times their original volume. The identical conditions in SCK tumors heated before irradiation caused a 5 day growth delay. Effect of heating before or after irradiation on cell survival in tumor was determined using in vivo-in vitro excision assay method. Heating FSall tumors before irradiation for 30 min at 41.5 deg. C caused marked reduction in the hypoxic cell fraction. Cell survival studies in the SCK and R3230 AC tumors are currently being studied as well as the radiation response of all three tumors after heating combined with carbogen breathing. Conclusion: These results indicate that MTH is very effective in increasing the tumor oxygenation and the response of human tumors to radiotherapy. The

  5. Radiosensitivity of mouse lip mucosa: Influence of anesthesia, carbogen, and a new high O2 carrying perfluorochemical emulsion

    International Nuclear Information System (INIS)

    The effect of a new perfluorochemical emulsion based on F-66E (54%, w/v) which carries, in combination with carbogen, twice as much oxygen as Fluosol-DA 20% was tested on the radiation response of the lip mucosa of unanesthetized mice. Mice were pretreated with 0.015 ml/g of the F-66E emulsion in the presence of carbogen for 1 h prior to and during irradiation. There was a significant increase in the mortality rate following the highest radiation dose in mice given F-66E emulsion plus carbogen. The reactions of lip mucosa of mice given F-66E emulsion and/or carbogen were not significantly different from that of the control group using three end points (average score, mean peak, incidence of mucosal desquamation), but the peak mucosal reaction was delayed. The radiosensitivity of the mouse lip mucosa to Ethrane, an anesthetic gas inhaled with carbogen, was also tested. The reaction of lip mucosa in the anesthetized mice was significantly greater than that of the control group. There was also a significant increase in the mortality rate following the two highest radiation doses

  6. Inhaled histamine increases human lung mucociliary transport

    International Nuclear Information System (INIS)

    Histamine, a mediator of airways constriction, alters ciliary beat frequency, bronchial mucus production, and epithelial ion transport; and in dogs, increases mucociliary transport. To evaluate the effect of inhaled histamine on human tracheobronchial mucociliary clearance, the authors measured lung mucociliary clearance (LMC) and tracheal mucociliary transport rate (TMTR) in 5 healthy, nonsmoking subjects in a randomized, double-blind, cross-over study. The concentration of inhaled histamine which produced a 20% fall in FEV1 was established for each subject. On a separate day the subjects inhaled a 9 μm MMAD /sup 99m/Tc-Fe2O3 aerosol. LMC and TMTR were then measured for 2.5h using a gamma camera and a tracheal multidetector probe. Simultaneously, the subjects were challenged every 26 +/- 4 min with either PBS or histamine in PBS. The Fe2O3 retained after 24h for histamine (14.4 +/- 7.6%) and PBS studies (13.1 +/- 8.6%) indicated no difference in deposition of Fe2O3 (ANOVA). Fe2O3 clearance at 30 min was increased in the histamine studies (61 +/- 21% compared to the PBS studies (44 +/- 29%; p < 0.02, ANOVA)). TMTR was also increased with histamine (7.6 +/- 3.4 mm/min) compared to PBS (4.6 +/- 1.7 mm/min; p < 0.001, ANOVA). Results indicate an acute stimulatory effect of inhaled histamine on mucous transport in humans

  7. Response of Hepatoma 9618a and Normal Liver to Host Carbogen and Carbon Monoxide Breathing

    OpenAIRE

    Robinson, Simon P.; Loreta M. Rodrigues; Griffiths, John R.; Marion Stubbs

    1999-01-01

    The effects of hyperoxia (induced by host carbogen 95% oxygen/5% carbon dioxide breathing. and hypoxia (induced by host carbon monoxide CO at 660 ppm. breathing) were compared by using noninvasive magnetic resonance (MR) methods to gain simultaneous information on blood flow/oxygenation and the bioenergetic status of rat Morris H9618a hepatomas. Both carbogen and CO breathing induced a 1.5- to 2-fold increase in signal intensity in blood oxygenation level dependent (BOLD) MR images. This was ...

  8. Effects of hyperbaric oxygen and normobaric carbogen on the radiation response of the rat rhabdomyosarcoma R1H

    International Nuclear Information System (INIS)

    Purpose: Hypoxic tumor cells are an important factor of radioresistance. Hyperbaric oxygen (HBO) and normobaric carbogen (95% oxygen, 5% carbon dioxide) increase the oxygen delivery to tumors. This study was performed to explore changes of tumor oxygenation during a course of fractionated irradiation and to determine the effectiveness of normobaric carbogen and HBO during the final phase of the radiation treatment. Methods and Materials: Experiments were performed on the rhabdomyosarcoma R1H growing on WAG/Rij rats. After 20 X-ray fractions of 2 Gy within 4 weeks, oxygen partial pressure (pO2) was measured using the Eppendorf oxygen electrode under ambient conditions, with normobaric carbogen or HBO at a pressure of 240 kPa. Following the 4-week radiation course, a top-up dose of 10-50 Gy was applied in 2-10 fractions of 5 Gy with or without hyperoxygenation. Results: HBO but not carbogen significantly increased the median pO2 in irradiated tumors. The radiation doses to control 50% of tumors were 38.0 Gy, 29.5 Gy, and 25.0 Gy for air, carbogen, and HBO, respectively. Both high oxygen content gas inspirations led to significantly improved tumor responses with oxygen enhancement ratios (OERs) of 1.3 for normobaric carbogen and 1.5 for HBO (air vs. carbogen: p=0.044; air vs. HBO: p=0.02; carbogen vs. HBO: p=0.048). Conclusion: Both normobaric carbogen and HBO significantly improved the radiation response of R1H tumors. HBO appeared to be more effective than normobaric carbogen, both with regard to tumor oxygenation and response to irradiation

  9. Response of Hepatoma 9618a and Normal Liver to Host Carbogen and Carbon Monoxide Breathing

    Directory of Open Access Journals (Sweden)

    Simon P. Robinson

    1999-12-01

    Full Text Available The effects of hyperoxia (induced by host carbogen 95% oxygen/5% carbon dioxide breathing. and hypoxia (induced by host carbon monoxide CO at 660 ppm. breathing were compared by using noninvasive magnetic resonance (MR methods to gain simultaneous information on blood flow/oxygenation and the bioenergetic status of rat Morris H9618a hepatomas. Both carbogen and CO breathing induced a 1.5- to 2-fold increase in signal intensity in blood oxygenation level dependent (BOLD MR images. This was due to a decrease in deoxyhemoglobin (deoxyHb, which acts as an endogenous contrast agent, caused either by formation of oxyhemoglobin in the case of carbogen breathing, or carboxyhemoglobin with CO breathing. The results were confirmed by observation of similar changes in deoxyHb in arterial blood samples examined ex vivo after carbogen or CO breathing. There was no change in nucleoside triphosphates (NTP/PI in either tumor or liver after CO breathing, whereas NTP/Pl increased twofold in the hepatoma (but not in the liver after carbogen breathing. No changes in tumor intracellular pH were seen after either treatment, whereas extracellular pH became more alkaline after CO breathing and more acid after carbogen breathing, respectively. This tumor type and the liver are unaffected by CO breathing at 660 ppm, which implies an adequate oxygen supply.

  10. Radiotherapy with carbogen breathing and nicotinamide in head and neck cancer: feasibility and toxicity

    International Nuclear Information System (INIS)

    The feasibility and early toxicity of radiotherapy with carbogen breathing and nicotinamide was tested in 74 head and neck cancer patients. Forty patients with laryngeal and hypopharyngeal tumors were treated with an accelerated schedule combined with carbogen alone (16) or with carbogen and nicotinamide (24). Thirty-four patients with far advanced unresectable tumors of the oral cavity and oropharynx received conventional radiotherapy with carbogen [16] or with carbogen and nicotinamide (18). Some enhancement of skin reaction was observed with nicotinamide but this remained well within limits of tolerance. With the accelerated regimen there was increased severity of mucosal damage expressed as confluent mucositis in 95% of patients which required healing times of 3-4 months in four patients. Eventually restoration of the mucosal lining was complete in all cases. Nausea and vomiting are the most frequent side effects of nicotinamide and were reported by 60% and 36% of the subjects, respectively. In 26% this was reason to discontinue drug intake. Severe renal dysfunction was associated with nicotinamide intake in two patients of this study and in one other patient who presented later. It is our conclusion that radiotherapy combined with carbogen and nicotinamide is a safe treatment with manageable side effects. We recommend not to give nicotinamide concomitantly with nephrotoxic medication or to patients who have impaired renal function. Preliminary tumor control rates are encouraging and clinical testing will be continued

  11. Blood oxygenation level-dependent magnetic resonance imaging during carbogen breathing: differentiation between prostate cancer and benign prostate hyperplasia and correlation with vessel maturity

    Science.gov (United States)

    Di, Ningning; Mao, Ning; Cheng, Wenna; Pang, Haopeng; Ren, Yan; Wang, Ning; Liu, Xinjiang; Wang, Bin

    2016-01-01

    Objective The aim of this study was to investigate whether the blood oxygenation level-dependent (BOLD) contrast magnetic resonance imaging (MRI) can evaluate tumor maturity and preoperatively differentiate prostate cancer (PCa) from benign prostate hyperplasia (BPH). Patients and methods BOLD MRI based on transverse relaxation time*-weighted echo planar imaging was performed to assess PCa (19) and BPH (22) responses to carbogen (95% O2 and 5% CO2). The average signal values of PCa and BPH before and after carbogen breathing and the relative increased signal values were computed, respectively. The endothelial-cell marker, CD31, and the pericyte marker, α-smooth muscle actin (mature vessels), were detected with immunofluorescence, and were assessed by microvessel density (MVD) and microvessel pericyte density (MPD). The microvessel pericyte coverage index (MPI) was used to evaluate the degree of vascular maturity. The changed signal from BOLD MRI was correlated with MVD, MPD, and MPI. Results After inhaling carbogen, both PCa and BPH showed an increased signal, but a lower slope was found in PCa than that in BPH (PMPI than BPH. The increased signal intensity was positively correlated with MPI in PCa and that in BPH (r=0.616, P=0.011; r=0.658, P=0.002); however, there was no correlation between the increased signal intensity and MPD or MVD in PCa than that in BPH (P>0.05). Conclusion Our results confirmed that the increased signal values induced by BOLD MRI well differentiated PCa from BPH and had a positive correlation with vessel maturity in both of them. BOLD MRI can be utilized as a surrogate marker for the noninvasive assessment of the degree of vessel maturity. PMID:27462169

  12. Radiosensitisation in normal tissues with oxygen, carbogen or nicotinamide: therapeutic gain comparisons for fractionated x-ray schedules

    International Nuclear Information System (INIS)

    Methods: Radiosensitisation with oxygen, carbogen or nicotinamide alone and oxygen or carbogen combined with nicotinamide was compared in early and late responding normal tissues in rodents. X-ray treatments were delivered as single doses or fractionated schedules of 2 fractions in 1 day, 2, 12 and 36 fractions in an overall time of 12 days and 10 fractions in 5 or 12 days. Acute skin reactions, survival of intestinal crypts, breathing rate, reduction in the packed red-cell volume and clearance of 51Cr-EDTA were used as assays of epidermal, gut, lung and renal damage. Results: Relative to air-breathing mice, carbogen or oxygen produced a small, and not always significant, increase in sensitivity (enhancement ratios ≤ 1.15) in gut, lung and kidneys; however, in skin a dose enhancement of 1.2-1.3 was observed. The effect of nicotinamide in air, carbogen or oxygen was studied only in lung and gut. The drug produced variable but generally significant increases in radiosensitisation (≤ 1.26) in all three gases. Relative to treatments in air, enhancement ratios for nicotinamide alone were usually slightly higher than those observed when either carbogen or oxygen were administered without the drug. With all three modifiers (i.e. oxygen, carbogen, nicotinamide alone or for the drug-gas combinations) there was no significant change in the enhancement ratios observed as the number of radiation dose fractions was varied. Conclusions: Comparisons with fractionated X-ray studies done previously in rodent tumours indicate that a therapeutic benefit, relative to lung, gut and renal damage, would be observed with oxygen or carbogen alone but not with nicotinamide alone. The greatest gain would be achieved with the combination of carbogen and nicotinamide, with which a benefit was observed even relative to epidermal damage. These results indicate that some decrease in normal tissue tolerance could be observed when using these modifiers in clinical radiotherapy and, although

  13. Formation Mechanism of Carbogenic Nanoparticles with Dual Photoluminescence Emission

    KAUST Repository

    Krysmann, Marta J.

    2012-01-18

    We present a systematic investigation of the formation mechanism of carbogenic nanoparticles (CNPs), otherwise referred to as C-dots, by following the pyrolysis of citric acid (CA)-ethanolamine (EA) precursor at different temperatures. Pyrolysis at 180 °C leads to a CNP molecular precursor with a strongly intense photoluminescence (PL) spectrum and high quantum yield formed by dehydration of CA-EA. At higher temperatures (230 °C) a carbogenic core starts forming and the PL is due to the presence of both molecular fluorophores and the carbogenic core. CNPs that exhibit mostly or exclusively PL arising from carbogenic cores are obtained at even higher temperatures (300 and 400 °C, respectively). Since the molecular fluorophores predominate at low pyrolysis temperatures while the carbogenic core starts forming at higher temperatures, the PL behavior of CNPs strongly depends on the conditions used for their synthesis. © 2011 American Chemical Society.

  14. Addition of a hypoxic cell selective cytotoxic agent (mitomycin C or porfiromycin) to Fluosol-DA/carbogen/radiation

    Energy Technology Data Exchange (ETDEWEB)

    Holden, S.A.; Teicher, B.A. (Dana-Farber Cancer Institute, Boston (USA)); Herman, T.S. (Dana-Farber Cancer Institute, Boston (USA) Joint Center for Radiation Therapy, Boston (USA))

    1990-05-01

    In an effort to develop effictive combination treatments for use with radiation against solid tumors, the cytotoxic effects of the addition of mitomycin C or porfiromycin on treatment with Fluosol-DA/carbogen breathing and radiation in the FSaIIC tumor system were studied. In vitro mitomycin C and porfiromycin were both preferentially cytotoxic toward hypoxic FSaIIC cells. After in vivo exposure, however, the cytotoxicity of mitomycin C toward single cell tumor suspensions obtained from whole tumors was exponential over the dose range studied, but for porfiromycin a plateau in cell killing was observed. With Fluosol-DA/carbogen breathing and single dose radiaiton, addition of either mitomycin C or porfiromycin increased the tumor cell kill achieved at 5 Gy by approximately 1.2 and 1.0 logs, respectively. Less effect was seen with addition of the drugs at the 10 and 15 Gy radiation doses. In tumor growth delay experiments, the addition of either mitomycin C or porfiromycin to Fluosol-DA/carbogen breathing and radiation resulted in primarily an additive increase in tumor growth delay. The survival of Hoechst 33342 dye-selected tumor cell subpopulations indicated that Fluosol-DA/carbogen breathing increased the cytotoxicity of radiation (10 Gy) more in the bright cell subpopulation (4-fold) than in the dim cell subpopulation (2-fold) resulting in an overall 4-fold sparing of the dim subpopulation. Mitomycin C and porfiromycin were both more toxic toward the dim cell subpopulations. Addition of mitomycin C or porfiromycin to Fluosol-DA/carbogen breathing and radiation (10 Gy) resulted in a primarily additive effect of the drugs and radiation killing in both tumor cell subpopulations. Thus, with mitomycin C/Fluosol-DA/carbogen and radiation there was a 2-fold sparing of dim cells and with profiromycin in the combined treatment a 1.6-fold sparing of the dim cell population. (Abstract Truncated)

  15. Inhalants

    Science.gov (United States)

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

  16. Inhalants

    Science.gov (United States)

    ... Listen Drug Facts Alcohol Anabolic Steroids Bath Salts Cocaine Cough and Cold Medicine (DXM and Codeine Syrup) Heroin Inhalants Marijuana MDMA (Ecstasy or Molly) Methamphetamine (Meth) Prescription Drugs Salvia Spice Brain and Addiction Tobacco, Nicotine, & E-Cigarettes HIV/AIDS ...

  17. Potential role of hypoxia imaging using 18F-FAZA PET to guide hypoxia-driven interventions (carbogen breathing or dose escalation) in radiation therapy

    International Nuclear Information System (INIS)

    Background and purpose: Hypoxia-driven intervention (oxygen manipulation or dose escalation) could overcome radiation resistance linked to tumor hypoxia. Here, we evaluated the value of hypoxia imaging using 18F-FAZA PET to predict the outcome and guide hypoxia-driven interventions. Material and methods: Two hypoxic rat tumor models were used: rhabdomyosarcoma and 9L-glioma. For the irradiated groups, the animals were divided into two subgroups: breathing either room air or carbogen. 18F-FAZA PET images were obtained just before the irradiation to monitor the hypoxic level of each tumor. Absolute pO2 were also measured using EPR oximetry. Dose escalation was used in Rhabdomyosarcomas. Results: For 9L-gliomas, a significant correlation between 18F-FAZA T/B ratio and tumor growth delay was found; additionally, carbogen breathing dramatically improved the tumor response to irradiation. On the contrary, Rhabdomyosarcomas were less responsive to hyperoxic challenge. For that model, an increase in growth delay was observed using dose escalation, but not when combining irradiation with carbogen. Conclusions: 18F-FAZA uptake may be prognostic of outcome following radiotherapy and could assess the response of tumor to carbogen breathing. 18F-FAZA PET may help to guide the hypoxia-driven intervention with irradiation: carbogen breathing in responsive tumors or dose escalation in tumors non-responsive to carbogen

  18. Perfusion changes in the RIF-1 tumour and normal tissues after carbogen and nicotinamide, individually and combined.

    OpenAIRE

    Honess, D. J.; Bleehen, N.M.

    1995-01-01

    The strategy of combining carbogen breathing and nicotinamide to overcome chronic and acute hypoxia respectively is being evaluated clinically. The effects of both agents individually and in combination on relative perfusion of 400-700 mm3 RIF-1 tumours and normal tissues were measured by 86Rb extraction. Carbogen breathing alone for 6 min increased relative tumour perfusion by 50-70% compared with control at flow rates of 50 to 200 ml min-1, but the effect was lost at 300 ml min-1. All flow ...

  19. Ozone increases susceptibility to antigen inhalation in allergic dogs

    Energy Technology Data Exchange (ETDEWEB)

    Yanai, M.; Ohrui, T.; Aikawa, T.; Okayama, H.; Sekizawa, K.; Maeyama, K.; Sasaki, H.; Takishima, T. (Tohoku Univ., Sendai (Japan))

    1990-06-01

    To determine whether O3 exposure increased airway responsiveness to antigen inhalation, we studied airway responsiveness to acetylcholine (ACh) and Ascaris suum antigen (AA) before and after O3 in dogs both sensitive and insensitive to AA. Airway responsiveness was assessed by determining the provocative concentration of ACh and AA aerosols that increased respiratory resistance (Rrs) to twice the base-line value. O3 (3 parts per million) increased airway responsiveness to ACh in dogs both sensitive and insensitive to AA, and it significantly decreased the ACh provocation concentration from 0.541 +/- 0.095 to 0.102 +/- 0.047 (SE) mg/ml (P less than 0.01; n = 10). AA aerosols, even at the highest concentration in combination with O3, did not increase Rrs in dogs insensitive to AA. However, O3 increased airway responsiveness to AA in AA-sensitive dogs and significantly decreased log AA provocation concentration from 2.34 +/- 0.22 to 0.50 +/- 0.17 (SE) log protein nitrogen units/ml (P less than 0.01; n = 7). O3-induced hyperresponsiveness to ACh returned to the base-line level within 2 wk, but hyperresponsiveness to AA continued for greater than 2 wk. The plasma histamine concentration after AA challenge was significantly higher after than before O3 (P less than 0.01). Intravenous infusion of OKY-046 (100 micrograms.kg-1.min-1), an inhibitor of thromboxane synthesis, inhibited the O3-induced increase in responsiveness to ACh, but it had no effects on the O3-induced increase in responsiveness to AA and the increase in the plasma histamine concentration. These results suggest that O3 increases susceptibility to the antigen in sensitized dogs via a different mechanism from that of O3-induced muscarinic hyperresponsiveness.

  20. Photoluminescent carbogenic nanoparticles directly derived from crude biomass

    KAUST Repository

    Krysmann, Marta J.

    2012-01-01

    We present an environmentally benign, energy efficient and readily scalable approach to synthesize photoluminescent carbogenic nanoparticles directly from soft tissue biomass. Our approach relies on the pyrolytic decomposition of grass that gives rise to the formation of well-defined nanoparticles. The carbogenic nanoparticles can be readily surface modified, generating a series of highly selective photoluminescent materials that exhibit remarkable stability upon prolonged exposure to aggressive, high-temperature, high-salinity environment. © 2012 The Royal Society of Chemistry.

  1. Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction

    International Nuclear Information System (INIS)

    We hypothesized that circulating microparticles (MPs) play a role in pro-inflammatory effects associated with carbon monoxide (CO) inhalation. Mice exposed for 1 h to 100 ppm CO or more exhibit increases in circulating MPs derived from a variety of vascular cells as well as neutrophil activation. Tissue injury was quantified as 2000 kDa dextran leakage from vessels and as neutrophil sequestration in the brain and skeletal muscle; and central nervous system nerve dysfunction was documented as broadening of the neurohypophysial action potential (AP). Indices of injury occurred following exposures to 1000 ppm for 1 h or to 1000 ppm for 40 min followed by 3000 ppm for 20 min. MPs were implicated in causing injuries because infusing the surfactant MP lytic agent, polyethylene glycol telomere B (PEGtB) abrogated elevations in MPs, vascular leak, neutrophil sequestration and AP prolongation. These manifestations of tissue injury also did not occur in mice lacking myeloperoxidase. Vascular leakage and AP prolongation were produced in naïve mice infused with MPs that had been obtained from CO poisoned mice, but this did not occur with MPs obtained from control mice. We conclude that CO poisoning triggers elevations of MPs that activate neutrophils which subsequently cause tissue injuries. - Highlights: • Circulating microparticles (MPs) increase in mice exposed to 100 ppm CO or more. • MPs are lysed by infusing the surfactant polyethylene glycol telomere B. • CO-induced MPs cause neutrophil activation, vascular leak and CNS dysfunction. • Similar tissue injuries do not arise with MPs obtained from air-exposed, control mice

  2. Carbogen Breathing Differentially Enhances Blood Plasma Volume and 5-Fluorouracil Uptake in Two Murine Colon Tumor Models with a Distinct Vascular Structure

    Directory of Open Access Journals (Sweden)

    Hanneke W.M. van Laarhoven

    2006-06-01

    Full Text Available For the systemic treatment of colorectal cancer, 5-fluorouracil (FU-based chemotherapy is the standard. However, only a subset of patients responds to chemotherapy. Breathing of carbogen (95% O2 and 5% CO2 may increase the uptake of FU through changes in tumor physiology. This study aims to monitor in animal models in vivo the effects of carbogen breathing on tumor blood plasma volume, pH, and energy status, and on FU uptake and metabolism in two colon tumor models C38 and C26a, which differ in their vascular structure and hypoxic status. Phosphorus-31 magnetic resonance spectroscopy (MRS was used to assess tumor pH and energy status, and fluorine-19 MRS was used to follow FU uptake and metabolism. Advanced magnetic resonance imaging methods using ultrasmall particles of iron oxide were performed to assess blood plasma volume. The results showed that carbogen breathing significantly decreased extracellular pH and increased tumor blood plasma volume and FU uptake in tumors. These effects were most significant in the C38 tumor line, which has the largest relative vascular area. In the C26a tumor line, carbogen breathing increased tumor growth delay by FU. In this study, carbogen breathing also enhanced systemic toxicity by FU.

  3. Addition of a hypoxic cell selective cytotoxic agent (mitomycin C or porfiromycin) to Fluosol-DA/carbogen/radiation.

    Science.gov (United States)

    Holden, S A; Herman, T S; Teicher, B A

    1990-05-01

    In an effort to develop effective combination treatments for use with radiation against solid tumors, the cytotoxic effects of the addition of mitomycin C or porfiromycin on treatment with Fluosol-DA/carbogen (95% O2/5% CO2) breathing and radiation in the FSaIIC tumor system were studied. In vitro mitomycin C and porfiromycin were both preferentially cytotoxic toward hypoxic FSaIIC cells. After in vivo exposure, however, the cytotoxicity of mitomycin C toward single cell tumor suspensions obtained from whole tumors was exponential over the dose range studied, but for porfiromycin a plateau in cell killing was observed. With Fluosol-DA/carbogen breathing and single dose radiation, addition of either mitomycin C or porfiromycin increased the tumor cell kill achieved at 5 Gy by approximately 1.2 and 1.0 logs, respectively. Less effect was seen with addition of the drugs at the 10 and 15 Gy radiation doses. In tumor growth delay experiments, the addition of either mitomycin C or porfiromycin to Fluosol-DA/carbogen breathing and radiation resulted in primarily an additive increase in tumor growth delay. The survival of Hoechst 33342 dye-selected tumor cell subpopulations indicated that Fluosol-DA/carbogen breathing increased the cytotoxicity of radiation (10 Gy) more in the bright cell subpopulation (4-fold) than in the dim cell subpopulation (2-fold) resulting in an overall 4-fold sparing of the dim subpopulation. Mitomycin C and porfiromycin were both more toxic toward the dim cell subpopulations. Addition of mitomycin C or porfiromycin to Fluosol-DA/carbogen breathing and radiation (10 Gy) resulted in a primarily additive effect of the drugs and radiation killing in both tumor cell subpopulations. Thus, with mitomycin C/Fluosol-DA/carbogen and radiation there was a 2-fold sparing of dim cells and with porfiromycin in the combined treatment a 1.6-fold sparing of the dim cell population. Our results indicate that treatment strategies directed against both oxic and

  4. Evaluation and Immunohistochemical Qualification of Carbogen-Induced ΔR{sub 2}* as a Noninvasive Imaging Biomarker of Improved Tumor Oxygenation

    Energy Technology Data Exchange (ETDEWEB)

    Baker, Lauren C.J., E-mail: lauren.baker@icr.ac.uk [Cancer Research UK and EPSRC Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey (United Kingdom); Boult, Jessica K.R.; Jamin, Yann; Gilmour, Lesley D.; Walker-Samuel, Simon; Burrell, Jake S. [Cancer Research UK and EPSRC Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey (United Kingdom); Ashcroft, Margaret [Division of Medicine, Centre for Cell Signalling and Molecular Genetics, University College London, London (United Kingdom); Howe, Franklyn A. [St. George' s, University of London, London (United Kingdom); Griffiths, John R. [Cancer Research UK Cambridge Institute, Cambridge (United Kingdom); Raleigh, James A. [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); Kogel, Albert J. van der [University of Nijmegen Medical Centre, Nijmegen (Netherlands); Robinson, Simon P. [Cancer Research UK and EPSRC Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey (United Kingdom)

    2013-09-01

    Purpose: To evaluate and histologically qualify carbogen-induced ΔR{sub 2}* as a noninvasive magnetic resonance imaging biomarker of improved tumor oxygenation using a double 2-nitroimidazole hypoxia marker approach. Methods and Materials: Multigradient echo images were acquired from mice bearing GH3 prolactinomas, preadministered with the hypoxia marker CCI-103F, to quantify tumor R{sub 2}* during air breathing. With the mouse remaining positioned within the magnet bore, the gas supply was switched to carbogen (95% O{sub 2}, 5% CO{sub 2}), during which a second hypoxia marker, pimonidazole, was administered via an intraperitoneal line, and an additional set of identical multigradient echo images acquired to quantify any changes in tumor R{sub 2}*. Hypoxic fraction was quantified histologically using immunofluorescence detection of CCI-103F and pimonidazole adduct formation from the same whole tumor section. Carbogen-induced changes in tumor pO{sub 2} were further validated using the Oxylite fiberoptic probe. Results: Carbogen challenge significantly reduced mean tumor R{sub 2}* from 116 ± 13 s{sup −1} to 97 ± 9 s{sup −1} (P<.05). This was associated with a significantly lower pimonidazole adduct area (2.3 ± 1%), compared with CCI-103F (6.3 ± 2%) (P<.05). A significant correlation was observed between ΔR{sub 2}* and Δhypoxic fraction (r=0.55, P<.01). Mean tumor pO{sub 2} during carbogen breathing significantly increased from 6.3 ± 2.2 mm Hg to 36.0 ± 7.5 mm Hg (P<.01). Conclusions: The combined use of intrinsic susceptibility magnetic resonance imaging with a double hypoxia marker approach corroborates carbogen-induced ΔR{sub 2}* as a noninvasive imaging biomarker of increased tumor oxygenation.

  5. Increased bioprotein production in rats with tumors induced by radon inhalation and benzonaphtoflavone administration

    International Nuclear Information System (INIS)

    Serial determinations of urinary biopterin were performed in rats during the development of lung tumors induced by radon inhalation and 5,6-benzonaphtoflavone administration. A striking increase in biopterin levels was observed in animals which developed single or multiple epidermoid carcinoma of the lung and this increase occurred several weeks before tumors could be detected radiographically. (author)

  6. Fractionated irradiation combined with carbogen breathing and nicotinamide of two human glioblastomas grafted in nude mice

    OpenAIRE

    SUN, Lin-Quan; Buchegger, Franz; COUCKE, Philippe; MIRIMANOFF

    2001-01-01

    This study addressed the potential radiosensitizing effect of nicotinamide and/or carbogen on human glioblastoma xenografts in nude mice. U-87MG and LN-Z308 tumors were irradiated with either 20 fractions over 12 days or 5 fractions over 5 days in air-breathing mice, mice injected with nicotinamide, mice breathing carbogen, or mice receiving nicotinamide plus carbogen. The responses to treatment were assessed using local control and moist desquamation. In U-87MG tumors, the enhancement ratios...

  7. 5% CO2 is a potent, fast acting inhalation anticonvulsant

    Science.gov (United States)

    Tolner, Else A.; Hochman, Daryl W.; Hassinen, Pekka; Otáhal, Jakub; Gaily, Eija; Haglund, Michael M.; Kubová, Hana; Schuchmann, Sebastian; Vanhatalo, Sampsa; Kaila, Kai

    2010-01-01

    Purpose CO2 has been long recognized for its anticonvulsant properties. We aimed to determine whether inhaling 5% CO2 can be used to suppress seizures in epilepsy patients. The effect of CO2 on cortical epileptic activity accompanying behavioral seizures was studied in rats and a non-human primate and based on these data, preliminary tests were carried out in humans. Methods In freely moving rats, cortical afterdischarges paralleled by myoclonic convulsions were evoked by sensorimotor cortex stimulation. 5% CO2 was applied for 5 minutes, 3 minutes before stimulation. In macaque monkeys, hypercarbia was induced by hypoventilation while seizure activity was electrically or chemically evoked in the sensorimotor cortex. Seven patients with drug-resistant partial epilepsy were examined with video-EEG and received 5% CO2 in medical carbogen shortly after electrographic seizure onset. Results In rats, 5% CO2 strongly suppressed cortical afterdischarges, by ca. 75%, while responses to single-pulse stimulation were reduced by about 15% only. In macaques, increasing pCO2 from 37 to 44-45 mmHg (corresponding to inhalation of 5% CO2 or less) suppressed stimulation-induced cortical afterdischarges by about 70% and single, bicuculline-induced epileptiform spikes by ca. 25%. In a pilot trial carried out in 7 patients, a rapid termination of electrographic seizures was seen despite the fact that the application of 5% CO2 was started after seizure generalization. Conclusions 5% CO2 has a fast and potent anticonvulsant action. The present data suggest that medical carbogen with 5% CO2 can be used for acute treatment to suppress seizures in epilepsy patients. PMID:20887367

  8. From dust to dose: Effects of forest disturbance on increased inhalation exposure

    International Nuclear Information System (INIS)

    Ecosystem disturbances that remove vegetation and disturb surface soils are major causes of excessive soil erosion and can result in accelerated transport of soils contaminated with hazardous materials. Accelerated wind erosion in disturbed lands that are contaminated is of particular concern because of potential increased inhalation exposure, yet measurements regarding these relationships are lacking. The importance of this was highlighted when, in May of 2000, the Cerro Grande fire burned over roughly 30% of Los Alamos National Laboratory (LANL), mostly in ponderosa pine (Pinus ponderosa) forest, and through areas with soils containing contaminants, particularly excess depleted and natural uranium. Additionally, post-fire thinning was performed in burned and unburned forests on about 25% of LANL land. The first goal of this study was to assess the potential for increased inhalation dose from uranium contaminated soils via wind-driven resuspension of soil following the Cerro Grande Fire and subsequent forest thinning. This was done through analysis of post-disturbance measurements of uranium air concentrations and their relationships with wind velocity and seasonal vegetation cover. We found a 14% average increase in uranium air concentrations at LANL perimeter locations after the fire, and the greatest air concentrations occurred during the months of April-June when wind velocities are highest, no snow cover, and low vegetation cover. The second goal was to develop a methodology to assess the relative contribution of each disturbance type towards increasing public and worker exposure to these resuspended soils. Measurements of wind-driven dust flux in severely burned, moderately burned, thinned, and unburned/unthinned forest areas were used to assess horizontal dust flux (HDF) in these areas. Using empirically derived relationships between measurements of HDF and respirible dust, coupled with onsite uranium soil concentrations, we estimate relative increases in

  9. Thoron and its decay products: consequences of increased indoor concentrations for inhalation dosimetry

    International Nuclear Information System (INIS)

    Recently, increased concentrations of 220Rn (thoron) and its progeny were measured in traditional residential dwellings in China, India and other countries and gave rise to a reconsideration of their contribution to inhalation dose. A complete assessment of the lung dose is performed, whereas thoron gas and 216Po contribute the least. The effective and organ equivalent doses of the progeny 212Pb and 212Bi in the lungs and in other organs were calculated as a function of activity median diameters in the range 1-10,000 nm, applying the human respiratory tract model and the biokinetic models developed by the ICRP. Taking into account the unattached fraction of 0.03 and a size of 1.5 nm for unattached particles and of 300 nm for attached particles in the indoor air, the dose conversion coefficient was estimated to be 3.8 mSv WLM-1, about 27.5% of the values of 13.8 mSv WLM-1 for 222Rn. This study provides the dose conversion coefficient for thoron decay products. It can be used to assess the inhalation dose for dwellers in areas with a higher thoron concentration

  10. Study on fluorescence properties of carbogenic nanoparticles and their application for the determination of ferrous succinate

    Energy Technology Data Exchange (ETDEWEB)

    Sun Wen [Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009 (China); Du Yingxiang, E-mail: du_yingxiang@126.co [Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009 (China) and Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009 (China) and Key Laboratory of Modern Chinese Medicines, Ministry of Education, China Pharmaceutical University, Nanjing 210009 (China); Wang Yunqing [Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003 (China)

    2010-08-15

    A new type of fluorescent nanomaterial named carbogenic nanoparticles (NPs) has drawn considerable attention recently. In this study, we adopted a direct and simple synthetic method to produce the carbogenic NPs and investigated the fluorescence properties of the as-prepared carbogenic NPs in detail. It was found that the fluorescence of carbogenic NPs was stable with the variance of environmental conditions such as pH, temperature and UV irradiation. More interestingly, we found carbogenic NPs exhibited high selectivity and sensitivity towards ferric ions. Under optimum conditions, a good linear relationship could be obtained between the fluorescence intensity and concentration of ferric ions in the range of 5.0x10{sup -5}-5.0x10{sup -4} mol L{sup -1}, and the limit of detection is 11.2 {mu}mol L{sup -1}. Based on the fluorescence quenching of carbogenic NPs, a rapid and specific quantitative method was proposed for the determination of ferrous succinate. The content of ferrous succinate in commercial tablets determined by the present method was agreed with the spectrophotometric method results and the reproducibility and the recovery of the proposed method were satisfactory.

  11. Study on fluorescence properties of carbogenic nanoparticles and their application for the determination of ferrous succinate

    International Nuclear Information System (INIS)

    A new type of fluorescent nanomaterial named carbogenic nanoparticles (NPs) has drawn considerable attention recently. In this study, we adopted a direct and simple synthetic method to produce the carbogenic NPs and investigated the fluorescence properties of the as-prepared carbogenic NPs in detail. It was found that the fluorescence of carbogenic NPs was stable with the variance of environmental conditions such as pH, temperature and UV irradiation. More interestingly, we found carbogenic NPs exhibited high selectivity and sensitivity towards ferric ions. Under optimum conditions, a good linear relationship could be obtained between the fluorescence intensity and concentration of ferric ions in the range of 5.0x10-5-5.0x10-4 mol L-1, and the limit of detection is 11.2 μmol L-1. Based on the fluorescence quenching of carbogenic NPs, a rapid and specific quantitative method was proposed for the determination of ferrous succinate. The content of ferrous succinate in commercial tablets determined by the present method was agreed with the spectrophotometric method results and the reproducibility and the recovery of the proposed method were satisfactory.

  12. Transient perfusion and radiosensitizing effect after nicotinamide, carbogen, and perflubron emulsion administration

    International Nuclear Information System (INIS)

    In order to improve the effect of radiation on tumour response, nicotinamide, perflubron emulsion and carbogen were administered which act on both diffusion limited hypoxia and intermittent perfusion limited hypoxia. These treatments were used in different combinations. The maximal radiosensitizing effect was found with the combination of the three treatments. The aim of this study was to use a double staining method (Hoechst 33342 and DiOC7(3)) to evaluate the influence of nicotinamide, perflubron emulsion and carbogen on transient perfusion in three tumour cell lines transplanted onto nude mice: one rodent (EMT6), two human (HRT18, a rectal adenocarcinoma; and Na11+, a melanoma). For untreated groups, the percentage of closed and mismatched vessels depended on the tumour cell line. Carbogen alone or carbogen plus perflubron emulsion decreased the number of mismatched and closed vessels only for the two human cell lines. Nicotinamide was effective in decreasing the percentage of mismatched and closed vessels only for the melanoma cell line. The combination of nicotinamide, carbogen and perflubron emulsion was the most effective at decreasing both percentage of mismatched and closed vessels in all three tumours studies. This combination was also the most effective at enhancing the radiation response in all three tumours

  13. Exercise increases the lung clearance of inhaled Tc-99m DTPA

    International Nuclear Information System (INIS)

    It has been suggested that blood flow have little effect on the lung clearance of Tc-99m DTPA which depends on the alveolar distension. However an increase of pulmonary blood flow, induces a recruitment of new vascular areas which can enhance this clearance. To assess this hypothesis the pulmonary apical and basal clearances of a sumicronic aerosol of Tc-99m DTPA were studied at rest and at exercise in seven non smoking volunteers in upright posture. As a matter of fact exercising upright is known to increase primarily the apical blood flow. After inhalation the subjects were seated on a bicycle their back against a gamma camera which was linked to a computer. The lung radioactivity was registered successively during a resting and an exercising period. At rest there was a gradient of clearance from the apex to the base of the lung, the apical clearance being significantly higher. At exercise (50 Watts, 60 c. min /sup -1/, 7 min.) this regional gradient was enhanced by a large and significant increase of the apical clearances (0.0340 min /sup -1/ +-0.0063 SD versus 0.00183 min /sup -1/ +- 0.074 SD at rest, n = 7, p < 0.01). By contrast the changes of the basal clearances were slight and unsignificant (0.0146 min /sup -1/ +- 0.0062 SD versus 0.0140 min /sup -1/ +- 0.0082 SD). Since exercise induces little distension of the apical alveoli but drastically enhances the apical blood flow, the observed increase of the apical lung clearance could be primarily attributed to the recruitment of new capillaries induced by exercise in the apices. This led to an increase of the surface area permeability product

  14. Inhaled corticosteroids and the increased risk of pneumonia: what's new? A 2015 updated review.

    Science.gov (United States)

    Iannella, Hernan; Luna, Carlos; Waterer, Grant

    2016-06-01

    There is a considerable amount of evidence that supports the possibility of an increased risk of pneumonia associated with prolonged use of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD). However, as yet, no statistically significant increase in pneumonia-related 30-day mortality in patients on ICS has been demonstrated. The lack of objective pneumonia definitions and radiological confirmations have been a major source of bias, because of the similarities in clinical presentation between pneumonia and acute exacerbations of COPD. One of the newer fluticasone furoate studies overcomes these limitations and also provides an assessment of a range of doses, suggesting that the therapeutic window is quite narrow and that conventional dosing has probably been too high, although the absolute risk may be different compared to other drugs. Newer studies were not able to rule out budesonide as responsible for pneumonia, as previous evidence suggested, and there is still need for evidence from head-to-head comparisons in order to better assess possible intra-class differences. Although the exact mechanisms by which ICS increase the risk of pneumonia are not fully understood, the immunosuppressive effects of ICS on the respiratory epithelium and the disruption of the lung microbiome are most likely to be implicated. Given that COPD represents such a complex and heterogeneous disease, attempts are being made to identify clinical phenotypes with clear therapeutic implications, in order to optimize the pharmacological treatment of COPD and avoid the indiscriminate use of ICS. If deemed necessary, gradual withdrawal of ICS appears to be well tolerated. Vaccination against pneumococcus and influenza should be emphasized in patients with COPD receiving ICS. Physicians should keep in mind that signs and symptoms of pneumonia in COPD patients may be initially indistinguishable from those of an exacerbation, and that patients with COPD

  15. Inhaled Steroids

    Science.gov (United States)

    ... Medications > Long-Term Control Medications > Inhaled Steroids Inhaled Steroids What are some common inhaled steroids? How are ... more about steroids? What are some common inhaled steroids? Common inhaled steroids include: Asmanex ® (mometasone) Alvesco ® (ciclesonide) ...

  16. High-dose inhaled terbutaline increases muscle strength and enhances maximal sprint performance in trained men

    DEFF Research Database (Denmark)

    Hostrup, Morten; Kalsen, Anders; Bangsbo, Jens;

    2014-01-01

    ) participated in a double-blinded randomized crossover study. After administration of inhaled terbutaline (30 × 0.5 mg) or placebo, subjects' maximal voluntary isometric contraction (MVC) of m.quadriceps was measured. After MVC, subjects performed a 30-s Wingate test. Sixty minutes following the Wingate test...

  17. CMTR1 is associated with increased asthma exacerbations in patients taking inhaled corticosteroids.

    Science.gov (United States)

    Dahlin, Amber; Denny, Joshua; Roden, Dan M; Brilliant, Murray H; Ingram, Christie; Kitchner, Terrie E; Linneman, James G; Shaffer, Christian M; Weeke, Peter; Xu, Hua; Kubo, Michiaki; Tamari, Mayumi; Clemmer, George L; Ziniti, John; McGeachie, Michael J; Tantisira, Kelan G; Weiss, Scott T; Wu, Ann Chen

    2015-12-01

    Inhaled corticosteroids (ICS) are the most effective controller medications for asthma, and variability in ICS response is associated with genetic variation. Despite ICS treatment, some patients with poor asthma control experience severe asthma exacerbations, defined as a hospitalization or emergency room visit. We hypothesized that some individuals may be at increased risk of asthma exacerbations, despite ICS use, due to genetic factors. A GWAS of 237,726 common, independent markers was conducted in 806 Caucasian asthmatic patients from two population-based biobanks: BioVU, at Vanderbilt University Medical Center (VUMC) in Tennessee (369 patients), and Personalized Medicine Research Project (PMRP) at the Marshfield Clinic in Wisconsin (437 patients). Using a case-control study design, the association of each SNP locus with the outcome of asthma exacerbations (defined as asthma-related emergency department visits or hospitalizations concurrent with oral corticosteroid use), was evaluated for each population by logistic regression analysis, adjusting for age, gender and the first four principal components. A meta-analysis of the results was conducted. Validation of expression of selected candidate genes was determined by evaluating an independent microarray expression data set. Our study identified six novel SNPs associated with differential risk of asthma exacerbations (P < 10(-05)). The top GWAS result, rs2395672 in CMTR1, was associated with an increased risk of exacerbations in both populations (OR = 1.07, 95% CI 1.03-1.11; joint P = 2.3 × 10(-06)). Two SNPs (rs2395672 and rs279728) were associated with increased risk of exacerbations, while the remaining four SNPs (rs4271056, rs6467778, rs2691529, and rs9303988) were associated with decreased risk. Three SNPs (rs2395672, rs6467778, and rs2691529) were present in three genes: CMTR1, TRIM24 and MAGI2. The CMTR1 mRNA transcript was significantly differentially expressed in nasal lavage samples

  18. Increased lung cancer risks are similar whether arsenic is ingested or inhaled

    OpenAIRE

    Smith, Allan H; Ercumen, Ayse; Yuan, Yan; Steinmaus, Craig M.

    2009-01-01

    In 1980, the International Agency for Research on Cancer (IARC) determined there was sufficient evidence that inorganic arsenic was a human lung carcinogen based on studies involving exposure through inhalation. In 2004, IARC listed arsenic in drinking water as a cause of lung cancer, making arsenic the first substance established to cause human cancer by two unrelated pathways of exposure. It may initially seem counterintuitive that arsenic in drinking water would cause human lung cancer, an...

  19. Increased use of inhaled corticosteroids among young Danish adult asthmatics: An observational study

    DEFF Research Database (Denmark)

    Davidsen, Jesper Rømhild; Søndergaard, Jens; Hallas, Jesper; Siersted, Hans Christian; Lykkegaard, Jesper; Andersen, Morten

    2010-01-01

    OBJECTIVE: This population-based longitudinal study aimed to investigate trends in use of inhaled corticosteroids (ICS) and determinants of ICS use in young Danish adults with asthma. METHODS: 106 757 users, aged 18-44 years, of anti-asthmatic drugs were identified in the Danish Register of Medical.......96-1.01) compared to 1.12 (95% CI 1.09-1.15) in 2001, and 1.81 (95% CI 1.75-1.87) in 2006. Other determinants of high ICS use were female gender, young age, and high annual IBA consumption. Among those using at least 400 DDD of IBA per year (corresponding to 4.4 powder inhalations daily), nearly 20% had no ICS...... Product Statistics during 1997-2006. One year prevalences of ICS use were calculated in categories of gender, age, and annual consumption of inhaled beta-2-agonists (IBA) in defined daily doses (DDD) per year. Determinants of ICS use were estimated by logistic regression models. RESULTS: The one year...

  20. Acute Toxicity Profile and Compliance to Accelerated Radiotherapy Plus Carbogen and Nicotinamide for Clinical Stage T2–4 Laryngeal Cancer: Results of a Phase III Randomized Trial

    International Nuclear Information System (INIS)

    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with cT2–4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2–4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Results: Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moist desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. Conclusion: With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2–4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit.

  1. Acute Toxicity Profile and Compliance to Accelerated Radiotherapy Plus Carbogen and Nicotinamide for Clinical Stage T2-4 Laryngeal Cancer: Results of a Phase III Randomized Trial

    Energy Technology Data Exchange (ETDEWEB)

    Janssens, Geert O., E-mail: g.janssens@rther.umcn.nl [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Terhaard, Chris H. [Department of Radiation Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Doornaert, Patricia A. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Bijl, Hendrik P. [Department of Radiation Oncology, University Medical Center Groningen, Groningen (Netherlands); Ende, Piet van den [Department of Radiation Oncology, Maastricht University Medical Centre, Maastricht (Netherlands); Chin, Alim [Department of Clinical Oncology, Leiden University Medical Centre, Leiden (Netherlands); Pop, Lucas A.; Kaanders, Johannes H. [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)

    2012-02-01

    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with cT2-4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2-4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Results: Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moist desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. Conclusion: With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2-4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit.

  2. Inhalation Injury

    Directory of Open Access Journals (Sweden)

    Coşkun Araz

    2011-07-01

    Full Text Available Despite significant advances in wound care of patients with burn injuries, inhalation injury remains as an important contributor to morbidity and mortality in these patients. Unfortunately, there are limited studies that have focused on the diagnosis, grading, pathophysiology, and therapy of inhalation injury, therefore a widely accepted consensus is lacking on these topics. Inhalation injury is generally defined as the inhalation of thermal or chemical irritants and can be divided into three types of injury: thermal injury, which is mostly restricted to the upper airway; chemical injury, which affects tracheobronchial tree; and systemic toxicity owing to toxic gases such as carbon monoxide. Inhalation injury increases the burn injury associated morbidity and mortality by causing airway problems and respiratory failure during the early phase and by contributing to the development of pneumonia and atelectasis during the late phase. Additionally, systemic effects of toxic gases such as carbon monoxide may also adversely affect the early and long-term outcome in burn victims. The early diagnosis and therapy of these problems plays a key role in improving the outcome of burn patients. (Journal of the Turkish Society Intensive Care 2011; 9 Suppl: 37-45

  3. Inhalation Injuries

    Science.gov (United States)

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

  4. Two-week inhalation of budesonide increases muscle Na,K ATPase content but not endurance in response to terbutaline in men

    DEFF Research Database (Denmark)

    Hostrup, Morten; Jessen, Søren; Onslev, Johan;

    2016-01-01

    While chronic systemic administration of glucocorticoids increases muscle Na+,K+ ATPase content, such effect is unexplored after therapeutic inhalation. We investigated the effect of therapeutic inhalation of the glucocorticoid budesonide on Na+,K+ ATPase content of skeletal muscle in men. Ten he...... present observations show that therapeutic inhalation of glucocorticoids increases muscle Na+,K+ ATPase content, but does not enhance high-intensity cycling endurance in response to terbutaline.......While chronic systemic administration of glucocorticoids increases muscle Na+,K+ ATPase content, such effect is unexplored after therapeutic inhalation. We investigated the effect of therapeutic inhalation of the glucocorticoid budesonide on Na+,K+ ATPase content of skeletal muscle in men. Ten...... healthy trained subjects, aged 23 ± 4 years (mean ± 95% CI), participated in the study. Before and after 2 weeks of daily inhalation of budesonide (1.6 mg/day), a biopsy was taken from the vastus lateralis muscle for measurement of Na+,K+ ATPase content and blood samples were drawn for determination of...

  5. 前列腺疾病吸入5%二氧化碳混合气体BOLD-MRI与微血管特征的对照研究%The correlative study of carbogen breathing BOLD-MRI and features of micro-vascular of prostatic disease

    Institute of Scientific and Technical Information of China (English)

    陈化峰; 焦自梅; 高珊珊; 胡娜; 王锡臻; 刘金刚; 李莉莉; 王滨

    2015-01-01

    Objective To investigate the relationship between micro-vascular features and carbogen breathing BOLD-MRI in be-nign prostatic hyperplasia (BPH)and prostate cancer (PCa).Methods Carbogen breathing BOLD-fMRI was performed using a 3.0 Tesla superconducting magnetic scanner (GE)equipped with a phased-array multi-coil.The regions of interest (ROI)of central zone (CZ),peripheral zone (PZ),BPH and PCa were drawn.The relative increase signal rates and time signal intensity curve (TIC) were recorded.The average diameter,area,circumference and special shape index of micro-vascular were analyzed using immunohis-tochemical stain.The relationship between micro-vascular features and BOLD-MRI was analyzed using SPSS 1 1 .5 .Results The sig-nal intensities of CZ,PZ,BPH and PCa during carbogen breathing were higher than those during air breathing (P<0.05).The rela-tive increasing rate of TIC of CZ,PZ,BPH and PCa after carbogen breathing were (5.07±1.08)%,(2.78±1.13)%,(6.44± 2.02)% and (1.77±0.40)% (P<0.05).The mean MVD of BPH and PCa were 12.32±3.14/field and 30.22±11.19/field (P<0.05).The average diameter,area,circumference and special-shape index of PCa were lower than those of BPH (P<0.05).Conclu-sion Carbogen inhaling BOLD-MRI is related with the micro-vascular structures in BPH and PCa,which will have potential to eval-uate the function and maturity of micro-vascular.%目的:探讨吸入5%二氧化碳混合气体BOLD-MRI与前列腺增生(BPH)和前列腺癌(PCa)中微血管特征的对应关系。方法采用美国 GE Signa Excite HD 3.0T超导型磁共振成像仪和腹部相控阵线圈,在吸入5%二氧化碳混合气体行 BOLD-MRI。画取正常前列腺外周带(PZ)、中央腺区(CZ)、BPH 和PCa感兴趣区(ROI),记录时间-信号强度曲线(TIC)和信号强度平均增加率。免疫组化分析BPH 和PCa微血管形态学特征:平均直径、平均面积、平均周长及异型指数。结果 CZ、PZ、BPH 及 PCa 区信号强度于吸入混合气体

  6. A therapeutic benefit from combining normobaric carbogen or oxygen with nicotinamide in fractionated X-ray treatments

    International Nuclear Information System (INIS)

    The ability of normobaric oxygen and carbogen (95 percent O2 + 5 percent CO2) combined with nicotinamide to enhance the radiosensitivity of two rodent adenocarcinomas and of mouse skin and kidneys was compared with the effects of radiation in air and without the drug. A comparison of the results in tumors and normal tissues showed that significant therapeutic benefit was obtained with normobaric oxygen and carbogen combined with nicotinamide. Toxic side effects of the treatment are unlikely, as prolonged administration of nicotinamide is well tolerated in man. The combination of normobaric carbogen with nicotinamide could be an effective method of enhancing tumor radiosensitivity in clinical radiotherapy where hypoxia limits the outcome of treatment. (author). 45 refs.; 4 fig.; 4 tabs

  7. Adrenal secretion of catecholamines by inhalation of radon water in relation to an increase of the tissue perfusion rate in rabbits

    International Nuclear Information System (INIS)

    To clarify the relationship between the increase in subcutaneous tissue perfusion rate (TPR) upon inhalation of radon water and the vasoactive effects of radon, rabbits inhaled nebulized water containing 14,000-18,000 Bq/1 radon (radon group) taken from Ikeda Mineral Spring, Shimane, Japan. Control rabbits inhaled radon water from the same springs which had been kept for over 10 radon half-life periods. TPR was evaluated 15 minutes after the beginning of inhalation by mass spectrometry. After inhalation for 90 minutes, plasma and adrenal glands were removed, and levels of adrenaline and noradrenaline were analyzed by high-performance liquid chromatography (THI method). Each group was divided into 4 subgroups according to intravenously injected medication as follows: 1) no medication (without adrenergic blocker), 2) phentolamine (α-blocker), 0.05 mg/kg/min, 3) propranolol (non-selective β-blocker), 1 mg/kg/, and 4) atenolol (selective β-blocker), 6 mg/kg. In the radon group, plasma adrenaline and noradrenaline levels were significantly higher (p1-action of catecholamines contributes to the increase in tissue perfusion. (author)

  8. Inhalation of tobacco smoke induces increased proliferation of urinary bladder epithelium and endothelium in female C57BL/6 mice

    International Nuclear Information System (INIS)

    Cigarette smoking is the major environmental risk factor for bladder cancer in humans. Aromatic amines, potent DNA-reactive bladder carcinogens present in cigarette smoke, contribute significantly. However, increased cell proliferation, caused by direct mitogenesis or in response to cytotoxicity, may also play a role since urothelial hyperplasia has been observed in human cigarette smokers. We examined the urothelial effects of cigarette smoke (whole body inhalation exposure (Teague) system) in female C57BL/6 mice at various times in two studies, including reversibility evaluations. In both studies, no urothelial hyperplasia was observed by light microscopy in any group. However, in study 1, the Ki-67 labeling index (LI) of the urothelium was significantly increased in the smoke exposed group compared to controls through 3 months, but was not present at 6, 9 or 12 months even with continued exposures. In the groups that discontinued smoke exposure, it returned to the same levels as controls or lower. In study 2, the bromodeoxyuridine LI was similar to controls on day 1 but significantly increased at 5 days in the smoke exposed group. In the group that discontinued smoke exposure for 2 days, the LI was increased compared to controls but not significantly. Superficial urothelial cell cytotoxicity and necrosis were detectable by scanning electron microscopy at 5 days. Changes in LI of submucosal endothelial cells generally followed those of the urothelium and effects were reversible upon cessation of exposure. The increased urothelial proliferation appeared to be due to superficial cell cytotoxicity with consequent regeneration

  9. Exercise increases the lung clearance of inhaled technetium-99m DTPA

    International Nuclear Information System (INIS)

    The regional lung clearance of a deposited aerosol of [/sup 99m/Tc] diethylenetriaminepentaacetic acid was successively computed at rest and at exercise in seven nonsmoking volunteers in upright posture. The subjects were seated on a bicycle with their backs against a gamma camera. At rest there was a gradient of clearance from the apex to the base of the lung, the apical clearance being significantly higher. At exercise this regional gradient was enhanced by a large and significant increase of the apical clearances (3.40 +/- 0.63% min-1 s.d. compared with 1.82 +/- 0.75% min-1 s.d. at rest, n = 7, p less than 0.01). By contrast the changes of the basal clearances were slight and unsignificant (1.46 +/- 0.71% min-1 s.d. compared with 1.40 +/- 0.82% min-1 s.d.). This increase of the apical lung clearance could be attributed primarily to the increase of apical blood flow induced by exercise and to the subsequent increase of the permeability surface area product

  10. Diesel Exhaust Inhalation Increases Cardiac Output, Bradyarrhythmias, and Parasympathetic Tone in Aged Heart Failure-Prone Rats

    Science.gov (United States)

    Acute air pollutant inhalation is linked to adverse cardiac events and death, and hospitalizations for heart failure. Diesel exhaust (DE) is a major air pollutant suspected to exacerbate preexisting cardiac conditions, in part, through autonomic and electrophysiologic disturbance...

  11. CMTR1 is associated with increased asthma exacerbations in patients taking inhaled corticosteroids

    DEFF Research Database (Denmark)

    Dahlin, Amber; Denny, Joshua; Roden, Dan M;

    2015-01-01

    or emergency room visit. We hypothesized that some individuals may be at increased risk of asthma exacerbations, despite ICS use, due to genetic factors. A GWAS of 237,726 common, independent markers was conducted in 806 Caucasian asthmatic patients from two population-based biobanks: BioVU, at Vanderbilt...... candidate genes was determined by evaluating an independent microarray expression data set. Our study identified six novel SNPs associated with differential risk of asthma exacerbations (P risk of exacerbations in both...... populations (OR = 1.07, 95% CI 1.03-1.11; joint P = 2.3 × 10(-06)). Two SNPs (rs2395672 and rs279728) were associated with increased risk of exacerbations, while the remaining four SNPs (rs4271056, rs6467778, rs2691529, and rs9303988) were associated with decreased risk. Three SNPs (rs2395672, rs6467778...

  12. Inhalation Injury

    OpenAIRE

    Coşkun Araz; Arash Pirat

    2011-01-01

    Despite significant advances in wound care of patients with burn injuries, inhalation injury remains as an important contributor to morbidity and mortality in these patients. Unfortunately, there are limited studies that have focused on the diagnosis, grading, pathophysiology, and therapy of inhalation injury, therefore a widely accepted consensus is lacking on these topics. Inhalation injury is generally defined as the inhalation of thermal or chemical irritants and can be divided into three...

  13. Inhalant Abuse

    Science.gov (United States)

    ... she is likely to try other kinds of drugs, especially alcohol and marijuana. Symptoms How can I tell if my child is abusing inhalants? It can be hard to recognize the signs of inhalant abuse. Teenagers who use inhalants may have some of the ...

  14. ACUTE TOXICITY PROFILE AND COMPLIANCE TO ACCELERATED RADIOTHERAPY PLUS CARBOGEN AND NICOTINAMIDE FOR CLINICAL STAGE T2-4 LARYNGEAL CANCER : RESULTS OF A PHASE III RANDOMIZED TRIAL

    NARCIS (Netherlands)

    Janssens, Geert O.; Terhaard, Chris H.; Doornaert, Patricia A.; Bijl, Hendrik P.; van den Ende, Piet; Chin, Alim; Pop, Lucas A.; Kaanders, Johannes H.

    2012-01-01

    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with

  15. Acute toxicity profile and compliance to accelerated radiotherapy plus carbogen and nicotinamide for clinical stage T2-4 laryngeal cancer: results of a phase III randomized trial.

    NARCIS (Netherlands)

    Janssens, G.O.R.J.; Terhaard, C.H.J.; Doornaert, P.A.; Bijl, H.P.; Ende, P. van den; Chin, A.; Pop, L.A.M.; Kaanders, J.H.A.M.

    2012-01-01

    PURPOSE: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. METHODS AND MATERIALS: From April 2001 to February 2008, 345 patients with

  16. The common inhaled anesthetic isoflurane increases aggregation of huntingtin and alters calcium homeostasis in a cell model of Huntington's disease

    International Nuclear Information System (INIS)

    Isoflurane is known to increase β-amyloid aggregation and neuronal damage. We hypothesized that isoflurane will have similar effects on the polyglutamine huntingtin protein and will cause alterations in intracellular calcium homeostasis. We tested this hypothesis in striatal cells from the expanded glutamine huntingtin knock-in mouse (STHdhQ111/Q111) and wild type (STHdhQ7/Q7) striatal neurons. The primary cultured neurons were exposed for 24 h to equipotent concentrations of isoflurane, sevoflurane, and desflurane in the presence or absence of extracellular calcium and with or without xestospongin C, a potent endoplasmic reticulum inositol 1,4,5-trisphosphate (InsP3) receptor antagonist. Aggregation of huntingtin protein, cell viability, and calcium concentrations were measured. Isoflurane, sevoflurane, and desflurane all increased the aggregation of huntingtin in STHdhQ111/Q111 cells, with isoflurane having the largest effect. Isoflurane induced greater calcium release from the ER and relatively more cell damage in the STHdhQ111/Q111 huntingtin cells than in the wild type STHdhQ7/Q7 striatal cells. However, sevoflurane and desflurane caused less calcium release from the ER and less cell damage. Xestospongin C inhibited the isoflurane-induced calcium release from the ER, aggregation of huntingtin, and cell damage in the STHdhQ111/Q111 cells. In summary, the Q111 form of huntingtin increases the vulnerability of striatal neurons to isoflurane neurotoxicity through combined actions on the ER IP3 receptors. Calcium release from the ER contributes to the anesthetic induced huntingtin aggregation in STHdhQ111/Q111 striatal cells.

  17. Inhaled Corticosteroids Use Is Not Associated With an Increased Risk of Pregnancy-Induced Hypertension and Gestational Diabetes Mellitus: Two Nested Case-Control Studies.

    Science.gov (United States)

    Lee, Chang-Hoon; Kim, Jimin; Jang, Eun Jin; Lee, Joon-Ho; Kim, Yun Jung; Choi, Seongmi; Kim, Deog Kyeom; Yim, Jae-Joon; Yoon, Ho Il

    2016-05-01

    There have been concerns that systemic corticosteroid use is associated with pregnancy-induced hypertension (PIH) and diabetes mellitus. However, the relationship between inhaled corticosteroids (ICSs) and the risk of PIH has not been fully examined, and there was no study investigating the association between ICS use and the development of gestational diabetes mellitus (GDM). The aims of the study are to determine whether the use of ICSs during pregnancy increases the risk of PIH and GDM in women.We conducted 2 nested case-control studies utilizing the nationwide insurance claims database of the Health Insurance Review and Assessment Service (Seoul, Republic of Korea), in which 1,306,281 pregnant women who delivered between January 1, 2009 and December 31, 2011 were included. Among them, PIH cases and GDM cases were identified and matched controls were included. Conditional logistic regression analyses adjusted by other concomitant drugs use during and before pregnancy and confounding covariates including comorbidities were performed.Total 43,908 PIH cases and 219,534 controls, and 34,190 GDM cases and 170,934 control subjects were identified. When other concomitant drugs use during pregnancy was adjusted, ICS use was associated with an increased rate of PIH (adjusted odds ratio, 1.40 [95% CI, 1.05-1.87]). ICS medication possession ratios and cumulative doses were associated with an increased risk of PIH. However, the statistical significance was not found in other models. In both unadjusted and adjusted multivariable models, ICSs use was not associated with increase in the risk of GDM.ICSs use is not associated with an increased risk of PIH and GDM. PMID:27258493

  18. Inhalation of fine particulate matter during pregnancy increased IL-4 cytokine levels in the fetal portion of the placenta.

    Science.gov (United States)

    de Melo, Juliana Oliveira; Soto, Sônia Fátima; Katayama, Isis Akemi; Wenceslau, Camilla Ferreira; Pires, Amanda Gonçalves; Veras, Mariana Matera; Furukawa, Luzia N S; de Castro, Isac; Saldiva, Paulo Hilário Nascimento; Heimann, Joel Claudio

    2015-01-22

    This study aimed to verify the development of placental and systemic inflammation in rats exposed to fine particulate matter before or during pregnancy. Wistar rats were exposed to filtered air (control) or to a load of 600 μg/m(3) of fine particles in the air. The gene expression of IL-1β, IL-4, IL-6, IL-10, INF-γ, TNF-α and Toll-like receptor 4 in the placenta was evaluated. The serum and placental concentrations of IL-1β, IL-4, IL-6, IL-10, INF-γ and TNF-α were measured. The total and differential blood leukocyte and blood platelet count was assessed. Compared to control animals, IL-4 content was elevated in the fetal portion of the placenta in rats exposed to air pollution before and during pregnancy. Increased IL-4 suggests that a placental inflammatory reaction may have occurred in response to exposure to fine particulate matter and that this cytokine was responsible, among possibly others factors, for resolution of the inflammatory reaction. PMID:25481569

  19. Increased expression of transforming growth factor-β and receptors in primary human airway fibroblasts from chemical inhalation patients.

    Directory of Open Access Journals (Sweden)

    Monireh Sadat Mirzamani

    2013-06-01

    Full Text Available The widespread use of sulfur mustard  (SM as a chemical warfare agent in the  past century has proved its long-lasting toxic effects. Despite a lot of research over the past decades on Iranian veterans, there are still major gaps in the SM literature. Transforming growth  factor  (TGF-β,  a  cytokine  that  affects  many  different  cell processes,  has  an important role in the lungs of patients with some of chronic airway diseases, especially with respect to airway remodeling in mustard lung.Primary airway fibroblasts from epibronchial biopsies were cultured, and gene expression of TGF-β1, TGF-β2, TbR-I and TbR-II in fibroblasts of SM injured patients and controls were investigated. Expression of TGF-βs and receptors was measured by RT-PCR. Protein level of TGF-β1was surveyed by western blot.Our  findings revealed that expression levels of TGF-β1,  TGF-β2,  TbR-I and TbR-II were upregulated in the  airway fibroblasts of  SM exposed patients  in comparison  with control samples. TGF-β1 expression was shown to be markedly increased in primary lung fibroblasts of chemically injured patients.Our  novel data, suggested that  over-expression of TGF-β  molecule and receptors  in primary airway fibroblasts of mustard gas injured patients may be involved in progression of airway remodeling of these patients.

  20. Inhalation exposure methodology.

    OpenAIRE

    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 ga...

  1. The study of aging change of normal prostate using carbogen-breathing BOLI-fMRI%吸入混合气BOLD-fMRI对正常前列腺组织加龄性变化的研究

    Institute of Scientific and Technical Information of China (English)

    焦自梅; 王锡臻; 胡娜; 刘金刚; 王滨; 王光彬; 李莉莉

    2013-01-01

    目的 通过比较正常前列腺志愿者吸入carbogen气体后不同年龄组正常中央腺区(CZ)和周围带(PZ)的相对信号强度平均增加率,探讨正常前列腺不同组织SI-TC的加龄性变化特征.方法 本研究纳入正常前列腺志愿者32例,按年龄分为<30岁,30~50岁和>50岁三组.吸入carbogen气体状态下行BOLD-fMRI成像.分别记录吸入carbogen气体前、后的CZ和PZ的平均信号强度值,计算吸入carbogen气体后相对信号强度平均增加率;比较不同年龄段CZ和PZ相对信号强度平均增加率之间的差别.结果 <30岁年龄组的CZ相对信号强度平均增加率高于>50岁年龄组(P =0.014);<30岁年龄组的PZ相对信号强度平均增加率高于30~50岁年龄组和>50岁年龄组,差异均具有统计学意义(P =0.015;P=0.007).结论 吸入carbogen气体状态下BOLD-fMRI信号改变能反映正常前列腺组织的加龄性变化规律,可为前列腺疾病发生机制的研究提供新的手段.%Objective The relative increase signal average rate in normal prostate central zone tissue (CZ), peripheral zone tissue (PZ) using blood oxygen level-dependent (BOLD) induced by carbogen (95% O2/ 5% CO2) breathing were analyzed. The objective of this study was to explore the changes of signal intensity-time curve (SI-TC) in CZ and PZ of different age. Methods BOLD-fMRI was performed using a 3. 0 Tesla superconducting magnetic scanner (GE) in 32 healthy volunteers and the volunteers were divided into three groups according to the age: under 30 years old, 30 — 50 years old and above 50 years old. The average signal values of CZ and PZ before/after carbogen breathing and the relative increase signal average rate were computed. Results There was statistical significance between every two groups. The relative increase signal average rate of CZ under 30 years old was higher than that of above 50 years old ( P =0. 014). The relative increase signal average rate of PZ under 30

  2. Substance use -- inhalants

    Science.gov (United States)

    ... get through daily life. Addiction can lead to tolerance. Tolerance means that more and more of the inhalant ... PhD, and the A.D.A.M. Editorial team. Related MedlinePlus Health Topics Inhalants Browse the Encyclopedia ...

  3. Fluticasone Oral Inhalation

    Science.gov (United States)

    ... medications a certain amount of time before and after you inhale fluticasone inhalation. If you were taking an ... your steroid dose starting at least 1 week after you begin to use fluticasone.Fluticasone helps to prevent ...

  4. Olodaterol Oral Inhalation

    Science.gov (United States)

    ... inhalation is used to control wheezing, shortness of breath, coughing, and chest tightness caused by chronic obstructive ... bottom of the clear base. Fill in the expiration date on the inhaler label, which is 3 ...

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

    Science.gov (United States)

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

    2000-01-01

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

  6. Inhaled Drug Delivery: A Practical Guide to Prescribing Inhaler Devices

    Directory of Open Access Journals (Sweden)

    Pierre Ernst

    1998-01-01

    Full Text Available Direct delivery of medication to the target organ results in a high ratio of local to systemic bioavailability and has made aerosol delivery of respiratory medication the route of choice for the treatment of obstructive lung diseases. The most commonly prescribed device is the pressurized metered dose inhaler (pMDI; its major drawback is the requirement that inspiration and actuation of the device be well coordinated. Other requirements for effective drug delivery include an optimal inspiratory flow, a full inspiration from functional residual capacity and a breath hold of at least 6 s. Available pMDIs are to be gradually phased out due to their use of atmospheric ozone-depleting chlorofluorocarbons (CFCs as propellants. Newer pMDI devices using non-CFC propellants are available; preliminary experience suggests these devices greatly increase systemic bioavailability of inhaled corticosteroids. The newer multidose dry powder inhalation devices (DPIs are breath actuated, thus facilitating coordination with inspiration, and contain fewer ingredients. Furthermore, drug delivery is adequate even at low inspired flows, making their use appropriate in almost all situations. Equivalence of dosing among different devices for inhaled corticosteroids will remain imprecise, requiring the physician to adjust the dose of medication to the lowest dose that provides adequate control of asthma. Asthma education will be needed to instruct patients on the effective use of the numerous inhalation devices available.

  7. Managing diabetes with inhaled insulin

    Directory of Open Access Journals (Sweden)

    Lucy D Mastrandrea

    2012-01-01

    Full Text Available The incidence of diabetes is increasing world-wide. Many individuals with diabetes require insulin to control their blood sugar and prevent both microvascular and macrovascular complications associated with this chronic disease. Current regimens involve delivery of subcutaneous insulin by injection or continuous insulin infusion. One area of research to advance diabetes care is aimed at developing alternate routes of insulin administration that will make daily management less invasive for patients. This review will focus on inhaled insulin, a novel formulation which takes advantage of drug delivery through the pulmonary system. The pharmacology, efficacy, and safety of inhaled insulin will be discussed. In addition, the status of inhaled insulin as a potential therapy for individuals with diabetes will be reviewed.

  8. Emitted dose and lung deposition of inhaled terbutaline from Turbuhaler at different conditions.

    Science.gov (United States)

    Abdelrahim, Mohamed E

    2010-05-01

    Turbuhaler has a very high resistance hence patient inhalation flow when using it would be low. The total emitted dose (TED) of 500microg terbutaline sulphate from a Bricanyl Turbuhaler was determined using a range of inhalation flows (10-60L min(-1)) with inhalation volume of 2 and 4L using a DPI sampling apparatus after one and two inhalations. The relative lung and systemic bioavailability of terbutaline from Bricanyl Turbuhaler when used by healthy subjects and COPD patients were determined after one and two inhalations at slow and fast inhalation flows using a novel urinary terbutaline pharmacokinetic method. The TED resulted from the one and two inhalations increased significantly (p<0.05) with the increase of the inhalation flow at both 2 and 4L inhalation volumes. The relative lung and systemic bioavailability after one inhalation at fast inhalation flow were significantly higher (p<0.01) than at slow inhalation flow in both healthy subjects and patients. Also the healthy subjects results were significantly higher (p<0.05) than the COPD patients after one inhalation. However after two inhalations there was no significant difference between slow and fast inhalation flow or healthy subjects and COPD patients. Hence it is essential to inhale twice and as deep and hard as possible from each dose of Turbuhaler for patients with low inspiratory flow and limited inhalation volume as they may not receive much benefit from one inhalation. PMID:20004090

  9. [Inhaled therapy in asthma].

    Science.gov (United States)

    Plaza Moral, Vicente; Giner Donaire, Jordi

    2016-04-01

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

  10. Inhaled transuranics in rodents

    International Nuclear Information System (INIS)

    The purpose of this project is to examine, in small animals, the fate and effects of inhaled transuranic compounds including plutonium dioxide, americium oxides, americium nitrates and curium oxides. This project should provide data for hazard evaluation and establishment of permissible exposure limits to man for inhaled transuranics, particularly with respect to the effects of radiation dose and dose distribution. Inhalation carcinogenesis was the primary effect evaluated

  11. Inhalational Lung Disease

    OpenAIRE

    S Kowsarian; Farzaneh; F Jamshidiha

    2010-01-01

    Inhalational lung diseases are among the most important occupational diseases. Pneumoconiosis refers to a group of lung diseases result from inhalation of usually inorganic dusts such as silicon dioxide, asbestos, coal, etc., and their deposition in the lungs. The resultant pulmonary disorders depend on the susceptibility of lungs; size, concentration, solubility and fibrogenic properties of the inhaled particles; and duration of exposure. Radiographic manifestations of pneumoconiosis become ...

  12. Inhalant Abuse and Dextromethorphan.

    Science.gov (United States)

    Storck, Michael; Black, Laura; Liddell, Morgan

    2016-07-01

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

  13. Formoterol Oral Inhalation

    Science.gov (United States)

    Bevespi Aerosphere® (as a combination product containing Glycopyrrolate, Formoterol) ... Formoterol inhalation powder (Foradil) and nebulizer solution (Perforomist) are used to treat wheezing, shortness of breath, and ...

  14. Inhalation injury: epidemiology, pathology, treatment strategies

    OpenAIRE

    Dries, David J; Endorf, Frederick W

    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 patie...

  15. Amorphous powders for inhalation drug delivery.

    Science.gov (United States)

    Chen, Lan; Okuda, Tomoyuki; Lu, Xiang-Yun; Chan, Hak-Kim

    2016-05-01

    For inhalation drug delivery, amorphous powder formulations offer the benefits of increased bioavailability for poorly soluble drugs, improved biochemical stability for biologics, and expanded options of using various drugs and their combinations. However, amorphous formulations usually have poor physicochemical stability. This review focuses on inhalable amorphous powders, including the production methods, the active pharmaceutical ingredients and the excipients with a highlight on stabilization of the particles. PMID:26780404

  16. A new multiple dose powder inhaler, (Turbuhaler), compared with a pressurized inhaler in a study of terbutaline in asthmatics.

    Science.gov (United States)

    Persson, G; Gruvstad, E; Ståhl, E

    1988-08-01

    Twelve adult asthmatic patients participated in an open, randomized, cross-over comparison between cumulatively increasing doses of terbutaline sulphate administered via the multiple dose powder inhaler (Turbuhaler) or via a pressurized inhaler. Turbuhaler and the pressurized inhaler showed equipotency both with respect to bronchodilatation and side effects. Both treatments produced a significant increase in pulmonary function measurements, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). No increase in pulse rate was seen with either treatment but there was an increase in tremor at higher doses with both treatments. Inhalation of beta-agonists via Turbuhaler seems to be an effective way of treating asthma. PMID:3234516

  17. Biodistribution study of carbogenic dots in cells and in vivo for optical imaging

    International Nuclear Information System (INIS)

    Blue fluorescent carbon dots (C-dots) were synthesized and evaluated for their cytotoxicity and also for their optical imaging performance. The results showed that the C-dots could enter into the Hela cells in 15 min incubation and the uptake increased rapidly from 15 min to 2 h. In cytotoxicity study, C-dots were biocompatible and nontoxic to three human cells including two cancer cells (Hela and SMCC-7721) and one normal cell (HEK 293) in concentrations up to 500 μg/mL. Since the endocytic interference factors, including NaN3, MβCD, sucrose, and low temperature, could not play an inhibitory effect on C-dots entering into cells, the direct nonendocytic pathway for C-dots was speculated. The C-dots showed encouraging cell-imaging applications in vitro and in vivo. They entered into cells without any further functionalization, and the fluorescence property of these particles can be used for fluorescence-based cell-imaging applications.

  18. Inhaled plutonium oxide in dogs

    International Nuclear Information System (INIS)

    This project is concerned with long-term experiments to determine the lifespan dose-effect relationships of inhaled 239PuO2 and 238PuO2 in beagles. The data will be used to estimate the health effects of inhaled transuranics. Beagle dogs given a single exposure to 239PuO2 or 238PuO2 aerosols to obtain graded levels of initial lung burdens are being observed for lifespan dose-effect relationships. Mortality due to radiation pneumonitis and lung tumor increased in the four highest dose-level groups exposed to 239PuO2, during the 13-yr postexposure period. During the 10 1/2 years after exposure to 238PuO2, mortality due to lung and/or bone tumors increased in the three highest dose-level groups. Chronic lymphopenia, occurring 0.5 to 2 year after exposure, was the earliest observed effect after inhalation of either 239PuO2 or 238PuO2 in the four highest dose-level groups that had initial lung burdens greater than or equal to 80 nCi. 3 figures, 6 tables

  19. Inhaled plutonium oxide in dogs

    International Nuclear Information System (INIS)

    This project is concerned with long-term experiments to determine the lifespan dose-effect relationships of inhaled 239PuO2 or 238PuO2 in beagles. The data will be used to estimate the health effects of inhaled transuranics. Beagle dogs given a single exposure to 239PuO2 or 238PuO2 aerosols to obtain graded levels of initial lung burdens (ILB) are being observed for lifespan dose-effect relationships. Mortality due to radiation pneumonitis and lung tumor increased in the four highest dose-level groups exposed to 239PuO2 during the 15-year postexposure period. During the 12 1/2 years after exposure to 238PuO2, mortality due to lung and/or bone tumors increased in the three highest dose-level groups. Chronic lymphopenia, occurring 0.5 to 2 years after exposure, was the earliest observed effect after inhalation of either 239PuO2 or 238PuO2 in the four highest dose-level groups that had ILB of ≥ 80 nCi. Other plutonium-exposure-related effects include sclerosis of the tracheobronchial lymph nodes, focal radiation pneumonitis, adenomatous hyperplasia of the liver, and dystrophic osteolytic lesions in the skeleton. 4 figures, 7 tables

  20. Inhaled plutonium oxide in dogs

    International Nuclear Information System (INIS)

    This project is concerned with long-term experiments to determine the life span dose-effect relationships of inhaled 239PuO2 or 238PuO2 in beagles. The data will be used to estimate the health effects of inhaled transuranics. Beagle dogs given a single exposure to 239PuO2 or 238PuO2 aerosols to obtain graded levels of initial lung burdens (ILB) are being observed for life span dose-effect relationships. Mortality due to radiation pneumonitis and lung tumor increased in the four highest dose-level groups exposed to 239PuO2 during the 16-year post exposure period. During the 13 years after exposure to 238PuO2, mortality due to lung and/or bone tumors increased in the three highest dose-level groups. Chronic lymphopenia, occurring 0.5 to 2 years after exposure, was the earliest observed effect after inhalation of either 239PuO2 or 238PuO2 in the four highest dose-level groups that had ILB of ≥ 80 nCi. Other plutonium-exposure-related effects include sclerosis of the tracheobronchial lymph nodes, focal radiation pneumonitis, adenomatous hyperplasia of the liver, and dystrophic osteolytic lesions in the skeleton

  1. Inhaled plutonium oxide in dogs

    International Nuclear Information System (INIS)

    This project is concerned with long-term experiments to determine the lifespan dose-effect relationships of inhaled 239PuO2 and 238PuO2 in beagles. The data will be used to estimate the health effects of inhaled transuranics. Beagle dogs given a single exposure to 239PuO2 or 238PuO2 aerosols to obtain graded levels of initial lung burdens (ILB) are being observed for lifespan dose-effect relationships. Mortality due to radiation pnuemonitis and lung tumor increased in the four highest dose-level groups exposed to 239PuO2 during the 14-year postexposure period. During the 11 1/2 years after exposure to 238PuO2, mortality due to lung and/or bone tumors increased in the three highest dose-level groups. Chronic lymphopenia, occurring 0.5 to 2 years after exposure, was the earliest observed effect after inhalation of either 239PuO2 or 238PuO2 in the four highest dose-level groups that had ILB of greater than or equal to80 nCi. Other plutonium-exposure-related effects include sclerosis of the tracheobronchial lymph nodes, focal radiation pneumonitis, adenomatous hyperplasia of the liver, and dystrophic osteolytic lesions in the skeleton. 5 figures, 7 tables

  2. Insulin Human Inhalation

    Science.gov (United States)

    ... is a short-acting, man-made version of human insulin. Insulin inhalation works by replacing the insulin ... and selegiline (Eldepryl, Emsam, Zelapar); niacin; oral contraceptives (birth control pills); oral medications for diabetes such as pioglitazone ( ...

  3. Nicotine Microaerosol Inhaler

    Directory of Open Access Journals (Sweden)

    Paul G Andrus

    1999-01-01

    Full Text Available OBJECTIVE: To measure the droplet size distribution of a nicotine pressurized metered-dose inhaler using a nicotine in ethanol solution formulation with hydrofluoroalkane as propellant.

  4. Arformoterol Oral Inhalation

    Science.gov (United States)

    ... inhalation is used to control wheezing, shortness of breath, coughing, and chest tightness caused by chronic obstructive ... store the medication in the refrigerator until the expiration date printed on the package has passed, or ...

  5. Exubera. Inhale therapeutic systems.

    Science.gov (United States)

    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

  6. Effect of inhaled yttrium-90 in fused clay particles on the pulmonary clearance of inhaled Staphylococcus aureus in mice

    International Nuclear Information System (INIS)

    The effect of 90Y inhaled in fused clay particles on the pulmonary clearance of inhaled Staphylococcus aurcus in mice was investigated to provide an improved understanding of the influence of localized irradiation from inhaled radionuclides on infectious processes. Pulmonary clearance of inhaled S. aurcus was suppressed in mice with initial lung burdens of 20 μCi 90Y or greater at 2, 3, and 4 weeks after inhalation exposure to 90Y. Suppressed clearance rates were accompanied by radiation-induced lifespan shortening, retarded increases in average body wieght, suppression of blood lymphocyte count, and pulmonary lesions. Only equivocal suppression of bacterial clearance was observed in mice with initial lung burdens of less than 20 μCi 90Y that were tested from 1 through 52 weeks after inhalation exposure. An initial lung burden of 1 μCi 90Y was estimated to result in 400 rad to the lung delivered within 24 days after exposure

  7. Inhaled americium dioxide

    International Nuclear Information System (INIS)

    This project includes experiments to determine the effects of Zn-DTPA therapy on the retention, translocation and biological effects of inhaled 241AmO2. Beagle dogs that received inhalation exposure to 241AmO2 developed leukopenia, clincial chemistry changes associated with hepatocellular damage, and were euthanized due to respiratory insufficiency caused by radiation pneumonitis 120 to 131 days after pulmonary deposition of 22 to 65 μCi 241Am. Another group of dogs that received inhalation exposure to 241AmO2 and were treated daily with Zn-DTPA had initial pulmonary deposition of 19 to 26 μCi 241Am. These dogs did not develop respiratory insufficiency, and hematologic and clinical chemistry changes were less severe than in the non-DTPA-treated dogs

  8. Albuterol and Ipratropium Oral Inhalation

    Science.gov (United States)

    ... sure it is inserted correctly. Replace the clear plastic base on the inhaler. Hold the inhaler upright ... face mask. Connect the nebulizer reservoir to the compressor. Put the mouthpiece in your mouth or put ...

  9. Inhalation anaesthetics and climate change

    DEFF Research Database (Denmark)

    Andersen, Mads Peter Sulbæk; Sander, S P; Nielsen, O J;

    2010-01-01

    Although the increasing abundance of CO(2) in our atmosphere is the main driver of the observed climate change, it is the cumulative effect of all forcing agents that dictate the direction and magnitude of the change, and many smaller contributors are also at play. Isoflurane, desflurane, and...... sevoflurane are widely used inhalation anaesthetics. Emissions of these compounds contribute to radiative forcing of climate change. To quantitatively assess the impact of the anaesthetics on the forcing of climate, detailed information on their properties of heat (infrared, IR) absorption and atmospheric...

  10. Liposomal formulations for inhalation.

    Science.gov (United States)

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

    2013-08-01

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

  11. Inhalational Lung Disease

    Directory of Open Access Journals (Sweden)

    S Kowsarian

    2010-01-01

    Full Text Available Inhalational lung diseases are among the most important occupational diseases. Pneumoconiosis refers to a group of lung diseases result from inhalation of usually inorganic dusts such as silicon dioxide, asbestos, coal, etc., and their deposition in the lungs. The resultant pulmonary disorders depend on the susceptibility of lungs; size, concentration, solubility and fibrogenic properties of the inhaled particles; and duration of exposure. Radiographic manifestations of pneumoconiosis become apparent several years after exposure to the particles. However, for certain types of dusts, e.g., silicone dioxide crystal and beryllium, heavy exposure within a short period can cause an acute disease. Pulmonary involvement in asbestosis is usually in the lower lobes. On the contrary, in silicosis and coal worker pneumoconiosis, the upper lobes are involved predominantly. For imaging evaluation of pneumoconiosis, high-resolution computed tomography (CT is superior to conventional chest x-ray. Magnetic resonance imaging (MRI and positron emission tomography (PET scan are helpful in those with suspected tumoral lesions. In this essay, we reviewed the imaging aspects of inhalational lung disease.

  12. Inhalants. Specialized Information Service.

    Science.gov (United States)

    Do It Now Foundation, Phoenix, AZ.

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

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

    OpenAIRE

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

    2007-01-01

    Introduction Inhalation injury in combination with a severe thermal injury increases mortality. Alterations in inflammatory mediators, such as cytokines, contribute to the incidence of multi-organ failure and mortality. The aim of the present study was to determine the effect of inhalation injury on cytokine expression in severely burned children. Methods Thirty severely burned pediatric patients with inhalation injury and 42 severely burned children without inhalation injury were enrolled in...

  14. Laboratory approach for diagnosis of toluene-based inhalant abuse in a clinical setting

    OpenAIRE

    Raka Jain; Arpita Verma

    2016-01-01

    The steady increase of inhalant abuse is a great challenge for analytical toxicologists. This review describes an overview of inhalant abuse including the extent of the problem, types of products abused, modes of administration, pharmacology and effects of inhalants, the role of laboratory, interpretation of laboratory results and clinical considerations. Regular laboratory screening for inhalant abuse as well as other substance abuse and health risk behaviors must be a part of standard clini...

  15. Laboratory approach for diagnosis of toluene-based inhalant abuse in a clinical setting

    Directory of Open Access Journals (Sweden)

    Raka Jain

    2016-01-01

    Full Text Available The steady increase of inhalant abuse is a great challenge for analytical toxicologists. This review describes an overview of inhalant abuse including the extent of the problem, types of products abused, modes of administration, pharmacology and effects of inhalants, the role of laboratory, interpretation of laboratory results and clinical considerations. Regular laboratory screening for inhalant abuse as well as other substance abuse and health risk behaviors must be a part of standard clinical care.

  16. Inhaled transuranics in rodents

    International Nuclear Information System (INIS)

    This project examines the interactions of external and internal radiation from mixtures of radionuclides present within the nuclear fuel inventory. The objective of the project is to evaluate the effects of mixed radiation insults, using key radiation sources as indicative of overall processes that may occur following release of nuclear fuel into the air. Previously initiated studies of immunological effects of plutonium inhalation are also being completed as part of this project

  17. Insulin inhalation--Pfizer/Nektar Therapeutics: HMR 4006, inhaled PEG-insulin--Nektar, PEGylated insulin--Nektar.

    Science.gov (United States)

    2004-01-01

    type 1 and type 2 diabetes mellitus in 120 centres worldwide, and will use a fourth prototype inhaler device that is half the size of the first prototype, and has reduced manufacturing costs. Pfizer and its partner, Aventis Pharma, are conducting additional long-term pulmonary safety data studies in patients with type 1 and type 2 diabetes. Pfizer is also conducting phase III clinical trials with inhaled insulin in paediatric patients aged 6-17 years. Nektar Therapeutics is using its Advanced PEGylation technology to develop a dry powder-inhaled polyethylene glycol (PEG) formulation for delivering peptides efficiently across the lungs and to promote prolonged serum concentration of the peptide. PEG is a neutral, water-soluble, nontoxic polymer comprising any number of repeating units of ethylene oxide. PEGylation is designed to increase the size of the active molecule and ultimately improve drug performance by optimising pharmacokinetics, increasing bioavailability, and decreasing immunogenicity and dosing frequency. The investigation has begun with inhaled, long-acting (PEGylated) insulin [inhaled PEG-insulin, PEGylated insulin--Nektar], and is funded by Pfizer. Preclinical results of a dry powder formulation of inhaled PEG-insulin presented at the 63rd Scientific Sessions of the American Diabetes Association (ADA-2003) [June 2003, New Orleans, LA, USA] demonstrated prolonged systemic activity of insulin in dogs. Nektar Therapeutics was granted US patent 5,997,848 on a method for delivering inhalable insulin. The patent covers a method for delivering of 0.5-15 mg of aerosol dry powder insulin per dosing session in 1-4 individual dosages into the deep lung for systemic absorption. The patent does not specify the formulation of insulin or aerosol delivery device. Nektar Therapeutics estimated in June 2002 that Exubera could earn the company potential revenues of >200 million US dollars. PMID:15139780

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

    Science.gov (United States)

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

    2007-01-01

    Introduction Inhalation injury in combination with a severe thermal injury increases mortality. Alterations in inflammatory mediators, such as cytokines, contribute to the incidence of multi-organ failure and mortality. The aim of the present study was to determine the effect of inhalation injury on cytokine expression in severely burned children. Methods Thirty severely burned pediatric patients with inhalation injury and 42 severely burned children without inhalation injury were enrolled in the study. Inhalation injury was diagnosed by bronchoscopy during the first operation. Blood was collected within 24 hours of admission and again at five to seven days following admission. Cytokine expression was profiled using multi-plex antibody-coated beads. Significance was accepted at a p value of less than 0.05. Results The mean percentages of total body surface area burned were 67% ± 4% (56% ± 6%, third-degree burns) in the inhalation injury group and 60% ± 3% (45% ± 3%, third-degree burns) in the non-inhalation injury group (p value not significant [NS]). Mean age was 9 ± 1 years in the inhalation injury group and 8 ± 1 years in the non-inhalation injury group (p value NS). Time from burn to admission in the inhalation injury group was 2 ± 1 days compared to 3 ± 1 days in the non-inhalation injury group (p value NS). Mortalities were 40% in the inhalation injury group and 12% in the non-inhalation injury group (p < 0.05). At the time of admission, serum interleukin (IL)-7 was significantly increased in the non-inhalation injury group, whereas IL-12p70 was significantly increased in the inhalation injury group compared to the non-inhalation injury group (p < 0.05). There were no other significant differences between groups. Five to seven days following admission, all cytokines decreased with no differences between the inhalation injury and non-inhalation injury cohorts. Conclusion In the present study, we show that an inhalation injury causes alterations in IL-7

  19. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... metered dose inhaler one to two inches from mouth Your browser does not support iframes Using a ... KB] Using a metered dose inhaler (inhaler in mouth) Your browser does not support iframes Using a ...

  20. Insulin inhalation: NN 1998.

    Science.gov (United States)

    2004-01-01

    Aradigm Corporation has developed an inhaled form of insulin using its proprietary AERx drug delivery system. The system uses liquid insulin that is converted into an aerosol containing very small particles (1-3 micro in diameter), and an electronic device suitable for either the rapid transfer of molecules of insulin into the bloodstream or localised delivery within the lung. The AERx insulin Diabetes Management System (iDMS), AERx iDMS, instructs the user on breathing technique to achieve the best results. Aradigm Corporation and Novo Nordisk have signed an agreement to jointly develop a pulmonary delivery system for insulin [AERx iDMS, NN 1998]. Under the terms of the agreement, Novo Nordisk has exclusive rights for worldwide marketing of any products resulting from the development programme. Aradigm Corporation will initially manufacture the product covered by the agreement, and in return will receive a share of the overall gross profits from Novo Nordisk's sales. Novo Nordisk will cover all development costs incurred by Aradigm Corporation while both parties will co-fund final development of the AERx device. Both companies will explore the possibilities of the AERx platform to deliver other compounds for the regulation of blood glucose levels. Additionally, the agreement gives Novo Nordisk an option to develop the technology for delivery of agents outside the diabetes area. In April 2001, Aradigm Corporation received a milestone payment from Novo Nordisk related to the completion of certain clinical and product development stages of the AERx drug delivery system. Profil, a CRO in Germany, is cooperating with Aradigm and Novo Nordisk in the development of inhaled insulin. Aradigm and Novo Nordisk initiated a pivotal phase III study with inhaled insulin formulation in September 2002. This 24-month, 300-patient trial is evaluating inhaled insulin in comparison with insulin aspart. Both medications will be given three times daily before meals in addition to basal

  1. Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis: A European consensus

    DEFF Research Database (Denmark)

    Heijerman, Harry; Westerman, Elsbeth; Conway, Steven;

    2009-01-01

    In cystic fibrosis inhalation of drugs for the treatment of 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. In this European consensus document we...

  2. Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis : A European consensus

    NARCIS (Netherlands)

    Heijerman, Harry; Westerman, Elsbeth; Conway, Steven; Touw, Daan; Döring, Gerd; Frijlink, Henderik

    2009-01-01

    In cystic fibrosis inhalation of drugs for the treatment of 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. In this European consensus document we revie

  3. Inhalation of two putative Gulf War toxins by mice.

    Science.gov (United States)

    Repine, John E; Wilson, Paul; Elkins, Nancy; Klawitter, Jelena; Christians, Uwe; Peters, Ben; Smith, Dwight M

    2016-06-01

    We employed our inhalation methodology to examine whether biomarkers of inflammation and oxidative stress would be produced in mice following inhalation of aerosols containing carbonaceous particles or the vapor of pesticides prevalent during the first Gulf War. Exposure to two putative Gulf War Illness toxins, fine airborne particles and the pesticide malathion, increased biomarkers of inflammation and oxidative stress in Friend virus B (FVB) female mice. Mice inhaling particles 24 h before had increased lung lavage and plasma Leukotriene B4 (LTB4) (a biomarker of inflammation) and PGF2α (a biomarker of oxidative stress) levels, lung lavage protein and lung lavage lactic dehydrogenase (LDH) levels. These changes were a function of particle density and exposure time. Compared to particle inhalation, mice inhaling malathion 24 h before had small increase in plasma LTB4 and PGF2α levels but no increase in lung lavage LTB4, lung lavage protein, lung lavage LDH, and lung lavage alveolar macrophage (AM) levels compared to unexposed control mice. AM from particle-exposed mice contained phagocytosed particles, while AM from malathion-exposed mice showed no abnormalities. Our results indicate that inhaling particles or malathion can alter inflammatory and oxidative biomarkers in mice and raise the possibility that these toxins may have altered inflammation and oxidative stress biomarkers in Gulf War-exposed individuals. PMID:26950528

  4. Experimental investigation of design parameters on dry powder inhaler performance.

    Science.gov (United States)

    Ngoc, Nguyen Thi Quynh; Chang, Lusi; Jia, Xinli; Lau, Raymond

    2013-11-30

    The study aims to investigate the impact of various design parameters of a dry powder inhaler on the turbulence intensities generated and the performance of the dry powder inhaler. The flow fields and turbulence intensities in the dry powder inhaler are measured using particle image velocimetry (PIV) techniques. In vitro aerosolization and deposition a blend of budesonide and lactose are measured using an Andersen Cascade Impactor. Design parameters such as inhaler grid hole diameter, grid voidage and chamber length are considered. The experimental results reveal that the hole diameter on the grid has negligible impact on the turbulence intensity generated in the chamber. On the other hand, hole diameters smaller than a critical size can lead to performance degradation due to excessive particle-grid collisions. An increase in grid voidage can improve the inhaler performance but the effect diminishes at high grid voidage. An increase in the chamber length can enhance the turbulence intensity generated but also increases the powder adhesion on the inhaler wall. PMID:24055597

  5. Hepatotoxic Alterations Induced by Inhalation of Trichloroethylene (TCE) in Rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective Trichloroethylene (TCE) is one of the most potent organic unsaturated solvents being used in dry cleaning, metal degreasing, thinner for paints varnishes and electroplating, etc. and has been reported to be a hepatotoxicant through oral and dermal exposure. However, its inhalation toxicity data is very limited in the literature due to the fact that the exposure levels associated with these effects were usually not reported. Hence, inhalation toxicity study was carried out for hepatotoxic studies. Method Inhalation toxicity studies was carried out by exposing rats to TCE for 8, 12 and 24 weeks in a dynamically operated whole body inhalation chamber. Sham treated control rats were exposed to compressed air in the inhalation chamber for the same period. Results Significant increase in liver weight (liver enlargement) appearance of necrotic lesions with fatty changes and marked necrosis were observed after longer duration (12 and 24 weeks) of TCE exposure. The lysosomal rupture resulted in increased activity of acid and alkaline phosphatase alongwith reduced glutathione content and total increased sulfhydryl content in liver tissue. Conclusion TCE exposure through Inhalation route induces hepatotoxicity in terms of marked necrosis with fatty changes and by modulating the lysosomal enzymes.

  6. Inhaled plutonium nitrate in dogs

    International Nuclear Information System (INIS)

    Beagle dogs given a single inhalation exposure to 239Pu(NO3)4 are being observed for life-span dose-effect relationships. Lymphopenia occurred at the two highest dosage levels as early as 1 mo following exposure and was associated with neutropenia and reduction in numbers of circulatory monocytes by 4 mo postexposure. Radiation pneumonitis developed in one dog at the highest dosage level at 14 mo postexposure. More rapid translocation to skeleton and liver occurred following inhalation of 238Pu(NO3)4 than after 239Pu(NO3)4 inhalation

  7. Intestinal circulation during inhalation anesthesia

    International Nuclear Information System (INIS)

    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 86Rb and 9-microns spheres labeled with 141Ce 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 (AVDO2) 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

  8. Influence of flow rate on aerosol particle size distributions from pressurized and breath-actuated inhalers.

    Science.gov (United States)

    Smith, K J; Chan, H K; Brown, K F

    1998-01-01

    Particle size distribution of delivered aerosols and the total mass of drug delivered from the inhaler are important determinants of pulmonary deposition and response to inhalation therapy. Inhalation flow rate may vary between patients and from dose to dose. The Andersen Sampler (AS) cascade impactor operated at flow rates of 30 and 55 L/min and the Marple-Miller Impactor (MMI) operated at flow rates of 30, 55, and 80 L/min were used in this study to investigate the influence of airflow rate on the particle size distributions of inhalation products. Total mass of drug delivered from the inhaler, fine particle mass, fine particle fraction, percentage of nonrespirable particles, and amount of formulation retained within the inhaler were determined by ultraviolet spectrophotometry for several commercial bronchodilator products purchased in the marketplace, including a pressurized metered-dose inhaler (pMDI), breath-actuated pressurized inhaler (BAMDI), and three dry powder inhalers (DPIs), two containing salbutamol sulphate and the other containing terbutaline sulphate. Varying the flow rate through the cascade impactor produced no significant change in performance of the pressurized inhalers. Increasing the flow rate produced a greater mass of drug delivered and an increase in respirable particle mass and fraction from all DPIs tested. PMID:10346666

  9. Inhalant Dependence and its Medical Consequences

    OpenAIRE

    Mehmet Hamid Boztaş

    2010-01-01

    The term of inhalants is used for matters easily vapors. Inhalants are preferred for rapid, positive reinforcement and mild high effects. Products including inhalants are cheap, accessible, legal substances and are prevalently used in community. The prevalence of inhalant use in secondary schools in Turkey is about 5.1%. Inhalant substance dependence is generally observed within 14-15 age group. Age at first use could be as low as 5 to 6 years of age. Substance dependence is more probable in ...

  10. Biological effects of inhaled radionuclides

    International Nuclear Information System (INIS)

    This report focuses on various types of radionuclides that may be inhaled and deposited in the respiratory tract. One of the primary goals of this ICRP Task Group is to assess specifically the biological implications of inhaled plutonium. Because other transuranics are becoming more abundant, information on americium, curium and einsteinium is included. Data are also included from studies of polonium and of several beta-gamma emitting isotopes. The Task Group evaluated most of the data on the biological effects of inhaled radionuclides in experimental animals to identify the tissues at risk and to assess possible dose-response relationships. Few data from human cases of inhaled radionuclides are available for this assessment. The biological effects of nonradioactive air pollutants were also considered to provide the perspective that all air pollutants can have a deleterious effect on human life and to emphasize the possibility for combined or synergistic effects of nonradioactive and radioactive substances on the respiratory tract. (orig./HP)

  11. Inhaled plutonium oxide in dogs

    International Nuclear Information System (INIS)

    This project is concerned with long-term experiments to determine the life-span dose-effect relationships of inhaled 239PuO2 and 238PuO2 in beagles. The data will be used to estimate the health effects of inhaled transuranics. The tissue distribution of plutonium, radiation effects in the lung and hematologic changes in plutonium-exposed beagles with lung tumors were evaluated

  12. Inhalational anesthesia for organ procurement: potential indications for administering inhalational anesthesia in the brain-dead organ donor.

    Science.gov (United States)

    Elkins, Laurie J

    2010-08-01

    Organs needed for transplantation far outweigh their availability. There is minimal research regarding perioperative care of the brain-dead organ donor during the procurement procedure. Current research attributes a great deal of organ damage to autonomic or sympathetic storm that occurs during brain death. Literature searches were performed with the terms brain death, organ donor, organ procurement, anesthesia and organ donor, anesthesia and brain death, anesthesia and organ procurement, inhalational anesthetics and organ procurement, and inhalational anesthetics and brain dead. Additional resources were obtained from reference lists of published articles. The literature review showed there is a lack of published studies researching the use of inhalational anesthetics in organ procurement. No studies have been published evaluating the effect of preconditioning with inhalational agents (administering 1.3 minimal alveolar concentration of an inhalational agent for the 20 minutes before periods of ischemia) in the brain-dead organ donor population. Further studies are required to determine if administration of inhalational anesthetics reduces catecholamine release occurring with surgical stimulation during the organ procurement procedure and whether this technique increases viability of transplanted organs. Anesthetic preconditioning before the ischemic period may reduce ischemia-reperfusion injury in transplanted organs, further increasing viability of transplanted organs. PMID:20879630

  13. Puffing and inhalation behaviour in cigarette smoking: Implications for particle diameter and dose

    Energy Technology Data Exchange (ETDEWEB)

    Dickens, Colin; McGrath, Conor; Warren, Nigel; Biggs, Philip; McAughey, John, E-mail: colin_dickens@bat.co [British American Tobacco, Group R and D Centre, Southampton, SO15 8TL (United Kingdom)

    2009-02-01

    Inhalation of tobacco smoke aerosol is a two-step process involving puffing followed by inhalation. Measured smoke deposition efficiencies in the lung (20-70%) are greater than expected for smoke particles of diameter 150 - 250 nm CMD. Various mechanisms have been put forward to explain this enhanced deposition pattern, including coagulation, hygroscopic growth, condensation and evaporation, changes in composition, or changes in inhalation behaviour. This paper represents one of a series of studies seeking to better quantify smoke chemistry, inhalation behaviour and cumulative particle growth. The studies have been conducted to better understand smoke dosimetry and links to disease as part of a wider programme defining risk and potential harm reduction. In this study, it was noted that particle deposition increased with increasing inhalation depth, and that smoke inhalation volumes were generally greater than normal tidal breathing volumes. A weak association was observed between particle diameter and puff flow, but no strong association between particle diameter and retention efficiency.

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

    Science.gov (United States)

    Soloveva, A G; Peretyagin, S P

    2016-01-01

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

  15. Pneumoconiosis after sericite inhalation

    Science.gov (United States)

    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

  16. Inhalant abuse: An exploratory study

    Directory of Open Access Journals (Sweden)

    Rohit Verma

    2011-01-01

    Full Text Available Background: Inhalants are being abused by large numbers of people throughout the world, particularly children and adolescents. It is also an often overlooked form of ubstance abuse in adolescents. Aims: The current study explored the inhalant abuse among adolescents seeking treatment from a tertiary care drug de-addiction clinic. Settings and Design: The study was conducted at a tertiary level multispecialty hospital. Materials and Methods: The current study was a chart review of the cases with inhalant abuse/dependence presenting to the clinic over a 1-year period. All the treatment records of the de-addiction clinic were reviewed, and information was gathered regarding patients with inhalant abuse/dependence. Statistical Analysis: Descriptive statistics with frequency distribution was carried out by using SPSS version 10.0. Results: The mean age of the subjects was 16.24 years (SD±1.9 years; range 12-18 years. Twenty-two percent of the subjects were illiterate. Forty percent of the adolescents had a family history of alcohol use problems and 48% that of tobacco use. The mean age of the initiation of inhalant use was 11.6 years (SD±2.17 years. It varied from 9 to 18 years. Forty percent of the adolescents had made a previous abstinence attempt. Conclusions: The findings provide important information on an underresearched area in psychiatry.

  17. Zinc toxicology following particulate inhalation.

    Science.gov (United States)

    Cooper, Ross G

    2008-04-01

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

  18. Zinc toxicology following particulate inhalation

    Directory of Open Access Journals (Sweden)

    Cooper Ross

    2008-01-01

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

  19. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Guidelines Air Pollution & Respiratory Health Know How to Use Your Asthma Inhaler Recommend on Facebook Tweet Share ... to follow along with the correct way to use your metered dose inhaler. Print the step-by- ...

  20. Inhaled plutonium nitrate in dogs

    International Nuclear Information System (INIS)

    The major objective of this project is to determine dose-effect relationships of inhaled plutonium nitrate in dogs to aid in predicting health effects of accidental exposure in man. For lifespan dose-effect studies, beagle dogs were given a single inhalation exposure to 239Pu(NO3)4, in 1976 and 1977. The earliest biological effect was on the hematopoietic system; lymphopenia and neutropenia occurred at the two highest dose levels. The authors have also observed radiation pneumonitis, lung cancer, and bone cancer at the three highest dose levels. 1 figure, 4 tables

  1. Inhaled plutonium nitrate in dogs

    International Nuclear Information System (INIS)

    The major objective of this project is to determine dose-effect relationships of inhaled plutonium nitrate in dogs to aid in predicting health effects of accidental exposure in man. For lifespan dose-effect studies, beagle dogs were given a single inhalation exposure to 239Pu(NO3)4, in 1976 and 1977. The earliest biological effect was on the hematopoietic system; lymphopenia and neutropenia occurred at the two highest dose levels. They have also observed radiation pneumonitis, lung cancer, and bone cancer at the three highest dose levels. 1 figure, 3 tables

  2. Age dependent systemic exposure to inhaled salbutamol

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus; Jespersen, Jakob Jessing; Bisgaard, Hans

    2007-01-01

    AIMS: To determine the effect of age on systemic exposure to inhaled salbutamol in children. METHODS: Fifty-eight asthmatic children, aged 3-16 years, inhaled 400 microg of salbutamol from a pressurized metered dose inhaler with spacer. The 20 min serum profile was analyzed. RESULTS: Prescribing a...

  3. 40 CFR 798.2450 - Inhalation toxicity.

    Science.gov (United States)

    2010-07-01

    ... CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Subchronic Exposure § 798.2450 Inhalation... initial information on toxicity has been obtained by acute testing. The subchronic inhalation study has... daily exposure of experimental animals to a chemical by inhalation for part (approximately 10...

  4. Impact of inhalation therapy on oral health

    Directory of Open Access Journals (Sweden)

    Navneet Godara

    2011-01-01

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

  5. Effect of Hyperoxygenation on Tissue pO2 and Its Effect on Radiotherapeutic Efficacy of Orthotopic F98 Gliomas

    International Nuclear Information System (INIS)

    Purpose: Lack of methods for repeated assessment of tumor pO2 limits the ability to test and optimize hypoxia-modifying procedures being developed for clinical applications. We report repeated measurements of orthotopic F98 tumor pO2 and relate this to the effect of carbogen inhalation on tumor growth when combined with hypofractionated radiotherapy. Methods and Materials: Electron paramagnetic resonance (EPR) oximetry was used for repeated measurements of tumor and contralateral brain pO2 in rats during 30% O2 and carbogen inhalation for 5 consecutive days. The T1-enhanced volumes and diffusion coefficients of the tumors were assessed by magnetic resonance imaging (MRI). The tumors were irradiated with 9.3 Gy x 4 fractions in rats breathing 30% O2 or carbogen to determine the effect on tumor growth. Results: The pretreatment F98 tumor pO2 varied between 8 and 16 mmHg, while the contralateral brain had 41 to 45 mmHg pO2 during repeated measurements. Carbogen breathing led to a significant increase in tumor and contralateral brain pO2; however, this effect declined over days. Irradiation of the tumors in rats breathing carbogen resulted in a significant decrease in tumor growth and an increase in the diffusion coefficient measured by MRI. Conclusions: The results provide quantitative measurements of the effect of carbogen inhalation on intracerebral tumor pO2 and its effect on therapeutic outcome. Such direct repeated pO2 measurements by EPR oximetry can provide temporal information that could be used to improve therapeutic outcome by scheduling doses at times of improved tumor oxygenation. EPR oximetry is currently being tested for clinical applications.

  6. Passive inhalation of cannabis smoke

    Energy Technology Data Exchange (ETDEWEB)

    Law, B.; Mason, P.A.; Moffat, A.C.; King, L.J.; Marks, V.

    1984-09-01

    Six volunteers each smoked simultaneously, in a small unventilated room (volume 27 950 liter), a cannabis cigarette containing 17.1 mg delta 9-tetrahydrocannabinol (THC). A further four subjects - passive inhalers - remained in the room during smoking and afterwards for a total of 3 h. Blood and urine samples were taken from all ten subjects and analyzed by radioimmunoassay for THC metabolites. The blood samples from the passive subjects taken up to 3 h after the start of exposure to cannabis smoke showed a complete absence of cannabinoids. In contrast, their urine samples taken up to 6 h after exposure showed significant concentrations of cannabinoid metabolites (less than or equal to 6.8 ng ml-1). These data, taken with the results of other workers, show passive inhalation of cannabis smoke to be possible. These results have important implications for forensic toxicologists who are frequently called upon to interpret cannabinoid levels in body fluids.

  7. Inhaled plutonium oxide in dogs

    International Nuclear Information System (INIS)

    This project is concerned with long-term experiments to determine the lifespan dose-effect relationships of inhaled 239PuO2 and 238PuO2 in beagles. Beagle dogs given a single exposure to 239PuO2 or 238PuO2 aerosols are being observed for lifespan dose-effect relationships. The 239Pu body burden of the nine dogs that died of pulmonary-fibrosis-induced respiratory insufficiency during the first 3 yr after exposure was 1 to 12μCi. Nineteen of the dogs exposed to 238Pu haved died during the first 7-1/2 yr after exposure due to bone and/or lung tumors; their body burdens at death ranged from 0.7 to 10μCi. Chronic lymphopenia was the earliest observed effect after inhalation of 239PuO2 or 238PuO2

  8. Radon inhalation protects against transient global cerebral ischemic injury in gerbils.

    Science.gov (United States)

    Kataoka, Takahiro; Etani, Reo; Takata, Yuji; Nishiyama, Yuichi; Kawabe, Atsushi; Kumashiro, Masayuki; Taguchi, Takehito; Yamaoka, Kiyonori

    2014-10-01

    Although brain disorders are not the main indication for radon therapy, our previous study suggested that radon inhalation therapy might mitigate brain disorders. In this study, we assessed whether radon inhalation protects against transient global cerebral ischemic injury in gerbils. Gerbils were treated with inhaled radon at a concentration of 2,000 Bq/m(3) for 24 h. After radon inhalation, transient global cerebral ischemia was induced by bilateral occlusion of the common carotid artery. Results showed that transient global cerebral ischemia induced neuronal damage in hippocampal CA1, and the number of damaged neurons was significantly increased compared with control. However, radon treatment inhibited ischemic damage. Superoxide dismutase (SOD) activity in the radon-treated gerbil brain was significantly higher than that in sham-operated gerbils. These findings suggested that radon inhalation activates antioxidative function, especially SOD, thereby inhibiting transient global cerebral ischemic injury in gerbils. PMID:24792782

  9. Inhaling to mitigate exhaled bioaerosols

    OpenAIRE

    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 ...

  10. Toxicological Assessment of Noxious Inhalants

    OpenAIRE

    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 x...

  11. Inhaled Therapies for Pulmonary Hypertension.

    Science.gov (United States)

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

    2015-06-01

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

  12. Hematologic effects of inhaled plutonium in beagles

    International Nuclear Information System (INIS)

    Beagle dogs were exposed, by inhalation, 5 to 11 years ago, to aerosols of 239PuO2, 238PuO2, or 239Pu(NO3)4, at six dose levels resulting in initial lung burdens ranging from ∼2 to ∼5500 nCi. Translocation of the plutonium to extrapulmonary sites was related to the physical-chemical characteristics of the plutonium compound. The highly insoluble 239PuO2 was retained primarily in the lung and associated lymph nodes, whereas 239Pu(NO3)4 was much more soluble and translocated relatively rapidly to the skeleton and other extrapulmonary tissues. The 238PuO2 was intermediate in solubility and translocation characteristics. The hematologic effects of plutonium inhalation were most pronounced on lymphocyte populations. Evidence suggests that these effects result from irradiation of lymphocytes via the pulmonary lymph nodes with insoluble 239PuO2, and via these same lymph nodes, extrapulmonary lymph nodes, and bone marrow lymphocytes with the more soluble forms, i.e., 238PuO2 and 239Pu(NO3)4. There is no evidence suggesting that these exposures increase the risk of developing myeloid or lymphoid neoplasia. 8 refs., 4 figs., 3 tabs

  13. Inhalational anaesthesia with low fresh gas flow

    Directory of Open Access Journals (Sweden)

    Christian Hönemann

    2013-01-01

    Full Text Available During the inhalation of anaesthesia use of low fresh gas flow (0.35-1 L/min has some important advantages. There are three areas of benefit: pulmonary - anaesthesia with low fresh gas flow improves the dynamics of inhaled anaesthesia gas, increases mucociliary clearance, maintains body temperature and reduces water loss. Economic - reduction of anaesthesia gas consumption resulting in significant savings of > 75% and Ecological - reduction in nitrous oxide consumption, which is an important ozone-depleting and heat-trapping greenhouse gas that is emitted. Nevertheless, anaesthesia with high fresh gas flows of 2-6 L/min is still performed, a technique in which rebreathing is practically negligible. This special article describes the clinical use of conventional plenum vaporizers, connected to the fresh gas supply to easily perform low (1 L/min, minimal (0.5 L/min or metabolic flow anaesthesia (0.35 L/min with conventional Primus Draeger® anaesthesia machines in routine clinical practice.

  14. [Significance of inhaled environmental allergens].

    Science.gov (United States)

    Zochert, J

    1983-01-01

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

  15. Cancer hazard from inhaled plutonium

    International Nuclear Information System (INIS)

    The best estimate of the lung cancer potential in humans for inhaled insoluble compounds of plutonium (such as PuO2 particles) has been grossly underestimated by such authoritative bodies as the International Commission on Radiological Protection and the British Medical Research Council. Calculations are presented of lung cancer induction by 239Pu as insoluble particles and for deposited reactor-grade Pu. The reason for the gross underestimate of the carcinogenic effects of Pu by ICRP or the British Medical Research Council (BMRC) is their use of a totally unrealistic idealized model for the clearance of deposited Pu from the lungs and bronchi plus their non-recognition of the bronchi as the true site for most human lung cancers. The erroneous model used by such organizations also fails totally to take into account the effect of cigarette-smoking upon the physiological function of human lungs. Plutonium nuclides, such as 239Pu, or other alpha particle-emitting nuclides, in an insoluble form represent an inhalation cancer hazard in a class some 100,000 times more potent than the potent chemical carcinogens, weight for weight. The already-existing lung cancer data for beagle dogs inhaling insoluble PuO2 particles is clearly in order of magnitude agreement with calculations for humans

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

    OpenAIRE

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

    2008-01-01

    Introduction Severely burned patients suffering from inhalation injury have a significantly increased risk for mortality compared with burned patients without inhalation injury. Severe burn is associated with a distinct serum cytokine profile and alterations in cytokines that contribute to morbidity and mortality. The aim of the present study was therefore to determine whether severely burned pediatric patients with concomitant inhalation injury who had a fatal outcome exhibited a different s...

  17. The Skeletal Effects of Inhaled Glucocorticoids.

    Science.gov (United States)

    Sutter, Stephanie A; Stein, Emily M

    2016-06-01

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

  18. The Ozone Layer and Metered Dose Inhalers

    OpenAIRE

    Louis-Philippe Boulet

    1998-01-01

    The stratospheric ozone layer plays a crucial role in protecting living organisms against ultraviolet radiation. Chlorofluorocarbons (CFC) contained in metered-dose inhalers (MDIs) contribute to ozone depletion and in accordance with the Montreal Protocol on Substances That Deplete the Ozone Layer established 10 years ago, phase-out strageies have been developed worldwide for this category of agents. Alternatives to CFC-containing inhalers have been developed, such as powder inhalers and thos...

  19. Training Issues in the Use of Inhalers

    OpenAIRE

    Martin Duerden; David Price

    2001-01-01

    Patient compliance and techniques used with inhalation devices can strongly influence the effectiveness of inhaled medications but these issues are often poorly recognized and may be neglected when these products are prescribed. The extent of these problems and the success of differing education and training programs designed to improve inhaler technique have been evaluated by a review of the literature using Medline, EMBASE and Biosis Database from 1985 to date. Drug delivery to the airways ...

  20. The importance of continuity in inhaler device choice for asthma and chronic obstructive pulmonary disease.

    Science.gov (United States)

    Bjermer, Leif

    2014-01-01

    Inhaled therapies are central to the treatment of asthma and chronic obstructive pulmonary disease. Physicians consider many factors when selecting the most appropriate inhaler device, including device efficacy and the cost to the health care system. This review aims to discuss the factors that are important when considering inhaler devices and the importance of continuity in the choice of inhaler device. A large number of factors can contribute to therapeutic outcomes with inhalation devices. The inhalation technique is critical to treatment success and differs substantially between inhaler devices. Misuse of an inhaler is common, and thorough training of patients and physicians is important to ensure correct utilization. Patient satisfaction is an important consideration because it is significantly correlated with compliance and better outcomes. Financial pressures contribute to decision making: although selecting the less expensive inhaler device might reduce direct treatment costs, it can have a large impact on disease control and the patient's well-being. Switching may be associated with a poor inhalation technique, reduced disease control and quality of life, increased use of other treatments and health care resources, and a greater chance of unsuccessful treatment. Nonconsensual switches can result in patient discontent, reduced confidence in the medication, and uncertainty regarding the degree of disease control. It is recommended that patients with stable disease remain on their current device. If a switch is considered, the patient should be consulted and the physician should take into account the patient's preference, their ability to correctly use the device, and the availability of the preferred drug in the preferred device. PMID:25195762

  1. Evidence for the efficacy of aztreonam for inhalation solution in the management of Pseudomonas aeruginosa in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Hansen, Christine; Skov, Marianne

    2015-01-01

    for 'inhaled aztreonam' and 'cystic fibrosis'. Inhaled aztreonam is an important new treatment option for chronic P. aeruginosa infection in CF. Long-term studies have shown that the drug is safe and superior to inhaled tobramycin in these specific infections.......Chronic airway infection in cystic fibrosis (CF) is a main cause of the increased morbidity and mortality found with this disease. The most common cause of Gram-negative infection is Pseudomonas aeruginosa. The introduction of inhaled antibiotics has changed the lives of affected patients and the...

  2. Inhalant abuse: youth at risk.

    Science.gov (United States)

    Ahern, Nancy R; Falsafi, Nasrin

    2013-08-01

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

  3. Airmax: a multi-dose dry powder inhaler.

    Science.gov (United States)

    Keating, Gillian M; Faulds, Diana

    2002-01-01

    Airmax is a multi-dose dry powder inhaler. An internal pump measures out the drug dose using controlled air pressure. Inhalation transports the drug into a cyclone separator (where active drug is separated from the lactose carrier) and then into the patient airway. In vitro studies indicate that Airmax may be less dependent on airflow than Turbuhaler for drug delivery; greater dose consistency was seen with administration of budesonide via Airmax than via Turbuhaler. At a low flow rate, the lung deposition of budesonide administered via Airmax was greater than that of budesonide administered via Turbuhaler or a pressurised metered dose inhaler in patients with asthma. In cumulative-dose studies, the mean forced expiratory volume in 1 second (FEV(1)) achieved with salbutamol (albuterol) or formoterol administered via Airmax was equivalent to that achieved with twice the dose administered via dry powder inhalers. black triangle In randomised, double-blind studies, budesonide administration via Airmax was equivalent to administration via Turbuhaler with regards to FEV(1) and improvement in asthma symptoms in both adults and children with asthma. The concentration of adenosine monophosphate producing a 20% fall in FEV(1) increased from pretreatment levels by a greater extent with budesonide administered via Airmax, compared with Turbuhaler. Both adults and children preferred Airmax to Turbuhaler, and more found Airmax easier to use. In one study, the majority of children found learning how to use Airmax trade mark easier than learning how to use Turbuhaler. PMID:12215059

  4. Evidence of Inhaled Tobramycin in Non-Cystic Fibrosis Bronchiectasis

    Science.gov (United States)

    Vendrell, Montserrat; Muñoz, Gerard; de Gracia, Javier

    2015-01-01

    There is currently less experience with inhaled tobramycin in non-cystic fibrosis bronchiectasis than in cystic fibrosis (CF). Intravenous formulation and solution for inhalation (TSI) have been studied in non-CF bronchiectasis patients with chronic P. aeruginosa bronchial infection. An improvement in clinical parameters and a reduction in bacterial density have been shown with both inhaled solutions in these patients. However, further trials are needed to determine the most effective dose and administration protocol in these patients. Based on the current evidence, recommendations cannot be made regarding the use of TSI to treat exacerbations. Although no systemic toxicity has been reported in studies specifically investigating this treatment, patients with known kidney disease or ear disorders should be treated with caution. Adverse respiratory effects are reported to be more common in non-CF patients than in CF patients, who tend to be non-smokers and younger. Research is being conducted into the possibility of combining tobramycin with other antibiotics to increase its antibacterial activity. In this review we will present and discuss the published evidence regarding the use of inhaled tobramycin in non–CF bronchiectasis. PMID:25893022

  5. Asthma and Adherence to Inhaled Corticosteroids

    DEFF Research Database (Denmark)

    Bårnes, Camilla Boslev; Ulrik, Charlotte Suppli

    2015-01-01

    Inhaled corticosteroids (ICS) are the cornerstone of maintenance asthma therapy. However, in spite of this, adherence to ICS remains low. The aim of this systematic literature review was to provide an overview of the current knowledge of adherence to ICS, effects of poor adherence, and means to...... was found to be between 22 and 63%, with improvement up to and after an exacerbation. Poor adherence was associated with youth, being African-American, having mild asthma, < 12 y of formal education, and poor communication with the health-care provider, whereas improved adherence was associated with...... asthma-related hospitalizations could be attributed to poor adherence. Most studies have reported an increase in adherence following focused interventions, followed by an improvement in quality of life, symptoms, FEV1, and oral corticosteroid use. However, 2 studies found no difference in health...

  6. A new mask to prevent environmental contamination during radio aerosol mouth-piece inhalation procedures

    International Nuclear Information System (INIS)

    Environmental contamination is frequent during labelled aerosol mouth-piece inhalation procedures. Previous personnel data showed that in 18/18 situations air background activity has increased after inhalation and this may create serious routine and economical problems. We have tested a new adherent mask made of 3 M's TEGADERM in sixty 99 m Tc-DTPA inhalation studies and the results indicates that the use of such a mask may eliminate the problem of environmental contamination. The device is useful but not entirely efficient in cases when good skin adherence cannot be obtained. 48 refs, 10 figs, 2 tabs

  7. Dose emission and aerodynamic characterization of the terbutaline sulphate dose emitted from a Turbuhaler at low inhalation flow.

    Science.gov (United States)

    Abdelrahim, M E; Assi, K H; Chrystyn, H

    2013-01-01

    Previously, dose emission below 30 L min(-1) through DPI has not been routinely determined. However, during routine use some patients do not achieve 30 L min(-1) inhalation flows. Hence, the aim of the present study was to determine dose emission characteristics for low inhalation flows from terbutaline sulphate Turbuhaler. Total emitted dose (TED), fine particle dose (FPD) and mass median aerodynamic diameter (MMAD) of terbutaline sulphate Turbuhaler were determined using inhalation flows of 10-60 L min(-1) and inhaled volume of 4 L. TED and FPD increase significantly with the increase of inhalation flows (p <0.05). Flows had more pronounced effect on FPD than TED, thus, faster inhalation increases respirable amount more than it increases emitted dose. MMAD increases with decrease of inhalation flow until flow of 20L min(-1) then it decreases. In vitro flow dependent dose emission has been demonstrated previously for Turbuhaler for flow rates above 30 L min(-1) but is more pronounced below this flow. Minimal FPD below 30 L min(-1) suggests that during routine use at this flow rate most of emitted dose will impact in mouth. Flow dependent dose emission results suggest that Pharmacopoeias should consider the use variety of inhalation flows rather than one that is equivalent to pressure drop of 4 KPa. PMID:21981637

  8. Inhalable PEGylated Phospholipid Nanocarriers and PEGylated Therapeutics for Respiratory Delivery as Aerosolized Colloidal Dispersions and Dry Powder Inhalers

    Directory of Open Access Journals (Sweden)

    Priya Muralidharan

    2014-06-01

    Full Text Available Nanomedicine is making groundbreaking achievements in drug delivery. The versatility of nanoparticles has given rise to its use in respiratory delivery that includes inhalation aerosol delivery by the nasal route and the pulmonary route. Due to the unique features of the respiratory route, research in exploring the respiratory route for delivery of poorly absorbed and systemically unstable drugs has been increasing. The respiratory route has been successfully used for the delivery of macromolecules like proteins, peptides, and vaccines, and continues to be examined for use with small molecules, DNA, siRNA, and gene therapy. Phospholipid nanocarriers are an attractive drug delivery system for inhalation aerosol delivery in particular. Protecting these phospholipid nanocarriers from pulmonary immune system attack by surface modification by polyethylene glycol (PEGylation, enhancing mucopenetration by PEGylation, and sustaining drug release for controlled drug delivery are some of the advantages of PEGylated liposomal and proliposomal inhalation aerosol delivery. This review discusses the advantages of using PEGylated phospholipid nanocarriers and PEGylated therapeutics for respiratory delivery through the nasal and pulmonary routes as inhalation aerosols.

  9. Toxicological Assessment of Noxious Inhalants

    Directory of Open Access Journals (Sweden)

    Kleinsasser, N. H.

    2004-12-01

    Full Text Available 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.

  10. Toxicological assessment of noxious inhalants.

    Science.gov (United States)

    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

  11. Persistent increases in inflammatory cytokines, Akt, and MAPK/ERK pathways after inhalation exposure of rats to Libby amphibole (LA) or amosite: comparison to effects after intratracheal exposure to LA or naturally occurring asbestos.

    Science.gov (United States)

    Human exposure to LA and other mined or processed asbestos increases risk of lung inflammation, fibrosis, and cancer. Health risks from exposure to naturally occurring asbestos (NOA) are not as well-understood. Mechanisms of long-term toxicity were compared in male F344 rats expo...

  12. Inhalants

    Science.gov (United States)

    ... liquids that vaporize at room temperature Industrial or household products , including paint thinners or removers, degreasers, dry-cleaning ... oil sprays Gases —found in household or commercial products and used as medical anesthetics Household or commercial products , including butane lighters and propane ...

  13. Inhalants

    Science.gov (United States)

    ... Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the ... Health Effects Statistics and Trends Swipe left or right to scroll. Monitoring the Future Study: Trends in ...

  14. Inhalant Dependence and its Medical Consequences

    Directory of Open Access Journals (Sweden)

    Mehmet Hamid Boztaş

    2010-12-01

    Full Text Available The term of inhalants is used for matters easily vapors. Inhalants are preferred for rapid, positive reinforcement and mild high effects. Products including inhalants are cheap, accessible, legal substances and are prevalently used in community. The prevalence of inhalant use in secondary schools in Turkey is about 5.1%. Inhalant substance dependence is generally observed within 14-15 age group. Age at first use could be as low as 5 to 6 years of age. Substance dependence is more probable in adults working in substance existing places. Inhalant usage is common in disadvantaged groups, children living in street, people with history of crimes, prison, depression, suicide, antisocial attitudes and conflict of family, history of abuse, violence and any other drug dependence and isolated populations. Inhalants are absorbed from lungs, after performing their quick and short effect metabolized by cytochrom P450 enzyme system except inhalant nitrites group which has a depressing effect like alcohol. In chronic use general atrophy, ventricular dilatation and wide sulcus were shown in cerebrum, cerebellum and pons by monitoring brain. Defects are mostly in periventricular, subcortical regions and in white matter. Demyelinization, hyperintensity, callosal slimming and wearing off in white and gray matter margins was also found. Ravages of brain shown by brain monitorisation are more and serious in inhalant dependence than in other dependences. It is important to decrease use of inhalants. Different approaches should be used for subcultures and groups in prevention. Prohibiting all the matters including inhalant is not practical as there are too many substances including inhalants. Etiquettes showing harmful materials can be used but this approach can also lead the children and adolescents recognize these substances easily.. Despite determintal effects of inhalant dependence, there are not yet sufficient number of studies conducted on prevention and

  15. Clinical effectiveness of the Respimat® inhaler device in managing chronic obstructive pulmonary disease: evidence when compared with other handheld inhaler devices

    Directory of Open Access Journals (Sweden)

    et al

    2011-02-01

    only outcome for which data were available for meta-analysis was exacerbations, which were not significantly different (RR 1.20: P = 0.12. In addition, five trials with 2136 patients showed that there was no difference in risk of exacerbations or nasopharyngitis when Respimat was compared with all other handheld inhaler devices (RR 1.18: P = 0.13 and RR 1.33: P = 0.19, respectively. None of the clinical outcome measures reported was significantly different when the same, higher, or lower doses of medication were used in the inhaler devices being compared. Unfortunately, none of the included trials reported mortality as an outcome measure.Conclusions: Evidence from high-quality trials published to date suggests that the Respimat inhaler does not provide any additional clinical benefit to that provided by other inhaler devices in the management of COPD. Although in vitro studies have reported differences between the Respimat inhaler device and other handheld devices, we found no difference in any clinical outcome measures, including lung function and adverse events. Although recent reports have highlighted concerns of increased mortality with the Respimat inhaler device, none of the included trials reported mortality as an outcome. Only a small number of trials reported data that could be used in this systematic review, and a limited number of studies have been published that compare Respimat with other inhaler devices using the same drug and strength. Therefore, further trials comparing Respimat with other handheld inhaler devices using the same drug and dose are required before firm conclusions can be drawn. The concern with increased mortality with Respimat use should be investigated urgently.Keywords: Respimat, aerosol cloud, handheld inhaler devices, COPD

  16. The Ozone Layer and Metered Dose Inhalers

    Directory of Open Access Journals (Sweden)

    Louis-Philippe Boulet

    1998-01-01

    Full Text Available The stratospheric ozone layer plays a crucial role in protecting living organisms against ultraviolet radiation. Chlorofluorocarbons (CFC contained in metered-dose inhalers (MDIs contribute to ozone depletion and in accordance with the Montreal Protocol on Substances That Deplete the Ozone Layer established 10 years ago, phase-out strageies have been developed worldwide for this category of agents. Alternatives to CFC-containing inhalers have been developed, such as powder inhalers and those using hydrofluoroalkanes (HFAs as propellants, which have been shown to be as safe and effective as CFC-containing inhalers and even offer interesting advantages over older inhalers. The transition to non-CFC MDIs requires a major effort to make the new products available and to ensure adequate comparision with the previous ones. It also requires a harmonization of actions taken by industry, government, licencing bodies and patients or health professional associations to ensure adequate information and education to the public and respiratory care providers.

  17. Moderating effects of perceived social benefits on inhalant initiation among American Indian and White youth.

    Science.gov (United States)

    Swaim, Randall C

    2016-05-01

    This study examined whether perceived social benefits moderated the relationship between social influence variables (school attachment, peer inhalant use, perceived family caring, and parental monitoring) and stage of inhalant initiation (Study 1) and lifetime inhalant use (Study 2). Participants were 7th to 12th grade students attending schools on or near American Indian reservations, with comparisons made between American Indian and White students. A total of 3,498 American Indian and 1,596 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. Structural equation models were evaluated to examine variable relationships for the 2 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 nonusers across measures of social influence (Study 2). Perceived social benefits generally did not moderate the relationships, with 2 exceptions. Low perceived social benefits provided greater protection against the influence of peers on lifetime inhalant use among White students, whereas high perceived social benefits increased risk of peer influence among American Indian students. (PsycINFO Database Record PMID:26962974

  18. Optimising Inhaled Pharmacotherapy for Elderly Patients with Chronic Obstructive Pulmonary Disease: The Importance of Delivery Devices.

    Science.gov (United States)

    Lavorini, Federico; Mannini, Claudia; Chellini, Elisa; Fontana, Giovanni A

    2016-07-01

    Chronic obstructive pulmonary disease (COPD) is common in older people. Inhaled medications are the mainstay of pharmacological treatment of COPD, and are typically administered by handheld inhalers, such as pressurised metered-dose inhalers and dry powder inhalers, or by nebulisers. For each of the three major categories of aerosol delivery devices, several new inhalers have recently been launched, each with their own particularities, advantages and disadvantages. Consequently, broader availability of new drug-device combinations will increase prescription opportunities. Despite this, however, there is limited guidance available in published guidelines on the choice of inhalers, and still less consideration is given to elderly patients with COPD. The aim of this article is to provide a guide for healthcare professionals on device selection and factors to be considered for effective inhaled drug delivery in elderly COPD patients, including device factors (device type and complexity of use), patient factors (inspiratory capabilities, manual dexterity and hand strength, cognitive ability, co-morbidities) and considerations for healthcare professionals (proper education of patients in device use). PMID:27216613

  19. An Analysis of Inhalation Injury Diagnostic Methods and Patient Outcomes.

    Science.gov (United States)

    Ching, Jessica A; Ching, Yiu-Hei; Shivers, Steven C; Karlnoski, Rachel A; Payne, Wyatt G; Smith, David J

    2016-01-01

    The purpose of this study was to compare patient outcomes according to the method of diagnosing burn inhalation injury. After approval from the American Burn Association, the National Burn Repository Dataset Version 8.0 was queried for patients with a diagnosis of burn inhalation injury. Subgroups were analyzed by diagnostic method as defined by the National Burn Repository. All diagnostic methods listed for each patient were included, comparing mortality, hospital days, intensive care unit (ICU) days, and ventilator days (VDs). Z-tests, t-tests, and linear regression were used with a statistical significance of P value of less than .05. The database query yielded 9775 patients diagnosed with inhalation injury. The greatest increase in mortality was associated with diagnosis by bronchoscopy or carbon monoxide poisoning. A relative increase in hospital days was noted with diagnosis by bronchoscopy (9 days) or history (2 days). A relative increase in ICU days was associated with diagnosis according to bronchoscopy (8 days), clinical findings (2 days), or history (2 days). A relative increase in VDs was associated with diagnosis by bronchoscopy (6 days) or carbon monoxide poisoning (3 days). The combination of diagnosis by bronchoscopy and clinical findings increased the relative difference across all comparison measures. The combination of diagnosis by bronchoscopy and carbon monoxide poisoning exhibited decreased relative differences when compared with bronchoscopy alone. Diagnosis by laryngoscopy showed no mortality or association with poor outcomes. Bronchoscopic evidence of inhalation injury proved most useful, predicting increased mortality, hospital, ICU, and VDs. A combined diagnosis determined by clinical findings and bronchoscopy should be considered for clinical practice. PMID:26594867

  20. Total Intravenous Versus Inhalation Anesthesia in Patients Undergoing Laparoscopic Cholecystectomies. Effects on Two Proinflammatory Cytokines Serum Levels: Il-32 and TNF-Alfa.

    Directory of Open Access Journals (Sweden)

    Hadade Adina

    2016-01-01

    Full Text Available Introduction: It has been reported that as compared with total intravenous anesthesia (TIVA, inhalation anesthesia is increasing the postoperative level of proinflammatory interleukins.

  1. Reproduction and evaluation of a rat model of inhalation lung injury caused by black gunpowder smog

    Directory of Open Access Journals (Sweden)

    Yi-fan LIU

    2013-09-01

    Full Text Available Objective To reproduce and evaluate a rat model of inhalation lung injury caused by black gunpowder smog. Methods The smog composition was analyzed and a rat model of inhalation lung injury was reproduced. Forty two healthy male Wistar rats were randomly divided into normal control (NC group and 1h, 2h, 6h, 24h, 48h and 96h after inhalation group (n=6. The arterial blood gas, wet to dry weight ratio (W/D of lung, leukocyte count, and protein concentration in broncho-alveolar lavage fluid (BALF were determined. Macroscopic and microscopic changes in lung tissue were observed. Results The composition of black gunpowder smog was composed mainly of CO2 and CO, and their concentrations remained stable within 12 minutes. Smog inhalation caused a significant hypoxemia, the concentration of blood COHb reached a peak value 1h, and the W/D of lung reached peak value 2h after inhalation (P<0.05. The amount of leukocytes and content of protein in BALF increased significantly within 24h after inhalation (P<0.05. Histopathological observation showed diffuse hemorrhage, edema and inflammatory cell infiltration in lung tissue as manifestations of acute lung injury, and the injury did not recover at 96h after inhalation. Conclusion The rat model of inhalation lung injury can be reproduced using black gunpowder smog, and it has the advantages of its readiness for reproduction, reliability and stability, and it could be used for the experiment of inhalation injury in a battlefield environment.

  2. The effect of codeine on the Urge-to-Cough response to inhaled capsaicin

    OpenAIRE

    Davenport, P.W.; Bolser, D. C.; Vickroy, T.; Berry, R.B.; Martin, A. D.; Hey, John A; Danzig, M.

    2006-01-01

    We have shown previously in normal subjects that a sensory measure, the Urge-to-Cough rating, increases at concentrations of inhaled capsaicin that are lower than those necessary to elicit reflex cough. This finding suggests that the Urge-to-Cough may represent an index of the cough response. Research on cough in the human has most often employed challenge with inhaled capsaicin to induce reflex cough. Current measures of cough sensitivity in the human provide no information regarding the int...

  3. Effect of inhaled terbutaline sulphate in relation to its deposition in the lungs.

    Science.gov (United States)

    Hultquist, C; Wollmer, P; Eklundh, G; Jonson, B

    1992-06-01

    We studied the effects of inhaled terbutaline on FEV1 and gas exchange, and the pattern of deposition within the lungs. To document this and to estimate the dose of terbutaline administered to the lungs, [99mTc]DTPA was added to nebulised terbutaline solution. The aerosol was deposited preferentially in large or small airways by using aerosols with different particle mass median diameters (1.5 and 4.8 microns) and different inhalation flow rates (0.25 and 1.0 l/s). The patients inhaled placebo and then three increasing doses of terbutaline (0.006, 0.02 and 0.08 mg to the lungs). Finally, 2 mg terbutaline was inhaled from a metered dose inhaler via a spacer. After each inhalation FEV1, PaO2 and PaCO2 was measured. The inhalation of small particles at a low flow resulted in a fairly uniform lung deposition, while larger particles at a higher flow resulted in heavy central deposition. Penetration index for small and large particles were 1.3 +/- 0.2 and 0.8 +/- 0.3 (P less than 0.001), respectively. In both groups FEV1 increased similarly with each dose, and at 0.02 and 0.08 mg the increase was significant (P less than 0.01). After eight metered doses of terbutaline sulphate (0.25 mg per dose) inhaled via a spacer, there was a further increase in FEV1 (P less than 0.001). Gas exchange did not differ between the two groups but if they were combined the DA-aO2 was significantly lower after metered doses than control (P less than 0.05). Thus, it appears that the site of deposition is not important for the bronchodilator effect of terbutaline, and gas exchange tended to improve with both modes of administration. PMID:1611230

  4. Ingestion, inhalation, and dermal exposures to chloroform and trichloroethene from tap water.

    OpenAIRE

    Weisel, C P; Jo, W K

    1996-01-01

    Individuals are exposed to volatile compounds present in tap water by ingestion, inhalation, and dermal absorption. Traditional risk assessments for water often only consider ingestion exposure to toxic chemicals, even though showering has been shown to increase the body burden of certain chemicals due to inhalation exposure and dermal absorption. We collected and analyzed time-series samples of expired alveolar breath to evaluate changes in concentrations of volatile organic compounds being ...

  5. Inhaled actinides: some safety issues and some research problems

    International Nuclear Information System (INIS)

    The following topics are discussed: limited research funds; risk coefficients for inhaled particles; the hot particle hypothesis; the Gofman-Martell contention; critical tissues for inhaled actinides inhalation hazards associated with future nuclear fuel cycles; and approach to be used by the inhalation panel

  6. Quantitative analysis of dynamic airway changes after methacholine and salbutamol inhalation on xenon-enhanced chest CT

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sang Joon; Goo, Jin Mo; Kim, Jong Hyo; Park, Eun-Ah [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Radiation Medicine, Medical Research Center, Seoul (Korea, Republic of); Lee, Chang Hyun [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Radiation Medicine, Medical Research Center, Seoul (Korea, Republic of); Seoul National University Hospital, Healthcare Gangnam Center, Seoul (Korea, Republic of); Jung, Jae-Woo; Park, Heung-Woo [Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Allergy and Clinical Immunology, Seoul (Korea, Republic of); Cho, Sang-Heon [Seoul National University Hospital, Healthcare Gangnam Center, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Allergy and Clinical Immunology, Seoul (Korea, Republic of)

    2012-11-15

    To investigate the dynamic changes in airways in response to methacholine and salbutamol inhalation and to correlate the xenon ventilation index on xenon-enhanced chest CTs in asthmatics. Thirty-one non-smokers (6 normal, 25 asthmatics) underwent xenon-enhanced chest CT and pulmonary function tests. Images were obtained at three stages (basal state, after methacholine inhalation and after salbutamol inhalation), and the total xenon ventilation index (TXVI) as well as airway values were measured and calculated. The repeated measures ANOVA and Spearman's correlation coefficient were used for statistical analysis. TXVI in the normal group did not significantly change (P > 0.05) with methacholine and salbutamol. For asthmatics, however, the TXVI significantly decreased after methacholine inhalation and increased after salbutamol inhalation (P < 0.05). Of the airway parameters, the airway inner area (IA) significantly increased after salbutamol inhalation in all airways (P < 0.01) in asthmatics. Airway IA, wall thickness and wall area percentage did not significantly decrease after methacholine inhalation (P > 0.05). IA of the large airways was well correlated with basal TXVI, FEV{sub 1} and FVC (P < 0.05). Airway IA is the most reliable parameter for reflecting the dynamic changes after methacholine and salbutamol inhalation, and correlates well with TXVI in asthmatics on xenon-enhanced CT. (orig.)

  7. Chemoradiation for Advanced Head and Neck Cancer: Potential for Improving Results to Match Those of Current Treatment Modalities for Early-Stage Tumors-Long-Term Results of Hyperfractionated Chemoradiation With Carbogen Breathing and Anemia Correction With Erythropoietin

    International Nuclear Information System (INIS)

    Purpose: To attempt to improve results of chemoradiation for head and neck cancer. Methods and Materials: From March 1996 to April 2007, 98 patients with head and neck cancer (15 Stage III and 83 Stage IV) were treated with a twice-daily hyperfractionated schedule. Eleven patients presented with N0, 11 with N1, 13 with N2A, 17 with N2B, 24 with N2C, and 22 with N3. Each fraction of treatment consisted of 5 mg/m2 of carboplatin plus 115 cGy with carbogen breathing. Treatment was given 5 days per week up to total doses of 350 mg/m2 of carboplatin plus 8050 cGy in 7 weeks. Anemia was corrected with erythropoietin. Results: Ninety-six patients tolerated the treatment as scheduled. All patients tolerated the planned radiation dose. Local toxicity remained at the level expected with irradiation alone. Chemotherapy toxicity was moderate. Ninety-seven complete responses were achieved. After 11 years of follow-up (median, 81 months), actuarial locoregional control, cause-specific survival, overall survival, and nodal control rates at 5 and 10 years were, respectively, 83% and 83%, 68% and 68%, 57% and 55%, and 100% and 100%. Median follow-up of disease-free survivors was 80 months. No significant differences in survival were observed between the different subsites or between the pretreatment node status groups (N0 vs. N+, N0 vs. N1, N0 vs. N2A, N0 vs. N2B, N0 vs. N2C, and N0 vs. N3). Conclusions: Improving results of chemoradiation for advanced head and neck cancer up to the level obtained with current treatments for early-stage tumors is a potentially reachable goal

  8. Clinical efficacy and safety of beclomethasone dipropionate inhalation capsules inhaled by Cyclohaler compared with Becotide Rotacaps inhaled by Rotahaler.

    Science.gov (United States)

    Vink-van Wijngaarden, T; Blom-Ross, M E; Lansdorp, D; Goedhart, D M; Eelhart, J; Guelen, P J; de Vos, D

    1998-09-01

    The study was undertaken to compare the efficacy and safety of beclomethasone dipropionate inhalation powder inhaled by Rotahaler (Becotide Rotacaps, Glaxo Wellcome) and by Cyclohaler (Beclomethasone Cyclocaps, Pharmachemie). Both the Cyclohaler and the Rotahaler are single-dose dry powder inhalation devices for inhalation capsules. 182 asthma patients stabilized on inhaled beclomethasone dipropionate 800 micrograms daily, were randomly assigned to treatment with 800 micrograms beclomethasone dipropionate inhaled by Rotahaler (91 patients) or Cyclohaler (91 patients) in a double-blind manner, using the double-dummy method. It was shown that the asthma remained stable during the 16-week study period with both preparations. There were no statistically significant differences in the pulmonary parameters (morning PEF, evening PEF, FEV1). The test/reference ratio of the morning PEF (99.5%, CI 93.0% - 106.5%) was well within the equivalence interval, which had been set a priori from 85% to 117.6%. There were no marked differences between the Cyclocaps and Rotacaps group in symptom scores and adverse events. A total of 12 patients had an asthma exacerbation: 8 exacerbations occurred in the Rotahaler group and 4 in the Cyclohaler group. The difference was not statistically significant. The use of rescue medication was somewhat higher in the Rotahaler group, but the difference did not reach statistical significance. Significantly more patients (17 patients) withdrew from the study in the Rotahaler group than in the Cyclohaler group (5 patients). In conclusion, there was no difference in asthma control of patients treated with Beclomethasone Cyclocaps inhaled by Cyclohaler and Becotide Rotacaps inhaled by Rotahaler. Both preparations are therapeutically equivalent. PMID:9760014

  9. Subchronic inhalation toxicity of gold nanoparticles

    Directory of Open Access Journals (Sweden)

    Chung Yong

    2011-05-01

    Full Text Available Abstract Background Gold nanoparticles are widely used in consumer products, including cosmetics, food packaging, beverages, toothpaste, automobiles, and lubricants. With this increase in consumer products containing gold nanoparticles, the potential for worker exposure to gold nanoparticles will also increase. Only a few studies have produced data on the in vivo toxicology of gold nanoparticles, meaning that the absorption, distribution, metabolism, and excretion (ADME of gold nanoparticles remain unclear. Results The toxicity of gold nanoparticles was studied in Sprague Dawley rats by inhalation. Seven-week-old rats, weighing approximately 200 g (males and 145 g (females, were divided into 4 groups (10 rats in each group: fresh-air control, low-dose (2.36 × 104 particle/cm3, 0.04 μg/m3, middle-dose (2.36 × 105 particle/cm3, 0.38 μg/m3, and high-dose (1.85 × 106 particle/cm3, 20.02 μg/m3. The animals were exposed to gold nanoparticles (average diameter 4-5 nm for 6 hours/day, 5 days/week, for 90-days in a whole-body inhalation chamber. In addition to mortality and clinical observations, body weight, food consumption, and lung function were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry tests, and organ weights were measured. Cellular differential counts and cytotoxicity measurements, such as albumin, lactate dehydrogenase (LDH, and total protein were also monitored in a cellular bronchoalveolar lavage (BAL fluid. Among lung function test measurements, tidal volume and minute volume showed a tendency to decrease comparing control and dose groups during the 90-days of exposure. Although no statistically significant differences were found in cellular differential counts, histopathologic examination showed minimal alveoli, an inflammatory infiltrate with a mixed cell type, and increased macrophages in the high-dose rats. Tissue

  10. Inhaled insulin for controlling blood glucose in patients with diabetes

    Directory of Open Access Journals (Sweden)

    Bernard L Silverman

    2008-01-01

    Full Text Available Bernard L Silverman1, Christopher J Barnes2, Barbara N Campaigne3, Douglas B Muchmore31Alkermes, Inc, Cambridge, MA, USA; 2i3 Statprobe, Ann Arbor, MI; 3Eli Lilly and Company, Indianapolis, IN, USAAbstract: Diabetes mellitus is a significant worldwide health problem, with the incidence of type 2 diabetes increasing at alarming rates. Insulin resistance and dysregulated blood glucose control are established risk factors for microvascular complications and cardiovascular disease. Despite the recognition of diabetes as a major health issue and the availability of a growing number of medications designed to counteract its detrimental effects, real and perceived barriers remain that prevent patients from achieving optimal blood glucose control. The development and utilization of inhaled insulin as a novel insulin delivery system may positively influence patient treatment adherence and optimal glycemic control, potentially leading to a reduction in cardiovascular complications in patients with diabetes.Keywords: diabetes, inhaled insulin, cardiovascular disease, blood glucose

  11. A perspective on the developmental toxicity of inhaled nanoparticles.

    Science.gov (United States)

    Hougaard, Karin Sørig; Campagnolo, Luisa; Chavatte-Palmer, Pascale; Tarrade, Anne; Rousseau-Ralliard, Delphine; Valentino, Sarah; Park, Margriet V D Z; de Jong, Wim H; Wolterink, Gerrit; Piersma, Aldert H; Ross, Bryony L; Hutchison, Gary R; Hansen, Jitka Stilund; Vogel, Ulla; Jackson, Petra; Slama, Rémy; Pietroiusti, Antonio; Cassee, Flemming R

    2015-08-15

    This paper aimed to clarify whether maternal inhalation of engineered nanoparticles (NP) may constitute a hazard to pregnancy and fetal development, primarily based on experimental animal studies of NP and air pollution particles. Overall, it is plausible that NP may translocate from the respiratory tract to the placenta and fetus, but also that adverse effects may occur secondarily to maternal inflammatory responses. The limited database describes several organ systems in the offspring to be potentially sensitive to maternal inhalation of particles, but large uncertainties exist about the implications for embryo-fetal development and health later in life. Clearly, the potential for hazard remains to be characterized. Considering the increased production and application of nanomaterials and related consumer products a testing strategy for NP should be established. Due to large gaps in data, significant amounts of groundwork are warranted for a testing strategy to be established on a sound scientific basis. PMID:26050605

  12. Inhaled delivery of Δ(9)-tetrahydrocannabinol (THC) to rats by e-cigarette vapor technology.

    Science.gov (United States)

    Nguyen, Jacques D; Aarde, Shawn M; Vandewater, Sophia A; Grant, Yanabel; Stouffer, David G; Parsons, Loren H; Cole, Maury; Taffe, Michael A

    2016-10-01

    Most human Δ(9)-tetrahydrocannabinol (THC) use is via inhalation, and yet few animal studies of inhalation exposure are available. Popularization of non-combusted methods for the inhalation of psychoactive drugs (Volcano(®), e-cigarettes) further stimulates a need for rodent models of this route of administration. This study was designed to develop and validate a rodent chamber suitable for controlled exposure to vaporized THC in a propylene glycol vehicle, using an e-cigarette delivery system adapted to standard size, sealed rat housing chambers. The in vivo efficacy of inhaled THC was validated using radiotelemetry to assess body temperature and locomotor responses, a tail-flick assay for nociception and plasma analysis to verify exposure levels. Hypothermic responses to inhaled THC in male rats depended on the duration of exposure and the concentration of THC in the vehicle. The temperature nadir was reached after ∼40 min of exposure, was of comparable magnitude (∼3 °Celsius) to that produced by 20 mg/kg THC, i.p. and resolved within 3 h (compared with a 6 h time course following i.p. THC). Female rats were more sensitive to hypothermic effects of 30 min of lower-dose THC inhalation. Male rat tail-flick latency was increased by THC vapor inhalation; this effect was blocked by SR141716 pretreatment. The plasma THC concentration after 30 min of inhalation was similar to that produced by 10 mg/kg THC i.p. This approach is flexible, robust and effective for use in laboratory rats and will be of increasing utility as users continue to adopt "vaping" for the administration of cannabis. PMID:27256501

  13. Abused inhalants enhance GABA-mediated synaptic inhibition

    OpenAIRE

    MacIver, M Bruce

    2009-01-01

    Abused inhalants are widely used, especially among school age children and teenagers, and are ‘gateway’ drugs leading to the abuse of alcohol and other addictive substances. In spite of this widespread use, little is known about the effects produced by inhalants on the central nervous system. The similarity in behavioral effects produced by inhalants and inhaled anesthetics, together with their common chemical features, prompted the present study of inhalant actions on a well characterized an...

  14. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, and Surveillance Most Recent Asthma Data AsthmaStats Asthma-related Missed School Days among Children ...

  15. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Brochures Facts Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, ... Mixed Methods 5. Purpose Informs Design Other Evaluation Resources Multimedia ... HHS/Open USA.gov

  16. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Quick Links Asthma Action Plan America Breathing Easier [PDF - 1.1 MB] ASL Asthma Film Asthma Clinical ... Using a metered dose inhaler with a spacer [ PDF - 377 KB] Your browser does not support iframes ...

  17. Late effects of inhaled plutonium in dogs

    International Nuclear Information System (INIS)

    An overview is presented summarizing the effects of inhaled 239PuO2 and 238PuO2 in dogs with emphasis on dose-response relationships at low exposure levels. With the dose levels studied to date, pulmonary neoplasia was the primary cause of death in beagles 5 to 10 years after inhalation of 239PuO2. None of the dogs exposed to 239PuO2 developed bone tumors. Bone neoplasia was the primary cause of death 5 to 6 years after inhalation of 238PuO2; however, one of the dogs had pulmonary tumors in addition to bone tumors. The earliest indication of a biological effect after the inhalation of 239PuO2 or 238PuO2 was dose related lymphocytopenia

  18. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Brochures Facts Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, ... Asthma NCHS Asthma FastStats Survey Questions Resources for Health Professionals and Schools Healthcare Professionals Public Health Professionals ...

  19. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Pollution & Respiratory Health Know How to Use Your Asthma Inhaler Recommend on Facebook Tweet Share Compartir You can control your asthma and avoid an attack by taking your medicine ...

  20. About Steroids (Inhaled and Oral Corticosteroids)

    Science.gov (United States)

    ... Medications > Long-Term Control Medications > About Steroids About Steroids (Inhaled and Oral Corticosteroids) What are corticosteroids (‘steroids’) ... considerations when your dosage changes? What are corticosteroids (‘steroids’)? Corticosteroids (steroids) are medicines that are used to ...

  1. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, and Surveillance ... gaining control over their asthma. Quick Links Asthma Action Plan America Breathing Easier [PDF - 1.1 MB] ...

  2. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Brochures Facts Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, ... Obesity Percentage of People with Asthma who Smoke Insurance coverage and barriers to care for people with ...

  3. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... J K L M N O P Q R S T U V W X Y Z # Start ... Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, and Surveillance Most Recent Asthma Data AsthmaStats Asthma- ...

  4. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... avoid an attack by taking your medicine exactly as your doctor or other medical professional tells you ... keep them with your Asthma Action Plan. Using a metered dose inhaler with a spacer Your browser ...

  5. Acute Respiratory Distress Due to Methane Inhalation

    OpenAIRE

    Jo, Jun Yeon; Kwon, Yong Sik; Lee, Jin Wook; Park, Jae Seok; Rho, Byung Hak; Choi, Won-Il

    2013-01-01

    Inhalation of toxic gases can lead to pneumonitis. It has been known that methane gas intoxication causes loss of consciousness or asphyxia. There is, however, a paucity of information about acute pulmonary toxicity from methane gas inhalation. A 21-year-old man was presented with respiratory distress after an accidental exposure to methane gas for one minute. He came in with a drowsy mentality and hypoxemia. Mechanical ventilation was applied immediately. The patient's symptoms and chest rad...

  6. Inhaler devices - from theory to practice

    DEFF Research Database (Denmark)

    Sanchis, Joaquin; Corrigan, Chris; Levy, Mark L;

    2013-01-01

    This brief overview of the factors determining lung deposition of aerosols provides background information required by health care providers when instructing patients to use their prescribed inhalers. We discuss differences in the optimal inhalation manoeuvres for each type of aerosol generator a...... the difficulties patients face. Provision of short, clear instructions with demonstration of critical steps and checking technique during later clinical visits are necessary if these aerosolised medications are to be fully beneficial....

  7. Manganese Inhalation as a Parkinson Disease Model

    OpenAIRE

    José Luis Ordoñez-Librado; Verónica Anaya-Martínez; Ana Luisa Gutierrez-Valdez; Laura Colín-Barenque; Enrique Montiel-Flores; Maria Rosa Avila-Costa

    2011-01-01

    The present study examines the effects of divalent and trivalent Manganese (Mn2+/Mn3+) mixture inhalation on mice to obtain a novel animal model of Parkinson disease (PD) inducing bilateral and progressive dopaminergic cell death, correlate those alterations with motor disturbances, and determine whether L-DOPA treatment improves the behavior, to ensure that the alterations are of dopaminergic origin. CD-1 male mice inhaled a mixture of Manganese chloride and Manganese acetate, one hour twice...

  8. Clearance of inhaled particles in ankylosing spondylitis.

    OpenAIRE

    Farquhar, D R; Chamberlain, M. J.; McCain, G A; Morgan, W K

    1989-01-01

    Patients with ankylosing spondylitis may uncommonly develop apical fibrobullous lung disease, the cause of which is unknown. It is postulated here that rigidity of the thoracic cage leads to reduced apical clearance of inhaled particles and may thereby predispose to chronic infection. Deposition and clearance of inhaled technetium-99m sulphur colloid particles were studied in eight male patients with ankylosing spondylitis who had chest wall rigidity (mean (SD) chest expansion 1.8 (1.07) cm) ...

  9. Dynamics of airflow in a short inhalation

    CERN Document Server

    Bates, Alister; Cetto, Raul; Calmet, Hadrien; Gambaruto, Alberto; Tolley, Neil; Houzeaux, Guillaume; Schroter, Robert

    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 trans- port 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 litre per second 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 20ms, 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...

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

    International Nuclear Information System (INIS)

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

  11. Protective effect of inhalation of hydrogen gas on radiation-induced dermatitis and skin injury in rats

    International Nuclear Information System (INIS)

    The effect of inhalation of hydrogen-containing gas (1.3% hydrogen + 20.8% oxygen + 77.9% nitrogen) (HCG) on radiation-induced dermatitis and on the healing of healing-impaired skin wounds in rats was examined using a rat model of radiation-induced skin injury. An X-ray dose of 20 Gy was irradiated onto the lower part of the back through two holes in a lead shield. Irradiation was performed before or after inhalation of HCG for 2 h. Inhalation of HCG significantly reduced the severity of radiodermatitis and accelerated healing-impaired wound repair. Staining with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) showed that the proportion of apoptotic keratinocytes and the level of staining in the X-irradiated skin of rats that pre-inhaled HCG were significantly lower than that of rats which did not pre-inhale HCG. Cutaneous full-thickness wounds were then created in the X-irradiated area to examine the time-course of wound healing. X-irradiation significantly increased the time required for wound healing, but the inhalation of HCG prior to the irradiation significantly decreased the delay in wound healing compared with the control and post-inhalation of HCG groups. Therefore, radiation-induced skin injury can potentially be alleviated by the pre-inhalation of HCG. (author)

  12. Atomized paclitaxel liposome inhalation treatment of bleomycin-induced pulmonary fibrosis in rats.

    Science.gov (United States)

    Zhou, Y; Zhu, W P; Cai, X J; Chen, M

    2016-01-01

    We sought to determine the efficacy of atomized paclitaxel liposome inhalation treatment of pulmonary fibrosis in a bleomycin-induced rat model. Forty male Sprague-Dawley rats were randomly divided into four groups: healthy control, pulmonary fibrosis without treatment, paclitaxel liposome inhalation-treated, and intravenous paclitaxel liposome-treated. Fibrosis was induced by bleomycin injection. A total of 20 mg/kg paclitaxel liposome was administered by inhalation every other day for a total of 10 doses. The intravenous group received 5 mg/kg paclitaxel liposome on days 1, 7, 14, and 21. We observed the general condition, weight change, survival index, and pathological changes in the lung tissue of the rats. Quantitative analysis of collagen types I and III and transforming growth factor (TGF)-β1 expression in the lungs was also performed. The paclitaxel liposome inhalation and intravenous delivery methods improved survival index and pulmonary fibrosis Ashcroft score, and decreased the thickness of the alveolar interval. No obvious difference was found between the two groups. Compared with the untreated group, paclitaxel liposome inhalation and intravenous injection significantly reduced the levels of collagen types I and III and TGF-β1 expression equally. In conclusion, atomized paclitaxel liposome inhalation protects against severe pulmonary fibrosis in a bleomycin-induced rat model. This delivery method has less systemic side effects and increased safety over intravenous injection. PMID:27173212

  13. Time course of pharmacokinetic and hormonal effects of inhaled high-dose salvinorin A in humans.

    Science.gov (United States)

    Johnson, Matthew W; MacLean, Katherine A; Caspers, Michael J; Prisinzano, Thomas E; Griffiths, Roland R

    2016-04-01

    Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the Salvia divinorum plant, which has been used for hallucinogenic effects. Previous research on salvinorin A pharmacokinetics likely underestimated plasma levels typically resulting from the doses administered due to inefficient vaporization and not collecting samples during peak drug effects. Six healthy adults inhaled a single high dose of vaporized salvinorin A (n = 4, 21 mcg/kg; n = 2, 18 mcg/kg). Participant- and monitor-rated effects were assessed every 2 min for 60 min post-inhalation. Blood samples were collected at 13 time points up to 90 min post-inhalation. Drug levels peaked at 2 min and then rapidly decreased. Drug levels were significantly, positively correlated with participant and monitor drug effect ratings. Significant elevations in prolactin were observed beginning 5 min post-inhalation and peaking at 15 min post-inhalation. Cortisol showed inconsistent increases across participants. Hormonal responses were not well correlated with drug levels. This is the first study to demonstrate a direct relationship between changes in plasma levels of salvinorin A and drug effects in humans. The results confirm the efficacy of an inhalation technique for salvinorin A. PMID:26880225

  14. Lung vasodilatory response to inhaled iloprost in experimental pulmonary hypertension: amplification by different type phosphodiesterase inhibitors

    Directory of Open Access Journals (Sweden)

    Weissmann Norbert

    2005-07-01

    Full Text Available Abstract Inhaled prostanoids and phosphodiesterase (PDE inhibitors have been suggested for treatment of severe pulmonary hypertension. In catheterized rabbits with acute pulmonary hypertension induced by continuous infusion of the stable thromboxane analogue U46619, we asked whether sildenafil (PDE1/5/6 inhibitor, motapizone (PDE3 inhibitor or 8-Methoxymethyl-IBMX (PDE1 inhibitor synergize with inhaled iloprost. Inhalation of iloprost caused a transient pulmonary artery pressure decline, levelling off within per se ineffective dose of each PDE inhibitor (200 μg/kg × min 8-Methoxymethyl-IBMX, 1 μg/kg × min sildenafil, 5 μg/kg × min motapizone with subsequent iloprost nebulization, marked amplification of the prostanoid induced pulmonary vasodilatory response was noted and the area under the curve of PPA reduction was nearly threefold increased with all approaches, as compared to sole iloprost administration. Further amplification was achieved with the combination of inhaled iloprost with sildenafil plus motapizone, but not with sildenafil plus 8MM-IBMX. Systemic hemodynamics and gas exchange were not altered for all combinations. We conclude that co-administration of minute systemic doses of selective PDE inhibitors with inhaled iloprost markedly enhances and prolongs the pulmonary vasodilatory response to inhaled iloprost, with maintenance of pulmonary selectivity and ventilation perfusion matching. The prominent effect of sildenafil may be operative via both PDE1 and PDE5, and is further enhanced by co-application of a PDE3 inhibitor.

  15. A Proposed In Vitro Method to Assess Effects of Inhaled Particles on Lung Surfactant Function.

    Science.gov (United States)

    Sørli, Jorid B; Da Silva, Emilie; Bäckman, Per; Levin, Marcus; Thomsen, Birthe L; Koponen, Ismo K; Larsen, Søren T

    2016-03-01

    The lung surfactant (LS) lining is a thin liquid film covering the air-liquid interface of the respiratory tract. LS reduces surface tension, enabling lung surface expansion and contraction with minimal work during respiration. Disruption of surface tension is believed to play a key role in severe lung conditions. Inhalation of aerosols that interfere with the LS may induce a toxic response and, as a part of the safety assessment of chemicals and inhaled medicines, it may be relevant to study their impact on LS function. Here, we present a novel in vitro method, based on the constrained drop surfactometer, to study LS functionality after aerosol exposure. The applicability of the method was investigated using three inhaled asthma medicines, micronized lactose, a pharmaceutical excipient used in inhaled medication, and micronized albumin, a known inhibitor of surfactant function. The surfactometer was modified to allow particles mixed in air to flow through the chamber holding the surfactant drop. The deposited dose was measured with a custom-built quartz crystal microbalance. The alterations allowed the study of continuously increasing quantified doses of particles, allowing determination of the dose of particles that affects the LS function. The tested pharmaceuticals did not inhibit the function of a model LS even at extreme doses--neither did lactose. Micronized albumin, however, impaired surfactant function. The method can discriminate between safe inhaled aerosols--as exemplified by the approved inhaled medicines and the pharmaceutical excipient lactose--and albumin known to impair lung functionality by inhibiting LS function. PMID:26524226

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

    OpenAIRE

    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.

    2012-01-01

    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 e...

  17. Improvement of inhaler efficacy by home-made spacer.

    Science.gov (United States)

    Sritara, P; Janvitayanuchit, S

    1993-12-01

    The delivery of aerosol from a metered dose inhaler (MDI) was reported to be more efficient with a spacer. Hence, a home-made spacer modified from a 950 ml low cost plastic bottle, was compared with a MDI and with a 750 ml imported spacer (Nebuhaler). On three consecutive days, at the same time of day, 20 adult patients with chronic asthma inhaled two puffs of terbutaline sulphate (0.5 mg), delivered from MDI alone, MDI with a 750 ml Nebuhlaer and MDI with a home-made spacer. The following measurements were made: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and pulse rate. These measurements were carried out immediately before and at 5, 20, 60 min after inhalation of terbutaline. FEV1 was significantly increased (P terbutaline with MDI via either spacers than with MDI alone but no significant difference was observed between Nebuhaler and the home-made spacer. FVC and pulse rate showed no significant change with each method of administration. In conclusion, terbutaline delivered by MDI and home-made spacer was more effective in bronchodilatation than by MDI alone and was just as effective as MDI and Nebuhaler. The home-made spacer therefore offers a simple, inexpensive and more effective method for delivering aerosol drug. PMID:7798822

  18. Exposures from external radiation and from inhalation of resuspended material

    International Nuclear Information System (INIS)

    In the modelling of external exposures due to cesium released during the reactor accident of Chernobyl, gamma dose rates in air over open undisturbed sites are considered to be different according to the unsoluble fraction in the deposit. This is taken into account by forming different classes according to the distance from the Chernobyl NPP. The effect of the different migration behavior in these distance classes on the gamma dose rate in air is found to increase with time. Predictions of gamma dose rates in air are based on measurements of the nuclear weapons tests fallout. Various population groups in the CIS countries are defined according to their place of residence (rural or urban), their occupation or age (indoor resp. outdoor workers, pensioners, school-children, or preschool-children), and their kind of residence (wooden, brick, or multi-storey house). Model results for various population groups are compared with the results of TLD-measurements of individual external exposures. For the calculation of inhalation doses, the new ICRP model for the respiratory tract was used. The dose assessments were conducted for measured size resolved activity distributions of resuspended material, obtained at different locations and for several kinds of agricultural operations. Inhalation doses vary considerably with respect to different kinds of work. Tractor drivers receive much higher doses than other agricultural workers, especially when the cabin window of the tractor is open. Effective doses due to the inhalation of resuspended plutonium are assessed to be a few μSv per initial deposit of one kBq/m2. Inhalation doses from 137Cs are usually smaller by an order of magnitude than the doses from Pu, provided a high solubility is assumed for resuspended Cs

  19. Translocation pathways for inhaled asbestos fibers

    Directory of Open Access Journals (Sweden)

    Mantegazza F

    2008-01-01

    Full Text Available Abstract We discuss the translocation of inhaled asbestos fibers based on pulmonary and pleuro-pulmonary interstitial fluid dynamics. Fibers can pass the alveolar barrier and reach the lung interstitium via the paracellular route down a mass water flow due to combined osmotic (active Na+ absorption and hydraulic (interstitial pressure is subatmospheric pressure gradient. Fibers can be dragged from the lung interstitium by pulmonary lymph flow (primary translocation wherefrom they can reach the blood stream and subsequently distribute to the whole body (secondary translocation. Primary translocation across the visceral pleura and towards pulmonary capillaries may also occur if the asbestos-induced lung inflammation increases pulmonary interstitial pressure so as to reverse the trans-mesothelial and trans-endothelial pressure gradients. Secondary translocation to the pleural space may occur via the physiological route of pleural fluid formation across the parietal pleura; fibers accumulation in parietal pleura stomata (black spots reflects the role of parietal lymphatics in draining pleural fluid. Asbestos fibers are found in all organs of subjects either occupationally exposed or not exposed to asbestos. Fibers concentration correlates with specific conditions of interstitial fluid dynamics, in line with the notion that in all organs microvascular filtration occurs from capillaries to the extravascular spaces. Concentration is high in the kidney (reflecting high perfusion pressure and flow and in the liver (reflecting high microvascular permeability while it is relatively low in the brain (due to low permeability of blood-brain barrier. Ultrafine fibers (length

  20. Assessing inhalation injury in the emergency room

    Directory of Open Access Journals (Sweden)

    Tanizaki S

    2015-07-01

    Full Text Available Shinsuke Tanizaki Department of Emergency Medicine, Fukui Prefectural Hospital, Fukui, Japan Abstract: 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. Keywords: inhalation injury, burn, carbon monoxide poisoning, cyanide poisoning

  1. Inhalation characteristics and their effects on in vitro drug delivery from dry powder inhalers .2. Effect of peak flow rate (PIFR) and inspiration time on the in vitro drug release from three different types of commercial dry powder inhalers

    NARCIS (Netherlands)

    deBoer, AH; Gjaltema, D; Hagedoorn, P

    1996-01-01

    Three commercial dry powder inhalers with completely different dosing and powder disintegration principles were evaluated in an in vitro deposition study. A four-stage cascade impactor was used for the range of flow rates between 20 and 60 1/min. Turbuhaler, Diskhaler and Spinhaler showed increasing

  2. Day-to-day variation of bronchodilatory response to an inhaled beta-2-stimulant in asthmatics.

    Science.gov (United States)

    Lindgren, S; Bake, B; Larsson, S

    1987-01-01

    The effect of inhaling 0.25 and 2.0 mg of terbutaline sulphate, a beta-2-stimulant, from a metered dose aerosol was studied in five asthmatic patients during two periods of five days each. During the first period, the patients used a good spontaneous inhalation technique; during the second period, the inhalation technique was optimized and controlled. The variation of basal FEV1 and of the increase (delta FEV1) caused by 0.25 mg of inhaled terbutaline was considerable. The effect was only slightly better and the variation only slightly smaller when the controlled inhalation technique was used. The differences were not significant. In individual patients, there was no or negative correlation between delta FEV1 and the corresponding basal FEV1 value. Accordingly, the most commonly used way of expressing delta FEV1 as a percentage of basal FEV1 value was found to be insensitive. Delta FEV1, expressed as a percentage of the maximum available FEV1 increase on the same day after 2.25 mg terbutaline sulphate, was found to be most sensitive. This way of expressing delta FEV1 will increase the possibilities of detecting differences between treatments in clinical trials. PMID:3453755

  3. Use of inhaled corticosteroids in pediatric asthma

    DEFF Research Database (Denmark)

    Bisgaard, H

    1997-01-01

    Inhaled corticosteroids reduce asthma symptoms and exacerbations, improve lung function, and reduce airway inflammation and bronchial hyperreactivity more effectively than other treatments. However, inhaled corticosteroids may be unable to return lung function and bronchial hyperreactivity to...... normal when introduced for moderately severe asthma. This finding highlights the need to improve treatment strategy in pediatric asthma. The natural progression of persistent asthma may lead to loss of lung function and chronic bronchial hyperreactivity for children and adults. There is evidence to...... suggest that asthma acts via a chronic inflammatory process that causes remodeling of the airways with mucosal thickening and smooth muscle hypertrophy. An optimal treatment strategy would be one aimed at reducing the ongoing airway inflammation. Inhaled steroids ameliorate the inflammation, whereas this...

  4. [Inhaled corticosteroids: Which regimens are appropriate?].

    Science.gov (United States)

    Giovannini-Chami, L; Piccini-Bailly, C; Albertini, M

    2016-06-01

    Inhaled corticosteroids are the cornerstone of asthma management. Inhaled corticosteroid regimens differ slightly in various international guidelines on asthma management but are based on the principles of continuous treatment and titration to the lowest effective dose. Several recent studies, nevertheless, appear to demonstrate the potential value of preemptive or "pro re nata" regimens in infants and children. These studies were included in GINA 2015 for children 5 years of age and younger in whom discontinuous treatment is proposed as a second-line option. Should we change our practices after a critical reading of these studies? PMID:27133372

  5. Fine particle mass from the Diskus inhaler and Turbuhaler inhaler in children with asthma

    DEFF Research Database (Denmark)

    Bisgaard, H; Klug, B; Sumby, B S;

    1998-01-01

    in an inhalation profile simulator to assess drug delivery from both a Diskus inhaler and a Turbuhaler inhaler, and in particular to assess the proportion of drug emitted in the coarse (>4.7 microm) and fine (... represents the changes in flow rate over time through the device than the constant flow rate usually applied with an impactor alone. The aerosol cloud was released before the peak inspiratory effort had been achieved and accordingly the early part and not the peak of the inspiratory performance...... is a determinant of the quality of the aerosol. The mean (SD) amount of drug in large particles (>4.7 microm), fine particles (

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

    Science.gov (United States)

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

    2004-01-01

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

  7. Assessment of smoke inhalation injury using volumetric optical frequency domain imaging in sheep models

    Science.gov (United States)

    Applegate, Matthew B.; Hariri, Lida P.; Beagle, John; Tan, Khay Ming; Chee, Chunmin; Hales, Charles A.; Suter, Melissa J.

    2012-02-01

    Smoke inhalation injury is a serious threat to victims of fires and explosions, however accurate diagnosis of patients remains problematic. Current evaluation techniques are highly subjective, often involving the integration of clinical findings with bronchoscopic assessment. It is apparent that new quantitative methods for evaluating the airways of patients at risk of inhalation injury are needed. Optical frequency domain imaging (OFDI) is a high resolution optical imaging modality that enables volumetric microscopy of the trachea and upper airways in vivo. We anticipate that OFDI may be a useful tool in accurately assessing the airways of patients at risk of smoke inhalation injury by detecting injury prior to the onset of symptoms, and therefore guiding patient management. To demonstrate the potential of OFDI for evaluating smoke inhalation injury, we conducted a preclinical study in which we imaged the trachea/upper airways of 4 sheep prior to, and up to 60 minutes post exposure to cooled cotton smoke. OFDI enabled the visualization of increased mucus accumulation, mucosal thickening, epithelial disruption and sloughing, and increased submucosal signal intensity attributed to polymorphonuclear infiltrates. These results were consistent with histopathology findings. Bronchoscopic inspection of the upper airways appeared relatively normal with only mild accumulation of mucus visible within the airway lumen. The ability of OFDI to not only accurately detect smoke inhalation injury, but to quantitatively assess and monitor the progression or healing of the injury over time may provide new insights into the management of patients such as guiding clinical decisions regarding the need for intubation and ventilator support.

  8. Modification of sleep-waking and electroencephalogram induced by vetiver essential oil inhalation

    Science.gov (United States)

    Cheaha, Dania; Issuriya, Acharaporn; Manor, Rodiya; Kwangjai, Jackapun; Rujiralai, Thitima; Kumarnsit, Ekkasit

    2016-01-01

    Background: Essential oils (EOs) have been claimed to modulate mental functions though the most of data were obtained from subjective methods of assessment. Direct effects of EO on brain function remained largely to be confirmed with scientific proof. This study aimed to demonstrate quantifiable and reproducible effects of commercial vetiver (Vetiveria zizanioides) EO inhalation on sleep-waking and electroencephalogram (EEG) patterns in adult male Wistar rats. The experiments were conducted during November 2013 - February 2014. Materials and Methods: The following electrode implantation on the skull, control, and treated animals were subjected for EEG recording while inhaling water and vetiver EO (20 and 200 µl), respectively. Fast Fourier transform was used for analysis of EEG power spectrum. Results: One-way ANOVA analysis confirmed that vetiver EO inhalation significantly increased total waking and reduced slow-wave sleep time. Moreover, EO inhalation decreased alpha and beta1 activity in both frontal and parietal cortices and increased gamma activity in the frontal cortex. Changes in these frequencies began almost from the start of the inhalation. Conclusion: These data suggest refreshing properties of vetiver EO on electrical brain activity and alertness. PMID:27069728

  9. Bronchoconstriction induced by inhaled methacholine delays desflurane uptake and elimination in a piglet model.

    Science.gov (United States)

    Kretzschmar, Moritz; Kozian, Alf; Baumgardner, James E; Schreiber, Jens; Hedenstierna, Göran; Larsson, Anders; Hachenberg, Thomas; Schilling, Thomas

    2016-01-01

    Bronchoconstriction is a hallmark of asthma and impairs gas exchange. We hypothesized that pharmacokinetics of volatile anesthetics would be affected by bronchoconstriction. Ventilation/perfusion (VA/Q) ratios and pharmacokinetics of desflurane in both healthy state and during inhalational administration of methacholine (MCh) to double peak airway pressure were studied in a piglet model. In piglets, MCh administration by inhalation (100 μg/ml, n=6) increased respiratory resistance, impaired VA/Q distribution, increased shunt, and decreased paO2 in all animals. The uptake and elimination of desflurane in arterial blood was delayed by nebulization of MCh, as determined by Micropore Membrane Inlet Mass Spectrometry (wash-in time to P50, healthy vs. inhalation: 0.5 min vs. 1.1 min, to P90: 4.0 min vs. 14.8 min). Volatile elimination was accordingly delayed. Inhaled methacholine induced severe bronchoconstriction and marked inhomogeneous VA/Q distribution in pigs, which is similar to findings in human asthma exacerbation. Furthermore, MCh-induced bronchoconstriction delayed both uptake and elimination of desflurane. These findings might be considered when administering inhalational anesthesia to asthmatic patients. PMID:26440992

  10. The inhalation device influences lung deposition and bronchodilating effect of terbutaline.

    Science.gov (United States)

    Borgström, L; Derom, E; Ståhl, E; Wåhlin-Boll, E; Pauwels, R

    1996-05-01

    The development of new inhalation devices for asthma drugs raises the issue of the relationship between pulmonary deposition and therapeutic effect of inhaled drugs in patients with obstructive lung diseases. We thus conducted a randomized, double-blind and double-dummy, four-period crossover study in 13 patients with moderate asthma (mean age 36 yr; FEV1 59% of predicted), who inhaled 0.25 and 0.5 mg terbutaline sulphate on separate occasions either via a pressurized metered dose inhaler (pMDI) or Turbuhaler (TBH). Pulmonary deposition was 8.1 +/- 2.7% and 8.3 +/- 2.3%, respectively, of the nominal dose for pMDI and 19.0 +/- 7.3%, and 22.0 +/- 8.1% for TBH. The FEV1 increase after 0.25 mg terbutaline sulphate via TBH was significantly greater than after 0.25 mg via pMDI. No significant differences in FEV1 increase were observed between 0.25 mg via TBH, 0.5 mg via pMDI, or 0.5 mg via TBH. Other lung function variables showed similar dose- and device-related changes. We concluded that: (1) the dose of terbutaline sulphate deposited in the lungs is dependent on which inhalation system is used; (2) TBH delivers about twice the amount of drug to the lungs as the pMDI; and (3) the observed difference in deposition is reflected in the bronchodilating effect. PMID:8630614

  11. Bronchodilatory therapy with nebuhaler: how important is the delay between firing the dose and inhaling?

    Science.gov (United States)

    Newman, S P; Woodman, G; Morén, F; Clarke, S W

    1988-07-01

    Metered dose inhalers are sometimes used in conjunction with NebuhalerR, a 750 ml holding chamber, but the permissible delay time between actuating the aerosol into Nebuhaler and commencing inhalation is unknown. We have compared in 10 asthmatic patients the bronchodilator responses following inhalations of terbutaline sulphate from Nebuhaler after delays of 1, 5 and 30 seconds and following placebo inhalation. Terbutaline sulphate was administered as 2 puffs, each of 250 micrograms, separated by approximately 15 minutes. After each delay time, terbutaline produced increases in forced expiratory volume in one second (FEV1), peak expiratory flow rate (PEFR) and maximum expiratory flow following exhalation of 75% of the forced vital capacity (V max25) significantly greater than those after placebo (P less than 0.01). Changes in PEFR did not vary significantly among the three delay times, but the increases in FEV1 and in V max25 were significantly reduced with 30 seconds' delay. It is concluded that the delay between actuation into Nebuhaler and commencing inhalation can be extended from 1 second to 5 seconds without significant loss of drug efficacy, and that further extension to 30 seconds causes only a small loss of bronchodilatation: hence the delay time is unlikely to be of major importance in clinical practice. PMID:3073806

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

    Science.gov (United States)

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

    2015-09-01

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

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

    Science.gov (United States)

    Roche, Nicolas; Dekhuijzen, P N Richard

    2016-08-01

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

  14. Effects of combined exposure of F344 rats to radiation and chronically inhaled cigarette smoke

    International Nuclear Information System (INIS)

    Nuclear workers may be exposed to radiation in various forms, such as low-LET γ-irradiation or α-irradiation from inhaled 239PuO2 particles. These workers may then have increased risk for lung cancer compared to the general population. Of additional concern is the possibility that interactions between radiation and other carcinogens may increase the risk of cancer induction, compared to the risks from either type of agent alone. An important and common lung carcinogen is cigarette smoke. The purpose of this project is to better determine the combined effects of chronically inhaled cigarette smoke and either inhaled 239PuO2 or external, thoracic X-irradiation on the induction of lung cancer in rats. Histologic and dosimetric evaluations of rats in the CS + 239PuO2 study continue, and the study of CS + X rays is beginning

  15. Effects of combined exposure of F344 rats to radiation and chronically inhaled cigarette smoke

    Energy Technology Data Exchange (ETDEWEB)

    Finch, G.L.; Nikula, K.J.; Barr, E.B. [and others

    1995-12-01

    Nuclear workers may be exposed to radiation in various forms, such as low-LET {gamma}-irradiation or {alpha}-irradiation from inhaled {sup 239}PuO{sub 2} particles. These workers may then have increased risk for lung cancer compared to the general population. Of additional concern is the possibility that interactions between radiation and other carcinogens may increase the risk of cancer induction, compared to the risks from either type of agent alone. An important and common lung carcinogen is cigarette smoke. The purpose of this project is to better determine the combined effects of chronically inhaled cigarette smoke and either inhaled {sup 239}PuO{sub 2} or external, thoracic X-irradiation on the induction of lung cancer in rats. Histologic and dosimetric evaluations of rats in the CS + {sup 239}PuO{sub 2} study continue, and the study of CS + X rays is beginning.

  16. 49 CFR 172.429 - POISON INHALATION HAZARD label.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false POISON INHALATION HAZARD label. 172.429 Section... REQUIREMENTS, AND SECURITY PLANS Labeling § 172.429 POISON INHALATION HAZARD label. (a) Except for size and color, the POISON INHALATION HAZARD label must be as follows: ER22JY97.023 (b) In addition to...

  17. 49 CFR 172.555 - POISON INHALATION HAZARD placard.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false POISON INHALATION HAZARD placard. 172.555 Section... REQUIREMENTS, AND SECURITY PLANS Placarding § 172.555 POISON INHALATION HAZARD placard. (a) Except for size and color, the POISON INHALATION HAZARD placard must be as follows: ER22JY97.025 (b) In addition...

  18. 42 CFR 84.90 - Breathing resistance test; inhalation.

    Science.gov (United States)

    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 airflow will be measured in the facepiece or mouthpiece while the apparatus is operated by a...

  19. Asbestos cement dust inhalation by hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Wehner, A.P.; Dagle, G.E.; Cannon, W.C.; Buschbom, R.L. (Pacific Northwest Laboratories, Richland, WA (USA))

    1978-12-01

    Two groups of 96 male Syrian golden hamsters were exposed to respirable asbestos cement aerosol at concentrations of approximately 1 and approximately 10 micrograms/liter, respectively, 3 hours/day, 5 days/week. Average fiber counts ranged from 5 to about 120 fibers/cm3. Each group was randomly divided into six subgroups of 16 animals. The first subgroup was sacrificed after 3 months of exposure, the second after 6 months, and the third after 15 months. The fourth subgroup was withdrawn from exposure after 3 months, observed for an additional 3 months, and then sacrificed. The fifth and sixth subgroups were withdrawn after 3 and 6 months of exposure, respectively, and maintained for observation up to the 15-month exposure point of the third subgroup at which time all surviving animals were sacrificed. All other experimental procedures were similar to those delineated in a previous publication describing the development of an animal model, techniques, and an exposure system for asbestos cement dust inhalation. The asbestos cement exposures had no significant effect on body weight and mortality of the animals. Higher aerosol concentration and longer exposure times increased the number of macrophages and ferruginous bodies found in the lungs of the exposed animals. Recovery periods had no effect on the incidence of macrophages and ferruginous bodies. The incidence of very slight to slight fibrosis in the animals sacrificed after 15 months of exposure shows a significant (P less than 0.01) trend when the untreated control group and the 1 and 10 microgram/liter dose level groups are compared, indicating a dose-response relationship. Development of minimal fibrosis continued in animals withdrawn from exposure. No primary carcinomas of the lung and respiratory tract and no mesotheliomas were found.

  20. Effects of inspiratory resistance, inhaled beta-agonists and histamine on canine tracheal blood flow

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, W.T.; Baile, E.M.; Brancatisano, A.; Pare, P.D.; Engel, L.A. (Dept. of Respiratory Medicine, Westmead Hospital, Westmead, NSW (Australia))

    1992-01-01

    Tracheobronchial blood flow is potentially important in asthma as it could either influence the clearance of mediators form the airways, thus affecting the duration and severity of bronchoispasm, or enhance oedema formation with a resultant increase in airflow obstruction. In anaesthetized dogs, spontaneously breathing via a tracheostomy, we investigated the effects of three interventions which are relevant to acute asthma attacks and could potentially influence blood flow and its distribution to the mucosa and remaining tissues of the trachea: (1) increased negative intrathoracic pressure swings (-25[+-]1 cmH[sub 2]O) induced by an inspiratory resistance; (2) variable inhaled doses of a beta-adrenoceptor-agonist (terbutaline); and (3) aerosolized histamine sufficient to produce a threefold increase in pulmonary resistance. Microspheres labelled with different radioisotopes were used to measure blood flow. Resistive breathing did not influence tracheobronchial blood flow. Following a large dose of terbutaline, mucosal blood flow (Qmb) increased by 50%. After inhaled histamine, Qmb reached 265% of the baseline value. We conclude that, whereas increased negative pressure swings do not influence tracheobronchial blood flow or its distribution, inhalation of aerosolized terbutaline, corresponding to a conventionally nebulized dose, increases mucosal blood flow. Our results also confirm that inhaled histamine, in a dose sufficient to produce moderate bronchoconstriction, increases tracheal mucosal blood flow in the area of deposition. (au).

  1. Effects of inspiratory resistance, inhaled beta-agonists and histamine on canine tracheal blood flow

    International Nuclear Information System (INIS)

    Tracheobronchial blood flow is potentially important in asthma as it could either influence the clearance of mediators form the airways, thus affecting the duration and severity of bronchoispasm, or enhance oedema formation with a resultant increase in airflow obstruction. In anaesthetized dogs, spontaneously breathing via a tracheostomy, we investigated the effects of three interventions which are relevant to acute asthma attacks and could potentially influence blood flow and its distribution to the mucosa and remaining tissues of the trachea: 1) increased negative intrathoracic pressure swings (-25±1 cmH2O) induced by an inspiratory resistance; 2) variable inhaled doses of a beta-adrenoceptor-agonist (terbutaline); and 3) aerosolized histamine sufficient to produce a threefold increase in pulmonary resistance. Microspheres labelled with different radioisotopes were used to measure blood flow. Resistive breathing did not influence tracheobronchial blood flow. Following a large dose of terbutaline, mucosal blood flow (Qmb) increased by 50%. After inhaled histamine, Qmb reached 265% of the baseline value. We conclude that, whereas increased negative pressure swings do not influence tracheobronchial blood flow or its distribution, inhalation of aerosolized terbutaline, corresponding to a conventionally nebulized dose, increases mucosal blood flow. Our results also confirm that inhaled histamine, in a dose sufficient to produce moderate bronchoconstriction, increases tracheal mucosal blood flow in the area of deposition. (au)

  2. Effect of carrier particle shape on dry powder inhaler performance.

    Science.gov (United States)

    Kaialy, Waseem; Alhalaweh, Amjad; Velaga, Sitaram P; Nokhodchi, Ali

    2011-12-12

    The aim of this study was to characterise the aerosolisation properties of salbutamol sulphate (SS) from dry powder inhaler (DPI) formulations containing different carrier products. The difference in the elongation ratio (ER) of the different carriers was highlighted. Different set of carriers, namely commercial mannitol (CM), commercial lactose (CL), cooling crystallised mannitol (CCM), acetone crystallised mannitol (ACM) and ethanol crystallised mannitol (ECM) were used and inspected in terms of size, shape, density, crystal form, flowability, and in vitro aerosolisation performance using Multi Stage Liquid Impinger (MSLI) and Aerolizer inhaler device. Solid-state and morphological characterization showed that CM product was in pure β-form having particles with smaller ER (CM: ER=1.62 ± 0.04) whereas ACM and ECM mannitol particles were in pure α form with higher ER (ACM: ER=4.83 ± 0.18, ECM: ER=5.89 ± 0.19). CCM product crystallised as mixtures of β-form and δ-form and showed the largest variability in terms of particle shape, size, and DPI performance. Linear relationships were established showing that carrier products with higher ER have smaller bulk density (D(b)), smaller tap density (D(t)), higher porosity (P), and poorer flow properties. In vitro aerosolisation assessments showed that the higher the ER of the carrier particles the greater the amounts of SS delivered to lower airway regions indicating enhanced DPI performance. Yet, DPI performance enhancement by increasing carrier ER reached a "limit" as increasing carrier ER from 4.83±0.18 (ACM) to 5.89±0.19 (ECM) did not significantly alter fine particle fraction (FPF) of SS. Also, carrier particles with higher ER were disadvantageous in terms of higher amounts of SS remained in inhaler device (drug loss) and deposited on throat. Linear relationship was established (r(2)=0.87) showing that the higher the carrier ER the lower the drug emission (EM) upon inhalation. Moreover, poorer flowability for

  3. Pneumonitis after Inhalation of Mercury Vapours

    Directory of Open Access Journals (Sweden)

    JD Glezos

    2006-01-01

    Full Text Available A 43-year-old man presented to hospital with pneumonia but only after discharge from hospital did he admit to deliberate prior inhalation of mercury. His pulmonary involvement appeared to resolve almost completely with antibiotics and supportive care. Nevertheless, persisting elevated urinary excretion of mercury required two courses of chelation therapy. No serious systemic sequelae were observed.

  4. Inhalant Use in Latina Early Adolescent Girls

    Science.gov (United States)

    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…

  5. Report of the panel on inhaled actinides

    International Nuclear Information System (INIS)

    Some topics discussed are as follows: assessment of risks to man of inhaling actinides; use of estimates for developing protection standards; epidemiology of lung cancer in exposed human populations; development of respiratory tract models; and effects in animals: dose- and effect-modifying factors

  6. Inhalation of antibiotics in cystic fibrosis

    NARCIS (Netherlands)

    Touw, D J; Brimicombe, R W; Hodson, M E; Heijerman, H G; Bakker, W

    1995-01-01

    Aerosol administration of antipseudomonal antibiotics is commonly used in cystic fibrosis. However, its contribution to the improvement of lung function, infection and quality of life is not well-established. All articles published from 1965 until the present time concerning the inhalation of antibi

  7. Manganese Inhalation as a Parkinson Disease Model

    Directory of Open Access Journals (Sweden)

    José Luis Ordoñez-Librado

    2011-01-01

    Full Text Available The present study examines the effects of divalent and trivalent Manganese (Mn2+/Mn3+ mixture inhalation on mice to obtain a novel animal model of Parkinson disease (PD inducing bilateral and progressive dopaminergic cell death, correlate those alterations with motor disturbances, and determine whether L-DOPA treatment improves the behavior, to ensure that the alterations are of dopaminergic origin. CD-1 male mice inhaled a mixture of Manganese chloride and Manganese acetate, one hour twice a week for five months. Before Mn exposure, animals were trained to perform motor function tests and were evaluated each week after the exposure. By the end of Mn exposure, 10 mice were orally treated with 7.5 mg/kg L-DOPA. After 5 months of Mn mixture inhalation, striatal dopamine content decreased 71%, the SNc showed important reduction in the number of TH-immunopositive neurons, mice developed akinesia, postural instability, and action tremor; these motor alterations were reverted with L-DOPA treatment. Our data provide evidence that Mn2+/Mn3+ mixture inhalation produces similar morphological, neurochemical, and behavioral alterations to those observed in PD providing a useful experimental model for the study of this neurodegenerative disease.

  8. THE METABOLISM OF NALED INHALED BY RATS

    Science.gov (United States)

    Naled (Dibrom) was prepared with a (14)carbon label in the 1-ethyl position. The labeled compound was administered in appropriate formulation vehicles to female rats by the inhalation, oral or intraperitoneal routes. Treated animals were either placed in metabolism cages and thei...

  9. DEVELOPMENTAL NEUROTOXICITY OF INHALED METHANOL IN RATS

    Science.gov (United States)

    Dr. Weiss and his colleagues conducted a controlled series of experiments in which they exposed pregnant rats and their newborn offspring to 4,500 parts per million (ppm) methanol by inhalation, and then submitted them to tests of behavioral function. Exposure to 4,500...

  10. Health risks associated with inhaled nasal toxicants

    NARCIS (Netherlands)

    Feron, V.J.; Arts, J.H.E.; Kuper, C.F.; Slootweg, P.J.; Woutersen, R.A.

    2001-01-01

    Health risks of inhaled nasal toxicants were reviewed with emphasis on chemically induced nasal lesions in humans, sensory irritation, olfactory and trigeminal nerve toxicity, nasal immunopathology and carcinogenesis, nasal responses to chemical mixtures, in vitro models, and nasal dosimetry- and me

  11. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, and Surveillance Most Recent Asthma Data AsthmaStats Asthma- ... 4. Gathering and Using Data 4A. Focus On: Data Collection Choices 4B. Focus on Using Mixed Methods 5. ...

  12. Inhalation drug delivery devices: technology update

    Directory of Open Access Journals (Sweden)

    Ibrahim M

    2015-02-01

    Full Text Available Mariam Ibrahim, Rahul Verma, Lucila Garcia-ContrerasDepartment of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USAAbstract: The pulmonary route of administration has proven to be effective in local and systemic delivery of miscellaneous drugs and biopharmaceuticals to treat pulmonary and non-pulmonary diseases. A successful pulmonary administration requires a harmonic interaction between the drug formulation, the inhaler device, and the patient. However, the biggest single problem that accounts for the lack of desired effect or adverse outcomes is the incorrect use of the device due to lack of training in how to use the device or how to coordinate actuation and aerosol inhalation. This review summarizes the structural and mechanical features of aerosol delivery devices with respect to mechanisms of aerosol generation, their use with different formulations, and their advantages and limitations. A technological update of the current state-of-the-art designs proposed to overcome current challenges of existing devices is also provided.Keywords: pulmonary delivery, asthma, nebulizers, metered dose inhaler, dry powder inhaler

  13. Use of inhaled corticosteroids in pediatric asthma

    DEFF Research Database (Denmark)

    Bisgaard, H

    1997-01-01

    suggest that asthma acts via a chronic inflammatory process that causes remodeling of the airways with mucosal thickening and smooth muscle hypertrophy. An optimal treatment strategy would be one aimed at reducing the ongoing airway inflammation. Inhaled steroids ameliorate the inflammation, whereas this...

  14. Particle engineering of materials for oral inhalation by dry powder inhalers. II - sodium cromoglicate

    OpenAIRE

    Healy, Anne Marie; Tajber, Lidia; Corrigan, Owen,

    2011-01-01

    Sodium cromoglicate is an antiasthmatic and antiallergenic drug used in inhalation therapy and commonly administered by a dry powder inhaler. In the present study we sought to examine the feasibility of producing nanoporous microparticles (NPMPs) of this hydrophilic material by adaptation of a spray drying process previously applied to hydrophobic drugs, and to examine the physicochemical and in vitro deposition properties of the spray dried particles in comparison to a commercial product....

  15. Effect of inhaled morphine on the development of breathlessness during exercise in patients with chronic lung disease.

    OpenAIRE

    Leung, R; Hill, P.; Burdon, J

    1996-01-01

    BACKGROUND: Inhaled morphine has previously been shown to increase exercise endurance in patients with chronic lung disease. A similar study was performed to determine whether inhaled morphine reduces the sensation of breathlessness in this group of patients. METHODS: A randomised double blind study on the effect of nebulised morphine on both exercise induced breathlessness and maximum achievable power output using isotonic saline as a control was performed in 10 patients with stable chronic ...

  16. The influence of inhaled propylene oxide on glutathione status and cell proliferation in the respiratory nasal epithelium of rats

    OpenAIRE

    Khan, Mohammad Delwar Hossain

    2010-01-01

    Inhaled propylene oxide (PO) induced tumors and cell proliferation at high concentrations (≥300 ppm) in rat respiratory nasal epithelium (RNE). The metabolic elimination of PO in the RNE occurs by the conjugation with Glutathione (GSH) which results the depletion of GSH. In order to substantiate the hypothesis that the increased cell proliferation is caused by GSH depletion, GSH status and cell proliferation were examined in the RNE of rats after inhalation exposure of PO, after co-treatment ...

  17. Performance of Combination Drug and Hygroscopic Excipient Submicrometer Particles from a Softmist Inhaler in a Characteristic Model of the Airways

    OpenAIRE

    Longest, P. Worth; Tian, Geng; Li, Xiang; Son, Yoen-Ju; Hindle, Michael

    2012-01-01

    Excipient enhanced growth (EEG) of inhaled submicrometer pharmaceutical aerosols is a recently proposed method intended to significantly reduce extrathoracic deposition and improve lung delivery. The objective of this study was to evaluate the size increase of combination drug and hygroscopic excipient particles in a characteristic model of the airways during inhalation using both in vitro experiments and CFD simulations. The airway model included a characteristic mouth-throat (MT) and upper ...

  18. Administration of cyclosporine by inhalation: A feasibility study in Beagle dogs

    International Nuclear Information System (INIS)

    Oral cyclosporine inhibits the primary,but-not the secondary immune responses in the lung. These findings suggest that the local administration of cyclosporine by inhalation could be a useful tool for increasing our understanding of lung immunity. Five dogs were each treated with inhaled, oral and intravenous cyclosporine, aerosol vehicle (ethyl alcohol), and no treatment, over a 5-wk period. One treatment per week was given to each dog. A radiolabel, 99mTc was included in the cyclosporine aerosol to allow visualization of lung distribution of the aerosol. Blood plasma concentrations of cyclosporine were approximately the same at 4 h and were essentially cleared by 24 h for all routes of administration. Aerosol distribution in the lung appeared uniform, based on 99mTc scintigrams. In a second study, two dogs inhaled cyclosporine once a day for five days, two dogs inhaled the aerosol vehicle, and one dog was not treated. No evidence of acute lung injury, based on cell counts, total protein, alkaline phosphatase, or lactic dehydrogenase levels in the bronchoalveolar lavage fluid, was found at 24 h after one or five administrations of cyclosporine. These data indicate that cyclosporine administered by aerosol either once or five times was distributed throughout the lung and was absorbed into the blood without producing an acute inflammatory reaction in the lung. Our results suggest that cyclosporine may be safely given by inhalation for studies of local immune responses in the lung. (author)

  19. Effect of inhaled inactivated Mycobacterium phlei in children with moderate asthma.

    Science.gov (United States)

    Ming, Moyu; Li, Chaoqian; Luo, Zhixi; Lv, Shengqiu

    2013-02-01

    Bacillus Calmette-Guérin and other mycobacterial vaccines are important therapeutic methods in a series of chronic inflammatory disorders characterized by Th1/Th2 imbalance in which Th2 type cells and cytokines often increase. However, few studies have investigated whether it can reduce or prevent the symptoms and attacks in children with asthma. This study evaluated the effect of inactivated Mycobacterium phlei inhaled by an atomizing device placed on asthmatic children. In this randomized, single-center, Seretide-controlled study, children aged 4-12 years with newly diagnosed, moderate, persistent asthma were treated with either inhaled inactivated M. phlei or inhaled Seretide patch. The efficacy of inhaled inactivated M. phlei was related with the alleviation of asthma symptoms, improvement of lung function and reduction of bronchial hyper-responsiveness and total serum IgE, which was similar with Seretide. These findings may have important clinical value in confirming inhaled inactivated M. phlei as a new therapeutic method in moderately asthmatic children. PMID:23413910

  20. [A case of eosinophilic pneumonia caused by inhalation of nickel dusts].

    Science.gov (United States)

    Toyoshima, M; Sato, A; Taniguchi, M; Imokawa, S; Nakazawa, K; Hayakawa, H; Chida, K

    1994-05-01

    A 16-year-old male, an industrial high school student working at an ironworks, without a dust mask, began to complain of dry cough and fever several hours after inhalation of stainless steel dusts including 0.1% nickel. A chest X-ray film revealed ground glass shadows, patchy shadows and Kerley B lines in the right lung fields. A high resolution chest CT scan showed fusing panlobular densities, thickening of bronchial walls and thickening of interlobular septa. Blood cells counts revealed leucocytosis with eosinophilia. Arterial blood gas analysis revealed hypoxemia. A bronchoalveolar lavage fluid specimen showed a marked increase in the total cell count and in eosinophils. A transbronchial biopsy specimen showed eosinophilic and lymphocytic infiltration in the alveolar septa. Steroid therapy with methylpredonisolne (250 mg x three days) resulted in clinical remission. As we suspected nickel-induced eosinophilic pneumonia, an inhalation provocation test with 0.5% nickel sulfate solution was carried out with the patient's informed consent. Six hours after inhalation he developed a dry cough and fever with leucocytosis and A-aDo2 widening. The positive results of the inhalation provocation test provided a definite diagnosis of nickel induced eosinophilic pneumonia. A review of the world literature revealed three case reports of nickel induced PIE syndrome, all of whom were clinically diagnosed without biopsy however. We believe that this is the first case diagnosed by transbronchial biopsy-proven tissue eosinophilia and a positive nickel inhalation provocation test. PMID:8084105

  1. Sidestream smoke inhalation decreases respiratory clearance of 99mTc-DTPA acutely

    International Nuclear Information System (INIS)

    The permeability of the alveolar-capillary barrier to an inhaled aerosol of technetium 99m labelled diethylenetriamine penta-acetate (99mTc-DTPA is used as an index of alveolar epithelial injury. Permeability is greatly increased in active smokers. The aim of this study was to determine the effect of sidestream smoke inhalation on permeability as this has not been described previously. Lung clearance of inhaled 99mTc-DTPA aerosol was measured in 20 normal non-smoking subjects before and after exposure to one hours sidestream smoke inhalation. Measured carbon monoxide (CO) levels rose to a maximum of 23.5 ±6.2 ppm from baseline values of 0.6±1.3 (p99mTc-DTPA clearance rose from baseline 69.1± 15.6 (mean ± to 77.4 ±17.8) after smoke exposure. No effect of 99mTc-DTPA scanning of sidestream smoke was demonstrated on lung function. It was concluded that low level sidestream smoke inhalation decreases 99mTc-DTPA clearance acutely in humans. The mechanism of this unexpected result is not established but may include differences in constituents between sidestream and mainstream smoke, alterations in pulmonary microvascular blood flow, or changes in surfactant due to an acute phase irritant response. 34 refs., 2 figs

  2. Developments and strategies for inhaled antibiotic drugs in tuberculosis therapy: a critical evaluation.

    Science.gov (United States)

    Hoppentocht, M; Hagedoorn, P; Frijlink, H W; de Boer, A H

    2014-01-01

    Inhaled antibiotics have been a valuable tool in treating pulmonary infections in cystic fibrosis patients for decades, and the pulmonary route is now becoming increasingly interesting for other infectious diseases like tuberculosis too. Especially with multidrug and extensively drug-resistant tuberculosis emerging, great effort is put into the improvement of pulmonary antibiotic administration to fight this global threat. Several reviews have been written on inhalable antibiotics, giving clear overviews of the compounds of interest. Furthermore, various formulation studies and administration strategies are on-going with these compounds. What is often missing is a critical evaluation of these developments. Several risks may be involved varying from obtaining insufficient local drug concentrations to adverse side effects and unwanted changes in physiological processes from the excipients used. In this manuscript, the pros and cons and feasibility of recent advances in pulmonary antibiotic tuberculosis therapy are presented and critically evaluated. Furthermore, the advantages of dry powder inhalation over wet nebulisation for inhaled antibiotics in developing countries where prevalence of tuberculosis is highest are discussed. It has to be concluded that a greater effort in good inhaler development and more research in the physico-chemical properties of the compounds of interest are needed. PMID:24189498

  3. Inhalation of the reactive aldehyde acrolein promotes antigen sensitization to ovalbumin and enhances neutrophilic inflammation.

    Science.gov (United States)

    O'Brien, Edmund; Spiess, Page C; Habibovic, Aida; Hristova, Milena; Bauer, Robert A; Randall, Matthew J; Poynter, Matthew E; van der Vliet, Albert

    2016-01-01

    Acrolein (ACR), an α,β-unsaturated aldehyde and a major component of tobacco smoke, is a highly reactive electrophilic respiratory irritant implicated in asthma pathogenesis and severity. However, few studies have directly investigated the influence of ACR exposure on allergen sensitization and pulmonary inflammation. The present study was designed to examine the impact of ACR inhalation on allergic sensitization to the inhaled antigen ovalbumin (OVA), as well as pulmonary inflammation during subsequent OVA challenge. Adult male C57BL/6 mice were exposed to inhaled OVA (1%, 30 min/day, 4 days/week) and/or ACR (5 ppm, 4 h/day, 4 days/week) over 2 weeks and subsequently challenged with aerosolized OVA (1%, 30 min/day) over three consecutive days. Serum anti-OVA IgG1 levels were increased significantly in animals exposed to both OVA and ACR, compared to animals exposed to either OVA or ACR alone. In addition, differential cell counts and histological analysis revealed an increase in BAL neutrophils in animals exposed to both OVA and ACR. However, exposure to both OVA and ACR did not influence mRNA expression of the cytokines il5, il10, il13 or tnfa, but significantly increased mRNA expression of ccl20. Moreover, ACR exposure enhanced lung mRNA levels of il17f and tgfb1, suggesting development of enhanced inhalation tolerance to OVA. Overall, the findings indicate that ACR inhalation can promote airway-mediated sensitization to otherwise innocuous inhaled antigens, such as OVA, but also enhances immune tolerance, thereby favoring neutrophilic airway inflammation. PMID:25875327

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

    Science.gov (United States)

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

    1996-12-01

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

  5. Bronchial effects of leukotriene D4 inhalation in normal human lung

    DEFF Research Database (Denmark)

    Bisgaard, H; Groth, S

    1987-01-01

    The aim of the study was to investigate whether inhaled leukotriene (LT) D4 could mimic the characteristics of asthmatic patients after allergen-induced attack, i.e. a prolonged subclinical bronchial obstruction, an increased reactivity of the airways and a late reaction. The effects of LTD4 were...... compared with those of histamine and the mechanism of action sought. Thirty-three non-atopic individuals participated in the study. The two drugs were inhaled as an aerosol of small particles causing a relative peripheral deposition pattern in order to mimic the preferential involvement of peripheral...... obstruction had decreased by 50% of the maximum effect, and no delayed reaction was observed within 10 h. The reactivity of the airways did not change during 10 h after inhalation of LTD4 as tested by repeated exercise challenges. Pretreatment with ipratropium bromide prevented the effect of LTD4 on FEV1, yet...

  6. Personal characteristics and environmental factors influencing lung dosimetry of inhaled radon decay products

    International Nuclear Information System (INIS)

    The attempt to interpret lung cancer incidence caused by inhaled radon decay products in items of radiation dose raises the question of the relevant dose. The various dosimetric approaches published by now are characterized by an increasing complexity in the structure of the models used. Due to uncertainties of physical and biological parameters involved and the application of different anatomical and physiological models the calculated doses are varying up to one order of magnitude. Independent of the choice of these dosimetric models applied to the calculation of lung doses, deposition, clearance and resulting dose are affected essentially by the properties of the inhaled aerosol as well as by personal characteristics. Both the properties of the exposed individual as well as of the inhaled environmental atmosphere have to be considered in radiation protection. It is the main objective of this paper to illustrate the influence of both parameter sets on basal cell doses by varying the above parameters

  7. 46. Micronuclei induced by chronical treatment of SO2 inhalation in mouse bone marrow cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In the chronical experiment of treating with sulfur dioxide(SO2) inhalation, Micronuclei(MN) frequencies in the polychromatophilic erythroblasts(PCE) of mouse bone marrow and the frequencies of cells with MN were significantly increased in dose-dependent manner. There is a significant difference between the male and the female animals. The results also showed that SO2 inhibited urethone-induced MN formation, it is a antagonistic joint action to Urethone. These results furtherly confirm that SO2 inhalation is a clastogenetic and genotoxic agent to mammalian cells, and the combination roles of SO2 and other mutagens are complexity.

  8. Effects of Radon Inhalation on Some Biophysical Properties of Blood in Rats

    Science.gov (United States)

    Essa, M. F.; Shahin, Fayez M.; Ahmed, Ashour M.; Abdel-Salam, Omar

    2013-03-01

    The major source of human exposure to natural radiation arises from the inhalation of radon (222Rn) gas. Exposure to high concentrations of radon 222Rn and its daughters for long period leads to pathological effects like lung cancer, leukaemia, skin cancer and kidney diseases. The present study was performed on rats to investigate the effect of radon exposure on the absorption spectra of hemoglobin. Measurements have been performed in a radon chamber where rats were exposed to radon for 1, 5 or 7 weeks. The inhalation of radon resulted in decrease in intensity of the absorption bands characterizing the hemoglobin molecular structure with increased radon doses.

  9. Use of Inhaled and Oral Corticosteroids in Pregnancy and the Risk of Malformations or Miscarriage

    DEFF Research Database (Denmark)

    Bjørn, Anne-Mette Bay; Ehrenstein, Vera; Nohr, Ellen Aagaard;

    2014-01-01

    databases, this MiniReview provides an overview of inhaled and oral corticosteroid use in pregnancy with specific emphasis on the association between use of corticosteroids during pregnancy and risk of miscarriage and congenital malformations in offspring. Use of corticosteroids among pregnant women ranged...... inconsistent. Use of inhaled corticosteroids was associated with a slightly increased the risk of miscarriage, whereas use of oral corticosteroids was not; however, confounding by indication could not be ruled out. This article is protected by copyright. All rights reserved....

  10. Lung Deposition And Biological Effects Of Inhaled Radon Progenies

    International Nuclear Information System (INIS)

    Inhaled radon progenies provide more than the half of natural radiation exposure. There is increasing evidence that the cellular distribution of radiation burden is an important factor regarding the biological response to ionisation radiation, thus, one of our tasks was the characterisation of the distribution of cellular exposure. Histological studies of former uranium miners presented strong correlation between primer deposition hot spots and neoplastic lesions. Most of these lesions were located along the carinal regions of the large bronchial airways. In the present work, computational fluid dynamics (CFD) approaches have been applied to simulate the deposition distribution of inhaled radon progenies along central human airways. The geometry and the cellular structure of epithelial lung tissue were numerically reconstructed based on anatomical and histological data. Single and multiple ha-hit and cellular dose distributions have been computed applying Monte Carlo modelling techniques at different breathing conditions. Figure 1. Deposition enhancement factor (EF) of inhaled radon progenies on a central airway bifurcation in airway generations 4-5 during light physical activity breathing condition. Size of scanning surface element is a 45μm side triangle. Left panel: EF max=1400,Dp=200 nm (attached). Right panel: EF max1290, Dp= 1 nm (unattached). Values of local per average deposition densities, that is, enhancement factors (Figure 1), hit probabilities and doses may be up to two-three orders of magnitude higher in the deposition hot spots than the average values. Dose calculations revealed that some cell clusters may receive high doses even at low exposure conditions. Applying the model to different radiation exposure conditions useful relations can be received regarding the linear-non threshold hypothesis

  11. Risks of pneumonia in patients with asthma taking inhaled corticosteroids

    DEFF Research Database (Denmark)

    O'Byrne, Paul M; Pedersen, Soren; Carlsson, Lars-Göran;

    2011-01-01

    Rationale: Inhaled corticosteroids (ICS) are the mainstay of asthma treatment. Studies in chronic obstructive pulmonary disease reported increased rates of pneumonia with ICS. Concerns exist about an increased pneumonia risk in patients with asthma taking ICS. Objectives: To evaluate the risks...... of pneumonia in patients with asthma taking ICS. Methods: A retrospective analysis evaluated studies of the ICS budesonide in asthma. The primary data set were all double-blind, placebo-controlled trials lasting at least 3 months, involving budesonide (26 trials, n = 9,067 for budesonide; n = 5.......70% (12.7 per TPY), whereas the percentage of patients reporting pneumonia SAEs was 0.17% (3.1 per TPY). There was no increased risk with higher budesonide doses or any difference between budesonide and fluticasone. Conclusions: There is no increased risk of pneumonia in patients with asthma, identified...

  12. Effects, side effects and plasma concentrations of terbutaline in adult asthmatics after inhaling from a dry powder inhaler device at different inhalation flows and volumes.

    Science.gov (United States)

    Engel, T; Scharling, B; Skovsted, B; Heinig, J H

    1992-04-01

    1. The efficacy of a metered dose inhaler (MDI) is highly dependent on the mode of inhalation. The relatively high built-in resistance in the Turbohaler (TBH), a new dry powder inhaler device for inhalation of terbutaline sulphate and budesonide, reduces the flow during inhalation. We compared five different modes of inhalation using the terbutaline TBH in 10 stable asthmatic subjects, who were tested on 5 consecutive days. 2. Measurement of 10 different parameters of pulmonary function indicated that the full bronchodilatory effect of an inhaled dose was already achieved at 5 min after the inhalation. Inspiratory flows through the TBH varying from 34 to 88 l min-1 resulted in comparable bronchodilation, and a previous exhalation to residual volume proved of no value. However, if, prior to inhalation, an exhalation through the device was performed, a substantially reduced effect was seen. 3. Reducing the inspiratory flow to approximately 34 l min-1 produced slightly reduced side effects and lower plasma terbutaline concentrations. PMID:1576070

  13. Comparison of pulmonary inflammatory responses following intratracheal instillation and inhalation of nanoparticles.

    Science.gov (United States)

    Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Tomonaga, Taisuke; Lee, Byeong-Woo; Okada, Takami; Oyabu, Takako; Myojo, Toshihiko; Kawai, Kazuaki; Yatera, Kazuhiro; Shimada, Manabu; Kubo, Masaru; Yamamoto, Kazuhiro; Kitajima, Shinichi; Kuroda, Etsushi; Horie, Masanori; Kawaguchi, Kenji; Sasaki, Takeshi

    2016-06-01

    In order to examine whether intratracheal instillation studies can be useful for determining the harmful effect of nanoparticles, we performed inhalation and intratracheal instillation studies using samples of the same nanoparticles. Nickel oxide nanoparticles (NiO) and titanium dioxide nanoparticles (TiO2) were used as chemicals with high and low toxicities, respectively. In the intratracheal instillation study, rats were exposed to 0.2 or 1 mg of NiO or TiO2. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the single intratracheal instillation. In the inhalation study, rats were exposed to inhaled NiO or TiO2 (1.65, 1.84 mg/m(3), respectively) for 4 weeks. The same endpoints were examined from 3 days to 3 months after the end of exposure. Inhalation of NiO induced an increase in the number of neutrophils in BALF and concentrations of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2 and heme oxygenase (HO)-1. Intratracheal instillation of NiO induced persistent inflammation and upregulation of these cytokines was observed in the rats. However, inhalation of TiO2 did not induce pulmonary inflammation, and intratracheal instillation of TiO2 transiently induced an increase in the number of neutrophils in BALF and the concentrations of CINC-1, CINC-2 and HO-1. Taken together, a difference in pulmonary inflammation was observed between the high and low toxicity nanomaterials in the intratracheal instillation studies, as in the inhalation studies, suggesting that intratracheal instillation studies may be useful for ranking the harmful effects of nanoparticles. PMID:26558952

  14. Safety assessment of inhaled xylitol in mice and healthy volunteers

    Directory of Open Access Journals (Sweden)

    Kline Joel N

    2004-09-01

    Full Text Available Abstract Background Xylitol is a 5-carbon sugar that can lower the airway surface salt concentration, thus enhancing innate immunity. We tested the safety and tolerability of aerosolized iso-osmotic xylitol in mice and human volunteers. Methods This was a prospective cohort study of C57Bl/6 mice in an animal laboratory and healthy human volunteers at the clinical research center of a university hospital. Mice underwent a baseline methacholine challenge, exposure to either aerosolized saline or xylitol (5% solution for 150 minutes and then a follow-up methacholine challenge. The saline and xylitol exposures were repeated after eosinophilic airway inflammation was induced by sensitization and inhalational challenge to ovalbumin. Normal human volunteers underwent exposures to aerosolized saline (10 ml and xylitol, with spirometry performed at baseline and after inhalation of 1, 5, and 10 ml. Serum osmolarity and electrolytes were measured at baseline and after the last exposure. A respiratory symptom questionnaire was administered at baseline, after the last exposure, and five days after exposure. In another group of normal volunteers, bronchoalveolar lavage (BAL was done 20 minutes and 3 hours after aerosolized xylitol exposure for levels of inflammatory markers. Results In naïve mice, methacholine responsiveness was unchanged after exposures to xylitol compared to inhaled saline (p = 0.49. There was no significant increase in Penh in antigen-challenged mice after xylitol exposure (p = 0.38. There was no change in airway cellular response after xylitol exposure in naïve and antigen-challenged mice. In normal volunteers, there was no change in FEV1 after xylitol exposures compared with baseline as well as normal saline exposure (p = 0.19. Safety laboratory values were also unchanged. The only adverse effect reported was stuffy nose by half of the subjects during the 10 ml xylitol exposure, which promptly resolved after exposure completion. BAL

  15. CARDIOVASCULAR RESPONSES IN UNRESTRAINED WKY-RATS TO INHALED ULTRAFINE CARBON PARTICLES

    Science.gov (United States)

    AbstractThis study provides evidence for adverse cardiac effects of inhaled ultrafine particles (UFPs) in healthy WKY rats. Short term exposure (24 h) with carbon UFPs (180 ?g?m ?) induced a moderate but significant heart rate increase of 18 bpm (4.8 %) in association with a ...

  16. Toxicological Assessments of Rats Exposed Prenatally to Inhaled Vapors of Gasoline and Gasoline-Ethanol Blends

    Science.gov (United States)

    The primary alternative to petroleum-based fuels is ethanol, which is blended with gasoline in the United States at concentrations up to 15% for most automobiles. Efforts to increase the amount of ethanol in gasoline have prompted concerns about the potential toxicity of inhaled ...

  17. Effect of oxygen inhalation on systemic, central, and splanchnic haemodynamics in cirrhosis

    DEFF Research Database (Denmark)

    Møller, S; Becker, U; Schifter, S;

    1996-01-01

    catecholamines, renin, endothelin-1, and calcitonin gene-related peptide were all increased in patients with cirrhosis, but only the catecholamine concentrations decreased significantly (noradrenaline -13%, p < 0.02 and adrenaline -16%, p < 0.01) in response to oxygen. CONCLUSION: During oxygen inhalation...

  18. SUBCHRONIC INHALATION EXPOSURE OF RATS TO LIBBY AMPHIBOLE AND AMOSITE ASBESTOS

    Science.gov (United States)

    Exposure to Libby amphibole (LA) is associated with significant increases in asbestosis, lung cancer, and mesothelioma. To support biological potency assessment and dosimetry model development, a subchronic nose-only inhalation exposure study (6 hr/d, 5 d/wk, 13 wk) was conducted...

  19. Effect of inhaled furosemide and torasemide on bronchial response to ultrasonically nebulized distilled water in asthmatic subjects.

    Science.gov (United States)

    Foresi, A; Pelucchi, A; Mastropasqua, B; Cavigioli, G; Carlesi, R M; Marazzini, L

    1992-08-01

    Inhaled furosemide has been shown to reduce the bronchoconstriction induced by several indirect stimuli, including ultrasonically nebulized distilled water (UNDW). Because the protective effect could be due to the inhibition of the Na(+)-2Cl(-)-K+ cotransport system of bronchial epithelium, we have compared the protective effect of inhaled furosemide with that of inhaled torasemide, a new and more potent loop diuretic, on UNDW-induced bronchoconstriction in a group of 12 asthmatic subjects. UNDW challenge was performed by constructing a stimulus-response curve with five increasing volume outputs of distilled water (from 0.5 to 5.2 ml/min) and the bronchial response expressed as the provocative output causing a 20% fall in FEV1 (PO20UNDW). On different days, each subject inhaled an equal dose (28 mg) of furosemide and torasemide in a randomized, double-blind, placebo-controlled study 5 min prior to an UNDW challenge. Furosemide and torasemide had no significant effect on resting lung function. The geometric mean value of PO20UNDW measured after placebo was 1.73 ml/min. This was significantly lower than that recorded after furosemide (4.25 ml/min; p < 0.025), but not after torasemide (3.05 ml/min; p = 0.07). Inhaled furosemide totally blocked bronchial response to UNDW in five subjects. In two of five subjects the response was also blocked by inhaled torasemide. A remarkable increase in diuresis was noted only after torasemide in most subjects. We conclude that inhaled furosemide has a better protective effect than does inhaled torasemide against UNDW-induced bronchoconstriction. However, the protective effect of furosemide is variable, with some asthmatic patients showing no change in bronchial response to UNDW.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1489126

  20. Exposure to acrolein by inhalation causes platelet activation

    International Nuclear Information System (INIS)

    Acrolein is a common air pollutant that is present in high concentrations in wood, cotton, and tobacco smoke, automobile exhaust and industrial waste and emissions. Exposure to acrolein containing environmental pollutants such as tobacco smoke and automobile exhaust has been linked to the activation of the coagulation and hemostasis pathways and thereby to the predisposition of thrombotic events in human. To examine the effects of acrolein on platelets, adult male C57Bl/6 mice were subjected acute (5 ppm for 6 h) or sub-chronic (1 ppm, 6 h/day for 4 days) acrolein inhalation exposures. The acute exposure to acrolein did not cause pulmonary inflammation and oxidative stress, dyslipidemia or induce liver damage or muscle injury. Platelet GSH levels in acrolein-exposed mice were comparable to controls, but acrolein-exposure increased the abundance of protein-acrolein adducts in platelets. Platelets isolated from mice, exposed to both acute and sub-chronic acrolein levels, showed increased ADP-induced platelet aggregation. Exposure to acrolein also led to an increase in the indices of platelet activation such as the formation of platelet-leukocyte aggregates in the blood, plasma PF4 levels, and increased platelet-fibrinogen binding. The bleeding time was decreased in acrolein exposed mice. Plasma levels of PF4 were also increased in mice exposed to environmental tobacco smoke. Similar to inhalation exposure, acrolein feeding to mice also increased platelet activation and established a pro-thrombotic state in mice. Together, our data suggest that acrolein is an important contributing factor to the pro-thrombotic risk in human exposure to pollutants such as tobacco smoke or automobile exhaust, or through dietary consumption.

  1. Pulmonary effects of inhaled diesel exhaust in aged mice

    International Nuclear Information System (INIS)

    Pulmonary morbidity and mortality resulting from exposure to fine particulate matter (PM) increases with age. The present studies analyzed potential mechanisms underlying increased susceptibility of the elderly to PM using diesel exhaust (DE) as a model. Mice (2 m and 18 m) were exposed to DE (0, 300, and 1000 μg/m3) for 3 h once (single) or 3 h/day for 3 days (repeated). Bronchoalveolar lavage fluid (BAL), serum and lung tissue were collected 0 and 24 h later. Exposure to DE resulted in structural alterations in the lungs of older but not younger mice, including patchy thickening of the alveolar septa and inflammatory cell localization in alveolar spaces. These effects were most pronounced 24 h after a single exposure to the higher dose of DE. Significant increases in BAL nitrogen oxides were also noted in older mice, as well as expression of lipocalin 24p3, an oxidative stress marker in the lung with no effects in younger mice. Following DE inhalation, expression of Tumor Necrosis Factor alpha (TNFα) was upregulated in lungs of both younger and older mice; however, this was attenuated in older animals. Whereas exposure to DE resulted in increases in lung Interleukin-6 (IL-6) expression in both older and younger mice, IL-8 increased only in older animals. In younger mice, constitutive expression of manganese superoxide dismutase (MnSOD) decreased after DE exposure, while in older mice, constitutive MnSOD was not detectable and DE had no effect on expression of this antioxidant. Taken together, these results suggest that altered generation of inflammatory mediators and MnSOD may contribute to increased susceptibility of older mice to inhaled DE.

  2. Acute myocardial involvement after heroin inhalation

    OpenAIRE

    Ritu Karoli; Fatima, J.; Pushker Singh; Kazmi, Khursheed I.

    2012-01-01

    Amongst the illicit drugs cocaine, amphetamines and cannabis have been studied and documented well to cause myocardial infarction by different mechanisms but there is very sparse data available on myocardial involvement after heroin abuse. We report a young man who developed acute myocardial injury after heroin inhalation and alcohol binge drinking. Heroin induced cardio toxic effect and vasospasm compounded by alcohol were suspected to be the cause of this.

  3. Inhalation Anthrax: Dose Response and Risk Analysis

    OpenAIRE

    Coleman, Margaret E.; Thran, Brandolyn; Morse, Stephen S.; Hugh-Jones, Martin; Massulik, Stacey

    2008-01-01

    The notion that inhalation of a single Bacillus anthracis spore is fatal has become entrenched nearly to the point of urban legend, in part because of incomplete articulation of the scientific basis for microbial risk assessment, particularly dose-response assessment. Risk analysis (ie, risk assessment, risk communication, risk management) necessitates transparency: distinguishing scientific facts, hypotheses, judgments, biases in interpretations, and potential misinformation. The difficulty ...

  4. Acute myocardial involvement after heroin inhalation

    Directory of Open Access Journals (Sweden)

    Ritu Karoli

    2012-01-01

    Full Text Available Amongst the illicit drugs cocaine, amphetamines and cannabis have been studied and documented well to cause myocardial infarction by different mechanisms but there is very sparse data available on myocardial involvement after heroin abuse. We report a young man who developed acute myocardial injury after heroin inhalation and alcohol binge drinking. Heroin induced cardio toxic effect and vasospasm compounded by alcohol were suspected to be the cause of this.

  5. Inhalation drug delivery devices: technology update

    OpenAIRE

    Ibrahim M.; Verma R; Garcia-Contreras L

    2015-01-01

    Mariam Ibrahim, Rahul Verma, Lucila Garcia-ContrerasDepartment of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USAAbstract: The pulmonary route of administration has proven to be effective in local and systemic delivery of miscellaneous drugs and biopharmaceuticals to treat pulmonary and non-pulmonary diseases. A successful pulmonary administration requires a harmonic interaction between the drug formulation, the inhaler d...

  6. Distribution and removal of transuranic elements and cerium deposited by the inhalation route

    International Nuclear Information System (INIS)

    Tissue distribution and excretion of inhaled radioactive isotopes varied with the chemical form and the particle size of the aerosols. In dogs, 30 d after inhalation of plutonium nitrate, 70% of the body burden was in the lungs, 10% in liver, and 15% in the skeleton. After inhalation of P239 O2 aerosols with a Count Median Diameter (CMD) of 0.12μm, 71% of the body burden was in the lungs, 3% in the bronchial lymph nodes, 4.4% in muscle, 1.3% in skeleton, and 20% was uniformly distributed throughout all remaining tissues. After inhalation of P239 O2 aerosols with CMD's of 0.3 to 0.6 μm; the lungs contained 98%, the bronchial lymph nodes about 1% and all other tissues the remaining one per cent. These data and the analysis of urine and faeces defined the relative importance of the three routes by which inhaled radioactive isotopes were cleared from the lung, e.g. movement up the trachea by ciliary action followed by excretion in the faeces, transport across the alveolar membrane and redistribution in other tissue with gradual excretion in urine and transport to the bronchial lymph nodes which accumulate inhaled insoluble materials. Therapy agents were tested that would be expected to increase the clearance of radioactive isotopes from the lung by routes which would avoid accumulation in other, perhaps more radiosensitive tissues. These include chelating agents, wetting agents, irritants, sympathomimetic, parasympathomimetic, parasympatholytic and antihistamine drugs. Diethylenetriamine-pentaacetic acid (DTPA), a chelating agent, administered by aerosols or intraperitoneally caused rapid transport of Ce144 -Pr144 from the lung and from the body via urinary excretion. One month after exposure to Ce144 O2 treated rats and dogs retained less than 10% of the Ce144 -Pr144 levels of untreated animals. (author)

  7. Effect of Formaldehyde on Asthmatic Response to Inhaled Allergen Challenge

    Science.gov (United States)

    Ezratty, Véronique; Bonay, Marcel; Neukirch, Catherine; Orset-Guillossou, Gaëlle; Dehoux, Monique; Koscielny, Serge; Cabanes, Pierre-André; Lambrozo, Jacques; Aubier, Michel

    2007-01-01

    Background Exposure to formaldehyde may lead to exacerbation of asthma. Objectives Our aim in this study was to investigate whether exposure to a low level (500 μg/m3) of formaldehyde enhances inhaled allergen responses. Methods Twelve subjects with intermittent asthma and allergy to pollen were exposed, at rest, in a double-blind crossover study to either formaldehyde or purified air for 60 min. The order of exposure to formaldehyde and air-only was randomized, and exposures were separated by 2 weeks. We also performed an allergen inhalation challenge after each exposure. Airway responsiveness to methacholine and lower airway inflammation (induced sputum) were assessed 8 hr after allergen challenge. Results The median dose of allergen producing a 15% decrease in forced expiratory volume in 1 sec (PD15FEV1) was 0.80 IR (index of reactivity) after formaldehyde exposure compared with 0.25 IR after air-only exposure (p = 0.06). Formaldehyde exposure did not affect allergen-induced increase in responsiveness to methacholine (p = 0.42). We found no formaldehyde-associated effect on the airway inflammatory response, in particular the eosinophilic inflammatory response, induced by the allergen challenge 8 hr before. Conclusion In this study, exposure to 500 μg/m3 formaldehyde had no significant deleterious effect on airway allergen responsiveness of patients with intermittent asthma; we found a trend toward a protective effect. PMID:17384766

  8. Inhaled oxytocin amplifies both vicarious reinforcement and self reinforcement in rhesus macaques (Macaca mulatta)

    Science.gov (United States)

    Chang, Steve W. C.; Barter, Joseph W.; Ebitz, R. Becket; Watson, Karli K.; Platt, Michael L.

    2012-01-01

    People attend not only to their own experiences, but also to the experiences of those around them. Such social awareness profoundly influences human behavior by enabling observational learning, as well as by motivating cooperation, charity, empathy, and spite. Oxytocin (OT), a neurosecretory hormone synthesized by hypothalamic neurons in the mammalian brain, can enhance affiliation or boost exclusion in different species in distinct contexts, belying any simple mechanistic neural model. Here we show that inhaled OT penetrates the CNS and subsequently enhances the sensitivity of rhesus macaques to rewards occurring to others as well as themselves. Roughly 2 h after inhaling OT, monkeys increased the frequency of prosocial choices associated with reward to another monkey when the alternative was to reward no one. OT also increased attention to the recipient monkey as well as the time it took to render such a decision. In contrast, within the first 2 h following inhalation, OT increased selfish choices associated with delivery of reward to self over a reward to the other monkey, without affecting attention or decision latency. Despite the differences in species typical social behavior, exogenous, inhaled OT causally promotes social donation behavior in rhesus monkeys, as it does in more egalitarian and monogamous ones, like prairie voles and humans, when there is no perceived cost to self. These findings potentially implicate shared neural mechanisms. PMID:22215593

  9. Decorporation of inhaled actinides by chelation therapy

    International Nuclear Information System (INIS)

    This article describes recent work in NRPB laboratories that has identified some of the factors influencing the behaviour of plutonium, americium and curium compounds in the body after inhalation, together with a number of experimental approaches that are being developed to optimise their treatment with DTPA. It is concluded that the most effective treatment has yet to be developed, but progress must depend on a better understanding of the factors governing the transport of actinides in the body. It cannot be assumed that because the inhaled material is readily translocated to blood, that treatment regimens with Ca-DTPA based solely on previous understanding of the metabolic fate of soluble actinide complexes will be successful. In fact, depending on the nature of the material involved in the accident, inhalation alone or combined with prolonged infusion of DTPA may be more effective than the periodic intravenous injections of the chelating agent alone. For poorly transportable materials such as insoluble plutonium-239 dioxide, chelation treatment remains essentially ineffective. (U.K.)

  10. Inhalation dose assessment for Maralinga and Emu

    International Nuclear Information System (INIS)

    Dose assessments for the inhalation of artificial radionuclides are presented for all types of contaminated areas at Maralinga and Emu. These enable Committed Effective Dose Equivalent (CEDE), to be estimated by scaling at any area of interest where activity concentrations are known. In the case of Aborigines, these dose are estimated assuming respirable dust loadings of 1 mg/m3 for adults and 1.5 mg/m3 for children and infants. Details of the calculations are presented in the appendix. The model of the respiratory system used in this assessment is that described in Interantional Commission on Radiological Protection (ICRP) Publication 30 (ICRP, 1979a). With the exception of Kuli, which is contaminated with uranium, at all other sites it is only the inhalation of plutonium and americium that contributes significantly to the dose, and of these 239Pu is the largest contributor. Therefore, considering the long half lives of the radionuclides concerned, it appears that the inhalation problems highlighted by this dose assessment will not diminish significantly within any reasonable period of time and hence management strategies must be developed to deal with such problems. 32 refs., 5 tabs., 1 fig

  11. Inhalation cancer risk assessment of cobalt metal.

    Science.gov (United States)

    Suh, Mina; Thompson, Chad M; Brorby, Gregory P; Mittal, Liz; Proctor, Deborah M

    2016-08-01

    Cobalt compounds (metal, salts, hard metals, oxides, and alloys) are used widely in various industrial, medical and military applications. Chronic inhalation exposure to cobalt metal and cobalt sulfate has caused lung cancer in rats and mice, as well as systemic tumors in rats. Cobalt compounds are listed as probable or possible human carcinogens by some agencies, and there is a need for quantitative cancer toxicity criteria. The U.S. Environmental Protection Agency has derived a provisional inhalation unit risk (IUR) of 0.009 per μg/m(3) based on a chronic inhalation study of soluble cobalt sulfate heptahydrate; however, a recent 2-year cancer bioassay affords the opportunity to derive IURs specifically for cobalt metal. The mechanistic data support that the carcinogenic mode of action (MOA) is likely to involve oxidative stress, and thus, non-linear/threshold mechanisms. However, the lack of a detailed MOA and use of high, toxic exposure concentrations in the bioassay (≥1.25 mg/m(3)) preclude derivation of a reference concentration (RfC) protective of cancer. Several analyses resulted in an IUR of 0.003 per μg/m(3) for cobalt metal, which is ∼3-fold less potent than the provisional IUR. Future research should focus on establishing the exposure-response for key precursor events to improve cobalt metal risk assessment. PMID:27177823

  12. Quantitative analysis of dynamic airway changes after methacholine and salbutamol inhalation on xenon-enhanced chest CT

    International Nuclear Information System (INIS)

    To investigate the dynamic changes in airways in response to methacholine and salbutamol inhalation and to correlate the xenon ventilation index on xenon-enhanced chest CTs in asthmatics. Thirty-one non-smokers (6 normal, 25 asthmatics) underwent xenon-enhanced chest CT and pulmonary function tests. Images were obtained at three stages (basal state, after methacholine inhalation and after salbutamol inhalation), and the total xenon ventilation index (TXVI) as well as airway values were measured and calculated. The repeated measures ANOVA and Spearman's correlation coefficient were used for statistical analysis. TXVI in the normal group did not significantly change (P > 0.05) with methacholine and salbutamol. For asthmatics, however, the TXVI significantly decreased after methacholine inhalation and increased after salbutamol inhalation (P 0.05). IA of the large airways was well correlated with basal TXVI, FEV1 and FVC (P < 0.05). Airway IA is the most reliable parameter for reflecting the dynamic changes after methacholine and salbutamol inhalation, and correlates well with TXVI in asthmatics on xenon-enhanced CT. (orig.)

  13. Hepatotoxic Alterations Induced by Subchronic Exposure of Rats to Formulated Fenvalerate (20% EC) by Nose Only Inhalation

    Institute of Scientific and Technical Information of China (English)

    U. MANI; A. K. PRASAD; V. SURESHKUMAR; P. KUMAR; KEWAL LAL; B. K. MAJI; K. K. DUTTA

    2004-01-01

    Fenvalerate (20% EC) is a synthetic pyrethroid, which is commonly used in India by farmers for the protection of many food and vegetable crops against a wide variety of insects. However, its inhalation toxicity data is very limited in the literature due to the fact that the exposure levels associated with these effects were usually not reported. Hence, inhalation exposure was carried out to investigate the hepatotoxic effects. Method Adult male rats were exposed to fen for 4 h/day, 5 days a week for 90 days by using Flow Past Nose Only Inhalation Chamber. Sham treated control rats were exposed to compressed air in the inhalation chamber for the same period. Results The results indicated hepatomegaly, increased activities of serum clinical enzymes (indicative of liver damage/dysfunction) along with pronounced histopathological damage of liver. Conclusion The hepatotoxic potential of formulated Fen (20% EC) in rats exposed by nose only inhalation is being reported for the first time and warrant adequate safety measures for human beings exposed to this insecticide, particularly by inhalation route.

  14. Whole-body nanoparticle aerosol inhalation exposures.

    Science.gov (United States)

    Yi, Jinghai; Chen, Bean T; Schwegler-Berry, Diane; Frazer, Dave; Castranova, Vince; McBride, Carroll; Knuckles, Travis L; Stapleton, Phoebe A; Minarchick, Valerie C; Nurkiewicz, Timothy R

    2013-01-01

    Inhalation is the most likely exposure route for individuals working with aerosolizable engineered nano-materials (ENM). To properly perform nanoparticle inhalation toxicology studies, the aerosols in a chamber housing the experimental animals must have: 1) a steady concentration maintained at a desired level for the entire exposure period; 2) a homogenous composition free of contaminants; and 3) a stable size distribution with a geometric mean diameter generation of aerosols containing nanoparticles is quite challenging because nanoparticles easily agglomerate. This is largely due to very strong inter-particle forces and the formation of large fractal structures in tens or hundreds of microns in size (6), which are difficult to be broken up. Several common aerosol generators, including nebulizers, fluidized beds, Venturi aspirators and the Wright dust feed, were tested; however, none were able to produce nanoparticle aerosols which satisfy all criteria (5). A whole-body nanoparticle aerosol inhalation exposure system was fabricated, validated and utilized for nano-TiO2 inhalation toxicology studies. Critical components: 1) novel nano-TiO2 aerosol generator; 2) 0.5 m(3) whole-body inhalation exposure chamber; and 3) monitor and control system. Nano-TiO2 aerosols generated from bulk dry nano-TiO2 powders (primary diameter of 21 nm, bulk density of 3.8 g/cm(3)) were delivered into the exposure chamber at a flow rate of 90 LPM (10.8 air changes/hr). Particle size distribution and mass concentration profiles were measured continuously with a scanning mobility particle sizer (SMPS), and an electric low pressure impactor (ELPI). The aerosol mass concentration (C) was verified gravimetrically (mg/m(3)). The mass (M) of the collected particles was determined as M = (Mpost-Mpre), where Mpre and Mpost are masses of the filter before and after sampling (mg). The mass concentration was calculated as C = M/(Q*t), where Q is sampling flowrate (m(3)/min), and t is the sampling

  15. Pulmonary and Systemic Immune Response to Chronic Lunar Dust Inhalation

    Science.gov (United States)

    Crucian, Brian; Quiriarte, Heather; Nelman, Mayra; Lam, Chiu-wing; James, John T.; Sams, Clarence

    2014-01-01

    Background: Due to millennia of meteorite impact with virtually no erosive effects, the surface of the Moon is covered by a layer of ultra-fine, reactive Lunar dust. Very little is known regarding the toxicity of Lunar dust on human physiology. Given the size and electrostatic characteristics of Lunar dust, countermeasures to ensure non-exposure of astronauts will be difficult. To ensure astronaut safety during any future prolonged Lunar missions, it is necessary to establish the effect of chronic pulmonary Lunar dust exposure on all physiological systems. Methods: This study assessed the toxicity of airborne lunar dust exposure in rats on pulmonary and system immune system parameters. Rats were exposed to 0, 20.8, or 60.8 mg/m3 of lunar dust (6h/d; 5d/wk) for up to 13 weeks. Sacrifices occurred after exposure durations of 1day, 7 days, 4 weeks and 13 weeks post-exposure, when both blood and lung lavage fluid were collected for analysis. Lavage and blood assays included leukocyte distribution by flow cytometry, electron/fluorescent microscopy, and cytokine concentration. Cytokine production profiles following mitogenic stimulation were performed on whole blood only. Results: Untreated lavage fluid was comprised primarily of pulmonary macrophages. Lunar dust inhalation resulted in an influx of neutrophils and lymphocytes. Although the percentage of lymphocytes increased, the T cell CD4:CD8 ratio was unchanged. Cytokine analysis of the lavage fluid showed increased levels of IL-1b and TNFa. These alterations generally persisted through the 13 week sampling. Blood analysis showed few systemic effects from the lunar dust inhalation. By week 4, the peripheral granulocyte percentage was elevated in the treated rats. Plasma cytokine levels were unchanged in all treated rats compared to controls. Peripheral blood analysis showed an increased granulocyte percentage and altered cytokine production profiles consisting of increased in IL-1b and IL-6, and decreased IL-2

  16. Oral and inhaled corticosteroids: Differences in P-glycoprotein (ABCB1) mediated efflux

    International Nuclear Information System (INIS)

    There is concern that P-glycoprotein mediated efflux contributes to steroid resistance. Therefore, this study examined bidirectional corticosteroid transport and induction capabilities for P-glycoprotein (P-gp) to understand which of the systemic and inhaled corticosteroids interacted with P-gp to the greatest extent. Hydrocortisone, prednisolone, prednisone, methylprednisolone, and dexamethasone represented systemically active drugs, while fluticasone propionate, beclomethasone dipropionate, ciclesonide and budesonide represented inhaled corticosteroids. Aldosterone and fludrocortisone represented mineralocorticoids. All drugs were detected using individually optimised HPLC protocols. Transport studies were conducted through Caco-2 monolayers. Hydrocortisone and aldosterone had efflux ratios below 1.5, while prednisone showed a P-gp mediated efflux ratio of only 1.8 compared to its active drug, prednisolone, with an efflux ratio of 4.5. Dexamethasone and beclomethasone had efflux ratios of 2.1 and 3.3 respectively, while this increased to 5.1 for methylprednisolone. Fluticasone showed an efflux ratio of 2.3. Protein expression studies suggested that all of the inhaled corticosteroids were able to induce P-gp expression, from 1.6 to 2 times control levels. Most of the systemic corticosteroids had higher passive permeability (> 20 × 10−6 cm/s) compared to the inhaled corticosteroids (> 5 × 10−6 cm/s), except for budesonide, with permeability similar to the systemic corticosteroids. Inhaled corticosteroids are not transported by P-gp to the same extent as systemic corticosteroids. However, they are able to induce P-gp production. Thus, inhaled corticosteroids may have greater interactions with other P-gp substrates, but P-gp itself is less likely to influence resistance to the drugs. -- Highlights: ► Inhaled corticosteroids are only weak substrates for P-gp, including budesonide. ► Inhaled corticosteroid potent P-gp inducers especially fluticasone and

  17. Oral and inhaled corticosteroids: Differences in P-glycoprotein (ABCB1) mediated efflux

    Energy Technology Data Exchange (ETDEWEB)

    Crowe, Andrew, E-mail: a.p.crowe@curtin.edu.au; Tan, Ai May

    2012-05-01

    There is concern that P-glycoprotein mediated efflux contributes to steroid resistance. Therefore, this study examined bidirectional corticosteroid transport and induction capabilities for P-glycoprotein (P-gp) to understand which of the systemic and inhaled corticosteroids interacted with P-gp to the greatest extent. Hydrocortisone, prednisolone, prednisone, methylprednisolone, and dexamethasone represented systemically active drugs, while fluticasone propionate, beclomethasone dipropionate, ciclesonide and budesonide represented inhaled corticosteroids. Aldosterone and fludrocortisone represented mineralocorticoids. All drugs were detected using individually optimised HPLC protocols. Transport studies were conducted through Caco-2 monolayers. Hydrocortisone and aldosterone had efflux ratios below 1.5, while prednisone showed a P-gp mediated efflux ratio of only 1.8 compared to its active drug, prednisolone, with an efflux ratio of 4.5. Dexamethasone and beclomethasone had efflux ratios of 2.1 and 3.3 respectively, while this increased to 5.1 for methylprednisolone. Fluticasone showed an efflux ratio of 2.3. Protein expression studies suggested that all of the inhaled corticosteroids were able to induce P-gp expression, from 1.6 to 2 times control levels. Most of the systemic corticosteroids had higher passive permeability (> 20 × 10{sup −6} cm/s) compared to the inhaled corticosteroids (> 5 × 10{sup −6} cm/s), except for budesonide, with permeability similar to the systemic corticosteroids. Inhaled corticosteroids are not transported by P-gp to the same extent as systemic corticosteroids. However, they are able to induce P-gp production. Thus, inhaled corticosteroids may have greater interactions with other P-gp substrates, but P-gp itself is less likely to influence resistance to the drugs. -- Highlights: ► Inhaled corticosteroids are only weak substrates for P-gp, including budesonide. ► Inhaled corticosteroid potent P-gp inducers especially

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

    Science.gov (United States)

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

    2013-09-01

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

  19. Inhalant abuse by adolescents: A new challenge for Indian physicians

    Directory of Open Access Journals (Sweden)

    Basu Debasish

    2004-06-01

    Full Text Available Inhalant abuse has been commonly reported especially in the young during the last decades globally. The reason for the relative paucity of literature from India may be attributed to a lack of knowledge about this growing problem among health professionals. A series of five cases of inhalant abuse is described in order to understand this growing public health concern. Most of the cases started inhalant abuse during adolescence. All patients except one abused typewriter erasing fluid and thinner which contains toluene. All the patients reported using inhalants as addictive substance because of their easy accessibility, cheap price, their faster onset of action and the regular ′high′ that it provided. Whereas several features of inhalant dependence were fulfilled, no physical withdrawal signs were observed. The diagnosis of inhalant abuse can be difficult and relies almost entirely on clinical judgment. Treatment is generally supportive.

  20. Inhaled Surfactant in the treatment of accidental Talc Powder inhalation: a new case report

    Directory of Open Access Journals (Sweden)

    Lo Piparo Caterina

    2011-09-01

    Full Text Available Abstract 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.

  1. Inhalation toxicity of propineb. Part I: Results of subacute inhalation exposure studies in rats.

    Science.gov (United States)

    Pauluhn, Jürgen; Rosenbruch, Martin

    2003-04-25

    This article addresses results from repeated 1- and 4-wk inhalation exposure studies in Wistar rats with solid aerosol (dust) atmospheres of propineb, a zinc bisdithiocarbamate homopolymer that is used as an agrochemical fungicide. Groups of 10 rats/sex were exposed nose-only to mean concentrations of 3.97, 11.24, and 21.95 mg propineb/m(3) using an exposure regimen of 6 h/day, 5 days/wk for 4 wk. Concentrations were selected based on results from a pilot study in which rats were exposed under identical conditions on 5 consecutive days for 6 h/day to mean concentrations of 10.1, 19.9, 38.1, and 78.7 mg/m(3). Both studies demonstrated that with respect to muscular effects female rats were remarkably more susceptible as compared to males. Female rats exposed to 11.24 mg/m(3) and above displayed characteristic signs of toxicity that included weakness and flaccid paralysis of hindlegs and ensuing immobilization that was considered to be the cause of emaciation and ensuing mortality in some rats. There was an apparent reciprocal relationship of concentration and the manifestation of clinical evidence of muscular dysfunction; that is, the onset in female rats exposed to 11.24, 21.95, 38.1, and 78.7 mg/m(3) was on days 15, 8, 4, and 3, respectively. In contrast, none of the male rats elaborated comparable effects up to 38.1 mg/m(3). Neuromuscular measures included leg grip strength and supplemented the clinical findings, whereas the landing foot splay was only minimally affected. Hematology and clinical pathology endpoints, including those addressing thyroidal function, were unobtrusive up to and including 78.7 mg/m(3). Lung weights were significantly increased in groups exposed to 21.95 mg/m(3) and above, especially in male rats. The microscopic examinations made in the 4-wk study demonstrated an increased incidence of intraalveolar material and enlarged, foamy alveolar macrophages at 3.97 mg/m(3) and above. Especially in female rats an atrophy of thigh muscle fibers

  2. Modulation of Immune Response in Asthmatic Patients by Using Inhaled Tuberculin

    International Nuclear Information System (INIS)

    Bronchial asthma is a chronic immuno inflammatory reversible lung disease with airway responsiveness to various stimuli which relived by proper therapy using inhaled steroids or the highly expensive recombinant interferon gamma (IFN-gamma). This study undertaken to investigate for the first time a novel treatment method using inhaled tuberculin (PPD) to determine whether PPD inhalation could be safely and effectively delivered into the airways of bronchial asthmatic patients in attempt to bring immurite deviation away from atopy via inhaling an economic dose of tuberculin. Sixty patients suffering from mild atopic bronchial asthma along with twenty healthy volunteers were included in our study. Patients were randomly categorized into three equally-sized groups received 2, 5 and 10 PPD units respectively. Treatment doses taken every 72 hours for two weeks. Respiratory function tests were examined before and after treatment regime. Interleukin 2 (IL-2), IL-4 and immunoglobulin E (IgE)w ere measured by ELISA technique in serum and bronchoalveolar lavage fluid (BALF) samples before and after treatment regime. Eosinophil count in BALF was also examined. The results showed that PPD treatment doses caused a significant increase in lung function standards (FEV1 and FEV1/FVC ratio) as compared with before treatment values. Also, the different doses of PPD resulted in a highly significant increase in the levels of serum and BALF IL-2 with a concomitant significant decrease in BALF IL-4

  3. Inhaled Cadmium Oxide Nanoparticles: Their in Vivo Fate and Effect on Target Organs

    Directory of Open Access Journals (Sweden)

    Jana Dumkova

    2016-06-01

    Full Text Available The increasing amount of heavy metals used in manufacturing equivalently increases hazards of environmental pollution by industrial products such as cadmium oxide (CdO nanoparticles. Here, we aimed to unravel the CdO nanoparticle destiny upon their entry into lungs by inhalations, with the main focus on the ultrastructural changes that the nanoparticles may cause to tissues of the primary and secondary target organs. We indeed found the CdO nanoparticles to be transported from the lungs into secondary target organs by blood. In lungs, inhaled CdO nanoparticles caused significant alterations in parenchyma tissue including hyperemia, enlarged pulmonary septa, congested capillaries, alveolar emphysema and small areas of atelectasis. Nanoparticles were observed in the cytoplasm of cells lining bronchioles, in the alveolar spaces as well as inside the membranous pneumocytes and in phagosomes of lung macrophages. Nanoparticles even penetrated through the membrane into some organelles including mitochondria and they also accumulated in the cytoplasmic vesicles. In livers, inhalation caused periportal inflammation and local hepatic necrosis. Only minor changes such as diffusely thickened filtration membrane with intramembranous electron dense deposits were observed in kidney. Taken together, inhaled CdO nanoparticles not only accumulated in lungs but they were also transported to other organs causing serious damage at tissue as well as cellular level.

  4. Inhaled Cadmium Oxide Nanoparticles: Their in Vivo Fate and Effect on Target Organs.

    Science.gov (United States)

    Dumkova, Jana; Vrlikova, Lucie; Vecera, Zbynek; Putnova, Barbora; Docekal, Bohumil; Mikuska, Pavel; Fictum, Petr; Hampl, Ales; Buchtova, Marcela

    2016-01-01

    The increasing amount of heavy metals used in manufacturing equivalently increases hazards of environmental pollution by industrial products such as cadmium oxide (CdO) nanoparticles. Here, we aimed to unravel the CdO nanoparticle destiny upon their entry into lungs by inhalations, with the main focus on the ultrastructural changes that the nanoparticles may cause to tissues of the primary and secondary target organs. We indeed found the CdO nanoparticles to be transported from the lungs into secondary target organs by blood. In lungs, inhaled CdO nanoparticles caused significant alterations in parenchyma tissue including hyperemia, enlarged pulmonary septa, congested capillaries, alveolar emphysema and small areas of atelectasis. Nanoparticles were observed in the cytoplasm of cells lining bronchioles, in the alveolar spaces as well as inside the membranous pneumocytes and in phagosomes of lung macrophages. Nanoparticles even penetrated through the membrane into some organelles including mitochondria and they also accumulated in the cytoplasmic vesicles. In livers, inhalation caused periportal inflammation and local hepatic necrosis. Only minor changes such as diffusely thickened filtration membrane with intramembranous electron dense deposits were observed in kidney. Taken together, inhaled CdO nanoparticles not only accumulated in lungs but they were also transported to other organs causing serious damage at tissue as well as cellular level. PMID:27271611

  5. Inhaled Cadmium Oxide Nanoparticles: Their in Vivo Fate and Effect on Target Organs

    Science.gov (United States)

    Dumkova, Jana; Vrlikova, Lucie; Vecera, Zbynek; Putnova, Barbora; Docekal, Bohumil; Mikuska, Pavel; Fictum, Petr; Hampl, Ales; Buchtova, Marcela

    2016-01-01

    The increasing amount of heavy metals used in manufacturing equivalently increases hazards of environmental pollution by industrial products such as cadmium oxide (CdO) nanoparticles. Here, we aimed to unravel the CdO nanoparticle destiny upon their entry into lungs by inhalations, with the main focus on the ultrastructural changes that the nanoparticles may cause to tissues of the primary and secondary target organs. We indeed found the CdO nanoparticles to be transported from the lungs into secondary target organs by blood. In lungs, inhaled CdO nanoparticles caused significant alterations in parenchyma tissue including hyperemia, enlarged pulmonary septa, congested capillaries, alveolar emphysema and small areas of atelectasis. Nanoparticles were observed in the cytoplasm of cells lining bronchioles, in the alveolar spaces as well as inside the membranous pneumocytes and in phagosomes of lung macrophages. Nanoparticles even penetrated through the membrane into some organelles including mitochondria and they also accumulated in the cytoplasmic vesicles. In livers, inhalation caused periportal inflammation and local hepatic necrosis. Only minor changes such as diffusely thickened filtration membrane with intramembranous electron dense deposits were observed in kidney. Taken together, inhaled CdO nanoparticles not only accumulated in lungs but they were also transported to other organs causing serious damage at tissue as well as cellular level. PMID:27271611

  6. Defence System of Respiratory Tract and Clearence of Inhalation Agents

    OpenAIRE

    Nesrin Ocal

    2016-01-01

    It is well known that inhaled urban air contains many particles and gases. On the other hand, the anesthetic agents used in respiratory diseases comprise pharmaceutical particles. Deposition and cleaning processes of both the inhaled foreign particles and gases from room air, and inhalation agents from respiratory tract are very important clinically. These processes are carried out by the defense mechanisms of the respiratory system. In this review, the defence system of respiratory tract and...

  7. Guidelines for the safe administration of inhaled nitric oxide.

    OpenAIRE

    Miller, O I; Celermajer, D S; Deanfield, J. E.; MacRae, D. J.

    1994-01-01

    Inhaled nitric oxide (NO) is a selective pulmonary vasodilator, potentially useful in the treatment of pulmonary hypertension and ventilation-perfusion mismatch. High doses of inhaled NO and its oxidative product nitrogen dioxide (NO2) may cause acute lung injury. Using a standard infant ventilator, ventilator circuit and test lung, an administration and monitoring strategy has been defined for inhaled NO and these observations validated in eight ventilated infants. In 90% oxygen, doses of in...

  8. Adolescent inhalant use prevention, assessment, and treatment: A literature synthesis.

    Science.gov (United States)

    Nguyen, Jacqueline; O'Brien, Casey; Schapp, Salena

    2016-05-01

    Inhalant use refers to the use of substances such as gases, glues, and aerosols in order to achieve intoxication, while inhalant use disorder (IUD) encompasses both DSM-IV-TR criteria for inhalant abuse and dependence. Inhalant use among adolescents is an international public health concern considering the severe medical and cognitive consequences and biopsychosocial correlates. In this paper, we summarize the current state of the literature on inhalant use among adolescents focusing on social context, prevention, assessment, and treatment strategies. Psychoeducation, skills training, and environmental supply reduction are helpful strategies for preventing adolescent inhalant use, while parent and adolescent self-report as well as physician report of medical signs and symptoms can aid in assessment and diagnosis. Although research has only begun to explore the treatment of inhalant use, preliminary findings suggest that a multimodal approach involving individual counselling (i.e., CBT brief intervention), family therapy, and activity and engagement programs is the first-line treatment, with residential treatment programs indicated for more severe presentations. The limited nature of treatments developed specifically for inhalant use combined with high prevalence rates and potential for significant impairment within the adolescent population indicate the need for further research. Research should focus on understanding the social context of use, establishing the efficacy of current adolescent substance use treatments adapted for inhalant use, and exploring long-term outcomes. PMID:26969125

  9. Efficacy of two educational interventions about inhalation techniques in patients with chronic obstructive pulmonary disease (COPD. TECEPOC: study protocol for a partially randomized controlled trial (preference trial

    Directory of Open Access Journals (Sweden)

    Leiva-Fernández Francisca

    2012-05-01

    Full Text Available Abstract Background Drugs for inhalation are the cornerstone of therapy in obstructive lung disease. We have observed that up to 75 % of patients do not perform a correct inhalation technique. The inability of patients to correctly use their inhaler device may be a direct consequence of insufficient or poor inhaler technique instruction. The objective of this study is to test the efficacy of two educational interventions to improve the inhalation techniques in patients with Chronic Obstructive Pulmonary Disease (COPD. Methods This study uses both a multicenter patients´ preference trial and a comprehensive cohort design with 495 COPD-diagnosed patients selected by a non-probabilistic method of sampling from seven Primary Care Centers. The participants will be divided into two groups and five arms. The two groups are: 1 the patients´ preference group with two arms and 2 the randomized group with three arms. In the preference group, the two arms correspond to the two educational interventions (Intervention A and Intervention B designed for this study. In the randomized group the three arms comprise: intervention A, intervention B and a control arm. Intervention A is written information (a leaflet describing the correct inhalation techniques. Intervention B is written information about inhalation techniques plus training by an instructor. Every patient in each group will be visited six times during the year of the study at health care center. Discussion Our hypothesis is that the application of two educational interventions in patients with COPD who are treated with inhaled therapy will increase the number of patients who perform a correct inhalation technique by at least 25 %. We will evaluate the effectiveness of these interventions on patient inhalation technique improvement, considering that it will be adequate and feasible within the context of clinical practice. Trial registration Current Controlled Trials ISRTCTN15106246

  10. BLUNTING AIRWAYS EOSINOPHILIC INFLAMMATION RESULTS IN A DECREASED AIRWAY NEUTROPHIL RESPONSE TO INHALED LPS IN ATOPIC ASTHMATICS A ROLE FOR CD-14

    Science.gov (United States)

    Recent data demonstrate that atopic inflammation might enhance airway responses to inhaled LPS in individuals with atopic asthma by increasing CD14 expression on airway macrophages. We sought to determine whether blunting airway eosinophilic inflammation decreases CD14 expressio...

  11. Inflammatory effects of inhaled sulfur mustard in rat lung

    International Nuclear Information System (INIS)

    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-α (TNFα), inducible nitric oxide synthase (iNOS), and matrix metalloproteinase-9 (MMP-9), each of which has been implicated in pulmonary toxicity. Whereas COX-2, TNFα 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.

  12. Inhalation carcinogenicity study with nickel metal powder in Wistar rats

    International Nuclear Information System (INIS)

    Epidemiological studies of nickel refinery workers have demonstrated an association between increased respiratory cancer risk and exposure to certain nickel compounds (later confirmed in animal studies). However, the lack of an association found in epidemiological analyses for nickel metal remained unconfirmed for lack of robust animal inhalation studies. In the present study, Wistar rats were exposed by whole-body inhalation to 0, 0.1, 0.4, and 1.0 mg Ni/m3 nickel metal powder (MMAD = 1.8 μm, GSD = 2.4 μm) for 6 h/day, 5 days/week for up to 24 months. A subsequent six-month period without exposures preceded the final euthanasia. High mortality among rats exposed to 1.0 mg Ni/m3 nickel metal resulted in the earlier termination of exposures in this group. The exposure level of 0.4 mg Ni/m3 was established as the MTD for the study. Lung alterations associated with nickel metal exposure included alveolar proteinosis, alveolar histiocytosis, chronic inflammation, and bronchiolar-alveolar hyperplasia. No increased incidence of neoplasm of the respiratory tract was observed. Adrenal gland pheochromocytomas (benign and malignant) in males and combined cortical adenomas/carcinomas in females were induced in a dose-dependent manner by the nickel metal exposure. The incidence of pheochromocytomas was statistically increased in the 0.4 mg Ni/m3 male group. Pheochromocytomas appear to be secondary to the lung toxicity associated with the exposure rather than being related to a direct nickel effect on the adrenal glands. The incidence of cortical tumors among 0.4 mg Ni/m3 females, although statistically higher compared to the concurrent controls, falls within the historical control range; therefore, in the present study, this tumor is of uncertain relationship to nickel metal exposure. The lack of respiratory tumors in the present animal study is consistent with the findings of the epidemiological studies

  13. Tolerability of inhaled N-chlorotaurine in the pig model

    Directory of Open Access Journals (Sweden)

    Scholl-Bürgi Sabine

    2009-07-01

    Full Text Available Abstract Background N-chlorotaurine, a long-lived oxidant produced by human leukocytes, can be applied in human medicine as an endogenous antiseptic. Its antimicrobial activity can be enhanced by ammonium chloride. This study was designed to evaluate the tolerability of inhaled N-chlorotaurine (NCT in the pig model. Methods Anesthetized pigs inhaled test solutions of 1% (55 mM NCT (n = 7, 5% NCT (n = 6, or 1% NCT plus 1% ammonium chloride (NH4Cl (n = 6, and 0.9% saline solution as a control (n = 7, respectively. Applications with 5 ml each were performed hourly within four hours. Lung function, haemodynamics, and pharmacokinetics were monitored. Bronchial lavage samples for captive bubble surfactometry and lung samples for histology and electron microscopy were removed. Results Arterial pressure of oxygen (PaO2 decreased significantly over the observation period of 4 hours in all animals. Compared to saline, 1% NCT + 1% NH4Cl led to significantly lower PaO2 values at the endpoint after 4 hours (62 ± 9.6 mmHg vs. 76 ± 9.2 mmHg, p = 0.014 with a corresponding increase in alveolo-arterial difference of oxygen partial pressure (AaDO2 (p = 0.004. Interestingly, AaDO2 was lowest with 1% NCT, even lower than with saline (p = 0.016. The increase of pulmonary artery pressure (PAP over the observation period was smallest with 1% NCT without difference to controls (p = 0.91, and higher with 5% NCT (p = 0.02, and NCT + NH4Cl (p = 0.05. Histological and ultrastructural investigations revealed no differences between the test and control groups. The surfactant function remained intact. There was no systemic resorption of NCT detectable, and its local inactivation took place within 30 min. The concentration of NCT tolerated by A549 lung epithelial cells in vitro was similar to that known from other body cells (0.25–0.5 mM. Conclusion The endogenous antiseptic NCT was well tolerated at a concentration of 1% upon inhalation in the pig model. Addition of

  14. Particle-induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular disease

    DEFF Research Database (Denmark)

    Saber, Anne T.; Jacobsen, Nicklas R.; Jackson, Petra;

    2014-01-01

    Inhalation of ambient and workplace particulate air pollution is associated with increased risk of cardiovascular disease. One proposed mechanism for this association is that pulmonary inflammation induces a hepatic acute phase response, which increases risk of cardiovascular disease. Induction of...... epidemiological studies. In this review, we present and review emerging evidence that inhalation of particles (e.g., air diesel exhaust particles and nanoparticles) induces a pulmonary acute phase response, and propose that this induction constitutes the causal link between particle inhalation and risk of...... cardiovascular disease. Increased levels of acute phase mRNA and proteins in lung tissues, bronchoalveolar lavage fluid and plasma clearly indicate pulmonary acute phase response following pulmonary deposition of different kinds of particles including diesel exhaust particles, nanoparticles, and carbon nanotubes...

  15. [Is it necessary to humidify inhaled low-flow oxygen or low-concentration oxygen?].

    Science.gov (United States)

    Miyamoto, Kenji

    2004-02-01

    In Japan, oxygen is routinely humidified in almost every hospital and clinic. In contrast, in Europe and North America, oxygen is not humidified as long as the oxygen flow is less than 4-5 L/min, according to the guidelines for oxygen therapy announced by the ACCP-NHLBI in 1984 and by AARC in 1992. In this paper, we demonstrate mathematically that: 1) the oxygen received through a nasal cannula at 0.5-4 L/min or through a Venturi mask at 24-40% constitutes only a small percentage of the patient's inspiratory tidal volume (2.4-19% and 3.8-24%, respectively), 2) the humidity deficit caused by inhaling unhumidified oxygen through a nasal cannula at 0.5-4 L/min or through a Venturi mask at 24% to 31% is very small compared with the water content delivered from the airway, and 3) this humidity deficit is easily compensated for by increasing the relative humidity of the room air a little, e.g., by only 4% in case of inhalation of 2 L/min of oxygen through a nasal cannula. Similar results are obtained when a Venturi mask is used to inhale oxygen. From these calculations, we conclude that routine humidification of low-flow oxygen or low-concentration oxygen is not justifiable in patients who need oxygen inhalation, as the humidity of room air is sufficient. PMID:15007913

  16. Comparison of MRI, CT, TCD and SPECT in patients with spongiform leukoencephalopathy after inhaling heroin vapor

    International Nuclear Information System (INIS)

    Objective: To compare the characteristics of MRI, CT, single photon emission computed tomography (SPECT) and transcranial Doppler sonography (TCD) in patients with spongiform leukoencephalopathy after inhaling heroin vapor. Methods: Seventeen patients were investigated. MRI or CT was scanned in 17 patients, SPECT in 9 patients' and TCD in 11 patients. Results: MRI or CT: Brain MRI and CT revealed extensive symmetric white matter involvement of bilateral cerebral and cerebellar hemispheres and the brainstem. The lesions, which showed no contrast enhancement, were hypodense on CT and hypointense on T1-weighted and hyperintense on T2-weighted MRI. SPECT: The regional cerebral blood flows (rCBF) of white matter involvement on bilateral cerebral and cerebellar hemispheres was reduced obviously. The rCBF of temporal lobes, parietal lobes, occipital lobes, cerebellar hemispheres, and basal ganglion was reduced in varying degrees. TCD: The systolic peak became sharpened, and end-diastolic flow velocity and mean flow velocity were reduced obviously and pulsatile index was increased markedly in patients with spongiform leukoencephalopathy after inhaling heroin vapor. Conclusion: The characteristic manifestations of MRI and CT imaging may be regarded as the main foundation of diagnosing spongiform leukoencephalopathy after inhaling heroin vapor; SPECT and TCD can help comprehend the changes of hemodynamics of cerebral vessels and the degree of cerebral ischemia in patients with spongiform leukoencephalopathy after inhaling heroin vapor

  17. Nanospray drying as a novel technique for the manufacturing of inhalable NSAID powders.

    Science.gov (United States)

    Aquino, Rita Patrizia; Stigliani, Mariateresa; Del Gaudio, Pasquale; Mencherini, Teresa; Sansone, Francesca; Russo, Paola

    2014-01-01

    The aim of this research was to evaluate the potential of the nanospray drier as a novel apparatus for the manufacturing of a dry powder for inhalation containing ketoprofen lysinate, a nonsteroidal anti-inflammatory drug able to control the inflammation in cystic fibrosis patients. We produced several ketoprofen lysinate and leucine powder batches by means of nanospray dryer, studying the influence of process parameters on yield, particle properties (size distribution and morphology), and, mainly, aerodynamic properties of powders. Micronized particles were prepared from different hydroalcoholic solutions (alcohol content from 0 to 30% v/v) using ketoprofen in its lysine salt form and leucine as dispersibility enhancer in different ratios (from 5 to 15% w/w) with a total solid concentration ranging from 1 to 7% w/v. Results indicated that the spray head equipped with a 7 µm nozzle produced powders too big to be inhaled. The reduction of nozzle size from 7 to 4 µm led to smaller particles suitable for inhalation but, at the same time, caused a dramatic increase in process time. The selection of process variables, together with the nozzle pretreatment with a surfactant solution, allowed us to obtain a free flowing powder with satisfying aerosol performance, confirming the usefulness of the nanospray drier in the production of powder for inhalation. PMID:25580462

  18. The determination of exogenous formaldehyde in blood of rats during and after inhalation exposure.

    Science.gov (United States)

    Kleinnijenhuis, Anne J; Staal, Yvonne C M; Duistermaat, Evert; Engel, Roel; Woutersen, Ruud A

    2013-02-01

    Formaldehyde (FA) is suspected of being associated with the development of leukemia. An inhalation experiment with FA was performed in rats to study whether FA can enter the blood and could thus cause systemic toxicity in remote tissues such as the bone marrow. Therefore, a sophisticated analytical method was developed to detect blood concentrations of FA during and after single 6-h exposure by inhalation. In order to differentiate between exogenous and endogenous FA the rats were exposed to stable isotope ((13)C) labeled FA by inhalation. During and after exposure of the rats to (13)C-FA their blood was analyzed to determine the ratio between labeled and natural FA in blood and the total blood concentration of FA. With respect to sensitivity, with the applied method exogenous (13)C-FA could have been detected in blood at a concentration approximately 1.5% of the endogenous FA blood concentration. Exogenous (13)C-FA was not detectable in the blood of rats either during or up to 30 min after the exposure. It was concluded that the inhalation of (13)C-FA at 10 ppm for 6h did not result in an increase of the total FA concentration in blood. PMID:23159914

  19. Simvastatin delivery via inhalation attenuates airway inflammation in a murine model of asthma.

    Science.gov (United States)

    Xu, Lan; Dong, Xing-wei; Shen, Liang-liang; Li, Fen-fen; Jiang, Jun-xia; Cao, Rui; Yao, Hong-yi; Shen, Hui-juan; Sun, Yun; Xie, Qiang-min

    2012-04-01

    The dose-response of the pleiotropic effects of statins on airway inflammation has not yet been established and may differ from that of their cholesterol-lowering effects. High oral doses of statins may have adverse effects, and it may be possible to overcome the side effects and low clinical efficacy by administering statins via inhalation. In this study, we hypothesize that simvastatin is a potential anti-inflammatory drug with biological and pharmacokinetic properties suitable for delivery by the inhaled route. Mice were immunized with ovalbumin (OVA) and then challenged with aerosol OVA. Simvastatin was locally delivered by inhalation (i.h.) and intratracheal injection (i.t.) or systematically delivered by intraperitoneal injection (i.p.) and gavage (i.g.) during the OVA challenge. In a mouse model of asthma, i.h. simvastatin significantly and dose-dependently attenuated airway inflammation, remodeling and hyperresponsiveness in a RhoA-dependent pathway. Upon comparing the pharmacodynamics, i.h. simvastatin had a more potent effect than that of i.g. and i.p. simvastatin, and the i.h. or i.t. delivery routes led to a higher drug concentration in local lung tissue and a lower drug concentration in the plasma than that obtained by the i.g. These results suggest that simvastatin is a potential anti-inflammatory drug for airway inflammatory diseases with properties suitable for delivery by inhalation, which will probably reduce the side effects and increase clinical efficacy. PMID:22326624

  20. Candida albicans chronic colonisation in cystic fibrosis may be associated with inhaled antibiotics.

    Science.gov (United States)

    Noni, Maria; Katelari, Anna; Kaditis, Athanasios; Theochari, Ioanna; Lympari, Ioulia; Alexandrou-Athanassoulis, Helen; Doudounakis, Stavros-Eleftherios; Dimopoulos, George

    2015-07-01

    Candida albicans is increasingly recognised as a coloniser of the respiratory tract in cystic fibrosis (CF) patients. Yet, the potential role, if any, of the micro-organism in the progress of the disease remains unclear. In this study, we investigated the association between inhaled antibiotics and C. albicans chronic colonisation in patients with CF. A cohort of 121 CF patients born from 1988 to 1996 was, respectively, studied. The medical records of each patient were reviewed from the first time they attended the CF Centre until the occurrence of C. albicans chronic colonisation or their last visit for the year 2010. Chronic colonisation was defined as the presence of C. albicans in more than 50% of cultures in a given year. A number of possible confounders were included in the multivariate logistic regression analysis to identify an independent association between inhaled antibiotics and C. albicans chronic colonisation. Fifty-four (44.6%) of the 121 patients enrolled in the study developed chronic colonisation by the micro-organism. Multivariate logistic regression analysis determined the independent effect of inhaled antibiotic treatment on the odds of chronic colonisation (OR 1.112, 95% CI [1.007-1.229], P = 0.036). Candida albicans chronic colonisation may be associated with the duration of inhaled antibiotic treatment. PMID:26058475

  1. 45. Damage effects of sulfur dioxide inhalation on DNA of brain cells from mice

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The damage effects of sulfur dioxide (SO2) inhalation on DNA of brain cells from mice were studied with the single cell microgel electrophoresis tecknique (Comet test). The results show that SO2 inhalation caused the damage effects to DNA of the mouse brain cells in a dose-dependent manner. The results indicate that even under SO2 inhalation at low concentrations as 7 mg SO2/m3, The brain cells with DNA damaged also reached to 98.8%, it implies the brain cells of mammalian animals are very sensitive to SO2 inhalation. The results also indicate that DNA damage of the brain cells from male mice is more serious than that from female mice, that remains to be further studied. These results led us to conclusion SO2 pollution even at low concentrations also has a potential risk to damage genetic material DNA of brain cells from mammalian animals. It might be explained by our conclusion that the recently published epidemiological studies of workers exposed to SO2 or it's derivatives (bi)sulfite) found increased mortality for brain cancer.

  2. Nanospray Drying as a Novel Technique for the Manufacturing of Inhalable NSAID Powders

    Directory of Open Access Journals (Sweden)

    Aquino Rita Patrizia

    2014-01-01

    Full Text Available The aim of this research was to evaluate the potential of the nanospray drier as a novel apparatus for the manufacturing of a dry powder for inhalation containing ketoprofen lysinate, a nonsteroidal anti-inflammatory drug able to control the inflammation in cystic fibrosis patients. We produced several ketoprofen lysinate and leucine powder batches by means of nanospray dryer, studying the influence of process parameters on yield, particle properties (size distribution and morphology, and, mainly, aerodynamic properties of powders. Micronized particles were prepared from different hydroalcoholic solutions (alcohol content from 0 to 30% v/v using ketoprofen in its lysine salt form and leucine as dispersibility enhancer in different ratios (from 5 to 15% w/w with a total solid concentration ranging from 1 to 7% w/v. Results indicated that the spray head equipped with a 7 µm nozzle produced powders too big to be inhaled. The reduction of nozzle size from 7 to 4 µm led to smaller particles suitable for inhalation but, at the same time, caused a dramatic increase in process time. The selection of process variables, together with the nozzle pretreatment with a surfactant solution, allowed us to obtain a free flowing powder with satisfying aerosol performance, confirming the usefulness of the nanospray drier in the production of powder for inhalation.

  3. Effects of inhalation of high concentration of oxygen on physiological and subjective responses and work performance

    Energy Technology Data Exchange (ETDEWEB)

    Iwata, T.; Tochihara, Y.; Ohnaka, T. [Institute of Public Health, Tokyo (Japan); Masuda, T. [Itochu Corp. (Japan)

    1995-12-31

    An experiment was conducted to show the significance of indoor air quality. The effects of high concentrations of oxygen inhalations on physiological and subjective responses, and work performance during vigilant work throughout the night, were investigated. Seven young and five middle-aged males participated in a nighttime driving simulation test. They sat in a driver`s seat equipped with monitors and their reaction time to a red signal was recorded. More than three seconds of reaction time was considered a missed signal. During the tests, air with 30% (high O{sub 2}) and air with 21% (normal O{sub 2}) of oxygen was inhaled. Sleepiness and subjective fatigue sensations were evaluated and scored. Results showed that a decrease in work performance and an increase in sleepiness occurred due to sitting up all night. It grew greater with the passage of time. The effects of high O{sub 2} inhalation on subjective fatigue were greater in the middle-aged males than in the young males. Physiological effects of the high O{sub 2} inhalation were found only in the EEG. Other physiological parameters showed no significant changes. 6 refs., 1 tab., 8 figs.

  4. Activation of Alveolar Macrophages after Plutonium Oxide Inhalation in Rats: Involvement in the Early Inflammatory Response

    International Nuclear Information System (INIS)

    Alveolar macrophages play an important role in the distribution, clearance and inflammatory reactions after particle inhalation, which may influence long-term events such as fibrosis and tumorigenesis. The objectives of the present study were to investigate the early inflammatory events after plutonium oxide inhalation in rats and involvement of alveolar macrophages. Lung changes were studied from 3 days to 3 months after inhalation of PuO2 or different isotopic compositions (70% or 97% 239Pu) and initial lung deposits (range 2.1 to 43.4 kBq/rat). Analyses of bronchoalveolar lavages showed early increases in the numbers of granulocytes, lymphocytes and multi-nucleated macrophages. The activation of macrophages was evaluated ex vivo by measurement of inflammatory mediator levels in culture supernatants. TNF-alpha and chemokine MCP-1, MIP-2 and CINC-1 production was elevated from 7 days after inhalation and remained so up to 3 months. In contrast, IL-1 beta, IL-6 and IL-10 production was unchanged. At 6 weeks, pulmonary macrophage numbers and activation state were increased as observed from an immunohistochemistry study of lung sections with anti-ED1. Similarly, histological analyses of lung sections also showed evidence of inflammatory responses. In conclusion, our results indicate early inflammatory changes in the lungs of PuO2-contaminated animals and the involvement of macrophages in this process. A dose-effect relationship was observed between the amount of radionuclide inhaled or retained at the time of analysis and inflammatory mediator production by alveolar macrophages 14 days after exposure. For similar initial lung deposits, the inflammatory manifestation appears higher for 97% 239Pu than for 70% 239Pu. (authors)

  5. Activation of Alveolar Macrophages after Plutonium Oxide Inhalation in Rats: Involvement in the Early Inflammatory Response

    Energy Technology Data Exchange (ETDEWEB)

    Van der Meeren, A.; Tourdes, F.; Gremy, O.; Grillon, G.; Abram, M.C.; Poncy, J.L.; Griffiths, N. [CEA, DSV, DRR, SRCA, Centre DAM Ile de France, F-91297 Bruyeres Le Chatel, Arpajon (France)

    2008-07-01

    Alveolar macrophages play an important role in the distribution, clearance and inflammatory reactions after particle inhalation, which may influence long-term events such as fibrosis and tumorigenesis. The objectives of the present study were to investigate the early inflammatory events after plutonium oxide inhalation in rats and involvement of alveolar macrophages. Lung changes were studied from 3 days to 3 months after inhalation of PuO{sub 2} or different isotopic compositions (70% or 97% {sup 239}Pu) and initial lung deposits (range 2.1 to 43.4 kBq/rat). Analyses of bronchoalveolar lavages showed early increases in the numbers of granulocytes, lymphocytes and multi-nucleated macrophages. The activation of macrophages was evaluated ex vivo by measurement of inflammatory mediator levels in culture supernatants. TNF-alpha and chemokine MCP-1, MIP-2 and CINC-1 production was elevated from 7 days after inhalation and remained so up to 3 months. In contrast, IL-1 beta, IL-6 and IL-10 production was unchanged. At 6 weeks, pulmonary macrophage numbers and activation state were increased as observed from an immunohistochemistry study of lung sections with anti-ED1. Similarly, histological analyses of lung sections also showed evidence of inflammatory responses. In conclusion, our results indicate early inflammatory changes in the lungs of PuO{sub 2}-contaminated animals and the involvement of macrophages in this process. A dose-effect relationship was observed between the amount of radionuclide inhaled or retained at the time of analysis and inflammatory mediator production by alveolar macrophages 14 days after exposure. For similar initial lung deposits, the inflammatory manifestation appears higher for 97% {sup 239}Pu than for 70% {sup 239}Pu. (authors)

  6. PROCESS VALIDATION OF DRY POWDER INHALERS (GENERALIZED APPROACH, THEORY AND PRACTICES): A REVIEW

    OpenAIRE

    Pandita Rachna; Rana A. C.; Seth Nimrata; Bala Rajni

    2011-01-01

    Drugs can be delivered to the lungs by inhalation, oral, parenteral routes. Different types of devices such as pressurised metered dose inhalers (p-MDI's), nebulizers or dry powder inhalers (DPI's) are used for the pulmonary delivery of drugs .This present review article focus on the process validation of dry powder inhalers. Dry powder inhaler is a device that deliver medication to the lungs in the form of dry powder. Validation of dry powder inhaler is done to ensure that a specific manufac...

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

    Science.gov (United States)

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

    2008-01-01

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

  8. Inhalant Abuse and Dependence among Adolescents in the United States

    Science.gov (United States)

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

    2004-01-01

    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…

  9. IMPROVED STREET SWEEPERS FOR CONTROLLING URBAN INHALABLE PARTICULATE MATTER

    Science.gov (United States)

    The report gives results of an experimental program to develop design modifications that can be used to improve the ability of municipal street sweepers to remove inhalable dust particles from streets. (Dust emissions from paved roads are a major source of urban inhalable particu...

  10. Inhaled Anesthetic Potency in Aged Alzheimer Mice

    Science.gov (United States)

    Bianchi, Shannon L.; Caltagarone, Breanna M.; LaFerla, Frank M.; Eckenhoff, Roderic G.; Kelz, Max B.

    2016-01-01

    BACKGROUND The number of elderly patients with frank or incipient Alzheimer’s disease (AD) requiring surgery is growing as the population ages. General anesthesia may exacerbate symptoms of and the pathology underlying AD, so minimizing anesthetic exposure may be important. This requires knowledge of whether the continuing AD pathogenesis alters anesthetic potency. METHODS We determined the induction potency and emergence time for isoflurane, halothane, and sevoflurane using the minimum alveolar anesthetic concentration for loss of righting reflex as an end point in 12- to 14-mo-old triple transgenic Alzheimer (3xTgAD) mice and wild type C57BL6 controls. 3xTgAD mice model AD by harboring three distinct mutations: the APPSwe, Tau, and PS1 human transgenes, each of which has been associated with familial forms of human AD. RESULTS The 3xTgAD mice exhibited mild resistance (from 8% to 30%) to volatile anesthetics but displayed indistinguishable emergence patterns from all three inhaled anesthetics. CONCLUSIONS These results show that the genetic vulnerabilities and neuropathology associated with AD produce a small but significant decrease in sensitivity to the hypnotic actions of three inhaled anesthetics. Emergence times were not altered. PMID:19820240

  11. Effect of inhaled steroids on laryngeal microflora.

    Science.gov (United States)

    Turan, Mahfuz; Ekin, Selami; Ucler, Rıfkı; Arısoy, Ahmet; Bayram, Yasemin; Yalınkılıç, Abdulaziz; Bozan, Nazım; Garca, Mehmet Fatih; Çankaya, Hakan

    2016-07-01

    Conclusions As is known, this study is the first study to evaluate the effect of inhaled steroids on laryngeal microflora. The data support that ICS usage causes changes in the larynx microflora. Purpose The aim of this study was to determine the alteration in larynx microbial flora of the patients treated with ICS comparing the culture results of a control group. In addition, laryngeal microflora was compared to the smears obtained from the vallecula and pharynx. Materials and methods The study included 39 patients (mean age = 45.56 ± 12.76 years) who had been using a corticosteroid inhaler and control group consisting of 27 persons (mean age = 43.07 ± 13.23 years). Culture samples were obtained from the pharynx, larynx, and vallecula in the patient and control groups, and they were evaluated in the microbiology laboratory. Obtained culture results were named by the same microbiologist according to the basic microorganism classification method. Results Coagulase-negative staphylococci (CNS), Streptococcus viridians (VGS) and candida albicans were detected to grow significantly more in the patient group in all three anatomic localizations compared to the control group. Neisseria spp, basillus spp, and Non-viridans alpha-hemolytic streptococcus were detected to grow significantly more in the control group in all three anatomic localizations compared to the patient group. PMID:26901427

  12. Whole-Body Nanoparticle Aerosol Inhalation Exposures

    Science.gov (United States)

    Yi, Jinghai; Chen, Bean T.; Schwegler-Berry, Diane; Frazer, Dave; Castranova, Vince; McBride, Carroll; Knuckles, Travis L.; Stapleton, Phoebe A.; Minarchick, Valerie C.; Nurkiewicz, Timothy R.

    2013-01-01

    Inhalation is the most likely exposure route for individuals working with aerosolizable engineered nano-materials (ENM). To properly perform nanoparticle inhalation toxicology studies, the aerosols in a chamber housing the experimental animals must have: 1) a steady concentration maintained at a desired level for the entire exposure period; 2) a homogenous composition free of contaminants; and 3) a stable size distribution with a geometric mean diameter < 200 nm and a geometric standard deviation σg < 2.5 5. The generation of aerosols containing nanoparticles is quite challenging because nanoparticles easily agglomerate. This is largely due to very strong inter-particle forces and the formation of large fractal structures in tens or hundreds of microns in size 6, which are difficult to be broken up. Several common aerosol generators, including nebulizers, fluidized beds, Venturi aspirators and the Wright dust feed, were tested; however, none were able to produce nanoparticle aerosols which satisfy all criteria 5. A whole-body nanoparticle aerosol inhalation exposure system was fabricated, validated and utilized for nano-TiO2 inhalation toxicology studies. Critical components: 1) novel nano-TiO2 aerosol generator; 2) 0.5 m3 whole-body inhalation exposure chamber; and 3) monitor and control system. Nano-TiO2 aerosols generated from bulk dry nano-TiO2 powders (primary diameter of 21 nm, bulk density of 3.8 g/cm3) were delivered into the exposure chamber at a flow rate of 90 LPM (10.8 air changes/hr). Particle size distribution and mass concentration profiles were measured continuously with a scanning mobility particle sizer (SMPS), and an electric low pressure impactor (ELPI). The aerosol mass concentration (C) was verified gravimetrically (mg/m3). The mass (M) of the collected particles was determined as M = (Mpost-Mpre), where Mpreand Mpost are masses of the filter before and after sampling (mg). The mass concentration was calculated as C = M/(Q*t), where Q is

  13. Design and evaluation of a new dry powder inhaler

    Directory of Open Access Journals (Sweden)

    "Rouholamini Najafabadi AH

    2001-08-01

    Full Text Available Three versions of a new dry powder inhaler (DPI, RG-haler, were designed using two kinds of grid inserts. Salbutamol sulfate/lactose blend (Ventolin Rotacaps® was selected as a model formulation to analyze the performance of all inhalers and compare their efficiency with three marketed devices (Rotahaler®, Spinhaler® and ISF inhalator® using the twin impinger (TI. Deposition of the drug in device was significantly (P<0.05 lower for ISF inhalator® and all kinds of RG-halers in comparison with those of Rotahaler® and Spinhaler®. The amount of drug deposited in the stage 2 and the respirable dose for RG-halers were similar to those of ISF inhalator® and significantly (P<0.05 higher than those of Rotahaler® and Spinhaler®. The results suggest efficient aerosol generating capability of the RG-haler.

  14. Disposition and safety of inhaled biodegradable nanomedicines: Opportunities and challenges.

    Science.gov (United States)

    Haque, Shadabul; Whittaker, Michael R; McIntosh, Michelle P; Pouton, Colin W; Kaminskas, Lisa M

    2016-08-01

    The inhaled delivery of nanomedicines can provide a novel, non-invasive therapeutic strategy for the more localised treatment of lung-resident diseases and potentially also enable the systemic delivery of therapeutics that are otherwise administered via injection alone. However, the clinical translation of inhalable nanomedicine is being hampered by our lack of understanding about their disposition and clearance from the lungs. This review provides a comprehensive overview of the biodegradable nanomaterials that are currently being explored as inhalable drug delivery systems and our current understanding of their disposition within, and clearance from the lungs. The safety of biodegradable nanomaterials in the lungs is discussed and latest updates are provided on the impact of inflammation on the pulmonary pharmacokinetics of inhaled nanomaterials. Overall, the review provides an in-depth and critical assessment of the lung clearance mechanisms for inhaled biodegradable nanomedicines and highlights the opportunities and challenges for their translation into the clinic. PMID:27033834

  15. Inhaled antibiotics for gram-negative respiratory infections.

    Science.gov (United States)

    Hudson, Ryan; Olson Blair, Brooke

    2011-10-01

    Several disease states create conditions that lead to opportunistic Gram-negative respiratory infections. Inhalation is the most direct and, until recently, underutilized means of antimicrobial drug targeting for respiratory tract infections. All approved antimicrobial agents for administration by inhalation are indicated for Pseudomonas aeruginosa infections in patients with cystic fibrosis. These inhaled therapies have directly contributed to a significant reduction in exacerbations and hospitalizations in this patient population over the last few decades. The relentless adaptation of pathogenic organisms to current treatment options demands that the pharmaceutical industry continue designing next-generation antimicrobial agents over 70 years after they were first introduced. Recent technological advances in inhalation devices and drug formulation techniques have broadened the scope of antimicrobial structural classes that can be investigated by inhalation; however, there is an urgent need to discover novel compounds with improved resistance profiles relative to those drugs that are already marketed. PMID:21942255

  16. Effects of inhalation of beta 2-sympathicomimetic and anticholinergic agents on the impedance of the respiratory system in normal subjects.

    Science.gov (United States)

    Wesseling, G; Vonk, H M; Wouters, E F

    1990-05-01

    Impedance measurement of the respiratory system by forced oscillations is a sensitive and accurate method to detect mechanical parameters, especially in normal subjects. The effects of inhalation of 0.2 mg of fenoterol and 0.02 mg of ipratropium bromide on the impedance of the respiratory system was studied in 20 healthy subjects in a frequency spectrum between 4 and 52 Hz. Both agents caused a statistically significant decrease in resistance (Rrs). Inhalation of fenoterol and ipratropium bromide caused a significant increase in reactance (Xrs). The decrease in Rrs was greater after inhalation of fenoterol than after ipratropium bromide. Fenoterol and ipratropium bromide caused qualitatively similar changes in Rrs and Xrs of the respiratory system. The changes in Rrs can be explained by dilation of the central airways. The changes in Xrs are supposed to be the result of an increase in the capacitance of the lungs. PMID:2139600

  17. Delivery of theophylline as dry powder for inhalation

    Directory of Open Access Journals (Sweden)

    Bing Zhu

    2015-12-01

    Full Text Available Theophylline (TP is a very well established orally or intravenously delivered antiasthma drug with many beneficial effects. This study aims to improve asthma treatment by creating a dry powder inhalable (DPI formulation of TP to be delivered directly to the lung, avoiding the side effects associated with conventional oral delivery. The DPI TP formulation was investigated for its physico-chemical characteristics using scanning electron microscopy, laser diffraction, thermal analysis and dynamic vapour sorption. Furthermore, aerosol performance was assessed using the Multi Stage Liquid Impinger (MSLI. In addition, a Calu-3 cell transport assay was conducted in vitro using a modified ACI to study the impact of the DPI formulation on lung epithelial cells. Results showed DPI TP to be physico-chemically stable and of an aerodynamic size suitable for lung delivery. The aerosolisation performance analysis showed the TP DPI formulation to have a fine particle fraction of 29.70 ± 2.59% (P < 0.05 for the TP formulation containing 1.0% (w/w sodium stearate, the most efficient for aerosolisation. Regarding the deposition of TP DPI on Calu-3 cells using the modified ACI, results demonstrated that 56.14 ± 7.62% of the total TP deposited (13.07 ± 1.69 µg was transported across the Calu-3 monolayer over 180 min following deposition, while 37.05 ± 12.62% of the deposited TP was retained in the cells. This could be due to the presence of sodium stearate in the current formulation that increased its lipophilicity. A DPI formulation of TP was developed that was shown to be suitable for inhalation.

  18. Acute respiratory toxicity following inhalation exposure to soman in guinea pigs

    International Nuclear Information System (INIS)

    Respiratory toxicity and lung injury following inhalation exposure to chemical warfare nerve agent soman was examined in guinea pigs without therapeutics to improve survival. A microinstillation inhalation exposure technique that aerosolizes the agent in the trachea was used to administer soman to anesthetized age and weight matched male guinea pigs. Animals were exposed to 280, 561, 841, and 1121 mg/m3 concentrations of soman for 4 min. Survival data showed that all saline controls and animals exposed to 280 and 561 mg/m3 soman survived, while animals exposed to 841, and 1121 mg/m3 resulted in 38% and 13% survival, respectively. The microinstillation inhalation exposure LCt50 for soman determined by probit analysis was 827.2 mg/m3. A majority of the animals that died at 1121 mg/m3 developed seizures and died within 15-30 min post-exposure. There was a dose-dependent decrease in pulse rate and blood oxygen saturation of animals exposed to soman at 5-6.5 min post-exposure. Body weight loss increased with the dose of soman exposure. Bronchoalveolar lavage (BAL) fluid and blood acetylcholinesterase and butyrylcholinesterase activity was inhibited dose-dependently in soman treated groups at 24 h. BAL cells showed a dose-dependent increase in cell death and total cell counts following soman exposure. Edema by wet/dry weight ratio of the accessory lung lobe and trachea was increased slightly in soman exposed animals. An increase in total bronchoalveolar lavage fluid protein was observed in soman exposed animals at all doses. Differential cell counts of BAL and blood showed an increase in total lymphocyte counts and percentage of neutrophils. These results indicate that microinstillation inhalation exposure to soman causes respiratory toxicity and acute lung injury in guinea pigs.

  19. Biokinetics and dosimetry of inhaled tritiated aerosols

    Energy Technology Data Exchange (ETDEWEB)

    Trivedi, A. [Radiation Biology and Health Physics Branch, Atomic Energy of Canada Limited, Chalk River, Ontario (Canada); Cheng, Y.S. [Lovelace Respiratory Research Institute, Albuquerque, New Mexico (United States)

    2000-05-01

    Inhalation of tritiated pump oils and metal tritides is a potential radiological protection problem in some situations in tritium facilities. At present, the biokinetic data and validated dose models do not generally exist for chemical forms of tritium other than tritiated water and tritium gas. This situation calls for improving our radiobiological and dosimetric understanding for inhalation of tritiated aerosols. When tritiated pump oils or metal tritides were instilled into the lung, tritium was biotransformed to organically bound tritium (OBT) and tritiated water (HTO) in the body. The biokinetics of tritium-in-urine exhibited a sum of two exponential functions for OBT and HTO: short and long-term clearance components. For tritiated pump oils, 68% of the instilled activity was excreted in feces and less than 10% in urine. More than 90% of the applied activity was retained in the lung up to 5 d post-exposure, this declined to 40% and 5% of the instilled activity 7 d and 28 d post-exposure, respectively. No major long-term storage of OBT was observed in the body. For metal tritides (i.e., titanium tritide), 37% of instilled activity was eliminated via urine, 29% via feces, and 16% through exhaled air. The results on distribution and dynamics of tritium in the body were remarkably similar with our earlier studies on percutaneous absorption of tritiated pump oils or skin-contact exposure to tritium-gas-contaminated metal surfaces. Urinary excretion bioassay data from workers exposed to metal tritides or pump oils were analyzed using the MS-Windows 95 PC version of GENMOD{sup TM} internal dosimetry code. (GENMOD implements the ICRP Publication 66 respiratory tract model and compartment models rather than retention functions of tritium compounds as describes by ICRP Publication 67). The simulated tritium urinary excretion data for exposed workers indicated that Type S solubility classification is more appropriate that Type M default as prescribed ICRP Publication 66

  20. Acute Adrenal Crisis in an Asthmatic Child Treated with Inhaled Fluticasone Proprionate

    Directory of Open Access Journals (Sweden)

    Angela H. Santiago

    2010-01-01

    Full Text Available Adrenal suppression secondary to prolonged inhaled corticosteroid use is usually limited to biochemical abnormalities, with no obvious clinical effects. Acute adrenal crisis is much rarer event but has been reported with increasing frequency. We report a case of a 7-year-old asthmatic child who presented with an acute history of lethargy after a respiratory infection. He was maintained on 220 μg/day of fluticasone propionate for several years. Initial evaluation revealed severe adrenal suppression, with undetectable cortisol levels and minimal response after stimulation with ACTH. After fluticasone was discontinued, a gradual recovery of the adrenal axis was seen. This case shows that acute adrenal crisis may be a consequence even at the usual prescribed doses, stressing the importance of using the lowest dose of inhaled steroids needed to control symptoms and having an increased awareness of this complication.

  1. Long-term effects of inhaled Ca-DTPA in rats previously exposed to 239Pu(NO3)4 aerosols

    International Nuclear Information System (INIS)

    Inhaled Ca-DTPA given 20 days after 239Pu(NO3)4 inhalation was marginally effective (p = 0.10) in reducing the amount of Pu in rat lung. This reduction in Pu lung burden did not, however, affect the later induction of lung tumors. An increased osteosarcoma incidence was noted in control rats exposed only to nitric acid aerosols. Complete tumor incidence data are not yet available. (U.S.)

  2. Chlorine gas inhalation: human clinical evidence of toxicity and experience in animal models.

    Science.gov (United States)

    White, Carl W; Martin, James G

    2010-07-01

    Humans can come into contact with chlorine gas during short-term, high-level exposures due to traffic or rail accidents, spills, or other disasters. By contrast, workplace and public (swimming pools, etc.) exposures are more frequently long-term, low-level exposures, occasionally punctuated by unintentional transient increases. Acute exposures can result in symptoms of acute airway obstruction including wheezing, cough, chest tightness, and/or dyspnea. These findings are fairly nonspecific, and might be present after exposures to a number of inhaled chemical irritants. Clinical signs, including hypoxemia, wheezes, rales, and/or abnormal chest radiographs may be present. More severely affected individuals may suffer acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). Up to 1% of exposed individuals die. Humidified oxygen and inhaled beta-adrenergic agents are appropriate therapies for victims with respiratory symptoms while assessments are underway. Inhaled bicarbonate and systemic or inhaled glucocorticoids also have been reported anecdotally to be beneficial. Chronic sequelae may include increased airways reactivity, which tends to diminish over time. Airways hyperreactivity may be more of a problem among those survivors that are older, have smoked, and/or have pre-existing chronic lung disease. Individuals suffering from irritant-induced asthma (IIA) due to workplace exposures to chlorine also tend to have similar characteristics, such as airways hyperresponsiveness to methacholine, and to be older and to have smoked. Other workplace studies, however, have indicated that workers exposed to chlorine dioxide/sulfur dioxide have tended to have increased risk for chronic bronchitis and/or recurrent wheezing attacks (one or more episodes) but not asthma, while those exposed to ozone have a greater incidence of asthma. Specific biomarkers for acute and chronic exposures to chlorine gas are currently lacking. Animal models for chlorine gas

  3. The Effects of Inhaled Nickel Nanoparticles on Murine Endothelial Progenitor Cells

    Science.gov (United States)

    Liberda, Eric N.

    Introduction. Particulate air pollution, specifically nickel found on or in particulate matter, has been associated with an increased risk of mortality in human population studies and can cause increases in vascular inflammation, generate reactive oxygen species, alter vasomotor tone, and potentiate atherosclerosis in murine exposures. With the discovery of endothelial progenitor cells (EPCs), a door has been opened which may explain these observed cardiovascular effects associated with inhaled air particles and nickel exposure. In order to further quantify the effects of inhaled nickel nanoparticles and attempt to elucidate how the observed findings from other studies may occur, several whole body inhalation exposure experiments to nickel nanoparticles were performed. Methods. Following whole body exposure to approximately 500mug/m3 of nickel nanoparticles for 5 hrs, bone marrow EPCs from C57BL/6 mice were isolated. EPCs were harvested for their RNA or used in a variety of assays including chemotaxis, tube formation, and proliferation. Gene expression was assessed for important receptors involved in EPC mobilization and homing using RT-PCR methods. EPCs, circulating endothelial progenitor cells, circulating endothelial cells (CECs), and endothelial microparticles (EMPs) were quantified on a BD FACSCalibur to examine endothelial damage and repair associated with the inhalation exposure. Plasma proteins were assessed using the 2D DIGE proteomic approach and commercially available ELISAs. Results and Conclusions. Exposure to inhaled nickel nanoparticles significantly increased both bone marrow EPCs as well as their levels in circulation. CECs were significantly upregulated suggesting that endothelial damage occurred due to the exposure. There was no significant difference in EMPs between the two groups. Tube formation and chemotaxis, but not proliferation, of bone marrow EPCs was impaired in the nickel nanoparticle exposed group. This decrease in EPC function

  4. Inhaled tolafentrine reverses pulmonary vascular remodeling via inhibition of smooth muscle cell migration

    Directory of Open Access Journals (Sweden)

    Weissmann Norbert

    2005-11-01

    Full Text Available Abstract Background The aim of the study was to assess the chronic effects of combined phosphodiesterase 3/4 inhibitor tolafentrine, administered by inhalation, during monocrotaline-induced pulmonary arterial hypertension (PAH in rats. Methods CD rats were given a single subcutaneous injection of monocrotaline to induce PAH. Four weeks after, rats were subjected to inhalation of tolafentrine or sham nebulization in an unrestrained, whole body aerosol exposure system. In these animals (i the acute pulmonary vasodilatory efficacy of inhaled tolafentrine (ii the anti-remodeling effect of long-term inhalation of tolafentrine (iii the effects of tolafentrine on the expression profile of 96 genes encoding cell adhesion and extracellular matrix regulation were examined. In addition, the inhibitory effect of tolafentrine on ex vivo isolated pulmonary artery SMC cell migration was also investigated. Results Monocrotaline injection provoked severe PAH (right ventricular systolic pressure increased from 25.9 ± 4.0 to 68.9 ± 3.2 after 4 weeks and 74.9 ± 5.1 mmHg after 6 weeks, cardiac output depression and right heart hypertrophy. The media thickness of the pulmonary arteries and the proportion of muscularization of small precapillary resistance vessels increased dramatically, and the migratory response of ex-vivo isolated pulmonary artery smooth muscle cells (PASMC was increased. Micro-arrays and subsequent confirmation with real time PCR demonstrated upregulation of several extracellular matrix regulation and adhesion genes, such as matrixmetalloproteases (MMP 2, 8, 9, 10, 11, 12, 20, Icam, Itgax, Plat and serpinb2. When chronically nebulized from day 28 to 42 (12 daily aerosol maneuvers, after full establishment of severe pulmonary hypertension, tolafentrine reversed about 60% of all hemodynamic abnormalities, right heart hypertrophy and monocrotaline-induced structural lung vascular changes, including the proportion of pulmonary artery

  5. Effect of compression pressure on inhalation grade lactose as carrier for dry powder inhalations

    OpenAIRE

    Raut, Neha Sureshrao; Jamaiwar, Swapnil; Umekar, Milind Janrao; Kotagale, Nandkishor Ramdas

    2016-01-01

    Introduction: This study focused on the potential effects of compression forces experienced during lactose (InhaLac 70, 120, and 230) storage and transport on the flowability and aerosol performance in dry powder inhaler formulation. Materials and Methods: Lactose was subjected to typical compression forces 4, 10, and 20 N/cm2. Powder flowability and particle size distribution analysis of un-compressed and compressed lactose was evaluated by Carr's index, Hausner's ratio, the angle of repose ...

  6. Difference in the action mechanism of radon inhalation and radon hot spring water drinking in suppression of hyperuricemia in mice.

    Science.gov (United States)

    Etani, Reo; Kataoka, Takahiro; Kanzaki, Norie; Sakoda, Akihiro; Tanaka, Hiroshi; Ishimori, Yuu; Mitsunobu, Fumihiro; Yamaoka, Kiyonori

    2016-06-01

    Although radon therapy is indicated for hyperuricemia, the underlying mechanisms of action have not yet been elucidated in detail. Therefore, we herein examined the inhibitory effects of radon inhalation and hot spring water drinking on potassium oxonate (PO)-induced hyperuricemia in mice. Mice inhaled radon at a concentration of 2000 Bq/m(3) for 24 h or were given hot spring water for 2 weeks. Mice were then administrated PO at a dose of 500 mg/kg. The results obtained showed that serum uric acid levels were significantly increased by the administration of PO. Radon inhalation or hot spring water drinking significantly inhibited elevations in serum uric acid levels through the suppression of xanthine oxidase activity in the liver. Radon inhalation activated anti-oxidative functions in the liver and kidney. These results suggest that radon inhalation inhibits PO-induced hyperuricemia by activating anti-oxidative functions, while hot spring water drinking may suppress PO-induced elevations in serum uric acid levels through the pharmacological effects of the chemical compositions dissolved in it. PMID:27021217

  7. Pathology associated with inhaled plutonium in beagles

    International Nuclear Information System (INIS)

    The pathology associated with the inhalation of plutonium was studied in beagle dogs given a single exposure to aerosols of 239PuO2, 238PuO2, or 239Pu(NO3)4. The temporal-spatial relationships between plutonium deposition and the development of lesions in dogs were evaluated up to 11 years, 8 years, or 5 years, respectively, after exposures, resulting in initial lung burdens ranging from ∼2 to ∼5500 nCi. Exposure of the lung to high dose levels produced a spectrum of progressively more severe morphological changes, ranging from radiation pneumonitis to fibrosis. Lung tumors occurred at exposure levels that did not result in early death from radiation pneumonitis or fibrosis. Bronchiolar-alveolar carcinomas, papillary adenocarcinomas, epidermoid carcinomas, and combined epidermoid and adenocarcinomas were observed. Sclerosing tracheobronchial lymphadenitis, radiation osteodystrophy, osteosarcoma, and hepatic adenomatous hyperplasia were the principal extrapulmonary lesions resulting from translocation of plutonium. 15 refs., 2 tabs

  8. Human biokinetics of inhaled terbium oxide

    International Nuclear Information System (INIS)

    Four healthy men inhaled a monodisperse aerosol of 160Tb-labelled terbium oxide particles. The behaviour of the tracer was studied through measurements of body radioactivity and of its urinary and faecal excretion. Estimated early faecal losses in the four subjects ranged from 3% to 31% of the initial respiratory-tract deposit; most of the residue had become systemic within a year, with the principal deposit apparently in bone. Interference from this systemic deposit prevented accurate determination of the long-term pulmonary clearance kinetics, but the pattern was broadly what would be expected for Type M materials in the ICRP's Human Respiratory Tract Model. Averaged trends in the whole-body residue after ∼ 1 year suggest a clearance half-life of about 5 y. (author)

  9. Toxic spongiform leucoencephalopathy after inhaling heroin vapour

    International Nuclear Information System (INIS)

    This is a report of clinical, CT and MRI findings in a patient with toxic spongiform leucoencephalopathy after heroin ingestion. The disease is observed in drug addicts who inhale pre-heated heroin. The clinical onset, which usually occurs some days or even longer after the last heroin consumption, is characterized by a cerebellar syndrome. The cerebellar hemispheres, the cerebellar and cerebral peduncles and the pyramidal tract may be affected. Spongiform demyelination is the morphological substrate of the lesions, which are not contrast enhancing, hypodense on CT and hyperintense on T2-weighted MRI. The frequently perfect symmetry of the affection of functional systems points to a toxic and/or metabolic pathophysiological mechanism. (orig.)

  10. Toxic spongiform leucoencephalopathy after inhaling heroin vapour

    Energy Technology Data Exchange (ETDEWEB)

    Weber, W.; Henkes, H.; Kuehne, D. [Klinik fuer Allgemeine Roentgendiagnostik und Neuroradiologie, Alfried-Krupp-Krankenhaus, Alfried Krupp Strasse 21, D-45117, Essen (Germany); Moeller, P.; Bade, K. [Neurologische Klinik, Knappschafts-Krankenhaus, D-45657 Recklinghausen (Germany)

    1998-06-02

    This is a report of clinical, CT and MRI findings in a patient with toxic spongiform leucoencephalopathy after heroin ingestion. The disease is observed in drug addicts who inhale pre-heated heroin. The clinical onset, which usually occurs some days or even longer after the last heroin consumption, is characterized by a cerebellar syndrome. The cerebellar hemispheres, the cerebellar and cerebral peduncles and the pyramidal tract may be affected. Spongiform demyelination is the morphological substrate of the lesions, which are not contrast enhancing, hypodense on CT and hyperintense on T2-weighted MRI. The frequently perfect symmetry of the affection of functional systems points to a toxic and/or metabolic pathophysiological mechanism. (orig.) With 2 figs., 2 tabs., 26 refs.

  11. Effects of prenatal inhalation exposure to copper nanoparticles on murine dams and offspring

    OpenAIRE

    Adamcakova-Dodd, Andrea; Monick, Martha M.; Powers, Linda S.; Gibson-Corley, Katherine N.; Thorne, Peter S.

    2015-01-01

    Background Increasing numbers of individuals may be exposed to nanomaterials during pregnancy. The overarching goal of this investigation was to determine if prenatal inhalation exposure to copper nanoparticles (Cu NPs) has an effect on dams and offspring, including an analysis of inflammatory markers (Th1/Th2 cytokine profiles). Methods Physicochemical characterization of Cu NPs was performed. Pregnant and non-pregnant mice (C57Bl/6 J) were exposed to Cu NPs or laboratory air in the whole-bo...

  12. Non-neoplastic pulmonary disease from inhaled radon daughters with uranium ore dust in beagle dogs

    International Nuclear Information System (INIS)

    Daily exposures of adult beagle dogs to inhaled radon daughters plus uranium ore dust, with and without concurrent cigarette smoking, for 2 to 5-1/2 yr have produced massive pulmonary fibrosis and severe emphysema. The cumulative exposure doses are similar to those associated with a 5-fold or greater increase in death rate of uranium miners due to chronic respiratory insufficiency, including pneumoconiosis, pulmonary fibrosis, and emphysema

  13. Airway response to inhaled salbutamol in hyperthyroid and hypothyroid patients before and after treatment.

    OpenAIRE

    Harrison, R N; Tattersfield, A. E.

    1984-01-01

    For many years the development of thyrotoxicosis has been known to cause a deterioration in asthma but the mechanism is unknown. We have studied the effect of thyroid function on airway beta adrenergic responsiveness in 10 hyperthyroid and six hypothyroid subjects before and after treatment of their thyroid disease. Airway adrenergic responsiveness was assessed by measuring specific airway conductance (sGaw) after increasing doses of inhaled salbutamol (10-410 micrograms). After treatment the...

  14. Iodinated NanoClusters as an inhaled CT contrast agent for lung visualization

    OpenAIRE

    Aillon, Kristin L.; El-Gendy, Nashwa; Norenberg, Jeffery P.; McDonald, Jacob; Dennis, Connor; BERKLAND, CORY

    2010-01-01

    Improvements to contrast media formulations may be an effective way to increase the accuracy and effectiveness of thoracic computed tomography (CT) imaging in disease evaluation. To achieve contrast enhancement in the lungs, a relatively large localized concentration of contrast media must be delivered. Inhalation offers a non-invasive alternative to intrapleural injections for local lung delivery, but effective aerosolization may deter successful imaging strategies. Here, NanoCluster technol...

  15. Oral and inhaled sodium cromoglicate in the management of systemic mastocytosis: a case report

    Directory of Open Access Journals (Sweden)

    Hagberg Hans

    2010-06-01

    Full Text Available Abstract Introduction Mastocytosis is a rare disease consisting of a group of disorders characterized by a pathologic increase in the number of mast cells in one or more organ system. Treatment is symptomatic. Oral sodium cromoglicate (SCG is the only treatment licensed for the treatment of mastocytosis. In this case we report how in a mastocytosis patient being treated with H1 and H2 antihistamines, and oral sodium cromoglicate, the addition of inhaled sodium cromoglicate resulted in further improvement. This is the first report of this use of the drug in this disease. Case presentation The subject is a Caucasian woman aged 40 years. Symptoms of mastocytosis began when she was aged 13 years, but the diagnosis was not made until after her first pregnancy aged 33 years. Symptoms improved with H1 and H2 antihistamines, and oral sodium cromoglicate, but it required the addition of inhaled sodium cromoglicate to produce further improvement, specifically in the symptoms of bone pain, fatigue and headache. Doses of oral sodium cromoglicate had to be increased if challenged with a food to which the subject was sensitive. Doses of inhaled sodium cromoglicate had to be increased during the menstrual period. Conclusions Patients suffering from the rare disease of mastocytosis have symptoms affecting many body systems. Symptoms result from the release of inflammatory mediators from mast cells. Sodium cromoglicate, a drug that reduces the release of mediators from mast cells, is effective in controlling gastrointestinal symptoms, but less effective in those affecting other body systems. In this case report we have shown that the addition of inhaled sodium cromoglicate controls the symptoms of bone pain, fatigue and headache and also that the doses have to be increased during the menstrual period.

  16. The Effects of Inhalation Aromatherapy on Anxiety in Patients With Myocardial Infarction: A Randomized Clinical Trial

    OpenAIRE

    Najafi, Zahra; Taghadosi, Mohsen; Sharifi, Khadijeh; Farrokhian, Alireza; Tagharrobi, Zahra

    2014-01-01

    Background: Anxiety is an important mental health problem in patients with cardiac disease. Anxiety reduces patients’ quality of life and increases the risk of different cardiac complications. Objectives: The aim of this study was to investigate the effects of inhalation aromatherapy on anxiety in patients with myocardial infarction. Patients and Methods: This was a randomized clinical trial conduced on 68 patients with myocardial infarction hospitalized in coronary care units of a large-scal...

  17. The effect of inhalation aromatherapy on anxiety level of the patients in preoperative period

    OpenAIRE

    Fayazi, Sadigheh; Babashahi, Monireh; Rezaei, Mehdi

    2011-01-01

    BACKGROUND: Anxiety is the one of the most common problems before the surgery. Its prevalence rate ranged from 11 to 80 percent in all the adult patients. Delay in wound healing and increasing use of narcotics and anesthetics are some of the other accompanying problems. Aromatherapy is one of the complementary medicine components. It is applied by special type of oil extracted from aromatic plants for medical objectives. This study aimed to investigate the effects of inhalation aromatherapy o...

  18. Radioaerosol inhalation lung scintigraphy in bronchial asthma

    International Nuclear Information System (INIS)

    A study on obstructive changes in airways and mucociliary clearance in children and youth with bronchial asthma was performed. Radioaerosol inhalation lung scintigraphies using 99Tc-human serum albumin (HSA) were applied to 50 children and youth with bronchial asthma. The deposition patterns of the radioaerosol and aerosol clearance curves were evaluated. Abnormal deposition patterns, which consisted of non-homogeneous distribution and/or hot spot formation, were likely to be seen in patients with asthmatic attacks at the time of measurements. However, a few asymptomatic patients also revealed abnormal deposition patterns. The deposition patterns were related to FEV1.0%, MMF, V50 and V25, but especially to FEV1.0%. As an index of mucociliary clearance, β, the rate constant of the 99mTc-HSA aerosol clearance curve, was introduced. β was significantly lower in patients with abnormal aerosol deposition patterns than in normal persons. β was also significantly lower in patients undergoing asthmatic attack at the time of the measurements than in asymptomatic patients. β correlated negatively with FEV1.0%, MMF, V50 and V25, but especially with FEV1.0%. Although patients with long term affection or moderate-to-severe asthma tended to reveal abnormal deposition patterns and had low β values, these differences were not statistically significant. Radioaerosol inhalation lung scintigraphy with 99mTc-HSA is useful for evaluating not only obstructive changes in the airways but also for evaluating mucociliary clearance in children with bronchial asthma. (author)

  19. Inhalation of racemic epinephrine in children with asthma. Dose-response relation and comparison with salbutamol.

    Science.gov (United States)

    Kjellman, B; Tollig, H; Wettrell, G

    1980-10-01

    In this study the effects of nebulized racemic epinephrine (Micronephrine) were investigated in children with asthma. The drug was inhaled by a compressor nebulizer with a plastic mask. In the first part of the study it is shown that nebulized Micronephrine has a dose-dependent bronchodilatory effect. In the second part the effect is compared with that of nebulized salbutamol in 10 children (7-16 years of age) with bronchial asthma. The highest dose used in the dose-response trials (=0.9 mg Micronephrine/kg body-weight) was compared with 0.15 mg salbutamol/kg body-weight, which is the dose commonly used in Sweden. There was no significant difference between the drugs as regards increase of forced expiratory volume in 1 sec or duration of the increase. There was a small but significant increase in systolic blood pressure, measured 5 min after the inhalation of Micronephrine but no significant change in diastolic pressure or heart rate. Four children complained of temporary sore throat after the inhalation. PMID:7468946

  20. Protection against inhaled oxidants through scavenging of oxidized lipids by macrophage receptors MARCO and SR-AI/II

    DEFF Research Database (Denmark)

    Dahl, Morten; Bauer, Alison K; Arredouani, Mohamed; Soininen, Raija; Tryggvason, Karl; Kleeberger, Steven R; Kobzik, Lester

    2007-01-01

    Alveolar macrophages (AMs) express the class A scavenger receptors (SRAs) macrophage receptor with collagenous structure (MARCO) and scavenger receptor AI/II (SRA-I/II), which recognize oxidized lipids and provide innate defense against inhaled pathogens and particles. Increased MARCO expression in......, consistent with SRA function in binding oxidized lipids. SR-AI/II-/- mice showed similar enhanced acute lung inflammation after beta-epoxide or another inhaled oxidant (aerosolized leachate of residual oil fly ash). In contrast, subacute ozone exposure did not enhance inflammation in SR-AI/II-/- versus SR-AI...

  1. Inhalation Toxicology Research Institute annual report 1987-1988

    International Nuclear Information System (INIS)

    The mission of the Inhalation Toxicology Research Institute is to investigate the magnitude of human health effects that result from the inhalation of airborne materials at home, in the work place, or in the general environment. Diseases of the respiratory tract are major causes of suffering and death, and many of these diseases are directly related to the materials that people breath. The Institute's research is directed toward obtaining a better understanding of the basic biology of the respiratory tract and the mechanisms by which inhaled materials produce respiratory disease. Special attention is focused on studying the airborne materials released by various energy technologies, as well as those associated with national defense activities. The research uses a wide-ranging, comprehensive array of investigative approaches that are directed toward characterizing the source of the airborne material, following the material through its potential transformation in the air, identifying the mechanisms that govern its inhalation and deposition in the respiratory tract, and determining the fate of these inhaled materials in the body and the health effects they produce. The ultimate objectives are to determine the roles played by inhaled materials in the development of disease processes adn to estimate the risk they pose by inhaled materials in the development of disease processes and to estimate the risk they pose to humans who may be exposed to them. This report contains brief research papers that reflect the scope and recent findings of the Institute's research funded by the U.S. Department of Energy, principally through the Office of Health and Environmental Research. The papers are divided into topical sections. The first section, Characterization of Airborne Materials and Generation of Experimental Exposure Atmospheres, reflects the Institute's capabilities for fundamental aerosol research and the application of that expertise to toxicological studies. The second

  2. Budesonide–formoterol (inhalation powder) in the treatment of COPD

    OpenAIRE

    Ceylan, Erkan

    2006-01-01

    The budesonide–formoterol dry powder inhaler (Symbicort® Turbuhaler® 160/4.5–640/18 μg/day) contains the long-acting β2-adrenoreceptor agonist formoterol and the inhaled corticosteroid budesonide. Two large, 12-month trials examined the effect of budesonide–formoterol 160/4.5 μg twice daily in COPD patients who met these criteria. The studies were identical, except one in which the patients had received oral prednisolone 30 mg/day and had inhaled formoterol 4.5 μg twice daily for 2 weeks befo...

  3. Measurements and prediction of inhaled air quality with personalized ventilation

    DEFF Research Database (Denmark)

    Cermak, Radim; Majer, M.; Melikov, Arsen Krikor

    2002-01-01

    This paper examines the performance of five different air terminal devices for personalized ventilation in relation to the quality of air inhaled by a breathing thermal manikin in a climate chamber. The personalized air was supplied either isothermally or non-isothermally (6 deg.C cooler than...... the room air) at flow rates ranging from less than 5 L/s up to 23 L/s. The air quality assessment was based on temperature measurements of the inhaled air and on the portion of the personalized air inhaled. The percentage of dissatisfied with the air quality was predicted. The results suggest...

  4. Inhalant Use, Abuse, and Dependence among Adolescent Patients: Commonly Comorbid Problems.

    Science.gov (United States)

    Sakai, Joseph T.; Hall, Shannon K.; Mikulich-Gilbertson, Susan K.; Crowley, Thomas J.

    2004-01-01

    Objective: Little is known about adolescents with DSM-IV-defined inhalant abuse and dependence. The aim of this study was to compare comorbidity among (1) adolescents with inhalant use disorders, (2) adolescents who reported using inhalants without inhalant use disorder, and (3) other adolescent patients drawn from an adolescent drug and alcohol…

  5. Age of Inhalant First Time Use and Its Association to the Use of Other Drugs

    Science.gov (United States)

    Ding, Kele; Chang, G. Andy; Southerland, Ron

    2009-01-01

    Inhalants are the 4th most commonly abused drugs after alcohol, tobacco, and marijuana. Although inhalants are often referred as Gateway Drugs this hypothesis is less examined. Using the 2003 National Survey on Drug Use and Health data, age of first time inhalant use was compared with the age of onset of other drugs among 6466 inhalant users who…

  6. Inflammogenic effect of well-characterized fullerenes in inhalation and intratracheal instillation studies

    Directory of Open Access Journals (Sweden)

    Yamamoto Kazuhiro

    2010-03-01

    Full Text Available Abstract Background We used fullerenes, whose dispersion at the nano-level was stabilized by grinding in nitrogen gas in an agitation mill, to conduct an intratracheal instillation study and an inhalation exposure study. Fullerenes were individually dispersed in distilled water including 0.1% Tween 80, and the diameter of the fullerenes was 33 nm. These suspensions were directly injected as a solution in the intratracheal instillation study. The reference material was nickel oxide in distilled water. Wistar male rats intratracheally received a dose of 0.1 mg, 0.2 mg, or 1 mg of fullerenes and were sacrificed after 3 days, 1 week, 1 month, 3 months, and 6 months. In the inhalation study, Wistar rats were exposed to fullerene agglomerates (diameter: 96 ± 5 nm; 0.12 ± 0.03 mg/m3; 6 hours/days for 5 days/week for 4 weeks and were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. The inflammatory responses and gene expression of cytokine-induced neutrophil chemoattractants (CINCs were examined in rat lungs in both studies. Results In the intratracheal instillation study, both the 0.1 mg and 0.2 mg fullerene groups did not show a significant increase of the total cell and neutrophil count in BALF or in the expression of CINC-1,-2αβ and-3 in the lung, while the high-dose, 1 mg group only showed a transient significant increase of neutrophils and expression of CINC-1,-2αβ and -3. In the inhalation study, there were no increases of total cell and neutrophil count in BALF, CINC-1,-2αβ and-3 in the fullerene group. Conclusion These data in intratracheal instillation and inhalation studies suggested that well-dispersed fullerenes do not have strong potential of neutrophil inflammation.

  7. Avanços na inaloterapia em pediatria Advances in inhalation therapy in pediatrics

    Directory of Open Access Journals (Sweden)

    Fábio Pereira Muchão

    2010-10-01

    -actuated inhalers are more attractive options. Among dry powder inhalers, we highlight those using passive and active powder dispersion mechanisms, which provide higher rates of drug deposition in the lung. Among pressurized metered-dose inhalers, we highlight breath-actuated, breath-coordinated, and velocity-modifying inhalers. These inhalers should be used preferably together with spacers, since the use of spacers produces a twofold increase in pulmonary drug deposition. CONCLUSIONS: For children younger than 8 years, pressurized metered-dose inhalers with spacers are the most appropriate devices, since they provide a practical approach associated with greater lung deposition. In children older than 8 years who can generate high inspiratory flow rates, dry powder devices are best suited.

  8. Effects of inhaled 144Ce on cardiopulmonary function and histopathology of the dog

    International Nuclear Information System (INIS)

    Twelve dogs inhaled single doses of relatively insoluble particles containing 144Ce and six dogs inhaled particles containing stable cerium as controls. Pulmonary function, clinical, and radiographic evaluations were performed serially. The dogs developed progressive radiation pneumonitis and pulmonary fibrosis similar to that previously reported for whole-lung irradiation from internal or external sources. Focal histologic changes in bronchioles and alveoli were detected functionally during treadmill and tube-breathing stresses at a time when the dogs' clinical and radiographic appearances were normal. Moderate functional impairment was associated with more severe inflammatory and proliferative changes in airways and alveoli. Severe impairment resulted from progressive fibrosis and scarring. These were several strong correlations between functional indices and histological scores. There was a nonlinear relationship between cumulative radiation dose and effects, and once the functional alterations became clinically evident, the disease progressed with little further increase in dose

  9. The Effects of Inhaled Budesonide on Lung Function in Smokers and Nonsmokers With Mild Persistent Asthma

    DEFF Research Database (Denmark)

    O'Byrne, Paul M; Lamm, Carl Johan; Busse, William W;

    2009-01-01

    BACKGROUND: Previous studies have suggested reduced benefit from inhaled corticosteroids (ICS) in smoking asthmatics. The objective of this post-hoc study was to study the effects of low dose inhaled budesonide on lung function in smokers and nonsmokers with mild persistent asthma. METHODS: Adult...... difference being -83.1 mL (p < 0.001). Budesonide treatment was associated with a statistically significant 3-year increase in post-bronchodilator FEV(1) in both groups. The effect of budesonide vs placebo was + 71.5 mL (p = 0.011) in smokers and + 46.5 mL (p = 0.001) in nonsmokers. The corresponding effect...... are similar in smokers and nonsmokers with mild persistent asthma....

  10. A pooled analysis of FEV1 decline in COPD patients randomized to inhaled corticosteroids or placebo

    DEFF Research Database (Denmark)

    Soriano, JB; Sin, DD; Zhang, X;

    2007-01-01

    Background: There is controversy about whether therapy with inhaled corticosteroids (ICSs) modifies the natural history of COPD, characterized by an accelerated decline in FEV1. Methods: The Inhaled Steroids Effect Evaluation in COPD (ISEEC) study is a pooled study of patient-level data from seven...... long-term randomized controlled trials of ICS vs placebo lasting 12 months in patients with moderate-to-severe COPD. We have previously reported a survival benefit for ICS therapy in COPD patients using ISEEC data. We aimed to determine whether the regular use of ICSs vs placebo improves FEV1 decline...... in COPD patients, and whether this relationship is modified by gender and smoking. Results: There were 3,911 randomized participants (29.2% female) in this analysis. In the first 6 months after randomization, ICS use was associated with a significant mean (± SE) relative increase in FEV1 of 2.42 ± 0...

  11. Repeated inhalation exposure of rats to aerosols of 239PuO2. V

    International Nuclear Information System (INIS)

    The biological responses following protracted alpha irradiation of rat lungs are being studied. Groups of rats have been exposed once, or repeatedly, to aerosols of 239PuO2 to achieve, or to re-establish, lung burdens of 239Pu that will result in projected lifetime alpha-radiation doses to the lungs of 20, 60, 200, or 600 rad. There were dose related increases in the incidence of primary lung tumors In the rats exposed once or repeatedly to 239PuO2. Repeated inhalation exposure of rats to 239PuO2 did not increase the incidence of lung tumors, their time of occurrence nor the risk of death with a lung tumor per unit of absorbed alpha dose to the lung compared to doses received following single exposures. These findings are consistent with those in Beagle dogs repeatedly exposed to 239PuO2 in other studies, but are not consistent with previous observations In mice. The findings in mice indicated protraction of the alpha dose to the lung by repeated inhalation exposure was more carcinogenic than similar doses after a single inhalation exposure. (author)

  12. Inhalation of Shin-I essential oil enhances lactate clearance in treadmill exercise

    Institute of Scientific and Technical Information of China (English)

    Hsuan-Ying Chen; Ming-Fu Wang; Jun-Ying Lin; Ying-Chieh Tsai; Fu-Chou Cheng

    2014-01-01

    Objective: To evaluate the effect of Shin-I essential oil inhalation on blood lactate changes in rats subjected to treadmill exercise.Methods: Adult male Sprague Dawley rats (n=12) were randomly divided into the control or the Shin-I group. Rats were subjected to a treadmill exercise program (15 m/min for 30 min). After exercise, rats were exposed to 200 µL of water or Shin-I essential oil, respectively, using a nebulizer for 180 min during the recovery period. Blood samples were collected every 15 min. Blood glucose and lactate concentrations were determined in a CMA 600 analyzer.Results: The basal glucose and lactate levels were no significantly different between two groups. After exercise, glucose levels were slightly increased to about 110%-120% of the basal level in both groups. Lactate levels of both groups reached to 110%-140% of basal levels during exercise. In the recovery period, lactate levels further increased to 180% of the basal level and were maintained at a plateau in the control group. However, lactate levels gradually decreased to 60%-65% of the basal level in the Shin-I group. Lactate clearance was significantly enhanced after Shin-I essential oil inhalation.Conclusions: Our results provide evidence that Shin-I essential oil inhalation may accelerate recovery after exercise in rats.

  13. Cytogenetic and other biological effects of 239PuO2 inhaled by the rhesus monkey

    International Nuclear Information System (INIS)

    Sixteen immature rhesus monkeys were exposed via inhalation to an insoluble, polydisperse 239PuO2 aerosol labeled with 169Yb which had an activity median aerodynamic diameter of 1.6 μm and a sigma/sub g/ of 1.6. Four groups with three monkeys per group were exposed to achieve initial 239Pu lung burdens of 1000 to 2000, 200 to 300, 20 to 65, and 2 to 10 nCi, respectively. To determine early retention and distribution of the aerosol, four additional monkeys were exposed with initial lung burdens of 200 to 600 nCi and were sacrificed 4 hr and 30 days after inhalation exposure. Two monkeys were sham exposed and served as controls. Using data derived from external whole-body counting of the 169Yb label, it was estimated that the inhaled 239PuO2 was retained in the body with an average effective half-life of 1000 days with some translocation from the lung to the pulmonary lymph nodes. Chromosome aberrations were scored in blood lymphocytes cultured 1, 3, 7, 19, 31, and 43 months after inhalation. Only in animals with cumulative lung doses greater than 1000 rad was there a significant increase in the frequency of rings and dicentrics when compared to the controls. An animal with an estimated initial lung burden of 1000 nCi showed marked alterations in respiratory function 30 days prior to his death from pulmonary fibrosis 990 days after inhalation exposure. Only slight respiratory changes were detected in the other animals evaluated. To date, three monkeys have died, two with initial lung burdens of 1800 and 1000 nCi 239Pu which died from radiation pneumonitis and the third with an initial lung burden of 20 nCi which died of gastric torsion presumably not related to Pu exposure. Comparison of survival data from rhesus monkeys with those obtained from baboons and beagles indicates that rhesus monkeys, baboons, and dogs are similar in their early response to inhaled 239PuO2

  14. Use of Respimat® Soft Mist™ Inhaler in COPD patients

    OpenAIRE

    Anderson, Paula

    2006-01-01

    Events of the past decade have stimulated development of new drug formulations and delivery devices that have improved the efficiency, ease of use, and environmental impact of inhaled drug therapy. Respimat® Soft Mist™ Inhaler is a novel, multidose, propellant-free, hand-held, liquid inhaler that represents a new category of inhaler devices. The aerosol cloud generated by Respimat contains a higher fraction of fine particles than most pressurized metered dose inhalers (pMDIs) and dry powder i...

  15. Reliability of Use, Abuse, and Dependence of Four Types of Inhalants in Adolescents and Young Adults

    OpenAIRE

    Ridenour, Ty A.; Bray, Bethany C.; Cottler, Linda B.

    2007-01-01

    Inhalants, as a class of drugs, consists of heterogeneous substances that include some of the most dangerous drugs on a per use basis. Research on inhalant abuse has lagged behind other drugs partly because of the need for a diagnostic instrument of different types of inhalants. This study was conducted to obtain reliability estimates for the new Substance Abuse Module DSM-IV inhalants diagnoses for four types of inhalants: aerosols, gases, nitrites, and solvents as well as different diagnost...

  16. The use of inhaled corticosteroids in pediatric asthma: update.

    Science.gov (United States)

    Hossny, Elham; Rosario, Nelson; Lee, Bee Wah; Singh, Meenu; El-Ghoneimy, Dalia; Soh, Jian Yi; Le Souef, Peter

    2016-01-01

    Despite the availability of several formulations of inhaled corticosteroids (ICS) and delivery devices for treatment of childhood asthma and despite the development of evidence-based guidelines, childhood asthma control remains suboptimal. Improving uptake of asthma management plans, both by families and practitioners, is needed. Adherence to daily ICS therapy is a key determinant of asthma control and this mandates that asthma education follow a repetitive pattern and involve literal explanation and physical demonstration of the optimal use of inhaler devices. The potential adverse effects of ICS need to be weighed against the benefit of these drugs to control persistent asthma especially that its safety profile is markedly better than oral glucocorticoids. This article reviews the key mechanisms of inhaled corticosteroid action; recommendations on dosage and therapeutic regimens; potential optimization of effectiveness by addressing inhaler technique and adherence to therapy; and updated knowledge on the real magnitude of adverse events. PMID:27551328

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

    Science.gov (United States)

    Gentile, Michael A

    2011-09-01

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

  18. Inhalation of Simulated Smog Affects Cardiac Function in Mice

    Science.gov (United States)

    Rationale: The health effects of individual criteria air pollutants have been well investigated. Little is known about health effects of inhaled multi-pollutant mixtures that more realistically represent environmental exposures. The present study was designed to evaluate the card...

  19. Mexican-American Adolescent Inhalant Abuse: A Proposed Model.

    Science.gov (United States)

    Dworkin, A. Gary; Stephens, Richard C.

    1980-01-01

    Drawing from literature on differences between the Mexican American experience and that of other groups, offers a model to explain the higher rates of inhalant abuse among Mexican American youth. Considers cultural, ecological, structural, and economic factors. (Author/GC)

  20. Urine and serum concentrations of inhaled and oral terbutaline

    DEFF Research Database (Denmark)

    Elers, Jimmi; Hostrup, Morten; Pedersen, Lars;

    2012-01-01

    We examined urine and serum concentrations after therapeutic use of single and repetitive doses of inhaled and supratherapeutic oral use of terbutaline. We compared the concentrations in 10 asthmatics and 10 healthy subjects in an open-label, cross-over study with 2 mg inhaled and 10 mg oral....... Median (IQR) urine concentrations peaked in the period 0-4 h after inhalation with Cmax 472 (324) ng/mL in asthmatics and 661 (517) ng/mL in healthy subjects, and 4-8 h after oral use with Cmax 666 (877) ng/mL in asthmatic and 402 (663) ng/mL in healthy subjects. In conclusion we found no significant...... differences in urine and serum concentrations between asthmatic and healthy subjects. We compared urine and serum concentrations after therapeutic inhaled doses and supratherapeutic oral doses and observed significant statistical differences in both groups but found it impossible to distinguish between...

  1. Inhaled therapy for the management of perioperative pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    C A Thunberg

    2015-01-01

    Full Text Available 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.

  2. Tritiated thymidine-labeled bronchioloalveolar cells and radiation dose following inhalation of plutonium in rats

    International Nuclear Information System (INIS)

    The goal of this study is to show the relationship of inhaled Pu particle distribution and alveolar-bronchiolar target-cell response with respect to the formation of pulmonary carcinoma. The proliferation of type 2 alveolar epithelium and nonciliated bronchiolar epithelium appears critical in the induction of lung tumors associated from inhaled 239PuO2. Female, Wistar rats were either sham-exposed (40 rats) or given a single inhalation to 169Yb-239PuO2 (99 rats, ILB, 3.9 +/- 1.2 kBq) and examined at 20 time intervals from 1 day to 700 days postexposure for Pu particle distribution in airways by SEM quantitative autoradiography and for cell labeling with tritiated thymidine. Initially, deposited Pu particles were rapidly cleared from the surface of the trachea, bronchi, and bronchioles within a few days. Thereafter, about 5 times more alpha track exposure to the bronchiolar epithelium was delivered from Pu particles found in peribronchiolar alveoli than from Pu particles being cleared from bronchiolar surfaces. Exposure of bronchiolar epithelium at later times was due mostly to the formation of peribronchiolar Pu particle aggregates. A maximal increase in labeled alveolar wall cells was seen at 60 days after exposure, decreasing gradually to control levels by 400 days. Cell labeling in focal alveolar regions of Pu aggregation was about 5 fold higher. Increased bronchiolar epithelium labeling appeared in two phases. The first phase was seen 15 days after exposure, associated with initial deposition and clearance of Pu particles. The second phase slowly reached a maximum at 250 days and was associated with peribronchiolar Pu aggregate formation. The temporal-spatial dose-distribution pattern for inhaled Pu particles is an important aspect of Pu-induced pulmonary carcinogenesis

  3. Respiratory and olfactory cytotoxicity of inhaled 2,3-pentanedione in Sprague-Dawley rats.

    Science.gov (United States)

    Hubbs, Ann F; Cumpston, Amy M; Goldsmith, W Travis; Battelli, Lori A; Kashon, Michael L; Jackson, Mark C; Frazer, David G; Fedan, Jeffrey S; Goravanahally, Madhusudan P; Castranova, Vincent; Kreiss, Kathleen; Willard, Patsy A; Friend, Sherri; Schwegler-Berry, Diane; Fluharty, Kara L; Sriram, Krishnan

    2012-09-01

    Flavorings-related lung disease is a potentially disabling disease of food industry workers associated with exposure to the α-diketone butter flavoring, diacetyl (2,3-butanedione). To investigate the hypothesis that another α-diketone flavoring, 2,3-pentanedione, would cause airway damage, rats that inhaled air, 2,3-pentanedione (112, 241, 318, or 354 ppm), or diacetyl (240 ppm) for 6 hours were sacrificed the following day. Rats inhaling 2,3-pentanedione developed necrotizing rhinitis, tracheitis, and bronchitis comparable to diacetyl-induced injury. To investigate delayed toxicity, additional rats inhaled 318 (range, 317.9-318.9) ppm 2,3-pentanedione for 6 hours and were sacrificed 0 to 2, 12 to 14, or 18 to 20 hours after exposure. Respiratory epithelial injury in the upper nose involved both apoptosis and necrosis, which progressed through 12 to 14 hours after exposure. Olfactory neuroepithelial injury included loss of olfactory neurons that showed reduced expression of the 2,3-pentanedione-metabolizing enzyme, dicarbonyl/L-xylulose reductase, relative to sustentacular cells. Caspase 3 activation occasionally involved olfactory nerve bundles that synapse in the olfactory bulb (OB). An additional group of rats inhaling 270 ppm 2,3-pentanedione for 6 hours 41 minutes showed increased expression of IL-6 and nitric oxide synthase-2 and decreased expression of vascular endothelial growth factor A in the OB, striatum, hippocampus, and cerebellum using real-time PCR. Claudin-1 expression increased in the OB and striatum. We conclude that 2,3-pentanedione is a respiratory hazard that can also alter gene expression in the brain. PMID:22894831

  4. Toll-Like Receptor 4 Signaling Pathway Mediates Inhalant Organic Dust-Induced Bone Loss.

    Science.gov (United States)

    Staab, Elizabeth; Thiele, Geoffrey M; Clarey, Dillon; Wyatt, Todd A; Romberger, Debra J; Wells, Adam D; Dusad, Anand; Wang, Dong; Klassen, Lynell W; Mikuls, Ted R; Duryee, Michael J; Poole, Jill A

    2016-01-01

    Agriculture workers have increased rates of airway and skeletal disease. Inhalant exposure to agricultural organic dust extract (ODE) induces bone deterioration in mice; yet, mechanisms underlying lung-bone crosstalk remain unclear. Because Toll-like receptor 2 (TLR2) and TLR4 are important in mediating the airway consequences of ODE, this study investigated their role in regulating bone responses. First, swine facility ODE stimulated wild-type (WT) bone marrow macrophages to form osteoclasts, and this finding was inhibited in TLR4 knock-out (KO), but not TLR2 KO cells. Next, using an established intranasal inhalation exposure model, WT, TLR2 KO and TLR4 KO mice were treated daily with ODE or saline for 3 weeks. ODE-induced airway neutrophil influx and cytokine/chemokine release were similarly reduced in TLR2 and TLR4 KO animals as compared to WT mice. Utilizing micro-computed tomography (CT), analysis of tibia showed loss of bone mineral density, volume and deterioration of bone micro-architecture and mechanical strength induced by ODE in WT mice were significantly reduced in TLR4 but not TLR2 KO animals. Bone marrow osteoclast precursor cell populations were analyzed by flow cytometry from exposed animals. In WT animals, exposure to inhalant ODE increased osteoclast precursor cell populations as compared to saline, an effect that was reduced in TLR4 but not TLR2 KO mice. These results show that TLR2 and TLR4 pathways mediate ODE-induced airway inflammation, but bone deterioration consequences following inhalant ODE treatment is strongly dependent upon TLR4. Thus, the TLR4 signaling pathway appears critical in regulating the lung-bone inflammatory axis to microbial component-enriched organic dust exposures. PMID:27479208

  5. FORMULATION AND QUALITY CONTROL OF METERED DOSE INHALER: A REVIEW

    OpenAIRE

    Ramteke K.H.; Gunjal S.S; Sharma Y.P

    2012-01-01

    The MDI is now established as the principal dosage form of inhalation drug therapy for bronchial asthma and chronic obstructive pulmonary disease (COPD). Metered dose inhalers (MDIs) are pharmaceutical delivery systems designed for oral or nasal use, which deliver discrete doses of aerosolized medicament to the respiratory tract. The MDI contains the active substance, dissolved or suspended in a liquefied propellant system held in a pressurized container that is sealed with a metering valve. ...

  6. Patient preference for and satisfaction with inhaler devices

    OpenAIRE

    Anderson, P

    2005-01-01

    Preference for and satisfaction with inhaler devices may be associated with improved clinical outcomes, but this has not been proven to date. A screened Medline search for papers on preference for inhaler devices produced 29 studies on a variety of devices, with Advair Diskus® and TurbuhalerTM featuring prominently. Of the 23 studies sponsored by the pharmaceutical industry, the sponsor's device was preferred in 19. Interpretation of results was made more difficult because only two studies us...

  7. Inhalational drug delivery from seven different spacer devices.

    OpenAIRE

    Barry, P W; O Callaghan, C.

    1996-01-01

    BACKGROUND: A study was performed to determine in vitro the difference in drug output of seven currently available spacer devices when used with different inhaled medications. METHODS: A glass multistage liquid impinger (MSLI) was used to determine the amount of disodium cromoglycate (DSCG, 5 mg), salbutamol (100 micrograms), or budesonide (200 micrograms) obtained in various particle size ranges from metered dose inhalers (MDIs) actuated directly into the MSLI or via one of seven different s...

  8. Carbon nanotube dosimetry: from workplace exposure assessment to inhalation toxicology

    OpenAIRE

    Erdely, Aaron; Dahm, Matthew; Chen, Bean T.; Zeidler-Erdely, Patti C.; Fernback, Joseph E.; Birch, M. Eileen; Evans, Douglas E.; Kashon, Michael L; Deddens, James A.; Hulderman, Tracy; Bilgesu, Suzan A; Battelli, Lori; Schwegler-Berry, Diane; Leonard, Howard D.; McKinney, Walter

    2013-01-01

    Background Dosimetry for toxicology studies involving carbon nanotubes (CNT) is challenging because of a lack of detailed occupational exposure assessments. Therefore, exposure assessment findings, measuring the mass concentration of elemental carbon from personal breathing zone (PBZ) samples, from 8 U.S.-based multi-walled CNT (MWCNT) manufacturers and users were extrapolated to results of an inhalation study in mice. Results Upon analysis, an inhalable elemental carbon mass concentration ar...

  9. Effects of inhaled acids on respiratory tract defense mechanisms.

    OpenAIRE

    Schlesinger, R B

    1985-01-01

    The respiratory tract is endowed with an interlocking array of nonspecific and specific defense mechanisms which protect it from the effects of inhaled microbes and toxicants, and reduce the risk of absorption of materials into the bloodstream, with subsequent systemic translocation. Ambient acids may compromise these defenses, perhaps providing a link between exposure and development of chronic and acute pulmonary disease. This paper reviews the effects of inhaled acids upon the nonspecific ...

  10. Willingness to Pay for Inhaled Insulin: A Contingent Valuation Approach

    OpenAIRE

    Hamid Sadri; MacKeigan, Linda D.; Leiter, Lawrence A.; Einarson, Thomas R

    2005-01-01

    Purpose: To determine the willingness to pay (WTP) of patients with diabetes mellitus for inhaled insulin. Methods: A contingent valuation survey was administered to 96 diabetic outpatients at St. Michael's Hospital, Toronto, Canada. Standardised information about inhaled insulin and subcutaneous rapid-acting insulin was provided via video. Participants' WTP for their preferred product was elicited in Canadian dollars ($Can) using a `payment-scale' method. Results: The mean age of participant...

  11. Engineering of an Inhalable DDA/TDB Liposomal Adjuvant

    DEFF Research Database (Denmark)

    Ingvarsson, Pall Thor; Yang, Mingshi; Mulvad, Helle;

    2013-01-01

    The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB).......The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB)....

  12. Radioaerosol Inhalation Imaging in Bronchial Asthma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bum Soo; Park, Young Ha; Park, Jeong Mi; Chung, Myung Hee; Chung, Soo Kyo; Shinn, Kyung Sub; Bahk, Yong Whee [Catholic University College of Medicine, Seoul (Korea, Republic of)

    1991-03-15

    Radioaerosol inhalation imaging (RII) has been used in radionuclide pulmonary studies for the past 20 years. The method is well accepted for assessing regional ventilation because of its usefulness, easy fabrication and simple application system. To evaluate its clinical utility in the study of impaired regional ventilation in bronchial asthma, we obtained and analysed RIIs in 31 patients (16 women and 15 men; age ranging 21-76 years) with typical bronchial asthma at the Department of Radiology, Kangnam St. Mary's Hospital, Catholic University Medical college, from January, 1988 to August, 1989. Scintiscans were obtained with radioaerosol produced by a HARC(Bhabha Atomic Research Center, India) nebulizer with 15 mCi of {sup 99m}Tc-phytate. The scanning was performed in anterior, posterior and lateral projections following 5-minute inhalation of radioaerosol on sitting position. The scans were analysed and correlated with the results of pulmonary function study and the findings of chest radiography. Fifteen patients had concomitant lung perfusion image with {sup 99m}Tc-MAA. Follow-up scans were obtained in 5 patients after bronchodilator therapy. 1 he patients were divided into (1) attack type (4 patients), (2) resistant type (5 patients), (3) remittent type (10 patients) and (4) bronchitic type (12 patients). Chest radiography showed hyperinflation, altered pulmonary vascularity, thickening of the bronchial wall and accentuation of hasal interstitial markings in 26 of the 31 patients. Chest radiographs were normal in the remaining 5 patients. Regardless of type, the findings of RII were basically the same, and characterized by the deposition of radioaerosol in the central parts or in the main respiratory air ways along with mottled nonsegmental ventilation defects in the periphery. Peripheral parenchymal defects were more extensive than that of expected findings from clinical symptoms, pulmonary function test and chest radiograph. Broomstick sign was present

  13. Radioaerosol Inhalation Lung Scan in Pulmonary Emphysema

    International Nuclear Information System (INIS)

    Perfusion and ventilation imagings of the lung are well established procedure for diagnosing pulmonary embolism, differentiation it from chronic obstructive lung disease, and making an early detection of chronic obstructive lung disease. To evaluate the usefulness of radioaerosol inhalation imaging (RII) in chronic obstructive lung disease, especially pulmonary emphysema, we analyzed RIIs of five normal adult non-smokers, five asymptomatic smokers (age 25-42 years with the mean 36), and 21 patients with pulmonary emphysema (age 59-78 years with the mean 67). Scintigrams were obtained with radioaerosol produced by a BARC nebuliser with 15 mCi of 99mTc-phytate. Scanning was performed in the anterior, posterior, and lateral projections after five to 10-minute inhalation of the radioaerosol on sitting position. The scans were analyzed and correlated with the results of pulmonary function studies and chest radiographs. Also lung perfusion scan with 99mTc-MAA was performed in 12 patients. In five patients, we performed follow-up scans for the evaluation of the effects of a bronchodilator. Based on the X-ray findings and clinical symptoms, pulmonary emphysema was classified into four types: centrilobular (3 patients), panlobular (4 patients), intermediate (10 patients), and combined (4 patients). RII findings were patternized according to the type, extent, and intensity of the aerosol deposition in the central bronchial and bronchopulmonary system and lung parenchyma. 10 controls, normal five non-smokers and three asymptomatic smokers revealed homogeneous parenchymal deposition in the entire lung fields without central bronchial deposition. The remaining two of asymptomatic smokers revealed mild central airway deposition. The great majority of the patients showed either central (9/21) or combined type (10/21) of bronchopulmonary deposition and the remaining two patients peripheral bronchopulmonary deposition. Parenchymal aerosol deposition in pulmonary emphysema was

  14. Radioaerosol Inhalation Imaging in Bronchial Asthma

    International Nuclear Information System (INIS)

    Radioaerosol inhalation imaging (RII) has been used in radionuclide pulmonary studies for the past 20 years. The method is well accepted for assessing regional ventilation because of its usefulness, easy fabrication and simple application system. To evaluate its clinical utility in the study of impaired regional ventilation in bronchial asthma, we obtained and analysed RIIs in 31 patients (16 women and 15 men; age ranging 21-76 years) with typical bronchial asthma at the Department of Radiology, Kangnam St. Mary's Hospital, Catholic University Medical college, from January, 1988 to August, 1989. Scintiscans were obtained with radioaerosol produced by a HARC(Bhabha Atomic Research Center, India) nebulizer with 15 mCi of 99mTc-phytate. The scanning was performed in anterior, posterior and lateral projections following 5-minute inhalation of radioaerosol on sitting position. The scans were analysed and correlated with the results of pulmonary function study and the findings of chest radiography. Fifteen patients had concomitant lung perfusion image with 99mTc-MAA. Follow-up scans were obtained in 5 patients after bronchodilator therapy. 1 he patients were divided into (1) attack type (4 patients), (2) resistant type (5 patients), (3) remittent type (10 patients) and (4) bronchitic type (12 patients). Chest radiography showed hyperinflation, altered pulmonary vascularity, thickening of the bronchial wall and accentuation of hasal interstitial markings in 26 of the 31 patients. Chest radiographs were normal in the remaining 5 patients. Regardless of type, the findings of RII were basically the same, and characterized by the deposition of radioaerosol in the central parts or in the main respiratory air ways along with mottled nonsegmental ventilation defects in the periphery. Peripheral parenchymal defects were more extensive than that of expected findings from clinical symptoms, pulmonary function test and chest radiograph. Broomstick sign was present in 1.7 patients

  15. Effects of inhaled nitric oxide on hemostasis in healthy adults treated with heparin: a randomized, controlled, blinded crossover study

    Directory of Open Access Journals (Sweden)

    Goldstein Brahm

    2012-01-01

    Full Text Available Abstract Background Effects of nitric oxide (NO on hemostasis have been studied in various investigational settings, but data regarding inhaled NO on bleeding and platelet function are conflicting. It is not known if inhaled NO has an effect when administered with drugs that influence hemostasis. This trial evaluated effects of inhaled NO on hemostasis in the presence of heparin using aspirin as a positive control. Patients/Methods Twelve healthy adult males were enrolled in a single-center, randomized, single-blind, four-way crossover trial. Subjects received 80 ppm NO or medical air (placebo inhalation for 30 min with simultaneous injection of placebo or heparin. Aspirin capsules were used as a positive control. Parameters of hemostasis were measured before treatment and at post-treatment intervals. Results Activated clotting time (ACT, prothrombin time (PT and activated partial thromboplastin time (aPTT increased only in groups that received heparin. Areas under the curve for ACT in heparin groups receiving inhaled NO were judged to be equivalent to those receiving medical air for both 0- to 4-h (ratio: 1.00; 90% CI, 0.90-1.11 and 0- to 24-h time intervals (ratio: 1.01; 90% CI, 0.92-1.12. Changes in bleeding time and platelet aggregation were observed only in aspirin groups. No clinically significant changes in hemoglobin, red blood cell counts or haematocrit were observed in any group. Conclusions Inhaled NO, when administered with heparin, exhibited no significant additive effects on ACT, PT, aPTT, bleeding time or platelet aggregation.

  16. Inhaling one hundred percent oxygen eliminates the systemic arterial hypoxemic response of broilers to intravenous microparticle injections.

    Science.gov (United States)

    Lorenzoni, A G; Wideman, R F

    2008-01-01

    The pathogenesis of pulmonary hypertension syndrome (PHS, ascites) includes the development of systemic arterial hypoxemia (reduction in the saturation of hemoglobin with O(2), HbO(2)), which can be mimicked in clinically healthy broilers by i.v. injections of microparticles (MP). In experiment 1, arterial blood samples were collected from clinically healthy broilers before and after i.v. MP injections, and during a subsequent 100% O(2) inhalation period. The arterial samples were analyzed for HbO(2), partial pressure of O(2) and CO(2), and pH using a blood gas analyzer. In experiment 2, broilers that initially averaged > or =75% HbO(2) were assigned to a "high O(2)" group, whereas those that initially averaged broilers in both groups inhaled 100% O(2). In experiment 3, HbO(2) and HR were measured using a pulse oximeter before, during, and after broilers inhaled 100% O(2), after i.v. MP injections, and during a second period of 100% O(2) inhalation. The HbO(2) rapidly decreased after i.v. MP injections, and subsequently providing 100% O(2) to breathe increased the HbO(2) above preinjection control levels in experiments 1 and 3. In experiment 2, inhaling 100% oxygen eliminated the initial spontaneous differences in HbO(2) between the high O(2) and low O(2) groups, whereas the return to breathing ambient air restored the initial group differences in HbO(2). These experiments indicate that MP-induced and spontaneous hypoxemia can be attributed to a diffusion limitation rather than to arterial-venous shunts, because the hypoxemia resulting from arterial-venous shunts cannot be wholly eliminated by providing 100% O(2) to inhale. PMID:18079464

  17. From inhaler to lung: clinical implications of the formulations of ciclesonide and other inhaled corticosteroids

    Directory of Open Access Journals (Sweden)

    Nave R

    2013-03-01

    Full Text Available Ruediger Nave, Helgert Mueller Nycomed: a Takeda Company, Nycomed GmbH, Konstanz, Germany Abstract: Asthma continues to be a global health problem and currently available treatments such as corticosteroids can cause unwanted side effects. Inhaled corticosteroids (ICS are recommended as first-line therapy for reducing airway inflammation and have a distinct advantage over oral preparations as they provide a direct route of delivery to the lungs. However, local deposition of ICS in the oropharynx can lead to oral candidiasis, dysphonia, and pharyngitis. The pharmaceutical quality is a primary concern of any ICS asthma treatment, with a higher quality product resulting in improved efficacy and safety profiles. The particle size distribution and the spray force velocity of an ICS may directly influence lung deposition, and the spray duration of a device is another important factor when coordinating inhalation. Recent advances in ICS device and formulation technology have resulted in significant improvements in the efficacy of available asthma treatments. In particular, hydrofluoroalkane (HFA solution technology and the development of smaller particle sizes have resulted in the production of new ICS formulations that have the ability to directly target drug delivery to the site of airway inflammation. Both the ICS formulation and the pressurized metered-dose inhaler device used to administer ciclesonide (CIC HFA have been developed to treat the underlying chronic inflammation associated with asthma. CIC is administered as a prodrug which is activated in the lungs, leading to minimal oropharyngeal deposition. The small particle size of CIC results in the delivery of a high fraction of respirable particles to the small airways of the lungs, resulting in high lung deposition and continual dose consistency. This review summarizes how CIC administered as an HFA formulation is an effective treatment for asthma. Keywords: ciclesonide, asthma, small airways

  18. The respiratory allergen glutaraldehyde in the local lymph node assay: sensitization by skin exposure, but not by inhalation.

    Science.gov (United States)

    van Triel, Jos J; van Bree, Bianca W J; Roberts, David W; Muijser, Hans; Duistermaat, Evert; Woutersen, Ruud A; Kuper, C Frieke

    2011-01-11

    Previously, a selection of low molecular weight contact and respiratory allergens had tested positive in both a skin and a respiratory local lymph node assay (LLNA), but formaldehyde was negative for sensitization by inhalation. To investigate whether this was due to intrinsic properties of aldehyde sensitizers, the structurally related allergen glutaraldehyde (GA) was tested. BALB/c mice were exposed by inhalation to 6 or 18ppm GA (respiratory LLNA), both generated as a vapor and as an aerosol. Other groups received 0.25% or 2.5% GA on the skin of the ears (skin LLNA). Lymphocyte proliferation and cytokine production were measured in the draining lymph nodes. GA was positive in the skin LLNA and its cytokine profile (IL-4/IFN-γ) skewed towards a Th2-type immune response with increasing dose. Inhalation exposure did not result in increased lymphocyte proliferation or increased cytokine levels, despite comparable tissue damage (irritation) in the skin and respiratory tract. We hypothesize that the highly reactive and hydrophilic GA oligomerizes in the protein-rich mucous layer of the respiratory tract, which impedes sensitization but still facilitates local irritation. Within the context of risk assessment in respiratory allergy, our results stress the importance of prevention of skin--besides inhalation-- exposure to aldehydes like GA. PMID:20933045

  19. The respiratory allergen glutaraldehyde in the local lymph node assay: Sensitization by skin exposure, but not by inhalation

    International Nuclear Information System (INIS)

    Previously, a selection of low molecular weight contact and respiratory allergens had tested positive in both a skin and a respiratory local lymph node assay (LLNA), but formaldehyde was negative for sensitization by inhalation. To investigate whether this was due to intrinsic properties of aldehyde sensitizers, the structurally related allergen glutaraldehyde (GA) was tested. BALB/c mice were exposed by inhalation to 6 or 18 ppm GA (respiratory LLNA), both generated as a vapor and as an aerosol. Other groups received 0.25% or 2.5% GA on the skin of the ears (skin LLNA). Lymphocyte proliferation and cytokine production were measured in the draining lymph nodes. GA was positive in the skin LLNA and its cytokine profile (IL-4/IFN-γ) skewed towards a Th2-type immune response with increasing dose. Inhalation exposure did not result in increased lymphocyte proliferation or increased cytokine levels, despite comparable tissue damage (irritation) in the skin and respiratory tract. We hypothesize that the highly reactive and hydrophilic GA oligomerizes in the protein-rich mucous layer of the respiratory tract, which impedes sensitization but still facilitates local irritation. Within the context of risk assessment in respiratory allergy, our results stress the importance of prevention of skin - besides inhalation - exposure to aldehydes like GA.

  20. Inhaled corticosteroids in COPD: the clinical evidence.

    Science.gov (United States)

    Ernst, Pierre; Saad, Nathalie; Suissa, Samy

    2015-02-01

    In this article, we focus on the scientific evidence from randomised trials supporting treatment with inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD), including treatment with combinations of long-acting β-agonist (LABA) bronchodilators and ICS. Our emphasis is on the methodological strengths and limitations that guide the conclusions that may be drawn. The evidence of benefit of ICS and, therefore, of the LABA/ICS combinations in COPD is limited by major methodological problems. From the data reviewed herein, we conclude that there is no survival benefit independent of the effect of long-acting bronchodilation and no effect on FEV1 decline, and that the possible benefit on reducing severe exacerbations is unclear. Our interpretation of the data is that there are substantial adverse effects from the use of ICS in patients with COPD, most notably severe pneumonia resulting in excess deaths. Currently, the most reliable predictor of response to ICS in COPD is the presence of eosinophilic inflammation in the sputum. There is an urgent need for better markers of benefit and risk that can be tested in randomised trials for use in routine specialist practice. Given the overall safety and effectiveness of long-acting bronchodilators in subjects without an asthma component to their COPD, we believe use of such agents without an associated ICS should be favoured. PMID:25537556

  1. Lupine inhalation induced asthma in a child.

    Science.gov (United States)

    Moreno-Ancillo, Alvaro; Gil-Adrados, Ana C; Domínguez-Noche, Carmen; Cosmes, Pedro M

    2005-09-01

    The ingestion of lupine seed flour has been reported as a cause of allergic reactions. There is some evidence of its allergenic potential after inhalation. An 8-year-old asthmatic child, who was allergic to peanut, was studied in our clinic with the suspicion of an adverse drug reaction due to salbutamol. He suffered an asthma attack while playing with his brother, who had been eating lupine seed as snack; surprisingly, the asthma attack worsened with salbutamol. The skin tests showed a positive result with Lupinus albus extract, peanut, garbanzo bean, navy bean, pea, green bean, lentil, soy, Olea europea pollen, grass pollen and Plantago lanceolata pollen. The prick-by-prick tests both from dried seeds and those preserved in salt and water were strongly positive. Serum specific IgE antibodies were positive to Lupine albus (1.43 kU/l), peanut (4.32 kU/l), soy (2.15 kU/l), lentil (3.12 kU/l) and garbanzo (0.7 kU/l). After informed consent salbutamol was well tolerated but the patient had asthma in 5 min of manipulation of the lupine seeds. In our case, reactivity with other legumes was also demonstrated, but only peanut allergy was relevant because boiled legumes were tolerated. It is also notorious that anamnesis is so important to assess the true etiological agents of asthma. PMID:16176404

  2. Introduction: Aerosol delivery of orally inhaled agents.

    Science.gov (United States)

    Corcoran, Timothy E; Devadason, Sunalene G; Kuehl, Philip J

    2012-12-01

    Deposition scintigraphy methods have been used extensively to provide qualitative and quantitative data on aerosol drug deposition in the lungs. However, differences in methodology among the different centers performing these studies have limited the application of these techniques, especially in regulatory roles. As an introduction to the standardized techniques developed by the International Society for Aerosols in Medicine (ISAM) Regulatory Affairs Networking Group, we present potential advantages of the use of standard techniques for deposition scintigraphy. Specifically, we propose that standardized techniques would allow for better comparisons between labs and would facilitate multicenter studies. They would allow for improved methods of establishing equivalence and could be better utilized to establish dosing for new medications. They would allow for the performance of more accurate dose ranging or multidose studies and complement pharmacokinetic studies of new inhaled medications. Standardized techniques could help to establish the relationship between the deposition of drug in the lungs and clinical effect, and may also facilitate clinical measurements of deposited dose for medications with narrow therapeutic indices. In the sections that follow, we discuss the best techniques used to perform deposition scintigraphy through planar, single-photon emission computed tomography, and positron emission tomography modalities and propose a detailed set of standardized methods for each. These include methods for radiolabel validation, radiolabel accountability and mass balance, and imaging acquisition and analysis. PMID:23215846

  3. Newer insulin analogues and inhaled insulin

    Directory of Open Access Journals (Sweden)

    Girish C

    2006-03-01

    Full Text Available Diabetes is a metabolic disease with high prevalence worldwide. Exogenous insulin is used in the management of this condition. The development of human insulin has provided tighter control of glycaemia in diabetic patients. Insulin analogues like insulin lispro and aspart were developed to closely match its profile with physiological secretion. The newer additions to this armamentarium are insulin glulisine, insulin detemir and albulin.Insulin glulisine is a short acting analogue with a rapid onset of action. The antiapoptotic property, mediated through insulin substrate receptor-2 has a favourable protective action on beta cells. Insulin detemir is a long acting analogue, soluble at neutral pH, which reversibly binds to albumin in plasma, prolonging its action. Its lower affinity for insulin receptors necessitates higher doses compared to human insulin. The reduction in body weight is an additional advantage of detemir. A major concern about all newer insulin analogues is their altered mitogenic properties and resultant risk of carcinogenicity on long term use. Albulin is a latest addition of insulin analogue which is under various in vitro and in vivo studies. Inhaled insulin in powder form (Exubera is recently approved by FDA and appears promising.

  4. The biological behaviour of inhaled transuranic elements

    International Nuclear Information System (INIS)

    The biological behaviour of inhaled transuranic elements has been reviewed by focus on different points of present interest. Lung clearance and translocation are largely affected by the chemistry of transuranic elements. However, especially for plutonium, some examples show that the kinetics of some chemical reactions are function of the element concentration: extrapolation to the biological concentrations must therefore be cautious. The importance of the specific activity is stressed by different behaviours of plutonium 238 and 239 oxides. In the case of 238Pu, it is responsible of the fast dissolution of the oxide by formation of nanometric particles. Whatever the isotopes, these particules have a particularly important function since their biological fate seems to disturb the established models. Their origin is still to be determined since they have been identified both in the combustion of Pu-Na or Pu-Mg simultaneously, and plutonium only. The bronchial clearance of micronic particles does not seem to be fast for the whole of the fraction cleared. A residual compartment, indeed low, will remain at the level of the bronchial epithelium for a rather long time. This must be taken into account by dosimetric evaluations at the cellular levels. In spite of the few restrictions stated, the body of knowledge makes a fair estimation of risks possible

  5. Biological effects of 239PuO2 inhalation in the Rhesus monkey

    International Nuclear Information System (INIS)

    Rhesus monkeys were exposed to polydisperse, high-fired 239PuO2 aerosols and have been studied for 3 yr to determine the biological effects associated with this inhalation exposure. Initial lung burdens in 16 monkeys exposed to aerosols of 239PuO2 ranged from 7 to 1800 nCi. Two monkeys are serving as controls. The inhaled 239 PuO2 was retained with a long effective half-life in the lung with some translocation from the lung to the pulmonary lymph nodes. In animals exposed to high levels of 239PuO2, there was a depression in the number of lymphocytes in the peripheral blood. However, blood lymphocytes cultured at time periods up to 30 mo after inhalation showed no increase in chromosome aberration frequency. An animal with an estimated initial lung burden of 1000 nCi showed marked alterations in respiratory function. Only slight respiratory changes were detected in the other animals evaluated. To date, three monkeys have died, two of radiation pneumonitis and the third of gastric torsion. Comparing these data from Rhesus monkeys with those obtained from baboons and Beagle dogs indicate that Rhesus monkeys are similar to dogs in their early radiation response

  6. Activity concentration of the inhaled air of the personnel of a radioiodine therapy station

    International Nuclear Information System (INIS)

    The mean activity concentration of 131I during inhalation by the nuclear medicine personnel was measured at therapeutic activity applications of 22 GBq (600 mCi) per week. The activity concentration reached its maximum in the exhaled air of the patients 2.5 to 4 hours after oral application. The normalized maximum was between 2x10-5 and 2x10-3 Bq.m-3 per administered Bq. The mean activity concentration of 131I inhaled by the personnel was 28 to 1300 Bq.m-3 (0.8 to 35 nCi.m-3). From this the 131I uptake per year was estimated to be 30 to 400 kBq/a (anti x = 250, SD = 50%). The maximum permitted uptake from air per year is, according to the German and Austrian radiation protection ordinances 22/21 μCi/a(= 8x105 Bq/a). At maximum 50% and, on the average, 30% of this threshold value are reached. The length of stay of the personnel in the patient rooms is already now limited to such an extent that 10% of the maximum permissible whole-body dose for external radiation is not exceeded. Therefore, increased attention should be paid also to radiation exposure by inhalation. (orig.)

  7. Potential inhalation exposure and containment efficiency when using hoods for handling nanoparticles

    International Nuclear Information System (INIS)

    Inhalation exposure to airborne nanoparticles (NPs) has been reported during manual activities using typical fume hoods. This research studied potential inhalation exposure associated with the manual handling of NPs using two new nanoparticle-handling enclosures and two biological safety cabinets, and discussed the ability to contain NPs in the hoods to reduce environmental release and exposure. Airborne concentrations of 5 nm to 20 μm diameter particles were measured while handling nanoalumina particles in various ventilated enclosures. Tests were conducted using two handling conditions and concentrations were measured using real-time particle counters, and particles were collected on transmission electron microscope grids to determine particle morphology and elemental composition. Airflow patterns were characterized visually using a laser-light sheet and fog. The average number concentration increase at breathing zone outside the enclosure was less than 1,400 particle/cm3 for each particle size at all tested conditions and the estimated overall mass concentration was about 83 μg/m3 which was less than the dosage of typical nanoparticle inhalation exposure studies. The typical front-to-back airflow was used in the studied hoods, which could potentially induce reverse turbulence in the wake region. However, containment of NPs using studied hoods was demonstrated with excellent performance. Smoke tests showed that worker’s hand motion could potentially cause nanoparticle escape. The challenge of front-to-back airflow can be partially overcome by gentle motion, low face velocity, and front exhaust to reduce nanoparticle escape

  8. Sex differences in bronchiolar epithelium response after the inhalation of lead acetate (Pb)

    International Nuclear Information System (INIS)

    In order to identify if there were sex differences in lead (Pb) lung concentrations and in bronchiolar response after its inhalation, a mice inhalation model was conducted. Sixty CD-1 adult mice from each sex inhaled separately, lead acetate 0.1 M for 1 h, thrice weekly during 15 days. Animals were evaluated for Pb-lung concentrations by atomic absorption spectrometry and for morphological evaluation by scanning electron microscopy (SEM). Higher Pb-lung concentrations were determined in females, however, more cell damage was found in males, finding that correlated with an increased loss of the nonciliated bronchiolar cells (NCBC) more sloughing and necrosis. Differences in particle clearance, oxidative stress handling, cytokines pathway activation and cytochrome P450 enzymes activity, all influenced by sex hormones, might be a possible explanation for our findings. The relevance of further studies in this field is stressed, as well as its relation to the different development expected for each sex in disease evolution, possible complications and treatment response

  9. Impact of gasoline inhalation on some neurobehavioural characteristics of male rats

    Directory of Open Access Journals (Sweden)

    Kinawy Amal A

    2009-11-01

    Full Text Available Abstract Background This paper examines closely and compares the potential hazards of inhalation of two types of gasoline (car fuel. The first type is the commonly use leaded gasoline and the second is the unleaded type enriched with oxygenate additives as lead substituent in order to raise the octane number. The impacts of gasoline exposure on Na+, K+-ATPase, superoxide dismutase (SOD, acetylcholinesterase (AChE, total protein, reduced glutathione (GSH, and lipid peroxidation (TBARS in the cerebral cortex, and monoamine neurotransmitters dopamine (DA, norepinephrine (NE and serotonin (5-HT in the cerebral cortex, hippocampus, cerebellum and hypothalamus were evaluated. The effect of gasoline exposure on the aggressive behaviour tests was also studied. Results The present results revealed that gasoline inhalation induced significant fluctuations in the levels of the monoamine neurotransmitters in the studied brain regions. This was concomitant with a decrease in Na+, K+-ATPase activity and total protein content. Moreover, the group exposed to the unleaded gasoline exhibited an increase in lipid peroxidation and a decrease in AChE and superoxide dismutase activities. These physiological impairments were accompanied with a higher tendency towards aggressive behaviour as a consequence to gasoline inhalation. Conclusion It is concluded from the present work that chronic exposure to either the leaded or the unleaded gasoline vapours impaired the levels of monoamine neurotransmitters and other biochemical parameters in different brain areas and modulated several behavioural aspects related to aggression in rats.

  10. Deposition and clinical efficacy of terbutaline sulphate from Turbuhaler, a new multi-dose powder inhaler.

    Science.gov (United States)

    Newman, S P; Morén, F; Trofast, E; Talaee, N; Clarke, S W

    1989-03-01

    A radioaerosol technique has been developed in order to assess deposition patterns from a new metered dose powder inhaler (Turbuhaler, Astra Pharmaceuticals). The radionuclide Tc99m dissolved in chloroform was added to a spheronised formulation of micronised terbutaline sulphate and the chloroform was allowed to evaporate. Turbuhaler subsequently delivered 0.5 mg of treated drug per metered dose. In vitro tests with a multistage liquid impinger showed that the fractionation of the drug dose between different particle size bands was similar to the fractionation of radioactivity. In a group of ten asthmatic patients, a mean 14.2% (SEM 2.1) of the drug dose was deposited in the lungs, with 71.6% (3.0) of the dose in the oropharynx. Of the remainder, 13.7% (2.1) was deposited on the mouthpiece, and 0.5% (0.2) recovered from exhaled air. The radiolabel was present in both central and peripheral zones of the lungs. All patients bronchodilated; forced expiratory volume in one second (FEV1) increased from 1.40 (0.24) l to 1.77 (0.24) l (p less than 0.01) 20 min after inhalation. These results suggest that both the distribution of drug and the clinical effect of terbutaline sulphate delivered from Turbuhaler are similar to those from a pressurised metered dose inhaler (MDI). PMID:2731602

  11. Talcum induced pneumoconiosis following inhalation of adulterated marijuana, a case report

    Directory of Open Access Journals (Sweden)

    Scheel Andreas

    2012-03-01

    Full Text Available Abstract Background Talcosis, a granulomatous inflammation of the lungs caused by inhalation of talcum dust, is a rare form of pneumoconiosis. Besides inhalative occupational exposure, intravenous abuse of adulterated drugs is a major cause for this condition. Minerals such as talcum (magnesium silicate and sand (predominant silicon dioxide are used to increase both volume and weight of illicit substances. In intravenous heroin-abuse, talcosis is a well-known complication. Here we describe a case of talcosis caused by inhalative abuse of adulterated marijuana. Clinical history A 29-year old man presented with persistent fever, dyspnea and cervical emphysema. He admitted consumption of 'cut' marijuana for several years, preferentially by water pipe smoking. Morphologic findings Lung-biopsies showed chronic interstitial lung disease, anthracotic pigments and birefringent material. Energy dispersive x-ray spectroscopy revealed silicon-containing particles (1-2 μm and fine aluminum particles ( Conclusions The exacerbated chronic interstitial lung disease in a 29-year old patient could be attributed to his prolonged abuse of talcum-adulterated marjuana by histopathology and x-ray spectroscopy. Since cannabis consumption is widely spread among young adults, it seems to be justified to raise attention to this form of interstitial pulmonary disease. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnomx.eu/vs/krause/html/start.html.

  12. Preparation, characterization and pulmonary pharmacokinetics of a new inhalable zanamivir dry powder.

    Science.gov (United States)

    Cai, Xingshi; Yang, Yang; Xie, Xiangyang; Yu, Fanglin; Yang, Yanfang; Yang, Zhenbo; Zhang, Tao; Mei, Xingguo

    2016-07-01

    This work describes a new dry powder for inhalation containing zanamivir, which is less hygroscopic than Relenza®. The powders were prepared via a spray-drying technique using mannitol as the carrier. A 5(3) central composite design was used to optimize the formulations. The final optimized powders, characterized with an angle of repose 37.48°, an aerodynamic diameter of 2.346 μm and in vitro deposition of 58.54%, were obtained by using the predicted variable values. Relenza® absorbed a significant amount of water at 66%, 75% and 85% relative humidity (RH; weight changes of approximately 1.38%, 2.18% and 3.72%, respectively). In contrast, the weight change for the zanamivir dry powder inhalation (DPI) was negligible when the RH was increased to 66%. The in vivo potential for the optimized powders was studied further in rats via the endotracheal administration of an 8.4 mg/kg dose. The bioavailability was 116% relative to Relenza®. Fluorescence imaging monitored the zanamivir dry powder inhalers in rats. The results indicated that the zanamivir DPIs were effectively delivered to the lung. These results indicate that the spray-dried zanamivir DPIs were promising for pulmonary delivery. PMID:26066037

  13. Anxiolytic-like effect of Citrus limon (L. Burm f. essential oil inhalation on mice

    Directory of Open Access Journals (Sweden)

    M.D.M. VIANA

    2016-03-01

    Full Text Available ABSTRACT Experimental in vivo study aimed to characterize the anxiolytic-like effect of the Citrus limon fruit peel’s essential oil (CLEO in animal models of anxiety, besides evaluating the viability J774.A1 cells in vitro through the MTT reduction method at the concentrations of 10 and 100 µg/mL. The anxiolytic behavior was evaluated in Swiss mice (n = 8 using the methodology of Elevated Plus-Maze (EPM and Open-Field (OF. CLEO was tested by inhalation at the doses of 100, 200, and 400 µL, and as control, animals were subjected to inhalation of the vehicle (saline solution 0.9% + Tween80® and intraperitoneal administration of diazepam (1.5 mg/kg. In the cell viability assay, it was observed that none of the concentrations showed cytotoxicity. OF test showed significant anxiolytic activity at all tested doses of OECL, compared to the control group, without changing the motor performance of the animals. Corroborating OF data, the EPM test confirmed anxiolytic activity in at least two doses of the tested oil (200 and 400 µL, justified by the number of entries and increase in the percentage of time in the open arms. The data analysis of this study evidenced that inhalation of OECL was able to induce an anxiolytic behavior in mice; however, further studies are required to ensure its safe use by the population.

  14. Pulmonary toxicity of well-dispersed cerium oxide nanoparticles following intratracheal instillation and inhalation

    Energy Technology Data Exchange (ETDEWEB)

    Morimoto, Yasuo, E-mail: yasuom@med.uoeh-u.ac.jp; Izumi, Hiroto; Yoshiura, Yukiko; Tomonaga, Taisuke; Oyabu, Takako; Myojo, Toshihiko; Kawai, Kazuaki; Yatera, Kazuhiro [University of Occupational and Environmental Health (Japan); Shimada, Manabu; Kubo, Masaru [Hiroshima University (Japan); Yamamoto, Kazuhiro [National Institute of Advanced Industrial Science and Technology (AIST) (Japan); Kitajima, Shinichi [National Sanatorium Hoshizuka Keiaien (Japan); Kuroda, Etsushi [Osaka University, Laboratory of Vaccine Science, WPI Immunology Frontier Research Center (Japan); Kawaguchi, Kenji; Sasaki, Takeshi [National Institute of Advanced Industrial Science and Technology (AIST) (Japan)

    2015-11-15

    We performed inhalation and intratracheal instillation studies of cerium dioxide (CeO{sub 2}) nanoparticles in order to investigate their pulmonary toxicity, and observed pulmonary inflammation not only in the acute and but also in the chronic phases. In the intratracheal instillation study, F344 rats were exposed to 0.2 mg or 1 mg of CeO{sub 2} nanoparticles. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the instillation. In the inhalation study, rats were exposed to the maximum concentration of inhaled CeO{sub 2} nanoparticles (2, 10 mg/m{sup 3}, respectively) for 4 weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were examined from 3 days to 3 months after the end of the exposure. The intratracheal instillation of CeO{sub 2} nanoparticles caused a persistent increase in the total and neutrophil number in BALF and in the concentration of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in BALF during the observation time. The inhalation of CeO{sub 2} nanoparticles also induced a persistent influx of neutrophils and expression of CINC-1, CINC-2, and HO-1 in BALF. Pathological features revealed that inflammatory cells, including macrophages and neutrophils, invaded the alveolar space in both studies. Taken together, the CeO{sub 2} nanoparticles induced not only acute but also chronic inflammation in the lung, suggesting that CeO{sub 2} nanoparticles have a pulmonary toxicity that can lead to irreversible lesions.

  15. Pulmonary toxicity of well-dispersed cerium oxide nanoparticles following intratracheal instillation and inhalation

    International Nuclear Information System (INIS)

    We performed inhalation and intratracheal instillation studies of cerium dioxide (CeO2) nanoparticles in order to investigate their pulmonary toxicity, and observed pulmonary inflammation not only in the acute and but also in the chronic phases. In the intratracheal instillation study, F344 rats were exposed to 0.2 mg or 1 mg of CeO2 nanoparticles. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the instillation. In the inhalation study, rats were exposed to the maximum concentration of inhaled CeO2 nanoparticles (2, 10 mg/m3, respectively) for 4 weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were examined from 3 days to 3 months after the end of the exposure. The intratracheal instillation of CeO2 nanoparticles caused a persistent increase in the total and neutrophil number in BALF and in the concentration of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in BALF during the observation time. The inhalation of CeO2 nanoparticles also induced a persistent influx of neutrophils and expression of CINC-1, CINC-2, and HO-1 in BALF. Pathological features revealed that inflammatory cells, including macrophages and neutrophils, invaded the alveolar space in both studies. Taken together, the CeO2 nanoparticles induced not only acute but also chronic inflammation in the lung, suggesting that CeO2 nanoparticles have a pulmonary toxicity that can lead to irreversible lesions

  16. Effects of formaldehyde inhalation on the junctional proteins of nasal respiratory mucosa of rats.

    Science.gov (United States)

    Arican, R Yavuz; Sahin, Zeliha; Ustunel, Ismail; Sarikcioglu, Levent; Ozdem, Sadi; Oguz, Nurettin

    2009-07-01

    Exposure to formaldehyde, which is an organic compound, disturbs the integrity of nasal mucosa. In this study, we aimed to clarify the protein changes in the junctional complex of nasal mucosa of Wistar rats exposed to formaldehyde inhalation. The study was performed in 20 female Wistar rats. Rats were divided into two groups randomly. Control rats were allowed free access to standard rat chaw and tap water (n:10). Experimental group was exposed to formaldehyde vapor at 15ppm, 6h/day, 5 days/week for 12 weeks (n:10). Histological evaluation of the experimental model was determined by hematoxylin-eosin (HE) and periodic acid Schiff (PAS) stainings of paraffin-embedded nasal mucosa tissues and by electron microscopy. The effects of formaldehyde inhalation on the distribution of occludin, E-cadherin, and gamma-catenin were assessed by immunohistochemistry. The nasal mucosa of the experimental group was correlated with hypertrophy in goblet cell, degeneration in basal lamina, stratification of epithelium, and proliferation. Thickness of basal lamina and also local degenerative regions, vacuole increase in cytoplasmic areas, irregular forms of kinocilium and loss of sharpness in the kinocilium membrane were the findings at the ultrastructural level. The expressions of E-cadherin, occludin, gamma-catenin proteins in intercellular junctional complexes of rat nasal mucosa were also decreased in experimental group compared to control group. The findings of the present study indicated that formaldehyde vapor inhalation in the concentrations and duration of exposure used in the present experiment significantly decreased the density of structural proteins of the junctional complex in the nasoepithelium. It was suggested that, the formaldehyde inhalation could cause complete impairment of intercellular junctional complexes and disturb the tissue integrity in nasal mucosa at higher concentrations. PMID:18996001

  17. Differential inflammatory response to inhaled lipopolysaccharide targeted either to the airways or the alveoli in man.

    Directory of Open Access Journals (Sweden)

    Winfried Möller

    Full Text Available Endotoxin (Lipopolysaccharide, LPS is a potent inducer of inflammation and there is various LPS contamination in the environment, being a trigger of lung diseases and exacerbation. The objective of this study was to assess the time course of inflammation and the sensitivities of the airways and alveoli to targeted LPS inhalation in order to understand the role of LPS challenge in airway disease.In healthy volunteers without any bronchial hyperresponsiveness we targeted sequentially 1, 5 and 20 µg LPS to the airways and 5 µg LPS to the alveoli using controlled aerosol bolus inhalation. Inflammatory parameters were assessed during a 72 h time period. LPS deposited in the airways induced dose dependent systemic responses with increases of blood neutrophils (peaking at 6 h, Interleukin-6 (peaking at 6 h, body temperature (peaking at 12 h, and CRP (peaking at 24 h. 5 µg LPS targeted to the alveoli caused significantly stronger effects compared to 5 µg airway LPS deposition. Local responses were studied by measuring lung function (FEV(1 and reactive oxygen production, assessed by hydrogen peroxide (H(2O(2 in fractionated exhaled breath condensate (EBC. FEV(1 showed a dose dependent decline, with lowest values at 12 h post LPS challenge. There was a significant 2-fold H(2O(2 induction in airway-EBC at 2 h post LPS inhalation. Alveolar LPS targeting resulted in the induction of very low levels of EBC-H(2O(2.Targeting LPS to the alveoli leads to stronger systemic responses compared to airway LPS targeting. Targeted LPS inhalation may provide a novel model of airway inflammation for studying the role of LPS contamination of air pollution in lung diseases, exacerbation and anti-inflammatory drugs.

  18. Pulmonary connective tissue modifications induced by internal α-irradiation. II. Alterations of collagen and non collagen proteins biosynthesis following inhalation of plutonium 239 dioxide aerosol in rat

    International Nuclear Information System (INIS)

    Preliminary studies have shown that internal α irradiation following inhalation of plutonium 239 dioxide in rat increased collagen content in the lung. Effect was maximal at 200 days with the highest dose. This increase was found transient and collagen dropped back to control values after 400 days in rats with the same initial lung burden or the same total dose. A new increase was observed later on, largely related to oncoming death. Here, we have studied, simultaneously, content and biosynthesis of collagen and non collagen proteins, 200 d and 400 d after 239PuO2 inhalation (100-150 nCi ILB). The results confirmed a biphasic effect of inhaled 239PuO2 on the pulmonary connective tissue: a/ A significant increase (p < 0.01) of soluble non-collagen proteins correlated to a decrease of the insoluble fraction was observed 200 d after inhalation. Similar parameters were not significantly different in controls on irradiated rats after 400 days. b/ Soluble and non-soluble collagen contents increased by a factor of 3 and 1.5 respectively 200 d after inhalation. No effect after 400 d. c/ Biosynthesis of non-collagen connective tissue components were 2 to 5 lower than in controls at 400d. d/collagen biosynthesis was decreased by a factor between 4 and 6 for the soluble and insoluble fractions at 200 d but normal at 400 d

  19. Particle engineering of materials for oral inhalation by dry powder inhalers. II-Sodium cromoglicate.

    Science.gov (United States)

    Nolan, Lorraine M; Li, Jianhe; Tajber, Lidia; Corrigan, Owen I; Healy, Anne Marie

    2011-02-28

    Sodium cromoglicate is an antiasthmatic and antiallergenic drug used in inhalation therapy and commonly administered by a dry powder inhaler. In the present study we sought to examine the feasibility of producing nanoporous microparticles (NPMPs) of this hydrophilic material by adaptation of a spray drying process previously applied to hydrophobic drugs, and to examine the physicochemical and in vitro deposition properties of the spray dried particles in comparison to a commercial product. The storage stability of successfully prepared NPMPs was assessed under a number of conditions (4°C with dessicant, 25°C at 60% relative humidity and 25°C with dessicant). Spray dried sodium cromoglicate was amorphous in nature. NPMPs of sodium cromoglicate displayed superior aerodynamic properties resulting in improved in vitro drug deposition, as assessed by Andersen Cascade Impactor and twin impinger studies, in comparison to the commercial product, Intal. Deposition studies indicated that porosity and sphericity were important factors in improving deposition properties. The optimum solvent system for NPMP production was water:methanol:n-butyl acetate, as spherical NPMPs spray dried from this solvent system had a higher respirable fraction than non-spherical NPMPs of sodium cromoglicate (spray dried from methanol:n-butyl acetate), non-porous sodium cromoglicate (spray dried from water) and micronised sodium cromoglicate (Intal). While particle morphology was altered by storage at high humidity (60% RH) and in vitro deposition performance deteriorated, it was possible to maintain NPMP morphology and aerosolisation performance by storing the powder with dessicant. PMID:21129460

  20. Results of a multicenter study of nebulized inhalant bronchodilator solutions.

    Science.gov (United States)

    Tashkin, D P; Bleecker, E; Braun, S; Campbell, S; DeGraff, A C; Hudgel, D W; Boyars, M C; Sahn, S

    1996-01-29

    The efficacy, persistence of bronchodilator action, and safety of the quaternary ammonium anticholinergic agent, ipratropium bromide (500 microgram), and placebo were compared when each was added in solution form to the beta-adrenergic agonist solution, metaproterenol sulfate (15 mg), and administered three times daily for 12 weeks to a total of 213 patients with chronic obstructive pulmonary disease (COPD). Subjects had a mean forced expiratory volume in 1 second (FEV1) of approximately 1 liter (37% of predicted) and were permitted to use nonanticholinergic therapy for COPD throughout the trial. The study was a randomized, double-blind, 85-day, parallel-group, eight-center study. On a 3 test days, 1, 43, and 85, mean peak responses for FEV1 and forced vital capacity and mean area under the curve were significantly higher for the iprathropium bromide-metaproterenol combination than for metaproterenol only. Duration of action was also significantly longer for the combination therapy than for the beta-agonist alone on test days 1 and 43. Neither treatment regimen produced an demonstrable effect on daily morning peak expiratory flow rates, reported respiratory symptoms, or quality of life. Both treatment regimens were similarly well tolerated with a comparable frequency of adverse events. These results suggest that the combination of iprathropium bromide and metaproterenol inhalation solutions offers a potential therapeutic advantage to patients with symptomatic COPD over nebulized metaproterenol alone without the risk of increased side effects. PMID:8610720

  1. Effects on inhaled uranium mine air contaminants in beagle dogs

    International Nuclear Information System (INIS)

    The high incidence of lung cancer among uranium miners of the Colorado plateau is a matter of national concern in a period of increasing demand for uranium ore. These miners are exposed to a variety of inhalation hazards, including radon daughters, uranium ore dust, and cigarette smoking, that may cause or contribute to respiratory tract pathology. Over 98 percent of the miners developing lung cancer have had histories of cigarette smoking. In order to determine the combined or separate roles of radon daughters and cigarette smoking in the development of lung cancer and other respiratory tract pathology, groups of 20 dogs each received daily life span exposures to 4 hours of 600 working levels of radon daughters with ore dust, and/or cigarette smoking over 16 hours per day, 7 days per week, or both; control dogs received sham smoking. After 4 years of exposure, respiratory tract pathology included macrophage accumulation, septal fibrosis, epithelial hyperplasia, endothelial proliferation, vesicular and bullous emphysema, and extensive epithelial changes involving squamous metaplasia with atypical nuclei. These effects were primarily related to exposure to radon daughters and uranium ore dust, with and without cigarette smoke

  2. Towards the optimisation and adaptation of dry powder inhalers.

    Science.gov (United States)

    Cui, Y; Schmalfuß, S; Zellnitz, S; Sommerfeld, M; Urbanetz, N

    2014-08-15

    Pulmonary drug delivery by dry powder inhalers is becoming more and more popular. Such an inhalation device must insure that during the inhalation process the drug powder is detached from the carrier due to fluid flow stresses. The goal of the project is the development of a drug powder detachment model to be used in numerical computations (CFD, computational fluid dynamics) of fluid flow and carrier particle motion through the inhaler and the resulting efficiency of drug delivery. This programme will be the basis for the optimisation of inhaler geometry and dry powder inhaler formulation. For this purpose a multi-scale approach is adopted. First the flow field through the inhaler is numerically calculated with OpenFOAM(®) and the flow stresses experienced by the carrier particles are recorded. This information is used for micro-scale simulations using the Lattice-Boltzmann method where only one carrier particle covered with drug powder is placed in cubic flow domain and exposed to the relevant flow situations, e.g. plug and shear flow with different Reynolds numbers. Therefrom the fluid forces on the drug particles are obtained. In order to allow the determination of the drug particle detachment possibility by lift-off, sliding or rolling, also measurements by AFM (atomic force microscope) were conducted for different carrier particle surface structures. The contact properties, such as van der Waals force, friction coefficient and adhesion surface energy were used to determine, from a force or moment balance (fluid forces versus contact forces), the detachment probability by the three mechanisms as a function of carrier particle Reynolds number. These results will be used for deriving the drug powder detachment model. PMID:24792975

  3. Species difference in metabolism of inhaled butadiene

    International Nuclear Information System (INIS)

    Chronic exposure of B6C3F1 mice and Sprague-Dawley rats to butadiene (BD) produced a very high incidence of cancer in mice while the incidence in rats was much lower with different tissues affected. Studies at this institute indicate that for equivalent exposures, the blood BD epoxide concentrations in mice are 5-fold higher than in rats and > 10-fold higher than in Cynomolgus monkeys. In this study, the profiles of urinary metabolites of butadiene were determined in Cynomolgus monkeys, F344/N rats, Sprague Dawley rats, B6C3F1 mice and Syrian hamsters, species containing widely divergent hepatic epoxide hydrolase (EH) activities. Animals were exposed for 2 hr to 8,000 ppm [14C]BD and 24-hr urine samples were analyzed for metabolites. Two major urinary metabolites were identified, N-acetyl-S-(-1(or 2)-3-butene-2(or 1)-ol)cysteine (1) and N-acetyl-S-(-4-butane-1,2-diol)cysteine (2). Monkeys exposed by inhalation produced primarily metabolite 2, while rodent species produced 1-4 times as much of 1 compared to 2. The ratio of 2/1 formation was related to the hepatic epoxide hydrolase activity in different species. The high 2/1 ratio in monkeys was consistent with the lower blood epoxide levels in this species. If BD metabolism by humans is similar to that in the monkey, exposure of humans to BD may result in lower tissue concentrations of reactive metabolites than an equivalent exposure of rodents. This has important implications for assessing the risk to humans of BD exposure based on rodent studies

  4. 1,2-Dichloropropane (DCP): Kinetics and metabolism in Fischer 344 rat following oral and inhalation exposure

    International Nuclear Information System (INIS)

    DCP is utilized as a chemical intermediate and chemical processing solvent. 14C-DCP was administered orally to groups of 4 rats/sex as a single dose of 1 or 100 mg/kg and as a multiple 1 mg/kg non-radiolabeled dose for 7 days followed by a single 1 mg 14C-DCP/kg dose on day 8. In addition, 4 rats/sex were exposed to 14C-DCP vapors for a 6 hr period in a head-only inhalation chamber at target concentrations of 5, 50, and 100 ppm. DCP was rapidly absorbed, metabolized and excreted after oral or inhalation exposure. The principal routes of elimination (oral and inhalation) were via the urine (37-65%) and as expired CO2 (16-36%). The tissues/carcass, feces, cage wash and expired organics contained less than 11, 9.7 3.8 and 0.14-16% of the dose, respectively. The major urinary metabolites, from the oral and inhalation exposures were identified as three N-acetylcysteine conjugates of DCP, N-acetyl-S-(2-hydroxypropyl)-L-cysteine, N-acetyl-S-(2-oxypropyl)-L-cysteine, and N-acetyl-S-(1-carboxyethyl)-L-cysteine. The majority (61-87%) of the expired volatile organic material was parent DCP in all samples analyzed. Increasing dose/concentration of 14C-DCP resulted in an increase in the percentage of exhaled 14C volatile organics. The peak DCP blood concentration (inhalation exposure) increased disproportionately to dose. However, upon termination of exposure, DCP was rapidly eliminated from the blood (t1/2=24-30 min). In all treatment groups the majority of the radioactivity was eliminated by 24 hr post-dosing, and no meaningful differences were noted between sexes

  5. PROCESS VALIDATION OF METERED DOSE INHALER: A REVIEW

    Directory of Open Access Journals (Sweden)

    Kaur Gaganpreet

    2012-03-01

    Full Text Available The purpose of this work is to present an introduction and general overview on process validation of Metered dose inhaler.The word validation simply means, “Assessment of validation or action of proving effectiveness”. The most common dosage form for inhalation is the metered-dose inhaler (MDI, by which the drug is delivered from a pressurized container using a liquefied gas propellant.Inhalation is the convenient way to deliver drugs to respiratory tract in treatment of respiratory disease like ASTHMA.The process validation process parameters are derived from the specifications for the device, component or other entity to be produced by the process. The process is developed in such a way that the required parameters are achieved and it ensures that the output of the process will consistently meet the required parameters during routine production, the process is validated. A manufacturer can assure through careful design of the device, processes, process controls and packaging that all manufactured units will meet specifications and have uniform quality. However, in-process and finished product testing still play an important role in assuring that products meet specifications Validation is defined as a collection and evaluation of data , from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality product. MDI is pocket-sized, hand-held, pressurise multiple-dose inhalation delivery system. It delivers small, precisely measured therapeutic doses, greatly minimizing the risk of adverse side effects. A metered dose inhaler (MDI is a device that delivers a specific amount of medication to the lungs in the form of a short burst of aerosolized medicine that is inhaled by the patient. Three consecutive batches of metered dose inhaler shall be taken up for process validation. Based on the results of all the 3 batches, suitable conclusions will be drawn

  6. Inhalability for aerosols at ultra-low windspeeds

    International Nuclear Information System (INIS)

    Most previous experimental studies of aerosol inhalability were conducted in wind tunnels for windspeeds greater than 0.5 ms-1. While that body of work was used to establish a convention for the inhalable fraction, results from studies in calm air chambers (for essentially zero windspeed) are being discussed as the basis of a modified criterion. However, information is lacking for windspeeds in the intermediate range, which - it so happens - pertain to most actual workplaces. With this in mind, we have developed a new experimental system to assess inhalability - and, ultimately, personal sampler performance - for aerosols with particle aerodynamic diameter within the range from about 9 to 90 μm for ultra-low windspeed environments from about 0.1 to 0.5 ms1. This new system contains an aerosol test facility, fully described elsewhere, that combines the physical attributes and performance characteristics of moving air wind tunnels and calm air chambers, both of which have featured individually in previous research. It also contains a specially-designed breathing, heated, life-sized mannequin that allows for accurate recovery of test particulate material that has been inhaled. Procedures have been developed that employ test aerosols of well-defined particle size distribution generated mechanically from narrowly-graded powders of fused alumina. Using this new system, we have conducted an extensive set of new experiments to measure the inhalability of a human subject (as represented by the mannequin), aimed at filling the current knowledge gap for conditions that are more realistic than those embodied in most previous research. These data reveal that inhalability throughout the range of interest is significantly different based on windspeed, indicating a rise in aspiration efficiency as windspeed decreases. Breathing flowrate and mode of breathing (i.e. nose versus mouth breathing) did not show significant differences for the inhalability of aerosols. On the whole

  7. Dry powder inhalable formulations for anti-tubercular therapy.

    Science.gov (United States)

    Parumasivam, Thaigarajan; Chang, Rachel Yoon Kyung; Abdelghany, Sharif; Ye, Tian Tian; Britton, Warwick John; Chan, Hak-Kim

    2016-07-01

    Tuberculosis (TB) is an intracellular infectious disease caused by the airborne bacterium, Mycobacterium tuberculosis. Despite considerable research efforts, the treatment of TB continues to be a great challenge in part due to the requirement of prolonged therapy with multiple high-dose drugs and associated side effects. The delivery of pharmacological agents directly to the respiratory system, following the natural route of infection, represents a logical therapeutic approach for treatment or vaccination against TB. Pulmonary delivery is non-invasive, avoids first-pass metabolism in the liver and enables targeting of therapeutic agents to the infection site. Inhaled delivery also potentially reduces the dose requirement and the accompanying side effects. Dry powder is a stable formulation of drug that can be stored without refrigeration compared to liquids and suspensions. The dry powder inhalers are easy to use and suitable for high-dose formulations. This review focuses on the current innovations of inhalable dry powder formulations of drug and vaccine delivery for TB, including the powder production method, preclinical and clinical evaluations of inhaled dry powder over the last decade. Finally, the risks associated with pulmonary therapy are addressed. A novel dry powder formulation with high percentages of respirable particles coupled with a cost effective inhaler device is an appealing platform for TB drug delivery. PMID:27212477

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

    Science.gov (United States)

    Pritchard, John N

    2015-12-30

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

  9. Withdrawal of inhaled glucocorticoids and exacerbations of COPD

    DEFF Research Database (Denmark)

    Magnussen, Helgo; Disse, Bernd; Rodriguez-Roisin, Roberto;

    2014-01-01

    BACKGROUND: Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long-acting bronchod......BACKGROUND: Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long......-acting bronchodilators has not been fully explored. METHODS: In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid...... fluticasone propionate (500 μg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric...

  10. Inhaled corticosteroids: hazardous effects on voice-an update.

    Science.gov (United States)

    Gallivan, Gregory J; Gallivan, K Holly; Gallivan, Helen K

    2007-01-01

    Inhaled corticosteroids (ICS) have become the prevalent treatment in asthmatics. Hazards to voice are under-recognized. A total of 38 patients with voice complaints associated with the use of ICS were assessed by 79 strobovideolaryngoscopy (SVL) examinations, 24 single and 14 multiple SVL. Hoarseness and dysphonia were the primary reasons for referral. The ICS initially used most frequently was Advair Diskus (fluticasone propionate and salmeterol-inhalation powder-[IP]) in 22 patients, followed by Flovent (fluticasone propionate inhalation aerosol-pressurized metered-dose inhaler-[PMDI]) in 11. Duration of ICS usage varied from 2 weeks to 4-5 years. Higher dosage and frequency of use exacerbated problems. Hazards to voice previously unrecognized by real-time indirect mirror or fiberoptic laryngoscopy were identified by meticulous attention to SVL abnormalities. There was essentially no difference in occurrence of abnormalities whether analyzed from the perspective of the initial 38 or all 79 examinations. These included abnormal mucosal wave symmetry/periodicity (76-63%), phase closure (74-63%), glottic closure (63-59%), mucosal wave amplitude/magnitude (50-35%), supraglottic hyperactivity (39-25%), mucosal quality (34-34%), and glottic plane (10-5%). Candidiasis of the larynx was infrequently observed. Fluticasone ICS were a cause of steroid inhaler laryngitis, and the best treatment was their avoidance or cessation. Further prospective studies ideally might include SVL documented as a pretherapy baseline and then repeated in each ICS patient who developed hoarseness/dysphonia. PMID:16442776

  11. Biological effects of inhaled radionuclides: summary of ICRP report 31

    International Nuclear Information System (INIS)

    The ICRP Task Group charged with evaluating the hazards associated with inhalation of plutonium and other radionuclides, enumerated the biological responses to inhaled radionuclides, identified tissues and cells at risk, derived risk coefficients for inhaled radionuclides from animal experiments for comparison with human data, and determined an equal effectiveness ratio of alpha emitters relative to beta-gamma emitters. High lung burdens of inhaled radionuclides result in profound structural and functional changes in which the pulmonary capillary endothelial cells are the most prominent cells at risk. Linear and nonlinear models used to evaluate lung cancer data from animal experiments project to risk coefficients between 0.84 and 1600 cases/106 animals/rad. The report concludes that the animal data support the current ICRP lung cancer risk of 2 x 10-3 Sv-1 (400 x 10+H-+H6 rad-1). Comparison of risk coefficients for beta-gamma emitters with those for alpha emitters, obtained using the same models, gave an Equal Effectiveness Ratio of 30 for inhaled alpha-emitting radionuclides. Thus, the experimental data support the ICRP decision to change the quality factor from 10 to 20 for alpha radiation. (H.K.)

  12. Accidental Cutaneous Burns Secondary to Salbutamol Metered Dose Inhaler

    Directory of Open Access Journals (Sweden)

    Ashutosh Kale

    2010-01-01

    Full Text Available We report a case of accidental cutaneous burns caused by salbutamol metered dose inhaler. A 9-year-old boy underwent dental extraction at a children's hospital and was incidentally noted to have burn injuries on dorsum of both hands. On questioning, the boy revealed that a few days ago his 14-year-old brother, who is an asthmatic, playfully sprayed his salbutamol metered dose inhaler on the back of both his hands with the inhaler's mouth piece being in direct contact with the patient's skin. On examination, there was a rectangular area of erythema with superficial peeling on the dorsum of both hands, the dimensions of which exactly matched those of the inhaler's mouthpiece. It is possible that the injury could have been a chemical burn from the pharmaceutical/preservative/propellant aerosol or due to the physical effect of severe cooling of the skin or mechanical abrasive effect of the aerosol blasts or a combination of some or all the above mechanisms. This case highlights the importance of informing children and parents of the potentially hazardous consequences of misusing a metered dose inhaler.

  13. Raxibacumab: potential role in the treatment of inhalational anthrax

    Directory of Open Access Journals (Sweden)

    Kummerfeldt CE

    2014-04-01

    Full Text Available Carlos E KummerfeldtDivision of Pulmonary, Critical Care, Allergy and Sleep Medicine, Medical University of South Carolina, Charleston, SC, USAAbstract: Anthrax is a highly contagious and potentially fatal human disease caused by Bacillus anthracis, an aerobic, Gram-positive, spore-forming rod-shaped bacterium with worldwide distribution as a zoonotic infection in herbivore animals. Bioterrorist attacks with inhalational anthrax have prompted the development of more effective treatments. Antibodies against anthrax toxin have been shown to decrease mortality in animal studies. Raxibacumab is a recombinant human monoclonal antibody developed against inhalational anthrax. The drug received approval after human studies showed its safety and animal studies demonstrated its efficacy for treatment as well as prophylaxis against inhalational anthrax. It works by preventing binding of the protective antigen component of the anthrax toxin to its receptors in host cells, thereby blocking the toxin's deleterious effects. Recently updated therapy guidelines for Bacillus anthracis recommend the use of antitoxin treatment. Raxibacumab is the first monoclonal antitoxin antibody made available that can be used with the antibiotics recommended for treatment of the disease. When exposure is suspected, raxibacumab should be given with anthrax vaccination to augment immunity. Raxibacumab provides additional protection against inhalational anthrax via a mechanism different from that of either antibiotics or active immunization. In combination with currently available and recommended therapies, raxibacumab should reduce the morbidity and mortality of inhalational anthrax.Keywords: anthrax, monoclonal antibody, protective antigen, raxibacumab

  14. Comparison of the effects of inhaled alpha- and beta-emitting radionuclides on pulmonary function of the dog

    International Nuclear Information System (INIS)

    Pulmonary function changes of representative dogs after inhalation of a relatively insoluble form of 144Ce in fused aluminosilicate particles and 238PuO2 were compared. Both radionuclide forms had approximately the same effective half-life, but the 238PuO2 irradiated 11 percent of the lung while the 144Ce irradiated 100 percent. Both groups developed restrictive lung disease progressing to pulmonary failure but the sequence of functional changes differed. The first change in dogs that inhaled 144Ce was a reduced CO diffusing capacity followed later by changes in breathing pattern, lung compliance and alveolar-capillary O2 exchange. The first change in dogs that inhaled 238PuO2 was an increase in respiratory frequency which persisted for several months before nearly simultaneous changes in diffusing capacity, compliance and gas mixing. An impairment in alveolar-capillary O2 exchange occurred later in dogs that inhaled 238PuO2. Functional alterations of both groups in pulmonary failure were similar. The differences in the pattern of functional changes were thought to be related to differences in dose pattern, but the exact relationships are unknown

  15. Comparison of the effects of inhaled alpha- and beta-emitting radionuclides on pulmonary function in the dog

    International Nuclear Information System (INIS)

    Alterations of pulmonary function in representative groups of dogs developing nonneoplastic lung disease, after single inhalation exposures to cerium-144 or plutonium-238 in relatively insoluble particulate forms, were compared. The inhaled particles had similar aerodynamic diameters and effective half-lives of retention in the lung. The mean initial lung burdens of the 144Ce- and 238Pu-exposed groups were 51 and 0.65 μCi/kg of body weight, respectively. Because of the respective ranges of the beta emissions from 144Ce and the alpha emissions from 238Pu, the lungs of the 144Ce-exposed dogs were relatively uniformly irradiated, whereas only approximately 6% of the lung tissue of rates to the 238Pu-exposed dogs was irradiated. The calculated average dose rates to the irradiated tissue were similar for both radionuclides. Pulmonary function was measured serially without sedation. Both groups developed progressive, restrictive lung disease, which ended in death from pulmonary failure. Dogs that inhaled 144Ce had an early reduction of CO diffusing capacity followed by a progressive mechanical and gas-exchange impairment similar to that reported for dogs and men exposed to external irradiation. Dogs that inhaled 238Pu had increased respiratory frequencies which often persisted for months before mechanical and gas-exchange abnormalities became evident

  16. Combined effects of radon inhalation and antioxidant vitamin administration on acute alcohol-induced hepatopathy in mice

    International Nuclear Information System (INIS)

    It has been reported that radon inhalation activates antioxidative functions in liver and has an antioxidative effect against hepatopathy similar to that of the antioxidative effects of ascorbic acid (VC) or α-tocopherol (VE). In this study, we examined the combined effects of radon inhalation and antioxidant vitamin administration on acute alcohol-induced hepatopathy in mice. ICR mice were subjected to intraperitoneal (i.p.) administration of alcohol after pretreating with air only (sham) or radon at a concentration of approximately 2000 Bq/m3 for 24 hours and i.p. administration of VC (300 mg/kg body weight) or VE (300 mg/kg body weight). In mice injected with alcohol, the combined radon and antioxidant vitamins treatment significantly decreased the activities of glutamic oxaloacetic transaminase in serum compared to not only the alcohol-administered group (sham group), but also the radon inhalation with alcohol administration group or the vitamin and alcohol administration group. In addition, radon inhalation significantly increased the antioxidant level, in such as the catalase activity and the total glutathione content in liver compared to the sham group. These results suggested that the combined radon and antioxidant vitamin treatment could effectively inhibit alcohol-induced hepatopathy in mice without any antagonizing action. (author)

  17. Inhalation toxicity of propineb. Part II: Results of mechanistic studies in rats.

    Science.gov (United States)

    Pauluhn, Jürgen; Emura, M; Mohr, U; Rosenbruch, Martin

    2003-04-25

    Previous repeated inhalation exposure studies revealed two independent organotropic effects of inhaled propineb dust: One was restricted to the lung, the other to muscle weakness of hindlimbs. These effects were believed to be causally related to the principle decomposition products of this type of dithiocarbamate in the biological milieu and related to zinc and carbon disulfide. Two mechanistic 1-wk inhalation studies were performed, each focusing on one of these findings. The 7 x 6-h/day repeated-exposure inhalation study analyzed whether the nature of the response occurring at the alveolar level is "adaptive" or "early adverse" and whether soluble zinc is the causative agent. Groups of 18 female rats were exposed nose-only to mean concentrations of 0, 1.1, 5.5, and 25.8 mg propineb/m(3) and 6.9 mg ZnO/m(3). On postexposure days 1, 3, and 15 the time course of responses was analyzed by bronchoalveolar lavage (BAL), including quantification of Zn and metallothionein (MT) in BAL cells. Clinical evidence of muscular weakness was investigated separately in 20 female Wistar rats exposed to 70 mg propineb/m(3) on 5 consecutive days (6 h/day), followed by a 2-wk postexposure period. Clinical signs, body weights, and feed and water consumption were recorded as frequently as technically feasible. Fifty percent of rats received an oral cysteine supplementation to verify/refute the hypothesis that the incapacitation observed in previous studies is the cause of emaciation and associated impairment of CS(2) detoxification. The findings of the first study are consistent with this hypothesis, namely, that soluble Zn triggers a series of pulmonary events that is consistent with the homeostasis of this essential metal. It is concluded, accordingly, that the adjusted maximal workplace level for ZnO is also valid for propineb to preclude Zn-mediated responses to occur in the lung. With respect to muscular effects, this mechanistic study demonstrates further that the increased

  18. [Evaluations of a specified number of inhalations and how to assess the contents in metered-dose inhalers].

    Science.gov (United States)

    Obata, T; Fujikawa, M; Obata, Y; Obata, J

    1996-10-01

    Many kinds of Metered-Dose Inhalers (MDI) have been clinically available for bronchial asthma. Although manufacturers demonstrate the specified number of inhalations per canister on an attached document or on a plastic bag, the information provided are usually inadequate and inconsistent. They provide no information on the problems of the Metered-Dose Inhalers beyond the maximum specified number of actuations and the time when to exchange for a new one. We examined the technique how to evaluate the contents of MDI and their accuracy. Patients and their parents depended on inaccurate methods, such as shaking the inhalers to listen to the sound of contents, estimating the weight of the canisters and the size of emissions, and only a half of them were able to distinguish between 1/3 and 2/ 3 of remaining doses. Three Metered-Dose Inhalers with anti-inflammatory drugs and one MDI with beta-stimulant supplied consistent doses until they reached the maximum specified number. The 4 MDIs floated in the water in different ways and provided information when to replace for new ones in some MDIs. PMID:8958655

  19. Limiting progressive hippocampal metabolic abnormalities after smoke inhalation injury.

    Science.gov (United States)

    Tobe, Edward; Pradhan, Basant K

    2014-01-01

    A 46-year-old man had a smoke inhalation injury. Within 1 month, he developed neuropsychiatric problems including toxic encephalopathy, cognitive disorder, depression symptoms and personality change. From 3 to 14 years after the toxic inhalation injury, the patient received treatment with sertraline and methylphenidate. The (18)F-fluorodeoxyglucose positron emission tomography scan at 3 years after injury showed deterioration of glucose metabolism in the hippocampus and orbital frontal region; at 14 years after injury, the hippocampus had no significant change but the orbital frontal region had deterioration of glucose metabolism. It was hypothesised that sertraline may have provided selective hippocampal neuroprotection. Further study is justified to evaluate sertraline as a possible neuroprotective agent after smoke inhalation injury. PMID:24577174

  20. Adolescents and inhalant abuse: how huffing affects the myelin sheath.

    Science.gov (United States)

    Baird, Carolyn A; Furek, Maxim W

    2012-05-01

    As concern grows over the impact that accidental chemical exposures may have on the long term health of individuals, our young people are deliberately exposing themselves to the effect of neurotoxic chemicals with the intent of feeling high. Over time the result of inhaling these chemicals is often the development of symptoms and behavior that may suggest serious physiological damage. Research is being conducted to examine what the exact nature of the damage might be, especially the impact of inhaled lipophilic chemicals on structures in the brain and other parts of the nervous system. Healthcare professionals responsible for assessing adolescents in all settings need to be aware of the prevalence of inhalant abuse, as well as the chemicals, terminology, and potential symptomatology in order to intervene in the behavior and provide diagnosis and treatment as indicated. Some implications for nursing are included. PMID:22471781

  1. Criteria for inhalation exposure systems utilizing concurrent flow spirometry

    International Nuclear Information System (INIS)

    Principles are given for the design and operation of a new class of inhalation exposure systems utilizing concurrent flow spirometry (CFS), a simple method for providing realtime measurement of respiratory volumes and rates during inhalation exposure by mouth or nose of individual experimental animals or man to aerosols or gases. This technique is especially useful for inhalation exposure of larger experimental animals, such as horses, where whole-body plethysmography is usually impractical. Difficulties encountered with conventional exposure systems in maintenance of uniform aerosol or gas concentrations and prevention of large pressure excursions in the exposure chamber during breathing are obviated by systems utilizing the principles of concurrent flow spirometry. For illustration, two exposure units with CFS are described, one for exposure of Beagle dogs and one for ponies. (U.S.)

  2. Contribution of inhalation by food animals to man's ingestion dose

    International Nuclear Information System (INIS)

    Animals' inhalation (AI) pathway was evaluated for 57 radionuclides using infant dose predictions from the food-chain model LIMCAL. With ingestion transfer coefficients fMi to define transfer from the respiratory tract to milk, the AI pathway appeared to be insignificant compared to animals' plant ingestion, as implicitly assumed in most environmental assessment models for nuclear installations. Using ICRP Publication 30 respiratory clearance models for man to adjust ingestion transfer coefficients, animals' inhalation appeared to be important, particularly for some actinide radionuclides. The AI pathway also appeared to be significant relative to man's inhalation, especially for infants. The importance of the AI pathway varied greatly between radionuclides, and results strongly suggest that it cannot be ignored in environmental assessments. Until better data become available to implement this pathway fully, adjusted ingestion transfer coefficient values can be used for transfer from animals' respiratory tract to milk and other food products

  3. Advances in metered dose inhaler technology: hardware development.

    Science.gov (United States)

    Stein, Stephen W; Sheth, Poonam; Hodson, P David; Myrdal, Paul B

    2014-04-01

    Pressurized metered dose inhalers (MDIs) were first introduced in the 1950s and they are currently widely prescribed as portable systems to treat pulmonary conditions. MDIs consist of a formulation containing dissolved or suspended drug and hardware needed to contain the formulation and enable efficient and consistent dose delivery to the patient. The device hardware includes a canister that is appropriately sized to contain sufficient formulation for the required number of doses, a metering valve capable of delivering a consistent amount of drug with each dose delivered, an actuator mouthpiece that atomizes the formulation and serves as a conduit to deliver the aerosol to the patient, and often an indicating mechanism that provides information to the patient on the number of doses remaining. This review focuses on the current state-of-the-art of MDI hardware and includes discussion of enhancements made to the device's core subsystems. In addition, technologies that aid the correct use of MDIs will be discussed. These include spacers, valved holding chambers, and breath-actuated devices. Many of the improvements discussed in this article increase the ability of MDI systems to meet regulatory specifications. Innovations that enhance the functionality of MDIs continue to be balanced by the fact that a key advantage of MDI systems is their low cost per dose. The expansion of the health care market in developing countries and the increased focus on health care costs in many developed countries will ensure that MDIs remain a cost-effective crucial delivery system for treating pulmonary conditions for many years to come. PMID:24357110

  4. Pneumonia risk with inhaled fluticasone furoate and vilanterol compared with vilanterol alone in patients with COPD

    DEFF Research Database (Denmark)

    Crim, Courtney; Dransfield, Mark T; Bourbeau, Jean; Jones, Paul W; Hanania, Nicola A; Mahler, Donald A; Vestbo, Jørgen; Wachtel, Andrew; Martinez, Fernando J; Barnhart, Frank; Lettis, Sally; Calverley, Peter M A

    2015-01-01

    RATIONALE: Radiographically confirmed pneumonia risk with inhaled corticosteroid use in chronic obstructive pulmonary disease (COPD) has not been assessed to date. OBJECTIVES: To determine the incidence of pneumonia, risk factors, and clinical attributes with inhaled fluticasone furoate (FF) in p...

  5. Asthma Patients in US Overuse Quick-Relief Inhalers, Underuse Control Medications

    Science.gov (United States)

    ... overuse quick-relief inhalers, underuse control medications Share | Asthma patients in US overuse quick-relief inhalers, underuse control medications Published Online: December 13, 2013 Asthma exacerbations and uncontrolled asthma result in poor health ...

  6. Urine concentrations of repetitive doses of inhaled salbutamol

    DEFF Research Database (Denmark)

    Elers, J; Pedersen, Lars; Henninge, J;

    2011-01-01

    We examined blood and urine concentrations of repetitive doses of inhaled salbutamol in relation to the existing cut-off value used in routine doping control. We compared the concentrations in asthmatics with regular use of beta2-agonists prior to study and healthy controls with no previous use of...... beta2-agonists. We enrolled 10 asthmatics and 10 controls in an open-label study in which subjects inhaled repetitive doses of 400 microgram salbutamol every second hour (total 1600 microgram), which is the permitted daily dose by the World Anti-Doping Agency (WADA). Blood samples were collected at...

  7. Determination of hepatic blood flow following inhalation of xenon

    International Nuclear Information System (INIS)

    The 133Xe inhalation technique causes a long-lasting inflow of xenon to the liver after the end of inhalation because of the residual concentration in the lungs starting from the formula according to Kety and Schmidt. A mathematical solution is proposed to eliminate, the influence of the arterial concentration on the measured values and to determine the real flow values. On the basis of the least squares method an algorithm is proposed that yields values which are in good correlation (r = 0.90, n = 15) to the original method of arterial Xe injection. Factors influencing the mathematical model are discussed. (author)

  8. Toxicity studies of inhaled beta-emitting radionuclides: status report

    International Nuclear Information System (INIS)

    The influence of total dose and dose rate on the effects of inhaled beta-emitting radionuclides is being studied in laboratory animals. The radionuclides are inhaled either in a relatively soluble form (90SrCl2, 144CeCl3, 91YCl3 or 137CsCl) or in a relatively insoluble form in fused aluminosilicate particles. The organs affected depend on the solubility and chemical characteristics of the radio isotopes. Studies with young adult dogs are complemented with comparable studies in other species (mice, rats and Syrian hamsters), with animals of different ages and with animals repeatedly exposed to 144Ce

  9. Toxicity studies of inhaled beta-emitting radionuclides - status report

    International Nuclear Information System (INIS)

    The influence of total dose and dose rate pattern on the effects of inhaled β-emitting radionuclides is being studied in laboratory animals. The inhaled radionuclides were either in a relatively soluble form (90SrCl2, 144CeCl3, 91YCl3, or 137CsCl), or in a relatively insoluble form in fused aluminosilicate particles. The organs affected depend on the solubility and chemical characteristics of the radionuclides. Studies with young adult dogs are complemented by comparable studies in other species (mice, rats, and Syrian hamsters), with animals of different ages and animals repeatedly exposed to 144Ce. 12 references, 2 figures, 2 tables

  10. Subchronic Inhalation Toxicity Study of n-pentane in Rats

    OpenAIRE

    Kim, Jong-Kyu; Cho, Hae-Won; Han, Jeong-Hee; Lee, Sung-Bae; Chung, Yong-Hyun; Rim, Kyung-Taek; Yang, Jeong-Sun

    2012-01-01

    Objectives This study was conducted in order to obtain information concerning the health hazards that may result from a 13 week inhalation exposure of n-pentane in Sprague-Dawley rats. Methods This study was conducted in accordance with the Organization for Economic Co-operation and Development (OECD) guidelines for the testing of chemicals No. 413 'Subchronic inhalation toxicity: 90-day study (as revised in 2009)'. The rats were divided into 4 groups (10 male and 10 female rats in each group...

  11. A Study on Subchronic Inhalation Toxicity of 1-Chloropropane

    OpenAIRE

    Chung, Yong Hyun; HAN, Jeong Hee; Lee, Yong-Hoon

    2015-01-01

    This study was conducted to measure toxicity of 1-chloropropane (CAS No. : 540-54-5). According to the OECD Test Guideline 413 (Subchronic inhalation toxicity: 90-day study), SD rats were exposed to 0, 310, 1,250, and 5,000 ppm of 1-chloropropane for 6 h/day, 5 day/week for 13 weeks via whole-body inhalation. Mortality, clinical signs, body weights, food consumption, motor activity, ophthalmoscopy, hematology, serum chemistry, urinalysis, organ weights, gross and histopathological findings we...

  12. A perspective on the developmental toxicity of inhaled nanoparticles

    DEFF Research Database (Denmark)

    Hougaard, Karin Sørig; Campagnolo, Luisa; Chavatte-Palmer, Pascale; Tarrade, Anne; Rousseau-Ralliard, Delphine; Valentino, Sarah; Park, Margriet V. D. Z.; de Jong, Wim H.; Wolterink, Gerrit; Piersma, Aldert H.; Ross, Bryony L.; Hutchison, Gary R.; Hansen, Jitka Stilund; Vogel, Ulla Birgitte; Jackson, Petra; Slama, Rémy; Pietroiusti, Antonio; Cassee, Flemming R.

    This paper aimed to clarify whether maternal inhalation of engineered nanoparticles (NP) may constitute a hazard to pregnancy and fetal development, primarily based on experimental animal studies of NP and air pollution particles. Overall, it is plausible that NP may translocate from the respirat......This paper aimed to clarify whether maternal inhalation of engineered nanoparticles (NP) may constitute a hazard to pregnancy and fetal development, primarily based on experimental animal studies of NP and air pollution particles. Overall, it is plausible that NP may translocate from the......, significant amounts of groundwork are warranted for a testing strategy to be established on a sound scientific basis....

  13. Concept for motivating toddlers to accept inhalation therapy

    OpenAIRE

    Anton Segarra, Rebeca

    2013-01-01

    This master thesis is conducted at the Institute of Product Design at NTNU. The subject of the assignment is “Concept for motivating toddlers to accept inhalation therapy”. The project aims at developing a concept for motivating hospitalized toddlers (2-3 years old) to accept inhalation therapy. The first part of the project was an investigation process to understand the situation: the disease, the children’s behaviour at 2-3 years age, the hospital environment, the treatment, etc. Secondly I...

  14. Ozone Inhalation Provokes Glucocorticoid-Dependent and -Independent Effects on Inflammatory and Metabolic Pathways.

    Science.gov (United States)

    Thomson, Errol M; Pal, Shinjini; Guénette, Josée; Wade, Michael G; Atlas, Ella; Holloway, Alison C; Williams, Andrew; Vincent, Renaud

    2016-07-01

    Growing evidence implicates air pollutants in adverse health effects beyond respiratory and cardiovascular disease, including metabolic impacts (diabetes, metabolic syndrome, obesity) and neurological/neurobehavioral outcomes (neurodegenerative disease, cognitive decline, perceived stress, depression, suicide). We have shown that inhalation of particulate matter or ozone activates the hypothalamic-pituitary-adrenal axis in rats and increases plasma levels of the glucocorticoid corticosterone. To investigate the role of corticosterone in mediating inflammatory and metabolic effects of pollutant exposure, in this study male Fischer-344 rats were administered the 11β-hydroxylase inhibitor metyrapone (0, 50, 150 mg/kg body weight) and exposed by nose-only inhalation for 4 h to air or 0.8 ppm ozone. Ozone inhalation provoked a 2-fold increase in plasma corticosterone, an effect blocked by metyrapone, but did not alter epinephrine levels. Inhibition of corticosterone production was associated with increased inflammatory signaling in the lungs and plasma in response to ozone, consistent with a role for glucocorticoids in limiting local and systemic inflammatory responses. Effects of ozone on insulin and glucagon, but not ghrelin or plasminogen activator inhibitor-1, were modified by metyrapone, revealing glucocorticoid-dependent and -independent effects on circulating metabolic and hemostatic factors. Several immunosuppressive and metabolic impacts of ozone in the lungs, heart, liver, kidney, and spleen were blocked by metyrapone and reproduced through exogenous administration of corticosterone (10 mg/kg body weight), demonstrating glucocorticoid-dependent effects in target tissues. Our results support involvement of endogenous glucocorticoids in ozone-induced inflammatory and metabolic effects, providing insight into potential biological mechanisms underlying health impacts and susceptibility. PMID:27037194

  15. Absorption, distribution and excretion of inhaled hydrogen fluoride in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Morris, J.B.

    1979-01-01

    Rats were subjected to whole body HF exposure for 6 hrs or to nose-only HF exposure for 1 hr. Total and/or ionic fluoride concentrations in selected tissues were determined at various times following exposure. In rats sacrificed 6 hrs after whole body exposure, dose-dependent increases in lung, plasma, and kidney total and ionic fluoride concentration occurred. Rats excreted more fluoride in the urine after whole body exposure than could be explained by the amount of HF inhaled. Considerable evidence suggests that airborne HF deposits on fur and is then ingested due to preening activity. Urinary fluoride excretion was increased by nose-only exposure. The urinary fluoride excretion accounted for approximately twice the fluoride estimated to be inhaled during exposure. Tissue fluoride concentrations were elevated immediately after nose-only exposure. Fluoride concentrations in lung and kidney returned to control levels within 12 hrs. Plasma fluoride concentration was slightly elevated 24 hrs after the start of the 1 hr exposure but was at control levels at 96 hrs. Immediately following nose-only exposure, lung ionic fluoride concentrations were less than plasma ionic fluoride concentrations suggesting that the fluoride in the lung had reached that site via plasma transport rather than by inhalation. A dose-dependent increase in plasma ionic fluoride concentration occurred after upper respiratory tract HF exposure providing strong evidence that fluoride is absorbed systemically from that site. The plasma ionic fluoride concentration after upper respiratory tract exposure was of sufficient magnitude to account for the plasma fluoride concentrations observed in intact nose-only exposed rats. (ERB)

  16. Dietary and inhalation exposure to polycyclic aromatic hydrocarbons and urinary excretion of monohydroxy metabolites – A controlled case study in Beijing, China

    International Nuclear Information System (INIS)

    Daily dietary and inhalation exposures to 16 parent polycyclic aromatic hydrocarbons (PAHs) and urinary excretion of 13 monohydroxy metabolites (OHPAHs) were monitored for 12 non-smoking university students in Beijing, China, during a controlled feeding experiment. The relationship between the urinary excretion of OHPAHs and the uptake of PAHs was investigated. The results suggest severe exposure of the subjects to PAHs via both dietary and inhalation pathways. Large increase of most urinary OHPAHs occurred after the ingestion of lamb kabob. Higher concentrations of OHPAHs were observed for female subjects, with the intakes of parent PAHs lower than those by males, likely due to the gender differences in metabolism. It appears that besides 1-PYR, metabolites of PHE could also be used as biomarkers to indicate the short-term dietary exposure to PAHs and urinary 3-BaA may serve as the biomarker for inhalation intake of high molecular weight PAHs. Highlights: • The dependence of urinary OHPAHs on PAH intake was explored. • Consumption of lamb kabob resulted in large increase of most urinary OHPAHs. • Gender differences in PAH metabolism was observed. • Urinary metabolites of PHE and PYR can be used as biomarkers for dietary PAH intake. • Urinary 3-BaA may serve as the indicator for the inhalation exposure to BaPeq. -- Severe exposure to PAHs via dietary and inhalation pathways indicated by the intake of parent PAHs as well as the urinary excretion of OHPAHs, was observed for students in Beijing

  17. A double-blind comparison between a new multidose powder inhaler (Turbuhaler) and metered dose inhaler in children with asthma.

    Science.gov (United States)

    Hultquist, C; Ahlström, H; Kjellman, N I; Malmqvist, L A; Svenonius, E; Melin, S

    1989-09-01

    Turbuhaler is a ready-loaded multiple dose inhaler which does not require co-ordination between release of dose and inhalation. 57 children with asthma participated in this clinical trial to compare the clinical effect and acceptance of terbutaline sulphate via Turbuhaler with that of metered dose inhaler (MDI). The trial consisted of two parts. In the first part of the study, which made use of a double-blind cross-over design, the clinical effect and number of treatment occasions with Turbuhaler were compared with those of MDI. In the second part, which was open, all patients were treated with Turbuhaler for 2 weeks. At the end of this period the patients were asked to make a subjective assessment of effect and to state their preference. There was no difference in clinical effect and number of treatment occasions between Turbuhaler and MDI. A majority of the patients thought Turbuhaler had the best effect and was easy to use. PMID:2683835

  18. Acute Response of Right Ventricular Function to Iloprost Inhalations in Patients with Pulmonary Arterial Hypertension: Preliminary Evaluation 
with Cardiac Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Qingqing LU

    2015-03-01

    Full Text Available Background and objective Pulmonary arterial hypertension (PAH is a progressive disorder characterized by abnormally elevated blood pressure of the pulmonary circulation. Without treatment, PAH progresses rapidly to right ventricular (RV failure and even death. Cardiac magnetic resonance imaging (CMRI has been an accurate and reproducible tool to assessment of RV morphology and function, which are important factors in the prognosis of patients with PAH. The aim of this study is to investigate acute RV response to inhalation of aerosolized iloprost in patients with PAH using CMRI. Method From March 2012 to March 2014, 48 patients with PAH underwent CMRI before and immediately after inhalation of iloprost with a single dose of 20 μg over 15 min-20 min. RV function parameters derived from CMRI images were analyzed before and after iloprost inhalation, including end-diastolic volume (EDV, end-diastolic area (EDA, end-systolic volume (ESV, end-systolic area (ESA, stroke volume (SV, ejection fraction (EF and cardiac output (CO. Percentage of RV area change was also calculated [%RVAC=(EDA-ESA/EDA×100%]. Wilcoxon's Sign Rank Test or Paired Samples t-Test was used to compare the differences of RV function parameters before and after inhalation. Results After iloprost inhalation, all patients showed significant decrease in RV EDV and RV ESV (P=0.007, P<0.001 respectively. Whereas, there were significant increase in RV SV (P=0.014, RV EF (P=0.009 and %RVAC (P=0.006. RV CO had no significant difference before and after inhalation (P=0.851. Conclusions Inhalation of iloprost can immediately improve RV function in patients with PAH, and noninvasive evaluation of the acute response with CMRI is feasibility.

  19. Study of antioxidative effects and anti-inflammatory effects in mice due to low-dose X-irradiation or radon inhalation

    International Nuclear Information System (INIS)

    Low-dose irradiation induces various stimulating effects, especially activation of the biological defense system including antioxidative and immune functions. Oxidative stress induced by reactive oxygen species (ROS) can cause cell damage and death and can induce many types of diseases. This paper reviews new insights into inhibition of ROS-related diseases with low-dose irradiation or radon inhalation. X-irradiation (0.5 Gy) before or after carbon tetrachloride (CCl4) treatment inhibits hepatopathy in mice. X-irradiation (0.5 Gy) before ischemia-reperfusion injury or cold-induced brain injury also inhibits edema. These findings suggest that low-dose X-irradiation has antioxidative effects due to blocking the damage induced by free radicals or ROS. Moreover, radon inhalation increases superoxide dismutase activity in many organs and inhibits CCl4-induced hepatic and renal damage and streptozotocin-induced type I diabetes. These findings suggest that radon inhalation also has antioxidative effects. This antioxidative effect against CCl4-induced hepatopathy is comparable to treatment with ascorbic acid (vitamin C) at a dose of 500 mg/kg weight, or α-tocopherol (vitamin E) treatment at a dose of 300 mg/kg weight, and is due to activation of antioxidative functions. In addition, radon inhalation inhibits carrageenan-induced inflammatory paw edema, suggesting that radon inhalation has anti-inflammatory effects. Furthermore, radon inhalation inhibits formalin-induced inflammatory pain and chronic constriction injury-induced neuropathic pain, suggesting that radon inhalation relieves pain. Thus, low-dose irradiation very likely activates the defense systems in the body, and therefore, contributes to preventing or reducing ROS-related injuries, which are thought to involve peroxidation. (author)

  20. Study of antioxidative effects and anti-inflammatory effects in mice due to low-dose X-irradiation or radon inhalation.

    Science.gov (United States)

    Kataoka, Takahiro

    2013-07-01

    Low-dose irradiation induces various stimulating effects, especially activation of the biological defense system including antioxidative and immune functions. Oxidative stress induced by reactive oxygen species (ROS) can cause cell damage and death and can induce many types of diseases. This paper reviews new insights into inhibition of ROS-related diseases with low-dose irradiation or radon inhalation. X-irradiation (0.5 Gy) before or after carbon tetrachloride (CCl4) treatment inhibits hepatopathy in mice. X-irradiation (0.5 Gy) before ischemia-reperfusion injury or cold-induced brain injury also inhibits edema. These findings suggest that low-dose X-irradiation has antioxidative effects due to blocking the damage induced by free radicals or ROS. Moreover, radon inhalation increases superoxide dismutase activity in many organs and inhibits CCl4-induced hepatic and renal damage and streptozotocin-induced type I diabetes. These findings suggest that radon inhalation also has antioxidative effects. This antioxidative effect against CCl4-induced hepatopathy is comparable to treatment with ascorbic acid (vitamin C) at a dose of 500 mg/kg weight, or α-tocopherol (vitamin E) treatment at a dose of 300 mg/kg weight, and is due to activation of antioxidative functions. In addition, radon inhalation inhibits carrageenan-induced inflammatory paw edema, suggesting that radon inhalation has anti-inflammatory effects. Furthermore, radon inhalation inhibits formalin-induced inflammatory pain and chronic constriction injury-induced neuropathic pain, suggesting that radon inhalation relieves pain. Thus, low-dose irradiation very likely activates the defense systems in the body, and therefore, contributes to preventing or reducing ROS-related injuries, which are thought to involve peroxidation. PMID:23420683

  1. Profile of inhalant users seeking treatment at a de-addiction centre in north India

    OpenAIRE

    Sunil Gupta; Naresh Nebhinani; Debasish Basu; Surendra Kumar Mattoo

    2014-01-01

    Background & objectives: Inhalants are substances whose chemical vapors are inhaled to produce euphoric, disinhibiting, and exciting effects. Data on inhalant abuse in India are relatively scarce. We report the demographic and clinical profile of inhalant users among the treatment seekers at a Drug De-addiction and Treatment Centre in north India. Methods: The records of treatment seekers at the Drug De-addiction and Treatment Centre, over 10 years (2002-2011) were scanned to identify 92...

  2. Otters Increasing - Threats Increasing

    OpenAIRE

    Andreas Kranz

    1994-01-01

    In some parts of Central Europe populations of otters are apparently increasing. Until recently, no research was being conducted on the ecology of otters in mainly artificial habitats like fish farms. Otters are not only a new source of conflict requiring species management, but appear once again threatened by illegal hunting. Austria is dealing with this problem using compensation for otter damage, electric fencing and translocation of problem otters. Despite a rise in illegal killing, Austr...

  3. Lesão por inalação de fumaça Smoke inhalation injury

    Directory of Open Access Journals (Sweden)

    Rogério Souza

    2004-12-01

    Full Text Available A lesão inalatória é hoje a principal causa de morte nos pacientes queimados, motivo pelo qual se justifica o grande número de estudos publicados sobre o assunto. Os mecanismos envolvidos na gênese da lesão inalatória envolvem tanto os fatores de ação local quanto os de ação sistêmica, o que acaba por aumentar muito as repercussões da lesão. Atualmente, buscam-se ferramentas que permitam o diagnóstico cada vez mais precoce da lesão inalatória e ainda estratégias de tratamento que minimizem as conseqüências da lesão já instalada. Esta revisão aborda os mecanismos fisiopatológicos, os métodos diagnósticos e as estratégias de tratamento dos pacientes vítimas de lesão inalatória. Ressalta ainda as perspectivas terapêuticas em desenvolvimento.Inhalation injury is the main cause of death in burn patients and has therefore, understandably, been the subject of numerous published studies. The pathogenesis of inhalation injury involves both local and systemic mechanisms, thereby increasing the repercussions of the injury. The search for tools that would allow earlier diagnosis of inhalation injury and for treatment strategies to lessen its deleterious effects is ongoing. In this review, we describe the physiopathological mechanisms of inhalation injury, as well as the current diagnostic tools and treatment strategies used in patients suffering from inhalation injury. We also attempt to put experimental therapeutic approaches into perspective.

  4. Co-spray dried resveratrol and budesonide inhalation formulation for reducing inflammation and oxidative stress in rat alveolar macrophages.

    Science.gov (United States)

    Trotta, Valentina; Lee, Wing-Hin; Loo, Ching-Yee; Young, Paul M; Traini, Daniela; Scalia, Santo

    2016-04-30

    Oxidative stress is instrumental in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD). Novel therapeutic strategies that target macrophages, based on the use of antioxidant compounds, could be explored to improve corticosteroid responses in COPD patients. In this study, inhalable microparticles containing budesonide (BD) and resveratrol (RES) were prepared and characterized. This approach was undertaken to develop a multi-drug inhalable formulation with anti-oxidant and anti-inflammatory activities for treatment of chronic lung diseases. The inhalable microparticles containing different ratios of BD and RES were prepared by spray drying. The physico-chemical properties of the formulations were characterized in terms of surface morphology, particle size, physical and thermal stability. Additionally, in vitro aerosol performances of these formulations were evaluated with the multi-stage liquid impinger (MSLI) at 60 and 90l/min, respectively. The cytotoxicity effect of the formulations was evaluated using rat alveolar macrophages. The biological responses of alveolar macrophages in terms of cytokine expressions, nitric oxide (NO) production and free radical scavenging activities were also tested. The co-spray dried (Co-SD) microparticles of all formulations exhibited morphologies appropriate for inhalation administration. Analysis of the deposition profiles showed an increase in aerosol performance proportional to BD concentration. Cell viability assay demonstrated that alveolar macrophages could tolerate a wide range of RES and BD concentrations. In addition, RES and BD were able to decrease the levels of tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in lipopolysaccharide (LPS) induced alveolar macrophages. This study has successfully established the manufacture of Co-SD formulations of RES and BD with morphology and aerosol properties suitable for inhalation drug delivery, negligible in vitro toxicity and enhanced

  5. Germline mutation rates in mice following in utero exposure to diesel exhaust particles by maternal inhalation

    DEFF Research Database (Denmark)

    Ritz, Caitlin; Ruminski, Wojciech; Hougaard, Karin S.;

    2011-01-01

    The induction of inherited DNA sequence mutations arising in the germline (i.e., sperm or egg) of mice exposed in utero to diesel exhaust particles (DEPs) via maternal inhalation compared to unexposed controls was investigated in this study. Previous work has shown that particulate air pollutants...... maturity and mated with control CBA mice. The F2 descendents were collected and ESTR germline mutation rates were derived from full pedigrees (mother, father, offspring) of F1 male and female mice. We found no evidence for increased ESTR mutation rates in females exposed in utero to DEP relative to control...

  6. Effect of oxygen inhalation on systemic, central, and splanchnic haemodynamics in cirrhosis

    DEFF Research Database (Denmark)

    Møller, Søren; Becker, Povl Ulrik; Schifter, S; Abrahamsen, J; Henriksen, Jens Henrik

    1996-01-01

    patients with cirrhosis (n = 19). RESULTS: Spirometry was normal, but the carbon monoxide diffusing capacity (transfer factor) was significantly decreased, 18.8 ml.min-1.mmHg-1 (-32% of that predicted, p < 0.0001), and correlated significantly with the cardiac output (r = 0.78, p < 0.0005), plasma volume......BACKGROUND/AIMS: Patients with cirrhosis exhibit a hyperdynamic circulation with increased cardiac output and low arterial blood pressure. The aim of the present study was to assess the effects of oxygen inhalation on systemic, central, and splanchnic haemodynamics and vasoactive systems in...

  7. Persistent effects of Libby amphibole and amosite asbestos following subchronic inhalation in rats

    OpenAIRE

    Gavett, Stephen H; Parkinson, Carl U.; Willson, Gabrielle A.; Wood, Charles E.; Jarabek, Annie M.; Roberts, Kay C.; Kodavanti, Urmila P; Dodd, Darol E.

    2016-01-01

    Background Human exposure to Libby amphibole (LA) asbestos increases risk of lung cancer, mesothelioma, and non-malignant respiratory disease. This study evaluated potency and time-course effects of LA and positive control amosite (AM) asbestos fibers in male F344 rats following nose-only inhalation exposure. Methods Rats were exposed to air, LA (0.5, 3.5, or 25.0 mg/m3 targets), or AM (3.5 mg/m3 target) for 10 days and assessed for markers of lung inflammation, injury, and cell proliferation...

  8. Behavioral effects of essential oil of Citrus aurantium L. inhalation in rats

    OpenAIRE

    Mariana P. Leite; Jaime Fassin Jr.; Eliane M. F. Baziloni; Reinaldo N. Almeida; Rita Mattei; José R. Leite

    2008-01-01

    The orange essential oil (OEO) and its components obtained from Citrus aurantium L. (Rutaceae) has been attracting interest due to its sedative and relaxing actions. In the present study, rats previously exposed to OEO at the concentrations of 1.0%; 2.5% and 5.0%, w/w, by inhalation during 7 minutes in acrylic boxes were evaluated in two anxiety models: elevated plus maze (EPM) and open-field. The OEO at the concentration of 2.5% increased both the time of the animals in the open arms of the ...

  9. TARGETED DELIVERY OF INHALED PHARMACEUTICALS USING AN IN SILICO DOSIMETRY MODEL

    Science.gov (United States)

    We present an in silico dosimetry model which can be used for inhalation toxicology (risk assessment of inhaled air pollutants) and aerosol therapy ( targeted delivery of inhaled drugs). This work presents scientific and clinical advances beyond the development of the original in...

  10. Design and application of a new modular adapter for laser diffraction characterization of inhalation aerosols

    NARCIS (Netherlands)

    de Boer, Anne; Gjaltema, D; Hagedoorn, P; Schaller, M; Witt, W; Frijlink, H W

    2002-01-01

    An inhaler adapter has been designed for the characterization of the aerosol clouds from medical aerosol generators such as nebulizers, dry powder inhalers (dpis) and metered dose inhalers (mdis) with laser diffraction technology. The adapter has a pre-separator, for separation of large particles (i

  11. 21 CFR 250.100 - Amyl nitrite inhalant as a prescription drug for human use.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Amyl nitrite inhalant as a prescription drug for... Prescription Status of Specific Drugs § 250.100 Amyl nitrite inhalant as a prescription drug for human use. (a) Amyl nitrite inhalant has been available over-the-counter for emergency use by the patient in...

  12. Health hazards due to the inhalation of amorphous silica.

    Science.gov (United States)

    Merget, R; Bauer, T; Küpper, H U; Philippou, S; Bauer, H D; Breitstadt, R; Bruening, T

    2002-01-01

    Occupational exposure to crystalline silica dust is associated with an increased risk for pulmonary diseases such as silicosis, tuberculosis, chronic bronchitis, chronic obstructive pulmonary disease (COPD) and lung cancer. This review summarizes the current knowledge about the health effects of amorphous (non-crystalline) forms of silica. The major problem in the assessment of health effects of amorphous silica is its contamination with crystalline silica. This applies particularly to well-documented pneumoconiosis among diatomaceous earth workers. Intentionally manufactured synthetic amorphous silicas are without contamination of crystalline silica. These synthetic forms may be classified as (1) wet process silica, (2) pyrogenic ("thermal" or "fumed") silica, and (3) chemically or physically modified silica. According to the different physicochemical properties, the major classes of synthetic amorphous silica are used in a variety of products, e.g. as fillers in the rubber industry, in tyre compounds, as free-flow and anti-caking agents in powder materials, and as liquid carriers, particularly in the manufacture of animal feed and agrochemicals; other uses are found in toothpaste additives, paints, silicon rubber, insulation material, liquid systems in coatings, adhesives, printing inks, plastisol car undercoats, and cosmetics. Animal inhalation studies with intentionally manufactured synthetic amorphous silica showed at least partially reversible inflammation, granuloma formation and emphysema, but no progressive fibrosis of the lungs. Epidemiological studies do not support the hypothesis that amorphous silicas have any relevant potential to induce fibrosis in workers with high occupational exposure to these substances, although one study disclosed four cases with silicosis among subjects exposed to apparently non-contaminated amorphous silica. Since the data have been limited, a risk of chronic bronchitis, COPD or emphysema cannot be excluded. There is no study

  13. Health hazards due to the inhalation of amorphous silica

    International Nuclear Information System (INIS)

    Occupational exposure to crystalline silica dust is associated with an increased risk for pulmonary diseases such as silicosis, tuberculosis, chronic bronchitis, chronic obstructive pulmonary disease (COPD) and lung cancer. This review summarizes the current knowledge about the health effects of amorphous (non-crystalline) forms of silica. The major problem in the assessment of health effects of amorphous silica is its contamination with crystalline silica. This applies particularly to well-documented pneumoconiosis among diatomaceous earth workers. Intentionally manufactured synthetic amorphous silicas are without contamination of crystalline silica. These synthetic forms may be classified as (1) wet process silica, (2) pyrogenic (''thermal'' or ''fumed'') silica, and (3) chemically or physically modified silica. According to the different physico-chemical properties, the major classes of synthetic amorphous silica are used in a variety of products, e.g. as fillers in the rubber industry, in tyre compounds, as free-flow and anti-caking agents in powder materials, and as liquid carriers, particularly in the manufacture of animal feed and agrochemicals; other uses are found in toothpaste additives, paints, silicon rubber, insulation material, liquid systems in coatings, adhesives, printing inks, plastisol car undercoats, and cosmetics. Animal inhalation studies with intentionally manufactured synthetic amorphous silica showed at least partially reversible inflammation, granuloma formation and emphysema, but no progressive fibrosis of the lungs. Epidemiological studies do not support the hypothesis that amorphous silicas have any relevant potential to induce fibrosis in workers with high occupational exposure to these substances, although one study disclosed four cases with silicosis among subjects exposed to apparently non-contaminated amorphous silica. Since the data have been limited, a risk of chronic bronchitis, COPD or emphysema cannot be excluded. There is no

  14. Effect of 144Ce inhaled in fused clay particles on the tracheobronchial lymph nodes

    International Nuclear Information System (INIS)

    Tracheobronchial lymph node changes and lymphopenia are sequelae to inhalation of relatively insoluble radioactive aerosols by Beagle dogs. To assess the development of these lesions, tracheobronchial lymph nodes from dogs that inhaled 144Ce in fused clay particles were examined at intervals from 2 to 730 days after exposure. Initial lung burdens in the dogs studied ranged from 33 to 63 μCi/kg body weight. The concentration of radioisotope in the tracheobronchial lymph nodes increased during the first year after exposure and exceeded that in the lung about 100 days after exposure. Autoradiographs of the lymph nodes showed that 144Ce particles were present in macrophages in the paracortical zone two days after exposure and that concentrations continued to increase in the paracortical zone and medullary cords. Histologic changes in the nodes included atrophy of the germinal centers and lymphocytic follicles, loss of lymphocytes and accumulation of macrophages in the paracortical zone, accumulation of pigment and isotope-laden macrophages in the medullary cords, occasional infiltrates of neutrophils in the medullary cords and, at later time periods, focal fibrosis of the medullary cords. Tracheobronchial lymph node weights of the dogs exposed to 144Ce in fused clay were not decreased until 512 days after exposure. These findings indicate that tracheobronchial lymph nodes accumulate relatively high burdens of 144Ce after inhalation of 144Ce in a relatively insoluble form and that the pathologic changes resulting from these burdens are basically atrophic in nature. Primary neoplasms in lymph nodes have not been observed in dogs with initial lung burdens from 0.0024 to over 30 μCi/kg body weight followed for up to 2000 days post-exposure. At the higher levels, however, a high incidence of primary pulmonary neoplasia has been observed. (U.S.)

  15. INDOOR AIR QUALITY AND INHALATION EXPOSURE - SIMULATION TOOL KIT

    Science.gov (United States)

    A Microsoft Windows-based indoor air quality (IAQ) simulation software package is presented. Named Simulation Tool Kit for Indoor Air Quality and Inhalation Exposure, or IAQX for short, this package complements and supplements existing IAQ simulation programs and is desi...

  16. Inhaled budesonide for treatment of recurrent wheezing in early childhood

    DEFF Research Database (Denmark)

    Bisgaard, H; Munck, Susanne; Nielsen, J P; Petersen, W; Ohlsson, S V

    1990-01-01

    77 children, aged 11 to 36 months (mean 24) with moderately severe recurrent wheezing, were treated with budesonide pressurised aerosol 400 micrograms twice daily or placebo for 12 weeks in a double-blind, parallel-group trial. Aerosols were inhaled from a spacer with a facemask. Budesonide signi...

  17. Personal exposure to inhalable cement dust among construction workers.

    NARCIS (Netherlands)

    Peters, S.M.; Thomassen, Y.; Fechter-Rink, E.; Kromhout, H.

    2009-01-01

    Objective- A case study was carried out to assess cement dust exposure and its determinants among construction workers and for comparison among workers in cement and concrete production.Methods- Full-shift personal exposure measurements were performed and samples were analysed for inhalable dust and

  18. Disposition and biological effect of inhaled 85Kr

    International Nuclear Information System (INIS)

    Half-lives of approximately 5, 30, and 100 min were obtained for whole-body clearance of inhaled 85Kr in beagle dogs. Analysis showed the highest partition coefficients in lungs, bone marrow, and fat. Circulating blood elements were not lowered permanently after 85Kr exposures

  19. Liposomal budesonide for dry powder inhaler: Preparation and stabilization

    OpenAIRE

    Joshi, Mayank R.; Misra, Ambikanandhan

    2001-01-01

    The purpose of the study was to prepare stable liposomally entrapped budesonide (BUD) for a dry powder inhaler (DPI) formulation. BUD liposomes composed of egg phosphatidyl choline and cholesterol were prepared by lipid film hydration technique and sonicated to have the desired size (

  20. Drug interactions between inhaled corticosteroids and enzymatic inhibitors

    OpenAIRE

    Daveluy, Amélie; Raignoux, Cécile; Miremont-Salamé, Ghada; Girodet, Pierre-Olivier; Moore, Nicholas; Haramburu, Françoise; Molimard, Mathieu

    2009-01-01

    Drug interactions between inhaled corticosteroids and enzymatic inhibitors phone: +33-557-571561 (Daveluy, Amelie) (Daveluy, Amelie) Centre Regional de Pharmacovigilance, Hopital Pellegrin - 33076 - Bordeaux Cedex - FRANCE (Daveluy, Amelie) Unite 657, INSERM - Bordeaux - FRANCE (Daveluy, Amelie) Departement de Pharmacologie, CHU de Bordeaux - Bordeaux - FRANCE (Daveluy, Amelie) Centre Regional de Pharmacovigilance, Hopital Pellegrin - 33076...

  1. Inhaled Antibiotics for Gram-Negative Respiratory Infections.

    Science.gov (United States)

    Wenzler, Eric; Fraidenburg, Dustin R; Scardina, Tonya; Danziger, Larry H

    2016-07-01

    Gram-negative organisms comprise a large portion of the pathogens responsible for lower respiratory tract infections, especially those that are nosocomially acquired, and the rate of antibiotic resistance among these organisms continues to rise. Systemically administered antibiotics used to treat these infections often have poor penetration into the lung parenchyma and narrow therapeutic windows between efficacy and toxicity. The use of inhaled antibiotics allows for maximization of target site concentrations and optimization of pharmacokinetic/pharmacodynamic indices while minimizing systemic exposure and toxicity. This review is a comprehensive discussion of formulation and drug delivery aspects, in vitro and microbiological considerations, pharmacokinetics, and clinical outcomes with inhaled antibiotics as they apply to disease states other than cystic fibrosis. In reviewing the literature surrounding the use of inhaled antibiotics, we also highlight the complexities related to this route of administration and the shortcomings in the available evidence. The lack of novel anti-Gram-negative antibiotics in the developmental pipeline will encourage the innovative use of our existing agents, and the inhaled route is one that deserves to be further studied and adopted in the clinical arena. PMID:27226088

  2. Physico-chemical characterisation of surface modified particles for inhalation.

    Science.gov (United States)

    Stank, Katharina; Steckel, Hartwig

    2013-05-01

    Surface modification of drugs for inhalation is a possibility to influence interparticulate forces. This can be necessary to achieve a sufficient aerosolisation during powder inhalation as the cohesiveness of the micronised drug can be reduced. In addition, the interaction with propellants in pressurised metered dose inhaler can be changed. This can be used to improve the physical stability of the suspension based formulations. A dry particle coating process was used for the alteration of particle surfaces. The blending of micronised salbutamol sulphate (SBS) with different concentrations of magnesium stearate (Mgst) or glycerol monostearate (GMS) was followed by co-milling with an air jet mill. The powder properties were characterised by SEM, EDX, laser diffraction, BET and inverse gas chromatography. Physical mixtures generated by Turbula blending were compared to co-milled samples. A slight particle size reduction was determined. The Mgst deposition on SBS particles was detected by EDX measurements. The dispersive surface energy of SBS is lowered and the energy distribution is more homogenous for the co-milled samples. This study proves the application of co-milling for surface modification in the inhalation area. PMID:23518364

  3. FATE OF INHALED NITROGEN DIOXIDE IN ISOLATED PERFUSED RAT LUNG

    Science.gov (United States)

    The fate of inhaled NO2 was studied with isolated perfused rat lungs. The isolated lungs were exposed to 5 ppm NO2 for 90 min at a ventilation rate of 45 ml/min. The NO2 exposure had no adverse effects on the lungs as judged from their weights, glucose uptake, or lactate producti...

  4. Inhaled Voriconazole for Prevention of Invasive Pulmonary Aspergillosis▿

    OpenAIRE

    Tolman, Justin A; Wiederhold, Nathan P.; McConville, Jason T.; Najvar, Laura K.; Bocanegra, Rosie; Peters, Jay I.; Coalson, Jacqueline J.; Graybill, John R.; Patterson, Thomas F.; Williams, Robert O.

    2009-01-01

    Targeted airway delivery of antifungals as prophylaxis against invasive aspergillosis may lead to high lung drug concentrations while avoiding toxicities associated with systemically administered agents. We evaluated the effectiveness of aerosolizing the intravenous formulation of voriconazole as prophylaxis against invasive pulmonary aspergillosis caused by Aspergillus fumigatus in an established murine model. Inhaled voriconazole significantly improved survival and limited the extent of inv...

  5. NEW APPROACHES TO QUANTITATING THE PULMONARY EFFECTS OF INHALED POLLUTANTS

    Science.gov (United States)

    The authors have developed a variety of non-invasive and other techniques to study effects of inhaled pollutants on the lung. In the area of airway mechanics they have developed and applied a diameter gauge to make continuous measurements of large airways caliber. The gauge provi...

  6. Brugada syndrome unmasked by accidental inhalation of gasoline vapors

    DEFF Research Database (Denmark)

    Kranjcec, Darko; Bergovec, Mijo; Rougier, Jean-Sébastien;

    2007-01-01

    Loss-of-function mutations in the gene SCN5A can cause Brugada syndrome (BrS), which is an inherited form of idiopathic ventricular fibrillation. We report the case of a 46-year-old patient, with no previous medical history, who had ventricular fibrillation after accidental inhalation of gasoline...

  7. Spontaneous pneumothorax associated with talc pulmonary granulomatosis after cocaine inhalation.

    Science.gov (United States)

    Fiorelli, Alfonso; Accardo, Marina; Rossi, Francesco; Santini, Mario

    2016-03-01

    We report a case of recurrent spontaneous pneumothorax in a patient with cocaine abuse through inhalation alone. He underwent thoracoscopic apical lung resection with mechanical pleurodesis. Despite the lack of significant radiological features of talc induced pulmonary granulomatosis, pathological findings showed granulomas with foreign materials suggestive of being talc. Electronic microscopy showed that the size of talc particles were alveoli. PMID:24942102

  8. Infant with Altered Consciousness after Cannabis Passive Inhalation

    Science.gov (United States)

    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. Inhaled corticosteroids and Aspergillus fumigatus isolation in cystic fibrosis.

    Science.gov (United States)

    Noni, Maria; Katelari, Anna; Dimopoulos, George; Kourlaba, Georgia; Spoulou, Vana; Alexandrou-Athanassoulis, Helen; Doudounakis, Stavros-Eleftherios; Tzoumaka-Bakoula, Chryssa

    2014-10-01

    Aspergillus fumigatus isolation in cultures from respiratory specimens of patients with cystic fibrosis (CF) is quite common; however, the role of A. fumigatus as a pathogen and whether its presence is associated with progression of pulmonary disease remain unclear. We investigated the association between inhaled corticosteroids and the recovery of A. fumigatus by performing a retrospective cohort study of CF patients born between 1988 and 1996. The patients' medical records from their first visit to the CF Center until December 2010 were reviewed. Outcomes were the occurrence of A. fumigatus first isolation, chronic colonization, or the last visit at the CF Center. A number of possible confounders were included in the multivariate logistic regression analysis in order to identify an independent association between inhaled corticosteroids and colonization status. A total of 121 patients were included in the study. Thirty-nine patients (32.2%) had at least one positive culture and 14 (11.6%) developed chronic colonization. Multivariate logistic regression analysis was used to determine the independent effect of inhaled corticosteroids on the odds of first isolation (odds ratio [OR], 1.165; 95% confidence interval [CI], 1.015-1.337; P = 0.029) and chronic colonization (OR, 1.180; 95% CI, 1.029-1.353; P = 0.018). In conclusion, A. fumigatus first isolation and chronic colonization are associated with the duration of inhaled corticosteroid treatment. PMID:25056962

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

    Science.gov (United States)

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

    2009-09-01

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

  11. Comparison of efficacy of high dose inhaled corticosteroids with a combination of low dose inhaled corticosteroids and long acting AND#946;2 agonists in patients of moderate persistent asthma : a randomised prospective comparative study

    OpenAIRE

    Vivek Sood; Parveen Sharma; Rekha Bansal; Dinesh Kansal

    2016-01-01

    Background: Asthma has global prevalence varying from 2-25%. Among various subtypes, moderate persistent asthma is a subtype currently managed by a combination therapy of low dose inhaled corticosteroids and LABA (long acting beta2 agonists). Search is on for LABA free regime because of safety concerns and increased risk of exacerbations as reported in meta-analysis conducted by FDA in 2008. Methods: Patients (new and old) of either sex and age having moderate persistent asthma as per GINA...

  12. Cytokine expression in mice exposed to diesel exhaust particles by inhalation. Role of tumor necrosis factor

    Directory of Open Access Journals (Sweden)

    Loft Steffen

    2006-02-01

    Full Text Available Abstract Background Particulate air pollution has been associated with lung and cardiovascular disease, for which lung inflammation may be a driving mechanism. The pro-inflammatory cytokine, tumor necrosis factor (TNF has been suggested to have a key-role in particle-induced inflammation. We studied the time course of gene expression of inflammatory markers in the lungs of wild type mice and Tnf-/- mice after exposure to diesel exhaust particles (DEPs. Mice were exposed to either a single or multiple doses of DEP by inhalation. We measured the mRNA level of the cytokines Tnf and interleukin-6 (Il-6 and the chemokines, monocyte chemoattractant protein (Mcp-1, macrophage inflammatory protein-2 (Mip-2 and keratinocyte derived chemokine (Kc in the lung tissue at different time points after exposure. Results Tnf mRNA expression levels increased late after DEP-inhalation, whereas the expression levels of Il-6, Mcp-1 and Kc increased early. The expression of Mip-2 was independent of TNF if the dose was above a certain level. The expression levels of the cytokines Kc, Mcp-1 and Il-6, were increased in the absence of TNF. Conclusion Our data demonstrate that Tnf is not important in early DEP induced inflammation and rather exerts negative influence on Mcp-1 and Kc mRNA levels. This suggests that other signalling pathways are important, a candidate being one involving Mcp-1.

  13. Effects of 7.5% Carbon Dioxide Inhalation on Anxiety and Mood in Cigarette Smokers

    Science.gov (United States)

    Attwood, Angela S.; Ataya, Alia F.; Bailey, Jayne E.; Lightman, Stafford L.; Munafò, Marcus R.

    2016-01-01

    Cigarette smoking is associated with elevated risk of anxiety and mood disorder. Using the 7.5% carbon dioxide (CO2) inhalation model of anxiety induction, we examined the effects of smoking status and abstinence from smoking on anxiety responses. Physiological and subjective responses to CO2 and medical air were compared in smokers and non-smokers (Experiment One) and in overnight abstinent and non-abstinent smokers (Experiment Two). CO2 induced greater increases in blood pressure in non-smokers compared with smokers (ps < 0.043), and greater increases in anxiety (p = 0.005) and negative affect (p = 0.054) in non-abstinent compared with abstinent smokers. CO2 increased physiological and subjective indices of anxiety. There were differences across smoking groups indicating that the CO2 inhalation model is a useful tool for examining the relationship between smoking and anxiety. The findings suggested that both acute smoking and acute abstinence may protect against anxious responding. Further investigation is needed in long-term heavy smokers. PMID:24763184

  14. Subacute (28-day) toxicity of furfural in Fischer 344 rats: a comparison of the oral and inhalation route.

    Science.gov (United States)

    Arts, Josje H E; Muijser, Hans; Appel, Marko J; Frieke Kuper, C; Bessems, Jos G M; Woutersen, Ruud A

    2004-09-01

    The subacute oral and inhalation toxicity of furfural vapour was studied in Fischer 344 rats to investigate whether route-to-route extrapolation could be employed to derive the limit value for inhalation exposure from oral toxicity data. Groups of 5 rats per sex were treated by gavage daily for 28 days at dose levels of 6-192 mg/kg bw/day, or exposed by inhalation to concentrations of 20-1280 mg/m3 (6 h/day, 5 days/week) or 160-1280 mg/m3 (3 h/day, 5 days/week) for 28 days. Controls received vehicle (corn oil) or were exposed to clean air. Daily oral treatment with the highest dose of furfural (initially 192 mg/kg bw/day, later reduced to 144 mg/kg bw/day and finally to 120 mg/kg bw/day) resulted in mortality, and in increases in absolute and relative kidney and liver weight in surviving females of this group. Exposure of rats by inhalation for 6 h/day, 5 days/week for 28 days induced mortality at concentrations of 640 mg/m3 and above within 1-8 days. At 640 mg/m3 (3 h/day) and at 320 mg/m3 (3 and 6 h/day) and below, however, exposure was tolerated without serious clinical effects. In contrast, histopathological nasal changes were seen even at the lowest concentration of 20 mg/m3. With increasing exposure concentration, the nasal effects increased in incidence and severity and also expanded from the anterior part to the posterior part, including the olfactory epithelium. It was concluded that the no-observed-adverse-effect level (NOAEL) for oral toxicity was 96 mg/kg bw/day. The NOAEL for systemic inhalation toxicity was comparable, i.e. 92 mg/kg bw/day (corresponding to 320 mg/m3 (6 h/day) or 640 mg/m3 (3 h/day)) assuming 100% absorption. The presence of the histopathological nasal changes at the lowest tested concentration of 20 mg/m3 (corresponding to 6 mg/kg bw/day) proves that for locally acting substances like furfural extrapolation from the oral to the inhalation route is not valid. PMID:15234069

  15. Suppression of the pulmonary clearance of Staphylococcus aureus in mice that had inhaled either 144CeO2 or 239PuO2

    International Nuclear Information System (INIS)

    The rate of pulmonary clearance of inhaled Staphylococcus aureus in mice was determined at intervals after inhalation exposure to either 144CeO2 or 239PuO2. In mice with mean initial lung burdens between 0.6 and 4.7 μCi 144Ce the pulmonary clearance of S. aureus was suppressed up to 12 weeks after inhalation of 144CeO2. In mice with mean initial lung burdens between 1.3 and 29.0 μCi 239Pu the pulmonary clearance of S. aureus was suppressed up to 26 weeks after inhalation of 239PuO2. The suppressed pulmonary clearance of S. aureus appeared to correlate with the radiation dose rate to the lungs at the time of exposure to bacteria but not with the cumulative radiation dose to the lungs. The changes in bacterial clearance did not appear to be correlated with changes in body weight, hematological parameters, or radiation-induced histopathological changes. Altered bacterial clearance may be related to radiation damage to pulmonary macrophages. It was concluded that irradiation of the lung from radionuclides inhaled in relatively insoluble forms may result in increased bacterial invasion of the lungs

  16. Effects of Inhalation of Essential Oil of Citrus aurantium L. var. amara on Menopausal Symptoms, Stress, and Estrogen in Postmenopausal Women: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Seo Yeon Choi

    2014-01-01

    Full Text Available This study aimed to investigate the effects of inhalation of the essential oil of Citrus aurantium L. var. amara (neroli oil on menopausal symptoms, stress, and estrogen in postmenopausal women. Sixty-three healthy postmenopausal women were randomized to inhale 0.1% or 0.5% neroli oil or almond oil (control for 5 minutes twice daily for 5 days. Menopause-related symptoms, as determined by the Menopause-Specific Quality of Life Questionnaire (MENQOL; sexual desire visual analog scale (VAS; serum cortisol and estrogen concentrations, blood pressure, pulse, and stress VAS, were measured before and after inhalation. Compared with the control group, the two neroli oil groups showed significant improvements in the physical domain score of the MENQOL and in sexual desire. Systolic blood pressure was significantly lower in the group inhaling 0.5% neroli oil than in the control group. Compared with the control group, the two neroli oil groups showed significantly lower diastolic blood pressure and tended to improve pulse rate and serum cortisol and estrogen concentrations. These findings indicate that inhalation of neroli oil helps relieve menopausal symptoms, increase sexual desire, and reduce blood pressure in postmenopausal women. Neroli oil may have potential as an effective intervention to reduce stress and improve the endocrine system.

  17. Effects of Inhalation of Essential Oil of Citrus aurantium L. var. amara on Menopausal Symptoms, Stress, and Estrogen in Postmenopausal Women: A Randomized Controlled Trial.

    Science.gov (United States)

    Choi, Seo Yeon; Kang, Purum; Lee, Hui Su; Seol, Geun Hee

    2014-01-01

    This study aimed to investigate the effects of inhalation of the essential oil of Citrus aurantium L. var. amara (neroli oil) on menopausal symptoms, stress, and estrogen in postmenopausal women. Sixty-three healthy postmenopausal women were randomized to inhale 0.1% or 0.5% neroli oil or almond oil (control) for 5 minutes twice daily for 5 days. Menopause-related symptoms, as determined by the Menopause-Specific Quality of Life Questionnaire (MENQOL); sexual desire visual analog scale (VAS); serum cortisol and estrogen concentrations, blood pressure, pulse, and stress VAS, were measured before and after inhalation. Compared with the control group, the two neroli oil groups showed significant improvements in the physical domain score of the MENQOL and in sexual desire. Systolic blood pressure was significantly lower in the group inhaling 0.5% neroli oil than in the control group. Compared with the control group, the two neroli oil groups showed significantly lower diastolic blood pressure and tended to improve pulse rate and serum cortisol and estrogen concentrations. These findings indicate that inhalation of neroli oil helps relieve menopausal symptoms, increase sexual desire, and reduce blood pressure in postmenopausal women. Neroli oil may have potential as an effective intervention to reduce stress and improve the endocrine system. PMID:25024731

  18. Evidence of validity of an inhalant-craving questionnaire.

    Science.gov (United States)

    Alonso-Matías, Lizeth; Páez-Martínez, Nayeli; Reyes-Zamorano, Ernesto; González-Olvera, Jorge J

    2015-01-01

    Inhalants are substances widely used as recreational drugs: their addictive potential has been demonstrated by many studies. There is no reported measurable evidence of craving in inhalant users. The main goal of this study was to design and obtain evidence of validity of the score of a questionnaire for the evaluation of inhalant craving (ICQ) in a Mexican population sample. The ICQ is a type of visual analog scale with ten items. Face validity was evaluated by a group of experts in the addiction field. Reviewers considered the completeness, semantics, and sentence structure to guarantee a conceptual representation of the items. The final ICQ was applied to a sample of 520 Mexican high school students, 46% women and 54% men, between 12-19 years of age (M=15.18; SD=1.48), from 7th to 12th grades. The internal consistency of the ICQ showed a Cronbach's Alpha of 0.947. The 10 items were grouped into one single factor, with a factor loading above 0.74 for each of them. ROC analysis breakpoint was located at 18.5 mm with a sensitivity of 0.855 and specificity of 0.753. Thirty-three per cent (n= 172) of the student population evaluated reported the use of inhalants at some point in their lifetimes, with an average of misuse beginning at 13.6 years of age. The ICQ showed adequate psychometric properties, suggesting that the instrument may be considered a useful tool for screening for craving in young inhalant users. PMID:26706810

  19. CSACI position statement: systemic effect of inhaled corticosteroids on adrenal suppression in the management of pediatric asthma

    OpenAIRE

    Issa-El-Khoury, Karine; Kim, Harold; Chan, Edmond S; Vander Leek, Tim; Noya, Francisco

    2015-01-01

    Asthma is a chronic inflammatory disease of the airways that affects a growing number of children and adolescents. Inhaled corticosteroids (ICS) are the mainstay of treatment in persistent asthma, with a stepwise approach to increasing doses of ICS depending on asthma severity and control. ICS have known local and systemic side effects, of which adrenal suppression is still under-recognized. The latter is associated with chronic exposure and higher doses, although it has rarely been reported ...

  20. Sensitization to common food and inhalant allergens in children attending Allergy and Asthma Pediatric Clinic in Doha, Qatar

    OpenAIRE

    Kerkadi, Abdelhamid; Al-Thani, Asma; Al-Boainain, Amina; al Janahi, Ibrahim; Singh, Rajiv

    2009-01-01

    The prevalence of allergic diseases such as asthma, allergic rhinitis and atopic dermatitis have risen at an alarming rate throughout the world in the past 50 years. Sensitization to food (FA) and inhalant allergens (IA) have been associated with an increase of allergic diseases. The objective of this study was to estimate the prevalence of sensitization to FA and IA among children attending Allergy and Asthma Pediatric Clinic in Doha, Qatar. A total of 134 children with age between 1 mont...

  1. Impact of different combinations of inhaled corticosteroids and long-acting sympathicomimetics on dental health of asthmatics.

    OpenAIRE

    George Christoff; Emilia Karova

    2012-01-01

    The aim of the investigation is to study the effect of inhaled corticosteroids and long-acting sympathicomimetics on dental health in asthmatics. Thirty patients, from 20 to 55 years old, participate in the study. D-, M-, F- and DMFT indexes are determined in a 6 months period. All participants fill in a questionnaire. Asthmatics complain most frequently from oral dryness, take frequently sugar and soft drinks and visit irregularly dental practitioners. A significant increase in M-index is fo...

  2. Analytical method for internal dose determination caused by chronically radionuclides inhalation to respiration system

    International Nuclear Information System (INIS)

    Analytical method for internal dose determination caused by chronically radionuclides inhalation to respiratory system with the constant rate of radionuclide concentration inhaled has been developed. The dose calculation is solved solved analytically using distribution and accumulation of radionuklida model in respiratory system. A computer program was then made to calculate internal dose in respiratory system easily and quickly. Computer program is arranged using Borland C++ 4.5 language. The value of internal dose on time t after inhalation depend on the radionuclides, the half time ,radionuclides AMAD, radionuclides class, radiation type, energy absorbed by respiratory organ, organ mass, the radionuclides concentration inhaled, the inhalation period

  3. Inhalation Toxicology Research Institute annual report, October 1, 1993--September 30, 1994

    Energy Technology Data Exchange (ETDEWEB)

    Belinsky, S. A.; Hoover, M. D.; Bradley, P. L. [eds.

    1994-11-01

    This document from the Inhalation Toxicology Research Institute includes annual reports in the following general areas: (I) Aerosol Technology and Characterization of Airborne Materials; (II) Deposition, transport, and clearance of inhaled Toxicants; (III) Metabolism and Markers of Inhaled Toxicants; (IV) Carcinogenic Responses to Toxicants; (V) Mechanisms of carcinogenic response to Toxicants; (VI) Non carcinogenic responses to inhaled toxicants; (VII) Mechanisms of noncarcinogenic Responses to Inhaled Toxicants; (VIII) The application of Mathematical Modeling to Risk Estimates. 9 appendices are also included. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.

  4. Inhalation Toxicology Research Institute annual report, October 1, 1993--September 30, 1994

    International Nuclear Information System (INIS)

    This document from the Inhalation Toxicology Research Institute includes annual reports in the following general areas: (I) Aerosol Technology and Characterization of Airborne Materials; (II) Deposition, transport, and clearance of inhaled Toxicants; (III) Metabolism and Markers of Inhaled Toxicants; (IV) Carcinogenic Responses to Toxicants; (V) Mechanisms of carcinogenic response to Toxicants; (VI) Non carcinogenic responses to inhaled toxicants; (VII) Mechanisms of noncarcinogenic Responses to Inhaled Toxicants; (VIII) The application of Mathematical Modeling to Risk Estimates. 9 appendices are also included. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database

  5. Plasma concentrations of fluticasone propionate and budesonide following inhalation from dry powder inhalers by healthy and asthmatic subjects

    OpenAIRE

    Harrison, T; Tattersfield, A

    2003-01-01

    Methods: The area under the plasma concentration-time curves (AUC) and the maximum concentration (Cmax) of fluticasone propionate and budesonide after a single inhaled dose of each drug were compared in 12 healthy control subjects and 12 subjects with moderately severe asthma.

  6. Effect of alpha-tocopherol on pulmonary antioxidant defence system and lipid peroxidation in cigarette smoke inhaling mice

    Directory of Open Access Journals (Sweden)

    Bhatia Vipin

    2001-11-01

    Full Text Available Abstract Background Free radicals generated in biological systems by cigarette smoke (CS inhalation can cause oxidative stress in tissues, resulting in lipid peroxidation (LPO. In view of the antioxidant properties of α-tocopherol (AT, in the present study, effects of AT on antioxidant defence system and LPO were investigated in mice inhaling CS for different time intervals. Results Male Balb/c mice were fed orally with AT (5 I.U./Kg.b.wt. and /or exposed to CS for 2, 4, 6 or 8 weeks. No effect was observed on body growth, diet consumption, water intake and lung weight due to AT and /or CS treatment in any of the groups as compared to their control counterparts. After two weeks of treatment, no change in LPO, reduced glutathione (GSH levels and antioxidant enzymes were observed except for glutathione reductase (GR which increased in all the treated groups. A significant increase in pulmonary LPO levels was observed in mice exposed to CS inhalation for 4, 6 or 8 weeks. There was a gradual increase in the LPO levels as the extent of CS inhalation increased from 4 to 8 weeks. However, the extent of increase in LPO levels due to CS exposure for 4, 6 or 8 weeks in the mice treated with AT was comparatively less. A significant decrease in the GSH levels was also observed in all the animals exposed to CS for 4, 6 or 8 weeks. There was a significant increase in the activities of catalase, glutathione peroxidase (GSH-Px and GR observed in all the groups exposed to CS for 4,6 or 8 weeks. The increase in above antioxidant enzymes seems to be insufficient to combat the oxidative stress posed by CS inhalation. There was a marked decrease observed in the LPO levels in the animals treated with AT alone for 4, 6, or 8 weeks, when compared to their control counterparts. However, the supplementation of AT for 4, 6 or 8 weeks demonstrated a significant increase in GSH levels. Conclusion It appears from our studies that AT exhibits its antioxidant role either

  7. Population pharmacokinetic and pharmacodynamic modeling of epinephrine administered using a mobile inhaler.

    Science.gov (United States)

    Frechen, Sebastian; Suleiman, Ahmed Abbas; Mohammad Nejad Sigaroudi, Ali; Wachall, Bertil; Fuhr, Uwe

    2015-12-01

    Inhaled epinephrine is a potential alternative to self-administered intramuscular epinephrine in imminent anaphylactic reactions. The objective was to develop a pharmacokinetic-pharmacodynamic model describing exposure and effects on heart rate of inhaled epinephrine. Data from a 4-phase cross-over clinical trial in 9 healthy volunteers including 0.3 mg intramuscular epinephrine, two doses of inhaled epinephrine (4 mg/mL solution administered during [mean] 18 and 25 min, respectively) using a mobile pocket inhaler, and an inhaled placebo were analyzed using mixed-effects modeling. Inhaled epinephrine was available almost immediately and more rapidly than via the intramuscular route (absorption half-live 29 min). Epinephrine plasma concentrations declined rapidly after terminating inhalation (elimination half-life 4.1 min) offering the option to stop exposure in case of adverse events. While the expected maximum concentration was higher for inhaled epinephrine, this was not associated with safety concerns due to only moderate additional hemodynamic effects compared to intramuscular administration. Bioavailability after inhalation (4.7%) was subject to high interindividual and interoccasional variability highlighting that training of inhalation would be essential for patients. The proposed model suggests that the use of a highly concentrated epinephrine solution via inhalation may offer an effective treatment option in anaphylaxis, while efficacy in patients remains to be shown. PMID:26615448

  8. Inhaled Methane Limits the Mitochondrial Electron Transport Chain Dysfunction during Experimental Liver Ischemia-Reperfusion Injury

    Science.gov (United States)

    Strifler, Gerda; Tuboly, Eszter; Szél, Edit; Kaszonyi, Enikő; Cao, Chun; Kaszaki, József; Mészáros, András; Boros, Mihály; Hartmann, Petra

    2016-01-01

    Background Methanogenesis can indicate the fermentation activity of the gastrointestinal anaerobic flora. Methane also has a demonstrated anti-inflammatory potential. We hypothesized that enriched methane inhalation can influence the respiratory activity of the liver mitochondria after an ischemia-reperfusion (IR) challenge. Methods The activity of oxidative phosphorylation system complexes was determined after in vitro methane treatment of intact liver mitochondria. Anesthetized Sprague-Dawley rats subjected to standardized 60-min warm hepatic ischemia inhaled normoxic air (n = 6) or normoxic air containing 2.2% methane, from 50 min of ischemia and throughout the 60-min reperfusion period (n = 6). Measurement data were compared with those on sham-operated animals (n = 6 each). Liver biopsy samples were subjected to high-resolution respirometry; whole-blood superoxide and hydrogen peroxide production was measured; hepatocyte apoptosis was detected with TUNEL staining and in vivo fluorescence laser scanning microscopy. Results Significantly decreased complex II-linked basal respiration was found in the normoxic IR group at 55 min of ischemia and a lower respiratory capacity (~60%) and after 5 min of reperfusion. Methane inhalation preserved the maximal respiratory capacity at 55 min of ischemia and significantly improved the basal respiration during the first 30 min of reperfusion. The IR-induced cytochrome c activity, reactive oxygen species (ROS) production and hepatocyte apoptosis were also significantly reduced. Conclusions The normoxic IR injury was accompanied by significant functional damage of the inner mitochondrial membrane, increased cytochrome c activity, enhanced ROS production and apoptosis. An elevated methane intake confers significant protection against mitochondrial dysfunction and reduces the oxidative damage of the hepatocytes. PMID:26741361

  9. Reducing the cytotoxicity of inhalable engineered nanoparticles via in situ passivation with biocompatible materials

    Energy Technology Data Exchange (ETDEWEB)

    Byeon, Jeong Hoon, E-mail: postjb@yu.ac.kr [School of Mechanical Engineering, Yeungnam University, Gyeongsan 712-749 (Korea, Republic of); Park, Jae Hong; Peters, Thomas M. [Department of Occupational and Environmental Health, University of Iowa, IA 52242 (United States); Roberts, Jeffrey T., E-mail: jtrob@purdue.edu [Department of Chemistry, Purdue University, IN 47907 (United States)

    2015-07-15

    Highlights: • The cytotoxicity of model welding particles was modulated through in situ passivation. • Model welding particles were incorporated with chitosan nanoparticles for passivation. • In vitro assay revealed that the passivated particles had a lower cytotoxicity. • Passivation with chitosan adhesive or graphite paste could also reduce cytotoxicity. • This method would be suitable for efficient reduction of inhalable toxic components. - Abstract: The cytotoxicity of model welding nanoparticles was modulated through in situ passivation with soluble biocompatible materials. A passivation process consisting of a spark discharge particle generator coupled to a collison atomizer as a co-flow or counter-flow configuration was used to incorporate the model nanoparticles with chitosan. The tested model welding nanoparticles are inhaled and that A549 cells are a human lung epithelial cell line. Measurements of in vitro cytotoxicity in A549 cells revealed that the passivated nanoparticles had a lower cytotoxicity (>65% in average cell viability, counter-flow) than the untreated model nanoparticles. Moreover, the co-flow incorporation between the nanoparticles and chitosan induced passivation of the nanoparticles, and the average cell viability increased by >80% compared to the model welding nanoparticles. As a more convenient way (additional chitosan generation and incorporation devices may not be required), other passivation strategies through a modification of the welding rod with chitosan adhesive and graphite paste did also enhance average cell viability (>58%). The approach outlined in this work is potentially generalizable as a new platform, using only biocompatible materials in situ, to treat nanoparticles before they are inhaled.

  10. Metabolomic changes in murine serum following inhalation exposure to gasoline and diesel engine emissions.

    Science.gov (United States)

    Brower, Jeremy B; Doyle-Eisele, Melanie; Moeller, Benjamin; Stirdivant, Steven; McDonald, Jacob D; Campen, Matthew J

    2016-04-01

    The adverse health effects of environmental exposure to gaseous and particulate components of vehicular emissions are a major concern among urban populations. A link has been established between respiratory exposure to vehicular emissions and the development of cardiovascular disease (CVD), but the mechanisms driving this interaction remain unknown. Chronic inhalation exposure to mixed vehicle emissions has been linked to CVD in animal models. This study evaluated the temporal effects of acute exposure to mixed vehicle emissions (MVE; mixed gasoline and diesel emissions) on potentially active metabolites in the serum of exposed mice. C57Bl/6 mice were exposed to a single 6-hour exposure to filtered air (FA) or MVE (100 or 300 μg/m(3)) by whole body inhalation. Immediately after and 18 hours after the end of the exposure period, animals were sacrificed for serum and tissue collection. Serum was analyzed for metabolites that were differentially present between treatment groups and time points. Changes in metabolite levels suggestive of increased oxidative stress (oxidized glutathione, cysteine disulfide, taurine), lipid peroxidation (13-HODE, 9-HODE), energy metabolism (lactate, glycerate, branched chain amino acid catabolites, butrylcarnitine, fatty acids), and inflammation (DiHOME, palmitoyl ethanolamide) were observed immediately after the end of exposure in the serum of animals exposed to MVE relative to those exposed to FA. By 18 hours post exposure, serum metabolite differences between animals exposed to MVE versus those exposed to FA were less pronounced. These findings highlight complex metabolomics alterations in the circulation following inhalation exposure to a common source of combustion emissions. PMID:27017952

  11. Reducing the cytotoxicity of inhalable engineered nanoparticles via in situ passivation with biocompatible materials

    International Nuclear Information System (INIS)

    Highlights: • The cytotoxicity of model welding particles was modulated through in situ passivation. • Model welding particles were incorporated with chitosan nanoparticles for passivation. • In vitro assay revealed that the passivated particles had a lower cytotoxicity. • Passivation with chitosan adhesive or graphite paste could also reduce cytotoxicity. • This method would be suitable for efficient reduction of inhalable toxic components. - Abstract: The cytotoxicity of model welding nanoparticles was modulated through in situ passivation with soluble biocompatible materials. A passivation process consisting of a spark discharge particle generator coupled to a collison atomizer as a co-flow or counter-flow configuration was used to incorporate the model nanoparticles with chitosan. The tested model welding nanoparticles are inhaled and that A549 cells are a human lung epithelial cell line. Measurements of in vitro cytotoxicity in A549 cells revealed that the passivated nanoparticles had a lower cytotoxicity (>65% in average cell viability, counter-flow) than the untreated model nanoparticles. Moreover, the co-flow incorporation between the nanoparticles and chitosan induced passivation of the nanoparticles, and the average cell viability increased by >80% compared to the model welding nanoparticles. As a more convenient way (additional chitosan generation and incorporation devices may not be required), other passivation strategies through a modification of the welding rod with chitosan adhesive and graphite paste did also enhance average cell viability (>58%). The approach outlined in this work is potentially generalizable as a new platform, using only biocompatible materials in situ, to treat nanoparticles before they are inhaled

  12. Subchronic inhalation of zinc sulfate induces cardiac changes in healthy rats

    International Nuclear Information System (INIS)

    Zinc is a common metal in most ambient particulate matter (PM), and has been proposed to be a causative component in PM-induced adverse cardiovascular health effects. Zinc is also an essential metal and has the potential to induce many physiological and nonphysiological changes. Most toxicological studies employ high levels of zinc. We hypothesized that subchronic inhalation of environmentally relevant levels of zinc would cause cardiac changes in healthy rats. To address this, healthy male WKY rats (12 weeks age) were exposed via nose only inhalation to filtered air or 10, 30 or 100 μg/m3 of aerosolized zinc sulfate (ZnSO4), 5 h/day, 3 days/week for 16 weeks. Necropsies occurred 48 h after the last exposure to ensure effects were due to chronic exposure rather than the last exposure. No significant changes were observed in neutrophil or macrophage count, total lavageable cells, or enzyme activity levels (lactate dehydrogenase, n-acetyl β-D-glucosaminidase, γ-glutamyl transferase) in bronchoalveolar lavage fluid, indicating minimal pulmonary effect. In the heart, cytosolic glutathione peroxidase activity decreased, while mitochondrial ferritin levels increased and succinate dehydrogenase activity decreased, suggesting a mitochondria-specific effect. Although no cardiac pathology was seen, cardiac gene array analysis indicated small changes in genes involved in cell signaling, a pattern concordant with known zinc effects. These data indicate that inhalation of zinc at environmentally relevant levels induces cardiac effects. While changes are small in healthy rats, these may be especially relevant in individuals with pre-existent cardiovascular disease

  13. HRCT and bronchial asthma: visualization of the pathophysiologic changes of the pulmonary parenchyma after inhalation provocation

    International Nuclear Information System (INIS)

    Purpose: To characterize parenchymal lung affections morphologically in patients with asthma and healthy subjects by high resolution computed tomography (HRCT) subsequent to histamine-triggered inhalation bronchoprovocation and salbutamolinduced broncholysis, and to compare the results with pulmonary function tests. Materials and Methods: Fifteen asthmatics with bronchial hyperreactivity, with a>20% decrease in FEV1 and a>10 mmHg decrease in PaO2 after bronchoprovocation (PC20%+), twelve asthmatics with a10 mmHg decrease in PaO2 after bronchoprovocation (PC20%-), and eight healthy persons without bronchial hyperreactivity underwent inhalation bronchoprovocation and broncholysis. Spirometer-triggered HRCT at high lung volumes was performed, and total and peripheral lung densities and the amount of solid lung structures, representing predominantly vessels, were measured. Results: After bronchoprovocation, we observed significant decreases in total and peripheral lung densities in all groups (p0.05), as compared to the baseline measurements. In hyperreactive patients, PaO2 significantly decreased after provocation and significantly increased after lysis (p<0.05). In PC20%+ asthmatics, a mean reduction of 27.8% in FEV1 was observed, which was <20% in the other groups. No significant correlations were observed between radiological data and the results of pulmonary function tests. In healthy persons, we demonstrated highly significant parenchymal response to bronchoprovocation and broncholysis, which was not otherwise documented by pulmonary function tests. Conclusion: In both PC20%+ and PC20%- patients as well as in healthy individuals, HRCT was efficient in the evaluation of pathoanatomical alterations of the lung parenchyma subsequent to inhalation provocation. In healthy individuals, these parenchymal alterations were not documented by pulmonary function tests. (orig.)

  14. A method for determination of the absolute pulmonary bioavailability of inhaled drugs: Terbutaline

    International Nuclear Information System (INIS)

    Terbutaline sulfate (4 X 0.250 mg) was given to 11 healthy volunteers by inhalation from a metered dose inhaler (MDI), with and without oral administration of a charcoal slurry. Before the inhalations, the adsorbing capacity of the charcoal slurry was tested. Deuterated terbutaline, 0.125 mg, was given intravenously at the same time as the test doses. The charcoal slurry adsorbed 97% of an oral dose. The oral contribution to the overall systemic bioavailability after inhalation, when charcoal was coadministered, could thus be neglected. After inhalation of terbutaline, 9.1% of the dose was deposited in the lungs and an additional 6.7% was systemically available via the oral route. The method presented measures the absolute pulmonary bioavailability after inhalation from a MDI. Since a deuterated analogue is given intravenously together with the inhalations, fewer subjects are needed to obtain reliable data

  15. Inhaled Foreign Bodies In Pediatric Patients: Proven Management Techniques In The Emergency Department.

    Science.gov (United States)

    Maraynes, Megan; Agoritsas, Konstantinos

    2015-10-01

    Foreign body inhalation affects thousands of children every year, and it remains a significant cause of morbidity and mortality in children. Inhaled organic or inorganic foreign bodies can become lodged in the posterior nasopharynx, larynx, trachea, or bronchi. Presentation of foreign body inhalation can range from nonspecific respiratory symptoms to respiratory failure associated with a choking episode. In this issue, an in-depth review of the etiology, pathophysiology, diagnosis, and treatment of inhaled foreign bodies is presented. Risk factors for foreign body inhalation and clinical clues to diagnosis, as well as emergent management of inhaled foreign bodies are reviewed. A systematic approach, as described in this issue, will aid in timely and accurate diagnosis and treatment of inhaled foreign bodies, thereby limiting future complications and morbidity. PMID:26510331

  16. Genuair® in chronic obstructive pulmonary disease: a novel, user-friendly, multidose, dry-powder inhaler

    NARCIS (Netherlands)

    Palen, van der Job

    2014-01-01

    Inhaled corticosteroids and bronchodilators, which are pivotal to the management of respiratory diseases, are delivered by numerous devices, including pressurized metered-dose inhalers and dry-powder inhalers. However, patient adherence to these medications is suboptimal and incorrect inhaler techni

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

    DEFF Research Database (Denmark)

    van Aalderen, W. M.; Garcia-Marcos, L.; Gappa, M.;

    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 inhale...

  18. Rat inhalation test with particles from biomass combustion and biomass co-firing exhaust

    International Nuclear Information System (INIS)

    The health effects of 6 different fly ash samples from biomass combustion plants (bark, wood chips, waste wood, and straw), and co-firing plants (coal, co-firing of coal and sawdust) were investigated in a 28-day nose-only inhalation study with Wistar WU rats. Respirable fractions of carbon black (Printex 90) and of titanium dioxide (Bayertitan T) were used as reference materials for positive and negative controls. The exposure was done 6 hours per day, 5 days per week at an aerosol concentration of 16 mg/m3. The MMAD of all fly ash samples and reference materials in the inhalation unit were in the range from 1.5 to 3 μm. The investigations focused predominantly on the analysis of inflammatory effects in the lungs of rats using bronchoalveolar lavage (BAL) and histopathology. Different parameters (percentage of polymorphonuclear neutrophils (PMN), interleukin-8 and interstitial inflammatory cell infiltration in the lung tissue) indicating inflammatory effects in the lung, showed a statistically significant increase in the groups exposed to carbon black (positive control), C1 (coal) and C1+BM4 (co-firing of coal and sawdust) fly ashes. Additionally, for the same groups a statistically significant increase of cell proliferation in the lung epithelium was detected. No significant effects were detected in the animal groups exposed to BM1 (bark), BM2 (wood chips), BM3 (waste wood), BM6 (straw) or titanium dioxide.

  19. Inhalant substance abuse among adolescents in Manipur, India: An upcoming issue

    Directory of Open Access Journals (Sweden)

    Rajkumari Bishwalata

    2014-07-01

    Full Text Available Background: Inhalant use, an important, yet-under recognized form of substance abuse has been reported commonly among adolescents in India but the true extent of the problem is not known due to paucity of data. Aims: To assess the prevalence and determinants of inhalant substance used amongst the adolescents in Manipur. Settings and Design: This cross sectional study was conducted among 1671 adolescent studying in Eighth to Twelfth standard in schools of Imphal-East District Manipur, India during March to June 2013. Materials and Methods: Schools were selected by simple random method and a semi-structured self-administered questionnaire adapted from the 'UNDCP/WHO Global initiative on Primary Prevention of substance abuse' was used for data collection. Univariate and Multiple logistic regression analysis were performed for association between ever users and selected variables. Results: Mean (SD age of the students was 14.5(1.32 years, with males constituting 923(55.2%. Prevalence of ever users was186 (11.1% and glue/dendrite was the commonest substance abused 98(52.7%. Being male, belonging to joint family and increase in age were found to have significant higher risk of being a user, whereas higher level of parental education shows a protective effect. Conclusion: An increased effort for prevention, treatment along with sensitization of parents and teachers is a distinct challenge for policy makers.

  20. Lung changes in rats following inhalation exposure to volcanic ash for two years

    Energy Technology Data Exchange (ETDEWEB)

    Wehner, A.P.; Dagle, G.E.; Clark, M.L.; Buschbom, R.L.

    1986-08-01

    Rats were exposed by inhalation to 5 or 50 mg/m/sup 3/ Mount St. Helens volcanic ash, to 50 mg/m/sup 3/ quartz (positive controls), or to filtered room air (sham-exposed controls), for 6 hr/day, 5 days/week, for up to 24 months to investigate biological effects of chronic inhalation exposure to volcanic ash under controlled laboratory conditions. Exposure-related lung changes comprised accelerated respiratory frequency; alveolar macrophage accumulation; interstitial reaction; lymphoreticular reaction in peribronchiolar regions and in mediastinal lymph nodes; alveolar proteinosis in the 50- mg/m/sup 3/ ash- or quartz-exposed groups; increase in fresh lung weights; decreased body weight and increased mortality in the quartz-exposed group; and epidermoid carcinomas especially in the quartz-exposed females and, to a lesser extent, in the 50-mg/m/sup 3/ ash-exposed females. The observed changes reflect significant dose-response and agent-response relationships.