Sample records for salbutamol administrado como
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Treatment of proctalgia fugax with salbutamol inhalation.
Eckardt, V F; Dodt, O; Kanzler, G; Bernhard, G
1996-04-01
Although no generally effective treatment for proctalgia fugax is known, inhalation of salbutamol has been reported to shorten pain attacks in isolated cases. We conducted a randomized, double-blind, placebo-controlled, crossover trial of inhaled salbutamol in 18 patients with proctalgia fugax. The clinical effect was evaluated by recording the duration of severe pain and discomfort during acute attacks. In addition, anorectal motility recordings were analyzed for possible changes in anal resting tone, sphincter relaxation during rectal distension and in rectal compliance prior to and following administration of the two test substances. Sixteen patients completed all investigations. Compared to placebo, salbutamol inhalation shortened the duration of severe pain (p = 0.019). The effect was most marked in patients having prolonged attacks. In the asymptomatic state, neither salbutamol nor placebo led to a significant change in anal resting pressure, anal relaxation during rectal distension, or rectal compliance. Salbutamol also did not alter the threshold for rectal sensation. Salbutamol inhalation shortens attacks of severe pain in patients with proctalgia fugax. The mechanism of this effect remains unexplained.
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Corrigan, Deirdre O; Corrigan, Owen I; Healy, Anne Marie
2006-09-28
The physicochemical and aerodynamic properties of spray dried powders of the drug/drug mixture salbutamol sulphate/ipratropium bromide were investigated. The in vitro deposition properties of spray dried salbutamol sulphate and the spray dried drug/excipient mixtures salbutamol sulphate/lactose and salbutamol sulphate/PEG were also determined. Spray drying ipratropium bromide monohydrate resulted in a crystalline material from both aqueous and ethanolic solution. The product spray dried from aqueous solution consisted mainly of ipratropium bromide anhydrous. There was evidence of the presence of another polymorphic form of ipratropium bromide. When spray dried from ethanolic solution the physicochemical characterisation suggested the presence of an ipratropium bromide solvate with some anhydrous ipratropium bromide. Co-spray drying salbutamol sulphate with ipratropium bromide resulted in amorphous composites, regardless of solvent used. Particles were spherical and of a size suitable for inhalation. Twin impinger studies showed an increase in the fine particle fraction (FPF) of spray dried salbutamol sulphate compared to micronised salbutamol sulphate. Co-spray dried salbutamol sulphate:ipratropium bromide 10:1 and 5:1 systems also showed an increase in FPF compared to micronised salbutamol sulphate. Most co-spray dried salbutamol sulphate/excipient systems investigated demonstrated FPFs greater than that of micronised drug alone. The exceptions to this were systems containing PEG 4000 20% or PEG 20,000 40% both of which had FPFs not significantly different from micronised salbutamol sulphate. These two systems were crystalline unlike most of the other spray dried composites examined which were amorphous in nature.
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Salbutamol intake and substrate oxidation during submaximal exercise.
Arlettaz, A; Le Panse, B; Portier, H; Lecoq, A-M; Thomasson, R; De Ceaurriz, J; Collomp, K
2009-01-01
In order to test the hypothesis that salbutamol would change substrate oxidation during submaximal exercise, eight recreationally trained men twice performed 1 h at 60% VO(2) peak after ingestion of placebo or 4 mg of salbutamol. Gas exchange was monitored and blood samples were collected during exercise for GH, ACTH, insulin, and blood glucose and lactate determination. With salbutamol versus placebo, there was no significant difference in total energy expenditure and substrate oxidation, but the substrate oxidation balance was significantly modified after 40 min of exercise. ACTH was significantly decreased with salbutamol during the last 10 min of exercise, whereas no difference was found between the two treatments in the other hormonal and metabolic parameters. The theory that the ergogenic effect of salbutamol results from a change in substrate oxidation has little support during relatively short term endurance exercise, but it is conceivable that longer exercise duration can generate positive findings.
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Fenoterol versus salbutamol nebulization in asthma.
Hockley, B.; Johnson, N. M.
1983-01-01
A double-blind crossover study was conducted in 10 stable asthmatics comparing 5 mg fenoterol with 5 mg salbutamol, both given via a Hudson nebulizer. Although both drugs caused significant bronchodilatation at the doses used, fenoterol had a significantly greater peak effect than salbutamol and its duration of action was 4 hr as opposed to 3 hr. PMID:6353397
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Effect of salbutamol on innervated and denervated rat soleus muscle.
Soić-Vranić, T; Bobinac, D; Bajek, S; Jerković, R; Malnar-Dragojević, D; Nikolić, M
2005-12-01
The objective of the present investigation was to perform a 14-day time-course study of treatment with salbutamol, a beta2 adrenoceptor agonist, on rat soleus muscle in order to assess fiber type selectivity in the hypertrophic response and fiber type composition. Male Wistar rats were divided into four groups: control (N = 10), treated with salbutamol (N = 30), denervated (N = 30), and treated with salbutamol after denervation (N = 30). Salbutamol was injected intraperitoneally in the rats of the 2nd and 4th groups at a concentration of 0.3 mg/kg twice a day for 2 weeks. The muscles were denervated using the crush method with pean. The animals were sacrificed 3, 6, 9, 12, and 14 days after treatment. Frozen cross-sections of soleus muscle were stained for myosin ATPase, pH 9.4. Cross-sectional area and percent of muscle fibers were analyzed morphometrically by computerized image analysis. Treatment with salbutamol induced hypertrophy of all fiber types and a higher percentage of type II fibers (21%) in the healthy rat soleus muscle. Denervation caused marked atrophy of all fibers and conversion from type I to type II muscle fibers. Denervated muscles treated with salbutamol showed a significantly larger cross-sectional area of type I muscle fibers, 28.2% compared to the denervated untreated muscle. Moreover, the number of type I fibers was increased. These results indicate that administration of salbutamol is able to induce changes in cross-sectional area and fiber type distribution in the early phase of treatment. Since denervation-induced atrophy and conversion from type I to type II fibers were improved by salbutamol treatment we propose that salbutamol, like other beta2 adrenoceptor agonists, may have a therapeutic potential in improving the condition of skeletal muscle after denervation.
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Hair Analysis to Monitor the Illegal Use of Salbutamol in Beef Cattle.
Zhang, Kai; Liang, Xiaowei; Zhang, Junmin; Zhao, Qingyu; Liu, Shengsheng; Tang, Chaohua; Su, Chuanyou; Meng, Qingshi
2017-01-01
This study measured the concentrations of salbutamol residues in red and white hair of cattle during and after salbutamol administration. Three Chinese Simmental beef cattle received an oral administration of 150 μg/kg body weight/d salbutamol for 21 consecutive days. Salbutamol concentrations were determined on Days 1, 7, 14, and 21 of administration and on Days 7, 14, 28, 42, and 70 following the last administration dose using ultra-performance liquid chromatography-tandem mass spectrometry. The concentrations of salbutamol that eluted from hair were determined. The results revealed that salbutamol concentrations were higher in red hair than in white hair on the same sampling day (P < 0.01). In red hair, salbutamol concentrations increased from 29.82 ± 1.8 ng/g on Day 1 of administration to 442.55 ± 250.29 ng/g on Day 21 of administration, and decreased to 33.36 ± 19.22 ng/g on Day 70 after the last administration. In white hair, salbutamol concentrations changed from 4.25 ± 0.32 ng/g on Day 1 of administration to 33.81 ± 6.44 ng/g and 12.25 ± 2.51 ng/g on Days 14 and 70, respectively, after the last administration. The concentrations of salbutamol that eluted from white hair on Days 1 and 7 were 22.94 ± 2.00 ng/g and 92.94 ± 22.49 ng/g, respectively. Our findings revealed that hair is an appropriate biological matrix for assessing the illegal use of salbutamol in animal husbandry. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Liu, Qing; Li, Qingrui; Han, Ting; Hu, Tingting; Zhang, Xuemei; Hu, Junhua; Hu, Hui; Tan, Wen
2017-09-01
Currently, all commercial available nebulized salbutamol in China is in its racemic form. It is known that only R-salbutamol (eutomer) has therapeutic effects, while S-salbutamol (distomer) may exacerbate asthma after chronic use. Therefore, it is an unmet clinical need to develop R-salbutamol as a nebulized product that is more convenient for young and old patients. In our study, a stable aerosol solution of R-salbutamol sulfate was established, and its antiasthmatic effects were confirmed. The decomposition rate and racemization effect of the R-salbutamol sulfate solution were evaluated over a pH range from 1 to 10 (except pH=7, 8) at 60°C. The aerodynamic particle size of the R-salbutamol sulfate solution and commercial RS-salbutamol sulfate solution were both tested in vitro by Next-Generation Impactor (NGI) in 5°C. Laser diffractometer was used to characterize the droplet-size distribution (DSD) of both solutions. We next conducted an in vivo animal study to document the antiasthmatic effect of R-salbutamol aerosol sulfate solution and determine the relationship to RS-salbutamol. The results showed that the R-salbutamol sulfate solution was more stable at pH 6. In vitro comparison studies indicated that there was no distribution difference between R-salbutamol sulfate solution and the commercial RS-salbutamol solution. The animal results showed that R-salbutamol was more potent than RS-salbutamol against the same dose of histamine challenge. Unlike commercial RS-salbutamol, which was acidified to a pH of 3.5 to extend bench life but may cause bronchoconstriction in asthmatic patients, the neutralized R-salbutamol solution was more suitable for clinic use.
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The role of various surfactants on the release of salbutamol from suppositories.
Hanaee, J; Javadzadeh, Y; Taftachi, S; Farid, D; Nokhodchi, A
2004-11-01
Salbutamol is a selective beta(2)-adrenoreceptor agonist with different pharmacological effects. In this research because of the simplicity of suppository application in elderly and its higher plasma concentration than tablets as well as its particular indication in premature labour, salbutamol suppositories were prepared. The suppositories were formulated containing 10 mg of the drug and Witepsol H15, the oleaginous soluble base using melting method. To optimize the release rate of drug, different surfactants namely, sodium lauryl sulphate (SLS) as an ionic surfactant and Tween 80 as well as Arlacel 60 as non-ionic surfactants with different HLBs were chosen. The effect of surfactant concentration on the release rate of salbutamol from suppositories were also investigated. All prepared formulations fulfilled the specifications set down in British Pharmacopoeia. The results showed that Tween 80 (2%w/w) and SLS (0.75%w/w) caused an increase in dissolution rate of salbutamol from suppositories. As anionic surfactants, such as SLS, cause greater damage on mucosa than non-ionic surfactant, such as Tween 80, this study recommended that Tween 80 could be added in suppository formulation in order to increase the dissolution rate of salbutamol. It was also shown that the release rate of salbutamol altered linearly with the amount of Tween 80 in suppository formulations.
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The enigma of inhaled salbutamol and sport: unresolved after 45 years.
Fitch, Ken D
2017-07-01
During the past 45 years, there have been more changes on the World Anti-Doping Agency's (WADA) Prohibited List (the List) to the status of inhaled salbutamol than any other substance. With 658 athletes, 6.1% of all participating athletes approved to inhale salbutamol at the 2008 Beijing Games, it is one of the medications used most frequently by Olympic athletes. Nevertheless, since the 2008 Games, WADA has made numerous changes to inhaled salbutamol on the List including prohibiting its use, then a year later permitting it without prior notification and recommending a pharmacokinetic study if an athlete exceeds the urinary threshold of 1000 ng/mL. Recently, an elite athlete undertook two pharmacokinetic studies and the results have raised several questions. These include whether WADA should continue to permit nebulized salbutamol as an acceptable method of inhalation and there is some justification for nebulized salbutamol to be prohibited in sport. Another question is whether the modified advisory on salbutamol in the 2017 List appropriately informs athletes of the risks of exceeding the urinary threshold and the recent changes may not inform athletes optimally. Finally, concern is expressed at the persistent failure of WADA to apply a correction down to a specific gravity of 1.020 when an exogenous substance is identified in the urine of a dehydrated athlete. It is recommended that this should be implemented. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.
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The effects of R-salbutamol on behavior and physiology of finishing pigs.
Marchant-Forde, J N; Lay, D C; Marchant-Forde, R M; McMunn, K A; Richert, B T
2008-11-01
Salbutamol has potential for use as a repartioning agent in swine. The aims of this experiment were to determine effects of salbutamol on behavior and physiology of finishing pigs. The study used 192 pigs (88.8 +/- 0.9 kg of BW) housed in groups of 6 in 32 pens and assigned to 1 of 4 treatments: 1) control-0 mg/kg of salbutamol, 2) 2R--control diet with 2 mg/kg of the pure R-enantiomer of salbutamol, 3) 4R--control diet with 4 mg/kg of pure R-salbutamol, or 4) 8RS--control diet with 8 mg/kg of a 50:50 mixture of the R- and S-enantiomers. All diets were offered ad libitum for 4 wk. Salbutamol diets were replaced with control diets 24 to 48 h before slaughter. Behavioral responses to handling during weighing were recorded immediately before assignment to the treatments (wk 0) and at weekly intervals over the next 4-wk period. Behavioral and heart rate (HR) responses to a 10-min human presence test in the home pen were measured during wk 0, wk 1, and wk 3. Heart rate responses to a 36-min transportation were recorded. One pig from each pen had blood collected 4 times: during wk 0, 2, 4, and at exsanguination. Blood was analyzed for NEFA, creatine kinase, glucose, lactate, blood urea nitrogen, ammonia, insulin, cortisol, norepinephrine, and epinephrine. Data were analyzed using PROC GLM of SAS, with pen as the experimental unit. Treatment had no effect on time spent lying laterally, overall activity, or time spent alert. Treatment had no effect on handling measures (P > 0.05) or on behavioral responses to human presence (P > 0.05), with all pigs willing to spend similar amounts of time close to and touching the human. However, during the human presence test in wk 1 and wk 3, control pigs had HR around 10 peats per minute less (P < 0.05) than pigs in the other 3 treatments. During transport, overall HR were similar across treatments (P > 0.05). However, at certain 1-min time points, control pigs had greater HR than salbutamol-treated pigs (P < 0.05). There were no
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Vietri, M; Pietrabissa, A; Spisni, R; Mosca, F; Pacifici, G M
2000-09-01
The aim of this investigation was to determine whether mefenamic acid and salicylic acid inhibit the sulfation of (-)-salbutamol and minoxidil in the human liver and duodenum, and if so, to ascertain whether the 50% inhibitory concentration (IC50) estimates are different in the two tissues. Sulfotransferase activities were measured for 10 mM (-)-salbutamol and 5 mM minoxidil, and the concentration of 3'-phosphoadenosine-5'-phosphosulphate-[35S] was 0.4 microM. The IC50 estimates for (-)-salbutamol and minoxidil sulfation of mefenamic acid were 72 +/- 5.4 nM and 1.5 +/- 0.6 microM (liver), respectively, and 161 + 23 microM and 420 +/- 18 microM (duodenum), respectively. The figures for the liver were significantly lower (P < 0.0001) than those for the duodenum. The IC50 estimates for (-)-salbutamol sulfation of salicylic acid were 93 +/- 11 microM (liver) and 705 +/- 19 microM (duodenum, P < 0.0001). Salicylic acid was a poor inhibitor of minoxidil sulfation. The IC50 estimates for (-)-salbutamol sulfation of mefenamic acid and salicylic acid are lower than their unbound plasma concentrations after standard dosing, suggesting that mefenamic acid and salicylic acid should inhibit the hepatic sulfation of (-)-salbutamol in vivo.
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Zimmer, Guido; Bernhörster, Markus; Pilz, Patrizius; Schuchmann-Fix, Jutta; Hüggelmeier, Rolf; Blüm, Nicole; Libertus, Herman
2006-01-01
Electron paramagnetic resonance (EPR) spectroscopy with spin labels 5- and 16-doxyl-stearic acid (DSA) was used to differentiate between actions of beta-agonists on human mononuclear cell membrane. Reproterol (CAS 13055-82-8), salbutamol (CAS 51022-70-9) and fenoterol (CAS 1944-12-3) compared to cromoglycate (CAS 15826-37-6) were used at concentrations of 10-100 nmol/l per 10(7) cells. With reproterol, order and polarity was not much changed, whereas salbutamol and fenoterol significantly destabilized the membrane to similar extent. Cromoglycate acted in a stabilizing fashion. With trypan blue exclusion, reproterol and cromoglycate showed stable values, whereas salbutamol and fenoterol augmented permeability. Thus, by conventional lipid spin labeling the discrimination between salbutamol and fenoterol could not be carried out. In contrast, previous lipid peroxidation studies in a model system had revealed a decrease by reproterol, no change by salbutamol and an increase by fenoterol. Also, using fenoterol, protein spin label 4-maleimido-TEMPO (2, 2, 6, 6-tetramethyl-1-piperidinyloxy) showed an increase of membrane rigidity of mononuclear cells. Moreover, mast cells of different origin were previously found tween beta-agonists. Reproterol in all tests behaved in a therapeutically profitable way. In conclusion, in addition to lipid spin labeling other methods and materials should be considered, to finally arrive at a more realistic differentiation between, for instance, salbutamol and fenoterol. The term "membrane (de) stabilization" should not generally be used without careful consideration of the type of cell/membrane in question.
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McMacken, Grace; Cox, Dan; Roos, Andreas; Müller, Juliane; Whittaker, Roger; Lochmüller, Hanns
2018-05-01
Inherited defects of the neuromuscular junction (NMJ) comprise an increasingly diverse range of disorders, termed congenital myasthenic syndromes (CMS). Therapies acting on the sympathetic nervous system, including the selective β2 adrenergic agonist salbutamol and the α and β adrenergic agonist ephedrine, have become standard treatment for several types of CMS. However, the mechanism of the therapeutic effect of sympathomimetics in these disorders is not understood. Here, we examined the effect of salbutamol on NMJ development using zebrafish with deficiency of the key postsynaptic proteins Dok-7 and MuSK. Treatment with salbutamol reduced motility defects in zebrafish embryos and larvae. In addition, salbutamol lead to morphological improvement of postsynaptic acetycholine receptor (AChR) clustering and size of synaptic contacts in Dok-7-deficient zebrafish. In MuSK-deficient zebrafish, salbutamol treatment reduced motor axon pathfinding defects and partially restored the formation of aneural prepatterned AChRs. In addition, the effects of salbutamol treatment were prevented by pre-treatment with a selective β2 antagonist. Treatment with the cyclic adenosine monophosphate (cAMP) activator forskolin, replicated the effects of salbutamol treatment. These results suggest that sympathomimetics exert a direct effect on neuromuscular synaptogenesis and do so via β2 adrenoceptors and via a cAMP-dependent pathway.
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McMacken, Grace; Cox, Dan; Roos, Andreas; Müller, Juliane; Whittaker, Roger; Lochmüller, Hanns
2018-01-01
Abstract Inherited defects of the neuromuscular junction (NMJ) comprise an increasingly diverse range of disorders, termed congenital myasthenic syndromes (CMS). Therapies acting on the sympathetic nervous system, including the selective β2 adrenergic agonist salbutamol and the α and β adrenergic agonist ephedrine, have become standard treatment for several types of CMS. However, the mechanism of the therapeutic effect of sympathomimetics in these disorders is not understood. Here, we examined the effect of salbutamol on NMJ development using zebrafish with deficiency of the key postsynaptic proteins Dok-7 and MuSK. Treatment with salbutamol reduced motility defects in zebrafish embryos and larvae. In addition, salbutamol lead to morphological improvement of postsynaptic acetycholine receptor (AChR) clustering and size of synaptic contacts in Dok-7-deficient zebrafish. In MuSK-deficient zebrafish, salbutamol treatment reduced motor axon pathfinding defects and partially restored the formation of aneural prepatterned AChRs. In addition, the effects of salbutamol treatment were prevented by pre-treatment with a selective β2 antagonist. Treatment with the cyclic adenosine monophosphate (cAMP) activator forskolin, replicated the effects of salbutamol treatment. These results suggest that sympathomimetics exert a direct effect on neuromuscular synaptogenesis and do so via β2 adrenoceptors and via a cAMP-dependent pathway. PMID:29462491
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Effect of salbutamol on neuromuscular function in endurance athletes.
Decorte, Nicolas; Bachasson, Damien; Guinot, Michel; Flore, Patrice; Levy, Patrick; Verges, Samuel; Wuyam, Bernard
2013-10-01
The potential ergogenic effects of therapeutic inhaled salbutamol doses in endurance athletes have been controversially discussed for decades. We hypothesized that salbutamol inhalation may increase peripheral muscle contractility, reduce fatigability, and improve force recovery after a localized exercise in endurance athletes. Eleven healthy, nonasthmatic male athletes with high aerobic capacities were recruited to be compared in a double-blinded, randomized crossover study of two dose levels of salbutamol (200 and 800 μg) and a placebo administered by inhalation before a quadriceps fatigue test. Subjects performed an incremental exercise protocol consisting in sets of 10 intermittent isometric contractions starting at 20% of maximum voluntary contraction (MVC) with 10% MVC increment until exhaustion. Femoral nerve magnetic stimulation was used during and after MVC to evaluate neuromuscular fatigue after each set, at task failure, and after 10 and 30 min of recovery. Initial MVC and evoked muscular responses were not modified with salbutamol (P > 0.05). The total number of submaximal contractions until task failure significantly differed between treatments (placebo, 72 ± 7; 200 µg, 78 ± 8; and 800 µg, 82 ± 7; P < 0.01). MVC and evoked muscular responses were similarly reduced with all treatments during the fatiguing task (all P > 0.05). Voluntary activation was unaffected by the fatiguing task and treatments (P > 0.05). Supratherapeutic inhaled doses of β2-agonists increased quadriceps endurance during an incremental and localized fatiguing task in healthy endurance-trained athletes without significant effect on neuromuscular fatigue. Further studies are needed to clarify the underlying mechanisms.
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Dickinson, John; Hu, Jie; Chester, Neil; Loosemore, Mike; Whyte, Greg
2014-11-01
To examine the impact of dehydration, ethnicity, and gender on urinary concentrations of salbutamol in relation to the threshold stipulated by the World Anti-Doping Agency (WADA). Repeated measures open-label. Eighteen male and 14 female athletes (9 white males, 9 white females, 2 Afro-Caribbean males, 2 Afro-Caribbean females, 6 Asian [Indian subcontinent] males, and 4 Asian females) were recruited. All participants were nonasthmatic. After inhalation of 800 μg or 1600 μg of salbutamol, athletes exercised in a hot controlled environment (35°C, 40% relative humidity) at a self-selected pace until a target weight loss (2% or 5%) was achieved. Urine concentration of free salbutamol. After inhalation of 1600 μg salbutamol, 20 participants presented with a urine salbutamol concentrations above the current WADA limit (1000 ng/mL) and decision limit (1200 ng/mL) resulting in an adverse analytical finding. There were no differences according to gender or ethnic origin. Dehydration equivalent to a body mass loss greater than 2% concomitant to the acute inhalation of 1600 μg of salbutamol may result in a urine concentration above the current WADA limit and decision limit leading to a positive test finding independent of gender or ethnic origin. Asthmatic athletes using salbutamol should receive clear dosing advise and education to minimize the risk of inhaling doses of salbutamol that may produce urine concentrations of salbutamol above 1200 ng/mL.
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Chang, Kai-Chun; Chang, Yu-Ting; Tsai, Chin-En
2018-04-01
A liquid chromatography tandem mass spectrometric method was developed for the determination of two β-agonists (ractopamine and salbutamol) in pig hair samples. An isotope of ractopamine-d5 or salbutamol-d6 as an internal standard was used to carry out quantitative analysis. Concentrated sodium hydroxide was used to pretreat hair samples and then purified by the solid phase extraction (SPE) procedure. The extracted solution was evaporated and reconstituted for injection in the instrument with electrospray ionization (ESI) operating in a positive multiple-reaction-monitoring (MRM) mode. Ractopamine and salbutamol separation were performed on C18 analytical column under gradient condition. The internal standard calibration curve was linear in the range of concentration from 0.5 to 100 ng mL -1 (R 2 > 0.995). Recoveries of this method estimated at three spiked concentrations of 100, 250 and 500 ng mL -1 in pig hair samples, were 79-82% for ractopamine and 77-96% for salbutamol. The corresponding inter-day and intra-day precisions expressed as relative standard deviation (RSD %) were 3.8-6.4% and 3.8-8.6%, respectively. The analytical time for one sample was 8 min. The detection limit of this method was 0.6 and 8.3 ng mL -1 for ractopamine and salbutamol, respectively. This developed method can be applied for monitoring the use of the β-agonists salbutamol and ractopamine in swine feed incurred pig hair. Copyright © 2017. Published by Elsevier B.V.
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Adhikari, S; Thapa, P; Rao, K S; Bk, G
2016-01-01
Background Acute bronchiolitis is common cause of hospitalization in infants and young children. There are widespread variations in the diagnosis and management. Despite the use of bronchodilators for decades, there is lack of consensus for the benefit of one above another. Objective To compare initial response of nebulized adrenaline and salbutamol. Method Children aged two months to two years admitted with acute bronchiolitis in the department of Paediatrics of Manipal teaching hospital, Pokhara, Nepal, from 1st March 2014 to 28th February 2015 were enrolled. Patients fulfilling inclusion criteria received either adrenaline or salbutamol nebulization. Data were collected in a predesigned proforma. Respiratory distress assessment instrument (RDAI) scores were considered primary outcome measure and respiratory rate at 48 hours, duration of hospital stay, requirement of supplemental oxygen and intravenous fluid were considered secondary outcome measure. Result A total of 40 patients were enrolled in each study group. Mean RDAI scores at admission was in 9.75 with (CI- 9.01, 10.49) in adrenaline and 9.77 (CI- 9.05, 10.50) in salbutamol group. There was gradual decline in mean RDAI scores in both the groups over 48 hours to 4.15 (CI- 3.57,4.73) and 4.13 (CI- 3.69,4.56) in adrenaline and salbutamol group respectively. Hospital stay was 5.32 days in adrenaline and 5.68 days in salbutamol group. Patients nebulized with adrenaline required oxygen for 33.30 hours compared with 36.45 hours in salbutamol. Intravenous fluid duration was also less in adrenaline group compared to salbutamol group (33.15 vs 37.80 hours). Conclusion Patients of acute bronchiolitis nebulized with either salbutamol or adrenaline experienced similar decline in RDAI scores in the first 48 hours. Duration of supplementary oxygen and intravenous fluid was less in adrenaline group compared with salbutamol group.
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Roberts, G; Newsom, D; Gomez, K; Raffles, A; Saglani, S; Begent, J; Lachman, P; Sloper, K; Buchdahl, R; Habel, A
2003-04-01
The relative efficacies of aminophylline and salbutamol in severe acute childhood asthma are currently unclear. A single bolus of salbutamol was compared with a continuous aminophylline infusion in children with severe asthma in a randomised double blind study. Children aged 1-16 years with acute severe asthma were enrolled if they showed little improvement with three nebulisers (combined salbutamol and ipratropium) administered over an hour and systemic steroids. Subjects were randomised to receive either a short intravenous bolus of salbutamol (15 micro g/kg over 20 minutes) followed by a saline infusion or an aminophylline infusion (5 mg/kg over 20 minutes) followed by 0.9 mg/kg/h. Forty four subjects were enrolled, with 18 randomly allocated to receive salbutamol and 26 to receive aminophylline. The groups were well matched at baseline. An intention to treat analysis showed that there was no statistically significant difference in the asthma severity score (ASS) at 2 hours between the two groups (median (IQR) 6 (6, 8) and 6.5 (5, 8) for salbutamol and aminophylline respectively, p=0.93). A similar improvement in ASS to 2 hours was seen in the two groups (mean difference -0.08, 95% CI -0.97 to 0.80), there was a trend (p=0.07) towards a longer duration of oxygen therapy in the salbutamol group (17.8 hours (95% CI 8.5 to 37.5) v 7.0 hours (95% CI 3.4 to 14.2)), and a significantly (p=0.02) longer length of hospital stay in the salbutamol group (85.4 (95% CI 66.1 to 110.2) hours v 57.3 hours (95% CI 45.6 to 72.0)). There was no significant difference in adverse events between the two groups. This study suggests that, in severe childhood asthma, there is no significant difference in the effectiveness of a bolus of salbutamol and an aminophylline infusion in the first 2 hours of treatment. Overall, the aminophylline infusion was superior as it significantly reduced the length of stay in hospital.
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Cardiovascular and hypokalaemic effects of inhaled salbutamol, fenoterol, and isoprenaline.
Crane, J; Burgess, C; Beasley, R
1989-01-01
The cardiovascular and hypokalaemic effects of equal doses of inhaled fenoterol, isoprenaline and salbutamol were compared in eight healthy male volunteers, in a double blind, placebo controlled study. Increasing doses of 400, 600, and 800 micrograms were given from a metered dose inhaler at 15 minute intervals, followed by measurements of heart rate, blood pressure, total electromechanical systole (as a measure of inotropic response), QTc interval, and plasma potassium concentration. After repeated inhalation, fenoterol resulted in significantly greater chronotropic, electrocardiographic, and hypokalaemic effects than either isoprenaline or salbutamol. The maximum inotropic effect of fenoterol was similar to that of isoprenaline. PMID:2928998
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Atrial fibrillation associated with chocolate intake abuse and chronic salbutamol inhalation abuse.
Patanè, Salvatore; Marte, Filippo; La Rosa, Felice Carmelo; Rocca, Roberto La
2010-11-19
The use of substances as the substrate for atrial fibrillation is not frequently recognized. Chocolate is derived from the roasted seeds of the plant theobroma cacao and its components are the methylxanthine alkaloids theobromine and caffeine. Caffeine is a methylxanthine whose primary biological effect is the competitive antagonism of the adenosine receptor. Normal consumption of caffeine was not associated with risk of atrial fibrillation or flutter. Sympathomimetic effects, due to circulating catecholamines cause the cardiac manifestations of caffeine overdose toxicity, produce tachyarrhythmias such as supraventricular tachycardia, atrial fibrillation, ventricular tachycardia, and ventricular fibrillation.The commonly used doses of inhaled or nebulized salbutamol induced no acute myocardial ischaemia, arrhythmias or changes in heart rate variability in patients with coronary artery disease and clinically stable asthma or chronic obstructive pulmonary disease. Two-week salbutamol treatment shifts the cardiovascular autonomic regulation to a new level characterized by greater sympathetic responsiveness and slight beta2-receptor tolerance. We present a case of atrial fibrillation associated with chocolate intake abuse in a 19-year-old Italian woman with chronic salbutamol inhalation abuse. This case focuses attention on chocolate intake abuse associated with chronic salbutamol abuse as the substrate for atrial fibrillation. Copyright © 2008 Elsevier Ireland Ltd. All rights reserved.
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Lu, Chenyang; Zhou, Jun; Li, Yanyan; Zhang, Dijun; Wang, Zuzhong; Li, Ye; Cheong, Lingzhi; Zhang, Chundan; Su, Xiurong
2017-07-01
Even though salbutamol (SAL) had remarkable effects on the enhancement of growth rate and carcass composition in different livestock species such as cattle, pigs, sheep and poultry, it was banned as a growth promoter because of its adverse effects on health. However, the specific mechanism by which salbutamol enhances growth efficiency remains unknown. In this study, Bama pigs were randomly allocated to receive salbutamol (5 mg/kg) for 30 or 60 days and were compared with untreated pigs. Pigs treated with salbutamol demonstrated enhanced growth rates and carcass composition; however, they showed deterioration in blood biochemical indices and organ development. We hypothesized that salbutamol exerts its effects by modulating the composition of the gut microbiota population. The faecal microbiome of pigs was characterized via pyrosequencing of the bacterial 16S rRNA gene. The gut microbiota population analysis showed that salbutamol caused shifts in the microbial composition of less abundant species. Redundancy analysis indicated an increase in abundance of the phylum Bacteroidetes, class Betaproteobacteria, family Christensenellaceae and genus Lactobacillus, and a decreased ratio of the phylum Firmicutes, class Clostridia and genera Ruminococcus, Blautia and Subdoligranulum. In conclusion, our study provided circumstantial evidence that the various effects of salbutamol are caused by gut microbiota modulation, and several potential candidates were identified for SAL detection via the gut microbiota. Our findings provided new insights into the roles of the gut microbiota during salbutamol treatment, and these findings will aid in the screening of alternative strategies for animal health improvement and production enhancement.
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Lipworth, B. J.; Newnham, D. M.; Clark, R. A.; Dhillon, D. P.; Winter, J. H.; McDevitt, D. G.
1995-01-01
BACKGROUND--There is controversy as to the relative safety of fenoterol and salbutamol. No differences have been found in the relative cardiac beta 1/beta 2 receptor activity of inhaled fenoterol and salbutamol in normal subjects. These initial findings have been extended by comparing the respective potencies of equivalent doses by weight of fenoterol and salbutamol in asthmatic subjects, in terms of airways and systemic responses. METHODS--Eighteen asthmatic patients of mean (SD) age 40 (14) years and a forced expiratory volume in one second (FEV1)% predicted of 56 (14)% (1.97 (0.66)1) were randomised to inhale fenoterol (100 micrograms/puff or 200 micrograms/puff), salbutamol, or placebo (100 micrograms/puff or 200 micrograms/puff) on three separate days. Dose-response curves were constructed using cumulative doses of 100 micrograms, 200 micrograms, 400 micrograms, 1000 micrograms, 2000 micrograms, and 4000 micrograms, and airways and systemic responses were measured 20 minutes after each dose with 40 minute increments. Dose ratios for the relative potency of fenoterol versus salbutamol were calculated from the dose-response curves using regression analysis of parallel slopes. RESULTS--There was no difference in bronchodilator potency between fenoterol and salbutamol (as median dose ratio): FEV1 1.1 (95% CI 0.4 to 4.6). In contrast, dose ratios for systemic responses showed that fenoterol was more potent than salbutamol: serum potassium 3.7 (95% CI 2.0 to 6.0), tremor 5.7 (95% CI 1.4 to 10.2), heart rate 1.6 (95% CI 1.0 to 2.3). At a conventional dose of 200 micrograms the only difference in response between the two drugs was observed for tremor (as mean difference): 0.23 log units (95% CI 0.06 to 0.41 log units). CONCLUSIONS--There was no difference in the bronchodilator potency between fenoterol and salbutamol on a microgram equivalent basis. In contrast, systemic potency was greater with fenoterol, although this difference was not clinically relevant at
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Dispas, Amandine; Desfontaine, Vincent; Andri, Bertyl; Lebrun, Pierre; Kotoni, Dorina; Clarke, Adrian; Guillarme, Davy; Hubert, Philippe
2017-02-05
In the last years, supercritical fluid chromatography has largely been acknowledged as a singular and performing technique in the field of separation sciences. Recent studies highlighted the interest of SFC for the quality control of pharmaceuticals, especially in the case of the determination of the active pharmaceutical ingredient (API). Nevertheless, quality control requires also the determination of impurities. The objectives of the present work were to (i) demonstrate the interest of SFC as a reference technique for the determination of impurities in salbutamol sulfate API and (ii) to propose an alternative to a reference HPLC method from the European Pharmacopeia (EP) involving ion-pairing reagent. Firstly, a screening was carried out to select the most adequate and selective stationary phase. Secondly, in the context of robust optimization strategy, the method was developed using design space methodology. The separation of salbutamol sulfate and related impurities was achieved in 7min, which is seven times faster than the LC-UV method proposed by European Pharmacopeia (total run time of 50min). Finally, full validation using accuracy profile approach was successfully achieved for the determination of impurities B, D, F and G in salbutamol sulfate raw material. The validated dosing range covered 50 to 150% of the targeted concentration (corresponding to 0.3% concentration level), LODs close to 0.5μg/mL were estimated. The SFC method proposed in this study could be presented as a suitable fast alternative to EP LC method for the quantitative determination of salbutamol impurities. Copyright © 2016 Elsevier B.V. All rights reserved.
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Salbutamol sulfate suppositories: influence of formulation on physical parameters and stability.
Taha, Ehab I; Zaghloul, Abdel-Azim A; Kassem, Alaa A; Khan, Mansoor A
2003-01-01
To prepare and evaluate a suppository dosage form of salbutamol sulfate. The prepared formulae with and without different concentrations of gels were tested for hardness, melting time, content uniformity, and drug release. The stability of some of the selected formulae was assessed. Salbutamol sulfate was formulated as a rectal suppository with emulsifying fatty bases (suppocire and witepsol) and water-soluble bases (PEG) adopting the molding from a melt technique. Physical characteristics and dissolution profiles of the prepared formulations were determined as the responses. The effects of adding gels, methyl cellulose (MC), and Eudispert (Eud) and their concentrations (1, 3, and 6%) on these responses were also investigated. Formulations showing high rank order were scaled up for shelf-life stability study for one year. The results showed that all the investigated formulae have acceptable physical characteristics with respect to hardness, melting time (except F7), and uniformity of drug content. The amount of drug dissolved in 100 min of dissolution time was inversely affected by the melting point of the fatty base. The release from PEG bases was found to be molecular weight dependent. Addition of 1% MC or Eud gel increased the release from all the investigated formulae. Increasing gel concentration to 3% then to 6% showed different effects on the release. The degradation of salbutamol sulfate in the investigated formulae was found to be a first-order reaction. Rectal suppository of salbutamol sulfate could be prepared as an alternative to the oral dosage form to circumvent the first-pass metabolism.
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Zhou, Ting; Zeng, Jing; Liu, Shan; Zhao, Ting; Wu, Jie; Lai, Wenshi; He, Mingzhi; Xu, Beining; Qu, Shanshan; Xu, Ling; Tan, Wen
2015-10-01
The chiral inversion has been a concerned issue during the research and development of a chiral drug. In this study, a sensitive chiral liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for determination of salbutamol enantiomers in human plasma and urine. The chiral inversion mechanism of R-salbutamol was fully investigated for the first time by studying the effects of physicochemical factors, including pH, temperature and time. A fitted model to predict the chiral inversion ratio of R-salbutamol was proposed using a Box-Behnken design. All the samples were separated on an Astec Chirobiotic T column and detected by a tandem mass spectrometer in multiple reaction monitoring mode. Lower limit of quantification of 0.100ng/mL was achieved under the optimized conditions. The method was fully validated and successfully applied to the clinical pharmacokinetic study of R-salbutamol in healthy volunteers. Chiral inversion of R-salbutamol to S-salbutamol has been detected in urine samples. The results indicated that pH and temperature were two dominant factors that caused the chiral inversion of R-salbutamol, which should be taken into consideration during the analysis of chiral drugs. The chiral inversion of R-salbutamol determined in this study was confirmed resulted from the gastric acid in stomach rather than caused by the analysis conditions. Moreover, the calculated results of the fitted model matched very well with the enantioselective pharmacokinetic study of R-salbutamol, and the individual difference of the chiral inversion ratio of R-salbutamol was related to the individual gastric environment. On the basis of the results, this study provides important and concrete information not only for the chiral analysis but also for the metabolism research of chiral drugs. Copyright © 2015 Elsevier B.V. All rights reserved.
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Sallans, Larry; Macha, Stephen; Brown, Kari; McGraw, Dennis W.; Kovacic, Melinda Butsch; Britigan, Bradley E.
2011-01-01
β2-Agonists are the most effective bronchodilators for the rapid relief of asthma symptoms, but for unclear reasons, their effectiveness may be decreased during severe exacerbations. Because peroxidase activity and nitrogen oxides are increased in the asthmatic airway, we examined whether salbutamol, a clinically important β2-agonist, is subject to potentially inactivating nitration. When salbutamol was exposed to myeloperoxidase, eosinophil peroxidase or lactoperoxidase in the presence of hydrogen peroxide (H2O2) and nitrite (NO2−), both absorption spectroscopy and mass spectrometry indicated formation of a new metabolite with features expected for the nitrated drug. The new metabolites showed an absorption maximum at 410 nm and pKa of 6.6 of the phenolic hydroxyl group. In addition to nitrosalbutamol (m/z 285.14), a salbutamol-derived nitrophenol, formed by elimination of the formaldehyde group, was detected (m/z 255.13) by mass spectrometry. It is noteworthy that the latter metabolite was detected in exhaled breath condensates of asthma patients receiving salbutamol but not in unexposed control subjects, indicating the potential for β2-agonist nitration to occur in the inflamed airway in vivo. Salbutamol nitration was inhibited in vitro by ascorbate, thiocyanate, and the pharmacological agents methimazole and dapsone. The efficacy of inhibition depended on the nitrating system, with the lactoperoxidase/H2O2/NO2− being the most affected. Functionally, nitrated salbutamol showed decreased affinity for β2-adrenergic receptors and impaired cAMP synthesis in airway smooth muscle cells compared with the native drug. These results suggest that under inflammatory conditions associated with asthma, phenolic β2-agonists may be subject to peroxidase-catalyzed nitration that could potentially diminish their therapeutic efficacy. PMID:20974700
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Treatment of acute asthma: salbutamol via jet nebuliser vs spacer and metered dose inhaler.
Robertson, C F; Norden, M A; Fitzgerald, D A; Connor, F L; Van Asperen, P P; Cooper, P J; Francis, P W; Allen, H D
1998-04-01
To compare the efficacy of salbutamol delivered by jet nebuliser (JN) with salbutamol via a pressurised metered dose inhaler (PMDI) and a large volume spacer (Volumatic) for management of acute asthma. A total of 160 children aged from 4 to 12 years presenting to an Emergency Department with acute asthma. The study was of multicentre (n=5) randomised, double blind, parallel design. Children weighing less than 25 kg received salbutamol 2.5 mg via the JN or 600 microg (six puffs) from the PMDI. Children over 25 kg received salbutamol 5 mg via the JN or 1200 microg (12 puffs) via the PMDI. Clinical score (range 0-12) and PEF (over 7 years) were recorded at baseline and 15, 30, 45 and 60 mins post administration. The improvement from baseline at 30 min in the clinical score was 1.87 for JN and 1.43 for PMDI (P=0.09) and at 60 min was 2.15 for JN and 1.12 for PMDI (P=0.0001). The improvement in PEF at 30 min was 51 L min(-1) for JN and 27 L min(-1) for PMDI (P=0.0007) and at 60 min was 57 L min(-1) for JN and 31.5 L min(-1) for PMDI (P=0.001). Administration of salbutamol via a PMDI and a large volume spacer device provides effective relief in the management of acute asthma in children, but to a lesser extent than a jet nebuliser. This difference may represent a dose response effect.
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[Spectroscopic Study of Salbutamol Molecularly Imprinted Polymers].
Ren, Hui-peng; Guan, Yu-yu; Dai, Rong-hua; Liu, Guo-yan; Chai, Chun-yan
2016-02-01
In order to solve the problem of on-site rapid detection of salbutamol residues in feed and animal products, and develop a new method of fast detection of salbutamol on the basis of the molecular imprinting technology, this article uses the salbutamol (SAL) working as template molecule, methacrylic acid (MAA) working as functional monomer. On this basis, a new type of core-shell type salbutamol molecularly imprinted polymers were prepared with colloidal gold particles as triggering core. Superficial characteristics of the MIPs and the related compounds were investigated by ultraviolet (UV) spectra and infrared (IR) spectra, Raman spectra, Scanning electron microscopy (SEM) respectively. The results indicated that a stable hydrogen bonding complex has been formed between the carboxyl groups of SAL and MA with a matching ratio of 1:1. The complex can be easily eluted by the reagent containing hydrogen bonding. The chemical binding constant K reaches -0.245 x 10⁶ L² · mol⁻². The possible binding sites of the hydrogen bonding was formed between the hydrogen atoms of -COOH in MA and the oxygen atoms of C==O in SAL. IR and Raman spectrum showed that, compared with MA, a significant red shift of -OH absorption peak was manifested in MIPs, which proved that SAL as template molecule occurred a specific bond between MA. Red shift of stretching vibration absorption peak of C==O was also detected in the un-eluted MIPs and obvious energy loss happened, which demonstrated a possible binding sites is SAL intramolecular of C==O atom of oxygen. If the hydrogen atoms of -COOH in MA wanted to generate hydrogen bond. However, the shapes of absorption peak of other functional groups including C==C, C==O, and -OH were very similar both in MIPs and NIPs. Specific cavities were formed after the template molecules in MIPs were removed. It was proved by the adsorption experiment that the specific sites in these cavities highly match with the chemical and space structure of SAL
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Hindle, M.; Peers, E. M.; Parry-Billings, M.; Chrystyn, H.
1997-01-01
Aims The number of dry powder inhaler (DPI) devices could increase because they are easier to use than a metered dose inhaler (MDI). Using urinary excretion, the relative bioavailability of salbutamol to the lungs and the body for a prototype DPI has been compared with an MDI. Methods A randomized, double-blind, two way crossover study compared the amount of salbutamol in the urine 30 min following inhalation of 2×100 μg salbutamol from a prototype DPI (Innovata Biomed Ltd, UK) and a Ventolin® (Allen and Hanburys Ltd, UK) MDI in 10 volunteers. The amount of salbutamol and its metabolite, the ester sulphate conjugate, renally excreted up to 24 h post inhalation was also determined to evaluate the relative bioavailability of salbutamol to the body. Results The mean (s.d.) 30 min post-treatment urinary excretion for the prototype DPI and MDI was 8.4 (2.6) and 5.0 (1.9) μg, respectively (P<0.001). The total amount of salbutamol and its ester metabolite excreted in the urine over the 24 h period after inhalation was 187.9 (77.6) and 137.6 (40.0) μg (P<0.05). Conclusions The prototype DPI delivered more salbutamol to the body and the lungs than a conventional MDI. This finding supports further development of the prototype DPI. The urinary salbutamol method is able to discriminate between two different inhalation systems. PMID:9088593
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Lavorini, Federico; Geri, Pietro; Mariani, Laura; Marmai, Cecilia; Maluccio, Nazzarena Maria; Pistolesi, Massimo; Fontana, Giovanni A
2006-01-01
Aims To evaluate the speed of onset of bronchodilation following salbutamol administered via a metered-dose inhaler with a spacer (pMDI + Volumatic) and a dry-powder inhaler (Diskus), as well as the relative potencies of these devices in asthmatic patients with methacholine-induced bronchoconstriction. Methods Eighteen patients inhaled methacholine (MCh) until FEV1 decreased by 35% of control. Following administration of placebo, 200 µg salbutamol or 400 µg salbutamol through the pMDI + Volumatic or the Diskus, we calculated the time elapsed from drug administration and the appearance of a 90% increase in post-MCh forced vital capacity (FVC), FEV1 and volume-adjusted mid-expiratory flow (recovery times). The salbutamol doses to be delivered by the two inhalation devices to achieve similar recovery times and the relative potencies of the devices were calculated by using the 2-by-2 Finney parallel regression method. Results For all functional variables, recovery times were significantly (P < 0.01) shorter in pMDI + Volumatic than Diskus trials. The salbutamol doses to be delivered by the Diskus to achieve recovery times for FVC, FEV1 and volume-adjusted mid-expiratory flow similar to those obtained with 200 µg salbutamol administered via the pMDI + Volumatic were 558 (95% CI 537, 579) µg, 395 (95% CI 388, 404) µg and 404 (95% CI 393, 415) µg, respectively, and corresponded to relative potencies of 2.79 (95% CI 2.68, 2.90), 1.98 (95% CI 1.94, 2.02), and 2.02 (95% CI 1.96, 2.07). Conclusions Administration of salbutamol via the pMDI + Volumatic provides faster reversal of induced bronchoconstriction than via the Diskus. The salbutamol dose targeting the lungs with the pMDI + Volumatic is approximately twice that with the Diskus. PMID:16995861
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Visser, R; van der Palen, J; de Jongh, F H C; Thio, B J
2015-04-01
Pulmonary medication is mostly delivered in the form of medical aerosols to minimize systemic side effects. A major drawback of inhaled medication is that the majority of inhaled particles impacts in the oropharynx at the sharp bend of the airway. Stretching the airway by a forward leaning body posture with the neck extended ("sniffing position") may improve pulmonary deposition and clinical effects. 41 asthmatic children who were planned for standard reversibility testing at the pulmonary function lab, alternately inhaled 200 μgr salbutamol with an Autohaler(®) in the standard or in the forward leaning body posture. Forced Expiratory Volume in 1 s (FEV1), Forced Vital Capacity (FVC), Peak Expiratory Flow (PEF), Mean Expiratory Flow at 25% of vital capacity (MEF25) and Mean Expiratory Flow at 75% of vital capacity (MEF75) were analysed. The children in the forward leaning body posture group showed a significantly higher mean FEV1 reversibility than the control group after inhalation of 200 μgr salbutamol (10.2% versus 4.1%, p = 0.019). Additionally, mean MEF75 was significantly more reversible in the forward leaning body posture group versus the standard body posture group (32.2% resp. 8.9%, p = 0.013). This pilot study showed a higher reversibility of FEV1 and MEF75 after inhaling salbutamol in a forward leaning body posture compared to the standard body posture in asthmatic children. This suggests that pulmonary effects of salbutamol can be improved by inhaling in a forward leaning body posture with the neck extended. This effect is possibly due to a higher pulmonary deposition of salbutamol and should be confirmed in a randomized controlled trial. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Chávez, Jaime; Segura, Patricia; Vargas, Mario H; Arreola, José Luis; Flores-Soto, Edgar; Montaño, Luis M
2007-04-01
Organophosphates induce bronchoobstruction in guinea pigs, and salbutamol only transiently reverses this effect, suggesting that it triggers additional obstructive mechanisms. To further explore this phenomenon, in vivo (barometric plethysmography) and in vitro (organ baths, including ACh and substance P concentration measurement by HPLC and immunoassay, respectively; intracellular Ca2+) measurement in single myocytes) experiments were performed. In in vivo experiments, parathion caused a progressive bronchoobstruction until a plateau was reached. Administration of salbutamol during this plateau decreased bronchoobstruction up to 22% in the first 5 min, but thereafter airway obstruction rose again as to reach the same intensity as before salbutamol. Aminophylline caused a sustained decrement (71%) of the parathion-induced bronchoobstruction. In in vitro studies, paraoxon produced a sustained contraction of tracheal rings, which was fully blocked by atropine but not by TTX, omega-conotoxin (CTX), or epithelium removal. During the paraoxon-induced contraction, salbutamol caused a temporary relaxation of approximately 50%, followed by a partial recontraction. This paradoxical recontraction was avoided by the M2- or neurokinin-1 (NK1)-receptor antagonists (methoctramine or AF-DX 116, and L-732138, respectively), accompanied by a long-lasting relaxation. Forskolin caused full relaxation of the paraoxon response. Substance P and, to a lesser extent, ACh released from tracheal rings during 60-min incubation with paraoxon or physostigmine, respectively, were significantly increased when salbutamol was administered in the second half of this period. In myocytes, paraoxon did not produce any change in the intracellular Ca2+ basal levels. Our results suggested that: 1) organophosphates caused smooth muscle contraction by accumulation of ACh released through a TTX- and CTX-resistant mechanism; 2) during such contraction, salbutamol relaxation is functionally antagonized by the
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Wouters, E F; Polko, A H; Visser, B F
1989-01-01
The bronchodilating effect of 1 mg and 0.4 mg salbutamol on the impedance of the respiratory system was studied in 25 asthmatic subjects after histamine-induced bronchoconstriction. Histamine caused an increase of respiratory resistance (Rrs) at lower frequencies and a frequency dependence of Rrs. Respiratory reactance (Xrs) decreased at all frequencies after histamine challenge. These changes can be explained by peripheral airway obstruction. Impedance measurements performed 5 min after inhalation of 1 mg and 0.4 mg salbutamol showed a decrease of Rrs values at lower frequencies, a disappearance of the frequency dependence of Rrs, and a significant increase of Xrs values. No significant differences in absolute changes of Rrs and Xrs are observed between the salbutamol regimens. These changes after inhalation of salbutamol can be explained by supposing a predominant action on the peripheral airways.
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Newnham, D M; Wheeldon, N M; Lipworth, B J; McDevitt, D G
1993-01-01
BACKGROUND--The aim of the present study was to compare the dose related effects of fenoterol and salbutamol on cardiac beta 1 and beta 2 receptors using the beta 1 selective antagonist atenolol, in order to dissect out relative beta 1/beta 2 mediated responses. METHODS--Fourteen normal volunteers were randomised to receive pretreatment with either atenolol 25 mg or placebo, followed by inhaled fenoterol or salbutamol in equal doses by weight (cumulative doses of 1 mg and 4 mg). Measurements were made 30 minutes after inhaling each dose of beta 2 agonist. Values (mean and 95% CI) were expressed as a change from baseline. RESULTS--At 4 mg fenoterol produced equivalent falls in serum potassium and increases in tremor to salbutamol. The mean (95% CI) increase in heart rate (beats/min) with fenoterol at 4 mg after placebo was 47 (41-53) and after atenolol was 34 (28-40), with values for salbutamol being 46 (40-52) after placebo and 30 (24-36) after atenolol. The inotropic response (stroke distance) after atenolol at the 4 mg dose was 5.0 (3.9-6.1) cm for fenoterol and 4.7 (3.5-5.9) cm for salbutamol. There were no significant differences in heart rate or stroke distance response between the two drugs after either placebo or atenolol. Furthermore, ECG effects (Q-Tc and T wave) of fenoterol and salbutamol were comparable at both doses. CONCLUSIONS--These results show that there is no difference in the respective chronotropic or inotropic activities of fenoterol and salbutamol on cardiac beta 1 or beta 2 receptors when given at higher than conventional doses. PMID:8102213
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Bellamy, D.; Penketh, A.
1987-01-01
The potency and side effects of salbutamol and fenoterol inhalers have been compared in 8 asthmatic patients using a dose response curve. There was no significant difference in the absolute or percentage increase in FEV1 with the two treatments, but fenoterol caused a significantly greater (P less than 0.01) increase in heart rate than did salbutamol. A greater degree of bronchodilatation was observed with increased doses and we suggest that regular higher doses may provide better bronchodilatation and control of asthma in selected patients. PMID:3432172
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Anti-inflammatory effects of theophylline, cromolyn and salbutamol in a murine model of pleurisy.
Saleh, T. S.; Calixto, J. B.; Medeiros, Y. S.
1996-01-01
1. The aim of this study was to examine the effect of theophylline, cromolyn and salbutamol, three well-known anti-asthmatic drugs, on the early (4 h) and late (48 h) phases of cell migration and fluid leakage induced by carrageenin in the pleural cavity of mice. 2. In the first set of experiments, animals were pretreated (30 min) with different doses of theophylline (0.5-50 mg kg-1, i.p.), cromolyn (0.02-0.2 mg per pleural cavity) or salbutamol (0.05-50 mg kg-1, i.p.); the total and differential cell content, and also the exudate were analysed 4 h after carrageenin (1%) administration. Afterwards, in order to evaluate the time course effects of these drugs on both phases of the inflammatory reaction, one dose employed in the above protocol was chosen, to pretreat (0.5-24 h) different groups of animals. The studied parameters were evaluated 4 and 48 h after pleurisy induction. 3. Acute administration of theophylline (1-50 mg kg-1, i.p.) cromolyn (0.02-0.2 mg per pleural cavity) and salbutamol (0.5-50 mg kg-1, i.p.), 30 min prior to carrageenin, caused significant inhibition of total cell and fluid leakage in the pleural cavity at 4 h (P < 0.01). All drugs exerted a long-lasting inhibitory effect on both exudation and cell migration (P < 0.01) when administered 0.5-8 h before pleurisy induction. However, the temporal profile of the inhibitory effect induced by these drugs on the first phase of the inflammatory reaction was clearly different. Thus, the inhibitory effect induced by theophylline and cromolyn on exudation was significantly longer (up to 24 h) in comparison to their effects on cell migration (only up to 8 h). In contrast, although salbutamol when administered 30 min before pleurisy induction abolished fluid leakage (P < 0.01), this effect was not sustained in the groups pretreated for 4-8 h. In these latter groups, a significant but much smaller reduction of exudation was observed (P < 0.01), whereas the magnitude of cell migration inhibition did not
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Simultaneous spectrophotometric determination of salbutamol and bromhexine in tablets.
Habib, I H I; Hassouna, M E M; Zaki, G A
2005-03-01
Typical anti-mucolytic drugs called salbutamol hydrochloride and bromhexine sulfate encountered in tablets were determined simultaneously either by using linear regression at zero-crossing wavelengths of the first derivation of UV-spectra or by application of multiple linear partial least squares regression method. The results obtained by the two proposed mathematical methods were compared with those obtained by the HPLC technique.
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Zhang, Kai; Tang, Chaohua; Liang, Xiaowei; Zhao, Qingyu; Zhang, Junmin
2018-01-10
Salbutamol, a selective β 2 -agonist, endangers the safety of animal products as a result of illegal use in food animals. In this study, an iTRAQ-based untargeted quantitative proteomic approach was applied to screen potential protein biomarkers in plasma of cattle before and after treatment with salbutamol for 21 days. A total of 62 plasma proteins were significantly affected by salbutamol treatment, which can be used as potential biomarkers to screen for the illegal use of salbutamol in beef cattle. Enzyme-linked immunosorbent assay measurements of five selected proteins demonstrated the reliability of iTRAQ-based proteomics in screening of candidate biomarkers among the plasma proteins. The plasma samples collected before and after salbutamol treatment were well-separated by principal component analysis (PCA) using the differentially expressed proteins. These results suggested that an iTRAQ-based untargeted quantitative proteomic strategy combined with PCA pattern recognition methods can discriminate differences in plasma protein profiles collected before and after salbutamol treatment.
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Alcohol, indomethacin, and salbutamol. A comparative trial of their use in preterm labor.
Spearing, G
1979-02-01
In a comparative trial, ethanol effectively arrested preterm labor for 48 hours for more in 32% of cases, a beta-adrenergic agent (salbutamol) in 60% of cases (not statistically significant), and a combination of ethanol and indomethacin in 70% of cases (statistically significant, P less than 0.5). Labor was delayed for 14 days or more in 36, 60, and 50%, respectively (not statistically significant). The numbers studied were small, and tests of statistical significance were of doubtful value. Salbutamol was more acceptable to patients and the staff than ethanol. The trial was suspended and eventually abandoned due to reports of prostaglandin synthetase inhibitors causing premature closure of the ductus arteriosus. In this series no problems were encountered with the use of indomethacin.
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Chan, Sue Hay; Lee, Warren; Asmawi, Mohd Zaini; Tan, Soo Choon
2016-07-01
A sequential solid-phase extraction (SPE) method was developed and validated using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) for the detection and quantification of salbutamol enantiomers in porcine urine. Porcine urine samples were hydrolysed with β-glucuronidase/arylsulfatase from Helix pomatia and then subjected to a double solid-phase extraction (SPE) first using the Abs-Elut Nexus SPE and then followed by the Bond Elut Phenylboronic Acid (PBA) SPE. The salbutamol enantiomers were separated using the Astec CHIROBIOTIC™ T HPLC column (3.0mm×100mm; 5μm) maintained at 15°C with a 15min isocratic run at a flow rate of 0.4mL/min. The mobile phase constituted of 5mM ammonium formate in methanol. Salbutamol and salbutamol-tert-butyl-d9 (internal standard, IS) was monitored and quantified with the multiple reaction monitoring (MRM) mode. The method showed good linearity for the range of 0.1-10ng/mL with limit of quantification at 0.3ng/mL. Analysis of the QC samples showed intra- and inter-assay precisions to be less than 5.04%, and recovery ranging from 83.82 to 102.33%. Copyright © 2016 Elsevier B.V. All rights reserved.
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Sharma, Deepak
2013-01-01
Recent developments in fast disintegrating tablets have brought convenience in dosing to pediatric and elderly patients who have trouble in swallowing tablets. The objective of the present study was to prepare the fast disintegrating tablet of salbutamol sulphate for respiratory disorders for pediatrics. As precision of dosing and patient's compliance become important prerequisites for a long-term treatment, there is a need to develop a formulation for this drug which overcomes problems such as difficulty in swallowing, inconvenience in administration while travelling, and patient's acceptability. Hence, the present investigation were undertaken with a view to develop a fast disintegrating tablet of salbutamol sulphate which offers a new range of products having desired characteristics and intended benefits. Superdisintegrants such as sodium starch glycolate was optimized. Different binders were optimized along with optimized superdisintegrant concentration. The tablets were prepared by direct compression technique. The tablets were evaluated for hardness, friability, weight variation, wetting time, disintegration time, and uniformity of content. Optimized formulation was evaluated by in vitro dissolution test, drug-excipient compatibility, and accelerated stability study. It was concluded that fast disintegrating tablets of salbutamol sulphate were formulated successfully with desired characteristics which disintegrated rapidly; provided rapid onset of action; and enhanced the patient convenience and compliance. PMID:23956881
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Schneider, Carl R; Everett, Alan W; Geelhoed, Elizabeth; Padgett, Cale; Ripley, Scott; Murray, Kevin; Kendall, Peter A; Clifford, Rhonda M
2010-01-01
Earlier work established an evidence practice gap during provision of nonprescription salbutamol (albuterol). Pharmacist interns are hypothesized to be in a position to improve professional practice in the community pharmacy setting. To explore the potential of intern pharmacists to improve the professional practice of community pharmacy staff in the provision of nonprescription salbutamol. Intern pharmacists (n = 157) delivered an asthma intervention in 136 pharmacies consisting of an educational activity to pharmacy staff and a health promotion campaign to consumers. Post-intervention, simulated patients presented to 100 intervention and 100 control community pharmacies with a request for salbutamol. The appropriate outcome was medical referral for poor asthma control and correction of poor inhaler technique. Incidence and quantity of patient assessment and counseling provided during the visit were also assessed. Logistic regression was used to determine the predictors of medical referral. A doubling in the rate of medical referral was seen in the intervention group (19% vs 40%; p = 0.001). Assessment of reliever use frequency was the main predictor of medical referral (OR = 22.7; 95% CI 9.06 to 56.9). Correction of poor inhaler technique did not improve; however, a reduction in salbutamol supplied without patient assessment (23% vs 8%; p = 0.009) or counseling (75% vs 48%; p < 0.001) was noted. A doubling in the rate of medical referral showed a clear improvement in professional practice during the provision of nonprescription salbutamol. The improved patient outcome in the intervention group was due to increased assessment of reliever use frequency. Identification of poor inhaler technique remained near zero in both groups, which suggests that intern pharmacists were able to improve the current practice of community pharmacies yet were unable to establish a new practice behavior. This study provides evidence that intern pharmacists can act as change agents to
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Guo, Zhening; Chen, Yangsheng; Ding, Xiaoliang; Huang, Chenrong; Miao, Liyan
2016-11-01
A rapid, selective and sensitive liquid chromatography-tandem mass spectrometry assay method was developed for simultaneous determination of ambroxol and salbutamol in human plasma using citalopram hydrobromide as internal standard (IS). The sample was alkalinized with ammonia water (33:67, v/v) and extracted by single liquid-liquid extraction with ethyl acetate. Separation was achieved on Waters Acquity UPLC BEH C 18 column using a gradient program at a flow rate of 0.2 mL/min. Detection was performed using electrospray ionization in positive ion multiple reaction monitoring mode by monitoring the ion transitions m/z 378.9 → 263.6 (ambroxol), m/z 240.2 → 147.7 (salbutamol) and m/z 325.0 → 261.7 (IS). The total analytical run time was relatively short (3 min). Calibration curves were linear in the concentration range of 0.5-100.0 ng/mL for ambroxol and 0.2-20.0 ng/mL for salbutamol, with intra- and inter-run precision (relative standard deviation) <15% and accuracy (relative error) ranging from 97.7 to 112.1% for ambroxol and from 94.5 to 104.1% for salbutamol. The method was successfully applied in a clinical pharmacokinetic study of the compound ambroxol and salbutamol tablets. Copyright © 2016 John Wiley & Sons, Ltd.
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Tahvanainen, Anna; Leskinen, Miia; Koskela, Jenni; Ilveskoski, Erkki; Alanko, Juha; Kähönen, Mika; Kööbi, Tiit; Lehtimäki, Lauri; Moilanen, Eeva; Mustonen, Jukka; Pörsti, Ilkka
2009-01-01
AIMS To examine the effects of salbutamol and L-arginine, two compounds acting largely on the endothelium, and the endothelium-independent agent nitroglycerin on blood pressure, arterial compliance, cardiac function and vascular resistance. METHODS Continuous radial pulse wave analysis, whole-body impedance cardiography, and plethysmographic blood pressure from fingers in the supine position and during head-up tilt were recorded in nine healthy subjects. Data were captured before and after L-arginine (10 mg mg−1 min−1) or saline infusion, salbutamol (400 µg) or placebo inhalation, and sublingual nitroglycerin (0.25 mg) or placebo resoriblet. RESULTS The results of all measurements were comparable before drug administration. The effects of inhaled salbutamol were apparent in the supine position: systemic vascular resistance (−9.2 ± 2.6%) and augmentation index (−4.0 ± 1.5%) decreased, and heart rate (8.6 ± 2.5%) and cardiac output (8.8 ± 3.1%) increased. L-arginine had no clear effects on supine haemodynamics, but during head-up tilt blood pressure was moderately decreased and reduction in aortic reflection time prevented, indicating improved large arterial compliance. Nitroglycerin reduced supine vascular resistance (−6.7 ± 1.8%) and augmentation index (−7.4 ± 1.6%), and increased cardiac output (+9.2 ± 2.7%). During head-up tilt, nitroglycerin increased cardiac output (+10.6 ± 5.6%) and heart rate (+40 ± 7.5%), decreased vascular resistance (−7.8 ± 5.8%) and augmentation index (−18.7 ± 3.2%), and prevented the decrease in aortic reflection time. CONCLUSIONS Inhaled salbutamol predominantly changed supine haemodynamics, whereas the moderate effects of L-arginine were observed during the head-up tilt. In contrast, small doses of nitroglycerin induced major changes in haemodynamics both supine and during the head-up tilt. Altogether, these results emphasize the importance of haemodynamic measurements in both the supine and upright
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Atanasovska, Tania; Smith, Robert; Graff, Claus; Tran, Cao Thach; Melgaard, Jacob; Kanters, Jørgen K; Petersen, Aaron C; Tobin, Antony; Kjeldsen, Keld P; McKenna, Michael John
2018-05-10
Intense exercise induces pronounced hyperkalemia, followed by transient hypokalemia in recovery. We investigated whether the β 2 -agonist salbutamol attenuated the exercise-hyperkalemia, and exacerbated the post-exercise hypokalemia, and whether hypokalemia was associated with impaired cardiac repolarization (QT hysteresis). Eleven healthy adults participated in a randomized, counterbalanced, double-blind trial receiving either 1000 µg salbutamol (SAL) or placebo (PLAC) by inhalation. Arterial plasma potassium concentration ([K + ] a ) was measured at rest, during 3 min intense rowing exercise and 60 min recovery. QT hysteresis was calculated from ECG (n=8). [K + ] a increased above baseline during exercise (rest, 3.72{plus minus}0.7 vs end-exercise, 6.81{plus minus}1.4 mM, P<0.001, mean{plus minus}SD) and decreased rapidly during early recovery to below baseline; restoration was incomplete at 60 min post-exercise (P<0.05). [K + ] a was less during SAL than PLAC (4.39{plus minus}0.13 vs. 4.73{plus minus}0.19 mM, pooled across all times, P=0.001, treatment main effect). [K + ] a was lower after SAL than PLAC, from 2 min pre-exercise until 2.5 min during exercise, and at 50 and 60 min post-exercise (P<0.05). The post-exercise decline in [K + ] a was correlated with QT hysteresis (r=0.343, n=112, pooled data, P=0.001). Thus the decrease in [K + ] a from end-exercise by ~4 mM was associated with reduced QT hysteresis by ~75 ms. Whilst salbutamol lowered [K + ] a during exercise, no additive hypokalemic effects occurred in early recovery, suggesting there may be a protective mechanism against severe or prolonged hypokalemia after exercise when treated by salbutamol. This is important since post-exercise hypokalemia impaired cardiac repolarization, which could potentially trigger arrhythmias and sudden cardiac death in susceptible individuals with pre-existing hypokalemia and/or heart disease.
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Quan-Jun, Yang; Jian-Ping, Zhang; Jian-Hua, Zhang; Yong-Long, Han; Bo, Xin; Jing-Xian, Zhang; Bona, Dai; Yuan, Zhang; Cheng, Guo
2017-03-01
Inhaled budesonide and salbutamol represent the most important and frequently used drugs in asthmatic children during acute exacerbation. However, there is still no consensus about their resulting metabolic derangements; thus, this study was conducted to determine the distinct metabolic profiles of these two drugs. A total of 69 children with asthma during acute exacerbation were included, and their serum and urine were investigated using high-resolution nuclear magnetic resonance (NMR). A metabolomics analysis was performed using a principal component analysis and orthogonal signal correction-partial least squares using SIMCA-P. The different metabolites were identified, and the distinct metabolic profiles were analysed using MetPA. A high-resolution NMR-based serum and urine metabolomics approach was established to study the overall metabolic changes after inhaled budesonide and salbutamol in asthmatic children during acute exacerbation. The perturbed metabolites included 22 different metabolites in the serum and 21 metabolites in the urine. Based on an integrated analysis, the changed metabolites included the following: increased 4-hydroxybutyrate, lactate, cis-aconitate, 5-hydroxyindoleacetate, taurine, trans-4-hydroxy-l-proline, tiglylglycine, 3-hydroxybutyrate, 3-methylhistidine, glucose, cis-aconitate, 2-deoxyinosine and 2-aminoadipate; and decreased alanine, glycerol, arginine, glycylproline, 2-hydroxy-3-methylvalerate, creatine, citrulline, glutamate, asparagine, 2-hydroxyvalerate, citrate, homoserine, histamine, sn-glycero-3-phosphocholine, sarcosine, ornithine, creatinine, glycine, isoleucine and trimethylamine N-oxide. The MetPA analysis revealed seven involved metabolic pathways: arginine and proline metabolism; taurine and hypotaurine metabolism; glycine, serine and threonine metabolism; glyoxylate and dicarboxylate metabolism; methane metabolism; citrate cycle; and pyruvate metabolism. The perturbed metabolic profiles suggest potential metabolic
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Malakar, Jadupati; Datta, Prabir Kumar; Purakayastha, Saikat Das; Dey, Sanjay; Nayak, Amit Kumar
2014-03-01
The present study deals with the development and evaluations of stomach-specific floating capsules containing salbutamol sulfate-loaded oil-entrapped alginate-based beads. Salbutamol sulfate-loaded oil-entrapped beads were prepared and capsulated within hard gelatin capsules (size 1). The effects of HPMC K4M and potato starch weight masses on drug encapsulation efficiency (DEE) of beads and cumulative drug release at 10h (R10 h) from capsules was analyzed by 3(2) factorial design. The optimization results indicate increasing of DEE in the oil-entrapped beads and decreasing R10 h from capsules with increment of HPMC K4M and potato starch weight masses. The optimized formulation showed DEE of 70.02 ± 3.16% and R10 h of 56.96 ± 2.92%. These capsules showed floatation over 6h and sustained drug release over 10h in gastric pH (1.2). In vivo X-ray imaging study of optimized floating capsules in rabbits showed stomach-specific gastroretention over a prolonged period. Copyright © 2013 Elsevier B.V. All rights reserved.
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Salbutamol in paediatrics: pharmacology, prescribing and controversies.
Andrzejowski, Paul; Carroll, Will
2016-08-01
Salbutamol has become a key drug in respiratory medicine since it was first developed by Sir David Jack et al in 1968, 5000 years after the β agonist ephedrine was first used in its raw form, as the Ma Huang herb in Chinese medicine to treat asthma. It is one of the most commonly encountered medicines in paediatric practice and the authors have found that an understanding of its pharmacology in clinical practice is incredibly helpful. In this article, we discuss its pharmacology and pharmacodynamics, practical prescribing points and some unresolved issues surrounding its use, which should serve to provide an essential working knowledge for the busy paediatrician. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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Design and Development of a Salbutamol Intake Detector for Low Respiratory Treatment
NASA Astrophysics Data System (ADS)
Vui Hin, Tsen; Ilyani Ramli, Nur
2017-08-01
This paper proposed a new salbutamol intake detector design using asthma spacer and gas sensor. The device enable real time monitoring of propellant level inhaled by the infant which will decrease the recovery time of the asthma attack. Microcontroller Arduino UNO is program to control the input and output of the system. MQ6 gas sensor detecting the propellant Hydrofluoroalkane from the metered dose inhaler (MDI) canister and demonstrated the level of propellant inhaled on the LCD in real time. MQ6 gas sensor suitable used to detect concentration of propellant inside the asthma spacer due to it is low sensitive to natural gas where include the carbon dioxide exhaled by the infant. Besides this, MQ6 gas sensor also highly sensitive to propane and the preview aerosol inventor mentioned propane as propellant which used for MDI to push the salbutamol out from MDI canister. Therefore, MQ6 gas sensor is suitable to detect propellant inside asthma spacer. The output voltage of MQ6 in initial state where no propellant inside asthma spacer is between 0.55V and 0.65V. Furthermore, when the MDI canister is been pressed, the concentration of propellant is increased and the output voltage of MQ6 gas sensor also increased in ranged between 1.1V and 1.2V.
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Li, Wei; Shi, Cai-Hong; Sheng, Yi-Ling; Cui, Ping; Zhao, Yu-Qing; Zhang, Xiang-Rong
2013-12-01
The aim of this study was to investigate the in vitro and in vivo performance of salbutamol sulfate press-coated tablets for delayed release. The in vitro release behavior of press-coated tablets with the outer layer of PEG 6000/ Eudragit S100 blends (2:1) in pH 1.2 (0.1 mol L-1 HCl) and then pH 6.8 buffer solution was examined. Morphological change of the press-coated tablet during in vitro release was recorded with a digital camera. Release of salbutamol sulfate from press-coated tablets was less than 5 % before 3 h and was completed after 8 h in pH 6.8 phosphate buffer solution. In vivo gamma scintigraphy study carried out on healthy men indicated that the designed system released the drug in lower parts of the GI tract after a lag time of 5 hours. The results showed the capability of the system of achieving delayed release of the drug in both in vitro and in vivo gamma scintigraphy studies.
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Molina, Carlos; Kaialy, Waseem; Chen, Qiao; Commandeur, Daniel; Nokhodchi, Ali
2017-12-19
Spray-drying allows to modify the physicochemical/mechanical properties of particles along with their morphology. In the present study, L -leucine with varying concentrations (0.1, 0.5, 1, 5, and 10% w/v) were incorporated into lactose monohydrate solution for spray-drying to enhance the aerosolization performance of dry powder inhalers containing spray-dried lactose-leucine and salbutamol sulfate. The prepared spray-dried lactose-leucine carriers were analyzed using laser diffraction (particle size), differential scanning calorimetry (thermal behavior), scanning electron microscopy (morphology), powder X-ray diffraction (crystallinity), Fourier transform infrared spectroscopy (interaction at molecular level), and in vitro aerosolization performance (deposition). The results showed that the efficacy of salbutamol sulfate's aerosolization performance was, in part, due to the introduction of L -leucine in the carrier, prior to being spray-dried, accounting for an increase in the fine particle fraction (FPF) of salbutamol sulfate from spray-dried lactose-leucine (0.5% leucine) in comparison to all other carriers. It was shown that all of the spray-dried carriers were spherical in their morphology with some agglomerates and contained a mixture of amorphous, α-lactose, and β-lactose. It was also interesting to note that spray-dried lactose-leucine particles were agglomerated during the spray-drying process to make coarse particles (volume mean diameter of 79 to 87 μm) suitable as a carrier in DPI formulations.
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Gefen, Eran; Gopalan, Gokul; McDonald, Rosie; Thomas, Vicky; Ming, Simon Wan Yau; Davis, Emily
2018-01-01
Introduction Ventolin Nebules® (reference product; GlaxoSmithKline) was the first licensed nebulizer solution containing the rapid-onset, short-acting β2-agonist salbutamol. Salbutamol Steri-Neb™ (comparator; Teva Pharmaceuticals, Inc.) has the same chemical composition as the reference product. This study evaluated whether the effectiveness of the comparator is non-inferior to the reference product alongside concomitant medications during real-life clinical management of COPD exacerbations. Safety in terms of adverse events (AEs) was also examined. Methods This matched (1:1) historical cohort study evaluated data from 2 UK primary care databases on patients prescribed the salbutamol comparator or reference. The study included a 1-year baseline period, starting 1 year before the index prescription date, and 1-year outcome period. Cohorts were matched for baseline COPD respiratory medications. The primary outcome was analysis of non-inferiority for the comparator versus reference product for the rate of moderate and severe COPD exacerbations. Non-inferiority was satisfied if the 95% confidence interval (CI) upper limit for mean differences in proportions between treatments was <15%. Secondary outcomes were examined through rate ratios (RR) of severe exacerbations and AEs. Results After matching, 1191 patients were included in each cohort. Adjusted upper 95% CI for the difference in proportion of patients experiencing moderate or severe exacerbations between comparator and reference groups was 0.032 (3.2%), demonstrating non-inferiority. No significant differences were observed in rates of moderate and severe exacerbations (RR: 1.00; 95% CI: 0.91, 1.10), severe exacerbations (RR: 0.76; 95% CI: 0.49, 1.17), or AEs (RR: 0.98; 95% CI: 0.78, 1.22) after adjusting for baseline confounders. No significant differences across cohorts were observed for rates of any AE or death. Conclusion This matched cohort study of real-life management of COPD patients supports the
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Lee, Daniel K C; Bates, Caroline E; Lipworth, Brian J
2004-01-01
The relationship between beta2-adrenoceptor polymorphisms at positions 16 and 27, and the acute systemic beta2-adrenoceptor effects of inhaled salbutamol is unclear. We therefore elected to evaluate the influence of common homozygous beta2-adrenoceptor haplotypes on the acute systemic beta2-adrenoceptor effects following inhaled salbutamol in asthmatic subjects. An initial database search of 531 asthmatic subjects identified the two commonest homozygous haplotypes at positions 16 and 27 to be Arg16-Gln27 (12%) and Gly16-Glu27 (19%). After a 1-week washout period where all beta2-adrenoceptor agonists were withdrawn, 16 Caucasian subjects (Arg16-Gln27: n = 8 and Gly16-Glu27: n = 8) were given a single dose of inhaled salbutamol (1200 microg), followed by serial blood sampling for serum potassium, along with measurements of diastolic blood pressure and heart rate, at 5-min intervals for 20 min. The two groups were well matched for age, sex, FEV1, and inhaled corticosteroid dose. Baseline values for serum potassium, diastolic blood pressure and heart rate were not significantly different comparing Arg16-Gln27 vs Gly16-Glu27. The mean +/- SEM maximum serum potassium change from baseline over 20 min was significantly greater (P = 0.04) for Arg16-Gln27: -0.37 +/- 0.05 mmol l(-1) vs Gly16-Glu27: -0.23 +/- 0.04 mmol l(-1); 95% CI for difference: -0.01 to -0.28 mmol l(-1). The maximum diastolic blood pressure change from baseline over 20 min was significantly greater (P = 0.0008) for Arg16-Gln27: -13 +/- 1 mmHg vs Gly16-Glu27: -4 +/- 2 mmHg; 95% CI for difference: -5, 14 mmHg. There was no significant difference comparing the maximum heart rate change from baseline for Arg16-Gln27: 10 +/- 3 beats min(-1) vs Gly16-Glu27: 10 +/- 3 beats min(-1). Caucasian asthmatic subjects with the Arg16-Gln27 haplotype exhibited a greater systemic response to inhaled salbutamol, compared with those with the Gly16-Glu27 haplotype. The attenuated beta2-adrenoceptor response in the Gly16-Glu27
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Sculpher, M J; Buxton, M J
1993-11-01
The construction of a composite effectiveness measure was explored using clinical data collected routinely in trials of drug therapies for asthma. The measure is the episode-free day (EFD), where an 'episode' is either an asthma attack, the need for rescue medication, sleep disturbance caused by asthma, or an adverse event. The EFD measure was used in a retrospective cost-effectiveness analysis of a previous Phase III controlled clinical trial of formoterol versus salbutamol, in which 145 patients with bronchial asthma were randomised to receive maintenance therapy with either inhaled formoterol or inhaled salbutamol over a 12-week period. Average and incremental cost-effectiveness ratios were assessed for the 2 drugs in terms of the total expected cost of drug plus rescue therapy, and EFD rates. The analysis suggests that, with relatively little addition to clinical data collection, economically and clinically meaningful composite measures can be constructed to assist in making cost-effectiveness comparisons between alternative asthma therapies.
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[Influence of CNTs on Photodegradation of Salbutamol in Water Environment].
Wang, Qi; Han, Jia-rui; Wei, Bo-fan; Zhou, Lei; Zhang, Ya; Yang, Xi
2015-08-01
The influence of CNTs on the photolysis of organic pollutant was investigated by studying the photodegradation kinetics of SAL under 1000 W Xenon lamp, in the presence of three kinds of CNTs (SCNT, MWNT-COOH, MWNT-OH). In addition, the interaction between CNTs and Fe3" was also investigated. The results showed that the photodegradation of salbutamol followed pseudo-first-order kinetics, which could be inhibited by all three kinds of CNTs through light screening effect. Formation of singlet oxygen was detected during the photolysis, using the molecular probe furfuryl alcohol. All three kinds of CNTs could absorb electrons through competition, i.e., inhibit SAL photodegradation by light screening effect; meanwhile, the CNTs could generate singlet oxygen through photoexcitation to promote the photodegradation reaction. Both mechanisms coexisted, and in most cases, the inhibition effect was dominant. In addition, CNTs could inactivate the photoactive substance Fe3 in the water body by electrostatic adsorption, and affect the photochemical behavior of organic pollutants in natural water body.
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Juergens, Uwe R; Stöber, M; Libertus, H; Darlath, W; Gillissen, A; Vetter, H
2004-07-30
Beta2-adrenergic receptor agonists have several effects on airway function, most of which are mediated in a variety of cell types resulting in increased c-AMP-production and inhibition of inflammatory mediator production. However, their stimulating effects on cAMP-production became known to be inversed by increasing phosphodiesterase (PDE) activity and degradation of cAMP. Therefore, in this study we have evaluated the efficacy of reproterol, a dual acting beta2-adrenoceptor agonist and PDE-inhibitor, as compared to salbutamol and fenoterol with respect to production of cAMP and LTB4 in cultured monocytes. Isolated human monocytes (10(5)/ml) were incubated (n = 9) in suspension with beta2-adrenoceptor agonists (10(-10) -10(-4) M) for 30 minutes with and without IBMX. Then, cAMP production was determined following treatment with Triton-X100. Production of LTB4 was measured following incubation of beta2-adrenoceptor agonists for 4 hrs in the presence of LPS (10 mg/ml). cAMP and LTB subset 4 were measured in culture supernatants by enzyme immunoassay. At 10(-5) M, production of cAMP was significantly stimulated by reproterol > fenoterol > salbutamol in a dose-dependent manner to an extent of *128%, *65%, 13% (*p<0.04) respectively. In contrast, LTB4-production was inhibited significantly to a similar degree by salbutamol and reproterol in a dose-dependent manner by 59% and 49% (10(-5) M, p<0.03), respectively, with decreasing inhibition (15%) after fenoterol. Following co-incubation with IBMX, cAMP production only increased significantly (p<0.002) after fenoterol (+110%) compared to salbutamol (+29%) and reproterol (+50%) (ANOVA, p<0.001). These data suggest effects of the theophylline constituent of reproterol to inhibit adenylyl cyclase induced phosphodiesterase activity. The advantageous synergistic effects of reproterol on cAMP-production need to be further explored in trials.
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Flint, K. C.; Hockley, B.; Johnson, N. M.
1983-01-01
The efficacy of a single metered dose inhaler containing a combination of fenoterol (100 micrograms/puff) and ipratropium bromide (40 micrograms/puff) has been assessed in 12 asthmatics. We conclude that the bronchodilator effect of 2 puffs of the combination inhaler was significantly greater than that achieved by 2 puffs of salbutamol (100 micrograms/puff). PMID:6227877
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Particle engineering using sonocrystallization: salbutamol sulphate for pulmonary delivery.
Dhumal, Ravindra S; Biradar, Shailesh V; Paradkar, Anant R; York, Peter
2009-02-23
The aim of present work was to produce fine elongated crystals of salbutamol sulphate (SS) by sonocrystallization for pulmonary delivery and compare with micronized and spray dried SS (SDSS) for in vitro aerosolization behavior. Application of ultrasound during anti-solvent crystallization resulted in fine elongated crystals (sonocrystallized SS; SCSS) compared to aggregates of large irregular crystals obtained without sonication. Higher sonication amplitude, time, concentration and lower processing temperatures favored formation of smaller crystals with narrow particle size distribution (PSD). SCSS was separated from dispersion by spray drying in the form of loose aggregates (SD-SCSS). The fine particle fraction (FPF) of formulations with coarse lactose carrier in cascade impactor increased from 16.66% for micronized SS to 31.12% for SDSS (obtained by spray drying aqueous SS solution) and 44.21% for SD-SCSS, due to reduced cohesive/adhesive forces and aerodynamic size by virtue of elongated shape of crystals. SD-SCSS was stable without any change in crystallinity and aerodynamic behavior for 3 months at 40 degrees C/75% RH, but amorphous SDSS showed recrystallization with poor aerosolization performance on storage. Sonocrystallization, a rapid and simple technique is reported for production of SS crystals suitable for inhalation delivery.
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NASA Astrophysics Data System (ADS)
Pokrovskiy, O. I.; Kayda, A. S.; Usovich, O. I.; Parenago, O. O.; Lunin, V. V.
2017-11-01
A regime is found in which chiral stationary phase based on macrocyclic glycopeptide eremomycin allows separation of salbutamol sulfate enantiomers in supercritical fluid chromatography. Enantioseparation occurs only when two dynamic modifiers are used simultaneously: isopropylamin + trifluoroacetic acid or isopropylamin + ammonium acetate. Amine molar concentration in mobile phase has to be higher than acid molar concentration, otherwise enantiomers coelute. We suppose that with amine excess a mechanism of enantiorecognition is realized which involves ionic sorbent-sorbate interactions. Such mechanism is well-known for glycopeptide chiral selectors in liquid chromatography, but for supercritical fluid chromatography it is reported for the first time.
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Yang, Ssu-Han; Yang, Tsung-Ming; Lin, Hui-Ling; Tsai, Ying-Huang; Fang, Tien-Pei; Wan, Gwo-Hwa
2018-02-01
Few studies have evaluated the size distribution of inhaled and exhaled aerosolized drugs, or the effect of heated humidification on particle size and lung deposition. The present study evaluated these aspects of bronchodilator (salbutamol/ipratropium) delivery using a lung model in the absence and presence of heat and humidification. We positioned filters to collect and measure the initial drug, inhaled drug, and exhaled drug. Particle size distribution was evaluated using an 8-stage Marple personal cascade impactor with 0.2-μm polycarbonate filters. A greater inhaled drug mass was delivered using a vibrating mesh nebulizer (VMN) than by using a small volume nebulizer (SVN), when heated humidifiers were not employed. When heated and humidified medical gas was used, there was no significant difference between the inhaled drug mass delivered by the VMN and that delivered by the SVN. A significantly greater mass of inhaled 1.55-μm drug particles was produced by the VMN than with the SVN, under heated and humidified conditions. However, the mass median aerodynamic diameters (MMADs) of the aerosolized drug produced by the SVN and VMN did not differ significantly under the same conditions. The VMN produced more fine particles of salbutamol/ipratropium, and the drug particle size clearly increased in the presence of heat and humidification. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Formulation and Development of Metered Dose Inhalations of Salbutamol in Solution Form
Khale, Anubha; Bajaj, Amrita
2011-01-01
In the present study attempts were made to prepare metered dose inhalation of salbutamol in solution form and compared it with the marketed metered dose inhalation in suspension form. Solution form of the drug was found better than marketed suspension formulation with respect to homogeneity and content uniformity. Propellant blend P-11 and P-12 in the proportion 30:70 was selected as it gave optimum vapour pressure. Surfactant oleic acid in concentration 10 mg per can was selected as it gave best results with clarity, spray pattern, vapour pressure, content per spray and rate of evaporation. Ethyl alcohol 2 ml per can was used as a cosolvent to give a clear solution, optimum vapour pressure, maximum content per spray and fair rate of evaporation. The selected formulation was subjected to the physico-chemical evaluation tests as per the standard pharmacopoeial procedures and the characteristics of the formulations were further compared with a conventional marketed formulation. In vitro study reveled the net respirable fraction was better than marketed preparation. PMID:22923867
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Driessen, Jean M M; Gerritsma, Margryt; Westbroek, Jaap; ten Hacken, Nick H T; de Jongh, Frans H C
2013-07-09
Prevalence of exercise-induced bronchoconstriction (EIB) is high in elite athletes, especially after many years training in cold and dry air conditions. The primary treatment of EIB is inhaling a short-acting beta-2-agonist such as salbutamol. However, professional speed skaters also inhale nebulized isotonic saline or tap water before and after a race or intense training. The use of nebulized isotonic saline or tap water to prevent EIB has not been studied before, raising questions about safety and efficacy. The aim of this study is to analyze the acute effect of nebulized isotonic saline or salbutamol on EIB in elite speed skaters following a 1,500-meter race. This randomized controlled trial compares single dose treatment of 1 mg nebulized salbutamol in 4 mL of isotonic saline, or with 5 mL of isotonic saline. A minimum of 13 participants will be allocated in each treatment group. Participants should be between 18 and 35 years of age and able to skate 1,500 m in less than 2 min 10 s (women) or 2 min 05 s (men). Repeated measurements of spirometry, forced oscillation technique, and electromyography will be performed before and after an official 1,500-m race. Primary outcome of the study is the difference in fall in FEV1 after exercise in the different treatment groups. The trial is currently enrolling participants. Elite athletes run the risk of pulmonary inflammation and remodeling as a consequence of their frequent exercise, and thus increased ventilation in cold and dry environments. Although inhalation of nebulized isotonic saline is commonplace, no study has ever investigated the safety or efficacy of this treatment. This trial protocol was registered with the Dutch trial registration for clinical trials under number NTR3550.
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Spin, Paul; Sketris, Ingrid; Hill-Taylor, Barbara; Ward, Courtney; Hurley, Katrina F
2017-01-01
Despite evidence demonstrating the advantages of metered-dose inhalers with spacers (MDI-s), nebulization (NEB) remains the primary method of asthma treatment in some pediatric emergency departments (PEDs). There is a perception that delivering salbutamol by MDI-s is more costly than by NEB. This research evaluates the relative costs of MDI-s and NEB using local, hospital-specific, patient-level data. Regression models estimated associations between the salbutamol inhalation method and costs, length of stay (LOS) in the PED and hospital, and the probability of admission. Our population was a random sample of 822 patients presenting with wheeze to the PED in 2008/2009. Control variables included age, sex, triage acuity, time of PED visit, other medications, and vitals. Costs were calculated using the prices and quantities of medical resources used per treatment. Probabilistic sensitivity analysis was used. Treatment with MDI-s versus NEB was associated with an absolute decrease in hospitalization of 4.4% (p<0.05) and a 25-hour (p<0.001) reduction in average inpatient stay, after controlling for triage acuity and patient characteristics. This resulted in savings of $24/patient in the PED and $180/patient overall (p<0.001). Inpatient care accounted for more than 90% of total patient costs. Our results suggest economic gains associated with MDI-s for salbutamol inhalation in PEDs. Sensitivity analyses show that this conclusion is not affected by changes in model parameters that may differ by jurisdiction. Since most facilities already collect the data used for this study, our methods could be adopted for a cross-jurisdictional account of the cost effectiveness of MDI-s.
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Sustained delivery of salbutamol and beclometasone from spray-dried double emulsions.
Learoyd, Tristan P; Burrows, Jane L; French, Eddie; Seville, Peter C
2010-01-01
The sustained delivery of multiple agents to the lung offers potential benefits to patients. This study explores the preparation of highly respirable dual-loaded spray-dried double emulsions. Spray-dried powders were produced from water-in-oil-in-water (w/o/w) double emulsions, containing salbutamol sulphate and/or beclometasone dipropionate in varying phases. The double emulsions contained the drug release modifier polylactide co-glycolide (PLGA 50 : 50) in the intermediate organic phase of the original micro-emulsion and low molecular weight chitosan (Mw<190 kDa: emulsion stabilizer) and leucine (aerosolization enhancer) in the tertiary aqueous phase. Following spray-drying resultant powders were physically characterized: with in vitro aerosolization performance and drug release investigated using a Multi-Stage Liquid Impinger and modified USP II dissolution apparatus, respectively. Powders generated were of a respirable size exhibiting emitted doses of over 95% and fine particle fractions of up to 60% of the total loaded dose. Sustained drug release profiles were observed during dissolution for powders containing agents in the primary aqueous and secondary organic phases of the original micro-emulsion; the burst release of agents was witnessed from the tertiary aqueous phase. The novel spray-dried emulsions from this study would be expected to deposit and display sustained release character in the lung.
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Sirichai, Somsak; Khanatharana, Proespichaya
2008-09-15
Capillary electrophoresis (CE) with UV detection for the simultaneous and short-time analysis of clenbuterol, salbutamol, procaterol, fenoterol is described and validated. Optimized conditions were found to be a 10 mmoll(-1) borate buffer (pH 10.0), an separation voltage of 19 kV, and a separation temperature of 32 degrees C. Detection was set at 205 nm. Under the optimized conditions, analyses of the four analytes in pharmaceutical and human urine samples were carried out in approximately 1 min. The interference of the sample matrix was not observed. The LOD (limits of detection) defined at S/N of 3:1 was found between 0.5 and 2.0 mgl(-1) for the analytes. The linearity of the detector response was within the range from 2.0 to 30 mgl(-1) with correlation coefficient >0.996.
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Aquatic photolysis of β2-agonist salbutamol: kinetics and mechanism studies.
Zhou, Lei; Wang, Qi; Zhang, Ya; Ji, Yuefei; Yang, Xi
2017-02-01
Salbutamol (SAL) has been widely used as medicine both in treating asthma and in animal primary production; an increasing number of reports have detected SAL in natural waters. The photolysis kinetic and pathway of SAL in aquatic system were studied, as well as the effect of several natural water constituents, such as nitrate, dissolved oxygen (DO) and ferric ions. According to our research, the direct photolysis of SAL followed pseudo-first-order reaction kinetics. Alkaline condition could promote the degradation of SAL; the increase of solution pH would simultaneously increase the fraction of the deprotonated forms of SAL (including the deprotonated and zwitterionic species), which were easier to be excited, and result in the bathochromic shift of the UV-Vis spectrum and, finally, accelerate the degradation rate of SAL. The presence of nitrate could enhance the removal rate of SAL via generation hydroxyl radical (·OH) under irradiation. In addition, the absence of oxygen in the reaction solution could decrease the photolysis. Moreover, Fe(III) was able to chelate with SAL to form an octahedral complex, which was photochemically reactive. The octahedral complex could generate ·OH to oxidize SAL itself in turn. The pathways of SAL photolysis were also investigated by means of the solid phase extraction (SPE)-LC-MS method. The major pathways of SAL photodegradation included oxidation and side-chain cleavage.
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van Meenen, David M P; van der Hoeven, Sophia M; Binnekade, Jan M; de Borgie, Corianne A J M; Merkus, Maruschka P; Bosch, Frank H; Endeman, Henrik; Haringman, Jasper J; van der Meer, Nardo J M; Moeniralam, Hazra S; Slabbekoorn, Mathilde; Muller, Marcella C A; Stilma, Willemke; van Silfhout, Bart; Neto, Ary Serpa; Ter Haar, Hans F M; Van Vliet, Jan; Wijnhoven, Jan Willem; Horn, Janneke; Juffermans, Nicole P; Pelosi, Paolo; Gama de Abreu, Marcelo; Schultz, Marcus J; Paulus, Frederique
2018-03-13
It remains uncertain whether nebulization of mucolytics with bronchodilators should be applied for clinical indication or preventively in intensive care unit (ICU) patients receiving invasive ventilation. To determine if a strategy that uses nebulization for clinical indication (on-demand) is noninferior to one that uses preventive (routine) nebulization. Randomized clinical trial enrolling adult patients expected to need invasive ventilation for more than 24 hours at 7 ICUs in the Netherlands. On-demand nebulization of acetylcysteine or salbutamol (based on strict clinical indications, n = 471) or routine nebulization of acetylcysteine with salbutamol (every 6 hours until end of invasive ventilation, n = 473). The primary outcome was the number of ventilator-free days at day 28, with a noninferiority margin for a difference between groups of -0.5 days. Secondary outcomes included length of stay, mortality rates, occurrence of pulmonary complications, and adverse events. Nine hundred twenty-two patients (34% women; median age, 66 (interquartile range [IQR], 54-75 years) were enrolled and completed follow-up. At 28 days, patients in the on-demand group had a median 21 (IQR, 0-26) ventilator-free days, and patients in the routine group had a median 20 (IQR, 0-26) ventilator-free days (1-sided 95% CI, -0.00003 to ∞). There was no significant difference in length of stay or mortality, or in the proportion of patients developing pulmonary complications, between the 2 groups. Adverse events (13.8% vs 29.3%; difference, -15.5% [95% CI, -20.7% to -10.3%]; P < .001) were more frequent with routine nebulization and mainly related to tachyarrhythmia (12.5% vs 25.9%; difference, -13.4% [95% CI, -18.4% to -8.4%]; P < .001) and agitation (0.2% vs 4.3%; difference, -4.1% [95% CI, -5.9% to -2.2%]; P < .001). Among ICU patients receiving invasive ventilation who were expected to not be extubated within 24 hours, on-demand compared with routine nebulization of
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Lei, Yajing; Li, Xiaoyi; Akash, Muhammad Sajid Hamid; Zhou, Lifang; Tang, Xiaojing; Shi, Weixing; Liu, Zhiming; Chen, Shuqing
2015-03-25
Salbutamol (SAL) is known as quick-acting β-2 receptor agonist and its use in humans for pulmonary diseases and/or in animal feed is limited because of associated potential hazardous effects on health. Several techniques are available for the detection of SAL, but are expensive and time consuming. Here for the first time, a novel pre-assembled DNA immunoprobe-based immuno-PCR assay was developed to investigate the levels of SAL in human urine samples and compared the proposed immuno-PCR assay for the detection of SAL with that of direct competitive ELISA. Under the optimized conditions, the assay showed a linear range over seven orders of magnitude, whereas the limit of detection of SAL in buffer was found to be 21 fg/mL. Current immuno-PCR assay exhibited a 300-fold better detection limit for SAL as compared to one achieved with direct competitive ELISA using the same antibody. In conclusion, it has been found that the developed method is highly sensitive and simple method that can significantly enhance the detection sensitivity for small molecules. Moreover it can be modified and used for detecting other small molecules and/or chemicals that exist in the environment and are responsible for the environmental pollution. Copyright © 2014 Elsevier B.V. All rights reserved.
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Sharma, Deepak; Singh, Gurmeet; Kumar, Dinesh; Singh, Mankaran
2015-01-01
The objective of the present study was to prepare the fast disintegrating tablet of Salbutamol Sulphate, Cetirizine Hydrochloride in combined tablet dosage form for respiratory disorders such as bronchitis, asthma, and coughing for pediatrics and geriatrics. The tablets were prepared by direct compression technique. Superdisintegrant such as Sodium Starch Glycolate was optimized as 4% on the basis of least disintegration time. Different binders such as MCC and PVP K-30 were optimized along with optimized superdisintegrant concentration. 1% MCC was selected as optimum binder concentration on the basis of least disintegration time. The tablets were evaluated for hardness, friability, weight variation, wetting time, disintegration time, and drug content uniformity. Optimized formulation was further evaluated by in vitro dissolution test, drug-excipient compatibility, and accelerated stability study. Percent weight variation and content uniformity were within the acceptable limit. The friability was less than 1%. The wetting time and disintegration time were practically good for all formulations. FTIR studies and accelerated stability study showed that there was no interaction between the drug and excipients. It was concluded that, by employing commonly available pharmaceutical excipients such as superdisintegrants, hydrophilic and swellable excipients and proper filler, a fast disintegrating tablet of Salbutamol Sulphate, Cetirizine Hydrochloride in combined tablet dosage form, were formulated successfully with desired characteristics. PMID:25810924
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Chiou, Herbert; Li, Li; Hu, Tingting; Chan, Hak-Kim; Chen, Jian-Feng; Yun, Jimmy
2007-02-22
The purpose of this study was to produce salbutamol sulfate (SS) as a model anti-asthmatic drug using high-gravity controlled precipitation (HGCP) through antisolvent crystallisation. An aqueous solution of SS was passed through a HGCP reactor with isopropanol as antisolvent to induce precipitation. Spray drying was employed to obtain dry powders. Scanning electron microscopy, X-ray powder diffraction (XRD), density measurement, thermal gravimetric analysis, and dynamic vapour sorption were carried out to characterise the powder physical properties. The aerosol performance of the powders was measured using an Aeroliser connected to a multiple stage liquid impinger operating at 60 L/min. The HGCP SS particles were elongated with 0.1 microm in width but varying length of several mum, which formed spherical agglomerates when spray dried. The particles showed the same XRD pattern and true density (1.3g/cm3) as the raw material, indicating that they belonged to the same crystalline form. However, the spray dried agglomerates had a much lower tapped density (0.1g/cm3) than the raw material (0.6g/cm3). Compared with the powder obtained by spray drying directly from an aqueous solution, the SS powders obtained from HGCP were much less hygroscopic (0.6% versus 10% water uptake at 90% RH). The in vitro aerosol performance showed a fine particle fraction FPFloaded and FPFemitted up to 54.5+/-4.9% and 71.3+/-10.0%, respectively. In conclusion, SS powder with suitable physical and aerosol properties can be obtained through antisolvent HGCP followed by spray drying.
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Peroxidative Metabolism of β2-Agonists Salbutamol and Fenoterol and Their Analogs
Reszka, Krzysztof J.; McGraw, Dennis W.; Britigan, Bradley E.
2009-01-01
Phenolic β2-adrenoreceptor agonists salbutamol, fenoterol and terbutaline relax smooth muscle cells that relieve acute airway bronchospasm associated with asthma. Why their use sometimes fails to relieve bronchospasm, and why the drugs appear to be less effective in patients with severe asthma exacerbations, remains unclear. We show that in the presence of hydrogen peroxide, both myeloperoxidase, secreted by activated neutrophils present in inflamed airways, and lactoperoxidase, which is naturally present in the respiratory system, catalyze oxidation of these β2-agonists. Azide, cyanide, thiocyanate, ascorbate, glutathione, and methimazole inhibited this process, while methionine was without effect. Inhibition by ascorbate and glutathione was associated with their oxidation to corresponding radical species by the agonists’-derived phenoxyl radicals. Using electron paramagnetic resonance (EPR), we detected free radical metabolites from β2-agonists by spin trapping with 2-methyl-2-nitrosopropane (MNP). Formation of these radicals was inhibited by pharmacologically-relevant concentrations of methimazole and dapsone. In alkaline buffers radicals from fenoterol and its structural analog, metaproteronol, were detected by direct EPR. Analysis of these spectra suggests that oxidation of fenoterol and metaproterenol, but not terbutaline, causes their transformation through intramolecular cyclization by addition of their amino nitrogen to the aromatic ring. Together, these results indicate that phenolic β2-agonists function as substrates for airway peroxidases and that the resulting products differ in their structural and functional properties from their parent compounds. They also suggest that these transformations can be modulated by pharmacological approaches using appropriate peroxidase inhibitors or alternative substrates. These processes may affect therapeutic efficacy and also play a role in adverse reactions of the β2-agonists. PMID:19462961
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Peroxidative metabolism of beta2-agonists salbutamol and fenoterol and their analogues.
Reszka, Krzysztof J; McGraw, Dennis W; Britigan, Bradley E
2009-06-01
Phenolic beta(2)-adrenoreceptor agonists salbutamol, fenoterol, and terbutaline relax smooth muscle cells that relieve acute airway bronchospasm associated with asthma. Why their use sometimes fails to relieve bronchospasm and why the drugs appear to be less effective in patients with severe asthma exacerbations remains unclear. We show that in the presence of hydrogen peroxide, both myeloperoxidase, secreted by activated neutrophils present in inflamed airways, and lactoperoxidase, which is naturally present in the respiratory system, catalyze oxidation of these beta(2)-agonists. Azide, cyanide, thiocyanate, ascorbate, glutathione, and methimazole inhibited this process, while methionine was without effect. Inhibition by ascorbate and glutathione was associated with their oxidation to corresponding radical species by the agonists' derived phenoxyl radicals. Using electron paramagnetic resonance (EPR), we detected free radical metabolites from beta(2)-agonists by spin trapping with 2-methyl-2-nitrosopropane (MNP). Formation of these radicals was inhibited by pharmacologically relevant concentrations of methimazole and dapsone. In alkaline buffers, radicals from fenoterol and its structural analogue, metaproteronol, were detected by direct EPR. Analysis of these spectra suggests that oxidation of fenoterol and metaproterenol, but not terbutaline, causes their transformation through intramolecular cyclization by addition of their amino nitrogen to the aromatic ring. Together, these results indicate that phenolic beta(2)-agonists function as substrates for airway peroxidases and that the resulting products differ in their structural and functional properties from their parent compounds. They also suggest that these transformations can be modulated by pharmacological approaches using appropriate peroxidase inhibitors or alternative substrates. These processes may affect therapeutic efficacy and also play a role in adverse reactions of the beta(2)-agonists.
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Doping dose of salbutamol and exercise training: impact on the skeleton of ovariectomized rats.
Bonnet, N; Laroche, N; Beaupied, H; Vico, L; Dolleans, E; Benhamou, C L; Courteix, D
2007-08-01
Previous studies in healthy rats have demonstrated a deleterious bone impact of beta-agonist treatment. The purpose of this study was to examine the trabecular and cortical effects of beta(2)-agonists at doping dose on treadmill exercising rats with estrogen deficiency. Adult female rats were ovariectomized (OVX; n = 44) or sham operated (n = 12). Then, OVX rats received a subcutaneous injection of salbutamol (SAB) or vehicle with (EXE) or without treadmill exercise for 10 wk. Bone mineral density (BMD) was analyzed by densitometry. Microcomputed tomography and histomorphometric analysis were performed to study trabecular bone structure and bone cell activities. After 10 wk, SAB rats presented a much more marked decrease of BMD and trabecular parameters. Exercise did not change the high level of bone resorption in OVX EXE SAB compared with OVX SAB group (both on COOH-terminal collagen cross-links and osteoclast number). These results confirm the deleterious effect of beta(2)-agonists on bone quantity (femoral BMD gain: OVX EXE, +6.8%, vs. OVX EXE SAB, -1.8%; P < 0.01) and quality (-8.0% of femoral trabecular thickness in OVX EXE SAB vs. OVX EXE), indicating that SAB suppresses the effect of EXE in OVX rats. Furthermore, we notice that the slight beneficial effect of exercise was mainly localized in the tibia. These findings indicate the presence of a bone alteration threshold below which there is no more alteration in structural bone quantity and quality. The negative effects of SAB on bone observed in this study in trained rats may indicate potential complications in doping female athletes with exercise-induced amenorrhea.
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Prasanth, V.V.; Puratchikody, A.; Mathew, S.T.; Ashok, K.B.
2014-01-01
The purpose of this work was to study the effect of various permeation enhancers on the permeation of salbutamol sulphate (SS) buccal patches through buccal mucosa in order to improve the bioavailability by avoiding the first pass metabolism in the liver and possibly in the gut wall and also achieve a better therapeutic effect. The influence of various permeation enhancers, such as dimethyl sulfoxide (DMSO), linoleic acid (LA), isopropyl myristate (IPM) and oleic acid (OA) on the buccal absorption of SS from buccal patches containing different polymeric combinations such as hydroxypropyl methyl cellulose (HPMC), carbopol, polyvinyl alcohol (PVA), polyvinyl pyrollidone (PVP), sodium carboxymethyl cellulose (NaCMC), acid and water soluble chitosan (CHAS and CHWS) and Eudragit-L100 (EU-L100) was investigated. OA was the most efficient permeation enhancer increasing the flux greater than 8-fold compared with patches without permeation enhancer in HPMC based buccal patches when PEG-400 was used as the plasticizer. LA also exhibited a better permeation enhancing effect of over 4-fold in PVA and HPMC based buccal patches. In PVA based patches, both OA and LA were almost equally effective in improving the SS permeation irrespective of the plasticizer used. DMSO was more effective as a permeation enhancer in HPMC based patches when PG was the plasticizer. IPM showed maximum permeation enhancement of greater than 2-fold when PG was the plasticizer in HPMC based buccal patches. PMID:25657797
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Mönckedieck, M; Kamplade, J; Fakner, P; Urbanetz, N A; Walzel, P; Steckel, H; Scherließ, R
2017-05-30
Nowadays, dry powder inhalation as applied in the therapy of pulmonary diseases is known as a very effective route of drug delivery to the lungs. Here, the system of coarse carrier and fine drug particles attached to the carrier surface has successfully been applied to overcome the cohesiveness of small drug particles. Particle properties of both carrier and drug are known to affect drug dispersion as has widely been discussed for lactose monohydrate and various drugs. This study utilises particle-engineered mannitol as an alternative carrier to discover the effect of mannitol carrier particle properties like particle shape, surface roughness, flowability or particle size on aerodynamic performance during inhalation. Spray drying as a technique to accurately control those properties was chosen for the generation of carrier sizes between 50 and 80 μm and different morphologies and therefore various carrier flowabilities. A set of these carriers has then been blended with different spray dried and jet-milled qualities of salbutamol sulphate as model drug to examine the influence of carrier particle properties on aerodynamic behaviour and at the same time to cover the effect of drug particle properties on particle-particle interactions. This experimental setup allowed a general view on how drug and carrier properties affect the Fine Particle Fraction (FPF) as indicator for inhalation performance and gave the first study to distinguish between mannitol carrier particle shape and surface roughness. Further it was possible to relate carrier particle size and shape to drug accumulation and detachment mechanisms during inhalation as size and shape had the main influence on drug detachment. The addition of jet-milled mannitol fines provided an initial insight into the improving effect of ternary powder blends as has been intensively studied for lactose monohydrate but not for mannitol yet. Copyright © 2017 Elsevier B.V. All rights reserved.
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Li, Liang; Leung, Sharon Shui Yee; Gengenbach, Thomas; Yu, Jiaqi; Gao, Ge Fiona; Tang, Patricia; Zhou, Qi Tony; Chan, Hak-Kim
2017-09-15
The aim of this study was to investigate the ability of L-leucine (LL) in preventing moisture-induced deterioration in the in vitro aerosolization performance of spray-dried (SD) salbutamol sulfate (SS). Increasing mass fraction of LL (5-80%) were co-spray dried with SS, and the physicochemical properties of the powders were characterized by laser diffraction, X-ray powder diffraction (XRD) and dynamic vapour sorption (DVS). Furthermore, the surface morphology and chemistry of fine particles was analyzed by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The in vitro aerosolization performance of powders stored at different relative humidity (RH) was evaluated by a next generation impactor (NGI). The SD SS powders were moderately hygroscopic and amorphous, of which the uptake of moisture upon storage caused a drop in the aerosolization performance. The results showed that 40% (w/w) LL was sufficient to eliminate the effect of moisture on the aerosolization performance at 60% RH. The formulation containing 40% (w/w) LL also maximized the aerosolization performance of SD SS powders (stored in desiccator) with the emitted fraction being 90.0±1.8%, and the fine particle fraction based on the recovered dose (FPF recovered ) and emitted dose (FPF emitted ) being 78.0±3.7% and 86.6±2.9%, respectively. The underlying mechanisms were that the crystalline LL increased the degree of particle surface corrugation, and reduced particle fusion and cohesiveness to facilitate dispersion. However, there is still a great challenge to prevent the moisture-induced deterioration in the aerosolization performance at 75% RH due to the recrystallization of SD SS. In conclusion, LL is a potential excipient for reducing moisture-induced deterioration in the aerosolization performance of SD amorphous powders, but still has drawbacks in preventing the recrystallization-induced deterioration. Copyright © 2017 Elsevier B.V. All rights reserved.
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TUBERCULOSIS COMO ENFERMEDAD OCUPACIONAL
Mendoza-Ticona, Alberto
2014-01-01
Existe evidencia suficiente para declarar a la tuberculosis como enfermedad ocupacional en diversos profesionales especialmente entre los trabajadores de salud. En el Perú están normados y reglamentados los derechos laborales inherentes a la tuberculosis como enfermedad ocupacional, como la cobertura por discapacidad temporal o permanente. Sin embargo, estos derechos aún no han sido suficientemente socializados. En este trabajo se presenta información sobre el riesgo de adquirir tuberculosis en el lugar de trabajo, se revisan las evidencias para declarar a la tuberculosis como enfermedad ocupacional en trabajadores de salud y se presenta la legislación peruana vigente al respecto. PMID:22858771
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David Christopher, J; Patel, Rajni B; Mitchell, Jolyon P; Tougas, Terrence P; Goodey, Adrian P; Quiroz, Jorge; Andersson, Patrik U; Lyapustina, Svetlana
2017-11-01
This article reports on results from a two-lab, multiple impactor experiment evaluating the abbreviated impactor measurement (AIM) concept, conducted by the Cascade Impaction Working Group of the International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS). The goal of this experiment was to expand understanding of the performance of an AIM-type apparatus based on the Andersen eight-stage non-viable cascade impactor (ACI) for the assessment of inhalation aerosols and sprays, compared with the full-resolution version of that impactor described in the pharmacopeial compendia. The experiment was conducted at two centers with a representative commercially available pressurized metered dose inhaler (pMDI) containing albuterol (salbutamol) as active pharmaceutical ingredient (API). Metrics of interest were total mass (TM) emitted from the inhaler, impactor-sized mass (ISM), as well as the ratio of large particle mass (LPM) to small particle mass (SPM). ISM and the LPM/SPM ratio together comprise the efficient data analysis (EDA) metrics. The results of the comparison demonstrated that in this study, the AIM approach had adequate discrimination to detect changes in the mass median aerodynamic diameter (MMAD) of the ACI-sampled aerodynamic particle size distribution (APSD), and therefore could be employed for routine product quality control (QC). As with any test method considered for inclusion in a regulatory filing, the transition from an ACI (used in development) to an appropriate AIM/EDA methodology (used in QC) should be evaluated and supported by data on a product-by-product basis.
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Gordon, Sarah E; Cartwright, Neil; Griffiths, Mark J D
2009-01-01
AIMS Pulse contour analysis (PCA) obtained by finger photoplethysmography produces a digital volume pulse (DVP) including an inflection point in its down-slope. The reflection index (RI: ratio of the inflection point height over the maximal DVP) is responsive to vasodilatation. We aimed to optimize the drug dose and time interval for assessing endothelial function using PCA in healthy volunteers and patients with severe coronary artery disease. METHODS Time and dose to RI response relationships were constructed in 16 volunteers and nine patients to inhaled salbutamol (100–400 µg) or sublingual nitroglycerin (NTG; 25–400 µg). RESULTS For the volunteers, the time to maximum RI response to inhaled salbutamol and sublingual NTG was 10.73 ± 0.41 and 3.66 ± 0.21 min, respectively. A plateau in the RI response to salbutamol occurred between 5 and 15 min after inhalation and results were averaged over this period. A dose-dependent response was observed to inhaled salbutamol and sublingual NTG (P= 0.05 and P < 0.001 by repeated-measures anova, respectively) in healthy volunteers. By contrast, in patients with severe coronary artery disease inhaled salbutamol (100–400 µg) did not cause a significant change in RI. CONCLUSIONS In healthy volunteers the RI response to inhaled salbutamol (100–200 µg) averaged over 5–15 min after administration may be used to investigate endothelial function by PCA. The response to sublingual NTG (50 µg) should be determined at 4 min. This technique may not be suitable for the assessment of endothelial function in subjects with extensive coronary artery disease owing to the small responses observed and potential confounding effect of vasoactive medication. PMID:19843066
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Liu, Bing; Wang, Lingling; Tong, Bei; Zhang, Yan; Sheng, Wei; Pan, Mingfei; Wang, Shuo
2016-11-15
In this study, the three nanomaterials: colloidal gold, nanogold-polyaniline-nanogold microspheres (GPGs) and colloidal carbon were respectively labeled with the antibody against salbutamol (SAL). We aimed to develop immunochromatographic strips with these nanomaterial labels and determine their performance in visual detection of SAL. For the colloidal gold-based strip, the detection limit of SAL was 1.0µgL(-1) in standard solution and 5.0µgkg(-1) in meat samples. For the GPG- and colloidal carbon-based strips, the limit of detection was 2.0µgL(-1) in standard solution and 10µgkg(-1) in meat samples. The results obtained using the test strips were found to be highly consistent with those obtained using a commercial kit, indicating the high accuracy of these strips. The three strips were also found to be stable up to 18 weeks under laboratory conditions. In terms of sensitivity, the colloidal gold-based strip was slightly better than the other two. For the GPG- and colloidal carbon-based strips, the difference between the results obtained for different batches was small (high consistency), and the stability was much better than that of the colloidal gold-based one. Our results indicate that colloidal carbon can be used as a label in immunochromatographic tests; it can also help reduce the cost involved and scale-up the production. The use of immunochromatographic test strips labeled with colloidal carbon can be a rapid and inexpensive method for SAL assays in on-site applications. Copyright © 2016 Elsevier B.V. All rights reserved.
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Tachibana, A; Kato, M; Kimura, H; Fujiu, T; Suzuki, M; Morikawa, A
2002-12-01
Agonists at beta2 adrenoceptors are used widely as bronchodilators in treating bronchial asthma. These agents also may have important anti-inflammatory effects on eosinophils in asthma. We examined whether widely prescribed beta2-adrenoceptor agonists differ in ability to suppress stimulus-induced eosinophil effector functions such as superoxide anion (O2-) generation and degranulation. To examine involvement of cellular adhesion in such responses, we also investigated effects of beta2 agonists on cellular adhesion and on CD11b expression by human eosinophils. O2- was measured using chemiluminescence. Eosinophil degranulation and adhesion were assessed by a radioimmunoassay for eosinophil protein X (EPX). CD11b expression was measured by flow cytometry. Fenoterol inhibited platelet-activating factor (PAF)-induced O2- generation by eosinophils significantly more than salbutamol or procaterol. Fenoterol partially inhibited PAF-induced degranulation by eosinophils similarly to salbutamol or procaterol. Fenoterol inhibited phorbol myristate acetate (PMA)-induced O2- generation and degranulation by eosinophils, while salbutamol or procaterol did not. Fenoterol inhibition of PMA-induced O2- generation was not reversed by ICI-118551, a selective beta2-adrenoceptor antagonist. Fenoterol, but not salbutamol or procaterol, significantly inhibited PAF-induced eosinophil adhesion. Fenoterol inhibited O2- generation and degranulation more effectively than salbutamol or procaterol; these effects may include a component involving cellular adhesion. Inhibition also might include a component not mediated via beta2 adrenoceptors.
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Liu, Haibo; Gan, Ning; Chen, Yinji; Ding, Qingqing; Huang, Jie; Lin, Saichai; Cao, Yuting; Li, Tianhua
2016-09-01
A quick and specific pretreatment method based on a series of extraction clean-up disks, consisting of molecularly imprinted polymer monoliths and C18 adsorbent, was developed for the specific enrichment of salbutamol and clenbuterol residues in food. The molecularly imprinted monolithic polymer disk was synthesized using salbutamol as a template through a one-step synthesis process. It can simultaneously and specifically recognize salbutamol and clenbuterol. The monolithic polymer disk and series of C18 disks were assembled with a syringe to form a set of tailor-made devices for the extraction of target molecules. In a single run, salbutamol and clenbuterol can be specifically extracted, cleaned, and eluted by methanol/acetic acid/H2 O. The target molecules, after a silylation derivatization reaction were detected by gas chromatography-mass spectrometry. The parameters including solvent desorption, sample pH, and the cycles of reloading were investigated and discussed. Under the optimized extraction and clean-up conditions, the limits of detection and quantitation were determined as 0.018-0.022 and 0.042-0.049 ng/g for salbutamol and clenbuterol, respectively. The assay described was convenient, rapid, and specific; thereby potentially efficient in the high-throughput analysis of β2 -agonists residues in real food samples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Ning, P; Guo, Y F; Sun, T Y; Zhang, H S; Chai, D; Li, X M
2016-09-01
To study the distinct clinical phenotype of chronic airway diseases by hierarchical cluster analysis and two-step cluster analysis. A population sample of adult patients in Donghuamen community, Dongcheng district and Qinghe community, Haidian district, Beijing from April 2012 to January 2015, who had wheeze within the last 12 months, underwent detailed investigation, including a clinical questionnaire, pulmonary function tests, total serum IgE levels, blood eosinophil level and a peak flow diary. Nine variables were chosen as evaluating parameters, including pre-salbutamol forced expired volume in one second(FEV1)/forced vital capacity(FVC) ratio, pre-salbutamol FEV1, percentage of post-salbutamol change in FEV1, residual capacity, diffusing capacity of the lung for carbon monoxide/alveolar volume adjusted for haemoglobin level, peak expiratory flow(PEF) variability, serum IgE level, cumulative tobacco cigarette consumption (pack-years) and respiratory symptoms (cough and expectoration). Subjects' different clinical phenotype by hierarchical cluster analysis and two-step cluster analysis was identified. (1) Four clusters were identified by hierarchical cluster analysis. Cluster 1 was chronic bronchitis in smokers with normal pulmonary function. Cluster 2 was chronic bronchitis or mild chronic obstructive pulmonary disease (COPD) patients with mild airflow limitation. Cluster 3 included COPD patients with heavy smoking, poor quality of life and severe airflow limitation. Cluster 4 recognized atopic patients with mild airflow limitation, elevated serum IgE and clinical features of asthma. Significant differences were revealed regarding pre-salbutamol FEV1/FVC%, pre-salbutamol FEV1% pred, post-salbutamol change in FEV1%, maximal mid-expiratory flow curve(MMEF)% pred, carbon monoxide diffusing capacity per liter of alveolar(DLCO)/(VA)% pred, residual volume(RV)% pred, total serum IgE level, smoking history (pack-years), St.George's respiratory questionnaire
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Inhibition by fenoterol of human eosinophil functions including β2-adrenoceptor-independent actions
TACHIBANA, A; KATO, M; KIMURA, H; FUJIU, T; SUZUKI, M; MORIKAWA, A
2002-01-01
Agonists at β2 adrenoceptors are used widely as bronchodilators in treating bronchial asthma. These agents also may have important anti-inflammatory effects on eosinophils in asthma. We examined whether widely prescribed β2-adrenoceptor agonists differ in ability to suppress stimulus-induced eosinophil effector functions such as superoxide anion (O2−) generation and degranulation. To examine involvement of cellular adhesion in such responses, we also investigated effects of β2 agonists on cellular adhesion and on CD11b expression by human eosinophils. O2− was measured using chemiluminescence. Eosinophil degranulation and adhesion were assessed by a radioimmunoassay for eosinophil protein X (EPX). CD11b expression was measured by flow cytometry. Fenoterol inhibited platelet-activating factor (PAF)-induced O2− generation by eosinophils significantly more than salbutamol or procaterol. Fenoterol partially inhibited PAF-induced degranulation by eosinophils similarly to salbutamol or procaterol. Fenoterol inhibited phorbol myristate acetate (PMA)-induced O2− generation and degranulation by eosinophils, while salbutamol or procaterol did not. Fenoterol inhibition of PMA-induced O2− generation was not reversed by ICI-118551, a selective β2-adrenoceptor antagonist. Fenoterol, but not salbutamol or procaterol, significantly inhibited PAF-induced eosinophil adhesion. Fenoterol inhibited O2− generation and degranulation more effectively than salbutamol or procaterol; these effects may include a component involving cellular adhesion. Inhibition also might include a component not mediated via β2 adrenoceptors. PMID:12452831
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Long-Acting β2-Agonists in Asthma: Enantioselective Safety Studies are Needed.
Jacobson, Glenn A; Raidal, Sharanne; Hostrup, Morten; Calzetta, Luigino; Wood-Baker, Richard; Farber, Mark O; Page, Clive P; Walters, E Haydn
2018-05-01
Long-acting β2-agonists (LABAs) such as formoterol and salmeterol are used for prolonged bronchodilatation in asthma, usually in combination with inhaled corticosteroids (ICSs). Unexplained paradoxical asthma exacerbations and deaths have been associated with LABAs, particularly when used without ICS. LABAs clearly demonstrate effective bronchodilatation and steroid-sparing activity, but long-term treatment can lead to tolerance of their bronchodilator effects. There are also concerns with regard to the effects of LABAs on bronchial hyperresponsiveness (BHR), where long-term use is associated with increased BHR and loss of bronchoprotection. A complicating factor is that formoterol and salmeterol are both chiral compounds, usually administered as 50:50 racemic (rac-) mixtures of two enantiomers. The chiral nature of these compounds has been largely forgotten in the debate regarding LABA safety and effects on BHR, particularly that (S)-enantiomers of β2-agonists may be deleterious to asthma control. LABAs display enantioselective pharmacokinetics and pharmacodynamics. Biological plausibility of the deleterious effects of β2-agonists (S)-enantiomers is provided by in vitro and in vivo studies from the short-acting β2-agonist (SABA) salbutamol. Supportive clinical findings include the fact that patients in emergency departments who demonstrate a blunted response to salbutamol are more likely to benefit from (R)-salbutamol than rac-salbutamol, and resistance to salbutamol appears to be a contributory mechanism in rapid asthma deaths. More effort should therefore be applied to investigating potential enantiospecific effects of LABAs on safety, specifically bronchoprotection. Safety studies directly assessing the effects of LABA (S)-enantiomers on BHR are long overdue.
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Beta-Adrenergic Modulation of Tremor and Corticomuscular Coherence in Humans
Baker, Mark R.; Baker, Stuart N.
2012-01-01
Coherence between the bioelectric activity of sensorimotor cortex and contralateral muscles can be observed around 20 Hz. By contrast, physiological tremor has a dominant frequency around 10 Hz. Although tremor has multiple sources, it is partly central in origin, reflecting a component of motoneuron discharge at this frequency. The motoneuron response to ∼20 Hz descending input could be altered by non-linear interactions with ∼10 Hz motoneuron firing. We investigated this further in eight healthy human subjects by testing the effects of the beta-adrenergic agents propranolol (non-selective β-antagonist) and salbutamol (β2-agonist), which are known to alter the size of physiological tremor. Corticomuscular coherence was assessed during an auxotonic precision grip task; tremor was quantified using accelerometry during index finger extension. Experiments with propranolol used a double-blind, placebo-controlled crossover design. A single oral dose of propranolol (40 mg) significantly increased beta band (15.3–32.2 Hz) corticomuscular coherence compared with placebo, but reduced tremor in the 6.2–11.9 Hz range. Salbutamol (2.5 mg) was administered by inhalation. Whilst salbutamol significantly increased tremor amplitude as expected, it did not change corticomuscular coherence. The opposite direction of the effects of propranolol on corticomuscular coherence and tremor, and the fact that salbutamol enhances tremor but does not affect coherence, implies that the magnitude of corticomuscular coherence is little influenced by non-linear interactions with 10 Hz oscillations in motoneurons or the periphery. Instead, we suggest that propranolol and salbutamol may affect both tremor and corticomuscular coherence partly via a central site of action. PMID:23185297
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Hooton, Jennifer C; Jones, Matthew D; Price, Robert
2006-06-01
The aim of this work was to utilize the recently developed cohesive-adhesive balance (CAB) technique for analyzing quantitative AFM measurements to compare the relative forces of interaction of micronized salbutamol sulfate particles and a selection of specifically grown sugar substrates (beta cyclodextrin, lactose, raffinose, trehalose and xylitol). The interfacial behavior was subsequently related to the in-vitro delivery performance of these sugars as carrier particles in dry powder inhalation (DPI) formulations. The CAB analysis indicated that the rank order of adhesion between salbutamol sulfate and the sugars was beta cyclodextrin < lactose < trehalose < raffinose < xylitol. The beta cyclodextrin was the only substrate with which salbutamol sulfate demonstrated a greater cohesive behavior. All other sugars exhibited an adhesive dominance. In-vitro deposition performance of the salbutamol sulfate based carrier DPI formulations showed that the rank order of the fine particle fraction (FPF) was beta cyclodextrin > lactose > raffinose > trehalose > xylitol. A linear correlation (R(2) = 0.9572) was observed between the FPF and cohesive-adhesive ratios of the AFM force measurements. The observed link between CAB analysis of the interactive forces and in-vitro performance of carrier based formulations suggested a fundamental understanding of the relative balance of the various forces of interaction within a dry powder formulation may provide a critical insight into the behavior of these formulations. (c) 2006 Wiley-Liss, Inc. and the American Pharmacists Association
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Recent DDT and PCB contamination in the sediment and biota of the Como Bay (Lake Como, Italy).
Bettinetti, R; Quadroni, S; Boggio, E; Galassi, S
2016-01-15
Due to its peculiar geographical and morphological characteristics, Lake Como (Northern Italy) represents an interesting study-case for investigating the sub-basin scale circulation of persistent organic pollutants (POPs) that, despite being banned since the 1970s, have reached surprisingly high concentrations in some southern alpine lakes as a consequence of their release from melting glaciers in recent years. In particular, the Como Bay, which is located in the city of Como, seems noteworthy because its waters have a longer residence time than the other areas of the lake. The analyses of the historical concentration of PCBs, pp′DDT and its metabolites in a sediment core sampled from the Como Bay covering a time-period from their ban to recent times, showed that the DDTs have never experienced a significant (p < 0.05) decrease over time, with concentrations of the most abundant homologue, pp′DDE, ranging from 27 to 75 ng g(-1) d.w. Conversely PCBs significantly (p < 0.05) decreased towards recent times, reaching concentrations around 80 ng g(-1) d.w. The contribution of high altitude and local sources was recorded also in the food web: both zooplankton and the zooplanktivorous fish agone were mainly contaminated by pp′DDE (81.4 ng g(-1) w.w. and 534.6 ng g(-1) w.w. respectively) and by the PCB metabolite hexa-CB (449.7 ng g(-1) w.w. and 1672.1 ng g(-1) w.w. respectively). The DDT concentrations in the agone (sampled during the years 2006–2009) never exceeded the limits for human consumption in Italy, while concentrations of six selected PCBs exceeded human health advisory recommendations in one of the fish samples analysed, when it was approximately two times higher than the recommended value of 125 ng g(-1) w.w.
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Warren, J B; Pixley, F J; Dollery, C T
1989-01-01
1. Seven atopic subjects received two injections of antigen and one of saline intradermally in the back on each of 4 separate days. They were pretreated with four different drug combinations: (a) adrenaline 0.3 mg subcutaneously over the deltoid muscle (b) subcutaneous adrenaline preceded by 5 mg of the specific beta 2-adrenoceptor antagonist ICI 118,551 orally (c) 8 mg of salbutamol orally (d) placebo. Tablets were given 2 h before and subcutaneous injections 15 min before the intradermal injections of saline and antigen. 2. The median flare response to intradermal low dose antigen and high dose antigen after pretreatment with adrenaline was 4% and 49% of the response seen following pretreatment with placebo (P less than 0.001). When adrenaline was preceded by ICI-118,551, the corresponding median flare responses were 2% and 44% (P less than 0.001) of the placebo response. The flare response after pretreatment with salbutamol was not significantly different from placebo. 3. Adrenaline suppressed the median weal response to the higher dose of antigen to 52% of the response after pretreatment with placebo (P less than 0.05). This suppression by adrenaline was blocked by pretreatment with ICI 118,551. The median weal response after the highest dose of antigen was suppressed by salbutamol to 66% of the response seen after placebo, although this was not significant even when a further three subjects were studied with either salbutamol or placebo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2565729
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2002-01-01
Miconazole Antifungal -- Paroxetine metabolite Metabolite of Paroxetine (antianxiety) 0.26 Ranitidine Antiulcerant; antacid 0.01 Salbutamol...LRL <LRL <LRL <LRL Lisinopril ND ND ND ND Metformin <LRL <LRL <LRL <LRL Miconazole ND ND ND ND Paroxetine metabolite <LRL <LRL <LRL <LRL Ranitidine... Miconazole ND ND ND ND Paroxetine metabolite <LRL <LRL <LRL <LRL Ranitidine <LRL <LRL <LRL <LRL Salbutamol (albuterol) <LRL <LRL <LRL <LRL Sulfamethoxazole
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Bel, E. H.; Zwinderman, A. H.; Timmers, M. C.; Dijkman, J. H.; Sterk, P. J.
1991-01-01
Beta 2 agonists reduce airway hypersensitivity to bronchoconstrictor stimuli acutely in patients with asthma and chronic obstructive lung disease. To determine whether these drugs also protect against excessive airway narrowing, the effect of inhaled salbutamol on the position and shape of the dose-response curves for histamine or methacholine was investigated in 12 patients with asthma and 11 with chronic obstructive lung disease. After pretreatment with salbutamol (200 or 400 micrograms) or placebo in a double blind manner dose-response curves for inhaled histamine and methacholine were obtained by a standard method on six days in random order. Airway sensitivity was defined as the concentration of histamine or methacholine causing a 20% fall in FEV1 (PC20). A maximal response plateau on the log dose-response curve was considered to be present if two or more data points for FEV1 fell within a 5% response range. In the absence of a plateau, the test was continued until a predetermined level of severe bronchoconstriction was reached. Salbutamol caused an acute increase in FEV1 (mean increase 11.5% predicted in asthma, 7.2% in chronic obstructive lung disease), and increase in PC20 (mean 15 fold in asthma, fivefold in chronic obstructive lung disease), and an increase in the slope of the dose-response curves in both groups. In subjects in whom a plateau of FEV1 response could be measured salbutamol did not change the level of the plateau. In subjects without a plateau salbutamol did not lead to the development of a plateau, despite achieving a median FEV1 of 44% predicted in asthma and 39% in chronic obstructive lung disease. These results show that, although beta 2 agonists acutely reduce the airway response to a given strength of bronchoconstrictor stimulus, they do not protect against excessive airflow obstruction if there is exposure to relatively strong stimuli. This, together with the steepening of the dose-response curve, could be a disadvantage of beta 2
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Valizadegan, Farhad; Oryan, Shahrbanoo; Nasehi, Mohammad; Zarrindast, Mohammad Reza
2013-05-01
The amygdala is the key brain structure for anxiety and emotional memory storage. We examined the involvement of β-adrenoreceptors in the basolateral amygdala (BLA) and their interaction with morphine in modulating these behaviors. The elevated plus-maze has been employed for investigating anxiety and memory. Male Wistar rats were used for this test. We injected morphine (4, 5, and 6 mg/kg) intraperitoneally, while salbutamol (albuterol) (1, 2, and 4 μg/rat) and propranolol (1, 2, and 4 μg/rat) were injected into the BLA. Open- arms time percentage (%OAT), open- arms entry percentage (%OAE), and locomotor activity were determined by this behavioral test. Retention was tested 24 hours later. Intraperitoneal injection of morphine (6 mg/kg) had an anxiolytic-like effect and improvement of memory. The highest dose of salbutamol decreased the anxiety parameters in test session and improved the memory in retest session. Coadministration of salbutamol and ineffective dose of morphine presenting anxiolytic response. In this case, the memory was improved. Intra-BLA administration of propranolol (4 μg/rat) decreased %OAT in the test session, while had no effect on memory formation. Coadministration of propranolol and morphine (6 mg/kg) showed an increase in %OAT. There was not any significant change in the above- mentioned parameter in the retest session. Coadministration of morphine and propranolol with the effective dose of salbutamol showed that propranolol could reverse anxiolytic-like effect. We found that opioidergic and β-adrenergic systems have the same effects on anxiety and memory in the BLA; but these effects are independent of each other.
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Beal, A M
2000-12-01
Intracarotid infusions of noradrenaline (0.15 nmol x kg(-1) x min(-1)) either alone or accompanied by phentolamine (1.5 nmol x kg(-1) x min(-1)) caused similar-sized increases in salivary protein, magnesium and bicarbonate, and decreases in osmolality, sodium, potassium and chloride whereas intravenous noradrenaline stimulated much smaller responses. Concurrent infusions of the beta1-antagonist, CGP20712A, blocked these noradrenaline-induced changes in salivary composition more effectively than equimolar infusions of the beta2-antagonist, ICI118551, thereby confirming the presence of beta1-adrenoceptors. Intracarotid infusion of salbutamol at 0.15, 0.3 and 1.5 nmol x kg(-1) x min(-1) caused increasing but qualitatively similar changes in salivary composition, sodium excepted, to intracarotid noradrenaline with 0.3 nmol being most similar quantitatively. Intravenous infusion of salbutamol caused larger changes in salivary composition than equimolar intravenous noradrenaline thereby indicating that the response to salbutamol may, in part, be mediated by reflex increases in general sympathetic tone triggered by lowered blood pressure. Eliminating this hypotensive effect by concurrent intravenous and intracarotid infusions of beta1-(CGP or atenolol) and beta2-(ICII18551) antagonists with intracarotid salbutamol showed that IC1118551 was more potent than the beta1-antagonists thereby demonstrating the presence of beta2-receptors. It was concluded that the kangaroo mandibular has functional beta1- and beta2-adrenoceptor subtypes in both endpieces and excurrent ducts and that the duct system has two populations of cells, each expressing one receptor subtype.
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Ipratropium bromide in patients with nocturnal asthma.
Cox, I. D.; Hughes, D. T.; McDonnell, K. A.
1984-01-01
Fourteen patients with nocturnal asthma were recruited to a two period crossover trial which compared a run-in period on nightly salbutamol (200 micrograms) with a period on nightly ipratropium bromide (160 micrograms) and a period on nightly salbutamol plus ipratropium at night. Morning dipping, as assessed by the fall in peak flow overnight, was significantly reduced in the periods when ipratropium bromide was taken. Peak flow in the morning and also at night was improved when taking ipratropium bromide. Ipratropium bromide in adequate dosage appears to be effective in reducing morning dipping in asthma. PMID:6236436
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Moustafa, Islam O F; Ali, Mohammed R A-A; Al Hallag, Moataz; Rabea, Hoda; Fink, James B; Dailey, Patricia; Abdelrahim, Mohamed E A
During mechanical ventilation medical aerosol delivery has been reported to be upto two fold greater with dry inhaled gas than with heated humidity. Urine levels at 0.5 h post dose (URSAL0.5%) has been confirmed as an index of lung deposition and 24 h (URSAL24%) as index of systemic absorption. Our aim was to determine the effect of humidification and aerosol device type on drug delivery to ventilated patients using urine levels. In a randomized crossover design, 36 (18female) mechanically ventilated patients were assigned to one of three groups. Groups 1 and 2 received 5000 μg salbutamol using vibrating mesh (VM) and jet nebulizers (JN), respectively, while group 3 received 1600 μg (16 puffs) of salbutamol via metered dose inhaler with AeroChamber Vent (MDI-AV). All devices were placed in the inspiratory limb of ventilator downstream from the humidifier. Each subject received aerosol with and without humidity at >24 h intervals with >12 h washout periods between salbutamol doses. Patients voided urine 15 min before each study dose and urine samples were collected at 0.5 h post dosing and pooled for the next 24 h. The MDI-AV and VM resulted in a higher percentage of urinary salbutamol levels compared to the JN (p < 0.05). Urine levels were similar between humidity and dry conditions. Our findings suggest that in-vitro reports overestimate the impact of dry vs. heated humidified conditions on the delivery of aerosol during invasive mechanical ventilation. Copyright © 2017 Elsevier Inc. All rights reserved.
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Lowe, Donna O; Lummis, Heather; Zhang, Ying; Sketris, Ingrid S
2008-01-01
Asthma and chronic obstructive pulmonary disease treatment guidelines support the preferential use of portable inhalers (PIs) over wet nebulization (WN) respiratory therapy. Hospital- and community-based educational initiatives and a community-based provincial drug program policy change were previously implemented to promote the conversion of WN therapy to PI and spacer device use in Nova Scotia. To examine the effect of these interventions on salbutamol, ipratropium bromide, and spacer device (Aerochamber) use at the Queen Elizabeth II Health Sciences Centre (QEII HSC). We conducted a time-series analysis of drug utilization data from August 1998 to July 2005. We used two intervention phases compared to the pre-intervention phase to determine whether the educational and policy interventions were associated with significant changes in monthly drug and spacer device utilization rates at the QEII HSC (1000-bed teaching hospital; Halifax, Nova Scotia). Salbutamol and ipratropium bromide PI use significantly increased in both intervention phases, compared to the pre-intervention phase. Mean (SD) defined daily doses/100 bed-days for salbutamol PI increased from 30.4 (0.4) in the pre-intervention phase to 34.6 (0.9) and 37.0 (0.4) in intervention phases I and II respectively (p<0.001 for both), and ipratropium bromide PI increased from 27.3 (3.5) to 32.8 (2.5) in intervention phase I (p=0.004) and 35.6 (3.5) in intervention phase II (p<0.001). However, a significant corresponding decrease was observed with salbutamol WN only. Mean (SD) Aerochamber units/100 bed-days significantly increased. Educational and policy interventions had limited effects on converting WN to PI use at the QEII HSC.
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Zhu, Kewu; Ng, Wai Kiong; Shen, Shoucang; Tan, Reginald B H; Heng, Paul W S
2008-11-01
To develop a device for simultaneous measurement of particle aerodynamic diameter and electrostatic charge of inhalation aerosols. An integrated system consisting of an add-on charge measurement device and a liquid impinger was developed to simultaneously determine particle aerodynamic diameter and electrostatic charge. The accuracy in charge measurement and fine particle fraction characterization of the new system was evaluated. The integrated system was then applied to analyze the electrostatic charges of a DPI formulation composed of salbutamol sulphate-Inhalac 230 dispersed using a Rotahaler. The charge measurement accuracy was comparable with the Faraday cage method, and incorporation of the charge measurement module had no effect on the performance of the liquid impinger. Salbutamol sulphate carried negative charges while the net charge of Inhalac 230 and un-dispersed salbutamol sulphate was found to be positive after being aerosolized from the inhaler. The instantaneous current signal was strong with small noise to signal ratio, and good reproducibility of charge to mass ratio was obtained for the DPI system investigated. A system for simultaneously measuring particle aerodynamic diameter and aerosol electrostatic charges has been developed, and the system provides a non-intrusive and reliable electrostatic charge characterization method for inhalation dosage forms.
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LA BIOÉTICA COMO QUEHACER FILOSÓFICO
Ferrer, Jorge José
2009-01-01
El artículo examina el estatuto epistemológico de la bioética como disciplina académica. El autor sostiene que el estatuto epistemológico de un discurso lo determina la pregunta fundamental que se plantea y la respuesta que se busca, focos integradores del discurso. En el caso de la bioética, la pregunta fundamental es de índole moral. La bioética es pues una disciplina ética que tiene su hogar epistemológico en la filosofía. El autor también defiende el concepto de “éticas aplicadas”. Sugiere finalmente que el método de la bioética, sobre todo la que se hace desde nuestras latitudes, debería adoptar el círculo hermenéutico como metodología para su filosofar. PMID:20463860
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The Effect of Mustard Gas on Salivary Trace Metals (Zn, Mn, Cu, Mg, Mo, Sr, Cd, Ca, Pb, Rb)
Zamani Pozveh, Elham; Seif, Ahmad; Ghalayani, Parichehr; Maleki, Abbas; Mottaghi, Ahmad
2015-01-01
We have determined and compared trace metals concentration in saliva taken from chemical warfare injures who were under the exposure of mustard gas and healthy subjects by means of inductively coupled plasma optical emission spectroscopy (ICP-OES) for the first time. The influence of preliminary operations on the accuracy of ICP-OES analysis, blood contamination, the number of restored teeth in the mouth, salivary flow rate, and daily variations in trace metals concentration in saliva were also considered. Unstimulated saliva was collected at 10:00–11:00 a.m. from 45 subjects in three equal groups. The first group was composed of 15 healthy subjects (group 1); the second group consisted of 15 subjects who, upon chemical warfare injuries, did not use Salbutamol spray, which they would have normally used on a regular basis (group 2); and the third group contained the same number of patients as the second group, but they had taken their regular medicine (Salbutamol spray; group 3). Our results showed that the concentration of Cu in saliva was significantly increased in the chemical warfare injures compared to healthy subjects, as follows: healthy subjects 15.3± 5.45(p.p.b.), patients (group 2) 45.77±13.65, and patients (Salbutamol spray; group 3) 29 ±8.51 (P <0.02). In contrast, zinc was significantly decreased in the patients, as follows: healthy subjects 37 ± 9.03(p.p.b.), patients (group 2) 12.2 ± 3.56, and patients (Salbutamol spray; group 3) 20.6 ±10.01 (P < 0.01). It is important to note that direct dilution of saliva samples with ultrapure nitric acid showed the optimum ICP-OES outputs. PMID:25965704
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Nebulisation of corticosteroid suspensions and solutions with a beta(2) agonist.
O'Callaghan, Christopher L; White, Judy A; Jackson, Judith M; Barry, Peter W; Kantar, Ahmad
2008-05-01
The aim of this study was to determine the output of salbutamol nebulised in combination with either flunisolide or beclometasone dipropionate (BDP) from two different nebulisers under simulated breathing conditions. The BimboNeb and Nebula nebulisers were used to nebulise 3.0 mL of the two drug mixtures (salbutamol, 5000 microg plus either flunisolide, 600 microg, or BDP, 800 microg). Particle size was determined by inertial impaction. Total outputs of all drugs from both nebulisers were measured using a sinus flow pump under simulated paediatric and adult breathing patterns. The mass median aerodynamic diameter (MMAD) of BDP particles from the mixture was 6.34 mum using the BimboNeb and 5.34 mum using the Nebula. Values for salbutamol in this mixture were 3.93 and 3.32 microm, respectively. The MMAD of flunisolide particles from the BimboNeb and Nebula were 3.74 and 3.65 microm, respectively, while for salbutamol were 3.79 and 3.74 microm, respectively. With the simulated adult breathing pattern, all drug outputs from both mixtures were greater from the BimboNeb than from the Nebula after 5 and 10 min' nebulisation. Drug delivery from the BimboNeb, but not the Nebula, was affected by the simulated breathing pattern. Outputs with the BimboNeb were lower with the paediatric breathing pattern than with the adult pattern. In the majority of cases, nebulising for 10 min produced significantly greater drug output than after 5 min. For the Nebula, outputs were generally similar at 5 and 10 min, irrespective of the breathing pattern. These results highlight the need to assess the amount of aerosolised drug available when drugs are combined, when different nebulisers are used and when they are used with patients of different ages.
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Emporiadou, Maria; Aivazis, Victor; Mauromixalis, John; Hatzistilianou, Maria
2012-01-01
Introduction Acute bronchiolitis is the most common lower respiratory tract infection in infants and toddlers concerning small bronchi or bronchioli. This retrospective study aimed to evaluate the incidence of acute bronchiolitis and the use of β2-agonists between two different decades. Material and methods During 1990-1991 and 2001-2002, the files of the 2nd Paediatric Emergency Department of Aristotle University of Thessaloniki, AHEPA Hospital were reviewed and cases of acute bronchiolitis were recorded and analysed. Results During 1990-1991, 14 538 children were identified with respiratory infections and bronchiolitis was diagnosed in 519/14 538 children (3.56%). Only 34 out of 519 patients received nebulised salbutamol (6.6%) and 221/519 were hospitalized (42.6%). During 2001-2002, 9001 children were found to have respiratory tract infections and acute bronchiolitis was diagnosed in 641/9001 of them (7.12%). In total, 411/641 children (64.1%) received salbutamol and ipratropium, and 89/641 patients (13.88%) were hospitalized. There was a predominance of male sex in both decades (p = 0.509). There was a statistically significant difference (p < 0.001) concerning the use of nebulised salbutamol with nebulised ipratropium between the two decades. Finally, during 2001-2002, the use of bronchodilators with or without corticosteroids was more frequent and it appears to be correlated with the reduced number of admissions to hospital (p < 0.05) compared with 1990-1991. Conclusions There was an increase in the incidence of acute bronchiolitis during the last decade. The admission rate decreased probably due to the use of nebulized salbutamol and ipratropium, but further multicentre comparative trials are required to define the role of bronchodilators in the treatment of acute bronchiolitis. PMID:22852008
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New insight into the assessment of asthma using xenon ventilation computed tomography.
Jung, Jae-Woo; Kwon, Jae-Woo; Kim, Tae-Wan; Lee, So-Hee; Kim, Kyung-Mook; Kang, Hye-Ryun; Park, Heung-Woo; Lee, Chang-Hyun; Goo, Jin-Mo; Min, Kyung-Up; Cho, Sang-Heon
2013-08-01
Image analyses include computed tomography (CT), magnetic resonance imaging, and xenon ventilation CT, which is new modality to evaluate pulmonary functional imaging. To examine the usefulness of dual-energy xenon ventilation CT in asthmatic patients. A total of 43 patients 18 years or older who were nonsmokers were included in the study. Xenon CT images in wash-in and wash-out phases were obtained at baseline and after inhalation of methacholine and salbutamol. The degrees of ventilation defects and xenon trappings were evaluated through visual analysis. Ventilation defects and xenon trapping were significantly increased and decreased after methacholine challenge and salbutamol inhalation, respectively (P < .005). The ventilation abnormalities were not significantly related to the percentage of forced expiratory volume in 1 second (FEV1) or the ratio of FEV1 to forced vital capacity. Xenon trappings after salbutamol inhalation were negatively related to the scores of the asthma control test, wheezing, or night symptoms, with statistical significance (P < .05), whereas, FEV1 showed no significant correlation with symptom scores. Baseline FEV1 was significantly lower and dyspnea and wheezing were more severe in the non-full reversal group than in the full reversal group after salbutamol inhalation in xenon CT (P < .05). The degree of ventilation defects were positively correlated with FEV1 improvement after 3 months of treatment (P = .02). The results of this study suggest that xenon ventilation CT can be used as a new method to assess ventilation abnormalities in asthma, and these ventilation abnormalities can be used as novel parameters that reflect the status of asthma control and symptom severity. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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Vogelmeier, C; Naya, I; Ekelund, J
2012-07-01
The combination of an inhaled corticosteroid (ICS), budesonide, and a rapid long-acting β(2)-agonist (LABA), formoterol, in a single inhaler for use as maintenance and reliever therapy (Symbicort Turbuhaler SMART™) effectively achieves a high level of asthma control and reduces exacerbations and asthma-related hospitalizations. The COSMOS study, a multinational, 12-month study (N = 2143), compared budesonide/formoterol maintenance and reliever therapy with salmeterol/fluticasone propionate plus as-needed salbutamol, allowing physicians to modify maintenance doses of both combinations according to routine clinical practice. The aim of this post hoc sub-group analysis of the COSMOS study is to provide focused data on budesonide/formoterol maintenance and reliever therapy compared with salmeterol/fluticasone propionate plus as-needed salbutamol in patients (aged ≥16 years) enrolled across Asian countries, specifically China, Korea, Taiwan and Thailand. This sub-analysis of the COSMOS study concerns all 404 randomized patients ≥16 years of age (mean forced expiratory volume in 1 second [FEV(1)] 69.1%) who were recruited from Asian countries. Patients received either budesonide/formoterol (Symbicort Turbuhaler SMART™, n = 198), starting dose 160 mg/4.5 mg two inhalations twice daily (bid) [plus additional as-needed inhalations], or salmeterol/fluticasone propionate (Seretide(®) Diskus(®), n = 206), starting dose 50 mg/250 mg bid (plus salbutamol [Ventolin(®)] as needed). Maintenance doses could be titrated by clinicians after the first 4 weeks (budesonide/formoterol maintenance plus as needed, n = 198; salmeterol/fluticasone propionate plus salbutamol, n = 206). To allow for free adjustment in maintenance doses in both arms, the trial was performed open-label; maintenance doses could be titrated by clinicians after the first 4 weeks. The time to first severe exacerbation (defined as deterioration in asthma resulting in hospitalization/emergency room
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Association between respiratory prescribing, air pollution and deprivation, in primary health care.
Sofianopoulou, Eleni; Rushton, Stephen P; Diggle, Peter J; Pless-Mulloli, Tanja
2013-12-01
We investigated the association between respiratory prescribing, air quality and deprivation in primary health care. Most previous studies have used data from secondary and tertiary care to quantify air pollution effects on exacerbations of asthma and chronic obstructive pulmonary disease (COPD). However, these outcomes capture patients who suffer from relatively severe symptoms. This is a population-based ecological study. We analysed respiratory medication (salbutamol) prescribed monthly by 63 primary care practices, UK. Firstly, we captured the area-wide seasonal variation in prescribing. Then, using the area-wide variation in prescribing as an offset, we built a mixed-effects model to assess the remaining variation in relation to air quality and demographic variables. An increase of 10 μg/m(3) in ambient PM10 was associated with an increase of 1% (95% CI: 0.1-2%) in salbutamol prescribing. An increase of 1 SD in income and employment deprivation was associated with an increase of 20.5% (95% CI: 8.8-33.4%) and 14.7% (95% CI: 4.3-26.2%) in salbutamol prescribing rate, respectively. The study provides evidence that monthly respiratory prescribing in primary care is a useful indicator of the extent to which air pollution exacerbates asthma and COPD symptoms. Respiratory prescribing was higher on deprived populations.
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Como Podar Arboles (Spanish Version), How to Prune Trees
Maureen McDonough; Russell; Lisa Burban; Lee Nancarrow; United States Department of Agriculture, Forest Service, Northeastern Area, State and Private Forestry
2004-01-01
Introduccion, El proposito de la poda es tener plantas fuertes, sanas y atractivas. Esta meta se puede alcanzar sabiendo como, cuando y por que podar, y siguiendo unos cuantos principios muy sencillos.
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Wang, Yao; Yuan, Jiamin; Qian, Zhiyong; Zhang, Xiwen; Chen, Yanhong; Hou, Xiaofeng; Zou, Jiangang
2015-01-08
β2-AR activation increases the risk of sudden cardiac death (SCD) in heart failure (HF) patients. Non-selective β-AR blockers have greater benefits on survival than selective β1-AR blockers in chronic HF patients, indicating that β2-AR activation contributes to SCD in HF. This study investigated the role of β2-AR activation on repolarization and ventricular arrhythmia (VA) in the experimental HF model. The guinea pig HF was induced by descending aortic banding. The effective refractoriness period (ERP), corrected QT (QTc) and the incidence of VA were examined using Langendorff and programmed electrical stimulation. Ikr and APD were recorded by the whole cell patch clamp. Selective β2-AR agonist salbutamol significantly increased the incidence of VA, prolonged QTc and shortened ERP. These effects could be prevented by the selective β2-AR antagonist, ICI118551. Salbutamol prolonged APD90 and reduced Ikr in guinea pig HF myocytes. The antagonists of cAMP (Rp-cAMP) and PKA (KT5720) attenuated Ikr inhibition and APD prolongation induced by salbutamol. However, the antagonists of Gi protein (PTX) and PDE III (amrinone) showed opposite effects. This study indicates that β2-AR activation increases the incidence of VA in the experimental HF model via activation of Gs/cAMP/PKA and/or inhibition of Gi/PDE pathways.
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Wang, Yao; Yuan, Jiamin; Qian, Zhiyong; Zhang, Xiwen; Chen, Yanhong; Hou, Xiaofeng; Zou, Jiangang
2015-01-01
β2-AR activation increases the risk of sudden cardiac death (SCD) in heart failure (HF) patients. Non-selective β-AR blockers have greater benefits on survival than selective β1-AR blockers in chronic HF patients, indicating that β2-AR activation contributes to SCD in HF. This study investigated the role of β2-AR activation on repolarization and ventricular arrhythmia (VA) in the experimental HF model. The guinea pig HF was induced by descending aortic banding. The effective refractoriness period (ERP), corrected QT (QTc) and the incidence of VA were examined using Langendorff and programmed electrical stimulation. Ikr and APD were recorded by the whole cell patch clamp. Selective β2-AR agonist salbutamol significantly increased the incidence of VA, prolonged QTc and shortened ERP. These effects could be prevented by the selective β2-AR antagonist, ICI118551. Salbutamol prolonged APD90 and reduced Ikr in guinea pig HF myocytes. The antagonists of cAMP (Rp-cAMP) and PKA (KT5720) attenuated Ikr inhibition and APD prolongation induced by salbutamol. However, the antagonists of Gi protein (PTX) and PDE III (amrinone) showed opposite effects. This study indicates that β2-AR activation increases the incidence of VA in the experimental HF model via activation of Gs/cAMP/PKA and/or inhibition of Gi/PDE pathways. PMID:25567365
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Effects of H sub 2 S addition on the performance of fresh vs. used CoMo catalysts
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rankel, L.A.
1991-01-01
When a Co/Mo catalyst is used for processing vanadium-containing heavy oils, vanadium deposits on the catalyst. As the amount of vanadium on the CoMo catalyst increases, the catalytic effects of CoMo decline and the presence of vanadium starts to influence the hydroprocessing products. Model feeds have been used to explore the changes in the catalytic activity of CoMo, aged CoMo, and VS{sub x} on alumina. Desulfurization, denitrogenation, deoxygenation, aromatics hydrogenation, and metals removal were monitored. This paper reports that, upon the addition of hydrogen sulfide to hydrogen, improvements in the catalysts for aromatics hydrogenation, denitrogenation and metals removal were observed.
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Microwave effects on NiMoS and CoMoS single-sheet catalysts.
Borges, I; Silva, Alexander M; Modesto-Costa, Lucas
2018-05-04
Single-sheet nanoclusters of MoS 2 , NiMoS or CoMoS are widely used in hydrodesulfurization (HDS) catalysis in the petroleum industry. In HDS reactions under microwave irradiation, experiments indirectly pointed out that for pristine MoS 2 reaction rates are accelerated because hot spots are generated on the catalyst bed. In this work, we investigated NiMoS and CoMoS isolated single-sheet substituted catalysts before and after thiophene adsorption focusing on quantifying the effect of microwave irradiation. For that purpose, density functional theory (DFT) molecular charge densities of each system were decomposed according to the distributed multipole analysis (DMA) of Stone. Site dipole values of each system were directly associated with a larger or smaller interaction with the microwave field according to a proposed general approach. We showed that microwave enhancement of HDS reaction rates can occur more efficiently in the CoMoS and NiMoS promoted clusters compared to pristine MoS 2 in the following order: CoMoS > NiMoS > MoS 2 . The atomic origin of the catalyst hot spots induced by microwaves was clearly established in the promoted clusters.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Veen, J.A.R. van; Hendriks, P.A.J.M.; Beens, H.
1992-01-01
A suite of 11 CoMo/Al{sub 2}O{sub 4} (and one CoMo/SiO{sub 2}) catalysts has been prepared employing four preparation routes, viz. one sequential-impregnation route and three different coimpregnation routes. Speciation of the Co present in the oxidic precursors (octahedral vs tetrahedral Co) and in the activated, sulfided catalysts (CoMoS, Co{sub 9}S{sub 8}, and unsulfided Co) was effected with the aid of {sup 57}Co Moessbauer emission spectroscopy (MES). A linear relation between the thiophene-hydrodesulfurization (HDS) activity and wt% Co-in-CoMoS was observed for each preparation route, but no unique correlation was found to exist. This was traced to the fact that the preparationmore » routes differ in the amount of CoMoS I and CoMoS II they produce in the activated catalyst. Although these two phases differ in specific activity, CoMoS II being twice as active in thiophene HDS as CoMoS I, they cannot be distinguished on the basis of their Moessbauer parameters. It appears that octahedral Co is easier to sulfide than tetrahedral Co, but a substantial fraction of the latter is also found to be capable of entering CoMoS upon sulfidation. The reduced effectiveness of high-loading catalysts is traced to their being prone to CoMoO{sub 4} formation in the calcination step. A rationalization of this behavior is offered.« less
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Como Lo Hago Yo: Myelomeningocele
Lazareff, Jorge
2014-01-01
Fortificación con ádico fólico es efectiva, pero aún falta conciencia en los jóvenes. La legalidad del aborto aumenta la importancia de la consulta prenatal. Realizo la cirugía bajo microcoscopio por razones didácticas. Irrigación continua para reducir la temperatura del tejido. Trato a la plaqueta como tejido viable. No suturo la plaqueta. No cierro músculo. ATB por una semana después de cirugía. Hidrocefalia: Válvula en todos los casos de ventriculomegalia. Médula anclada: Desanclar una sola vez. Chiari II: Revisar la válvula. Incluir en el seguimiento rendimiento escolar, puede indicar obstrucción de la válvula o médula anclada. PMID:24791217
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Infórmese sobre el programa de WIFIA
La Ley de finanzas e innovación de la infraestructura del agua de 2014 estableció el programa de WIFIA, un programa federal crediticio administrado por la EPA para proyectos elegibles de infraestructura de agua y aguas sanitarias.
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Cúmulos globulares como trazadores de bimodalidad estelar en galaxias cD
NASA Astrophysics Data System (ADS)
Forte, J. C.
Se muestra que tanto la forma de los perfiles de brillo como de color observados en dos galaxias arquetípicas de tipo cD (NGC 1399 y NGC 4486) son compatibles con la presencia de poblaciones estelares bi-modales que comparten la misma distribución espacial y composición química de las familias dominantes de cúmulos globulares asociadas con ellas. El modelo resultante también predice una variación de la frecuencia específica de los cúmulos como función del radio galactocéntrico. Se discute este resultado en el contexto de una variedad de escenarios astrofísicos que intentan describir la formación de galaxias cD.
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Valorisation of Como Historical Cadastral Maps Through Modern Web Geoservices
NASA Astrophysics Data System (ADS)
Brovelli, M. A.; Minghini, M.; Zamboni, G.
2012-07-01
Cartographic cultural heritage preserved in worldwide archives is often stored in the original paper version only, thus restricting both the chances of utilization and the range of possible users. The Web C.A.R.T.E. system addressed this issue with regard to the precious cadastral maps preserved at the State Archive of Como. Aim of the project was to improve the visibility and accessibility of this heritage using the latest free and open source tools for processing, cataloguing and web publishing the maps. The resulting architecture should therefore assist the State Archive of Como in managing its cartographic contents. After a pre-processing consisting of digitization and georeferencing steps, maps were provided with metadata, compiled according to the current Italian standards and managed through an ad hoc version of the GeoNetwork Opensource geocatalog software. A dedicated MapFish-based webGIS client, with an optimized version also for mobile platforms, was built for maps publication and 2D navigation. A module for 3D visualization of cadastral maps was finally developed using the NASA World Wind Virtual Globe. Thanks to a temporal slidebar, time was also included in the system producing a 4D Graphical User Interface. The overall architecture was totally built with free and open source software and allows a direct and intuitive consultation of historical maps. Besides the notable advantage of keeping original paper maps intact, the system greatly simplifies the work of the State Archive of Como common users and together widens the same range of users thanks to the modernization of map consultation tools.
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The Chocuhaler: sweet deliverance in asthma management.
Hayden, M J; Wildhaber, J H; Eber, E; Devadason, S G
To determine the characteristics of a new cocoa-based edible spacer device for the delivery of aerosol bronchodilator. In-vitro comparison of two spacer devices (standard and edible) and determination of bronchodilator response using the edible spacer. A university children's hospital in Western Australia. Two volunteers with moderate asthma. Compared with a standard spacer, the edible spacer delivered significantly more bronchodilator in droplets of a size likely to enter the respiratory tract. A significant bronchodilator response occurred in two out of two subjects when salbutamol was inhaled orally via the chocolate spacer. No significant bronchodilator response occurred in either subject when the spacer was eaten at the end of the study. The chocolate spacer used in this study is a suitable device to deliver salbutamol by inhalation. However, there may be potential drawbacks of weight gain in some patients and meltdown in hot climates.
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Zhu, Yanyan; Yuan, Yuan; Xiao, Xiuchan; Zhang, Liyun; Guo, Yanzhi; Pu, Xuemei
2014-11-01
G-protein-coupled receptors (GPCRs) are currently one of the largest families of drug targets. The constitutive activation induced by mutation of key GPCR residues is associated closely with various diseases. However, the structural basis underlying such activation and its role in drug binding has remained unclear. Herein, we used all-atom molecular dynamics simulations and free energy calculations to study the effects of a D130N mutation on the structure of β2 adrenergic receptor (β2AR) and its binding of the agonist salbutamol. The results indicate that the mutation caused significant changes in some key helices. In particular, the mutation leads to the departure of transmembrane 3 (TM3) from transmembrane 6 (TM6) and marked changes in the NPxxY region as well as the complete disruption of a key ionic lock, all of which contribute to the observed constitutive activation. In addition, the D130N mutation weakens some important H-bonds, leading to structural changes in these regions. Binding free energy calculations indicate that van der Waals and electrostatic interactions are the main driving forces in binding salbutamol; however, binding strength in the mutant β2AR is significantly enhanced mainly through modifying electrostatic interactions. Further analysis revealed that the increase in binding energy upon mutation stems mainly from the H-bonds formed between the hydroxyl group of salbutamol and the serine residues of TM5. This observation suggests that modifications of the H-bond groups of this drug could significantly influence drug efficacy in the treatment of diseases associated with this mutation.
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Yip, Lian Yee; Lim, Yen Fang; Chan, Hong Ngee
2011-11-01
Nebulised heparin, N-acetylcysteine (NAC) and salbutamol were shown to decrease reintubation rates, incidence of atelectasis and mortality in paediatric patients and reduce lung injury scores in adult burns patients with inhalational lung injury (ILI). Nebulised heparin, NAC and salbutamol treatment protocol was introduced in Singapore General Hospital (SGH) Burns Centre in 2006. However, safety data on the use of nebulised heparin and NAC for burns patients with ILI is not well established. In this study, we investigated the safety and potential anticoagulant effects of nebulised heparin in burns patients with ILI. A retrospective study with historical control was conducted. The treatment group consisted of 52 mechanically ventilated adult patients, with a diagnosis of ILI as confirmed by bronchoscopy, admitted to burn intensive care unit (BICU) from the year 2006 to 2009. The group was treated with nebulised heparin, NAC and salbutamol. The control group consists of 11 mechanically ventilated BICU ILI patients treated from year 2001 to 2005 before protocol initiation. Blood coagulation indices (prothrombin time (PT), activated partial thromboplastin time (APTT) and platelet count) were monitored and bleeding incidences were assessed. Blood coagulation indices did not suggest an increase risk of bleeding with nebulised heparin. The APTT, PT and platelet count followed a similar trend for both groups over 7 days. No clinically significant increase in bleeding risk was found to be associated with nebulised heparin. Nebulised heparin was not found to potentiate the risk of bleeding in burns patients with ILI. Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.
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Balamurugan, Jayaraman; Li, Chao; Peera, Shaik Gouse; Kim, Nam Hoon; Lee, Joong Hee
2017-09-21
Layered transition metal sulfides (TMS) are emerging as advanced materials for energy storage and conversion applications. In this work, we report a facile and cost-effective anion exchange technique to fabricate a layered, multifaceted, free standing, ultra-thin ternary cobalt molybdenum sulfide nanosheet (Co-Mo-S NS) architecture grown on a 3D porous Ni foam substrate. The unique Co-Mo layered double hydroxides are first synthesized as precursors and consequently transformed into ultra-thin Co-Mo-S NS. When employed as an electrode for supercapacitors, the Co-Mo-S NS delivered an ultra-high specific capacitance of 2343 F g -1 at a current density of 1 mA cm -2 with tremendous rate capability and extraordinary cycling performance (96.6% capacitance retention after 20 000 cycles). Furthermore, assembled Co-Mo-S/nitrogen doped graphene nanosheets (NGNS) in an asymmetric supercapacitor (ASC) device delivered an excellent energy density of 89.6 Wh kg -1 , an amazing power density of 20.07 kW kg -1 , and superior cycling performance (86.8% capacitance retention after 50 000 cycles). Such exceptional electrochemical performance of Co-Mo-S NS is ascribed to the good electrical contact with the 3D Ni foam, ultra-high contact area with the electrolyte, and enhanced architectural softening during the charging/discharging process. It is expected that the fabricated, unique, ultra-thin Co-Mo-S NS have great potential for future energy storage devices.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Muralidhar, G.; Massoth, F.E.; Shabtai, J.
1984-01-01
C-S hydrogenolysis (HDS) of thiophene, hydrogenation (HYD) of 1-hexene, and hydrocracking (HCG) of 2,4,4-trimethyl-1-pentene, were used as separate model test reactions to differentiate and assess the catalytic functionalities of sulfided CoMo catalysts, and their dependence on the nature of the support and incorporation of additives. Rate constants and relative catalyst activities for these three reaction types were determined. HDS and HYD activities of CoMo supported on different types of Al/sub 2/O/sub 3/ were higher, while the HCG activity was lower compared with CoMo supported on SiO/sub 2/-Al/sub 2/O/sub 3/, SiO/sub 2/-MgO, or TiO/sub 2/. For SiO/sub 2/-Al/sub 2/O/sub 3/ supportsmore » both HDS and HYD activities decreased with increase in SiO/sub 2/ content from 10 to 75%, while HCG activity showed the opposite trend. Additives to a finished CoMo catalyst at 0.5% level caused variations in HDS and HCG activities, while HYD was essentially unaffected. HDS was promoted by NH/sub 4/HF/sub 2/ and NH/sub 4/Cl, but depressed by NaNO/sub 3/, Ca(NO/sub 3/)/sub 2/, and H/sub 3/BO/sub 3/. HCG was promoted by NH/sub 4/HF/sub 2/, NH/sub 4/Cl, and H/sub 3/BO/sub 3/. Additives at 5% level, prior to or after CoMo impregnation, showed a strong depressing effect on HDS and a lesser effect on HYD, while HCG was strongly promoted by NH/sub 4/HF/sub 2/, Ti isopropoxide, and H/sub 3/BO/sub 3/. The changes in catalytic functionalities are rationalized in terms of different interactions between CoMo phase, support, and additives. 3 tables, 1 figure.« less
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San Mauro-Martín, Ismael; Collado-Yurrita, Luis; Blumenfeld-Olivares, Javier Andrés; Cuadrado-Cenzual, María Ángeles; Calle-Purón, María Elisa; Hernández-Cabria, Marta; Garicano-Vilar, Elena; Pérez-Arruche, Eva; Arce-Delgado, Esperanza; CiudadCabañas, María José
2016-06-30
Introducción: la hipercolesterolemia es uno de los principales factores de riesgo en la enfermedad cardiovascular. Los esteroles vegetales se han postulado como agentes reguladores y beneficiosos para el control de esta.Objetivo: analizar el efecto de los esteroles vegetales añadidos en una leche en la reducción del colesterol plasmático en adultos jóvenes.Métodos: ensayo clínico, controlado, aleatorizado, doble ciego y cruzado. Los esteroles (2,24 g diarios) fueron administrados en dos tomas de 350 ml de una leche comercial desnatada, durante dos periodos de 3 semanas, separados por una "fase de lavado" de 2 semanas, en el grupo experimental. Al grupo control se le administró la misma cantidad de leche desnatada, sin esteroles. Tanto al inicio como al final de cadaperiodo de intervención se extrajeron muestras sanguíneas. Se analizaron la composición corporal, hábitos de salud y los siguientes marcadores sanguíneos: perfil lipídico, hematológico, inflamación, etc.Resultados: se incluyeron 54 personas en el estudio con una edad media de 38,8 ± 7,3 años. La diferencia porcentual entre los marcadores basales y finales para el colesterol total, colesterol-LDL, colesterol-HDL, triglicéridos y colesterol no-HDL fueron del 9,73%, 12,5%, 1,9%, 3,15% y 13,2%, respectivamente. Se obtuvieron diferencias estadísticamente significativas entre el grupo experimental y el grupo control, para todos los marcadores analizados excepto para los triglicéridos.Conclusión: los esteroles vegetales suministrados en un alimento de consumo habitual, como la leche, pueden ser una estrategia terapéutica no farmacológica para el control de la hipercolesterolemia de alto interés sanitario.
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Malik, Poonam; Bhushan, Ravi
2018-01-01
Direct enantiomeric resolution of commonly used five racemic β-adrenolytics, namely, bisoprolol, atenolol, propranolol, salbutamol and carvedilol has been achieved by thin layer chromatography using bovine serum albumin (BSA) as chiral additive in stationary phase. Successful resolution of the enantiomers of all racemic β-adrenolytics was achieved by use of different composition of simple organic solvents having no buffer or inorganic ions. The effect of variation in pH, temperature, amount of BSA as the additive, and composition of mobile phase on resolution was systematically studied. Spots were visualized in iodine vapors. Native enantiomers for each of the five analytes were isolated and identified and their elution order was determined. The limit of detection was found to be 0.7, 1.2, 0.84, 1.6 and 0.9 μg (per spot) for each enantiomer of bisoprolol, atenolol, propranolol, salbutamol and carvedilol, respectively. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Determination of beta-agonists in swine hair by μFIA and chemiluminescence.
Chen, Xu; Luo, Yong; Shi, Bo; Gao, Zhigang; Du, Yuguang; Liu, Xianming; Zhao, Weijie; Lin, Bingcheng
2015-04-01
β-Agonists are a group of illegal feed additives. In this paper, it was found that the light emission produced by the oxidation of luminol by potassium ferricyanide was enhanced by the β-agonists (ractopamine, salbutamol, and terbutaline). Based on chemiluminescence phenomenon, a novel, rapid, and sensitive microflow injection analysis system on a microfluidic glass chip was established for determination of the β-agonists. The chip was fabricated from two glass plates (64 mm × 32 mm) with microchannels of 200 μm width and 100 μm depth. The detection limits were achieved at 2.0 × 10(-8) mol/L of ractopamine, 1.0 × 10(-8) mol/L of terbutaline and 5.0 × 10(-7) mol/L of salbutamol. In this report, our method was applied for determination of the β-agonists in swine hair from three different sources with satisfactory results. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Do we really ponder about necessity of intravenous hydration in acute bronchiolitis?
Yıldırım, Şule; Kaymaz, Nazan; Topaloğlu, Naci; Köksal Binnetoğlu, Fatih; Tekin, Mustafa; Aylanç, Hakan; Battal, Fatih; Gön Uuml Ll Uuml, Burçin
2016-03-30
The goal was to establish the role of intravenous hydration therapy on mild bronchiolitis. This was a retrospective case control study. Infants between 1 month and 2 years of age admitted to our general pediatrics ward between June 2012 and June 2013 with a diagnosis of uncomplicated acute bronchiolitis were enrolled to the study. Hospital medical files were reviewed to get information about children personal history, symptoms of the disease, disease severity scores and their management. Patients were classified into 4 groups according to the management; nebulized short-acting β2-agonist (salbutamol) +hydration; nebulized short-acting β2-agonist (salbutamol); hydration and neither bronchodilator nor hydration. We examined length of stay in the hospital as an outcome measure. A total of 94 infants were studied. There was no significant difference between groups in terms of length of stay in hospital. IV hydration is not effective on length of stay in hospital in mild acute bronchiolitis patients.
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Thermophysical properties of undercooled liquid Co-Mo alloys
NASA Astrophysics Data System (ADS)
Han, X. J.; Wei, B.
2003-05-01
Using electromagnetic levitation in combination with the oscillating drop technique and drop calorimeter method, the surface tensions and specific heats of undercooled liquid Co-10 wt% Mo, Co-26.3 wt% Mo, and Co-37.6 wt% Mo alloys were measured. The containerless state during levitation produces substantial undercoolings up to 223 K (0.13TL), 213 K (0.13TL) and 110 K (0.07TL) respectively for these three alloys. In their respective undercooling ranges, the surface tensions were determined to be 1895 m 0.31(T m 1744), 1932 m 0.33(T m 1682), and 1989 m 0.34(T m 1607) mN mу. According to the Butler equation, the surface tensions of these three Co-Mo alloys were also calculated, and the results agree well with the experimental data. The specific heats of these three alloys are determined to be 41.85, 43.75 and 44.92 J molу Kу. Based on the determined surface tensions and specific heats, the changes in thermodynamics functions such as enthalpy, entropy and Gibbs free energy are predicted. Furthermore, the crystal nucleation, dendrite growth and Marangoni convection of undercooled Co-Mo alloys are investigated in the light of these measured thermophysical properties.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Fiveland, W.A.; Oberjohn, W.J.; Cornelius, D.K.
1985-12-01
This report summarizes the work conducted during a 30-month contract with the United States Department of Energy (DOE) Pittsburgh Energy Technology Center (PETC). The general objective is to develop and verify a computer code capable of modeling the major aspects of pulverized coal combustion. Achieving this objective will lead to design methods applicable to industrial and utility furnaces. The combustion model (COMO) is based mainly on an existing Babcock and Wilcox (B and W) computer program. The model consists of a number of relatively independent modules that represent the major processes involved in pulverized coal combustion: flow, heterogeneous and homogeneousmore » chemical reaction, and heat transfer. As models are improved or as new ones are developed, this modular structure allows portions of the COMO model to be updated with minimal impact on the remainder of the program. The report consists of two volumes. This volume (Volume 1) contains a technical summary of the COMO model, results of predictions for gas phase combustion, pulverized coal combustion, and a detailed description of the COMO model. Volume 2 is the Users Guide for COMO and contains detailed instructions for preparing the input data and a description of the program output. Several example cases have been included to aid the user in usage of the computer program for pulverized coal applications. 66 refs., 41 figs., 21 tabs.« less
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Morphological investigation of nanostructured CoMo catalysts
NASA Astrophysics Data System (ADS)
Pawelec, B.; Castaño, P.; Zepeda, T. A.
2008-04-01
This work reports the morphological investigation of nanostructured sulfided CoMo catalysts by means of high-resolution transmission electron microscopy (HRTEM). The catalysts were supported on Ti-modified hexagonal mesoporous silica (HMS-Ti) and P-modified HMS-Ti (P/HMS-Ti) materials. The oxide precursors were characterized by specific surface area (S BET), temperature-programmed reduction (TPR), diffuse reflectance infrared Fourier transform spectroscopy in the OH region (DRIFTS-OH) and X-ray photoelectron spectroscopy (XPS) in order to elucidate the influence of the impregnation sequence (successive vs. simultaneous) and the effect of P-incorporation into HMS-Ti material on the morphology of calcined CoMo catalysts. Both TPR and XPS measurements indicate that the catalysts prepared by successive impregnation possess well-dispersed MoO 3 and CoO phases, whereas their counterparts prepared by simultaneous impregnation additionally possess the CoMoO 4 phase. For all sulfided catalysts, the presence of MoS 2 phase with particle size in the range 3.3-4.4 nm was confirmed by HRTEM. Catalytic activity was evaluated in the reaction of hydrodesulfurization (HDS) of dibenzothiophene (DBT) carried out in a flow reactor at 593 K and hydrogen pressure of 5.5 MPa. P-incorporation into the HMS-Ti material led to an overall increase in HDS activity and the hydrogenation ability of the sulfided catalysts. All catalysts proved to be stable during 10 h time-on-stream (TOS) operation. The activity of sulfide catalysts in the target reaction depends linearly on the surface exposure of Co species in the oxide precursors, as determined by XPS, and on the morphology of the sulfide form of catalysts (surface density of MoS 2 particles and their sizes) as determined by HRTEM.
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Clinical application of inert gas Multiple Breath Washout in children and adolescents with asthma.
Zwitserloot, Annelies; Fuchs, Susanne I; Müller, Christina; Bisdorf, Kornelia; Gappa, Monika
2014-09-01
Children with asthma often have normal spirometry despite significant disease. The pathology of the small airways in asthma may be assessed using Multiple Breath Washout (MBW) and calculating the Lung Clearance Index (LCI). There are only few studies using MBW in children with asthma and existing data regarding bronchodilator effect are contradictory. The aim of the present pilot study was to compare LCI in asthma and controls and assess the effect of salbutamol in children with asthma on the LCI. Unselected patients with a diagnosis of asthma visiting the outpatient department of our hospital between 04-2010 and 03-2011 were recruited and compared to a healthy control group. MBW was performed as inert gas MBW using sulfurhexafluorid (SF6) as the tracer gas. Clinical data were documented and spirometry and MBW (EasyOne Pro, MBW module, NDD Switzerland) were performed before and after the use of salbutamol (200-400 μg). Healthy controls performed baseline MBW only. 32 children diagnosed with asthma (4.7-17.4 years) and 42 controls (5.3-20.8) were included in the analysis. LCI differed between patients and controls, with a mean LCI (SD) of 6.48 (0.48) and 6.21 (0.38) (P = 0.008). Use of salbutamol had no significant effect on LCI for the group. These pilot data show that clinically stable asthma patients and controls both have a LCI in the normal range. However, in patients the LCI is significantly higher indicating that MBW may have a role in assessing small airways disease in asthma. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Steam inhalation or humidified oxygen for acute bronchiolitis in children up to three years of age.
Umoren, Rachel; Odey, Friday; Meremikwu, Martin M
2011-01-19
Acute bronchiolitis is a common respiratory infection and a major cause of morbidity in young children. It is treated with bronchodilators (for example, salbutamol), corticosteroids or humidified air (steam inhalation or cool mist). Steam inhalation is preferred in low-income countries as it is inexpensive and easily available. It is thought to act as a secretolytic agent to lighten secretions in the respiratory tract and relieve respiratory distress. To evaluate the effect of steam inhalation or humidified oxygen to relieve respiratory distress and to evaluate adverse events in children up to three years old with acute bronchiolitis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 1) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1950 to February Week 4, 2010), EMBASE.com (1974 to March 2010), CINAHL (1981 to March 2010), AMED (1985 to March 2010), Web of Science (2000 to March 2010) and LILACS (1982 to March 2010). Randomised controlled trials involving children up to three years old with bronchiolitis comparing steam inhalation (or cool mist) or humidified oxygen against bronchodilators, corticosteroids or placebo; alone or in combination. Two review authors independently assessed trial quality and extracted data. Only one study (156 children aged between seven weeks and 24 months with signs and symptoms of bronchiolitis) met the eligibility criteria for inclusion. Participants were randomised into three groups: nebulised salbutamol, nebulised saline and mist in a tent. The results showed a significant decrease in respiratory distress symptom (RDS) score in the nebulised salbutamol group but no significant decrease in the RDS score in the mist in a tent or nebulised saline groups. The study did not report on adverse effects of the interventions. Steam inhalation (or cool mist therapy) is commonly used to treat acute bronchiolitis in resource-constrained settings
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Matran, R; Naline, E; Advenier, C; Duroux, P
1989-01-01
The aim of this study was to investigate quantitatively the action of and the interaction between beta-adrenergic receptor agonists in desensitizing guinea pig isolated trachea. It was also to evaluate the influence of substances whose effects on desensitization are either disputed (theophylline, indomethacin, ketotifen, hydrocortisone) or unknown (nicardipine, Bay K 8644, fenspiride, adenosine). Tracheal strips were contracted with histamine (5 x 10(-5) M) or acetylcholine (5.10(-5) M) and concentration-response (C/R) curves for various beta-adrenoceptor agonists were determined before and after incubation (20 min to 4 h) with the same beta-adrenoceptor agonist (autodesensitization), with other beta-adrenoceptor agonists (cross-desensitization), or with a beta-adrenoceptor agonist and another substance. Our results show that the autodesensitization induced by isoprenaline is concentration dependent and that concentration dependence is more pronounced with salbutamol and fenoterol than with isoprenaline and adrenaline with respect to autodesensitization: shifts (log unit) of the C/R curves were 0.59 +/- 0.06 (N = 5) for salbutamol (10(-5) M), 0.78 +/- 0.09 (N = 5) for fenoterol (10(-6) M), 0.30 +/- 0.04 (N = 9) for isoprenaline (10(-5) M), and 0.33 +/- 0.05 (N = 5) for adrenaline (10(-5) M). Our studies of cross-desensitization (desensitization to isoprenaline, adrenaline, salbutamol, and fenoterol induced by incubation with isoprenaline 10(-5) M) showed a significantly greater shift in the C/R curves for fenoterol (0.56 +/- 0.08, N = 5) and salbutamol (0.62 +/- 0.05, N = 5) than for adrenaline (0.35 +/- 0.07, N = 5) and isoprenaline itself (0.30 +/- 0.05, N = 9). Of the substances we studied, none modified the desensitization induced by isoprenaline except hydrocortisone and adenosine. Hydrocortisone (10(-8) M) reduced it significantly, although to a negligible extent. Adenosine (3 x 10(-4) M) did not shift the C/R curve to isoprenaline by itself, but incubation
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Geophysical investigations of the Olonium Roman site (Northern Como Lake)
NASA Astrophysics Data System (ADS)
Arlsan, Ermanno; Biella, Giancarlo; Boniolo, Graziano; Caporusso, Donatella; de Franco, Roberto; Lozej, Alfredo; Veronese, Luigi
1999-03-01
The study area is located at S. Agata (Gera Lario), a small center at the northern end of Como Lake, near the junction of Valchiavenna and Valtellina Valleys. This site played a strategic role since ancient times, providing the control on the communications routes to both the Como Lake and the Spluga and Septimer alpine passes. Since the end of the last century archaeological findings are reported in literature, also supported, from the early XI century, by archival documents confirming the existence of the `Olonium' settlement, an administrative and fiscal center of primary importance, as well as a parish amongst the most influential in the Como Lake area. Within an area of 45,000 m 2 an electrical survey has been carried out in conjunction with magnetic and GPR investigations. These studies have indicated the presence of a number of sub-areas characterized by significant anomalies defined by the overlapping of the results obtained from two or more geophysical methods. In two of such sub-areas, excavation tests have been conducted, which have brought to light a number of archaeological findings of interest. In one of the two sub-areas, which is characterized by the superimposition of electrical and radar anomalies, a deposit of large pebbles has been found. The origin of this deposit has not been ascertained, whether it is of fluvial origin, related to the deviation of the Adda river in the Pian di Spagna region in Roman times, or it is part of reclamation works, still of Roman times, of paleolacustrine marshes. The overlapping stratigraphy, however, suggests the development of fluvial channels between Roman and Low-Medieval times. In the other sub-area, excavations were carried out on sites defined by electrical and radar anomalies, and confirmed by the results from magnetic survey. The excavations brought to light, below the fluvial deposits, a large medieval edifice, which could be identified as the S. Stefano church abandoned in 1444. The church is built on
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Corrado, Giovanni; Durante, Alessandro; Genchi, Vincenzo; Trabattoni, Loris; Beretta, Sandro; Rovelli, Enza; Foglia-Manzillo, Giovanni; Ferrari, Giovanni
2016-08-01
The prognosis for abdominal aortic aneurysm (AAA) rupture is poor. Long-term follow-up of population-based randomized trials has demonstrated that ultrasound (US) screening for abdominal aortic aneurysms (AAAs) measuring 3 cm or greater decreases AAA-related mortality rates and is cost-effective. We though to prospectively perform during a 26-month period a limited US examination of the infrarenal aorta in volunteers of both gender aged 60-85 years without history of AAA living in the area of Como, Italy. From September 2010 to November 2013 ComoCuore, a no-profit nongovernmental association, enrolled 1555 people (aged 68.8 ± 6.8 years; 48.6 % males). Clinical data and a US imaging of the aorta were collected for each participant. AAA was found in 22 volunteers (1.4 %) mainly males (2.5 % in males vs. 0.4 % in females p = 0.005). Overall, the prevalence of cardiovascular risk factors was higher in patients with vs. without AAA (mean 2.9 ± 3.0 vs. 1.4 ± 1.0 respectively, p < 0.0001). Independent predictors of AAA on multivariate analysis were age (OR 1.14, 1.06-1.22; p < 0.0001), male gender (OR 8.23, 1.79-37.91; p = 0.007), and both current (OR 4.98, 1.57-15.79; p = 0.007) and previous smoking (OR 2.76, 1.12-8.94; p = 0.03). Our study confirms the feasibility of one time US screening for AAA in a large cohort of asymptomatic people. Independent predictors of AAA were male sex, older age and a history of smoking. Accordingly to recent data the prevalence of AAA seems to be declining, maybe due to a reduction of smoking in Italy.
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Funston, Wendy; Howard, Simon J
2016-01-01
Objectives. The primary objective of this study was to assess the rules governing secondary school pupils' carriage of inhalers for emergency treatment of asthma in the North East of England. Design. This study was based upon a postal questionnaire survey. Setting. The setting for this study was mainstream free-to-attend secondary schools which admit 16 year old pupils within the 12 Local Authority areas which make up the North East of England. Participants. All 153 schools meeting the inclusion criteria were invited to participate in the study, of which 106 (69%) took part. Main Outcome Measures. Our three main outcome measures were: whether pupils are permitted to carry inhalers on their person while at school; whether advance permission is required for pupils to carry inhalers, and from whom; and whether the school has an emergency 'standby' salbutamol inhaler for use in asthma emergencies, as permitted since October 2014 under recent amendments to The Human Medicines Regulations 2012. Results. Of 98 schools submitting valid responses to the question, 99% (n = 97) permitted pupils to carry inhalers on their person while at school; the remaining school stored pupils' inhalers in a central location within the school. A total of 22% of included schools (n = 22) required parental permission before pupils were permitted to carry inhalers. Of 102 schools submitting valid responses to the question, 44% (n = 45) had purchased a 'standby' salbutamol inhaler for use in asthma emergencies. Conclusions. Most secondary schools in North East England permit pupils to carry inhalers on their person. The requirement in a minority of schools for parental permission to be given possibly contravenes the standard ethical practices in clinical medicine for children of this age. Only a minority of schools hold a 'standby' salbutamol inhaler for use in asthma emergencies. Wider availability may improve outcomes for asthma emergencies occurring in schools.
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Elías, Pedro C; Sagua, Delia; Alvarez, Edgardo O
2004-02-04
The purpose of the present work was to examine if the conventional asthma treatments in humans (inhalation of glucocorticoids or beta-agonists, administered in a chronic regimen) might affect behavioral processes (learning and exploratory motivation) in rats. Adult male rats were exposed to an atmosphere saturated with either saline, budesonide (a glucocorticoid), or salbutamol (a beta-adrenergic receptor agonist) in a forced ventilation cage, connected to a nebulizer for 5 min twice a day for 15 days at the same hours of the day. Doses of budesonide in the nebulizing solution were 0.116, 1.16, and 11.6mM. Doses of salbutamol in the nebulizing solution were 1.3, 13, and 130 mM. Forty-eight hours after treatment, the different groups were subjected to exploration of an elevated asymmetric plus-maze (APM, model of exploratory motivation), and 24h later to learning of an avoidance response to an ultrasonic tone in a two-compartment cage (model of memory and learning). Results showed that budesonide induces moderate effects on exploratory motivation. In one of the fear-inducing arms (single wall arm), exploration decreased and this effect was not dose dependent. In the cognitive model, glucocorticoids affected slightly the latency to escape but with no interference in memory efficiency. On the other hand, at the lower dose in the APM, salbutamol increased significantly the exploration of both fear-inducing arms (no walls and single wall arms). In the learning model, the beta-agonist induced two opposing effects. The lower dose (1.3mM) facilitated learning and the higher dose (13 mM) inhibited learning instead. In conclusion, results are compatible with the notion that inhaled glucocorticoids or beta-agonists might cross the lung aerial barrier into the blood compartment, exerting effects on learning and motivation functions.
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Boskabady, Mrteza; Boskabady, Mohammad Hossein; Zabihi, Narges Amel; Boskabady, Marzie
2015-01-01
Pulmonary complications due to mustard gas exposure range from no effect to severe bronchial stenosis. Pulmonary function tests (PFTs) and respiratory symptoms in chemical war victims were studied 23-25 years after exposure to sulfur mustard (SM). Respiratory symptoms were evaluated in a sample of 142 chemical war victims and 120 control subjects with similar age from the general population using a questionnaire including questions on respiratory symptoms in the past year. PFT values were also measured in chemical war victims before and 15 min after the inhalation of 200 µg salbutamol and baseline PFT in controls. All chemical war victims (100%) reported respiratory symptoms. Wheezing (66.19%), cough (64.78%), and chest tightness (54.4%) were the most common symptoms and only 15.5% of chemical war victims reported sputum (p < 0.01 for sputum and p < 0.001 for other symptoms compared with control group). In addition, 49.3% of chemical war victims had wheeze in chest examination, which were significantly higher than control group (p < 0.001). The severity of respiratory symptoms was also significantly higher than control subjects (p < 0.05 for sputum and p < 0.001 for other symptoms). All the PFT values were also significantly lower in chemical war victims than that in control subjects (p < 0.001 for all cases). In addition, all the PFT values improved significantly after the inhalation of 200 µg salbutamol (p < 0.05-p < 0.001). These results showed that chemical war victims, 23-25 years after exposure to chemical warfare have higher frequencies and severity of respiratory symptoms. PFT values were also significantly reduced among chemical war victims, which showed reversibility due to the inhalation of 200 µg salbutamol. © The Author(s) 2012.
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Solé, D; Rizzo, M C; Porto, I M; Gomez, I D; Sano, F; Figueiredo, M A; Naspitz, C K
1996-01-01
Patients during a mild to moderate acute attack of asthma (FEV1: 50 - 80% of predicted) were treated with Salmeterol MDI - 50mcg or Rotadisk - 50mcg or Salbutamol (MDI -200mcg). The children were followed by Spirometry, measuring FEV1 (basal) and after treatment: at 30 minutes, 60 minutes and thereafter every 60 minutes until 780 minutes, if the patients maintained the FEV1 above 80% of the predicted value and/or an increment of 20% in the VEF1 basal value. The Salmeterol group showed a significant bronchodilation at 60 minutes which was maintained in half of the patients up to 9 hours. This was not observed in the Salbutamol group: the peak bronchodilatation was observed at 30 minutes and the bronchodilation effect was observed in half of the patients up to 6 hours. There were no significant differences between both presentations of Salmeterol. This drug allowed a prolonged bronchodilator effect and is, according to the several consensus on management of asthma, an adequate option in the treatment of moderate to severe asthma.
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78 FR 38287 - Bitterroot National Forest, Darby Ranger District, Como Forest Health Project
Federal Register 2010, 2011, 2012, 2013, 2014
2013-06-26
... DEPARTMENT OF AGRICULTURE Forest Service Bitterroot National Forest, Darby Ranger District, Como Forest Health Project AGENCY: Forest Service. ACTION: Notice; Correction. SUMMARY: The Department of Agriculture (USDA), Forest Service, Bitterroot National Forest, Darby Ranger District published a document in...
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78 FR 36163 - Bitterroot National Forest, Darby Ranger District, Como Forest Health Project
Federal Register 2010, 2011, 2012, 2013, 2014
2013-06-17
... Lake Como and Lost Horse Roads, about XX miles northwest of Darby in Ravalli County, Montana. The... Lost Horse Road, about three miles northwest of Darby, Montana (R22W,T4N, Sec. 13, 24, 25, 36; R21W,T4N...
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Efficient preparation of α-ketoacetals.
Ayala-Mata, Francisco; Barrera-Mendoza, Citlalli; Jiménez-Vázquez, Hugo A; Vargas-Díaz, Elena; Zepeda, L Gerardo
2012-11-22
The Weinreb amides 2a,b were prepared from the α,α-dimethoxyacetic acids 1c,d. A number of representative nucleophilic additions (RMgX and RLi) on 2 afforded α-ketoacetals 3a-j in 70-99% yield. These compounds represent a versatile arrangement of functional groups of significant synthetic value, as demonstrated in the synthesis of (±)-salbutamol.
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Mirza, Zafar Nazir; Kato, Masahiko; Kimura, Hirokazu; Tachibana, Atsushi; Fujiu, Toru; Suzuki, Masato; Mochizuki, Hiroyuki; Tokuyama, Kenichi; Morikawa, Akihiro
2002-05-01
Beta2-adrenoceptor agonists, used widely as bronchodilator in treating bronchial asthma, may have anti-inflammatory activity. We examined whether various widely prescribed beta2-adrenoceptor agonists differ in anti-inflammatory mechanisms. We investigated effects of these drugs on superoxide anion generation by stimulated human polymorphonuclear leukocytes in vitro using chemiluminescence. At high concentrations, fenoterol significantly inhibited both N-formylmethionyl-leucyl-phenylalanine- and phorbol myristate acetate-induced superoxide generation by neutrophils. In contrast, salbutamol or procaterol partially inhibited generation with the former stimulus but not the latter. Inhibition by salbutamol or procaterol was completely reversed by either propranolol, a nonselective beta-adrenoceptor antagonist, or ICI-118551, a beta2-adrenoceptor-selective antagonist. In contrast, the effect of fenoterol at concentrations exceeding 10(-6) M against superoxide generation with the former stimulus was only partially reversed by antagonists, and the effect of high concentrations of fenoterol against generation with the latter stimulus was not reversed. No drugs scavenged superoxide at the highest concentration used (10(-5) M). Fenoterol at high concentrations has an inhibitory effect on superoxide generation that includes a component not mediated via beta2-adrenoceptors. Direct inhibition at or downstream from protein kinase C may be involved.
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Improvement of the Prediction of Drugs Demand Using Spatial Data Mining Tools.
Ramos, M Isabel; Cubillas, Juan José; Feito, Francisco R
2016-01-01
The continued availability of products at any store is the major issue in order to provide good customer service. If the store is a drugstore this matter reaches a greater importance, as out of stock of a drug when there is high demand causes problems and tensions in the healthcare system. There are numerous studies of the impact this issue has on patients. The lack of any drug in a pharmacy in certain seasons is very common, especially when some external factors proliferate favoring the occurrence of certain diseases. This study focuses on a particular drug consumed in the city of Jaen, southern Andalucia, Spain. Our goal is to determine in advance the Salbutamol demand. Advanced data mining techniques have been used with spatial variables. These last have a key role to generate an effective model. In this research we have used the attributes that are associated with Salbutamol demand and it has been generated a very accurate prediction model of 5.78% of mean absolute error. This is a very encouraging data considering that the consumption of this drug in Jaen varies 500% from one period to another.
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Quintana, José Benito; Rodil, Rosario; Cela, Rafael
2012-06-01
The degradation of two β-blockers (atenolol and propranolol) and one β-receptor agonist (salbutamol) during water chlorination was investigated by liquid chromatography-mass spectrometry (LC-MS). An accurate-mass quadrupole time-of-flight system (QTOF) was used to follow the time course of the pharmaceuticals and also used in the identification of the by-products. The degradation kinetics of these drugs was investigated at different concentrations of chlorine, bromide and sample pH by means of a Box-Behnken experimental design. Depending on these factors, dissipation half-lives varied in the ranges 68-145 h for atenolol, 1.3-33 min for salbutamol and 42-8362 min for propranolol. Normally, an increase in chlorine dosage and pH resulted in faster degradation of these pharmaceuticals. Moreover, the presence of bromide in water samples also resulted in a faster transformation of atenolol at low chlorine doses. The use of an accurate-mass high-resolution LC-QTOF-MS system permitted the identification of a total of 14 by-products. The transformation pathway of β-blockers/agonists consisted mainly of halogenations, hydroxylations and dealkylations. Also, many of these by-products are stable, depending on the chlorination operational parameters employed.
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Combat Identification Systems COMO Integrated Air Defense Model Evaluation (CISE) Study
1989-02-01
use K or IR , whichever one applies) E-6 CAA-SR-89- 3 Subroutine PDECLR 1/21/88 Before label 1000 Insert: IF (IR.GT.10) IR a 10 These changes were made...Internal Distribution: Unclassified Library 2 F-2 CAA-SR-89- 3 GLOSSARY 1. ABBREVIATIONS, ACRONYMS, AND SHORT TERMS ADM2 Air Defense Models Modification...STUDY REPORT ’ , CAA-Sn-89- 3 i , .- CD o COMBAT IDENTIFICATION SYSTEMS N COMO INTEGRATED AIR DEFENSE MODEL EVALUATION (CISE) STUDY FEBRUARY 1989
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Monitoring adverse drug reactions in children using community pharmacies: a pilot study
Stewart, Derek; Helms, Peter; McCaig, Dorothy; Bond, Christine; McLay, James
2005-01-01
Aims To determine the feasibility of a community pharmacy-based parental adverse drug reaction (ADR) reporting system for children. Design Prospective study of parent-reported ADRs using a questionnaire issued to the parent or guardians of children 0–11 years of age collecting prescribed medicine for amoxicillin, and/or salbutamol, and collecting prescribed medicine for, or purchasing, paracetamol or ibuprofen suspension. Setting Seven community pharmacies in Grampian, Scotland. Results During a 4-week period 360 prescriptions or purchases for the study medications occurred. Two hundred and sixty-seven parents (85.5%) agreed to participate in the study. One hundred and six participants (40%) returned a total of 122 questionnaires. The demographics of responders and nonresponders including medication, age of child, and social status as assessed by the Depcat score were similar. There was no evidence of under-representation of any socio-economic group. Possible adverse events were detected using a symptom tick list and perceived ADRs using free text entry. Using the symptom tick list approach the most commonly reported symptoms were diarrhoea (28.9%) and tiredness (31.6%) for amoxicillin. The levels of diarrhoea and tiredness reported for ibuprofen, paracetamol and salbutamol were 15% and 20%, 7.4% and 18.5%, and 20% and 0%, respectively. Using the freehand section of the questionnaire 15 specific ADRs were reported by parents (12.3%). Eight children (21.2%) reported ADRs attributed to amoxicilin [diarrhoea (n = 4), fever (n = 1), anorexia (n = 1), hyperactivity (n = 1) and nonspecific (n = 1)], five to paracetamol [diarrhoea (n = 3), anorexia, irritability, crying and very angry (n = 1) and not stated (n = 1)], two to ibuprofen [diarrhoea (n = 1), not stated (n =)]. Only one off-label prescription was identified and this was for salbutamol syrup prescribed to a child under 2 years of age. Conclusions The prospective monitoring of paediatric ADRs, using a
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Ayres, J G; Frost, C D; Holmes, W F; Williams, D R R; Ward, S M
1998-01-01
Objective To evaluate the safety of a non-chlorofluorocarbon metered dose salbutamol inhaler. Design This was a postmarketing surveillance study, conducted under formal guidelines for company sponsored safety assessment of marketed medicines (SAMM). A non-randomised, non-interventional, observational design compared patients prescribed metered doses of salbutamol delivered by inhalers using either hydrofluoroalkane or chlorofluorocarbon as the propellant. Follow up was three months. Setting 646 general practices throughout the United Kingdom. Subjects 6614 patients with obstructive airways disease (1667 patient years of exposure). Main outcome measures Proportions of patients who were: admitted to hospital for respiratory diseases, reported adverse side effects, or withdrew because of adverse affects. Results There were no significant differences between the hydrofluoroalkane (HFA 134a) and chlorofluorocarbon inhaler groups in relation to the proportions of patients admitted to hospital for respiratory diseases (odds ratio 0.75; 95% confidence interval 0.51 to 1.08) or the proportions who reported adverse events (1.01; 0.88 to 1.17). However, more patients using the hydrofluoroalkane inhaler than the chlorofluorocarbon inhaler withdrew because of adverse events (3.8% and 0.9% respectively). Conclusion The hydrofluoroalkane inhaler was as safe as the chlorofluorocarbon inhaler when judged by hospital admissions and adverse affects. The study design successfully fulfilled the recommendations of the guidelines. Differences between postmarketing surveillance studies and randomised clinical trials in assessing safety were identified. These may lead to difficulties in the design of postmarketing surveillance studies. Key messagesCredibility of postmarketing surveillance studies is expected to increase after the introduction of guidelines covering their conduct The study design successfully fulfilled the requirements of these guidelines in terms of the number, rate, and
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Yang, Quan; Battistini, Bruno; Pelletier, Stéphane; Sirois, Pierre
2007-10-01
The effects of cyclic AMP-related compounds and beta adrenoceptor agonists on the basal and lipopolysaccharide (LPS)-stimulated release of endothelin-1 (ET-1) from guinea-pig tracheal epithelial cells (GPTEpCs) in culture were studied. Forskolin (a potent activator of adenylyl cyclase), 8-bromo-cyclic AMP (a cyclic AMP analogue), salbutamol and salmeterol (two beta 2-adrenoceptor agonists), were used to increase cyclic AMP levels. Cultured GPTEpCs released ET-1 continuously over a 24 h incubation period. The values reached 1,938 +/- 122 pg/mg of total cell proteins after 24 h. LPS (10 microg/ml) significantly stimulated the release of ET-1 by 1.6- to 1.8-fold, up to 1,262 +/- 56 pg/mg total cell proteins after an 8 h incubation period. Compound 8-bromo-cyclic AMP (10(-5), 10(-4) and 10(-3) M) reduced the basal release of ET-1 from GPTEpCs by up to 31% (P < 0.01) and the LPS stimulated release by up to 42% (P < 0.05), after an 8 h incubation period. Forskolin (10(-6), 10(-5) and 10(-4) M) also inhibited the basal release of ET-1 by up to 28% (P < 0.05) and LPS-stimulated release of ET-1 by up to 50% (P < 0.05), after an 8 h incubation period. At the concentration of 10(-5) M, forskolin increased cyclic AMP levels in GPTEpCs by 17-fold (P < 0.001) in the medium, 15 min after the beginning of the incubation. Salbutamol (10(-8) to 10(-6) M) had no effect on the basal production and release of ET-1 after 8 h. Conversely, this short acting beta 2-adrenoceptor agonist significantly reduced LPS-mediated increase of ET-1 production by up to 55% (P < 0.05) after an 8 h incubation period. Salmeterol (10(-9) M to 10(-5) M) inhibited basal and LPS-stimulated production and release of ET-1 after an 8 h incubation period (between 44 and 51%, P < 0.01). Both salbutamol and salmeterol (10(-6) M) increase cyclic AMP levels by five- and twofold, respectively (P < 0.05). In summary, these observations indicate that beta 2-adrenoceptor agonists or cyclic AMP enhancers can modulate both
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Generating monodisperse pharmacological aerosols using the spinning-top aerosol generator.
Biddiscombe, Martyn F; Barnes, Peter J; Usmani, Omar S
2006-01-01
Pharmacological aerosols of precisely controlled particle size and narrow dispersity can be generated using the spinning-top aerosol generator (STAG). The ability of the STAG to generate monodisperse aerosols from solutions of raw drug compounds makes it a valuable research instrument. In this paper, the versatility of this instrument has been further demonstrated by aerosolizing a range of commercially available nebulized pulmonary therapy preparations. Nebules of Flixotide (fluticasone propionate), Pulmicort (budesonide), Combivent (salbutamol sulphate and ipratropium bromide), Bricanyl (terbutaline sulphate), Atrovent(ipratropium bromide), and Salamol (salbutamol sulphate) were each mixed with ethanol and delivered to the STAG. Monodisperse drug aerosol distributions were generated with MMADs of 0.95-6.7 microm. To achieve larger particle sizes from the nebulizer drug suspensions, the STAG formed compound particle agglomerates derived from the smaller insoluble drug particles. These compound agglomerates behaved aerodynamically as a single particle, and this was verified using an aerodynamic particle sizer and an Andersen Cascade Impactor. Scanning electron microscope images demonstrated their physical structure. On the other hand using the nebulizer drug solutions, spherical particles proportional to the original droplet diameter were generated. The aerosols generated by the STAG can allow investigators to study the scientific principles of inhaled drug deposition and lung physiology for a range of therapeutic agents.
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McLean, Kathleen E.; Yao, Jiayun; Henderson, Sarah B.
2015-01-01
The British Columbia Asthma Monitoring System (BCAMS) tracks forest fire smoke exposure and asthma-related health outcomes, identifying excursions beyond expected daily counts. Weekly reports during the wildfire season support public health and emergency management decision-making. We evaluated BCAMS by identifying excursions for asthma-related physician visits and dispensations of the reliever medication salbutamol sulfate and examining their corresponding smoke exposures. A disease outbreak detection algorithm identified excursions from 1 July to 31 August 2014. Measured, modeled, and forecasted concentrations of fine particulate matter (PM2.5) were used to assess exposure. We assigned PM2.5 levels to excursions by choosing the highest value within a seven day window centred on the excursion day. Smoky days were defined as those with PM2.5 levels ≥ 25 µg/m3. Most excursions (57%–71%) were assigned measured or modeled PM2.5 concentrations of 10 µg/m3 or higher. Of the smoky days, 55.8% and 69.8% were associated with at least one excursion for physician visits and salbutamol dispensations, respectively. BCAMS alerted most often when measures of smoke exposure were relatively high. Better performance might be realized by combining asthma-related outcome metrics in a bivariate model. PMID:26075727
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Effects of high flavanol dark chocolate on cardiovascular function and platelet aggregation.
Rull, Gurvinder; Mohd-Zain, Zetty N; Shiel, Julian; Lundberg, Martina H; Collier, David J; Johnston, Atholl; Warner, Timothy D; Corder, Roger
2015-08-01
Regular consumption of chocolate and cocoa products has been linked to reduced cardiovascular mortality. This study compared the effects of high flavanol dark chocolate (HFDC; 1064mg flavanols/day for 6weeks) and low flavanol dark chocolate (LFDC; 88mg flavanols/day for 6weeks) on blood pressure, heart rate, vascular function and platelet aggregation in men with pre-hypertension or mild hypertension. Vascular function was assessed by pulse wave analysis using radial artery applanation tonometry in combination with inhaled salbutamol (0.4mg) to assess changes due to endothelium-dependent vasodilatation. HFDC did not significantly reduce blood pressure compared to baseline or LFDC. Heart rate was increased by LFDC compared to baseline, but not by HFDC. Vascular responses to salbutamol tended to be greater after HFDC. Platelet aggregation induced by collagen or the thromboxane analogue U46619 was unchanged after LFDC or HFDC, whereas both chocolates reduced responses to ADP and the thrombin receptor activator peptide, SFLLRNamide (TRAP6), relative to baseline. Pre-incubation of platelets with theobromine also attenuated platelet aggregation induced by ADP or TRAP6. We conclude that consumption of HFDC confers modest improvements in cardiovascular function. Platelet aggregation is modulated by a flavanol-independent mechanism that is likely due to theobromine. Copyright © 2015 Elsevier Inc. All rights reserved.
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beta-Adrenoceptor agonists enhance 5-hydroxytryptamine-mediated behavioural responses.
Cowen, P. J.; Grahame-Smith, D. G.; Green, A. R.; Heal, D. J.
1982-01-01
The beta-adrenoceptor agonists, salbutamol, terbutaline and clenbuterol, were investigated for their effect on 5-hydroxytryptamine-mediated (5-HT) hyperactivity. 2 The lipophilic beta-adrenoceptor agonist, clenbuterol (5 mg/kg) enhanced the behaviours induced by quipazine (25 mg/kg), including headweaving, forepaw treading and hind-limb abduction and thus increased automated activity recording. Clenbuterol (5 mg/kg) also enhanced the hyperactivity syndrome produced by the 5-HT agonist, 5-methoxy N,N-dimethyltryptamine (2 mg/kg) and the combination of tranylcypromine (10 mg/kg) and L-tryptophan (50 mg/kg). Salbutamol and terbutaline potentiated quipazine-induced hyperactivity only when given at the higher dose of 20 mg/kg. 3 The effect of clenbuterol in enhancing quipazine hyperactivity was blocked by the centrally acting beta 1-adrenoceptor antagonist, metoprolol (5 mg/kg), but not by the beta 2-adrenoceptor antagonist, butoxamine (5 mg/kg) or the peripherally acting beta 1-adrenoceptor antagonist, atenolol (5 mg/kg). 4 Clenbuterol (5 mg/kg) did not enhance the circling responses produced by methamphetamine (0.5 mg/kg) in unilateral nigrostriatal-lesioned rats. 5 The results suggest that beta-adrenoceptor agonists in common with some established antidepressant treatments produce enhancement of 5-HT-mediated behavioural responses. PMID:6124294
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Alejarse como proceso social: niños y ancianos «abandonados» en Ayacucho1
Leinaweaver, Jessaca
2013-01-01
En investigaciones previas sobre el acogimiento familiar y la adopción en Ayacucho, se ha podido descubrir cómo los ayacuchanos adquieren y producen relaciones sociales. Mientras negocian creativamente los discursos y espacios construidos simultáneamente por instituciones, comunidades, y estructuras sociales, van adquiriendo nuevas formas de relacionarse. Este artículo discute el proceso opuesto: el deshacerse de relaciones de parentesco, y el proceso social del abandono o alejamiento. Cuando se aleja a una persona de su familia o su comunidad, los que se quedan en ella llegan a entenderse como ciertos tipos de personas. En los estudios de caso discutidos aquí, recopilados a través de una detallada y cuidadosa observación participante y de entrevistas etnográficas grabadas entre 2001 y 2007, se puede ver cómo, después de un alejamiento social, los individuos que alejan se reinterpretan como sujetos que se encuentran superándose o volviéndose modernos, o bien sacrificándose. PMID:25177044
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NASA Astrophysics Data System (ADS)
Xu, Xuejun; Si, Zhichun; Liu, Liping; Wang, Zehao; Chen, Ze; Ran, Rui; He, Yonghong; Weng, Duan
2018-03-01
Noble metal free MoS2/g-C3N4 catalyst has attracted intense attentions for visible light photocatalytic hydrogen evolution as a result of its earth abundance, low cost and unique heterojunctions stacked with two dimensional sheets. However, the low charge separation efficiency resulted from the poor conductivity of g-C3N4 and MoS2, and lack of abundant active sites from coordinative unsaturated atoms in MoS2, restricts the photocatalytic hydrogen evolution activity and stability enhancement of MoS2/C3N4 composite catalysts. Herein, CoMoS2/rGO/g-C3N4 catalysts with ternary heterojunctions are prepared by facile solvothermal method, which exhibit high visible light photocatalytic activity and stability for hydrogen evolution. The optimal hydrogen evolution rate of CoMoS2/rGO/g-C3N4 catalysts is 684 μmol g-1 h-1 when the content of CoMoS2 is 2% and the content of rGO is 0.5%. The stability of CoMoS2/rGO/C3N4 catalysts just decrease about 3% after 4 cycling runs for 16 h. The good catalytic performances of catalysts are attributed to the synergistic effect among the g-C3N4 nanosheets, rGO nanosheets and CoMoS2 nanosheets. The high conductivity of rGO nanosheets enhances the electron-hole separation and charge transfer, and Co doping increases the active sites for hydrogen evolution due to the increase of unsaturated atoms in CoMoS2 nanosheets.
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Sakai, Nobumitsu; Mohd Yusof, Roslan; Sapar, Marni; Yoneda, Minoru; Ali Mohd, Mustafa
2016-04-01
Beta-agonists and sulfonamides are widely used for treating both humans and livestock for bronchial and cardiac problems, infectious disease and even as growth promoters. There are concerns about their potential environmental impacts, such as producing drug resistance in bacteria. This study focused on their spatial distribution in surface water and the identification of pollution sources in the Langat River basin, which is one of the most urbanized watersheds in Malaysia. Fourteen beta-agonists and 12 sulfonamides were quantitatively analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A geographic information system (GIS) was used to visualize catchment areas of the sampling points, and source profiling was conducted to identify the pollution sources based on a correlation between a daily pollutant load of the detected contaminant and an estimated density of human or livestock population in the catchment areas. As a result, 6 compounds (salbutamol, sulfadiazine, sulfapyridine, sulfamethazine, sulfadimethoxine and sulfamethoxazole) were widely detected in mid catchment areas towards estuary. The source profiling indicated that the pollution sources of salbutamol and sulfamethoxazole were from sewage, while sulfadiazine was from effluents of cattle, goat and sheep farms. Thus, this combination method of quantitative and spatial analysis clarified the spatial distribution of these drugs and assisted for identifying the pollution sources. Copyright © 2016 Elsevier B.V. All rights reserved.
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Wu, Huaxun; Chen, Jingyu; Song, Shasha; Yuan, Pingfan; Liu, Lihua; Zhang, Yunfang; Zhou, Aiwu; Chang, Yan; Zhang, Lingling; Wei, Wei
2016-01-01
Rheumatoid arthritis (RA) is characterized by inflammation of the synovium, which leads to the progressive destruction of cartilage and bone. Adrenoreceptor (AR) signaling may play an important role in modulating dendritic cell (DC), which may be involved in the pathogenesis of RA. We examined the effect of the β-AR agonist isoprenaline (ISO) on DC function, the impact of the β2-AR agonist salbutamol on adjuvant-induced arthritic (AA) rats, and changes in β2-AR signaling in DCs during the course of AA. ISO inhibited the expression of the surface molecules CD86 and MHC-II, inhibited the stimulation of T lymphocyte proliferation by DC and TNF-α secretion, and promoted DC antigen uptake and IL-10 secretion. The effects of ISO on MHC-II expression, DC stimulation of T lymphocyte proliferation, and DC antigen uptake were mediated by β2-AR. Treatment with salbutamol ameliorated the severity of AA and histopathology of the joints and inhibited proliferation of thymus lymphocytes and FLS in vivo. β2-AR signaling was weaker in AA rats compared to the control. Elevated GRK2 and decreased β2-AR expression in DC cytomembranes were observed in AA and may have decreased the anti-inflammatory effect of β2-AR signaling. Decreased β2-AR signaling may be relevant to the exacerbation of arthritis inflammation. PMID:27079168
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Como Lo Hago Yo: Mielomeningocele En Bolivia
Dabdoub, Carlos F.; Dabdoub, Carlos B.; Villavicencio, Ramiro; Quevedo, Germán
2014-01-01
Introducción: Las malformaciones del tubo neural (MTN) representan la segunda causa más frecuente de anomalías congénitas, luego de las cardiopatías. En este grupo se destaca el mielomeningocele (MMC) por su mayor incidencia, y por ser la más incapacitante y la más compleja entre todas las demás malformaciones del sistema nervioso c`entral (SNC). En Bolivia, como en muchos países de Sudamérica, los bajos niveles socio-culturales y la debilidad en el sistema sanitario, hacen que su incidencia y su morbilidad, sean mayores que en las naciones más desarrolladas. Material y Métodos: Se realizó un estudio retrospectivo y descriptivo de 70 casos de MMC, atendidos por un equipo multidisciplinario en el Hospital Universitario Japonés (HUJ) de Santa Cruz de la Sierra, entre 2008-2011. De ellos, 60 fueron intervenidos quirúrgicamente. Resultados: Se realizaron controles prenatales sólo en 27 mujeres (38.6%), diagnosticándose una disrafia espinal en apenas dos casos (7.4%). La edad de ingreso del MMC en su mayoría fue después de las 24 horas (65.6%), predominando su localización en la región lumbosacra (64.3%). De ellos, 67.2% eran abiertos, presentando un 32.9% un daño neurológico motor parcial mientras que 47.1% tenían paraplejia por debajo de la lesión. De los 70 casos, tres (4.3%) no fueron intervenidos, por presentar defectos congénitos severos o estado general grave. Las principales complicaciones posoperatorias inmediatas fueron: dehiscencia de sutura y/o infección de la herida (16.6%), fístula de líquido cefalorraquídeo (LCR) (10%) e infección del SNC (11.7%). La mortalidad general y postoperatoria fue de 7.1% y 3.3%, respectivamente. Al mes de vida presentaban hidrocefalia un 80% de los pacientes operados, colocándose una derivación ventriculoperitoneal (DVP) de presión media. De 9 pacientes que tuvieron un acompanamiento de dos o más años, seis presentaron una médula anclada, que fueron intervenidas quirúrgicamente. Conclusi
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ERIC Educational Resources Information Center
Department of Education, Washington, DC.
This booklet, written in Spanish, is intended to be used with a set of slides as part of a presentation to students on "How To Apply for Federal Student Aid" ("Como Solicitar la Asistencia Economica Federal para Estudiantes"). The first part of the book is a script based on the slides. After the script is a guide to hosting a financial aid…
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Wu, Yuping; Bi, Yanfeng; Bingga, Gali; Li, Xiaowei; Zhang, Suxia; Li, Jiancheng; Li, Hui; Ding, Shuangyang; Xia, Xi
2015-06-26
The illegal use of β2-agonists in livestock production was previously detected by efficient methods based on mass spectrometry to control the residues of these drugs. Nevertheless, such methods still remain a challenging task for authorities who monitor these residues because the use of "cocktails" composed of mixtures of low amounts of several substances as well as the synthesis of new compounds of unknown structure prevent efficient prevention of illegal use of growth-promoting agents. Here, we outlined a metabolomics-based strategy for detecting the use of "cocktails" composed of mixtures of low amounts of three β2-agonists via urine profiling. Urine profiles of controls and swine treated with mixture of low amounts of three substances (clenbuterol, salbutamol, and ractopamine) were analyzed with ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The metabolic differences between controls and β2-agonists-treated groups were compared using multivariate data analysis. Fourteen metabolites were identified related with the β2-agonists treatment, while two co-biomarkers, 2-indolecarboxylic acid and fluorometholone acetate, either in single or "cocktails" of low-dose mixture of clenbuterol, salbutamol, and ractopamine, could be considered as diagnostic markers for the detection of illegal use of β2-agonists. The results of depletion study demonstrated that it is practical to use the markers for monitoring of β2-agonists. Copyright © 2015 Elsevier B.V. All rights reserved.
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Status asthmaticus in children: a one-year study.
McKenzie, S A; Edmunds, A T; Godfrey, S
1979-01-01
50 children were admitted on 72 occasions during one year in status asthmaticus, defined as wheezing not relieved by two doses of bronchodilator 4 hours apart. At least one-third of children were hypercapnoeic on admission. They were managed with either oral prednisolone and nebulised salbutamol. Those with peak expiratory flow rates of greater than 25% expected for height were satisfactorily managed on the oral regimen. One child needed assisted ventilation. 73% were fit for discharge within 4 days and more than half of them needed a change in maintanance treatment. PMID:389173
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Rascón-Martínez, Dulce María; Guzmán-Sánchez, Joaquín Antonio; Corral-Urdapilleta, Nora Paulina; Arguelles-Uribe, Gema Damaris; Velázquez-Loeza, Jazmín; Soto-Palma, Gustavo; Carrillo-Torres, Orlando
Observar el comportamiento de la gabapentina para aminorar la hipertensión reactiva secundaria a ansiedad y dolor en pacientes sometidos a cirugía oftálmica, así como el consumo de opiáceos entre los grupos. Ensayo clínico controlado aleatorizado y doble ciego que analizó a 125 pacientes divididos en tres grupos: grupo A, gabapentina 300 mg; grupo B, gabapentina 450 mg; grupo C, amaranto en grageas como control 2 horas antes del procedimiento quirúrgico. Se utilizó la prueba de ji al cuadrado para variables sociodemográficas y ANOVA de un factor para variables numéricas continuas. Se consideró como significativo un valor de p < 0.05 para un estudio de dos colas con un poder beta del 80%. La ansiedad y la analgesia transoperatoria y posoperatoria tuvieron diferencias significativas entre los grupos. Se encontró menor consumo de opiáceos en los grupos que usaron gabapentina. La gabapentina por vía oral, 300 o 450 mg, 2 horas antes de la cirugía, reduce el dolor, la ansiedad y el consumo de opiáceos durante el posoperatorio en pacientes sometidos a cirugía oftalmológica. Copyright: © 2018 SecretarÍa de Salud
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Flow-injection chemiluminescence method to detect a β2 adrenergic agonist.
Zhang, Guangbin; Tang, Yuhai; Shang, Jian; Wang, Zhongcheng; Yu, Hua; Du, Wei; Fu, Qiang
2015-02-01
A new method for the detection of β2 adrenergic agonists was developed based on the chemiluminescence (CL) reaction of β2 adrenergic agonist with potassium ferricyanide-luminol CL. The effect of β2 adrenergic agonists including isoprenaline hydrochloride, salbutamol sulfate, terbutaline sulfate and ractopamine on the CL intensity of potassium ferricyanide-luminol was discovered. Detection of the β2 adrenergic agonist was carried out in a flow system. Using uniform design experimentation, the influence factors of CL were optimized. The optimal experimental conditions were 1 mmol/L of potassium ferricyanide, 10 µmol/L of luminol, 1.2 mmol/L of sodium hydroxide, a flow speed of 2.6 mL/min and a distance of 1.2 cm from 'Y2 ' to the flow cell. The linear ranges and limit of detection were 10-100 and 5 ng/mL for isoprenaline hydrochloride, 20-100 and 5 ng/mL for salbutamol sulfate, 8-200 and 1 ng/mL for terbutaline sulfate, 20-100 and 4 ng/mL for ractopamine, respectively. The proposed method allowed 200 injections/h with excellent repeatability and precision. It was successfully applied to the determination of three β2 adrenergic agonists in commercial pharmaceutical formulations with recoveries in the range of 96.8-98.5%. The possible CL reaction mechanism of potassium ferricyanide-luminol-β2 adrenergic agonist was discussed from the UV/vis spectra. Copyright © 2014 John Wiley & Sons, Ltd.
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NASA Astrophysics Data System (ADS)
Höbig, N.; Martinelli, E.; Motella, S.; Michetti, A. M.; Livio, F.; Tinner, W.; Reicherter, K.; Castelletti, L.
2012-04-01
Lake Como (northern Italy) is the deepest Italian lake, reaching a depth of about 425 m. The lambda-shaped lake expands about 45 km in NE-SW direction. Southwards of the hydrologically closed western branch, two sediment cores of 70 m (S1) and 65 m length (S2) were taken in the year 2005 close to the cathedral of Como (Piazza Verdi). The drilling sites are located in the middle of the Southern Alps, some 300 m from the present-day lakeshore. The cores provide the first detailed Late Glacial to Holocene multi-proxy record for the Lake Como basin. Our research is aimed at investigating the environmental and geological evolution of the Insubria Region. The multi-proxy study of the stratigraphic sequences contain geophysical, geotechnical, sedimentological, paleobotanical, and radiocarbon analyses. They have been performed for core S1 and are still in progress on core S2. With this data the working group focuses on two main issues. The first topic is the reconstruction of the natural and anthropogenic processes controlling the ground subsidence in the Como urban area (e.g., Comerci et al., 2007) and another aim is to reconstruct vegetation and land-use dynamics. In particular, 150 samples of vegetal macroremains have been collected in the palustrine deposits along S1 core, down to 31,00 m. Below this depth (dated 14C 12,496 ± 55 yr BP - 15,050 - 14,250 cal yr BP), the amount of plant macroremains in the sediment drops dramatically. The taxonomic determination was carried out on more than 800 macroremains. They are represented by fragments of wood, leaves, needles, seeds, fruits, mosses and tiny charcoals (Motella, 2009, unpublished PhD Thesis). Picea/Larix, Pinus sp., Juniperus with Betula, found in the deeper levels (30.80 - 30.00 m), are the first arboreal taxa that colonized the shores of Lake Como, and show that the reforestation began in this area about 16,000 years ago. During the early Holocene (25.10 m) Abies alba expanded and further upwards the sequence
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Izdebska-Straszak, Grazyna; Gubala, Elzbieta; Jedrzejowska-Szypulka, Halina; Klencki, Mariusz; Wiczkowski, Andrzej; Jarzab, Barbara
2006-01-01
beta-adrenergic ligands have been shown to influence sexual differentiation of the brain. In the present study we document that short postnatal treatment with beta-adrenergic agonists or antagonists may permanently reverse the morphological sex of the brain, as judged by the volume of sexually dimorphic nucleus of the preoptic area (SDN-POA). Female rats treated by beta(2)-adrenergic stimulating ligands exhibit an increased, male type SDN-POA volume while male rats treated by beta1-adrenergic antagonists show a decreased, female type of SDN-POA volume. To analyze the volume of SDN-POA of adult rats after postnatal administration of betaadrenergic ligands. From the second day of life, over 5 consecutive days, all the neonates were injected subcutaneously with the following drugs: isoproterenol, salbutamol, metoprolol alprenolol or saline. SDN-POA volumes were estimated planimetrically on serial brain slides. In male rats the mean volume of SDN-POA was 9.97 +/- 1.66 x 10(-3) mm(3), in female rats the respective volume reached 4.02 +/- 1.26 x 10(-3) mm(3) only and was 2.5 times lower, the difference being highly statistically significant. Postnatal administration of isoproterenol remained without effect in male rats but diminished the SDN-POA volume in female rats, thus increasing the sexual dimorphism. The disappearance of sexual dimorphism was noted in rats treated postnatally with salbutamol. This effect was due to the increase in SDN-POA volumes in female rats, up to 9.81 +/- 2.64 x 10(-3) mm(3), the levels approaching the male type of POA differentiation. Postnatal alprenolol treatment influenced the sexual dimorphism of the brain by decreasing the SDN-POA volume reached by adult males. In fact, in rats treated postnatally with alprenolol, the volume of the nucleus reached only 4,44 +/- 1,61 x 10(-3) mm(3), being not statistically different from female nuclei. The effect of metoprolol pretreatment was similar to alprenolol. Male volumes of SDN-POA were restored
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WITHDRAWN: Symptomatic treatment of the cough in whooping cough.
Pillay-Van Wyk, Victoria; Swingler, George H
2008-10-08
Whooping cough is an important cause of childhood morbidity and mortality. There are 20 to 40 million cases of whooping cough annually world-wide, 90% of which occur in developing countries, resulting in an estimated 200 to 300,000 fatalities each year. Much of the morbidity is due to the effects of the paroxysmal cough. Corticosteroids, salbutamol (beta 2 - adrenergic stimulant), and pertussis-specific immunoglobulin have been proposed as standard treatment for the cough. Antihistamines have also been administered. No systematic review of the effectiveness of any of these interventions or others has been performed. To assess the effectiveness and safety of interventions used to reduce the severity of the coughing paroxysms in whooping cough in children and adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2003, issue 2); MEDLINE (January 1966 to June 2003); EMBASE (1990 to June 2003) and LILACS (1982 to November 2001). Randomised and quasi-randomised controlled trials of any intervention aimed at suppressing the cough in whooping cough; excluding antibiotics and vaccines. Two review authors independently selected studies and extracted data. Our primary outcome was frequency of paroxysms of coughing. Secondary outcomes were frequency of vomiting, frequency of whoop, frequency of cyanosis, development of serious complications, mortality from any cause, side effects due to medication, admission to hospital and duration of hospital stay. Disagreements were resolved by discussion. Nine studies satisfied the inclusion criteria but four had insufficient data for meta - analysis of pre-specified outcomes. Studies were small and poorly reported. The largest study had a sample size of 49 and the smallest study 18. All studies were performed in industrialised settings.Eligible studies assessed diphenhyramine, pertussis immunoglobulin, dexamethasone and salbutamol. No statistically significant benefit was found for any of
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Honey for acute cough in children.
Oduwole, Olabisi; Udoh, Ekong E; Oyo-Ita, Angela; Meremikwu, Martin M
2018-04-10
Cough causes concern for parents and is a major cause of outpatient visits. Cough can impact quality of life, cause anxiety, and affect sleep in children and their parents. Honey has been used to alleviate cough symptoms. This is an update of reviews previously published in 2014, 2012, and 2010. To evaluate the effectiveness of honey for acute cough in children in ambulatory settings. We searched CENTRAL (2018, Issue 2), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (2014 to 8 February 2018), Embase (2014 to 8 February 2018), CINAHL (2014 to 8 February 2018), EBSCO (2014 to 8 February 2018), Web of Science (2014 to 8 February 2018), and LILACS (2014 to 8 February 2018). We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trial Registry Platform (WHO ICTRP) on 12 February 2018. The 2014 review included searches of AMED and CAB Abstracts, but these were not searched for this update due to lack of institutional access. Randomised controlled trials comparing honey alone, or in combination with antibiotics, versus no treatment, placebo, honey-based cough syrup, or other over-the-counter cough medications for children aged 12 months to 18 years for acute cough in ambulatory settings. We used standard methodological procedures expected by Cochrane. We included six randomised controlled trials involving 899 children; we added three studies (331 children) in this update.We assessed two studies as at high risk of performance and detection bias; three studies as at unclear risk of attrition bias; and three studies as at unclear risk of other bias.Studies compared honey with dextromethorphan, diphenhydramine, salbutamol, bromelin (an enzyme from the Bromeliaceae (pineapple) family), no treatment, and placebo. Five studies used 7-point Likert scales to measure symptomatic relief of cough; one used an unclear 5-point scale. In all studies, low score indicated better cough symptom relief
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Como os Alunos do Ensino Médio da Rede Estadual de São Paulo obtém Conhecimentos Astronômicos?
NASA Astrophysics Data System (ADS)
da Cunha, W. S.; Voelzke, M. R.; Amaral, L. H.
2005-08-01
Atualmente vivencia-se um mundo globalizado onde os computadores e a internet permitiram um acesso rápido e seguro a todo tipo de informação e conhecimento. O presente trabalho visa analisar a maneira pela qual alunos de segundo grau da rede estadual da cidade de São Paulo obtiveram, caso tenham, conhecimentos básicos de astronomia quanto aos fenômenos celestes que os rodeiam, tais como a sucessão dos dias e das estações do ano, além de questioná~los sobre fatos genéricos tais como: o que vem a ser o Sol, o Big Bang, o que ocasionou a extinção dos dinossauros. Para tanto foi elaborado um formulário constando de questões de múltipla escolha, o qual foi aplicado no primeiro colegial diurno da Escola Estadual Guilherme de Almeida. Num espaço amostral de 44 alunos constatou-se que 41% dos alunos adquiriram seus conhecimentos astronômicos na escola e 59% através da mídia em geral. Neste mesmo espaço amostral apenas 11% dos alunos usaram computadores na escola, 41% na residência, 5% no trabalho e 43% não utilizaram. O presente estudo revelou também que para 50% dos alunos o professor jamais utilizou um programa de computador a respeito de astronomia ou fez alguma apresentação sobre o tema. Embora em sua fase inicial este estudo revela claramente que a maioria dos alunos não obtém na escola seus conhecimentos astronômicos, estes provém de fontes não especificamente didático-pedagógicas tais como filmes e revistas populares que não raramente geram conhecimentos incompletos e em muitos casos inclusive falhos.
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XAS Study at Mo and Co K-Edges of the Sulfidation of a CoMo / Al2O3 Hydrotreating Catalyst
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pichon, C.; Gandubert, A. D.; Legens, C.
2007-02-02
Because of its impact on environment, the removal of sulfur is an indispensable step, called hydrotreatment, in the refining of petroleum. One of the most commonly used hydrotreating catalysts is CoMo-type catalyst which is composed of molybdenum disulfide slabs promoted by cobalt atoms (CoMoS phase) and well dispersed on a high specific area alumina. As far as the highest sulfur content allowed in gasoline and diesel is continually decreasing, more and more efficient and active hydrotreating catalysts are required. In order to optimize the reactivity of the CoMo-type catalyst in hydrotreatment, a better understanding of the processes used to producemore » the active phase (CoMoS slabs) of the catalyst is necessary. The study reported here deals with the sulfiding mechanism of the slabs and the influence of temperature on the phenomenon. Ex situ X-ray absorption spectroscopy (XANES and EXAFS) was used to study the evolution of the structure of CoMo-type catalyst sulfided at various temperatures (from 293 to 873 K). XAS analysis was performed at both molybdenum and cobalt K-edges to obtain a cross-characterization of the sulfidation of the slabs. It evidenced the formation of various compounds, including two molybdenum oxides, MoS3 (or MoS3-like compound) and Co9S8, at specific steps of the sulfiding process. It showed the role of intermediate played by MoS3 (or MoS3-like compound) during the formation of the slabs and the competition between the appearance of promoted slabs (CoMoS phase) and Co9S8. At last, it leaded to the proposal of a mechanism for the sulfidation of the catalyst.« less
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Phillips, Jonathan E; Renteria, Lorena; Burns, Lisa; Harris, Paul; Peng, Ruoqi; Bauer, Carla M T; Laine, Dramane; Stevenson, Christopher S
2016-06-01
In allergen-induced asthma, activated mast cells start the lung inflammatory process with degranulation, cytokine synthesis, and mediator release. Bruton's tyrosine kinase (Btk) activity is required for the mast cell activation during IgE-mediated secretion. This study characterized a novel inhaled Btk inhibitor RN983 in vitro and in ovalbumin allergic mouse models of the early (EAR) and late (LAR) asthmatic response. RN983 potently, selectively, and reversibly inhibited the Btk enzyme. RN983 displayed functional activities in human cell-based assays in multiple cell types, inhibiting IgG production in B-cells with an IC50 of 2.5 ± 0.7 nM and PGD2 production from mast cells with an IC50 of 8.3 ± 1.1 nM. RN983 displayed similar functional activities in the allergic mouse model of asthma when delivered as a dry powder aerosol by nose-only inhalation. RN983 was less potent at inhibiting bronchoconstriction (IC50(RN983) = 59 μg/kg) than the β-agonist salbutamol (IC50(salbutamol) = 15 μg/kg) in the mouse model of the EAR. RN983 was more potent at inhibiting the antigen induced increase in pulmonary inflammation (IC50(RN983) = <3 μg/kg) than the inhaled corticosteroid budesonide (IC50(budesonide) = 27 μg/kg) in the mouse model of the LAR. Inhalation of aerosolized RN983 may be effective as a stand-alone asthma therapy or used in combination with inhaled steroids and β-agonists in severe asthmatics due to its potent inhibition of mast cell activation.
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Evaluation of a wildfire smoke forecasting system as a tool for public health protection.
Yao, Jiayun; Brauer, Michael; Henderson, Sarah B
2013-10-01
Exposure to wildfire smoke has been associated with cardiopulmonary health impacts. Climate change will increase the severity and frequency of smoke events, suggesting a need for enhanced public health protection. Forecasts of smoke exposure can facilitate public health responses. We evaluated the utility of a wildfire smoke forecasting system (BlueSky) for public health protection by comparing its forecasts with observations and assessing their associations with population-level indicators of respiratory health in British Columbia, Canada. We compared BlueSky PM2.5 forecasts with PM2.5 measurements from air quality monitors, and BlueSky smoke plume forecasts with plume tracings from National Oceanic and Atmospheric Administration Hazard Mapping System remote sensing data. Daily counts of the asthma drug salbutamol sulfate dispensations and asthma-related physician visits were aggregated for each geographic local health area (LHA). Daily continuous measures of PM2.5 and binary measures of smoke plume presence, either forecasted or observed, were assigned to each LHA. Poisson regression was used to estimate the association between exposure measures and health indicators. We found modest agreement between forecasts and observations, which was improved during intense fire periods. A 30-μg/m3 increase in BlueSky PM2.5 was associated with an 8% increase in salbutamol dispensations and a 5% increase in asthma-related physician visits. BlueSky plume coverage was associated with 5% and 6% increases in the two health indicators, respectively. The effects were similar for observed smoke, and generally stronger in very smoky areas. BlueSky forecasts showed modest agreement with retrospective measures of smoke and were predictive of respiratory health indicators, suggesting they can provide useful information for public health protection.
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Edwards, Llifon; Perrin, Kyle; Williams, Mathew; Weatherall, Mark; Beasley, Richard
2012-11-01
The comparative safety of oxygen versus air-driven nebulised bronchodilators in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) is uncertain. A randomised controlled trial was performed to assess the effect on the arterial partial pressure of carbon dioxide of nebulised bronchodilator driven with oxygen versus air in stable severe COPD. In an open label randomised study, 18 subjects with stable severe COPD attended on 2 days to receive nebulised bronchodilator therapy driven by air or oxygen. Subjects received 5 mg salbutamol and 0.5 mg ipratropium bromide by nebulisation over 15 min, then, after 5 min, 5 mg salbutamol nebulised over 15 min, followed by 15 min of observation. Transcutaneous carbon dioxide tension (PtCO(2)) and oxygen saturations were recorded at 5 min intervals during the study. The primary outcome was the PtCO(2) after the completion of the second bronchodilator treatment. PtCO(2) was higher with nebulised bronchodilator therapy delivered by oxygen, but decreased back to the level associated with air nebulisation 15 min after completion of the second nebulised dose. One subject experienced an increase in PtCO(2) of 11 mm Hg after the first bronchodilator nebulisation driven by oxygen. The mean PtCO(2) difference between the oxygen and air groups after the second nebulisation was 3.1 mm Hg (95% CI 1.6 to 4.5, p<0.001). Nebulisers driven with oxygen result in significantly higher levels of PtCO(2) than those driven with air in patients with severe COPD. The study was registered on the Australian New Zealand Clinical Trials Registry (ACTRN12610000080022).
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Sun, Xiaoli; Zhang, Yan; Yang, Wenlan; Liu, Jinming
2015-04-01
This study in healthy adults was conducted to explore the clinical application of capnovolumetric indices as compared to lung function parameters using histamine provocation. Forty healthy subjects received aerosol histamine or salbutamol in an automatic stimulation system with escalating doses of histamine. Dead space volumes of capnovolumetry and lung function parameters were examined with increased concentrations of histamine at a fixed time interval. The doses of histamine were selected from 0.0562 mg-2.2 mg and 0.1 mg salbutamol was inhaled when a maximal dose of histamine was reached. Baseline values in each group were calculated prior to histamine inhalation. Fowler dead space (VDF), Wolff dead space (VDW), threshold dead space (VDT), Bohr dead space (VDB), forced expiratory volume in 1 s (FEV1 ) and peak expiratory flow (PEF) showed a dose-dependent reduction following histamine provocation, but there were no statistical differences in the measurements at baseline and post S6 provocation. The value of dC3/DV at the maximal dose was significantly increased over its baseline value (P < 0.05). VDF, VDT and VDW were significantly increased after bronchodilator use (P < 0.05 or <0.01). The changes in capnovolumetry did not correspond with the results of lung function test. The dC3/DV and airway dead spaces of capnovolumetry in healthy adults are significantly increased compared to lung function parameters before or after bronchodilator use, suggesting that capnovolumetry is feasible in diagnostic evaluation of airway reactivity, especially for persons who are unable to undertake lung function test. © 2014 John Wiley & Sons Ltd.
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Varas-Díaz, Nelson; Neilands, Torsten B.; Guilamo-Ramos, Vincent; Cintrón Bou, Francheska N.
2009-01-01
El estigma relacionado con el VIH/SIDA continúa siendo un obstáculo para la prevención primaria y secundaria del VIH. Las consecuencias para las personas que viven con la enfermedad han sido muy documentadas y continúan siendo una gran preocupación para las personas que proveen servicios de salud y para aquellas que investigan el tema. Estas consecuencias son preocupantes cuando el estigma emana de profesionales de la salud porque se puede limitar el acceso a los servicios. Uno de los principales obstáculos para la investigación del estigma relacionado con el VIH en Puerto Rico es la falta de instrumentos cuantitativos para evaluar las manifestaciones del estigma entre profesionales de la salud. El objetivo principal de este estudio fue desarrollar y probar las propiedades psicométricas de una escala sobre el estigma relacionado con el VIH/SIDA culturalmente apropiada para personas que proveen servicios de salud puertorriqueñas y desarrollar una versión corta de la escala que pudiera usarse en escenarios clínicos con tiempo limitado. El instrumento desarrollado estuvo basado en evidencia cualitativa recopilada entre profesionales y estudiantes de profesiones de la salud puertorriqueños/as (n=80) y administrado a una muestra de 421 profesionales de la salud en adiestramiento. La escala contenía 12 dimensiones del estigma relacionado con el VIH/SIDA. El análisis cuantitativo corroboró 11 de ellas, teniendo como resultado un instrumento con validez y confiabilidad satisfactoria. Estas dimensiones, a su vez, fueron subcomponentes de un factor de estigma general superior. PMID:20333258
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Telescópio de pequeno porte como suporte ao ensino em cidades com intensa poluição luminosa II
NASA Astrophysics Data System (ADS)
Pereira, P. C. R.; Santos-Júnior, J. M.; Cruz, W. S.
2003-08-01
Para a maioria dos estudantes, sua passagem pelo ensino formal fundamental envolve a transmissão de fatos que devem ser guardados para um exame, a habilidade para lembrar fórmulas e, eventualmente, a repetição de experimentos que devem produzir resultados exigidos pelo professor. O resultado deste modelo de ensino, ao longo dos anos, é conhecido por todos: desconhecimento e descontentamento, por parte dos estudantes, de temas relativos ao papel e aos processos da ciência. Acreditamos que a Astronomia, pelo seu caráter observacional, é uma das áreas do conhecimento que pode contribuir neste cenário. A Fundação Planetário da Cidade do Rio de Janeiro possui um telescópio Meade LX-200 (25cm) que, juntamente com as câmeras CCD ST-7E e ST8E, tem sido utilizado em projetos voltados aos estudantes do ensino médio desde o ano 2000. Tais projetos envolvem a condução de um projeto de pesquisa observacional num nível apropriado, e possibilitam o contato com técnicas e novas tecnologias: computador, software para manipulação de dados e gráficos, programas de tratamento e redução de dados, uso de equipamentos óptico-eletrônicos (telescópio e CCD), bem como o processo de aquisição de conhecimento. Dentro da proposta dos anos anteriores, priorizamos projetos de uma noite, ou seja, procuramos trabalhar com fenômenos que apresentem variabilidade com intervalo de recorrência relativamente curto. Em todos os casos, optamos pela fotometria diferencial, que tem se mostrado bastante eficiente para o céu luminoso como o da cidade do Rio de Janeiro. Neste painel, apresentamos alguns dos projetos desenvolvidos no último ano, com 25 estudantes. Apresentamos os resultados da observação da variável pulsante AI Vel (V = 6,6) e da variável cataclísmica FO Aqr (V = 13,5), e do monitoramento do trânsito da lua de Júpiter, Europa, ocorrido em 30 de abril de 2003. As curvas de luz produzidas para as primeiras estão concordantes com as da literatura, assim
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Gracia, Tannia; Hilscherova, Klara; Jones, Paul D.
2007-12-01
The H295R cell bioassay was used to evaluate the potential endocrine disrupting effects of 18 of the most commonly used pharmaceuticals in the United States. Exposures for 48 h with single pharmaceuticals and binary mixtures were conducted; the expression of five steroidogenic genes, 3{beta}HSD2, CYP11{beta}1, CYP11{beta}2, CYP17 and CYP19, was quantified by Q-RT-PCR. Production of the steroid hormones estradiol (E2), testosterone (T) and progesterone (P) was also evaluated. Antibiotics were shown to modulate gene expression and hormone production. Amoxicillin up-regulated the expression of CYP11{beta}2 and CYP19 by more than 2-fold and induced estradiol production up to almost 3-fold. Erythromycin significantlymore » increased CYP11{beta}2 expression and the production of P and E2 by 3.5- and 2.4-fold, respectively, while production of T was significantly decreased. The {beta}-blocker salbutamol caused the greatest induction of CYP17, more than 13-fold, and significantly decreased E2 production. The binary mixture of cyproterone and salbutamol significantly down-regulated expression of CYP19, while a mixture of ethynylestradiol and trenbolone, increased E2 production 3.7-fold. Estradiol production was significantly affected by changes in concentrations of trenbolone, cyproterone, and ethynylestradiol. Exposures with individual pharmaceuticals showed the possible secondary effects that drugs may exert on steroid production. Results from binary mixture exposures suggested the possible type of interactions that may occur between drugs and the joint effects product of such interactions. Dose-response results indicated that although two chemicals may share a common mechanism of action the concentration effects observed may be significantly different.« less
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Babar, Zaheer-Ud-Din; Lessing, Charon; Mace, Cécile; Bissell, Karen
2013-11-01
Almost 300 million people suffer from asthma, yet many in low- and middle-income countries have difficulty accessing essential asthma medicines. Availability, price and affordability of medicines are likely to affect access. Very few studies have included asthma medicines, particularly inhaled corticosteroids, in these countries. Reflections about international reference prices (IRPs) are generally absent from pricing studies, yet some IRPs may be masking the extent of access problems. Our objective was to determine the availability, pricing and affordability of beclometasone, budesonide and salbutamol, the three asthma medicines on the World Health Organization's Model List of Essential Medicines (EML) in selected low- and middle-income countries and to reflect on the appropriateness of using IRPs. A cross-sectional pricing survey was conducted in 52 countries. Data were collected on country demographics including national currency, $US exchange rate and daily wage of the lowest-paid unskilled government worker. Pricing and availability data were collected for salbutamol, beclometasone and budesonide in two private retail pharmacies, the national procurement centre and a main public hospital. Availability was particularly poor for corticosteroids, and worse in national procurement centres and main hospitals. The surveyed strength of beclometasone was only on the EML of ten countries. Considerable variability was found in pricing and affordability across countries. Procurement systems appeared largely inefficient when Asthma Drug Facility prices were applied as references. Some countries appear to be subsidising asthma medicines, making them free or less expensive for patients, while other countries are applying very high margins, which can significantly increase the price for patients unless a reimbursement system exists. Findings raise important policy concerns. Availability of inhaled corticosteroids is poor; many EMLs are not updated; IRPs can be misleading
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Proliferation of the human urothelium is induced by atypical β1 -adrenoceptors.
Winder, M; Wasén, C; Aronsson, P; Giglio, D
2015-09-01
We wanted to assess whether β-adrenoceptors mediate proliferation in the normal and malignant urothelial cell lines UROtsa and T24, respectively. Urothelial cells were cultured for 24 h in the presence of the β-adrenoceptor agonists isoprenaline (β1/2/3 ), dobutamine (β1 ), salbutamol (β2 ), BRL 37344 (β3 ), CGP 12177 (a partial β-agonist) or β-adrenoceptor antagonists (metoprolol; β1 , propranolol; β1/2 ). Phosphorylation of kinases was screened with a Human Phospho-Kinase Array Kit (R&D systems). Intracellular pathways activated by proliferation of urothelial cells were characterized by incubating cells with the MEK1/2 inhibitor PD 98,059, the p38 kinase inhibitor losmapimod or with the Akt 1/2 kinase inhibitor. Proliferation was assessed with the MTT proliferation assay (ATCC). Western blot and immunocytochemistry were used for detection of the β1 -adrenoceptor. Isoprenaline and dobutamine induced proliferation, while salbutamol and BRL 37344 did not. Dobutamine-induced proliferation was not affected by metoprolol or propranolol but was instead antagonized by CGP 12177 in T24 but not in UROtsa. In response to stimulation with dobutamine, Akt1/2/3 was phosphorylated in UROtsa, while ERK1/2 and p38 were phosphorylated in T24. MEK1/2 inhibition blocked basal and dobutamine-induced proliferation in T24 but only basal proliferation in UROtsa. Losmapimod slightly inhibited basal proliferation in T24 but not dobutamine-induced proliferation. Akt 1/2 inhibitor blocked basal and dobutamine-induced proliferation in UROtsa. Immunocytochemistry and Western blot revealed expression of β1 -adrenoceptors in both urothelial cell lines. The present data show that the urothelium expresses atypical β1-adrenoceptors that activate intracellular kinases inducing urothelial proliferation. © 2016 John Wiley & Sons Ltd.
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Conroy, D. M.; Samhoun, M. N.; Piper, P. J.
1991-01-01
1. The effect of vasoactive intestinal peptide (VIP) was studied on the contractile response of guinea-pig lung parenchymal strips (GPP) induced by bronchoconstrictor agonists, such as leukotriene D4 (LTD4), histamine and acetylcholine (ACh). This effect of VIP was compared with helodermin, a peptide that is structurally related to VIP, and galanin, another neuropeptide that is thought to co-exist with VIP. 2. VIP (10 nM) induced a potent and reversible inhibition of the contractions of GPP induced by LTD4 (1-30 pmol) but did not affect those due to ACh (1-100 nmol) or histamine (1-30 nmol). A ten fold higher concentration of VIP (100 nM) did not further inhibit LTD4-induced responses or reduce those induced by histamine or ACh. 3. Helodermin (10 nM) had a similar inhibitory effect on contractions of GPP induced by LTD4 (3-30 pmol) but did not affect contractions induced by histamine (1-10 nmol). 4. Indomethacin (2.8 microM) and salbutamol (10 nM) significantly reduced responses elicited by LTD4 and histamine but not those due to ACh. A ten fold higher concentration of salbutamol (100 nM) further inhibited the contractions due to LTD4 and histamine and at this concentration responses induced by ACh were inhibited. 5. VIP (10 nM) and helodermin (10 nM) significantly reduced the LTD4-induced release of thromboxane A2 (TXA2), measured as TxB2 by radioimmunoassay, from GPP. The smaller release of TxA2 induced by histamine was not significantly reduced in the presence of VIP. 6. In comparative studies, galanin (10-100 nM) did not affect contractions of GPP induced by either LTD4, histamine or ACh.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1725762
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Budesonide reduces hospital admission rates in preschool children with acute wheezing.
Razi, Cem Hasan; Cörüt, Nazlı; Andıran, Nesibe
2017-06-01
The object of this study was to determine whether high doses of inhaled budesonide provide additional benefits to a standardized treatment regimen that includes systemic steroids and salbutamol in preschool patients presented to the emergency department (ED) with acute wheezing attacks. Methods This randomized, double-blind, placebo-controlled, parallel group trial was conducted in children, 6 months-6 years with moderate or severe acute wheezing epizode, as determined based on a pulmonary index score (PIS) of 7-13 points. We compared the addition of budesonide 3 mg versus placebo to standard acute asthma treatment, which included salbutamol and a single 1 mg/kg dose of methylprednisolone given at the beginning of therapy. The primary outcome was differences in hospitalization rates within 4 hr. Secondary outcome was difference in median PIS between treatment groups at 2 hr. Results One hundred patients were enrolled. Cumulative hospitalization rate at 120, 180, and 240 min were 0.72, 0.62, and 0.58 in placebo group; and 0.44, 0.30, and 0.24 in budesonide group. Discharged rate in budesonide group was significantly higher than the placebo group (log-rank = 12.407 ve P < 0.001). Expected mean discharged times were 200.4 (95%CI = 185.3-215.5) min in placebo group and 164.4 (95%CI = 149.4-179.4) min in budesonide group. Median (25-75%) PIS at the 120th min was significantly lower in budesonide group than the placebo group (5 [4-8] vs. 8 [5-9] respectively, P = 0.006). Conclusions The addition of budesonide nebulization may decrease the admission rate of preschool children who have moderate to severe acute wheezing epizodes. Pediatr Pulmonol. 2017;52:720-728. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
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Renteria, Lorena; Burns, Lisa; Harris, Paul; Peng, Ruoqi; Bauer, Carla M.T.; Laine, Dramane; Stevenson, Christopher S.
2016-01-01
Abstract Background: In allergen-induced asthma, activated mast cells start the lung inflammatory process with degranulation, cytokine synthesis, and mediator release. Bruton's tyrosine kinase (Btk) activity is required for the mast cell activation during IgE-mediated secretion. Methods: This study characterized a novel inhaled Btk inhibitor RN983 in vitro and in ovalbumin allergic mouse models of the early (EAR) and late (LAR) asthmatic response. Results: RN983 potently, selectively, and reversibly inhibited the Btk enzyme. RN983 displayed functional activities in human cell-based assays in multiple cell types, inhibiting IgG production in B-cells with an IC50 of 2.5 ± 0.7 nM and PGD2 production from mast cells with an IC50 of 8.3 ± 1.1 nM. RN983 displayed similar functional activities in the allergic mouse model of asthma when delivered as a dry powder aerosol by nose-only inhalation. RN983 was less potent at inhibiting bronchoconstriction (IC50(RN983) = 59 μg/kg) than the β-agonist salbutamol (IC50(salbutamol) = 15 μg/kg) in the mouse model of the EAR. RN983 was more potent at inhibiting the antigen induced increase in pulmonary inflammation (IC50(RN983) = <3 μg/kg) than the inhaled corticosteroid budesonide (IC50(budesonide) = 27 μg/kg) in the mouse model of the LAR. Conclusions: Inhalation of aerosolized RN983 may be effective as a stand-alone asthma therapy or used in combination with inhaled steroids and β-agonists in severe asthmatics due to its potent inhibition of mast cell activation. PMID:27111445
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A Utilização da Astronomia como Tema Interdisciplinar e Aplicações de Objetos de Aprendizagem
NASA Astrophysics Data System (ADS)
da Silva, L. A.; Voelzke, M. R.
2008-09-01
Este trabalho visa analisar a possibilidade de relacionar conteúdos aplicados no ensino fundamental e médio de forma interdisciplinar por intermédio da astronomia, com a intervenção de objetos de aprendizagem que possam integrar as disciplinas e a utilização de recursos tecnológicos. Em uma pesquisa prévia com 20 professores de uma escola estadual situada na cidade de Guarulhos foi observado que apenas 25% dos professores utilizam algum recurso tecnológico para o desenvolvimento de conteúdos pertinentes à sua disciplina, tais como sites e softwares educativos, sendo que a maioria absoluta continua ensinando apenas com livros didáticos. A maior parte dos professores apresenta dificuldades em trabalhar sua disciplina de forma interdisciplinar, ou seja, 75% dos professores preferem aplicar os conteúdos seguindo uma hierarquia linear de tópicos, evitando a discussão de temas que de alguma forma estão relacionados. A astronomia pode vir à fascinar o ser humano e despertar sua curiosidade promovendo um maior interesse no aprendizado, podendo favorecer análises interdisciplinares de forma lógica e objetiva, desta forma colocar a astronomia como tema motivador interdisciplinar, pode ser relevante no que se refere ao distanciamento da fragmentação dos conteúdos. No Estado de São Paulo, a implantação da proposta curricular no ensino fundamental e médio mostra claramente a inserção da astronomia na maior parte das séries, principalmente na 6ª série em que todo o bimestre se fala de astronomia.
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One-Pot Synthesis of N-Substituted β-Amino Alcohols from Aldehydes and Isocyanides.
Cioc, Răzvan C; van der Niet, Daan J H; Janssen, Elwin; Ruijter, Eelco; Orru, Romano V A
2015-05-18
A practical two-stage one-pot synthesis of N-substituted β-amino alcohols using aldehydes and isocyanides as starting materials has been developed. This method features mild reaction conditions, broad scope, and general tolerance of functional groups. Based on a less common central carbon-carbon bond disconnection, this protocol complements traditional approaches that involve amines and various carbon electrophiles (epoxides, α-halo ketones, β-halohydrins). Medicinally relevant products can be prepared in a concise and efficient way from simple building blocks, as demonstrated in the synthesis of the antiasthma drug salbutamol. Upgrading the synthesis to an enantioselective variant is also feasible. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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RODRÍGUEZ, Yarimar ROSA; DÍAZ, Nelson VARAS
2009-01-01
El proceso de estigmatización asume una devaluación de la persona debido a una característica o marca que haya sido identificada socialmente y que permita que se le describa como diferente. Desde que se desató la epidemia del VIH/SIDA, vivir con la enfermedad ha sido señalado de manera social como una marca estigmatizante. Las manifestaciones de dicha estigmatización se han documentado entre profesionales de la salud. Este estigma puede afectar los servicios de salud que las personas que viven con VIH/SIDA reciben de estos profesionales. Los objetivos de esta investigación fueron explorar: 1) la percepción que tienen estudiantes y profesionales de la salud sobre su nivel de competencia para ofrecer servicios a personas que viven con VIH/SIDA, 2) las opiniones de éstos sobre el tipo de adiestramiento profesional recibido y la necesidad del mismo, y 3) la manifestación de actitudes estigmatizantes como indicadores de necesidad de adiestramiento profesional. La muestra total del estudio estuvo compuesta por 80 de diversas profesiones de la salud. Los resultados reflejan que algunos/as de los/as participantes han recibido formación en VIH pero ésta no ha sido suficiente para contrarrestar las nociones estigmatizantes. Discutimos las implicaciones de los resultados para investigaciones futuras y el desarrollo de intervenciones con vías de minimizar las nociones estigmatizantes en los escenarios de salud. PMID:20011236
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Teamwork: relevance and interdependence of interprofessional education.
Tamayo, M; Besoaín-Saldaña, A; Aguirre, M; Leiva, J
2017-04-27
Determine the perception of university students regarding interprofessional and interdependent work between team members in their inclusion in primary care. Analytical cross-sectional study. The sampling had a probabilistic, stratified random type with 95% confidence and 5% margin of error. Seven-hundred and four students of Public Universities in Santiago (Chile) answered self-administered questionnaire. Ninety-seven point eight of students say that interprofessional work is important; 27.1% of them declare that their university did not seem to show that their study plans were important. The professionals listed as most important in teams are physicians and nurses. Spaces for development and institutional support are key elements to promote interprofessional work. If this competence can involve each academic unit in their different formative spaces there will be a significant contribution to said promotion. Teamwork is a pending task. Determinar la percepción de estudiantes universitarios respecto al trabajo interprofesional e interdependencia entre los miembros del equipo en su inserción en la atención primaria. Estudio de tipo analítico y transversal. El muestreo fue de tipo aleatorio, probabilístico estratificado con un 95% de confianza y un 5% de margen de error. Se utilizó un cuestionario auto-administrado en 704 estudiantes de Universidades del Estado en Santiago de Chile. Un 97,8% de los estudiantes opinan que el trabajo interprofesional es importante; un 27,1% de ellos declara que su universidad no le ha entregado importancia en sus planes de estudios. Los profesionales mencionados como más importantes en el equipo son los médicos y enfermeras. Espacios de desarrollo y respaldo institucional son elementos claves para promover el trabajo interprofesional. Que esta competencia logre involucrar a cada unidad académica en sus diferentes espacios formativos será un aporte significativo en aquello. Trabajo en equipo es una tarea pendiente.
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NASA Astrophysics Data System (ADS)
Martinelli, Elisa; Michetti, Alessandro Maria; Colombaroli, Daniele; Mazzola, Eleonora; Motella De Carlo, Sila; Livio, Franz; Gilli, Adrian; Ferrario, Maria Francesca; Höbig, Nicole; Brunamonte, Fabio; Castelletti, Lanfredo; Tinner, Willy
2017-04-01
Combined pollen, charcoal and modeling evidence from the Insubria Region suggests that fire was a major driver of late Holocene vegetation change. However, the extent and timing of fire response dynamics are not clear yet. We use lacustrine sediments from Lago di Como (N-Italy, S-Alps) to assess if the reconstructed vegetation and fire dynamics were relevant at large scales and if they coincided in time with those observed at smaller sites. The lake, due to its size (142 km2) and economic potential, was very attractive for early land use and human presence in this area is well documented since ca. 10,000 yrs ago (Mesolithic). We used pollen, plant macrofossils and charcoal to reconstruct the vegetation composition and fire activity. During the Younger Dryas and the Early Holocene until ca. 8000 cal BP natural dynamics prevailed. Subsequently, land use and slash-and-burn activities increased at the Mesolithic-Neolithic transition and became widespread around ca. 6500 cal BP. Microscopic charcoal and numerical analyses demonstrate that anthropogenic fires had a determinant influence on long-term vegetation dynamics at regional scales in Insubria. Microscopic charcoal and pollen and spores indicative of land use show that human pressure intensified after ca. 5300 cal yr BP and even more since ca. 4300 cal yr BP. Our results suggest that important species which disappeared or were strongly reduced by land use and fire (e.g. Abies alba, Tilia, Ulmus) will potentially reestablish in the Lago di Como area and elsewhere in Insubria, if land abandonment initiated in the 1950s will continue.
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NASA Astrophysics Data System (ADS)
Yazami, Rachid
This paper reviews the main areas of research performed at different Laboratories of the Institut National Polytechnique de Grenoble (INPG) over the past 20 years, specifically on cabonaceous materials for electrode applications in lithium batteries. The most significant event was the discovery in the early 1980s of reversible lithium intercalation into graphite in polymer electrolytes, which led to the use of this material in today's lithium-ion batteries. Important work was also carried out on positive electrode for primary and secondary batteries, especially graphite oxide and graphite fluoride. Most of these results were presented at the 10 IMLB series Symposia, which started in Rome in 1982 and were back to Como, Italy, in 2000.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Dabros, Trine Marie Hartmann; Gaur, Abhijeet; Pintos, Delfina Garcia
Here in this work, density functional theory (DFT), catalytic activity tests, and in-situ X-ray absorption spectroscopy (XAS) was performed to gain detailed insights into the activity and stability of MoS 2, Ni-MoS 2, and Co-MoS 2 catalysts used for hydrodeoxygenation (HDO) of ethylene glycol upon variation of the partial pressures of H 2O and H 2S. The results show high water tolerance of the catalysts and highlight the importance of promotion and H 2S level during HDO. DFT calculations unraveled that the active edge of MoS 2 could be stabilized against SO exchanges by increasing the partial pressure of Hmore » 2S or by promotion with either Ni or Co. The Mo, NiMo, and CoMo catalysts of the present study were all active and fairly selective for ethylene glycol HDO at 400 °C, 27 bar H 2, and 550–2200 ppm H 2S, and conversions of ≈50–100%. The unpromoted Mo/MgAl 2O 4 catalyst had a lower stability and activity per gram catalyst than the promoted analogues. The NiMo and CoMo catalysts produced ethane, ethylene, and C1 cracking products with a C 2/C 1 ratio of 1.5–2.0 at 550 ppm H 2S. This ratio of HDO to cracking could be increased to ≈2 at 2200 ppm H 2S which also stabilized the activity. Removing H 2S from the feed caused severe catalyst deactivation. Both DFT and catalytic activity tests indicated that increasing the H 2S concentration increased the concentration of SH groups on the catalyst, which correspondingly activated and stabilized the catalytic HDO performance. In-situ XAS further supported that the catalysts were tolerant towards water when exposed to increasing water concentration with H2O/H2S ratios up to 300 at 400–450 °C. Raman spectroscopy and XAS showed that MoS2 was present in the prepared catalysts as small and highly dispersed particles, probably owing to a strong interaction with the support. Linear combination fitting (LCF) analysis of the X-ray absorption near edge structure (XANES) spectra obtained during in-situ sulfidation
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Dabros, Trine Marie Hartmann; Gaur, Abhijeet; Pintos, Delfina Garcia; ...
2017-12-10
Here in this work, density functional theory (DFT), catalytic activity tests, and in-situ X-ray absorption spectroscopy (XAS) was performed to gain detailed insights into the activity and stability of MoS 2, Ni-MoS 2, and Co-MoS 2 catalysts used for hydrodeoxygenation (HDO) of ethylene glycol upon variation of the partial pressures of H 2O and H 2S. The results show high water tolerance of the catalysts and highlight the importance of promotion and H 2S level during HDO. DFT calculations unraveled that the active edge of MoS 2 could be stabilized against SO exchanges by increasing the partial pressure of Hmore » 2S or by promotion with either Ni or Co. The Mo, NiMo, and CoMo catalysts of the present study were all active and fairly selective for ethylene glycol HDO at 400 °C, 27 bar H 2, and 550–2200 ppm H 2S, and conversions of ≈50–100%. The unpromoted Mo/MgAl 2O 4 catalyst had a lower stability and activity per gram catalyst than the promoted analogues. The NiMo and CoMo catalysts produced ethane, ethylene, and C1 cracking products with a C 2/C 1 ratio of 1.5–2.0 at 550 ppm H 2S. This ratio of HDO to cracking could be increased to ≈2 at 2200 ppm H 2S which also stabilized the activity. Removing H 2S from the feed caused severe catalyst deactivation. Both DFT and catalytic activity tests indicated that increasing the H 2S concentration increased the concentration of SH groups on the catalyst, which correspondingly activated and stabilized the catalytic HDO performance. In-situ XAS further supported that the catalysts were tolerant towards water when exposed to increasing water concentration with H2O/H2S ratios up to 300 at 400–450 °C. Raman spectroscopy and XAS showed that MoS2 was present in the prepared catalysts as small and highly dispersed particles, probably owing to a strong interaction with the support. Linear combination fitting (LCF) analysis of the X-ray absorption near edge structure (XANES) spectra obtained during in-situ sulfidation
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Effects of several potassium channel openers and glibenclamide on the uterus of the rat.
Piper, I.; Minshall, E.; Downing, S. J.; Hollingsworth, M.; Sadraei, H.
1990-01-01
1. The ability of several potassium (K+) channel openers to inhibit spasm of the uterus of the nonpregnant rat and their susceptibility to antagonism by glibenclamide was assessed in vitro and in vivo. 2. In the isolated uterus exposed to oxytocin (0.2 nM), cromakalim, RP 49356 and pinacidil were of similar potency (mean pD2 = 6.4, 6.0 and 6.2 respectively) while minoxidil sulphate was of lower potency (pD2 = 4.7). Glibenclamide antagonized cromakalim and RP 49356 with the interactions consistent with competitive antagonism (mean pA2 of 6.57 and 7.00 respectively). Glibenclamide also antagonized pinacidil (pA2 = 6.22) but the slope of the Schild plot was significantly greater than -1. Neither salbutamol nor minoxidil sulphate was antagonized by glibenclamide (10 microM). 3. Cromakalim (1 and 10 microM), RP 49356 (1 and 10 microM), pinacidil (1 microM) and minoxidil sulphate (100 microM) suppressed spasm evoked by low (less than 40 mM) but not high (greater than or equal to 40 mM) KCl concentrations. Glibenclamide (10 microM) prevented cromakalim (10 microM)-, RP 49356 (10 microM)- and pinacidil (10 microM)-induced suppression of KCl (20 mM)-evoked spasm. Pinacidil (10 and 100 microM), cromakalim (100 microM) and salbutamol (0.01-1 microM) inhibited spasm evoked by all concentrations of KCl (10-80 mM). Suppression of spasm evoked by KCl (10-80 mM) by cromakalim (100 microM) and pinacidil (100 microM) was insensitive to glibenclamide (10 microM). 4. Cromakalim (0.1 mg kg-1) and RP 49356 (0.1 mg kg-1), given by i.v. bolus injection, inhibited uterine contractions, produced a fall in blood pressure and a slight tachycardia in the conscious ovariectomized rat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2128195
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Nielsen, Ole Bækgaard; Clausen, Johannes D.; Pedersen, Thomas Holm; Hayward, Lawrence J.
2011-01-01
In patients with hyperkalemic periodic paralysis (HyperKPP), attacks of muscle weakness or paralysis are triggered by K+ ingestion or rest after exercise. Force can be restored by muscle work or treatment with β2-adrenoceptor agonists. A missense substitution corresponding to a mutation in the skeletal muscle voltage-gated Na+ channel (Nav1.4, Met1592Val) causing human HyperKPP was targeted into the mouse SCN4A gene (mutants). In soleus muscles prepared from these mutant mice, twitch, tetanic force, and endurance were markedly reduced compared with soleus from wild type (WT), reflecting impaired excitability. In mutant soleus, contractility was considerably more sensitive than WT soleus to inhibition by elevated [K+]o. In resting mutant soleus, tetrodotoxin (TTX)-suppressible 22Na uptake and [Na+]i were increased by 470 and 58%, respectively, and membrane potential was depolarized (by 16 mV, P < 0.0001) and repolarized by TTX. Na+,K+ pump–mediated 86Rb uptake was 83% larger than in WT. Salbutamol stimulated 86Rb uptake and reduced [Na+]i both in mutant and WT soleus. Stimulating Na+,K+ pumps with salbutamol restored force in mutant soleus and extensor digitorum longus (EDL). Increasing [Na+]i with monensin also restored force in soleus. In soleus, EDL, and tibialis anterior muscles of mutant mice, the content of Na+,K+ pumps was 28, 62, and 33% higher than in WT, respectively, possibly reflecting the stimulating effect of elevated [Na+]i on the synthesis of Na+,K+ pumps. The results confirm that the functional disorders of skeletal muscles in HyperKPP are secondary to increased Na+ influx and show that contractility can be restored by acute stimulation of the Na+,K+ pumps. Calcitonin gene-related peptide (CGRP) restored force in mutant soleus but caused no detectable increase in 86Rb uptake. Repeated excitation and capsaicin also restored contractility, possibly because of the release of endogenous CGRP from nerve endings in the isolated muscles. These
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Montejo Fernández, Marta; Benito Manrique, Iñaki; Montiel Eguía, Arantza; Benito Fernández, Javier
2018-05-23
Although evidence-based guidelines for acute bronchiolitis recommend primarily supportive care unnecessary treatments remain well documented. The objective of this study was to analyse a quality improvement initiative to reduce overuse of unnecessary treatments in infants with acute bronchiolitis in primary care settings. To determine the number of unnecessary treatments we reviewed the charts corresponding to infants aged <24 months of age diagnosed with acute bronchiolitis in two Primary Care areas during two bronchiolitis seasons [October-Mars of 2015-2016 (pre-intervention period) and 2016-2017 (post-intervention period)]. Between those seasons we distributed an evidence-based management protocol and developed interactive sessions with on-line data collection and feed-back. Outcomes were the rate of infants receiving salbutamol, steroids or antibiotics. Twenty outpatient clinics contributed with 1,277 chart reviews (619 in the pre-intervention period and 658 in the post-intervention period). Overall, the use of any medication was reduced from 72.5% (95% CI, 68.8-75.9) to 52.1% (95% CI, 48.3-55.9) (p<0.01): salbutamol from 56.0% (95% CI, 52.1-59.9) to 38.3% (95% CI, 34.6-42.0) (p<0.01), corticosteroids from 23.7% (95% CI, 20.5-27.2) to 12.9% (95% CI, 10.5-15.7) (p<0.01) and antibiotics from 36.1% (95% CI; 32.5-40.0) to 29.6% (95% CI; 26.2-33.2) (p<0.05). The number of medications per patient decreased from a mean of 1.81 (SD: 0.86) to 1.62 (SD: 0.81) (p<0.01). We significantly decreased the use of unnecessary treatments in infants with acute bronchiolitis. This quality improvement initiative may be applied to the settings where the majority of infants with acute bronchiolitis are attended in western countries. Copyright © 2018. Publicado por Elsevier España, S.L.U.
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Evaluation of a Wildfire Smoke Forecasting System as a Tool for Public Health Protection
Brauer, Michael; Henderson, Sarah B.
2013-01-01
Background: Exposure to wildfire smoke has been associated with cardiopulmonary health impacts. Climate change will increase the severity and frequency of smoke events, suggesting a need for enhanced public health protection. Forecasts of smoke exposure can facilitate public health responses. Objectives: We evaluated the utility of a wildfire smoke forecasting system (BlueSky) for public health protection by comparing its forecasts with observations and assessing their associations with population-level indicators of respiratory health in British Columbia, Canada. Methods: We compared BlueSky PM2.5 forecasts with PM2.5 measurements from air quality monitors, and BlueSky smoke plume forecasts with plume tracings from National Oceanic and Atmospheric Administration Hazard Mapping System remote sensing data. Daily counts of the asthma drug salbutamol sulfate dispensations and asthma-related physician visits were aggregated for each geographic local health area (LHA). Daily continuous measures of PM2.5 and binary measures of smoke plume presence, either forecasted or observed, were assigned to each LHA. Poisson regression was used to estimate the association between exposure measures and health indicators. Results: We found modest agreement between forecasts and observations, which was improved during intense fire periods. A 30-μg/m3 increase in BlueSky PM2.5 was associated with an 8% increase in salbutamol dispensations and a 5% increase in asthma-related physician visits. BlueSky plume coverage was associated with 5% and 6% increases in the two health indicators, respectively. The effects were similar for observed smoke, and generally stronger in very smoky areas. Conclusions: BlueSky forecasts showed modest agreement with retrospective measures of smoke and were predictive of respiratory health indicators, suggesting they can provide useful information for public health protection. Citation: Yao J, Brauer M, Henderson SB. 2013. Evaluation of a wildfire smoke
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Ozkan, Melike Hacer; Uma, Serdar
2018-06-01
Endothelial IK C a and/or SK C a channels play an important role in the control of vascular tone by participating in endothelium-dependent relaxation. Whether β-AR antagonists, mainly used in hypertension, affect endothelial K C a channel function is unknown. In this study, we examined the effect of the β2-AR antagonist and inverse agonist ICI 118,551 on the IK C a /SK C a channel activity by assessing functional relaxation responses to several agonists that stimulate these channels. Mesenteric arterial rings isolated from male Sprague Dawley mounted to organ baths. Acetylcholine elicited IK C a - and SK C a -mediated relaxations that were abolished by TRAM-34 and apamin, respectively. ICI 118,551, which did not dilate the arteries per se, increased the IK C a -mediated relaxations, whereas SK C a -mediated relaxations remained unaltered. Same potentiating effect was also detected on the IK C a -mediated relaxations to carbachol and A23187, but not to NS309. Neither acetylcholine-induced nitric oxide-mediated relaxations nor SNP relaxations changed with ICI 118,551. The PKA inhibitor KT-5720, the selective β2-AR agonist salbutamol, the selective β2-AR antagonist butoxamine, the non-selective β-AR antagonist propranolol, and the inverse agonists carvedilol or nadolol failed to affect the IK C a -mediated relaxations. ICI 118,551-induced increase was not reversed by salbutamol or propranolol as well. Besides, low potassium-induced relaxations in endothelium-removed arteries remained the same in the presence of ICI 118,551. These data demonstrate a previously unrecognized action of ICI 118,551, the ability to potentiate endothelial IK C a channel-mediated vasodilation, through a mechanism independent of β2-AR antagonistic or inverse agonistic action. Instead, the enhancement of acetylcholine relaxation seems likely to occur by a mechanism secondary to endothelial calcium increase. © 2017 Nordic Association for the Publication of BCPT (former Nordic
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Physical stability of highly concentrated injectable drugs solutions used in intensive care units.
Closset, M; Hecq, J D; Soumoy, L; Simar, J; Gonzalez, E; Charlet, L; Declave, C; Gillet, P; Galanti, L
2017-05-01
The intensive care department of the institution use drug solutions within higher concentration to avoid fluid overload. The purpose of the study is to prove the physical stability of different injectable drugs within high concentration (amiodarone 25mg/mL, isosorbide 0.60mg/mL, lorazepam 0.16mg/mL, noradrenalin 0.120 and 0.240mg/mL, salbutamol 0.06mg/mL and sodium valproate 12mg/mL) to ensure the patients safety. Five of 30 or 50mL polypropylene syringes were prepared for each solution under aseptic conditions and stored at room temperature. Immediately after the preparation (hour 0) and after 1, 4, 8, 24 and 48hours, 2mL of each solution were withdrawn from each syringe and placed in glass tubes to proceed to the stability test. All specimens were visually inspected in front of a black and of a white background and aliquots of each solution were centrifuged to proceed to microscopic inspection with a ten-fold magnification. The pH of each solution was measured with glass electrode pH-meter (Inolab level 1, WTW Weilhem, Germany with biotrode electrode, Hamilton, Bonaduz, Switzerland) and spectrophotometric measurements (Genesys 10 series, New-York, USA) were performed at three wavelengths (350, 410 and 550nm) to avoid the apparition of turbidity. For all the drugs included in the study, there was no significant change in pH, no color change, no turbidity or opacity and no precipitation observed in the solutions during the storage at room temperature for 48hours. No microaggregates were detected by microscope neither revealed by a change of absorbance. Within these limits, the preparations of amiodarone in 5% glucose polypropylene syringes and isosorbide, lorazepam, noradrenalin, salbutamol, valproate in 0.9% sodium chloride polypropylene syringes are physically stable at room temperature for 48hours. These results allow us to consider a study of chemical stability by high-performance liquid chromatography (HPLC). Copyright © 2016 Académie Nationale de Pharmacie
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Hatley, Ross Hm; Byrne, Sarah M
2017-01-01
To improve convenience to patients, there have been advances in the operation of nebulizers, resulting in fast treatment times and less drug lost to the environment. However, limited attention has been paid to the effects of these developments on the delivered dose (DD) and respirable delivered dose (RDD). Published pharmacopoeia and ISO testing guidelines for adult-use testing utilize a single breathing pattern, which may not be sufficient to enable effective comparisons between the devices. The DD of 5 mg of salbutamol sulfate into adult breathing patterns with inhalation:exhalation (I:E) ratios between 1:1 and 1:4 was determined. Droplet size was determined by laser diffraction and RDD calculated. Nine different nebulizer brands with different modes of operation (conventional, venturi, breath-enhanced, mesh, and breath-activated) were tested. Between the non-breath-activated nebulizers, a 2.5-fold difference in DD (~750-1,900 µg salbutamol) was found; with RDD, there was a more than fourfold difference (~210-980 µg). With increasing time spent on exhalation, there were progressive reductions in DD and RDD, with the RDD at an I:E ratio of 1:4 being as little as 40% of the dose with the 1:1 I:E ratio. The DD and RDD from the breath-activated mesh nebulizer were independent of the I:E ratio, and for the breath-activated jet nebulizer, there was less than 20% change in RDD between the I:E ratios of 1:1 and 1:4. Comparing nebulizers using the I:E ratio recommended in the guidelines does not predict relative performance between the devices at other ratios. There was significant variance in DD or RDD between different brands of non-breath-activated nebulizer. In future, consideration should be given to revision of the test protocols included in the guidelines, to reflect more accurately the potential therapeutic dose that is delivered to a realistic spectrum of breathing patterns.
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Fang, Tien-Pei; Lin, Hui-Ling; Chiu, Shu-Hua; Wang, Szu-Hui; DiBlasi, Robert M; Tsai, Ying-Huang; Fink, James B
2016-10-01
High frequency oscillatory ventilation (HFOV) is used in critically ill patients with severe hypoxemic respiratory failure. The purpose of this in vitro study was to determine the efficiency of aerosol delivery with different lung parameters during simulated neonatal, pediatric, and adult HFOV. Sensormedics 3100A/B ventilators were used to deliver infant, pediatric, and adult HFOV. Two types of aerosol generators were chosen for testing: 1) a continuous jet nebulizer (JN) with a unit-dose of 5.0 mg/2.5 mL salbutamol sulfate diluted into 4 mL, and 2) a vibrating mesh nebulizer (VMN) with salbutamol sulfate were run to completion of aerosol generation. Both aerosol devices were placed 1) between the ventilator circuit and the endotracheal tube (ETT) (proximal position); and 2) at the inlet of the heated humidifier (distal position) (n = 5). Drug was collected on a bacterial filter placed distal to the ETT, and the drug eluted and analyzed with a UV Spectrophotometer at 276 nm. T- test and ANOVA tests were used for comparison (p < 0.05). The inhaled drug delivered by JN was 0%-0.6% of the nominal dose when placed at distal position, and 0%-3% at proximal position (p < 0.01), while the VMN was 0%-0.5% at distal and 8.6%-22.7% at proximal position (p < 0.01). Aerosol delivery during HFOV was greater with adult settings than pediatric and infant settings with VMN and JN (22.7%, 8.6%, and 17.4% respectively, p < 0.01). When the aerosol delivery device was placed at the distal position, negligible drug mass was observed (<0.5%), regardless of the nebulizer device used. During HFOV, aerosol delivery with the nebulizer placed at proximal was greater than placement distal from the ETT, with VMN delivering more drug than JN. The inhaled drug was delivery correlated positively with ETT size, MAP, and bias flow, and inversely proportional to power settings.
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Beta 2 adrenergic receptor gene restriction fragment length polymorphism and bronchial asthma.
Ohe, M.; Munakata, M.; Hizawa, N.; Itoh, A.; Doi, I.; Yamaguchi, E.; Homma, Y.; Kawakami, Y.
1995-01-01
BACKGROUND--Beta 2 adrenergic dysfunction may be one of the underlying mechanisms responsible for atopy and bronchial asthma. The gene encoding the human beta 2 adrenergic receptor (beta 2ADR) has recently been isolated and sequenced. In addition, a two allele polymorphism of this receptor gene has been identified in white people. A study was carried out to determine whether this polymorphism is functionally important and has any relation to airways responsiveness, atopy, or asthma. METHODS--The subjects studied were 58 family members of four patients with atopic asthma. Restriction fragment length polymorphism (RFLP) with Ban-I digestion of the beta 2ADR gene was detected by a specific DNA probe with Southern blot analysis. Airways responses to inhaled methacholine and the beta 2 agonist salbutamol, the skin prick test, and serum IgE levels were also examined and correlated to the beta 2ADR gene RFLP. In addition, measurements of cAMP responses to isoproterenol in peripheral mononuclear cells were performed in 22 healthy subjects whose genotype for beta 2ADR was known. RESULTS--A two allele polymorphism (2.3 kb and 2.1 kb) of the beta 2ADR gene was detected in the Japanese population. Family members without allele 2.3 kb (homozygote of allele 2.1 kb) had lower airways responses to inhaled salbutamol than those with allele 2.3 kb. The incidence of asthma was higher in those without allele 2.3 kb than in those with allele 2.3 kb. The beta 2ADR gene RFLP had no relation to airways responses to methacholine and atopic status. cAMP responses in peripheral mononuclear cells of the subjects without allele 2.3 kb tended to be lower than those of the subjects with allele 2.3 kb. CONCLUSIONS--These results suggest that Ban-I RFLP of the beta 2ADR gene may have some association with the airways responses to beta 2 agonists and the incidence of bronchial asthma. Images PMID:7785006
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Poirier Larabie, S; Houde, M; Gagnon, C
2017-11-03
Aquatic systems near major urban centers are constantly contaminated with effluent from wastewater treatment plants. Pharmaceuticals are part of the contamination and several classes of drugs have been detected in surface waters in the last decade. To better understand the impact of those pharmaceuticals in ecosystems, the exposure to aquatic species needs to be investigated. This study presents a new simple and rugged quantitative method for the determination of several classes of drugs using 100μL of plasma from fish environmentally exposed to a major but highly diluted urban effluent. Six common drugs (i.e., diclofenac, ibuprofen, naproxen, salbutamol, sulfamethoxazole and trimethoprim) and one major metabolite (2-hydroxy-ibuprofen), present in significant amount in impacted waterways have been selected for the development and validation of the method. First, all drugs were extracted using cation exchange solid phase extraction (SPE) and eluted with two solvent mixtures. Then, the extracts were analyzed using a reverse-phase analytical column Waters ® CORTECS C 18 + (150×2.1mm, 2.7μm) within 14min. MS/MS was performed with an electrospray (ESI) interface in positive ion mode, with multiple reaction monitoring (MRM) experiment acquiring two product ions per drugs. Quantification has been made with standard curves for each analyte using isotopically labeled internal standards. This method has high sensitivity with limits of quantification of 1ngmL -1 for each drug, except for ibuprofen and its metabolite 2-hydroxy-ibuprofen at 2ngmL -1 . The precision of the method was below 11%, the accuracy between 94 and 105% and overall recovery between 94 and 111% for all drugs, with high selectivity. Application of the method to plasma samples from wild northern pike inhabiting the St. Lawrence River collected over a three-year period showed the presence of naproxen, diclofenac, trimethoprim and salbutamol at very low concentrations (around 1ngmL -1 ). Crown Copyright
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NASA Astrophysics Data System (ADS)
Fekih, Z.; Ghellai, N.; Fortas, G.; Chiboub, N.; Sam, S.; Chabanne-sari, N. E.; Gabouze, N.
In this work, thin films of metal alloys (Co-Mo) have been electrodeposited onto silicon (Si) surface. The effects of two different additives (H3BO3 and Na2CO3) and the pH of the solution on the electrochemically deposited films (morphology, stochiometry…) have been investigated. The properties of the deposits were characterized by using X-Rays Diffraction (XRD), Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray Spectroscopy (EDS). The results show that the morphology and the film composition depend on both the pH of the solution and the additives. The presence of boric acid favors the Mo deposition. Crack-free homogeneous deposits with a low percentage of molybdenum can be easily obtained from high pH bath. The deposits were shown to exhibits a good crystalline structure.
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Les déformations eburnéennes de l'unité birrimienne de la comoé (côte d'ivoire)
NASA Astrophysics Data System (ADS)
Vidal, M.
The analysis of Eburnean strain fields in the Upper (?) Birrimian Comoé Unit shows four great stages of tectogenesis: an early cleavage subparallel to stratification which results from synkinematic granitoïd intrusions; a folding (N40°E to N60°E); a transcurrent faulting period, essentially ductile N-S sinistral; N120°E schistosity, and a N110°E transcurrent ductile sinistral (?) faulting phase. The importance of the sinistral N-S faulting system and, to a lesser extent, the N120°E schistosity direction, is shown. The probable rôle of these directions (particularly N-S) from Liberian to Upper Cretaceous is shown by the within-plate tectonic occurrences in the West-African craton.
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Chaibva, Faith A; Khamanga, Sandile M M; Walker, Roderick B
2010-12-01
Hydrophilic matrix formulations are important and simple technologies that are used to manufacture sustained release dosage forms. Hydroxypropyl methylcellulose-based matrix tablets, with and without additives, were manufactured to investigate the rate of hydration, rate of erosion, and rate and mechanism of drug release. Scanning electron microscopy was used to assess changes in the microstructure of the tablets during drug release testing and whether these changes could be related to the rate of drug release from the formulations. The results revealed that the rate of hydration and erosion was dependent on the polymer combination(s) used, which in turn affected the rate and mechanism of drug release from these formulations. It was also apparent that changes in the microstructure of matrix tablets could be related to the different rates of drug release that were observed from the test formulations. The use of scanning electron microscopy provides useful information to further understand drug release mechanisms from matrix tablets.
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PREVENCION DE VIH PARA MUJERES HISPANAS DE 50 AÑOS Y MÁS
Villegas, N.; Cianelli, R.; Ferrer, L.; Kaelber, L.; Peragallo, N.; Yaya, Alexandra O.
2012-01-01
Introducción Las mujeres Hispanas de 50 años y más (MHC) son una minoría en Estados Unidos que está a elevado riesgo de adquirir VIH y son el grupo menos estudiado en lo que respecta a salud, características sociales y de comportamiento sexual. Objetivo Investigar los factores que incrementan el riesgo de VIH en las MHC con el propósito de desarrollar o adaptar una intervención apropiada para la “edad y la cultura "de este grupo de mujeres. Metodología Estudio descriptivo de corte transversal con una muestra de 50 MHC, sexualmente activas y que residían en Miami, Florida, Estados Unidos. Se utilizó un cuestionario estructurado administrado por entrevistadores entrenados y bilingües (inglés/español). Las participantes fueron reclutadas en diferentes lugares en el Sur de Florida. Para el análisis de los datos se utilizó estadística descriptiva, tanto medidas de tendencia central como medidas de dispersión. Resultados La edad promedio de las MHC fue de 55,7 ± 6 años (rango 50–76 años). Todas las MHC estaban en la menopausia. Prevención del VIH Las MHC reportaron niveles medios de conocimientos sobre VIH y comunicación con la pareja. En la muestra se reportó la presencia de síntomas depresivos, violencia en la pareja, actitudes negativas hacia las personas viviendo con VIH y baja percepción de riesgo de adquirir VIH. Las MHC mencionaron necesidades de aprendizaje en tópicos relacionados con prevención de VIH y cambios de la edad. Conclusión Las MHC están a riesgo de adquirir VIH y tienen necesidades especiales en términos de educación sobre prevención de VIH. PMID:25242862
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Bronchodilators for the prevention and treatment of chronic lung disease in preterm infants.
Ng, Geraldine; da Silva, Orlando; Ohlsson, Arne
2016-12-14
standard method described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Two review authors extracted and assessed all data provided by each study. We reported risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) with 95% confidence interval (CI) for dichotomous outcomes and mean difference (MD) for continuous data. We assessed the quality of the evidence by using the GRADE approach. For this update, we identified one new randomised controlled trial investigating effects of bronchodilators in preterm infants. This study, which enrolled 73 infants but reported on 52 infants, examined prevention of CLD with the use of aminophylline. According to GRADE, the quality of the evidence was very low. One previously included study enrolled 173 infants to look at prevention of CLD with the use of salbutamol. According to GRADE, the quality of the evidence was moderate. We found no eligible trial that studied the use of bronchodilator therapy for treatment of individuals with CLD. Prophylaxis with salbutamol led to no statistically significant differences in mortality (RR 1.08, 95% CI 0.50 to 2.31; RD 0.01, 95% CI -0.09 to 0.11) nor in CLD (RR 1.03, 95% CI 0.78 to 1.37; RD 0.02, 95% CI -0.13 to 0.17). Results showed no statistically significant differences in other complications associated with CLD nor in preterm birth. Investigators in this study did not comment on side effects due to salbutamol. Prophylaxis with aminophylline led to a significant reduction in CLD at 28 days of life (RR 0.18, 95% CI 0.04 to 0.74; RD -0.35, 95% CI -0.56 to -0.13; NNTB 3, 95% CI 2 to 8) and no significant difference in mortality (RR 3.0, 95% CI 0.33 to 26.99; RD 0.08, 95% CI -0.07 to 0.22), along with a significantly shorter dependency on supplementary oxygen in the aminophylline group compared with the no treatment group (MD -17.75 days, 95% CI -27.56 to -7.94). Tests for heterogeneity were not applicable for any
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Powell, C V E; Kolamunnage-Dona, R; Lowe, J; Boland, A; Petrou, S; Doull, I; Hood, K; Williamson, P R
2013-10-01
There are few data on the role of nebulised magnesium sulphate (MgSO4) in the management of acute asthma in children. Those studies that have been published are underpowered, and use different methods, interventions and comparisons. Thus, no firm conclusions can be drawn. Does the use of nebulised MgSO4, when given as an adjunct to standard therapy in acute severe asthma in children, result in a clinical improvement when compared with standard treatment alone? Patients were randomised to receive three doses of MgSO4 or placebo, each combined with salbutamol and ipratropium bromide, for 1 hour. The Yung Asthma Severity Score (ASS) was measured at baseline, randomisation, and at 20, 40, 60 (T60), 120, 180 and 240 minutes after randomisation. Emergency departments and children's assessment units at 30 hospitals in the UK. Children aged 2-15 years with acute severe asthma. Patients were randomised to receive nebulised salbutamol 2.5 mg (ages 2-5 years) or 5 mg (ages ≥ 6 years) and ipratropium bromide 0.25 mg mixed with either 2.5 ml of isotonic MgSO4 (250 mmol/l, tonicity 289 mOsm; 151 mg per dose) or 2.5 ml of isotonic saline on three occasions at approximately 20-minute intervals. The primary outcome measure was the ASS after 1 hour of treatment. Secondary measures included 'stepping down' of treatment at 1 hour, number and frequency of additional salbutamol administrations, length of stay in hospital, requirement for intravenous bronchodilator treatment, and intubation and/or admission to a paediatric intensive care unit. Data on paediatric quality of life, time off school/nursery, health-care resource usage and time off work were collected 1 month after randomisation. A total of 508 children were recruited into the study; 252 received MgSO4 and 256 received placebo along with the standard treatment. There were no differences in baseline characteristics. There was a small, but statistically significant difference in ASS at T60 in those children who received
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NASA Astrophysics Data System (ADS)
Terrana, Silvia; Brunamonte, Fabio; Frascoli, Francesca; Ferrario, Maria Francesca; Michetti, Alessandro Maria; Pozzi, Andrea; Gambillara, Roberto; Binda, Gilberto
2016-04-01
One of the greatest environmental and social-economics threats is climate change. This topic, in the next few years, will have a significant impact on the availability of water resources of many regions. This is compounded by the strong anthropization of water systems that shows an intensification of conflicts for water resource exploitation. Therefore, it is necessary a sustainable manage of natural resources thorough knowledge of the hosting territories. The development of investigation and data processing methods are essential to reduce costs for the suitable use and protection of resources. Identify a sample area for testing the best approach is crucial. This research aims to find a valid methodology for the characterization, modeling and management of subalpine urban aquifers, and the urban district of Como appears perfect. The city of Como is located at the southern end of the western sector of Lake Como (N Italy). It is a coastal town, placed on a small alluvial plain, therefore in close communication with the lake. The plain is drained by two streams, which are presently artificially buried, and have an underground flow path in the urban section till the mouth. This city area, so, is suitable for this project as it is intensely urbanized, its dimensions is not too extensive and it is characterized by two aquifers very important and little known. These are a shallow aquifer and a deep aquifer, which are important not only for any water supply, but also for the stability of the ground subsidence in the city. This research is also the opportunity to work in a particular well-known area with high scientific significance; however, there is complete absence of information regarding the deep aquifer. Great importance has also the chosen and used of the more powerful open source software for this type of area, such as PHREEQC, EnvironInsite, PHREEQE etc., used for geological and geochemical data processing. The main goal of this preliminary work is the
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Estimación de pequeñas perturbaciones en satélites geocéntricos como un problema inverso
NASA Astrophysics Data System (ADS)
Zadunaisky, P. E.
El movimiento geocéntrico de un satélite artificial es simulado automáticamente por un sistema de ecuaciones diferenciales de segundo orden que incluyen dos funciones perturbadoras. La primera representa el segundo término del potencial gravitatorio de la Tierra y la segunda corresponde al frenado atmosférico. Asumiendo como conocidas, por hipótesis o por mediciones, la posición y velocidad del satélite en instantes sucesivos se estiman las perturbaciones a intervalos sucesivos por un método determinístico. Para ilustrar el método y comprobar la precisión de nuestros resultados hemos simulado dos ejemplos incluyendo valores conocidos de las perturbaciones que luego comparamos con los resultados de nuestro método. El método puede aplicarse por ejemplo para el intervalo de una revolución satelital lo cual permitiría el diseño inmediato de una maniobra correctiva de la órbita satelital.
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Pseudoaneurisma de aorta abdominal como complicação de pancreatite crônica: relato de caso
Barbosa, Eduardo Carvalho Horta; Nóbrega, Leonardo Pires de Sá; Rodrigues, Daniel Augusto de Souza; Cunha, Josué Rafael Ferreira; Kalume, Claudio Eluan
2017-01-01
Resumo A pancreatite crônica é uma enfermidade associada a diversas complicações vasculares, como pseudocisto hemorrágico, trombose do sistema venoso portal e formações varicosas e pseudoaneurismáticas. O pseudoaneurisma de aorta abdominal secundário à pancreatite crônica é uma complicação rara, de difícil suspeição clínica, que requer tratamento complexo. A fisiopatologia dessa condição envolve a corrosão enzimática tecidual após a liberação e ativação de enzimas exócrinas proteolíticas das células acinares do pâncreas. O presente estudo relata o caso de um paciente de 52 anos, etilista crônico, internado com dor abdominal difusa, cuja propedêutica revelou se tratar de um pseudoaneurisma em aorta infrarrenal. Optou-se pelo tratamento cirúrgico convencional, levando-se em consideração a idade, as condições clínicas do paciente e a disponibilidade de endopróteses compatíveis com o diâmetro da aorta. PMID:29930654
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Ngala, R A; O'Dowd, J; Wang, S J; Agarwal, A; Stocker, C; Cawthorne, M A; Arch, J R S
2008-01-01
Background and purpose: Picomolar concentrations of the β3-adrenoceptor agonist BRL37344 stimulate 2-deoxyglucose uptake in soleus muscle via undefined receptors. Higher concentrations alter uptake, apparently via β2-adrenoceptors. Effects of BRL37344 and β2-adrenoceptor agonists are compared. Experimental approach: Mouse soleus muscles were incubated with 2-deoxy[1-14C]-glucose, [1-14C]-palmitate or [2-14C]-pyruvate, and BRL37344, β2-adrenoceptor agonists and selective β-adrenoceptor antagonists. Formation of 2-deoxy[1-14C]-glucose-6-phosphate or 14CO2 was measured. 2-Deoxy[1-14C]-glucose uptake and β-adrenoceptor mRNA were measured in C2C12 cells. Key results: 10 pM BRL37344, 10 pM clenbuterol and 100 pM salbutamol stimulated 2-deoxyglucose uptake in soleus muscle by 33–54%. The effect of BRL37344 was prevented by 1 μM atenolol but not by 300 nM CGP20712A or IC3118551, or 1 μM SR59230A; that of clenbuterol was prevented by ICI118551 but not atenolol. 10 nM BRL37344 st4mulated 2-deoxyglucose uptake, whereas 100 nM clenbuterol and salbutamol inhibited uptake. These effects were blocked by ICI118551. Similar results were obtained in C2C12 cells, in which only β2-adrenoceptor mRNA could be detected by RT-PCR. 10 nM BRL37344 and 10 pM clenbuterol stimulated muscle palmitate oxidation. In the presence of palmitate, BRL37344 no longer stimulated 2-deoxyglucose uptake and the effect of clenbuterol was not significant. Conclusions and implications: Stimulation of glucose uptake by 10 pM BRL37344 and clenbuterol involves different atypical pharmacologies. Nanomolar concentrations of BRL37344 and clenbuterol, probably acting via β2-adrenoceptors, have opposite effects on glucose uptake. The agonists preferentially stimulate fat rather than carbohydrate oxidation, but stimulation of endogenous fat oxidation cannot explain why 100 nM clenbuterol inhibited 2-deoxyglucose uptake. PMID:18552870
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Maternal drug use and the risk of anorectal malformations: systematic review and meta-analysis.
Zwink, Nadine; Jenetzky, Ekkehart
2018-05-10
Origin of anorectal malformations (ARM) are considered multifactorial. Several genetic and non-genetic risk factors are discussed in literature. Maternal periconceptional medical drug use as possible risk factor, however, has not been reviewed systematically. Studies published between 1977 and April 2017 were reviewed through systematic search in PubMed, ISI Web of Knowledge and Scopus databases. Furthermore, related and cross-referencing publications were reviewed. Pooled odds ratios (95% confidence intervals) were determined to quantify associations of maternal periconceptional use of folic acid, multivitamins, anti-asthma medication (separated in any anti-asthma medication, inhaled corticosteroids and salbutamol), thyroid hormone supplements, psychiatric drugs (separated in antidepressants, any selective serotonin reuptake inhibitors [SSRI], sertraline, citalopram, fluoxetine, paroxetine, hypnotics and benzodiazepine) and aspirin with ARM using meta-analyses. Thirty-seven studies that reported on the association between maternal periconceptional drug intake and infants born with ARM were included in this review. These were conducted in the United States of America (n = 14), Sweden (n = 6), Hungary (n = 5), Germany (n = 3), the Netherlands (n = 3), Denmark (n = 2), France (n = 2), Norway (n = 1) and the UK (n = 1). However, only few of these studies reported on the same risk factors. Studies were heterogeneous with respect to case numbers, period ingestion of medical drug use, control selection and adjustment for covariates. Consistently increased risks were observed for any anti-asthma medication, and hypnotics and benzodiazepine, but not for folic acid, multivitamins, inhaled corticosteroids, salbutamol, thyroid hormone supplements, antidepressants, any SSRI, sertraline, citalopram, fluoxetine, paroxetine and aspirin. In meta-analyses, pooled odds ratios (95% confidence intervals) for any anti-asthma medication, and hypnotics
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Futrakul, Sitthivuddhi; Deerojanawong, Jitladda; Prapphal, Nuanchan
2005-07-01
The objectives of this study were to identify possible risk factors of bronchial hyperesponsiveness (BHR) in children up to 5 years of age with wheezing-associated respiratory infection (WARI), and to study the prevalence of BHR. Children up to 5 years of age with WARI were enrolled in the study. The parents or caregivers of children were asked about their demographic data and clinical histories. Physical examination and clinical score assessment were performed. Pulmonary function tests, i.e., tidal breathing flow volume (TBFV), were performed to measure tidal breathing parameters before and after salbutamol nebulization. If volume at peak tidal expiratory flow/expiratory tidal volume and time to peak expiratory flow/total expiratory time increased > or = 20%, or tidal expiratory flow at 25% of tidal volume/peak tidal expiratory flow increased > or = 20% after nebulization therapy, BHR was diagnosed. The number in the positive BHR group was used to calculate the prevalence of BHR, and clinical features were compared with those of the negative BHR group. Categorical data were analyzed for statistical significance (P < 0.05) by chi-square test or Fisher's exact test, or Student's t-test, as appropriate. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for those with statistical significance. One hundred and six wheezing children underwent pulmonary function tests before and after salbutamol nebulization. With the aforementioned criteria, 41 cases (38.7%) were diagnosed with BHR. History of reactive airway disease, (OR, 6.31; 95% CI, 1.68-25), maternal history of asthma (OR, 3.45; 95% CI, 1.34-9), breastfeeding less than 3 months (OR, 3.18; 95% CI, 1.26-8.12), and passive smoking (OR, 3; 95% CI, 1.15-7.62) were significant risk factors of BHR. The eosinophil count was significantly higher in the BHR (+) group particularly, in children 1-5 years of age (P < or = 0.01). Patchy infiltrates were more commonly found in patients with negative BHR but not
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Hellstern, K.; Curtis, C.G.; Powell, G.M.
1990-04-01
The incorporation of {sup 14}C-leucine into rabbit lung slices was monitored in the absence and presence of selected drugs and chemicals relevant to the perturbation of lung function and the development of lung disease. Known inhibitors of protein synthesis (cycloheximide and ricin) inhibited the incorporation of {sup 14}C-leucine. Marked inhibition was also recorded with the lung toxins paraquat and 4-ipomeanol. By contrast, orciprenaline, salbutamol, and terbutaline were without effect although some response was recorded with isoprenaline. The filtered gas phase of cigarette smoke and acrolein, one of its components, were inhibitory but protection was afforded by N-acetylcysteine. It is suggestedmore » that the inhibitory effects of cigarette smoke may be due to its acrolein content. It is further suggested that the use of lung slices and measurements of {sup 14}C-leucine incorporation provide valuable means for monitoring potential pulmonary toxins.« less
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Liu, Chun-Sen; Sun, Chun-Xiao; Tian, Jia-Yue; Wang, Zhuo-Wei; Ji, Hong-Fei; Song, Ying-Pan; Zhang, Shuai; Zhang, Zhi-Hong; He, Ling-Hao; Du, Miao
2017-05-15
Two unique immunosensors made of aluminum-based metal-organic frameworks (MOFs), namely, 515- and 516-MOFs, with 4,4',4''-nitrilotribenzoic acid (H 3 NTB) were successfully obtained to efficiently assess food safety. The as-prepared 515- and 516-MOFs exhibited superior thermal and physicochemical stability, high electrochemical activity, and good biocompatibility. Among these immunosensors, 516-MOF showed a preferable biosensing ability toward analytes determined by electrochemical techniques. The developed 516-MOF-based electrochemical biosensor not only demonstrated high sensitivity with low detection limits of 0.70 and 0.40pgmL -1 toward vomitoxin and salbutamol, respectively, but also showed good selectivity in the presence of other interferences. Therefore, with the advantages of high sensitivity, good selectivity, and simple operation, this new strategy is believed to exhibit great potential for simple and convenient detection of poisonous and harmful residues in food. Copyright © 2017 Elsevier B.V. All rights reserved.
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Mazzoni, Michela; Boggio, Emanuela; Manca, Marina; Piscia, Roberta; Quadroni, Silvia; Bellasi, Arianna; Bettinetti, Roberta
2018-05-30
Despite DDT and PCB having been banned for about 40 years, they are still detectable in the environment. In the present research we specifically investigated the trophic transfer of these organochlorine contaminants (OC) through a pelagic food web of a deep lake in Northern Italy (Lake Como) over time. Zooplankton and fish were sampled each season of a year and OC concentrations and the carbon and nitrogen isotopic ratios were measured. By using stable isotopes, the direct trophic relationship between pelagic zooplankton and zooplanktivorous fish was confirmed for Alosa agone only in summer. Based on this result, the biomagnification factor normalized on the trophic level (BMF TL ) for organic contaminants was calculated. BMF TL values were within the range 0.9-1.9 for DDT isomers and 1.6-4.9 for some PCB congeners (PCB 95, PCB 101, PCB 149, PCB 153, PCB 138 - present both in zooplankton and in fish and representing >60% of the PCB contamination), confirming the biomagnification of these compounds in one of the two zooplanktivorous fish species of the lake. Copyright © 2018. Published by Elsevier B.V.
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Ramirez-Valles, Jesus; Kuhns, Lisa M.; Manjarrez, Dianna
2013-01-01
In this paper we describe the development and dissemination of a film-based educational intervention to reduce negative attitudes towards gay and bisexual men and transgender women (GBT) and people living with HIV/AIDS (PLWHA) in Latino communities, with a focus on youth. The intervention, Tal Como Somos/Just as We Are, is based on stigma and attribution theories, extensive formative research, and community input. Evaluation findings among educators and school youth suggest the film has the potential to effectively impact attitudes towards GBT and PLWHA. The film and intervention are being disseminated using diffusion of innovations theory through community-based organizations, schools, television broadcasting and film festivals. PMID:24377496
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Nanospray mass spectrometry with indirect conductive graphite coating.
Viberg, Peter; Nilsson, Staffan; Skog, Kerstin
2004-07-15
An easy and cost-effective method to manufacture a robust conductive graphite coating for nanospray mass spectrometry (nESI-MS) and capillary electrophoresis (CE)-nESI-MS is described. The method involves graphite coating of a tube sleeve, into which the nESI emitter is inserted and connected to a transfer capillary, instead of coating the actual emitter. The coating, made of graphite from a pencil and epoxy glue, was stable over long periods of use (>80 h) and showed excellent resistance toward various solvents. Stable electrospray was achieved in the investigated flow range (150-900 nL x min(-)(1)), and salbutamol, diphenhydramine, and nortriptyline (M(w): 239-263 g x mol(-)(1)) were detected in the nanomole per liter range during continuous pumping. CE-nESI-MS analysis gave excellent signal-to-noise ratios for 100-fmol injections. The technique allows simple exchange of the nESI emitter to suit a specific flow rate, and it minimizes risk of corona discharge.
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Analysis of antigen-induced changes in pulmonary mechanics in sensitized inbred rats.
Holroyde, M C; Smith, S Y; Holme, G
1982-05-01
An inbred line of rats was derived which develop marked and consistent dyspnea following sensitization and then exposure to aerosolized antigen. This pulmonary response was investigated in detail by determining forced pulmonary mechanics to derive respiratory rate, peak expiratory flow rate (PEFR), forced vital capacity (FVC), forced expiratory volume in 0.1 s (FEV0.1), and maximal midexpiratory flow rate (MMFR). Challenging anesthetized rats for 5 min with an aerosol of 3% egg albumin produced minimal change in respiratory rate, a 20% fall in PEFR, a 50% fall in FVC, and a 30% decrease in FEV0.1 and MMFR. The response could be inhibited or reversed by salbutamol (0.5 mg/kg, i.v.) and aminophylline (25 mg/kg, i.v.) administered either before or after challenge. The pulmonary changes are consistent with antigen-induced asthma in the rats. The response shows similarities to human asthma and may provide a relevant experimental model.
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Inhibition of artificially induced cough in man by bronchodilators.
Lowry, R; Higenbottam, T; Johnson, T; Godden, D
1987-01-01
1. The antitussive properties of bronchodilators were evaluated in a total of 47 normal volunteers. 2. Cough was induced by inhalation of ultrasonically nebulized solutions of distilled water and hypotonic saline. 3. Inhaled fenoterol hydrobromide (360 micrograms; 20 volunteers) and inhaled ipratropium bromide (72 micrograms; 14 volunteers) both significantly reduced couch compared with placebo (P less than 0.01). Oral salbutamol sulphate (4 mg; 11 volunteers) and oral pirenzepine hydrochloride (50 mg; 14 volunteers) had lesser effects. 4. Cough inhibition correlated with a small but statistically significant degree of bronchodilatation as measured by specific airway conductance (sGaw) and forced expiratory volume in one second (FEV1) in six normal subjects studied with each treatment in a placebo controlled, double blind study (r = 0.67, P less than 0.001). 5. Small reductions in airway tone are associated with a reduced cough response elicited by inhaled ultrasonically nebulized distilled water. PMID:3689630
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A brief history of inhaled asthma therapy over the last fifty years.
Crompton, Graham
2006-12-01
This year is the 50th anniversary of the introduction into clinical use of the first modern inhaler for the management of asthma--the pressurised metered-dose inhaler (pMDI). The pMDI was initially used for the administration of the non-selective beta-agonists adrenaline and isoprenaline. However, the epidemic of asthma deaths which occurred in the 1960s led to these drugs being superseded by the selective short-acting beta-agonist salbutamol, and the first inhaled corticosteroid (ICS) beclomethasone. At the same time, sodium cromoglycate was introduced, to be administered via the first dry-powder inhaler--the Spinhaler--but owing to its relatively weak anti-inflammatory action its use is now very limited. Over the last 10 years, the long-acting beta-agonists (LABAs) have become an important add-on therapy for the management of asthma, and they are now often used with ICS in a single ICS/LABA combination inhaler.
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Bosak, Anita; Knežević, Anamarija; Gazić Smilović, Ivana; Šinko, Goran; Kovarik, Zrinka
2017-12-01
We investigated the influence of bronchodilating β2-agonists on the activity of human acetylcholinesterase (AChE) and usual, atypical and fluoride-resistant butyrylcholinesterase (BChE). We determined the inhibition potency of racemate and enantiomers of fenoterol as a resorcinol derivative, isoetharine and epinephrine as catechol derivatives and salbutamol and salmeterol as saligenin derivatives. All of the tested compounds reversibly inhibited cholinesterases with K i constants ranging from 9.4 μM to 6.4 mM and had the highest inhibition potency towards usual BChE, but generally none of the cholinesterases displayed any stereoselectivity. Kinetic and docking results revealed that the inhibition potency of the studied compounds could be related to the size of the hydroxyaminoethyl chain on the benzene ring. The additional π-π interaction of salmeterol's benzene ring and Trp286 and hydrogen bond with His447 probably enhanced inhibition by salmeterol which was singled out as the most potent inhibitor of all the cholinesterases.
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Patterns of pregnancy exposure to prescription FDA C, D and X drugs in a Canadian population.
Wen, S W; Yang, T; Krewski, D; Yang, Q; Nimrod, C; Garner, P; Fraser, W; Olatunbosun, O; Walker, M C
2008-05-01
To examine prescription Food and Drug Administration (FDA) C, D and X drugs in general obstetric population. Historical cohort study. A total of 18 575 women who gave a birth in Saskatchewan between January 1997 and December 2000 were included. Among them, 3604 (19.4%) received FDA C, D or X drugs at least once during pregnancy. The pregnancy exposure rates were 15.8, 5.2 and 3.9%, respectively, for category C, D and X drugs, and were 11.2, 7.3 and 8.2%, respectively, in the first, second and third trimesters. Salbutamol (albuterol), trimethoprim/sulfamethoxazole (co-trimoxazole), ibuprofen, naproxen and oral contraceptives were the most common C, D, X drugs used during pregnancy. About one in every five women uses FDA C, D and X drugs at least once during pregnancy, and the most common prescription drugs in pregnancy are antiasthmatic, antibiotics, nonsteroid anti-inflammation drugs, antianxiety or antidepressants and oral contraceptives.
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Ramirez-Valles, Jesus; Kuhns, Lisa M; Manjarrez, Dianna
2014-04-01
In this article, the authors describe the development and dissemination of a film-based educational intervention to reduce negative attitudes toward gay and bisexual men, transgender women, and people living with HIV/AIDS in Latino communities, with a focus on youth. The intervention, Tal Como Somos/Just as We Are, is based on stigma and attribution theories, extensive formative research, and community input. Evaluation findings among educators and school youth suggest the film has the potential to effectively influence attitudes toward gay and bisexual men, transgender women, and people living with HIV/AIDS. The film and intervention are being disseminated using diffusion of innovations theory through community-based organizations, schools, television broadcasting, and film festivals.
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Olaizola, Inés; Caorsi, Hena; Fajardo, Laura; Ferreiro, Alejandro; Campistrus, Nieves; Dolinsky, Deyanira; Petraglia, Alicia; Ambrosoni, Pablo
2016-01-01
administrado durante um período de 6 meses no tratamento do hiperparatireoidismo secundário (SHPT) em pacientes submetidos a hemodiálise convencional, com acompanhamento de perto da resposta do tratamento. Realizou-se um ensaio clínico de fase 4 que comparava os dados clínicos com os dados do laboratório antes e depois dos 6 meses de tratamento. Incluíram-se os pacientes SHPT em hemodiálise sem experiência com os metabólitos da vitamina D ou que fracassaram com a terapia em uso. Analisaram-se as características clínicas e de laboratório. As análises de eficácia se basearam nos níveis do hormônio da paratireóide intacto (iPTH) e foram realizadas usando dados dos pacientes que completaram os 6 meses de tratamento. Dezenove dos 26 pacientes registrados completaram os 6 meses de tratamento. Todos os pacientes mostraram níveis de referência iPTH reduzidos (redução média, 371,8 pg/mL; 95% CI, 273,3-470.2 pg/mL]; 17 pacientes (89,5%) tiveram reduções superiores a 30%. Doze pacientes (63%) conseguiram o sucesso terapêutico (definido como níveis de soros iPTH de 150-300 pg/mL), com um tempo médio de 2 meses a partir do início do tratamento. Todos os episódios de hipercalcemia (n = 2) e de hiperfosfatemia (n = 34) reportados foram assintomáticos. Não se informaram AEs graves importantes relacionados à terapia. O paricalcitol foi administrado de forma segura e se associou às reduções significativas nos níveis de iPTH durante o período do estudo.
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Staszak-Jirkovský, Jakub; Malliakas, Christos D.; Lopes, Pietro P.; ...
2015-11-30
Three of the fundamental catalytic limitations that have plagued the electrochemical production of hydrogen for decades still remain: low efficiency, short lifetime of catalysts and a lack of low-cost materials. Here, we address these three challenges by establishing and exploring an intimate functional link between the reactivity and stability of crystalline (CoS 2 and MoS 2) and amorphous (CoS x and MoS x) hydrogen evolution catalysts. We propose that Co 2+ and Mo 4+ centers promote the initial discharge of water (alkaline solutions) or hydronium ions (acid solutions). We establish that although CoS x materials are more active than MoSmore » x they are also less stable, suggesting that the active sites are defects formed after dissolution of Co and Mo cations. Finally, by combining the higher activity of CoS x building blocks with the higher stability of MoS x units into a compact and robust CoMoS x structure, we are able to design a low-cost alternative to noble metal catalysts for efficient electrocatalytic production of hydrogen in both alkaline and acidic environments.« less
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Drug delivery to the human and mouse uterus using immunoliposomes targeted to the oxytocin receptor.
Paul, Jonathan W; Hua, Susan; Ilicic, Marina; Tolosa, Jorge M; Butler, Trent; Robertson, Sarah; Smith, Roger
2017-03-01
The ability to provide safe and effective pharmacotherapy during obstetric complications, such as preterm labor or postpartum hemorrhage, is hampered by the systemic toxicity of therapeutic agents leading to adverse side effects in the mother and fetus. Development of novel strategies to target tocolytic and uterotonic agents specifically to uterine myocytes would improve therapeutic efficacy while minimizing the risk of side effects. Ligand-targeted liposomes have emerged as a reliable and versatile platform for targeted drug delivery to specific cell types, tissues or organs. Our objective was to develop a targeted drug delivery system for the uterus utilizing an immunoliposome platform targeting the oxytocin receptor. We conjugated liposomes to an antibody that recognizes an extracellular domain of the oxytocin receptor. We then examined the ability of oxytocin receptor-targeted liposomes to deliver contraction-blocking (nifedipine, salbutamol and rolipram) or contraction-enhancing (dofetilide) agents to strips of spontaneously contracting myometrial tissue in vitro (human and mouse). We evaluated the ability of oxytocin receptor-targeted liposomes to localize to uterine tissue in vivo, and assessed if targeted liposomes loaded with indomethacin were capable of preventing lipopolysaccharide-induced preterm birth in mice. Oxytocin receptor-targeted liposomes loaded with nifedipine, salbutamol or rolipram consistently abolished human myometrial contractions in vitro, while oxytocin receptor-targeted liposomes loaded with dofetilide increased contraction duration. Nontargeted control liposomes loaded with these agents had no effect. Similar results were observed in mouse uterine strips. Following in vivo administration to pregnant mice, oxytocin receptor-targeted liposomes localized specifically to the uterine horns and mammary tissue. Targeting increased localization to the uterus 7-fold. Localization was not detected in the maternal brain or fetus. Targeted
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DIABETES MELLITUS COMO FACTOR DE RIESGO DE DEMENCIA EN LA POBLACIÓN ADULTA MAYOR MEXICANA
Silvia, Mejía-Arango; Clemente, y Zúñiga-Gil
2012-01-01
Introduccion La diabetes mellitus y las demencias constituyen dos problemas crecientes de salud entre la población adulta mayor del mundo y en particular de los paises en desarrollo. Hacen falta estudios longitudinales sobre el papel de la diabetes como factor de riesgo para demencia. Objetivo Determinar el riesgo de demencia en sujetos Mexicanos con diabetes mellitus tipo 2. Materiales y Metodos Los sujetos diabéticos libres de demencia pertenecientes al Estudio Nacional de Salud y Envejecimiento en México fueron evaluados a los dos años de la línea de base. Se estudió el papel de los factores sociodemográficos, de otras comorbilidades y del tipo de tratamiento en la conversión a demencia. Resultados Durante la línea de base 749 sujetos (13.8%) tuvieron diabetes. El riesgo de desarrollar demencia en estos individuos fue el doble (RR, 2.08 IC 95%, 1.59–2.73). Se encontró un riesgo mayor en individuos de 80 años y más (RR 2.44 IC 95%, 1.46–4.08), en los hombres (RR, 2.25 IC 95%, 1.46–3.49) y en sujetos con nivel educativo menor de 7 años. El estar bajo tratamiento con insulina incrementó el riesgo de demencia (RR, 2.83, IC 95%, 1.58–5.06). Las otras comorbilidades que aumentaron el riesgo de demencia en los pacientes diabéticos fueron la hipertensión (RR, 2.75, IC 95%, 1.86–4.06) y la depresión (RR, 3.78, 95% IC 2.37–6.04). Conclusión Los sujetos con diabetes mellitus tienen un riesgo mayor de desarrollar demencia, La baja escolaridad y otras comorbilidades altamente prevalentes en la población Mexicana contribuyen a la asociación diabetes-demencia. PMID:21948010
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Rotifer neuropharmacology--III. Adrenergic drug effects on Brachionus plicatilis.
Keshmirian, J; Nogrady, T
1987-01-01
Norepinephrine (NE) induces three pharmacological effects in Brachionus plicatilis. As a result of excitation the rate of ciliary motion and swimming increases, and the animals flip their foot constantly at a rapid rate. This rapid foot flipping was used as a specific model to measure adrenergic effects in B. plicatilis. Phenylephrine induces the same effect at identical efficacy, while isoproterenol and salbutamol, two beta-agonists, show one-half and one-tenth NE efficacy. The beta blocker propranolol and the alpha blocker tolazoline both antagonize foot flipping induced by NE. However, propranolol shows antagonism because it causes foot paralysis by itself. Timolol, another beta blocker but without the membrane effect of propranolol, does not antagonize the alpha receptor mediated NE effect, nor does it cause foot paralysis. Propranolol, timolol and tolazoline also show agonist activity, inducing foot flipping. NE does not antagonize the foot paralysis induced by propranolol, only its anesthetic effect by delaying its onset. These results indicate that the foot flipping induced by NE is a receptor-mediated alpha adrenergic effect, while the foot paralysis is caused by membrane phenomena.
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beta. -Adrenoceptors in human tracheal smooth muscle: characteristics of binding and relaxation
DOE Office of Scientific and Technical Information (OSTI.GOV)
van Koppen, C.J.; Hermanussen, M.W.; Verrijp, K.N.
1987-06-29
Specific binding of (/sup 125/I)-(-)-cyanopindolol to human tracheal smooth muscle membranes was saturable, stereo-selective and of high affinity (K/sub d/ = 5.3 +/- 0.9 pmol/l and R/sub T/ = 78 +/- 7 fmol/g tissue). The ..beta../sub 1/-selective antagonists atenolol and LK 203-030 inhibited specific (/sup 125/I)-(-)-cyanopindolol binding according to a one binding site model with low affinity in nearly all subjects, pointing to a homogeneous BETA/sub 2/-adrenoceptor population. In one subject using LK 203-030 a small ..beta../sub 1/-adrenoceptor subpopulation could be demonstrated. The beta-mimetics isoprenaline, fenoterol, salbutamol and terbutaline recognized high and low affinity agonist binding sites. Isoprenaline's pK/sub H/-more » and pK/sub L/-values for the high and low affinity sites were 8.0 +/- 0.2 and 5.9 +/- 0.3 respectively. In functional experiments isoprenaline relaxed tracheal smooth muscle strips having intrinsic tone with a pD/sub 2/-value of 6.63 +/- 0.19. 32 references, 4 figures, 2 tables.« less
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Nguyen, Thi Anh Huong; Pham, Thi Ngoc Mai; Doan, Thi Tuoi; Ta, Thi Thao; Sáiz, Jorge; Nguyen, Thi Quynh Hoa; Hauser, Peter C; Mai, Thanh Duc
2014-09-19
An inexpensive, robust and easy to use portable capillary electrophoresis instrument with miniaturized high-voltage capacitively coupled contactless conductivity detection was developed. The system utilizes pneumatic operation to manipulate the solutions for all flushing steps. The different operations, i.e. capillary flushing, interface rinsing, and electrophoretic separation, are easily activated by turning an electronic switch. To allow the analysis of samples with limited available volume, and to render the construction less complicated compared to a computer-controlled counterpart, sample injection is carried out hydrodynamically directly from the sample vial into the capillary by manual syphoning. The system is a well performing solution where the financial means for the highly expensive commercial instruments are not available and where the in-house construction of a sophisticated automated instrument is not possible due to limited mechanical and electronic workshop facilities and software programming expertise. For demonstration, the system was employed successfully for the determination of some β-agonists, namely salbutamol, metoprolol and ractopamine down to 0.7ppm in pharmaceutical and pig-feed sample matrices in Vietnam. Copyright © 2014 Elsevier B.V. All rights reserved.
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Fitzgerald, C; Hosny, N A; Tong, H; Seville, P C; Gallimore, P J; Davidson, N M; Athanasiadis, A; Botchway, S W; Ward, A D; Kalberer, M; Kuimova, M K; Pope, F D
2016-08-21
We describe a technique to measure the viscosity of stably levitated single micron-sized aerosol particles. Particle levitation allows the aerosol phase to be probed in the absence of potentially artefact-causing surfaces. To achieve this feat, we combined two laser based techniques: optical trapping for aerosol particle levitation, using a counter-propagating laser beam configuration, and fluorescent lifetime imaging microscopy (FLIM) of molecular rotors for the measurement of viscosity within the particle. Unlike other techniques used to measure aerosol particle viscosity, this allows for the non-destructive probing of viscosity of aerosol particles without interference from surfaces. The well-described viscosity of sucrose aerosol, under a range of relative humidity conditions, is used to validate the technique. Furthermore we investigate a pharmaceutically-relevant mixture of sodium chloride and salbutamol sulphate under humidities representative of in vivo drug inhalation. Finally, we provide a methodology for incorporating molecular rotors into already levitated particles, thereby making the FLIM/optical trapping technique applicable to real world aerosol systems, such as atmospheric aerosols and those generated by pharmaceutical inhalers.
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Xu, Dongsheng; Shao, Huikai; Luo, Rongying; Wang, Qiqin; Sánchez-López, Elena; Fanali, Salvatore; Marina, Maria Luisa; Jiang, Zhengjin
2018-07-06
A facile single-step preparation strategy for fabricating vancomycin functionalized organic polymer-based monolith within 100μm fused-silica capillary was developed. The synthetic chiral functional monomer, i.e 2-isocyanatoethyl methacrylate (ICNEML) derivative of vancomycin, was co-polymerized with the cross-linker ethylene dimethacrylate (EDMA) in the presence of methanol and dimethyl sulfoxide as the selected porogens. The co-polymerization conditions were systematically optimized in order to obtain satisfactory column performance. Adequate permeability, stability and column morphology were observed for the optimized poly(ICNEML-vancomycin-co-EDMA) monolith. A series of chiral drugs were evaluated on the monolith in either polar organic-phase or reversed-phase modes. After the optimization of separation conditions, baseline or partial enantioseparation were obtained for series of drugs including thalidomide, colchicine, carteolol, salbutamol, clenbuterol and several other β-blockers. The proposed single-step approach not only resulted in a vancomycin functionalized organic polymer-based monolith with acceptable performance, but also significantly simplified the preparation procedure by reducing time and labor. Copyright © 2018 Elsevier B.V. All rights reserved.
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Liou, Saou-Hsing; Yang, Gordon C C; Wang, Chih-Lung; Chiu, Yu-Han
2014-07-30
This 5-month study contains two parts: (1) to monitor the concentrations of 11 phthalate esters metabolites (PAEMs) and two beta-agonists in human urine samples collected from a small group of consented participants including 16 females and five males; and (2) to analyze the residues of phthalate esters (PAEs) and beta-agonists in various categories of drinking water consumed by the same group of subjects. Each category of human urine and drinking water had 183 samples of its own. The analytical results showed that nine PAEMs were detected in human urine and eight PAEs were detected in drinking water samples. It was found that average concentrations of PAEMs increased as the age increased, but no significant difference between sexes. Further, using the principal component analysis, the loadings of age effect were found to be two times greater than that of gender effect in terms of four DEHP metabolites. Regarding beta-agonists of concern (i.e., ractopamine and salbutamol), they were neither detected in human urine nor drinking water samples in this study. Copyright © 2014 Elsevier B.V. All rights reserved.
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Treatment of Cutaneous Lupus Erythematosus
Kim, Grace K.; Del Rosso, James Q.
2013-01-01
The treatment of cutaneous lupus erythematosus is centered upon formulating a regimen of topical and systemic therapies designed to reduce disease activity and minimize cosmetic damage. Sun avoidance and sunscreen are important preventative measures proven to minimize cutaneous lupus erythematosus exacerbations. Limited disease is typically managed with topical corticosteroids or calcineurin inhibitors. Antimalarial therapy is the gold standard of systemic therapy. Many other treatments have been studied in patients with recalcitrant cutaneous lupus erythematosus, and their use must be evaluated based on individual risk-benefit concerns. R-salbutamol and pulsed dye laser therapy have proven to be effective topical alternatives. Additional systemic agents include retinoids, immunosuppressants, immunomodulators, biologics, and other experimental therapies with novel modes of action. According to the Oxford Centre for Evidence-based Medicine criteria for evaluating the strength of evidence supporting an individual treatment measure, no therapy for cutaneous lupus erythematosus has achieved Level 1 status. This demonstrates the need for randomized, controlled trials and systematic reviews of all cutaneous lupus erythematosus interventions in order to meet increasing standards and demand for evidence-based practice. PMID:23320123
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NASA Astrophysics Data System (ADS)
Roncoli, Carla; Kirshen, Paul; Etkin, Derek; Sanon, Moussa; Somé, Léopold; Dembélé, Youssouf; Sanfo, Bienvenue J.; Zoungrana, Jacqueline; Hoogenboom, Gerrit
2009-10-01
This study focuses on the potential role of technical and institutional innovations for improving water management in a multi-user context in Burkina Faso. We focus on a system centered on three reservoirs that capture the waters of the Upper Comoé River Basin and servicing a diversity of users, including a sugar manufacturing company, a urban water supply utility, a farmer cooperative, and other downstream users. Due to variable and declining rainfall and expanding users’ needs, drastic fluctuations in water supply and demand occur during each dry season. A decision support tool was developed through participatory research to enable users to assess the impact of alternative release and diversion schedules on deficits faced by each user. The tool is meant to be applied in the context of consultative planning by a local user committee that has been created by a new national integrated water management policy. We contend that both solid science and good governance are instrumental in realizing efficient and equitable water management and adaptation to climate variability and change. But, while modeling tools and negotiation platforms may assist users in managing climate risk, they also introduce additional uncertainties into the deliberative process. It is therefore imperative to understand how these technological and institutional innovations frame water use issues and decisions to ensure that such framing is consistent with the goals of integrated water resource management.
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Oxygen as a driving gas for nebulisers: safe or dangerous?
Gunawardena, K A; Patel, B; Campbell, I A; MacDonald, J B; Smith, A P
1984-01-28
Changes in blood gas tensions occurring when 100% oxygen or air was used as the driving gas for nebulised salbutamol were studied in 23 patients with severe airways obstruction. The patients fell into three groups: nine had chronic bronchitis and emphysema with carbon dioxide retention, seven had emphysema and chronic bronchitis without carbon dioxide retention, and seven had severe asthma (no carbon dioxide retention). When oxygen was used as the driving gas patients who retained carbon dioxide showed a mean rise of 1.03 kPa (7.7 mm Hg) in their pressure of carbon dioxide (Pco2) after 15 minutes (p less than 0.001) but the Pco2 returned to baseline values within 20 minutes of stopping the nebuliser. The other two groups showed no rise in Pco2 with oxygen. When air was used as the driving gas none of the groups became significantly more hypoxic. Although it is safe to use oxygen as the driving gas for nebulisers in patients with obstructive airways disease with normal Pco2, caution should be exercised in those who already have carbon dioxide retention.
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Langford, Katherine H; Reid, Malcolm; Thomas, Kevin V
2011-08-01
A robust multi-residue method was developed for the analysis of a selection of pharmaceutical compounds, illicit drugs and personal care product bactericides in sediments and sludges. Human pharmaceuticals were selected for analysis in Scottish sewage sludge and freshwater sediments based on prescription, physico-chemical and occurrence data. The method was suitable for the analysis of the selected illicit drugs amphetamine, benzoylecgonine, cocaine, and methamphetamine, the pharmaceuticals atenolol, bendroflumethiazide, carbamazepine, citalopram, diclofenac, fluoxetine, ibuprofen, and salbutamol, and the bactericides triclosan and triclocarban in sewage sludge and freshwater sediment. The method provided an overall recovery of between 56 and 128%, RSDs of between 2 and 19% and LODs of between 1 and 50 ng g(-1). Using the methodology the human pharmaceuticals atenolol, carbamazepine and citalopram and the bactericides triclosan and triclocarban were detected in Scottish sewage sludge. The illicit drugs cocaine, its metabolite benzoylecgonine, amphetamine and methamphetamine were not detected in any of the samples analysed. Triclosan and triclocarban were present at the highest concentrations with triclocarban detected in all but one sample and showing a pattern of co-occurrence in both sludge and sediment samples.
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Taylor, S M; Paré, P D; Armour, C L; Hogg, J C; Schellenberg, R R
1985-07-01
This study aimed to determine whether in vivo airways hyperreactivity was manifested by either enhanced bronchial smooth muscle responses to contractile stimuli or by deficient responses to relaxant stimuli in vitro. Quantitative responses to nebulized methacholine were obtained in 12 human subjects prior to pulmonary resection. The provocative concentration of methacholine producing a 20% reduction in FEV1 (PC20) was calculated, and these values were compared with in vitro responses of bronchial smooth muscle strips from the surgical specimens. Both contractile cholinergic responses and relaxant nonadrenergic noncholinergic dose-response data were obtained for the in vitro bronchial specimens by electrical field stimulation. In addition, cumulative dose responses were obtained to exogenously added methacholine, the beta-adrenergic agonist salbutamol, and the adenylate cyclase activator forskolin. Despite a wide range of PC20 values, the in vivo airway responsiveness did not correlate with any of the in vitro responses examined, suggesting that airway reactivity is not due solely to the responsiveness of smooth muscle to contractile agonists nor to a localized deficiency in the nonadrenergic inhibitory system, beta-adrenergic inhibition, or abnormal cyclic-AMP-mediated pathways of relaxation.
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Cossío-Bayúgar, Raquel; Miranda-Miranda, Estefan; Fernández-Rubalcaba, Manuel; Narváez Padilla, Verónica; Reynaud, Enrique
2015-01-01
The tyraminergic/octopaminergic system is central for the control of arthropod oviposition. Previous works demonstrated that the pharmacological perturbation of this system inhibits oviposition in the cattle tick Rhipicephalus microplus. In this work, we describe a physiologically active whole-mount preparation of the contractile tick ovary that allows the quantitative videometrical analysis of ovary contraction in response to different compounds. Eight adrenergic ligands known to inhibit oviposition, including octopamine and tyramine were tested. These compounds exhibited antagonistic effects; octopamine relaxes the ovary preparation while tyramine induces a very strong contraction. The other adrenergic compounds tested were classified as able to contract or relax ovary muscle tissue. Isoprotenerol has a stronger relaxative effect than octopamine. Tyramine induces the biggest contraction observed of all the compounds tested, followed, in descending amount of contraction, by salbutamol, prazosin, epinastine, clonidine and the acaricide amitraz. The effect of these adrenergic ligands on the ovary preparation, explains why these molecules inhibit tick oviposition and suggest a regulatory mechanism for ovary contraction and relaxation during oviposition. Our results also provide a physiological explanation of the egg-laying inhibition effect of amitraz when used on the cattle tick. PMID:26456007
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Cossío-Bayúgar, Raquel; Miranda-Miranda, Estefan; Fernández-Rubalcaba, Manuel; Narváez Padilla, Verónica; Reynaud, Enrique
2015-10-12
The tyraminergic/octopaminergic system is central for the control of arthropod oviposition. Previous works demonstrated that the pharmacological perturbation of this system inhibits oviposition in the cattle tick Rhipicephalus microplus. In this work, we describe a physiologically active whole-mount preparation of the contractile tick ovary that allows the quantitative videometrical analysis of ovary contraction in response to different compounds. Eight adrenergic ligands known to inhibit oviposition, including octopamine and tyramine were tested. These compounds exhibited antagonistic effects; octopamine relaxes the ovary preparation while tyramine induces a very strong contraction. The other adrenergic compounds tested were classified as able to contract or relax ovary muscle tissue. Isoprotenerol has a stronger relaxative effect than octopamine. Tyramine induces the biggest contraction observed of all the compounds tested, followed, in descending amount of contraction, by salbutamol, prazosin, epinastine, clonidine and the acaricide amitraz. The effect of these adrenergic ligands on the ovary preparation, explains why these molecules inhibit tick oviposition and suggest a regulatory mechanism for ovary contraction and relaxation during oviposition. Our results also provide a physiological explanation of the egg-laying inhibition effect of amitraz when used on the cattle tick.
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Lui, Kung-Jong; Chang, Kuang-Chao
2016-10-01
When the frequency of event occurrences follows a Poisson distribution, we develop procedures for testing equality of treatments and interval estimators for the ratio of mean frequencies between treatments under a three-treatment three-period crossover design. Using Monte Carlo simulations, we evaluate the performance of these test procedures and interval estimators in various situations. We note that all test procedures developed here can perform well with respect to Type I error even when the number of patients per group is moderate. We further note that the two weighted-least-squares (WLS) test procedures derived here are generally preferable to the other two commonly used test procedures in the contingency table analysis. We also demonstrate that both interval estimators based on the WLS method and interval estimators based on Mantel-Haenszel (MH) approach can perform well, and are essentially of equal precision with respect to the average length. We use a double-blind randomized three-treatment three-period crossover trial comparing salbutamol and salmeterol with a placebo with respect to the number of exacerbations of asthma to illustrate the use of these test procedures and estimators. © The Author(s) 2014.
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Hyperosmolar diabetic non-ketotic coma, hyperkalaemia and an unusual near death experience.
Ting, J Y
2001-03-01
Generally, cardiac arrest due to pulseless electrical activity has a poor outcome, except when reversible factors such as acute hyperkalaemia are identified and managed early. Hyperosmolar diabetic non-ketotic coma may lead to acute hyperkalaemia. Hyperosmolar diabetic non-ketotic coma is a metabolic emergency usually seen in elderly non-insulin dependent diabetics, characterized by severe hyperglycaemia, volume depletion, altered consciousness, confusion and less frequently neurological deficit. Cerebrovascular accident or transient ischaemic attack may be mistakenly diagnosed, particularly if the patient has no history of diabetes mellitus. Delays in diagnosis and management of glycaemic emergencies presenting as a constellation of neurological abnormalities can be avoided by routine early measurement of blood glucose. Hyperosmolar diabetic non-ketotic coma should be considered in any patient with altered consciousness or neurologic deficit in conjunction with hyperglycaemia. As hyperosmolar diabetic non-ketotic coma results in severe fluid depletion, electrolyte disturbance, profound hyperglycaemia and an altered mental state, the guiding principles of therapy include aggressive rehydration, insulin therapy, correction of electrolyte abnormalities and treatment of any underlying illnesses. Treatment of acute hyperkalaemia includes calcium ions, insulin with dextrose, salbutamol and haemodialysis.
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Deerojanawong, J; Prapphal, N
1994-07-01
The responsiveness to bronchodilator is variable in infants with wheezing associated respiratory illness (WARI). Factors for prediction of the response will lead to more rational use of the bronchodilator in these infants. We examined the possible predictive factors in 44 children under 2 years of age who had their first episode of WARI. All of them were treated with 0.15 mg/kg of nebulized salbutamol. Thirty patients (68%) with decreasing clinical score > or = 3 after treatment were considered as the responders while the remainder (14 infants) were non responders. By using Chi-square test, Fisher exact test and Mann-Whitney U test to compare the data of the 2 groups, the significant factors for the responders were older than 6 months and history of previous LRI (p < 0.01). The significant factors for the non-responders included concurrent diarrhea, patchy pulmonary infiltration and positive RSV in the nasopharyngeal secretion (p < 0.01). These results suggested effective bronchodilator therapy in infants older than 6 months or having a history of previous LRI. Those who had acute RSV infection or patchy infiltration in chest X-ray and associated diarrhea were less likely to respond.
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Jones, Matthew D; Buckton, Graham
2016-07-25
The abilities of the cohesive-adhesive balance approach to atomic force microscopy (AFM) and the measurement of Hansen partial solubility parameters by inverse gas chromatography (IGC) to predict the performance of carrier-based dry powder inhaler (DPI) formulations were compared. Five model drugs (beclometasone dipropionate, budesonide, salbutamol sulphate, terbutaline sulphate and triamcinolone acetonide) and three model carriers (erythritol, α-lactose monohydrate and d-mannitol) were chosen, giving fifteen drug-carrier combinations. Comparison of the AFM and IGC interparticulate adhesion data suggested that they did not produce equivalent results. Comparison of the AFM data with the in vitro fine particle delivery of appropriate DPI formulations normalised to account for particle size differences revealed a previously observed pattern for the AFM measurements, with a slightly cohesive AFM CAB ratio being associated with the highest fine particle fraction. However, no consistent relationship between formulation performance and the IGC data was observed. The results as a whole highlight the complexity of the many interacting variables that can affect the behaviour of DPIs and suggest that the prediction of their performance from a single measurement is unlikely to be successful in every case. Copyright © 2016 Elsevier B.V. All rights reserved.
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Recessive variants of MuSK are associated with late onset CMS and predominant limb girdle weakness.
Owen, David; Töpf, Ana; Preethish-Kumar, Veeramani; Lorenzoni, Paulo José; Vroling, Bas; Scola, Rosana Herminia; Dias-Tosta, Elza; Geraldo, Argemiro; Polavarapu, Kiran; Nashi, Saraswati; Cox, Daniel; Evangelista, Teresinha; Dawson, John; Thompson, Rachel; Senderek, Jan; Laurie, Steven; Beltran, Sergi; Gut, Marta; Gut, Ivo; Nalini, Atchayaram; Lochmüller, Hanns
2018-04-28
Congenital myasthenic syndrome (CMS) is a heterogeneous disorder that causes fatigable muscle weakness. CMS has been associated with variants in the MuSK gene and, to date, 16 patients have been reported. MuSK-CMS patients present a different phenotypic pattern of limb girdle weakness. Here, we describe four additional patients and discuss the phenotypic and clinical relationship with those previously reported. Two novel damaging missense variants are described: c.1742T > A; p.I581N found in homozygosis, and c.1634T > C; p.L545P found in compound heterozygosis with p.R166*. The reported patients had predominant limb girdle weakness with symptom onset at 12, 17, 18, and 30 years of age, and the majority exhibited a good clinical response to Salbutamol therapy, but not to esterase inhibitors. Meta-analysis including previously reported variants revealed an increased likelihood of a severe, respiratory phenotype with null alleles. Missense variants exclusively affecting the kinase domain, but not the catalytic site, are associated with late onset. These data refine the phenotype associated with MuSK-related CMS. © 2018 Wiley Periodicals, Inc.
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Wilson, Jennifer T.; Van Metre, Peter C.; Werth, Charles J.; Yang, Yanning
2006-01-01
A previous study by the U.S. Geological Survey of impaired water bodies in Fort Worth, Texas, reported elevated but variable concentrations of particle-associated contaminants (PACs) comprising chlorinated hydrocarbons, polycyclic aromatic hydrocarbons, and trace elements in suspended and bed sediment of lakes and streams affected by urban land use. The U.S. Geological Survey, in cooperation with the City of Fort Worth, collected additional samples during October 2004 to investigate sources of PACs in the watersheds of two impaired lakes: Lake Como and Fosdic Lake. Source materials and aquatic sediment were sampled and analyzed for PACs. Source materials sampled consisted of street dust and soil from areas with residential and commercial land use and parking lot dust from sealed and unsealed parking lots. Aquatic sediment sampled consisted of bottom-sediment cores from the two lakes and suspended and streambed sediment from the influent stream of each lake. Samples were analyzed for chlorinated hydrocarbons (organochlorine pesticides and polychlorinated biphenyls), polycyclic aromatic hydrocarbons, major and trace elements, organic carbon, grain size, and radionuclides.
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Characterization and pharmacodynamic properties of Arnica montana complex.
Šutovská, M; Capek, P; Kočmalová, M; Pawlaczyk, I; Zaczyńska, E; Czarny, A; Uhliariková, I; Gancarz, R; Fraňová, S
2014-08-01
A dark brown polymeric complex was isolated from flowering parts of medicinal plant Arnica montana L. by hot alkaline extraction followed by neutralization and multi-step extractions with organic solvents. It was recovered in 5.7% yield, on GPC showed two peaks of molecular mass of 9 and 3.5kDa. The compositional analyses of Arnica complex revealed the presence of carbohydrates (26%), uronic acids (12%), phenolics (1.25mM or 213mg of GAE/1g), and low protein content (∼1%). The carbohydrate moiety was rich mainly in rhamnogalacturonan and arabinogalactan. The antitussive tests showed the reduction of the cough efforts by Arnica complex, however, its total antitussive effect was lower compared with that of codeine, the strongest antitussive agent. The bronchodilatory activity of Arnica complex was similar to salbutamol, a classic antiasthmatic drug, and was confirmed by significantly decreased values of specific airways resistance in vivo and by considerably attenuated the amplitude of acetylcholine and histamine-induced contractions in vitro. Arnica complex did not show any cytotoxic effect on mouse fibroblast cultures and human lung cells, up to the dose of 500μg/mL. Copyright © 2014 Elsevier B.V. All rights reserved.
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Muir, J F; Bertin, L; Georges, D
1992-11-01
We wished to assess the efficacy of inhaled salmeterol (SML; 50 micrograms b.i.d.) compared to a combination of slow-release theophylline and ketotifen p.o. (TK; T 300 mg+K 1 mg b.i.d.) for the treatment of nocturnal asthma. Ninety six patients with nocturnal asthma, (forced expiratory volume in one second (FEV1) 60-90% of predicted value, reversibility > or = 15%, at least two nocturnal awakenings per week) were eligible for a multicentre, double-blind, double-dummy cross-over study (14-day run-in, two successive 28-day treatment periods). Efficacy was assessed as success/failure, success being defined as the complete disappearance of nocturnal symptoms/awakening during the last week of each treatment period. There was a statistically significant difference between SML and TK for this criterion: 46% and 39% success with SML during periods I (first 28-day period) and II (following the cross-over), compared to only 15% and 26% with TK, respectively (p < 0.01). SML was also significantly better for the other criteria (lung function, rescue salbutamol intake during day and night). Side-effects were five times less frequent in SML-treated patients (p < 0.004). Efficacy and tolerance of SML were obviously far better than those of TK in patients with nocturnal asthma.
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Zhou, Qi Tony; Qu, Li; Gengenbach, Thomas; Larson, Ian; Stewart, Peter J; Morton, David A V
2013-03-01
The objective of this study was to investigate the effect of particle surface coating with magnesium stearate on the aerosolization of dry powder inhaler formulations. Micronized salbutamol sulphate as a model drug was dry coated with magnesium stearate using a mechanofusion technique. The coating quality was characterized by X-ray photoelectron spectroscopy. Powder bulk and flow properties were assessed by bulk densities and shear cell measurements. The aerosol performance was studied by laser diffraction and supported by a twin-stage impinger. High degrees of coating coverage were achieved after mechanofusion, as measured by X-ray photoelectron spectroscopy. Concomitant significant increases occurred in powder bulk densities and in aerosol performance after coating. The apparent optimum performance corresponded with using 2% w/w magnesium stearate. In contrast, traditional blending resulted in no significant changes in either bulk or aerosolization behaviour compared to the untreated sample. It is believed that conventional low-shear blending provides insufficient energy levels to expose host micronized particle surfaces from agglomerates and to distribute guest coating material effectively for coating. A simple ultra-high-shear mechanical dry powder coating step was shown as highly effective in producing ultra-thin coatings on micronized powders and to substantially improve the powder aerosolization efficiency.
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Acute respiratory failure revealing a multilocular thymic cyst in an infant: a case report.
Asma, Bouziri; Ammar, Khaldi; Khaled, Menif; Najoua, Guandoura; Nejla, Ben Jaballah
2009-11-30
Multilocular thymic cysts are rare benign lesions of the neck and mediastinum that can occur at any age. In children, multilocular thymic cysts are usually symptomatic after the age of 2 years and produce few symptoms. We present an unusual case of a multilocular thymic cyst diagnosed in a 3-month-old girl and causing severe respiratory failure. A 3 month-old-girl, with a medical history of dyspnea and wheezing since the age of 20 days, presented in our pediatric intensive care unit for acute respiratory failure requiring mechanical ventilation. The chest radiograph showed thoracic distension without any other abnormalities. The diagnosis of severe asthma was initially suspected and the patient was treated by intravenous corticosteroids and continuous perfusion of salbutamol without any improvement. A chest tomography scan was performed and demonstrated an anterior mediastinal multiseptated cystic mass extending from the inferior face of the thyroid gland to the left cardiophrenic angle. Sternotomy and excision biopsy were planned urgently. The cystic mass was excised completely. The histopathological examination confirmed the diagnosis of a multilocular thymic cyst. The particularities of our observation are the occurrence of a multilocular thymic cyst in a young infant and its presentation by a severe acute respiratory failure mimicking asthma.
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Looking for immunotolerance: a case of allergy to baker's yeast (Saccharomyces cerevisiae).
Pajno, G B; Passalacqua, G; Salpietro, C; Vita, D; Caminiti, L; Barberio, G
2005-09-01
We describe one case of baker's yeast true allergy in a boy with previously diagnosed mite-allergy and atopic dermatitis. At the age of 6, being atopic dermatitis and rhinitis well controlled by drugs, he began to experience generalized urticaria and asthma after eating pizza and bread, but only fresh from the oven. The diagnostic workup revealed single sensitization to baker's yeast (Saccharomyces cerevisiae), and a severe systemic reaction also occurred during the prick-by-prick procedure. After discussing with parents, no special dietary restriction was suggested but the use of autoinjectable adrenaline and on demand salbutamol. A diary of symptoms was recorded by means of a visual-analog scale. During the subsequent 2 years, the severity of symptoms was progressively reduced, and presently urticaria has disappeared. Only cough persists, invariantly after eating just-baked and yeast-containing foods. If bread, pizza and cakes are ate more than one hour after preparation, no symptom occur at all. Baker's yeast is a common component of everyday diet and it usually acts as an allergen only by the inhalatory route. We speculate that the continuous exposure to saccharomyces in foods may have lead to an immunotolerance with a progressive reduction of symptoms, whereas why the allergens is active only in ready-baked foods remains unexplained.
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Bozzolino, Cristina; Leporati, Marta; Gani, Federica; Ferrero, Cinzia; Vincenti, Marco
2018-02-20
A fast analytical method for the simultaneous detection of 24 β 2 -agonists in human urine was developed and validated. The method covers the therapeutic drugs most commonly administered, but also potentially abused β 2 -agonists. The procedure is based on enzymatic deconjugation with β-glucuronidase followed by SPE clean up using mixed-phase cartridges with both ion-exchange and lipophilic properties. Instrumental analysis conducted by UHPLC-MS/MS allowed high peak resolution and rapid chromatographic separation, with reduced time and costs. The method was fully validated according ISO 17025:2005 principles. The following parameters were determined for each analyte: specificity, selectivity, linearity, limit of detection, limit of quantification, precision, accuracy, matrix effect, recovery and carry-over. The method was tested on real samples obtained from patients subjected to clinical treatment under chronic or acute therapy with either formoterol, indacaterol, salbutamol, or salmeterol. The drugs were administered using pressurized metered dose inhalers. All β 2 -agonists administered to the patients were detected in the real samples. The method proved adequate to accurately measure the concentration of these analytes in the real samples. The observed analytical data are discussed with reference to the administered dose and the duration of the therapy. Copyright © 2017 Elsevier B.V. All rights reserved.
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Balani, Prashant N; Ng, Wai Kiong; Tan, Reginald B H; Chan, Sui Yung
2010-05-01
The feasibility of using excipients to suppress the amorphization or structural disorder of crystalline salbutamol sulphate (SS) during milling was investigated. SS was subjected to ball-milling in the presence of alpha-lactose monohydrate (LAC), adipic acid (AA), magnesium stearate (MgSt), or polyvinyl pyrrolidone (PVP). X-ray powder diffraction, dynamic vapor sorption (DVS), high sensitivity differential scanning calorimetry (HSDSC) were used to analyze the crystallinity of the milled mixtures. Comilling with crystalline excipients, LAC, AA, and MgSt proved effective in reducing the amorphization of SS. LAC, AA, or MgSt acting as seed crystals to induce recrystallization of amorphous SS formed by milling. During comilling, both SS and LAC turned predominantly amorphous after 45 min but transformed back to a highly crystalline state after 60 min. Amorphous content was below the detection limits of DVS (0.5%) and HSDSC (5%). Comilled and physical mixtures of SS and ALM were stored under normal and elevated humidity conditions. This was found to prevent subsequent changes in crystallinity and morphology of comilled SS:LAC as compared to significant changes in milled SS and physical mixture. These results demonstrate a promising application of comilling with crystalline excipients in mitigating milling induced amorphization of pharmaceutical actives.
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Relaxant effect of superimposed length oscillation on sensitized airway smooth muscle.
Jo-Avila, Miguel; Al-Jumaily, Ahmed M; Lu, Jun
2015-03-01
Asthma is associated with reductions in the airway lumen and breathing difficulties that are attributed to airway smooth muscles (ASM) hyperconstriction. Pharmaceutical bronchodilators such as salbutamol and isoproterenol are normally used to alleviate this constriction. Deep inspirations and tidal oscillations (TO) have also been reported to relax ASM in healthy airways with less response in asthmatics. Little information is available on the effect of other forms of oscillation on asthmatic airways. This study investigates the effect of length oscillations (LO), with amplitude 1 and 1.5% in the frequency range 5-20 Hz superimposed on breathing equivalent LO, on contracted ASM dissected from sensitized mice. These mice are believed to show some symptoms such as airway hyperreactivity similar to those associated with asthma in humans. In the frequency range used in this work, this study shows an increase in ASM relaxation of an average of 10% for 1.5% amplitude when compared with TO, ISO, or the combination of both. No similar finding is observed with 1% amplitude. This suggests that superimposed length oscillation acting over the interaction of myosin and actin during contraction may lead to temporal rearrangement and disturbance of the cross-bridge process in asthmatic airways. Copyright © 2015 the American Physiological Society.
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Guidance on the diagnosis and management of asthma among adults in resource limited settings.
Kirenga, Bruce J; Schwartz, Jeremy I; de Jong, Corina; van der Molen, Thys; Okot-Nwang, Martin
2015-12-01
Optimal management of asthma in resource limited settings is hindered by lack of resources, making it difficult for health providers to adhere to international guidelines. The purpose of this review is to identify steps for asthma diagnosis and management in resource limited settings. Review of international asthma guidelines and other published studies on diagnosis and management of asthma. We establish that clinical diagnosis of asthma can be made if recurrent respiratory symptoms especially current wheeze or wheeze in the last 12 months are present. Presence of a trigger, other allergic diseases, personal or family history of asthma; clinical improvement and increase in the peak flow and forced expiratory volume in one second of ≥12% after salbutamol administration increases the likelihood of asthma. At diagnosis severity grading, patient education, removal or reduction of trigger should be done. Follow up 2-6 weeks and assessment of control during therapy is essential. Therapy should be adjusted up or down depending on control levels. Patients should be instructed to increase the frequency of their bronchodilators and/or steroids therapy when they start to experience worsening symptoms. Good quality asthma care can be achieved in resource limited settings by use of clinical data and simple tests.
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Principal findings of systematic reviews for the management of acute bronchiolitis in children.
Castro-Rodriguez, Jose A; Rodriguez-Martinez, Carlos E; Sossa-Briceño, Monica P
2015-09-01
Bronchiolitis is the most common cause of hospitalization among infants during the first 12 months of life, with high direct and indirect cost for health system and families. Different treatment approaches co-exist worldwide resulting in many drugs prescribed, without any proven benefit. Twenty systematic reviews of randomized clinical trials (SRCTs) on management of acute bronchiolitis in children were retrieved through 5 databases and their methodological quality was determined using an AMSTAR tool. Epinephrine showed impact only in short-term outcomes among outpatients (reduced admission at day 1 and improved the clinical score in the first 2 hours, compared to placebo) and inpatients (decreased length of stay (LOS) and improved saturation only in the first 2 hours, compared to nebulized salbutamol, but with high heterogeneity). Nebulized 3% saline among inpatients (but not in the emergency department setting) decreased hospital LOS. In small trials, exogenous surfactant among children may decrease the duration of mechanical ventilation and intensive care unit LOS and had favorable effects on oxygenation and CO2 elimination at 24 hrs. Although several SRCTs are currently available, only few treatments show clinically important improvements. Therefore, it is still difficult to prepare a well-established and accepted guideline for the treatment of acute bronchiolitis. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Kubota, Shohei; Nozawa, Asako; Yanai, Takanori; Ozasa, Koji; Mori, Satomi; Kurihara, Kazuyuki
2017-01-01
We report a case of jellyfish allergy diagnosed via an oral food challenge. A 14-year-old boy had no history of jellyfish stings and had been eating commercially available jellyfish products twice yearly for the past 5-6 years. Five minutes after eating a commercially available boiled jellyfish product (100g), he experienced nausea, wheezing, and erythema and had visited our hospital. We suspected an anaphylactic reaction and treated him with intramuscular adrenaline injection, corticosteroid and antihistamine infusions, volume resuscitation, and salbutamol sulfate inhalation, which resulted in an improvement of the symptoms. One-month later in our hospital, we administered an oral food challenge of the same boiled jellyfish product bought at the same grocery store to the patient. After ingesting 14g of boiled jellyfish, he experienced erythema, wheezing, nausea, and abdominal pain. Several reports have described anaphylaxis caused by the ingestion of jellyfish, but the allergens in jellyfish have not been analyzed. A skin prick test for poly-gamma-glutamic acid (PGA) which is a component of jellyfish stings was negative. This suggests that he was sensitized to some allergen other than PGA via a route different from that of jellyfish sting. Our skin prick test for several kinds of edible jellyfish suggests that allergenicity may be different for different jellyfish.
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Khalili, Shadi Farshbaf; Ghanbarzadeh, Saeed; Nokhodchi, Ali; Hamishehkar, Hamed
2018-01-01
In the process of quality control of pulmonary drug delivery products, aerosolization efficiency is mainly determined using impactors, e.g. next generation impactor (NGI). However, particle bounce may interfere with the validity and accuracy of results due to the overestimation of the respirable fraction. It is suggested that the coating of impactor's stages may prevent the particle bounce. Therefore, coating materials may influence the results of the aerosolization indexes of pulmonary dosage forms. The aim of this study was to investigate if the aerosolization indices are affected differently by using the different coating materials. In this study, the effects of using different materials including Span® 85, Tween® 80, silicon® oil, glycerin and Brij® 35/glycerin mixture recommended for the coating of NGI stages on the aerosolization indices such as fine particle fraction, fine particle dose, mass median aerodynamic diameter, and geometric standard deviation of salbutamol emitted from a commercial metered dose inhaler (MDI), were assessed. Three statistically different results were obtained on using Tween® 80, Span® 85 and silicon oil, and glycerin and Brij®35/glycerin mixture. It can be concluded that the type of coating material influenced the aerosolization indices of the examined MDI in NGIs. PMID:29853937
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Khalili, Shadi Farshbaf; Ghanbarzadeh, Saeed; Nokhodchi, Ali; Hamishehkar, Hamed
2018-06-01
In the process of quality control of pulmonary drug delivery products, aerosolization efficiency is mainly determined using impactors, e.g. next generation impactor (NGI). However, particle bounce may interfere with the validity and accuracy of results due to the overestimation of the respirable fraction. It is suggested that the coating of impactor's stages may prevent the particle bounce. Therefore, coating materials may influence the results of the aerosolization indexes of pulmonary dosage forms. The aim of this study was to investigate if the aerosolization indices are affected differently by using the different coating materials. In this study, the effects of using different materials including Span ® 85, Tween ® 80, silicon ® oil, glycerin and Brij ® 35/glycerin mixture recommended for the coating of NGI stages on the aerosolization indices such as fine particle fraction, fine particle dose, mass median aerodynamic diameter, and geometric standard deviation of salbutamol emitted from a commercial metered dose inhaler (MDI), were assessed. Three statistically different results were obtained on using Tween ® 80, Span ® 85 and silicon oil, and glycerin and Brij ® 35/glycerin mixture. It can be concluded that the type of coating material influenced the aerosolization indices of the examined MDI in NGIs.
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Fort Casamartina, Eduard; Arribas Hortiguela, Lorena; Bleda Pérez, Carmen; Muñoz Sánchez, Carme; Peiro Martínez, Imma; Perayre Badía, María; Clopés Estela, Ana
2016-06-03
Durante la última década, el conocimiento de nuevos mecanismos implicados en el desarrollo del cáncer ha permitido el diseño de nuevos fármacos para su tratamiento y la mayor parte de ellos son fármacos que se administran por vía oral. Uno de los principales problemas de los pacientes oncohematológicos es la desnutrición, que suele tener causas multifactoriales (de la propia enfermedad, de los pacientes y de los diferentes tratamientos administrados). Para minimizar el impacto de la desnutrición es necesaria una intervención nutricional, ya sea adaptando la dieta o mediante la instauración de soporte nutricional artificial, en función de la gravedad de cada caso. En cualquier paciente que esté recibiendo un tratamiento oncológico hay que evaluar las posibles interacciones que pueden existir con el soporte nutricional instaurado, ya sea dieta oral, suplementación oral o nutrición enteral. Estas interacciones pueden disminuir la eficacia, aumentar la toxicidad de los tratamientos o producir déficits nutricionales. Se detallan las principales interacciones que se pueden producir, las interacciones entre los tratamientos oncológicos y el soporte nutricional.
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Como Lo Hago Yo: Lipomas Medulares
Portillo, Santiago
2014-01-01
Basados en la experiencia de 82 casos; en 5% se observaron anomalías pélvicas asociadas. En los menores de 3 años el motivo de consulta (85%) fue la tumoración. En los mayores de 3 años (42%) tenía problemas neurológicos. Solo el 24% preocupados por la tumoración. El objetivo de la cirugía es desanclar la médula y no remover la totalidad del lipoma. El lipoma de filum es el que es mas simple para operar. Aún cuando la escuela francesa propone operar solamente cuando hay síntomas favorezco cirugía preventiva. Favorezco una segunda cirugía si hay signos de anclaje postoperatorio, aún cuando observamos empeoramiento postoperatorio motor en 2.5% de los operados y urológico a largo plazo en 6% de los operados. PMID:24791218
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Gugliemetti, G; Sukhu, R; Conca Baenas, M A.; Meeks, J; Sjoberg, D D.; Eastham, J A.; Scardino, P T.; Touijer, K
2017-01-01
Resumen Antecedentes La presencia de metástasis en los ganglios linfáticos (MGL) en la prostatectomía radical de rescate (PRs) se asocia con un mal pronóstico. Los factores predictivos de resultados en este contexto siguen siendo indeterminados. El objetivo fue evaluar el papel de número de ganglios linfáticos positivos sobre el resultado de los pacientes con MGL después de PRs y para el cáncer de próstata de radio-recurrente. Material y métodos Se analizaron los datos de una cohorte consecutiva de 215 hombres tratados con PRr en una sola institución. Se utilizaron los modelos de regresión de riesgos proporcionales de Cox univariante para la recurrencia bioquímica (RBQ) y los resultados metastásicos, con el antígeno prostático específico, la puntuación de Gleason, la extensión extraprostática, la invasión de vesículas seminales, el tiempo entre la terapia de radiación y PRr y el número de ganglios positivos como factores predictivos. Resultados De los 47 pacientes con MGL, 37 desarrollaron RBQ, 11 desarrollaron metástasis a distancia y 4 fallecieron con una mediana de seguimiento de 2,3 años para los supervivientes. El riesgo de metástasis aumentó con mayores niveles preoperatorios de PSA (HR 1,19 por 1 ng/ml; IC del 95%: 1,06, 1,34; p = 0,003). Los factores predictivos restantes no alcanzaron niveles convencionales de significación. Sin embargo, la eliminación de 3 o más ganglios linfáticos positivos demostró una asociación positiva, como se esperaba, con enfermedad metastásica (HR 3,44, IC: 0,91, 13,05; p = 0,069) en comparación con uno o dos ganglios positivos. Del mismo modo, la presencia de extensión extraprostática, invasión de vesículas seminales y grado de Gleason superior a 7 también demostraron una asociación positiva con un mayor riesgo de metástasis, con índices de riesgo de 3,97 (IC del 95% 0,50; 31,4; p = 0,2), 3,72 (IC 95% 0,80, 17,26; p = 0,1) y 1,45 (IC del 95% 0,44, 4,76; p = 0,5), respectivamente
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Treatment of severe bronchiolitis: A survey of Canadian pediatric intensivists.
Bradshaw, Matthew L; Déragon, Alexandre; Puligandla, Pramod; Emeriaud, Guillaume; Canakis, Anne-Marie; Fontela, Patricia S
2018-05-01
To describe management practices and the factors guiding admission and treatment decisions for viral bronchiolitis across Canadian pediatric intensive care units (PICUs). Cross-sectional survey. Canadian PICUs. Pediatric intensivists. A survey using two case scenarios (non-intubated vs intubated patients) was developed using focus groups and a literature review. We analyzed our results using descriptive statistics and multivariate logistic regression. Our response rate was 55% (57/103). Regarding bronchiolitis management, 75% (42/56) of respondents would use inhaled therapies, with nebulized epinephrine (33/56, 59%) and salbutamol (20/56, 36%) being the most common. Antibiotic use within the first hour of admission to PICU almost doubled in frequency (36% vs 71%) in patients who required mechanical ventilation (p 0.0004). High flow nasal cannula (HFNC; 32/56, 57%) and continuous positive airway pressure (CPAP; 16/56, 29%) were the preferred modes of non-invasive ventilation (NIV). The management of severe viral bronchiolitis is similar across Canadian PICUs. The use of NIV, inhaled treatments, and antibiotics is frequent, which differs from the recommendations made by published guidelines. Canadian pediatric intensivists use homogeneous PICU admission criteria based on patients' characteristics and severity of the clinical picture. Clinical practice guidelines for children with viral bronchiolitis should address the management of patients with severe clinical disease. © 2018 Wiley Periodicals, Inc.
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Yoo, Young; Seo, Sung Chul; Kim, Young Il; Chung, Bo Hyun; Song, Dae Jin; Choung, Ji Tae
2012-09-01
Bronchodilator responsiveness (BDR) and eosinophilic inflammation are characteristic features of asthma. Objective. The aim of this study was to compare the relationships of BDR after methacholine challenge or adenosine 5'-monophosphate (AMP) challenge to blood eosinophil markers in children with asthma. Methacholine and AMP challenges were performed on 69 children with mild intermittent to moderate persistent asthma. BDR was calculated as the change in forced expiratory volume in 1 second, expressed as percentage change of the value immediately after the each challenge and the value after inhalation of salbutamol. Serum total IgE levels, blood eosinophil counts, and serum eosinophil cationic protein (ECP) levels were determined for each subject. A positive relationship between serum total IgE levels and BDR was found only after the AMP challenge (R(2) = 0.345, p = .001) rather than after the methacholine challenge (R(2) = 0.007, p = .495). Peripheral blood eosinophil counts correlated more significantly with BDR after AMP challenge (R(2) = 0.212, p = .001) than BDR after methacholine challenge (R(2) = 0.002, p = .724). Both BDR after methacholine challenge (R(2) = 0.063, p = .038) and BDR after AMP challenge (R(2) = 0.192, p = .001) were significantly correlated with serum ECP levels. BDR after AMP challenge may be more closely related to eosinophilic inflammation, compared with that after methacholine challenge.
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Ohyama, Katsuhiro; Inoue, Michiko
2016-01-01
Selective beta-adrenergic drugs are used clinically to treat various diseases. Because of imperfect receptor selectivity, beta-adrenergic drugs cause some adverse drug events by stimulating other adrenergic receptors. To examine the association between selective beta-adrenergic drugs and blood pressure elevation, we reviewed the Japanese Adverse Drug Event Reports (JADERs) submitted to the Japan Pharmaceuticals and Medical Devices Agency. We used the Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms extracted from Standardized MedDRA queries for hypertension to identify events related to blood pressure elevation. Spontaneous adverse event reports from April 2004 through May 2015 in JADERs, a data mining algorithm, and the reporting odds ratio (ROR) were used for quantitative signal detection, and assessed by the case/non-case method. Safety signals are considered significant if the ROR estimates and lower bound of the 95% confidence interval (CI) exceed 1. A total of 2021 reports were included in this study. Among the nine drugs examined, significant signals were found, based on the 95%CI for salbutamol (ROR: 9.94, 95%CI: 3.09-31.93) and mirabegron (ROR: 7.52, 95%CI: 4.89-11.55). The results of this study indicate that some selective beta-adrenergic drugs are associated with blood pressure elevation. Considering the frequency of their indications, attention should be paid to their use in elderly patients to avoid adverse events.
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Wang, Jian; Liu, Yuan; Zhang, Junhua; Han, Zhengzheng; Wang, Wei; Liu, Yang; Wei, Dong; Huang, Wei
2017-11-01
Large-scale expression of β 2 -adrenergic receptor (β 2 -AR) in functional form is necessary for establishment of receptor assays for detecting illegally abused β-adrenergic agonists (β-agonists). Cell-based heterologous expression systems have manycritical difficulties in synthesizing this membrane protein, such as low protein yields and aberrant folding. To overcome these challenges, the main objective of the present work was to synthesize large amounts of functional β 2 -AR in a cell-free system based on Escherichia coli extracts. A codon-optimized porcine β 2 -AR gene (codon adaptation index: 0.96) suitable for high expression in E. coli was synthesized and transcribed to the cell-free system, which contributed to increase the expression up to 1.1 mg/ml. After purification using Ni-affinity chromatography, the bioactivity of the purified receptor was measured by novel enzyme-linked receptor assays. It was determined that the relative affinities of the purified β 2 -AR for β-agonists in descending order were as follows: clenbuterol > salbutamol > ractopamine. Moreover, their IC 50 values were 45.99, 60.38, and 78.02 µg/liter, respectively. Although activity of the cell-free system was slightly lower than activity of systems based on insect and mammalian cells, this system should allow production of β 2 -AR in bulk amounts sufficient for the development of multianalyte screening methods for detecting β-agonist residues.
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Tsai, Ching-Piao; Lin, Feng-Cheng; Lee, Charles Tzu-Chi
2014-10-01
The aim of this study was to investigate whether the use of fenoterol, a beta2-adrenergic agonist, was associated with multiple sclerosis (MS) risk by conducting a total population-based case-control study in Taiwan. A total of 578 patients with newly diagnosed MS who had a severely disabling disease (SDD) certificate between January 1, 2002 and December 1, 2008 comprised the case group. These cases were compared with 2890 gender-, age-, residence-, and insurance premium-matched controls. Fenoterol use was analyzed using a conditional logistic regression model that controlled for asthma, chronic obstructive pulmonary disease (COPD), salbutamol and steroid use. Compared with the group of people who did not use fenoterol, the adjusted odds ratios were 0.67 (95% confidence interval (CI) = 0.48-0.93, p = 0.016) for the group prescribed fenoterol below 2.25 cumulative defined daily dose (cDDD) and 0.49 (95% CI = 0.33-0.71, p < 0.001) for the group with a cumulative fenoterol use of more than 2.25 cDDD. The dose-response relationship was similar within the non-asthma patients. The associations were similar between males and females, but differences between age groups were observed. The results of this study suggest that fenoterol use may reduce the risk of MS. © The Author(s), 2014.
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El-Gindy, Alaa; Emara, Samy; Shaaban, Heba
2007-02-19
Three methods are developed for the determination of two multicomponent mixtures containing guaiphenesine (GU) with salbutamol sulfate (SL), methylparaben (MP) and propylparaben (PP) [mixture 1]; and acephylline piperazine (AC) with bromhexine hydrochloride (BX), methylparaben (MP) and propylparaben (PP) [mixture 2]. The resolution of the two multicomponent mixtures has been accomplished by using numerical spectrophotometric methods such as partial least squares (PLS-1) and principal component regression (PCR) applied to UV absorption spectra of the two mixtures. In addition HPLC method was developed using a RP 18 column at ambient temperature with mobile phase consisting of acetonitrile-0.05 M potassium dihydrogen phosphate, pH 4.3 (60:40, v/v), with UV detection at 243 nm for mixture 1, and mobile phase consisting of acetonitrile-0.05 M potassium dihydrogen phosphate, pH 3 (50:50, v/v), with UV detection at 245 nm for mixture 2. The methods were validated in terms of accuracy, specificity, precision and linearity in the range of 20-60 microg ml(-1) for GU, 1-3 microg ml(-1) for SL, 20-80 microg ml(-1) for AC, 0.2-1.8 microgml(-1) for PP and 1-5 microg ml(-1) for BX and MP. The proposed methods were successfully applied for the determination of the two multicomponent combinations in laboratory prepared mixtures and commercial syrups.
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Miraglia Del Giudice, Michele; Indolfi, Cristiana; Capasso, Michele; Maiello, Nunzia; Decimo, Fabio; Ciprandi, Giorgio
2017-03-07
Allergic rhinitis (AR) and allergic asthma are caused by an IgE-mediated inflammatory reaction. Probiotics may exert anti-inflammatory and immune-modulatory activity. Thus, this study aimed at investigating whether a Bifidobacteria mixture could be able to relieve nasal symptoms, and affect quality of life (QoL) in children with AR and intermittent asthma due to Parietaria allergy. The present study was conducted as placebo-controlled, double-blinded, and randomized. Globally, 40 children (18 males; mean age 9 ± 2.2 years) were enrolled. They were treated with probiotics or placebo: 1 sachet/day for 4 weeks. AR symptoms, and QoL were assessed at baseline and after treatment. Use of rescue medications, such as cetirizine syrup and salbutamol spray, was also permitted and recorded. Children treated with probiotic mixture achieved a significant improvement of symptoms (p < 0.005), and QoL ((p < 0.001). Placebo group had worsening of symptoms (p < 0.005) and QoL (p < 0.001). The use of rescue medications was overlapping in the two groups. The intergroup analysis showed that probiotic mixture was significantly superior than placebo for all parameters. The current study demonstrated that a Bifidobacteria mixture was able of significantly improving AR symptoms and QoL in children with pollen-induced AR and intermittent asthma. ClinicalTrials.gov ID NCT02807064 .
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Tay, Justin Yong Soon; Liew, Celine Valeria; Heng, Paul Wan Sia
2018-04-22
Dissolution testing for inhalers were previously conducted either on unfractionated drug-carrier powders or drug of specific aerodynamic particle size. In this study, the collection of the full fine particle fraction (FPF) was attempted on a single stage. Capsules containing 30 mg of 2% salbutamol sulfate (SS) was tested to have a FPF of 9 ± 1% using the full set of Andersen cascade impactor (ACI) and a modified Rotahaler® capable of achieving 4.0 kPa pressure drop at 60 L/min air flow rate. A truncated ACI comprising the USP throat, pre-separator, stage 0, stage 4, stage F, polytetrafluoroethylene funnel (TF) and small collection plate (sCP) was found to be capable of achieving a FPF of 9% collected on TF and sCP. An adhesive tape was used to collect the FPF from the TF and sCP and held in place by an enhancer cell in a 200 mL round bottom vessel containing 50 mL Gamble's solution with 0.2 v/v, % Tween 80. Dissolution testing of SS and Seretide® showed burst release of SS and salmeterol while sustained release of fluticasone. This study demonstrated a reproducible method which may be used for evaluation of the full FPF of orally inhaled products. Copyright © 2018 Elsevier B.V. All rights reserved.
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Mukherjee, Manali; Pritchard, D I; Bosquillon, C
2012-04-15
A physiologically pertinent in vitro model is urgently needed for probing interactions between inhaled drugs and the organic cation transporters (OCT) in the bronchial epithelium. This study evaluated OCT expression, functionality, inhibition by common inhaled drugs and impact on formoterol transepithelial transport in layers of human bronchial epithelial Calu-3 cells grown at an air-liquid interface. 21 day old Calu-3 layers expressed OCT1, OCT3, OCTN1 and OCTN2 whereas OCT2 could not be detected. Quantification of the cellular uptake of the OCT substrate ASP(+) in presence of inhibitors suggested several OCT were functional at the apical side of the cell layers. ASP(+) uptake was reduced by the bronchodilators formoterol, salbutamol (albuterol), ipratropium and the glucocorticoid budesonide. However, the OCT inhibitory properties of the two β(2)-mimetics were suppressed at therapeutically relevant concentrations. The absorptive permeability of formoterol across the cell layers was enhanced at a high drug concentration shown to decrease ASP(+) uptake by ∼50% as well as in presence of the OCT inhibitor tetraethylammonium (TEA). Secretory transport was unaffected by the drug concentration but was reduced by TEA. Our data indicate air-interfaced Calu-3 layers offer a low-cost in vitro model suitable for assessing inhaled drug-OCT interactions in the bronchial epithelium. Copyright © 2011 Elsevier B.V. All rights reserved.
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Hu, Lei; Zuo, Peng; Ye, Bang-Ce
2010-10-01
An automated multicomponent mesofluidic system (MCMS) based on biorecognitions carried out on meso-scale glass beads in polydimethylsiloxane (PDMS) channels was developed. The constructed MCMS consisted of five modules: a bead introduction module, a bioreaction module, a solution handling module, a liquid driving module, and a signal collection module. The integration of these modules enables the assay to be automated and reduces it to a one-step protocol. The MCMS has successfully been applied toward the detection of veterinary drug residues in animal-derived foods. The drug antigen-coated beads (varphi250 microm) were arrayed in the PDMS channels (varphi300 microm). The competitive immunoassay was then carried out on the surface of the glass beads. After washing, the Cy3-labeled secondary antibody was introduced to probe the antigen-antibody complex anchored to the beads. The fluorescence intensity of each bead was measured and used to determine the residual drug concentration. The MCMS is highly sensitive, with its detection limits ranging from 0.02 (salbutamol) to 3.5 microg/L (sulfamethazine), and has a short assay time of 45 min or less. The experimental results demonstrate that the MCMS proves to be an economic, efficient, and sensitive platform for multicomponent detection of compound residues for contamination in foods or the environment. Copyright 2010 Elsevier Inc. All rights reserved.
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Central α- and β-adrenoceptors modifying arterial blood pressure and heart rate in conscious cats
Day, M.D.; Roach, A.G.
1974-01-01
1 In conscious unrestrained cats noradrenaline, α-methylnoradrenaline and clonidine, infused into the lateral cerebral ventricles (i.c.v.) caused dose-related falls in blood pressure and heart rate; both effects were abolished after i.c.v. phentolamine. 2 In 12 out of 20 cats, i.c.v. isoprenaline and salbutamol when given caused dose-related pressor responses and tachycardias. These effects were abolished after i.c.v. β-adrenoceptor blocking drugs but were unaffected by α-adrenoceptor blocking agents. 3 In 5 out of 20 cats, i.c.v. isoprenaline regularly produced dose-related falls in blood pressure with associated tachycardias; both effects were abolished after i.c.v. β-adrenoceptor blocking agents. 4 Intracerebroventricular dopamine produced cardiovascular responses which were qualitatively similar to those produced by i.c.v. isoprenaline. 5 Intracerebroventricular adrenaline produced complex responses in untreated animals but typical α-effects were obtained after prior i.c.v. treatment with a β-adrenoceptor blocking agent and typical β-effects after i.c.v. pretreatment with an α-adrenoceptor blocking agent. 6 The cardiovascular changes produced by i.c.v. β-adrenoceptor agonists were abolished after systemic administration of hexamethonium or bethanidine. 7 The results are discussed in the light of the mode of action of β-adrenoceptor stimulants and β-adrenoceptor blocking agents in the treatment of hypertension. PMID:4451747
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Potential of a cyclone prototype spacer to improve in vitro dry powder delivery.
Parisini, Irene; Cheng, Sean J; Symons, Digby D; Murnane, Darragh
2014-05-01
Low inspiratory force in patients with lung disease is associated with poor deagglomeration and high throat deposition when using dry powder inhalers (DPIs). The potential of two reverse flow cyclone prototypes as spacers for commercial carrier-based DPIs was investigated. Cyclohaler®, Accuhaler® and Easyhaler® were tested with and without the spacers between 30 and 60 Lmin−1. Deposition of particles in the next generation impactor and within the devices was determined by high performance liquid chromatography. Reduced induction port deposition of the emitted particles from the cyclones was observed due to the high retention of the drug within the spacers (e.g. salbutamol sulphate (SS): 67.89 ± 6.51% at 30 Lmin−1 in Cheng 1). Fine particle fractions of aerosol as emitted from the cyclones were substantially higher than the DPIs alone. Moreover, the aerodynamic diameters of particles emitted from the cyclones were halved compared to the DPIs alone (e.g. SS from the Cyclohaler® at 4 kPa: 1.08 ± 0.05 μm vs. 3.00 ± 0.12 μm, with and without Cheng 2, respectively) and unaltered with increased flow rates. This work has shown the potential of employing a cyclone spacer for commercial carrier-based DPIs to improve inhaled drug delivery.
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Du, Ping; Du, Ju; Smyth, Hugh D C
2017-01-01
Previously, granulated lactose carriers were shown to improve uniformity and aerosolization of a low-dose model drug. In the present study, the blending uniformity and aerosol dispersion performance were assessed for 2 model drugs salbutamol sulfate (SS) and rifampicin (RIF), blended at high loadings (10% or 30% drug) with granulated lactose carriers. The model drug powders differed in particle size distribution, morphology, density, and surface energies. Content uniformity of RIF blends was better than that of SS. Aerosolization studies showed that all blend formulations had acceptable emitted fractions (>70%). The SS blends showed low induction-port deposition (6%-10%) compared to RIF (5%-30%). This difference was greater at high flow rates. At 90 L/min, the low induction port deposition of SS blends allowed high fine particle fraction (FPF) of 73%-81%, whereas the FPF of the RIF blends was around 43%-45% with higher induction port deposition. However, SS blends exhibited strong flow rate-dependent performance. Increasing the flow rate from 30 L/min to 90 L/min increased SS FPF from approximately 20% to 80%. Conversely, RIF blends were flow rate and drug loading independent. It was concluded that the aerosolization of high drug-loaded dry powder inhaler formulations using granulated lactose, particularly flow rate dependency, varies with active pharmaceutical ingredient properties. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
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Lian, Lushi; Yao, Bo; Hou, Shaodong; Fang, Jingyun; Yan, Shuwen; Song, Weihua
2017-03-07
Advanced oxidation processes (AOPs), such as hydroxyl radical (HO • )- and sulfate radical (SO 4 •- )-mediated oxidation, are alternatives for the attenuation of pharmaceuticals and personal care products (PPCPs) in wastewater effluents. However, the kinetics of these reactions needs to be investigated. In this study, kinetic models for 15 PPCPs were built to predict the degradation of PPCPs in both HO • - and SO 4 •- -mediated oxidation. In the UV/H 2 O 2 process, a simplified kinetic model involving only steady state concentrations of HO • and its biomolecular reaction rate constants is suitable for predicting the removal of PPCPs, indicating the dominant role of HO • in the removal of PPCPs. In the UV/K 2 S 2 O 8 process, the calculated steady state concentrations of CO 3 •- and bromine radicals (Br • , Br 2 •- and BrCl •- ) were 600-fold and 1-2 orders of magnitude higher than the concentrations of SO 4 •- , respectively. The kinetic model, involving both SO 4 •- and CO 3 •- as reactive species, was more accurate for predicting the removal of the 9 PPCPs, except for salbutamol and nitroimidazoles. The steric and ionic effects of organic matter toward SO 4 •- could lead to overestimations of the removal efficiencies of the SO 4 •- -mediated oxidation of nitroimidazoles in wastewater effluents.
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NASA Astrophysics Data System (ADS)
Dcruz, Noella L.
2014-07-01
estudiantes que escribieran dos ensayos cortos de tres que se proponían. Los ensayos contenían partes descriptivas y conceptuales. Los mismos estaban destinados a servir como herramientas de enseñanza. 62% de los 106 ensayos de 55 estudiantes obtuvo grados A, B o C. 21% de los 47 encuestados que respondieron al cuestionario posterior consideró que los ensayos aumentaron su interés por la astronomía. 49% de los encuestados consideró que los ensayos no eran educacionalmente útiles y que no deben ser propuestos de nuevo. Las respuestas escritas más comunes a nuestra encuesta indicaran que los estudiantes necesitan más orientación y una mejor preparación en la redacción de ensayos exitosos. Dado que los estudiantes encontraron las piezas conceptuales de los ensayos difíciles, en el futuro vamos a ofrecer actividades pertinentes antes de los plazos de redacción para ayudar a los estudiantes a crear ensayos de mayor calidad. Nós ocasionalmente incluímos projetos em nosso curso universitário introdutório centrado no aluno para permitir aos estudantes que pertencem às carreiras não científicas explorar alguns conceitos astronômicos em mais detalhes do que o normal. Tais projetos também enfatizam eventos astronômicos em curso ou futuros. Esperamos que os alunos se sintam mais interessados na astronomia através de projetos ligados a eventos astronômicos. No termo de Primavera de 2012 (EUA), propomos ensaios curtos focados em eclipses, trânsitos e ocultações para promover o raro trânsito de Vênus que ocorreu no dia 5 de junho de 2012. Pedimos aos alunos que escrevessem dois ensaios curtos dentre três que foram propostos. Os ensaios continham partes descritivas e conceituais. Eles foram feitos para servir como ferramentas de ensino. 62% de 106 ensaios de 55 alunos ganhou graus A, B ou C. 21% dos 47 entrevistados que responderam ao levantamento posterior sentiu que os ensaios aumentaram seu interesse na astronomia. 49% dos inquiridos consideraram que os
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Micoinseticidas e Micoacaricidas no Brasil: Como estamos?
USDA-ARS?s Scientific Manuscript database
Mycoinsecticides and mycoacaricides can be defined as biopesticide products based on living propagules of entomopathogenic fungi developed for inundative and inoculative biological control of insects and mites. Based on recently published data on global use of entomopathogenic fungi and a proposal f...
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Donovan, Chantal; Seow, Huei Jiunn; Bourke, Jane E; Vlahos, Ross
2016-05-01
β2-adrenoceptor agonists are the mainstay therapy for patients with asthma but their effectiveness in cigarette smoke (CS)-induced lung disease such as chronic obstructive pulmonary disease (COPD) is limited. In addition, bronchodilator efficacy of β2-adrenoceptor agonists is decreased during acute exacerbations of COPD (AECOPD), caused by respiratory viruses including influenza A. Therefore, the aim of the present study was to assess the effects of the β2-adrenoceptor agonist salbutamol (SALB) on small airway reactivity using mouse precision cut lung slices (PCLS) prepared from CS-exposed mice and from CS-exposed mice treated with influenza A virus (Mem71, H3N1). CS exposure alone reduced SALB potency and efficacy associated with decreased β2-adrenoceptor mRNA expression, and increased tumour necrosis factor α (TNFα) and interleukin-1β (IL-1β) expression. This impaired relaxation was restored by day 12 in the absence of further CS exposure. In PCLS prepared after Mem71 infection alone, responses to SALB were transient and were not well maintained. CS exposure prior to Mem71 infection almost completely abolished relaxation, although β2-adrenoceptor and TNFα and IL-1β expression were unaltered. The present study has shown decreased sensitivity to SALB after CS or a combination of CS and Mem71 occurs by different mechanisms. In addition, the PCLS technique and our models of CS and influenza infection provide a novel setting for assessment of alternative bronchodilators. © 2016 The Author(s).
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Simulations of Biased Agonists in the β2 Adrenergic Receptor with Accelerated Molecular Dynamics
2013-01-01
The biased agonism of the G protein-coupled receptors (GPCRs), where in addition to a traditional G protein-signaling pathway a GPCR promotes intracellular signals though β-arrestin, is a novel paradigm in pharmacology. Biochemical and biophysical studies have suggested that a GPCR forms a distinct ensemble of conformations signaling through the G protein and β-arrestin. Here we report on the dynamics of the β2 adrenergic receptor bound to the β-arrestin and G protein-biased agonists and the empty receptor to further characterize the receptor conformational changes caused by biased agonists. We use conventional and accelerated molecular dynamics (aMD) simulations to explore the conformational transitions of the GPCR from the active state to the inactive state. We found that aMD simulations enable monitoring of the transition within the nanosecond time scale while capturing the known microscopic characteristics of the inactive states, such as the ionic lock, the inward position of F6.44, and water clusters. Distinct conformational states are shown to be stabilized by each biased agonist. In particular, in simulations of the receptor with the β-arrestin-biased agonist N-cyclopentylbutanepherine, we observe a different pattern of motions in helix 7 when compared to simulations with the G protein-biased agonist salbutamol that involves perturbations of the network of interactions within the NPxxY motif. Understanding the network of interactions induced by biased ligands and the subsequent receptor conformational shifts will lead to development of more efficient drugs. PMID:23879802
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Chemical exposure and respiratory health of children in an industrial setting.
McCarty, Kathleen M; Cleveland, Rebecca J; Franklin, Peter; Sly, Peter D
2014-01-01
Parental exposures to chemicals, and the interplay between chemical exposures in utero and in infancy leading to respiratory disease in childhood, are not yet fully understood. In this study we investigated the impact of chemical exposures to the parent in occupational settings and to the child in the home and children's respiratory health. A cross-sectional study of lung function and respiratory health was conducted in primary school children in the Kwinana industrial area, south of Perth, Western Australia. Respiratory health was assessed using a standardized questionnaire and lung function was measured using the forced oscillation technique before and after inhaling 200 μg of salbutamol. Univariate logistic regression models were used to explore the relationship between the child's respiratory health (asthma, lung function, bronchodilator response) and exposures to ceramics, dry cleaning fluid, electroplating fluid, glues, leather, fabrics, dyes, insecticides, plastics, metal cleaning fluid, petrol, paint, photochemicals, electric wiring, machining, welding, X-rays, cleaning products, nail products, and "other exposures". The impact of cigarette smoking in the home and family history on respiratory health were also investigated. No associations were found between parental occupational exposures or child's exposures in the home and respiratory health. Significant associations were observed between current smoking in the home and cigarette exposure in the first year of life and poor respiratory health in the children. We found no strong evidence of main effects of occupational exposures in impairing the respiratory health of primary school-aged children.
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Subcutaneous adrenaline versus terbutaline in the treatment of acute severe asthma.
Spiteri, M A; Millar, A B; Pavia, D; Clarke, S W
1988-01-01
Subcutaneous adrenaline and terbutaline have been compared in a double blind study of 20 patients with acute severe asthma presenting to an accident and emergency department. Ten patients received adrenaline 0.5 mg (0.5 ml) and 10 terbutaline 0.5 mg (0.5 ml) subcutaneously. Further treatment with nebulised salbutamol (5 mg), hydrocortisone (200 mg), and aminophylline (0.9 mg/kg/hour) was started 15 minutes later. All patients reported a reduction in chest tightness within three minutes of receiving both adrenaline and terbutaline and reported no adverse effects. Mean baseline values of peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1) did not differ significantly between the adrenaline group (130 1 min-1 and 0.83 l) and the terbutaline group (111 1 min-1 and 0.63 l). After administration of adrenaline PEF had increased by 21% and FEV1 by 40% five minutes after the injection, and by 35% and 64% at 15 minutes. Terbutaline caused a 23% increase in PEF and a 37% increase in FEV1 at five minutes, and a 40% and 58% increase at 15 minutes. There was no significant difference in PEF, FEV1, heart rate, blood pressure, or pulsus paradoxus between the two groups at any time. Continuous electrocardiographic recording showed no abnormalities in either group. Thus in this study subcutaneous adrenaline (0.5 mg) and terbutaline (0.5 mg) produced effective rapid bronchodilatation without serious side effects. PMID:3281307
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Predicting the Fine Particle Fraction of Dry Powder Inhalers Using Artificial Neural Networks.
Muddle, Joanna; Kirton, Stewart B; Parisini, Irene; Muddle, Andrew; Murnane, Darragh; Ali, Jogoth; Brown, Marc; Page, Clive; Forbes, Ben
2017-01-01
Dry powder inhalers are increasingly popular for delivering drugs to the lungs for the treatment of respiratory diseases, but are complex products with multivariate performance determinants. Heuristic product development guided by in vitro aerosol performance testing is a costly and time-consuming process. This study investigated the feasibility of using artificial neural networks (ANNs) to predict fine particle fraction (FPF) based on formulation device variables. Thirty-one ANN architectures were evaluated for their ability to predict experimentally determined FPF for a self-consistent dataset containing salmeterol xinafoate and salbutamol sulfate dry powder inhalers (237 experimental observations). Principal component analysis was used to identify inputs that significantly affected FPF. Orthogonal arrays (OAs) were used to design ANN architectures, optimized using the Taguchi method. The primary OA ANN r 2 values ranged between 0.46 and 0.90 and the secondary OA increased the r 2 values (0.53-0.93). The optimum ANN (9-4-1 architecture, average r 2 0.92 ± 0.02) included active pharmaceutical ingredient, formulation, and device inputs identified by principal component analysis, which reflected the recognized importance and interdependency of these factors for orally inhaled product performance. The Taguchi method was effective at identifying successful architecture with the potential for development as a useful generic inhaler ANN model, although this would require much larger datasets and more variable inputs. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
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Liang, Yuan; Wang, Jing; Fei, Fuhuan; Sun, Huanmei; Liu, Ting; Li, Qian; Zhao, Xinfeng; Zheng, Xiaohui
2018-02-23
Investigations of drug-protein interactions have advanced our knowledge of ways to design more rational drugs. In addition to extensive thermodynamic studies, ongoing works are needed to enhance the exploration of drug-protein binding kinetics. In this work, the beta2-adrenoceptor (β 2 -AR) was immobilized on N, N'-carbonyldiimidazole activated amino polystyrene microspheres to prepare an affinity column (4.6 mm × 5.0 cm, 8 μm). The β 2 -AR column was utilized to determine the binding kinetics of five drugs to the receptor. Introducing peak profiling method into this receptor chromatographic analysis, we determined the dissociation rate constants (k d ) of salbutamol, terbutaline, methoxyphenamine, isoprenaline hydrochloride and ephedrine hydrochloride to β 2 -AR to be 15 (±1), 22 (±1), 3.3 (±0.2), 2.3 (±0.2) and 2.1 (±0.1) s -1 , respectively. The employment of nonlinear chromatography (NLC) in this case exhibited the same rank order of k d values for the five drugs bound to β 2 -AR. We confirmed that both the peak profiling method and NLC were capable of routine measurement of receptor-drug binding kinetics. Compared with the peak profiling method, NLC was advantageous in the simultaneous assessment of the kinetic and apparent thermodynamic parameters. It will become a powerful method for high throughput drug-receptor interaction analysis. Copyright © 2018 Elsevier B.V. All rights reserved.
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Akhter, Khalid P; Ahmad, Mahmood; Khan, Shujaat Ali; Ramzan, Munazza; Shafi, Ishrat; Muryam, Burhana; Javed, Zafar; Murtaza, Ghulam
2012-01-01
This study presents an application of the piecewise rational quadratic interpolant to the AUC calculation in the bioavailability study. The objective of this work is to find an area under the plasma concentration-time curve (AUC) for multiple doses of salbutamol sulfate sustained release tablets (Ventolin oral tablets SR 8 mg, GSK, Pakistan) in the group of 24 healthy adults by using computational mathematics techniques. Following the administration of 4 doses of Ventolin tablets 12 hourly to 24 healthy human subjects and bioanalysis of obtained plasma samples, plasma drug concentration-time profile was constructed. The approximated AUC was computed by using computational mathematics techniques such as extended rectangular, extended trapezium and extended Simpson's rule and compared with exact value of AUC calculated by using software - Kinetica to find best computational mathematics method that gives AUC values closest to exact. The exact values of AUC for four consecutive doses of Ventolin oral tablets were 150.58, 157.81, 164.41 and 162.78 ngxh/mL while the closest approximated AUC values were 149.24, 157.33, 164.25 and 162.28 ngxh/mL, respectively, as found by extended rectangular rule. The errors in the approximated values of AUC were negligible. It is concluded that all computational tools approximated values of AUC accurately but the extended rectangular rule gives slightly better approximated values of AUC as compared to extended trapezium and extended Simpson's rules.
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Maestroni, Georges J M; Mazzola, Paola
2003-11-01
We showed that norepinephrine (NE) hampers IL-12 and stimulates IL-10 production via adrenoceptors (ARs) in bone marrow-derived dendritic cells (BMDC) influencing their Th priming ability. Others have shown that Langerhans cells (LC) express mRNA for beta1-, beta2- and alpha1(A)-(ARs) and that catecholamines may inhibit the antigen-presenting capability via beta2-ARs. Here, we show that also BMDC express mRNA for beta1-, beta2-, alpha2(A)- and alpha2(C)-ARs. Inhibition of IL-12 is mediated by both beta2- and alpha2(A)-ARs, while stimulation of IL-10 by beta2-ARs only. In addition, LC migration, the contact hypersensitivity response (CHS) and production of IFN-gamma and IL-2 in draining lymph node cells is increased in mice treated topically with the beta2-AR antagonist ICI 118,551 during FITC sensitization. Activation of beta2-ARs in BMDC before adoptive transfer could reduce both migration and CHS response to FITC. Finally, preincubation of BMDC with LPS in presence of the specific beta2-AR agonist salbutamol impaired their chemotactic response to CCL19 and CCL21 and this effect was neutralized by anti-IL-10 mAb. We suggest that the physiological activation of beta2-ARs in DC (LC) results in stimulation of IL-10 which in turn restrains DC (LC) migration influencing antigen presentation and the consequent CHS response.
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El Mays, Tamer Y; Choudhury, Parichita; Leigh, Richard; Koumoundouros, Emmanuel; Van der Velden, Joanne; Shrestha, Grishma; Pieron, Cora A; Dennis, John H; Green, Francis Hy; Snibson, Ken J
2014-09-16
The low toxicity of perfluorocarbons (PFCs), their high affinity for respiratory gases and their compatibility with lung surfactant have made them useful candidates for treating respiratory diseases such as adult respiratory distress syndrome. We report results for treating acute allergic and non-allergic bronchoconstriction in sheep using S-1226 (a gas mixture containing carbon dioxide and small volumes of nebulized perflubron). The carbon dioxide, which is highly soluble in perflubron, was used to relax airway smooth muscle. Sheep previously sensitized to house dust mite (HDM) were challenged with HDM aerosols to induce early asthmatic responses. At the maximal responses (characterised by an increase in lung resistance), the sheep were either not treated or treated with one of the following; nebulized S-1226 (perflubron + 12% CO2), nebulized perflubron + medical air, 12% CO2, salbutamol or medical air. Lung resistance was monitored for up to 20 minutes after cessation of treatment. Treatment with S-1226 for 2 minutes following HDM challenge resulted in a more rapid, more profound and more prolonged decline in lung resistance compared with the other treatment interventions. Video bronchoscopy showed an immediate and complete (within 5 seconds) re-opening of MCh-constricted airways following treatment with S-1226. S-1226 is a potent and rapid formulation for re-opening constricted airways. Its mechanism(s) of action are unknown. The formulation has potential as a rescue treatment for acute severe asthma.
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Faulhammer, E; Zellnitz, S; Wutscher, T; Stranzinger, S; Zimmer, A; Paudel, A
2018-01-30
This study investigates engineered carrier, as well as engineered API particles, and shows that there are distinct performance indicators of particle engineering for carrier-based dry powder inhalers (DPIs). Spray dried (SDSS) and jet-milled (JMSS) salbutamol sulphate (SS) was blended with untreated α-lactose monohydrate (LAC_R) and α-lactose monohydrate engineered (LAC_E). Subsequent capsule filling was performed with different process settings on a dosator nozzle capsule filling machine in order to reach a target fill weight of 20-25 mg. To evaluate the performance of the different mixtures, in vitro lung deposition experiments were carried out with a next generation impactor, the emitted dose (ED) and fine particle fraction (FPF) were calculated based on the specification of the European pharmacopoeia. The FPF of micronised powder blends is significantly higher (20%) compared to the FPF of spray dried blends (5%). Compared to API engineering, carrier engineering had a positive effect on the capsule filling performance (weight variability and mean fill weight) at lower compression ratios (setting 1). Results further showed that higher compression ratios appear to be beneficial in terms of capsule filling performance (higher fill weight and less fill weight variation). Concluding, it can be stated that the carrier engineering, or generally carrier properties, govern downstream processing, whereas the API engineering and API properties govern the aerosolisation performance and thereby significantly affect the dose delivery to the lungs. Copyright © 2017 Elsevier B.V. All rights reserved.
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Oscillometric and spirometric bronchodilator response in preschool children with and without asthma
Shin, Youn Ho; Jang, Sun Jung; Yoon, Jung Won; Jee, Hye Mi; Choi, Sun Hee; Yum, Hye Yung; Warburton, David; Han, Man Yong
2012-01-01
BACKGROUND: Bronchodilator responses (BDR) are routinely used in the diagnosis and management of asthma; however, their acceptability and repeatability have not been evaluated using quality control criteria for preschool children. OBJECTIVES: To compare conventional spirometry with an impulse oscillometry system (IOS) in healthy and asthmatic preschool children. METHODS: Data from 30 asthmatic children and 29 controls (two to six years of age) who underwent IOS and spirometry before and after salbutamol administration were analyzed. RESULTS: Stable asthmatic subjects significantly differed versus controls in their spirometry-assessed BDR (forced expiratory volume in 1 s [FEV1], forced vital capacity and forced expiratory flow at 25% to 75% of forced vital capacity) as well as their IOS-assessed BDR (respiratory resistance at 5 Hz [Rrs5], respiratory reactance at 5 Hz and area under the reactance curve). However, comparisons based on the area under the ROC curve for ΔFEV1 % initial versus ΔRrs5 % initial were 0.82 (95% CI 0.71 to 0.93) and 0.75 (95% CI 0.62 to 0.87), respectively. Moreover, the sensitivity and specificity for ΔFEV1 ≥9% were 0.53 and 0.93, respectively. Importantly, sensitivity increased to 0.63 when either ΔFEV1 ≥9% or ΔRrs5 ≥29% was considered as an additional criterion for the diagnosis of asthma. CONCLUSION: The accuracy of asthma diagnosis in preschool children may be increased by combining spirometry with IOS when measuring BDR. PMID:22891189
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Sundram, Francis; Notghi, Alp; Smith, Neil B
2009-03-01
Stress radionuclide myocardial perfusion scintigraphy (MPS) using adenosine pharmacological vasodilatation is the preferred method in many centres because of its convenience, safety and speed. It can, however, cause bronchospasm and hence its use is avoided in patients with known or suspected bronchospasm. Owing to service pressures, we use technologist-led adenosine stressing for patients referred for MPS studies. We use a modified adenosine infusion protocol under medical supervision for patients with asthma to prevent and minimize adenosine-induced bronchospasm. In this study, we audited our use of this modified protocol in asthmatic patients and compared the side-effect profile with the standard adenosine protocol used in nonasthmatic patients. We audited 50 consecutive patients with asthma attending our department for stress MPS. All patients were taking regular inhalers+/-oral steroids. Patients who had exacerbation of asthma requiring hospital admission during the preceding 6 months were excluded. Before commencing the infusion, two inhaled puffs of salbutamol were administered. A modified adenosine infusion protocol was used, starting initially at a rate of 70 microg/kg/min and increasing to the standard 140 microg/kg/min within 1 min and then maintained for a further 5 min. Technetium-99m tetrofosmin was injected at 3 min. Blood pressure (BP), pulse rate (PR), oxygen saturation and ECG were monitored before, during and at the end of the infusion. All side effects were recorded. Fifty-eight consecutive patients without asthma were included as controls and received the standard 140 microg/kg/min infusion over 6 min. One hundred and eight patients, 50 with asthma and 58 without asthma, were entered into the study. The test was stopped early in two patients (4%) with asthma and 11 patients (19%) without asthma (chi=5.679; P=0.017). Proportionally, more nonasthmatics developed shortness of breath (SOB) (47 of 58, 81% without asthma vs. 35 of 50, 70% with asthma
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Centeno, A.; Laurent, E.; Delmon, B.
1995-07-01
The present work corresponds to part of a program aimed at upgrading oil obtained by pyrolysis of biomass by hydrotreatment (hydrodeoxygenation HDO). CoMo sulfide catalysts, nonsupported, supported on different supports (alumina, carbon, silica), or modified by K or Pt, were used. The authors used a model reacting mixture containing compounds representative of the molecules that must react to permit a primary stabilisation of the pyrolytic oil: 4-methy lacetophenone (4-MA), diethylsebacate (DES), and guaiacol (GUA). In the reaction of the carbonyl group of the 4-MA it is shown that no important role is played by any acid-base mechanism; dispersion determines themore » activity. Acidity of the support influences the formation of active sites for decarboxylation and hydrogenation of the carboxyl group of DES. It was confirmed that guaiacol-type molecules lead to coking reactions. The role of acidity in the mechanism of these reactions is confirmed, but the modifications made in the catalysts in this work are still not sufficient to control coke deposition. The catalysts supported on carbon lead to the direct elimination of the methoxyl group of the guaiacol. Carbon, on the whole, seems to be a promising support. This work suggests that appropriate modifications of the hydrotreating catalysts can lead to a more effective process for stabilisation of the bio-oils by reaction with hydrogen. 55 refs., 3 figs., 5 tabs.« less
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Cosmic Web of Galaxies in the COMOS Field
NASA Astrophysics Data System (ADS)
Darvish, Behnam; Martin, Christopher D.; Mobasher, Bahram; Scoville, Nicholas; Sobral, David; COSMOS science Team
2017-01-01
We use a mass complete sample of galaxies with accurate photometric redshifts in the COSMOS field to estimate the density field and to extract the components of the cosmic web. The comic web extraction algorithm relies on the signs and the ratio of eigenvalues of the Hessian matrix and is enable to integrate the density field into clusters, filaments and the field. We show that at z < 0.8, the median star-formation rate in the cosmic web gradually declines from the field to clusters and this decline is especially sharp for satellite galaxies (~1 dex vs. ~0.4 dex for centrals). However, at z > 0.8, the trend flattens out. For star-forming galaxies only, the median star-formation rate declines by ~ 0.3-0.4 dex from the field to clusters for both satellites and centrals, only at z < 0.5. We argue that for satellite galaxies, the main role of the cosmic web environment is to control their star-forming/quiescent fraction, whereas for centrals, it is mainly to control their overall star-formation rate. Given these, we suggest that most satellite galaxies experience a rapid quenching mechanism as they fall from the field into clusters through the channel of filaments, whereas for central galaxies, it is mostly due to a slow quenching process. Our preliminary results highlight the importance of the large-scale cosmic web on the evolution of galaxies.
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Como Lo Hago Yo: Tratamiento Quirurgico Del Mielomeningocele
Portillo, Santiago
2014-01-01
En Argentina hay plan de fortificación con ácido fólico. Diagnostico prenatal no siempre es correcto. Cierre según técnica. Cerramos músculo. No favorecemos corpectomía temprana en casos de cifosis. Suturamos la plaqueta. Cerramos el plano muscular. Hidrocefalia: Válvula de derivación, generalmente dentro de los dos primeros meses. Ventriculostomía no está indicada. Chiari II. Laminectomia cervical alta. Siringomielia: Derivación desde la cavidad al peritoneo. PMID:24791219
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Los mitos como memoria colectiva de Los Pueblos.
NASA Astrophysics Data System (ADS)
Martín, P. T.
Myths are essentially something practical that allows those who believe in them to solve any ambiguity which could come up in their relation with nature. Since they bring information about the condition of the reality to which they belong, they are but the appropriate instrument to insert nature into culture by actually achieving an adaptation to the environment. The purpose of this essay is to show how the deification of plants, animals, and stars, which are present in the daily lives of "Amerindian" people, not only constitutes a source of rich mythology but also turns out to be an effective measure towards the continuity of social groups. Similarities or identifications between human life and the life of plants, animals and stars as well as mutual interplay are somehow present in those myths: stars which create or are changed into human being, animals or plants; human beings who create or are transformed into astral bodies; battles between peoples and stars, etc. On this base, mythology can provide not only keys to show how certain human groups have achieved their adaptation to the environment and how the different social systems and their relations to nature have developed, but also hints of changes which have taken place in other heavenly spheres such as the falling of meteors, the appearance of comets or any other significant events of this kind in the lives of these groups.
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[Parenting Information. Informacion Sobre Como Ser Padres Mejores.
ERIC Educational Resources Information Center
Moreno, Steve
These five booklets, containing information on how parenting can effect children's school achievement, are part of a series of 22 innovative booklets designed specifically to help parents understand and help their children learn. Booklet #1, "Parents--Teach Your Children to Learn [Before They Go to School]," defines intelligence and…
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Pérez Benítez, Carlos I.; Vicente, Benjamin; Zlotnick, Caron; Kohn, Robert; Johnson, Jennifer; Valdivia, Sandra; Rioseco, Pedro
2010-01-01
RESUMEN Durante la década de 1990 en los Estados Unidos (EU), el conocimiento sobre el trastorno de estrés post-traumático (TEPT) evolucionó de estudios específicos en un principio, sobre veteranos de guerra y sobre víctimas de desastres, a estudios epidemiológicos más tarde, sin embargo, la epidemiología del TEPT en países en desarrollo ha sido un área poco estudiada hasta ahora. Los expertos en el área de trauma han propuesto que los sucesos traumáticos que ocurren en la niñez son más perjudiciales para la salud mental que aquellos que ocurren más tarde en la vida. Este trabajo revisa los resultados de un estudio epidemiológico llevado a cabo en Chile. Específicamente, se revisan los resultados sobre las tasas de prevalencia del TEPT, traumas asociados más frecuentemente con él, así como la comorbilidad de este trastorno con otros trastornos psiquiátricos a lo largo de la vida. Igualmente se analizaron las diferencias del TEPT en cada sexo, así como la exposición a traumas en una muestra representativa de chilenos. Además se comparó la prevalencia de trastornos psiquiátricos en personas que sufrieron su primer trauma durante la niñez, durante la edad adulta, o que no reportaron traumas durante su vida. En estos estudios epidemiológicos se usaron módulos del TEPT y trastorno de personalidad antisocial (TPA) de la entrevista diagnóstica siguiendo los criterios del DSM-III-R (DIS–III-R). Para evaluar el resto de los trastornos psiquiátricos se usó la Entrevista Diagnóstica Internacional Compuesta (CIDI). Estos instrumentos fueron administrados en tres ciudades chilenas a 2390 personas mayores de 15 años. Para estimar los errores estándares (EE) debido al diseño de la muestra y a la necesidad de ajuste se usó el método Taylor de linearización seriada. También se usó un análisis de regresión logística para examinar la relación entre el TEPT, los factores demográficos de riesgo y el tipo de trauma. Además se utilizó la
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Effect of Uruguay’s National 100% Smokefree Law on Emergency Visits for Bronchospasm
Kalkhoran, Sara; Sebrié, Ernesto M; Sandoya, Edgardo; Glantz, Stanton A.
2014-01-01
Introduction Implementation of smokefree laws is followed by drops in hospital admissions for cardiovascular diseases and asthma. The impact of smokefree laws on use of non-hospital medical services has not been assessed. The purpose of this study is to evaluate the impact of Uruguay’s national 100% smokefree legislation on non-hospital emergency care visits and hospitalizations for bronchospasm and bronchodilator use. Methods The monthly number of non-hospital emergency care visits and hospitalizations for bronchospasm, as well as monthly puffs of bronchodilators (total and per person), from 3 years prior to the adoption of the 100% smokefree policy on March 1, 2006 through 5 years after the policy were assessed using interrupted time series negative binomial regression. Data analysis was conducted in 2014. Results The incidence of non-hospital emergency visits for bronchospasm decreased by 15% (incidence rate ratio [IRR]=0.85, 95% CI=0.76, 0.94) following implementation of the law. Hospitalizations for bronchospasm did not change significantly (IRR=0.89, 95% CI=0.66, 1.21). Total monthly puffs of salbutamol and ipratropium administered in the non-hospital emergency setting decreased by 224 (95% CI= −372, −76) and 179 (95% CI= −340, −18.6), respectively, from means of 1,222 and 1,007 before the law. Conclusions Uruguay’s 100% smokefree law was followed by fewer emergency visits for bronchospasm and less need for treatment, supporting adoption of such policies in low- and middle-income countries to reduce the disease burden and healthcare costs associated with smoking. PMID:25997906
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Effect of Uruguay's National 100% Smokefree Law on Emergency Visits for Bronchospasm.
Kalkhoran, Sara; Sebrié, Ernesto M; Sandoya, Edgardo; Glantz, Stanton A
2015-07-01
Implementation of smokefree laws is followed by drops in hospital admissions for cardiovascular diseases and asthma. The impact of smokefree laws on use of non-hospital medical services has not been assessed. The purpose of this study is to evaluate the impact of Uruguay's national 100% smokefree legislation on non-hospital emergency care visits, hospitalizations for bronchospasm, and bronchodilator use. The monthly number of non-hospital emergency care visits and hospitalizations for bronchospasm, as well as monthly puffs of bronchodilators (total and per person), from 3 years prior to the adoption of the 100% smokefree policy on March 1, 2006, through 5 years after the policy were assessed using interrupted time series negative binomial regression. Data analysis was conducted in 2014. The incidence of non-hospital emergency visits for bronchospasm decreased by 15% (incidence rate ratio [IRR]=0.85, 95% CI=0.76, 0.94) following implementation of the law. Hospitalizations for bronchospasm did not change significantly (IRR=0.89, 95% CI=0.66, 1.21). Total monthly puffs of salbutamol and ipratropium administered in the non-hospital emergency setting decreased by 224 (95% CI=-372, -76) and 179 (95% CI=-340, -18.6), respectively, from means of 1,222 and 1,007 before the law. Uruguay's 100% smokefree law was followed by fewer emergency visits for bronchospasm and less need for treatment, supporting adoption of such policies in low- and middle-income countries to reduce the disease burden and healthcare costs associated with smoking. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
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Use of heat of adsorption to quantify amorphous content in milled pharmaceutical powders.
Alam, Shamsul; Omar, Mahmoud; Gaisford, Simon
2014-01-01
Isothermal calorimetry operated in gas perfusion mode (IGPC) is often used to quantify the amorphous content of pharmaceutical powders. Typically, the calibration line is constructed using the heat of crystallisation as the sample is exposed to high levels of a plasticising vapour. However, since the physical form to which the amorphous fraction crystallises may be dependent on the presence of any crystalline seed, the calibration line is often seen to be non-linear, especially as the amorphous content of the sample approaches 100% w/w. Redesigning the experiment so that the calibration line is constructed with the heat of adsorption is an alternative approach that, because it is not dependent upon crystallisation to a physical form should ameliorate this problem. The two methods are compared for a model compound, salbutamol sulphate, which forms either a hydrate or an anhydrate depending on the amorphous content. The heat of adsorption method was linear between amorphous contents of 0 and 100% w/w and resulted in a detection limit of 0.3% w/w and a quantification limit of 0.92% w/w. The heat of crystallisation method was linear only between amorphous contents of 0 and 80% w/w and resulted in a detection limit of 1.7% w/w and a quantification limit of 5.28% w/w. Thus, the use of heat of adsorption is shown to be a better method for quantifying amorphous contents to better than 1% w/w. Copyright © 2013 Elsevier B.V. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Nadel, G.L.; Malik, K.U.; Lew, D.B.
The purpose of this study was to examine arachidonic acid (AA) metabolism and to characterize the type of adrenergic receptor (AR) involved in the production of the major metabolite of this fatty acid. ({sup 14}C)AA was incubated with GPT-rings and the radiolabelled products were extracted and separated by TLC method. The medium was also assayed for radiolabelled immunoreactive PG's (iPG's) and leukotrienes (LT) B4 and C4 by RIA or Enzyme immunoassay (EIA) after exposure to various AR agonists. ({sup 14}C)AA was incorporated into GPT-rings and metabolized mainly into iPGE2 and smaller amounts into PGF2{alpha}. Trace amounts of PGD2 and 6-keto-PGF1{alpha}more » but not LTB4 or LTC4 were detected by RIA and/or EIA. Incubation of GPT rings for 15 minutes with isoproterenol and salbutamol resulted in a significant increase of PGE2 synthesis (optimum conc: 10{sup {minus}7}, 10{sup {minus}7}M respectively). In contrast, dobutamine, norepinephrine, phenylnephrine and xylazine (up to 10{sup {minus}6}M) did not significantly increase PGE2 production. Isoproterenol-induced iPGE2 production was inhibited by a selective {beta}2 antagonist, butoxamine (70%: 10{sup {minus}7}M, 91%: 10{sup {minus}6}M) and somewhat reduced by {beta}1 antagonists practolol and metoprolol (30-64%:10{sup {minus}6}M). These data suggest that isoproterenol induced iPGE2 synthesis is primarily mediated via activation of {beta}2 adrenergic receptor.« less
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The role of indacaterol for chronic obstructive pulmonary disease (COPD)
Bardaro, Floriana; Stirpe, Emanuele
2013-01-01
Indacaterol is the first long-acting β2-agonist (LABAs) approved for the treatment of chronic obstructive pulmonary disease (COPD) that allows for once-daily (OD) administration. It is rapidly acting, with an onset of action in 5 minutes, like salbutamol and formoterol but with a sustained bronchodilator effect, that last for 24 hours, like tiotropium. In long-term clinical studies (12 weeks to 1 year) in patients with moderate to severe COPD, OD indacaterol 150 or 300 μg improved lung function (primary endpoint) significantly more than placebo, and improvements were significantly greater than twice-daily formoterol 12 μg or salmeterol 50 μg, and noninferior to OD tiotropium bromide 18 μg. Indacaterol was well tolerated at all doses and with a good overall safety profile. Cost-utility analyses show that indacaterol 150 μg has lower total costs and better outcomes than tiotropium and salmeterol. These findings suggest that indacaterol can be considered a first choice drug in the treatment of the patient with mild/moderate stable COPD. However, in people with COPD who remain symptomatic on treatment with indacaterol, adding a long-acting muscarinic antagonist (LAMA) is the preferable option. In any case, it is advisable to combine indacaterol with a OD inhaled corticosteroid (ICS), such as mometasone furoate or ciclesonide, in patients with low FEV1, and, in those patients who have many symptoms and a high risk of exacerbations, to combine it with a LAMA and a OD ICS. PMID:23991316
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Townend, John; Minelli, Cosetta; Mortimer, Kevin; Obaseki, Daniel O; Al Ghobain, Mohammed; Cherkaski, Hamid; Denguezli, Myriam; Gunesekera, Kirthi; Hafizi, Hasan; Koul, Parvaiz A; Loh, Li C; Nejjari, Chakib; Patel, Jaymini; Sooronbayev, Talant; Buist, Sonia A; Burney, Peter G J
2017-06-01
Poverty is strongly associated with mortality from COPD, but little is known of its relation to airflow obstruction.In a cross-sectional study of adults aged ≥40 years from 12 sites (N=9255), participating in the Burden of Obstructive Lung Disease (BOLD) study, poverty was evaluated using a wealth score (0-10) based on household assets. Obstruction, measured as forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) (%) after administration of 200 μg salbutamol, and prevalence of FEV 1 /FVC
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Alangari, Abdullah A; Malhis, Nidal; Mubasher, Mohamed; Al-Ghamedi, Najwa; Al-Tannir, Mohamad; Riaz, Muhammad; Umetsu, Dale T; Al-Tamimi, Saleh
2014-04-01
Inhaled corticosteroids, known to be effective as a maintenance medication in chronic asthma, have also been suggested as a therapy for acute asthma when given at high doses. A double-blind, randomized, placebo-controlled trial was conducted in children aged 2 to 12 years with moderate or severe acute asthma, as determined based on a clinical score of 5 to 15 points, where 15 is the most severe. We compared the addition of budesonide 1,500 μg vs placebo to standard acute asthma treatment, which included salbutamol, ipratropium bromide, and a single dose of prednisolone 2 mg/kg given at the beginning of therapy. The primary outcome was hospital admission rate within 4 h. A total of 906 ED visits by children with moderate or severe acute asthma were evaluated. Seventy-five cases out of 458 (16.4%) in the budesonide group vs 82 of 448 (18.3%) in the placebo group were admitted (OR, 0.84; 95% CI, 0.58-1.23; P=.38). However, among cases with high baseline clinical score (≥13), significantly fewer children were admitted in the budesonide group (27 of 76 [35.5%]) than in the placebo group (39 of 73 [53.4%]; OR, 0.42; 95% CI, 0.19-0.94; P=.03). The addition of budesonide nebulization did not decrease the admission rate of children with acute asthma overall. However, it may decrease the admission rate of children with severe acute asthma. ClinicalTrials.gov; No.: NCT01524198; URL: www.clinicaltrials.gov
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Larocca, Nancy; Moreno, Dolores; Garmendia, Jenny Valentina; Velasquez, Olga; Martin-Rojo, Joana; Talamo, Carlos; Garcia, Alexis; De Sanctis, Juan Bautista
2013-12-01
One of the gene polymorphisms often studied in asthmatic patients is the β2 adrenergic receptor (ADRβ2). Even though in the Venezuelan Mestizo population there is a high incidence of asthma, there are no direct reports of ADRβ2 gene polymorphism, and treatment response. The aim of this study was to assess, in this population, the gene frequency of ADRβ2 polymorphisms at codons 16 Arg/Gly and 27 Gln/Glu, allergen sensitization, and its relationship to bronchodilator response. Purified genomic DNA was obtained form 105 Mestizo asthmatic and 100 Mestizo healthy individuals from Venezuela. The two polymorphisms were assessed by PCR-RFLP. Patient sensitization to aeroallergens and their response to bronchodilatation were correlated. Significant differences between patients and controls were recorded in: 1) the prevalence of Arg/Arg at codon 16 (28.6% in patients vs. 47% in controls, P<0.01), 2) the frequency of heterozygotes Arg/Gly (55% in patients vs. 35% in controls, P<0.01). Conversely, no differences in polymorphism frequencies were found at codon 27. The haplotypes Arg/Gly-Gln/Gln were more common in patients than controls (P <0.01), whereas the Arg/Arg-Gln/Glu combination prevailed in the control group (P<0.01). The Arg/Gly and Gln/Glu genotypes were associated with better responses after salbutamol. The asthmatic homozygotes Arg/Arg have higher sensitivity to aeroallergens. The difference in Arg/Arg frequency between groups suggests that this could be a protective genotype although the asthmatic group had a higher sensitivity to aeroallergens. The asthmatic heterozygotes had better bronchodilator responses than the homozygotes.
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Yan, Shuwen; Yao, Bo; Lian, Lushi; Lu, Xinchen; Snyder, Shane A; Li, Rui; Song, Weihua
2017-03-07
The photochemical transformation of pharmaceutical and personal care products (PPCPs) in wastewater effluents is an emerging concern for environmental scientists. In the current study, the photodegradation of 29 PPCPs was examined in effluents under simulated solar irradiation. Direct photodegradation, triplet state effluent organic matter ( 3 EfOM*)-mediated and hydroxyl radical (HO • )-mediated degradation are three major pathways in the removal process. With the photodegradation of trace levels of PPCPs, the excitation-emission matrix (EEM) fluorescence intensities of the effluents were also gradually reduced. Therefore, fluorescence peaks have been identified, for the first time, as appropriate surrogates to assess the photodegradation of PPCPs. The humic-like fluorescence peak is linked to direct photolysis-labile PPCPs, such as naproxen, ronidazole, diclofenac, ornidazole, tinidazole, chloramphenicol, flumequine, ciprofloxacin, methadone, and dimetridazole. The tyrosine-like EEM peak is associated with HO • /CO 3 •- -labile PPCPs, such as trimethoprim, ibuprofen, gemfibrozil, atenolol, carbamazepine, and cephalexin. The tryptophan-like peak is associated with 3 EfOM*-labile PPCPs, such as clenbuterol, metoprolol, venlafaxine, bisphenol A, propranolol, ractopamine, salbutamol, roxithromycin, clarithromycin, azithromycin, famotidine, terbutaline, and erythromycin. The reduction in EEM fluorescence correlates well with the removal of PPCPs, allowing a model to be constructed. The solar-driven removal of EEM fluorescence was applied to predict the attenuation of 11 PPCPs in five field samples. A close correlation between the predicted results and the experimental results suggests that fluorescence may be a suitable surrogate for monitoring the solar-driven photodegradation of PPCPs in effluents.
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Guenette, Estelle; Barrett, Andrew; Kraus, Debbie; Brody, Rachel; Harding, Ljiljana; Magee, Gavin
2009-10-01
Medicines for delivering therapeutic agents to the lung as dry powders primarily consist of a carrier and a micronised active pharmaceutical ingredient (API). The performance of an inhaled formulation will depend on a number of factors amongst which the particle size distribution (PSD) plays a key role. It is suggested that increasing the number of fine particles in the carrier can improve the aerosolisation of the API. In addition the effect of PSD upon a bulk powder is also broadly understood in terms of powder flow. Other aspects of functionality that different size fractions of the carrier affect are not clearly understood; for example, it is not yet clearly known how different size fractions contribute to the different functionalities of the carrier. It is the purpose of this investigation to examine the effects of different lactose size fractions on fine particle dose, formulation stability and the ability to process and fill the material in the preferred device. In order to understand the true impact of the size fractions of lactose on the performance of dry powder inhaled (DPI) products, a statistically designed study has been conducted. The study comprised various DPI blend formulations prepared using lactose monohydrate carrier systems consisting of mixtures of four size fractions. Interactive mixtures were prepared containing 1% (w/w) salbutamol sulphate. The experimental design enabled the evaluation of the effect of lactose size fractions on processing and performance attributes of the formulation. Furthermore, the results of the study demonstrate that an experimental design approach can be used successfully to support dry powder formulation development.
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Bond, G R; Pièche, S; Sonicki, Z; Gamaluddin, H; El Guindi, M; Sakr, M; El Seddawy, A; Abouzaid, M; Youssef, A
2008-03-01
Unintended hydrocarbon ingestion is a common reason for pediatric hospitalization in the developing world. To derive a clinical decision rule, to identify patients likely to require a higher level facility (resource-requiring cases), that can be used at primary health care facilities with limited diagnostic and therapeutic resources. A prospective study of children 2 to 59 months old presenting to a poison treatment facility within 2 hours of oral hydrocarbon exposure. History and objective signs were recorded at admission and at 6, 12, 24 and, if present, 48 hours. Inclusion in the resource-requiring outcome group required: oxygen saturation <94%; any CNS depression; any treatment with (salbutamol); any care in the ICU; or death. 256 met the inclusion criteria and completed the study. Of these, 170 had a course requiring resources unavailable at most primary health care facilities, and 86 did not. The presence of wheezing, any alteration in consciousness (lethargy or any restlessness), or a rapid respiratory rate for age (RR >or= 50/min if age < 12 mo, >or= 40/min if age >or= 12 mo) at presentation identified 167 of 170 of these patients (sensitivity 0.98). Thirty-six of 86 patients classified as non-resource requiring were correctly identified (specificity 0.42). No combination of clinical symptoms provided better discrimination while preserving sensitivity. This study suggests a triage decision rule based on the presence of wheezing, altered consciousness, or a rapid respiratory rate within 2 hours of hydrocarbon exposure. Such a rule requires validation in other settings.
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Effect of smoking status on the efficacy of the SMART regimen in high risk asthma.
Pilcher, Janine; Patel, Mitesh; Reddel, Helen K; Pritchard, Alison; Black, Peter; Shaw, Dominick; Holt, Shaun; Weatherall, Mark; Beasley, Richard
2016-07-01
The optimal management of people with asthma with a significant smoking history is uncertain. The aim of this study was to determine whether the efficacy/safety profile of single combination inhaled corticosteroid (ICS)/long acting beta-agonist (LABA) inhaler maintenance and reliever therapy is influenced by smoking status. We undertook secondary analyses from an open-label 24-week randomized study of 303 high risk adult asthma patients randomized to budesonide/formoterol 200/6-µg-metred dose inhaler for maintenance (two actuations twice daily) and either budesonide/formoterol 200/6-µg-metred dose inhaler one actuation ('single ICS/LABA maintenance and reliever therapy (SMART)' regimen) or salbutamol 100 µg 1-2 actuations for symptom relief ('Standard' regimen). Smoking status was classified in to three groups, as 'current', 'ex' or 'never', and a smoking/treatment interaction term tested for each outcome variable. The primary outcome variable was number of participants with at least one severe exacerbation. There were 59 current, 97 ex and 147 never smokers included in the analyses. The smoking status/treatment interaction term was not statistically significant for any of the outcome measures. With adjustment for smoking status, the number of participants with severe exacerbations was lower with the SMART regimen (OR 0.45, 95% CI: 0.26-0.77, P = 0.004; P value for interaction between smoking status and treatment 0.29). We conclude that the favourable safety/efficacy profile of the SMART regimen applies to patients with high risk asthma, irrespective of smoking status. © 2016 Asian Pacific Society of Respirology.
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Wu, Kesheng; Guo, Liang; Xu, Wei; Xu, Hengyi; Aguilar, Zoraida P; Xu, Guomao; Lai, Weihua; Xiong, Yonghua; Wan, Yiqun
2014-11-01
A magnetic solid-phase extraction method (MSPE) was developed to pre-concentrate and cleanup clenbuterol (CLE) from pork muscle. Novel sulfonated polystyrene magnetic nanobeads (spMNBs) were synthesized via a one-pot emulsion copolymerization method by using divinylbenzene, styrene, and sodium styrene sulfonate in the presence of oleic acid-modified and 10-undecylenic acid-modified magnetic ferrofluid. The resulting spMNBs exhibited high adsorption efficiency for CLE and for 10 other common beta-adrenergic agonists, namely, brombuterol, ractopamine, tulobuterol, bambuterol, cimbuterol, mabuterol, clorprenaline, penbutolol, salbutamol, and cimaterol. The adsorption behavior of the spMNBs for CLE was described by the Langmuir equation with a maximum adsorption capacity of 0.41 mg/g. Under the optimized parameters, the extraction of CLE from 0.5 g of pork muscle required 25mg of the spMNBs at a shortened adsorption time (0.5 min). The proposed MSPE was coupled with colloidal gold nanoparticle-based immunochromatographic assay (MSPE-AuNPIA) for the quantitative detection of CLE residue in pork muscle. The limit of detection and limit of quantification for the pork muscle were 0.10 and 0.24 ng/g, respectively. The intra-day and inter-day assay recoveries at three CLE spiked concentrations ranged from 92.5% to 98.1%, with relative standard deviations ranging from 3.2% to 13.0%. The results of MSPE-AuNPIA were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The CLE values obtained with MSPE-AuNPIA agreed with those obtained with LC-MS/MS. Copyright © 2014 Elsevier B.V. All rights reserved.
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Proctalgia fugax, an evidence-based management pathway.
Jeyarajah, Santhini; Chow, Andre; Ziprin, Paul; Tilney, Henry; Purkayastha, Sanjay
2010-09-01
Proctalgia fugax (PF) is a benign anorectal condition which has been described in the literature since the nineteenth century commonly presenting to general surgeons. There is little high level evidence on the subject and its therapeutic modalities. We aimed through this systematic literature review to outline the definition and diagnostic criteria of this condition, the aetiology and differential diagnoses and describe the different treatment modalities that have been attempted and their success. A literature search of Google Scholar and Medline using Pubmed as the search engine was used to identify all studies directly related to the definition, aetiology and treatment options for this condition (latest at 12 August 2008) was performed. The search produced 61 references with three others obtained from the references of these papers. The prevalence of PF in the general population ranges from 4% to 18%. The diagnosis is based on the presence of characteristic symptoms as defined by Rome III guidelines and physical examination. The mainstay of treatment is reassurance and careful counselling with evidence in the literature for warm baths, topical treatment with glyceryl trinitrate or diltiazem and salbutamol inhalation. In persistent cases, local anaesthetic blocks, clonidine or Botox injections can be considered after clarification of risk and benefit. Based on this we suggest that diagnosis should be made through exclusion of common organic causes such as haemorrhoids, anal fissure or anorectal carcinoma and on the fulfillment of Rome III criteria. The main treatment for this benign condition remains reassurance and topical treatment.
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Efficacy of nebulised budesonide versus oral prednisolone in acute severe asthma.
Arulparithi, Cuddalore Subramanian; Babu, Thirunavukkarasu Arun; Ravichandran, C; Santhanam, Indumathy; Sathyamurthi, B; Parivathini, S; Hemachitra, J
2015-04-01
To compare the efficacy of nebulised budesonide with that of oral prednisone in the treatment of acute severe asthma in children. Children aged 5-12 y with acute exacerbation of bronchial asthma were included. The study (budesonide) group received budesonide respirator solution (800 μg) at intervals of 20 min and a single dose of placebo tablets. The control (prednisolone) group received placebo solution at intervals of 20 min and a single dose of oral prednisolone (2 mg/kg). Both groups received three doses of nebulised salbutamol (0.15 mg/kg). Heart rate, respiratory rate, oxygen saturation, PEFR (Peak Expiratory Flow Rate) and fitness for discharge were assessed. Both groups showed a progressive decrease in tachycardia with treatment, but it was significantly greater in study group (p = 0.0002). There was significant decrease in tachypnea and improvement in oxygen saturation in both groups, but the difference between the groups (p = 0.334 and p = 0.814 respectively) was not significant. There was significant improvement in PEFR values in budesonide group (p = 0.024). Both groups showed significant improvement in clinical severity scores at the end of 2 h (p < 0.0001). Budesonide group had significantly higher proportion of patients fit for discharge at 2 h (based on clinical severity scores) (p = 0.0278). Nebulised budesonide significantly improves PEFR levels and fitness for discharge at 2 h when compared to oral prednisolone in children between 5 and 12 y with acute severe asthma.
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Control of nasal vasculature and airflow resistance in the dog.
Lung, M A; Phipps, R J; Wang, J C; Widdicombe, J G
1984-01-01
Nasal vascular and airflow resistances have been measured in dogs, simultaneously on both sides separately. Vascular resistance was measured either by constant flow perfusion of the terminal branch of the maxillary artery (which supplies, via the sphenopalatine artery, the nasal septum, most of the turbinates and the nasal sinuses) or by measuring blood flow through this artery, maintained by the dog's own blood pressure. Airflow resistance was assessed by inserting balloon-tipped endotracheal catheters into the back of each nasal cavity via the nasopharynx, and measuring transnasal pressure at constant airflow through each side of the nose simultaneously. Preliminary experiments indicated that there was 5-10% collateral anastomosis between the two sides. Close-arterial injection of drugs showed different patterns of response. Adrenaline, phenylephrine, chlorpheniramine and low doses of prostaglandin F2 alpha increased vascular resistance and lowered airway resistance. Salbutamol, methacholine and histamine lowered vascular resistance and increased airway resistance. Dobutamine decreased airway resistance with a small increase in vascular resistance. Prostaglandins E1, E2 and F2 alpha (high dose) decreased both vascular and airway resistances. Substance P, eledoisin-related peptide and vasoactive intestinal polypeptide lowered vascular resistance with little change in airway resistance. The results are interpreted in terms of possible drug actions on precapillary resistance vessels, sinusoids and venules, and arteriovenous anastomoses. It is concluded that nasal airway resistance cannot be correlated with vascular resistance or blood flow, since the latter has a complex and ill-defined relationship with nasal vascular blood volume. PMID:6204040
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Control of nasal vasculature and airflow resistance in the dog.
Lung, M A; Phipps, R J; Wang, J C; Widdicombe, J G
1984-04-01
Nasal vascular and airflow resistances have been measured in dogs, simultaneously on both sides separately. Vascular resistance was measured either by constant flow perfusion of the terminal branch of the maxillary artery (which supplies, via the sphenopalatine artery, the nasal septum, most of the turbinates and the nasal sinuses) or by measuring blood flow through this artery, maintained by the dog's own blood pressure. Airflow resistance was assessed by inserting balloon-tipped endotracheal catheters into the back of each nasal cavity via the nasopharynx, and measuring transnasal pressure at constant airflow through each side of the nose simultaneously. Preliminary experiments indicated that there was 5-10% collateral anastomosis between the two sides. Close-arterial injection of drugs showed different patterns of response. Adrenaline, phenylephrine, chlorpheniramine and low doses of prostaglandin F2 alpha increased vascular resistance and lowered airway resistance. Salbutamol, methacholine and histamine lowered vascular resistance and increased airway resistance. Dobutamine decreased airway resistance with a small increase in vascular resistance. Prostaglandins E1, E2 and F2 alpha (high dose) decreased both vascular and airway resistances. Substance P, eledoisin-related peptide and vasoactive intestinal polypeptide lowered vascular resistance with little change in airway resistance. The results are interpreted in terms of possible drug actions on precapillary resistance vessels, sinusoids and venules, and arteriovenous anastomoses. It is concluded that nasal airway resistance cannot be correlated with vascular resistance or blood flow, since the latter has a complex and ill-defined relationship with nasal vascular blood volume.
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Haroun, Huda M.; Ali, Hassan M.; Tag Eldeen, Imad Eldeen M.
2012-01-01
This audit of hospital care of acute wheeze and asthma aimed to assess the degree of adherence of the acute care of the asthma patients to the published international guidelines. Information was collected in six key areas: patient demographics; initial asthma severity assessment; in-hospital treatment; asthma prophylaxis; asthma education and emergency planning; and follow-up arrangements. The area of initial asthma severity assessment showed defciencies in the clinical measures currently used to verify case severity. In- hospital treatment on the other hand was consistent with recommendations in the use of the inhaled β-2 agonist salbutamol as bronchodilator, the discrete use of aminophylline and the small number of patients ordered chest X-ray. However, the treatment was incoherent with recommendations in the delivery method used for inhaled bronchodilator in relation to the age group of treated patients, absence of ipratropium bromide as a bronchodilator in the management and the large use of antibiotics. Assessment of the areas of asthma prophylaxis, asthma education and emergency- planning and follow-up arrangements illustrated that little efforts were made to assure safe discharge, although these measures have been shown to reduce morbidity after the exacerbation and reduce relapse rates and signifcantly reduce hospitalizations, unscheduled acute visits, missed work days, as well as improving quality of life. This audit emphasizes the need for the adoption of a management protocol for acute asthma care in the emergency department based on published international guidelines and the assurance of its implementation, monitoring and evaluation using the right tools to improve patient care. PMID:27493337
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The Variation of Catalyst and Carrier Gas on Anisole Deoxygenation Reaction
NASA Astrophysics Data System (ADS)
Ariyani, D.; Dwi Nugrahaningtyas, Khoirina; Heraldy, E.
2018-03-01
This research aims to determine the best catalyst and carrier gas in anisole deoxygenation reaction. The reaction was carried out over a flow system with a variation of catalyst CoMo A (CoMo/USY reduction), CoMo B (CoMo/USY oxidation-reduction), and CoMo C (CoMo/ZAA oxidation-reduction). In addition, variation of carrier gas nitrogen and hydrogen was investigated. The result was analyzed using Gas Chromatography-Mass Spectroscopy (GC-MS). The deoxygenation anisole result showed that CoMo A catalyst with hydrogen as the carrier gas has the highest total product yield (50.72 %), intermediate product yield (38.49 % in phenol and 6.99 % in benzaldehyde), and deoxygenation yield (5.24 %). The CoMo C catalyst exhibited the most selective deoxygenation product. The nitrogen carrier gas with the CoMo C catalyst has the best selectivity of benzene product (93.92 %).
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Sanjar, S.; Aoki, S.; Kristersson, A.; Smith, D.; Morley, J.
1990-01-01
1. Guinea-pigs were sensitized with 3 injections of ovalbumin (OA) (1 or 10 micrograms per animal) using Al(OH)3 and pertussis vaccine as adjuvants at two week intervals. 2. Sensitized guinea-pigs were challenged with an aerosol of OA (0.1%) over a one hour period and both airway reactivity and cellular content of bronchoalveolar lavage (BAL) fluid were assessed at intervals for up to 7 days. 3. Guinea-pigs sensitized with 1 microgram of ovalbumin responded to an aerosol of OA with increased pulmonary airway eosinophilia, which was evident 1 day after challenge and was present for up to 7 days. Airway hyperreactivity was not detectable in these animals. 4. Guinea-pigs sensitized with 10 micrograms of ovalbumin responded to an aerosol of OA with increased pulmonary airway neutrophilia and eosinophilia and with increased airway reactivity which was maximal between 8 and 24 h after exposure to OA. 5. Depletion of circulating platelets or neutrophils, by use of selective antisera, did not alter either the magnitude of eosinophilia or the intensity of airway reactivity in sensitized guinea-pigs (10 micrograms) exposed to an aerosol of OA. 6. Pretreatment of sensitized guinea-pigs (10 micrograms) for 6 days with AH 21-132, aminophylline, dexamethasone or ketotifen inhibited pulmonary airway eosinophilia, but did not diminish airway hyperreactivity. Neither eosinophil accumulation nor development of airway hyperreactivity was influenced by treatment with mepyramine or salbutamol over a 6 day period before OA inhalation. 7. Although eosinophilia may occur in association with increased airway reactivity in this animal model, there is no evidence of a causal relationship. PMID:2361168
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Clinical features of the myasthenic syndrome arising from mutations in GMPPB.
Rodríguez Cruz, Pedro M; Belaya, Katsiaryna; Basiri, Keivan; Sedghi, Maryam; Farrugia, Maria Elena; Holton, Janice L; Liu, Wei Wei; Maxwell, Susan; Petty, Richard; Walls, Timothy J; Kennett, Robin; Pitt, Matthew; Sarkozy, Anna; Parton, Matt; Lochmüller, Hanns; Muntoni, Francesco; Palace, Jacqueline; Beeson, David
2016-08-01
Congenital myasthenic syndrome (CMS) due to mutations in GMPPB has recently been reported confirming the importance of glycosylation for the integrity of neuromuscular transmission. Review of case notes of patients with mutations in GMPPB to identify the associated clinical, neurophysiological, pathological and laboratory features. In addition, serum creatine kinase (CK) levels within the Oxford CMS cohort were retrospectively analysed to assess its usefulness in the differential diagnosis of this new entity. All patients had prominent limb-girdle weakness with minimal or absent craniobulbar manifestations. Presentation was delayed beyond infancy with proximal muscle weakness and most patients recall poor performance in sports during childhood. Neurophysiology showed abnormal neuromuscular transmission only in the affected muscles and myopathic changes. Muscle biopsy showed dystrophic features and reduced α-dystroglycan glycosylation. In addition, myopathic changes were present on muscle MRI. CK was significantly increased in serum compared to other CMS subtypes. Patients were responsive to pyridostigimine alone or combined with 3,4-diaminopyridine and/or salbutamol. Patients with GMPPB-CMS have phenotypic features aligned with CMS subtypes harbouring mutations within the early stages of the glycosylation pathway. Additional features shared with the dystroglycanopathies include myopathic features, raised CK levels and variable mild cognitive delay. This syndrome underlines that CMS can occur in the absence of classic myasthenic manifestations such as ptosis and ophthalmoplegia or facial weakness, and links myasthenic disorders with dystroglycanopathies. This report should facilitate the recognition of this disorder, which is likely to be underdiagnosed and can benefit from symptomatic treatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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Desalu, Olufemi Olumuyiwa; Adeoti, Adekunle Olatayo; Ogunmola, Olarinde Jeffrey; Fadare, Joseph Olusesan; Kolawole, Tolutope Fasanmi
2016-01-01
To audit the quality of acute asthma care in two tertiary hospitals in a state in the southwestern region of Nigeria and to compare the clinical practice against the recommendations of the Global Initiative for Asthma (GINA) guideline. We carried out a retrospective analysis of 101 patients who presented with acute exacerbation of asthma to the hospital between November 2010 and October 2015. Majority of the cases were females (66.3%), <45 years of age (60.4%), and admitted in the wet season (64.4%). The median duration of hospital stay was 2 days (interquartile range; 1-3 days) and the mortality was 1.0%. At admission, 73 (72.3%) patients had their triggering factors documented and 33 (32.7%) had their severity assessed. Smoking status, medication adherence, serial oxygen saturation, and peak expiratory flow rate measurement were documented in less than half of the cases, respectively. Seventy-six (75.2%) patients had nebulized salbutamol, 89 (88.1%) had systemic corticosteroid, and 78 (77.2%) had within 1 h. On discharge, 68 (67.3%) patients were given follow-up appointment and 32 (31.7%) were reviewed within 30 days after discharge. Less than half were prescribed an inhaled corticosteroid (ICS), a self-management plan, or had their inhaler technique reviewed or controller medications adjusted. Overall, adherence to the GINA guideline was not satisfactory and was very poor among the medical officers. The quality of acute asthma care in our setting is not satisfactory, and there is a low level of compliance with most recommendations of asthma guidelines. This audit has implicated the need to address the non-performing areas and organizational issues to improve the quality of care.
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Calligaro, Gregory L; Raine, Richard I; Bateman, Mary E; Bateman, Eric D; Cooper, Christopher B
2014-02-01
Dynamic hyperinflation (DH) during exercise is associated with both dyspnea and exercise limitation in COPD. Metronome-paced tachypnoea (MPT) is a simple alternative for studying DH. We compared MPT with exercise testing (XT) as methods of provoking DH, and assessed their relationship with dyspnea. We studied 24 patients with moderate COPD (FEV1 59 ± 9% predicted) after inhalation of ipratropium/salbutamol combination or placebo in a double-blind, crossover design. Inspiratory capacity (IC) was measured at baseline and after 30 seconds of MPT with breathing frequencies (fR) of 20, 30 and 40 breaths/min and metronome-defined I:E ratios of 1:1 and 1:2, in random sequence, followed by incremental cycle ergometry with interval determinations of IC. DH was defined as a decline in IC from baseline (∆IC) for both methods. Dyspnea was assessed using a Borg CR-10 scale. ∆IC during MPT was greater with higher fR and I:E ratio of 1:1 versus 1:2, and less when patients were treated with bronchodilator rather than placebo (P = 0.032). DH occurred during 19 (40%) XTs, and during 35 (73%) tests using MPT. Eleven of 18 (61%) non-congruent XTs (where DH occurred on MPT but not XT) terminated before fR of 40 breaths/min was reached. Although greater during XT, the intensity of dyspnea bore no relationship to DH during either MPT and XT. MPT at 40 breaths/min and I:E of 1:1 elicits the greatest ∆IC, and is a more sensitive method for demonstrating DH. The relationship between DH and dyspnea is complex and not determined by DH alone.
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Cros, Caroline; Brette, Fabien
2013-01-01
β-adrenergic stimulation is a key regulator of cardiac function. The localization of major cardiac adrenergic receptors (β1 and β2) has been investigated using biochemical and biophysical approaches and has led to contradictory results. This study investigates the functional subcellular localization of β1- and β2-adrenergic receptors in rat ventricular myocytes using a physiological approach. Ventricular myocytes were isolated from the hearts of rat and detubulated using formamide. Physiological cardiac function was measured as Ca2+ transient using Fura-2-AM and cell shortening. Selective activation of β1- and β2-adrenergic receptors was induced with isoproterenol (0.1 μmol/L) and ICI-118,551 (0.1 μmol/L); and with salbutamol (10 μmol/L) and atenolol (1 μmol/L), respectively. β1- and β2-adrenergic stimulations induced a significant increase in Ca2+ transient amplitude and cell shortening in intact rat ventricular myocytes (i.e., surface sarcolemma and t-tubules) and in detubulated cells (depleted from t-tubules, surface sarcolemma only). Both β1- and β2-adrenergic receptors stimulation caused a greater effect on Ca2+ transient and cell shortening in detubulated myocytes than in control myocytes. Quantitative analysis indicates that β1-adrenergic stimulation is ∼3 times more effective at surface sarcolemma compared to t-tubules, whereas β2- adrenergic stimulation occurs almost exclusively at surface sarcolemma (∼100 times more effective). These physiological data demonstrate that in rat ventricular myocytes, β1-adrenergic receptors are functionally present at surface sarcolemma and t-tubules, while β2-adrenergic receptors stimulation occurs only at surface sarcolemma of cardiac cells. PMID:24303124
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Kaialy, Waseem; Nokhodchi, Ali
2015-02-20
The purpose of this work was to evaluate the physicochemical and inhalation characteristics of different size fractions of a promising carrier, i.e., freeze-dried mannitol (FDM). FDM was prepared and sieved into four size fractions. FDMs were then characterized in terms of micromeritic, solid-state and bulk properties. Dry powder inhaler (DPI) formulations were prepared using salbutamol sulphate (SS) and then evaluated in terms of drug content homogeneity and in vitro aerosolization performance. The results showed that the crystalline state of mannitol was maintained following freeze-drying for all size fractions of FDM. All FDM particles showed elongated morphology and contained mixtures of α-, β- and δ-mannitol. In comparison to small FDM particles, FDMs with larger particle sizes demonstrated narrower size distributions, higher bulk and tap densities, lower porosities and better flowability. Regardless of particle size, all FDMs generated a significantly higher (2.2-2.9-fold increase) fine particle fraction (FPF, 37.5 ± 0.9%-48.6 ± 2.8%) of SS in comparison to commercial mannitol. The FPFs of SS were related to the shape descriptors of FDM particles; however, FPFs did not prove quantitative apparent relationships with either particle size or powder bulk descriptors. Large FDM particles were more favourable than smaller particles because they produced DPI formulations with better flowability, better drug content homogeneity, lower amounts of the drug depositing on the throat and contained lower fine-particle-mannitol. Optimized stable DPI formulations with superior physicochemical and pharmaceutical properties can be achieved using larger particles of freeze-dried mannitol (FDM). Copyright © 2014 Elsevier B.V. All rights reserved.
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A new method for examining the cost savings of reducing COPD exacerbations.
Mapel, Douglas W; Schum, Michael; Lydick, Eva; Marton, Jeno P
2010-01-01
Some treatments for chronic obstructive pulmonary disease (COPD) can reduce exacerbations, and thus could have a favourable impact on overall healthcare costs. To evaluate a new method for assessing the potential cost savings of COPD controller medications based on the incidence of exacerbations and their related resource utilization in the general population. Patients with COPD (n = 1074) enrolled in a regional managed care system in the US were identified using administrative data and divided by their medication use into three groups (salbutamol, ipratropium and salmeterol). Exacerbations were captured using International Classification of Diseases, Ninth Edition (ICD-9) and current procedural terminology (CPT) codes, then logistic regression models were created that described the risk of exacerbations for each comparator group and exacerbation type over a 6-month period. A Monte Carlo simulation was then applied 1000 times to provide the range of potential exacerbation reductions and cost consequences in response to a range of hypothetical examples of COPD controller medications. Exacerbation events for each group could be modelled such that the events predicted by the Monte Carlo estimates were very close to the actual prevalences. The estimated cost per exacerbation avoided depended on the incidence of exacerbation in the various subpopulations, the assumed relative risk reduction, the projected daily cost for new therapy, and the costs of exacerbation treatment. COPD exacerbation events can be accurately modelled from the healthcare utilization data of a defined cohort with sufficient accuracy for cost-effectiveness analysis. Treatments that reduce the risk or severity of exacerbations are likely to be cost effective among those patients who have frequent exacerbations and hospitalizations.
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Fawzy, Manal S.; Hussein, Mohammad H.; Abdelaziz, Eman Z.; Yamany, Hussain A.; Ismail, Hussein M.; Toraih, Eman A.
2016-01-01
Chronic obstructive pulmonary disease (COPD) is a multifactorial chronic respiratory disease, characterized by an obstructive pattern. Understanding the genetic predisposition of COPD is essential to develop personalized treatment regimens. MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs that modulate the expression levels of specific proteins based on sequence complementarity with their target mRNA molecules. Emerging evidences demonstrated the potential use of miRNAs as a disease biomarker. This pilot study aimed to investigate the association of the MIR-196a2 rs11614913 (C/T) polymorphism with COPD susceptibility, the clinical outcome and bronchodilator response to short-acting β2-agonist. Genotyping of rs11614913 polymorphism was determined in 108 COPD male patients and 116 unrelated controls using real-time polymerase chain reaction technology. In silico target prediction and network core analysis were performed. COPD patients did not show significant differences in the genotype distribution (p = 0.415) and allele frequencies (p = 0.306) of the studied miRNA when compared with controls. There were also no associations with GOLD stage, dyspnea grade, disease exacerbations, COPD assessment test for estimating impact on health status score, or the frequency of intensive care unit admission. However, COPD patients with CC genotype corresponded to the smallest bronchodilator response after Salbutamol inhalation, the heterozygotes (CT) had an intermediate response, while those with the TT genotype showed the highest response (p < 0.001). In conclusion MIR-196a2 rs11614913 polymorphism is associated with the bronchodilator response of COPD in our sample of the Egyptian population, generating hypothesis of the potential use of MIR-196a2 variant as a pharmacogenetic marker for COPD. PMID:27043015
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Rational drug use for acute bronchiolitis in emergency care.
Uysalol, Metin; Haşlak, Fatih; Özünal, Zeynep Güneş; Vehid, Hayriye; Uzel, Nedret
2017-01-01
Uysalol M, Haşlak F, Özünal ZG, Vehid H, Uzel N. Rational drug use for acute bronchiolitis in emergency care. Turk J Pediatr 2017; 59: 155-161. Despite the large variety of inhaled treatment options of acute bronchiolitis, there is no generally agreed treatment regime. This study aimed to determine the most appropriate treatment option. This was a double-blind randomized prospective clinical trial and has been performed in emergency department. The mean age of the 378 infants included in the study was 7.63 ± 4.6 months, and 54.8% (207) were boys. Patients were randomized by using the lottery method for simple random sample into 5 different treatment options; 3% hypertonic saline, nebulized adrenaline, nebulized adrenaline mixed with 3% hypertonic saline, nebulized salbutamol, and as control group; normal saline (0.9% NaCl). From the first treatment time until discharge time; treatment durations, adverse events and readmission rates within the first fifteen days were recorded for each patient. Nebulized adrenaline mixed with 3% hypertonic saline, as compared with other options, were associated with a significantly higher discharge rate at 4th hours (p < 0.001) and shorter length of hospital stay (p=0.039). However, there was no significant difference between options with regard to adverse events, discharge rates at 24th hours, and readmission rates within the first fifteen days. The superiority of discharge rates at 4 hours of nebulized adrenaline mixed with 3% hypertonic saline, was evaluated as `better acute response` and can be helpful to reduce hospitalization needs. Additionally, this option seems to be more effective to reduce length of hospital stay.
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Lee, Ji Yun; Moon, Hee; Kim, Chang Jong
2010-01-01
For the identification of anti-inflammatory ingredients from Forsythiae fructus (FF), we isolated three hydroxyl pentacyclic triterpene acids (HTAs), namely, oleanolic acid, ursolic acid, and betulinic acid, from an ethylacetate fraction of FF, and evaluated the effect of these triterpene acids on asthmatic guinea pigs by measuring specific airway resistance (sRaw) during both immediate-phase response (IAR) and late-phase response (LAR) following ovalbumin challenge using a double-chambered plethysmograph. Evaluation of leukocytes and chemical mediators in bronchoalveolar lavage fluid (BALF), in addition to a histopathological survey, was also performed. Ursolic, oleanolic and betulinic acids dosed at 12.5 mg/kg significantly (p<0.05) decreased sRaw by 46.80%, 46.54% and 44.27% during in IAR, respectively. And ursolic acid (25 mg/kg), and oleanolic and betulinic acids (50 mg/kg) significantly (p<0.05) decreased sRaw by 38.19%, 38.15% and 35.55% in LAR, respectively. Histamine and phospholipase A(2) activity in BALF were significantly decreased by HTAs at 12.5 mg/kg, whereas eosinophil peroxide (EPO) activity in BALF and recruitment of eosinophils were significantly decreased by HTAs at 25 mg/kg, as well as improvement of pathological changes. However, betulinic acid at 12.5 mg/kg, and ursolic and oleanolic acids at 25 mg/kg significantly inhibited leukocytes in BALF, especially eosinophils and neutrophils. Three HTAs were found to have dose-dependent anti-asthmatic effects and ursolic acid is the most active, but their activities were less than those of sodium cromoglycate, salbutamol, and dexamethasone. These results indicate HTAs had anti-asthmatic activity by decreasing of sRaw, and eosinophil recruitment and release of inflammatory mediators into the lungs.
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Doping and respiratory system.
Casali, L; Pinchi, G; Puxeddu, E
2007-03-01
Historically many different drugs have been used to enhance sporting performances. The magic elixir is still elusive and the drugs are still used despite the heavy adverse effects. The respiratory system is regularly involved in this research probably because of its central location in the body with several connections to the cardiovascular system. Moreover people are aware that O2 consumption and its delivery to mitochondria firstly depend on ventilation and on the respiratory exchanges. The second step consists in the tendency to increase V'O2 max and to prolong its availability with the aim of improving the endurance time and to relieve the fatigue. Many methods and substances had been used in order to gain an artificial success. Additional oxygen, autologous and homologous transfusion and erythropoietin, mainly the synthetic type, have been administered with the aim of increasing the amount of oxygen being delivered to the tissues. Some compounds like stimulants and caffeine are endowed of excitatory activity on the CNS and stimulate pulmonary ventilation. They did not prove to have any real activity in supporting the athletic performances. Beta-adrenergic drugs, particularly clenbuterol, when administered orally or parenterally develop a clear illicit activity on the myosin fibres and on the muscles as a whole. Salbutamol, terbutaline, salmeterol and formoterol are legally admitted when administrated by MDI in the treatment of asthma. The prevalence of asthma and bronchial hyperactivity is higher in athletes than amongst the general population. This implies that clear rules must be provided to set a correct diagnosis of asthma in the athletes and a correct therapy to align with the actual guidelines according to the same rights of the "other" asthmatic patients.
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Peters, Ubong; Hernandez, Paul; Dechman, Gail; Ellsmere, James; Maksym, Geoffrey
2016-05-01
Obesity is associated with respiratory symptoms that are reported to improve with weight loss, but this is poorly reflected in spirometry, and few studies have measured respiratory mechanics with oscillometry. We investigated whether early changes in lung mechanics following weight loss are detectable with oscillometry. Furthermore, we investigated whether the changes in lung mechanics measured in the supine position following weight loss are associated with changes in sleep quality. Nineteen severely obese female subjects (mean body mass index, 47.2 ± 6.6 kg/m(2)) were evaluated using spirometry, oscillometry, plethysmography, and the Pittsburgh Sleep Quality Index before and 5 weeks after bariatric surgery. These tests were conducted in both the upright and the supine position, and pre- and postbronchodilation with 200 μg of salbutamol. Five weeks after surgery, weight loss of 11.5 ± 2.5 kg was not associated with changes in spirometry and plethysmography, with the exception of functional residual capacity. There were also no changes in upright respiratory system resistance (Rrs) or reactance following weight loss. Importantly, however, in the supine position, weight loss caused a substantial reduction in Rrs. In addition, sleep quality improved significantly and was highly correlated with the reduction in supine Rrs. Prior to weight loss, subjects did not respond to the bronchodilator when assessed in the upright position with either spirometry or oscillometry; however, with modest weight loss, bronchodilator responsiveness returned to the normal range. Improvements in lung mechanics occur very early after weight loss, mostly in the supine position, resulting in improved sleep quality. These improvements are detectable with oscillometry but not with spirometry.
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Guns, P-J; Johnson, DM; Van Op den bosch, J; Weltens, E; Lissens, J
2012-01-01
BACKGROUND AND PURPOSE QT prolongation is commonly used as a surrogate marker for Torsade de Pointes (TdP) risk of non-cardiovascular drugs. However, use of this indirect marker often leads to misinterpretation of the realistic TdP risk, as tested compounds may cause QT prolongation without evoking TdP in humans. A negative electro-mechanical (E-M) window has recently been proposed as an alternative risk marker for TdP in a canine LQT1 model. Here, we evaluated the E-M window in anaesthetized guinea pigs as a screening marker for TdP in humans. EXPERIMENTAL APPROACH The effects of various reference drugs and changes in body temperature on the E-M window were assessed in instrumented guinea pigs. The E-M window was defined as the delay between the duration of the electrical (QT interval) and mechanical (QLVPend) systole. KEY RESULTS Drugs with known TdP liability (quinidine, haloperidol, domperidone, terfenadine, thioridazine and dofetilide), but not those with no TdP risk in humans (salbutamol and diltiazem) consistently decreased the E-M window. Interestingly, drugs with known clinical QT prolongation, but with low risk for TdP (amiodarone, moxifloxacin and ciprofloxacin) did not decrease the E-M window. Furthermore, the E-M window was minimally affected by changes in heart rate or body temperature. CONCLUSIONS AND IMPLICATIONS A decreased E-M window was consistently observed with drugs already known to have high TdP risk, but not with drugs with low or no TdP risk. These results suggest that the E-M window in anaesthetized guinea pigs is a risk marker for TdP in humans. PMID:22122450
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Graham, U M; McCance, D R; Young, I S; Mullan, K R
2014-05-01
There is limited evidence on the effect of potassium supplementation on the vasculature in patients at increased cardiovascular risk. Potassium increases aldosterone and there is a strong association of hyperaldosteronism with poor cardiac outcomes. We aimed to determine whether potassium supplementation has a significant medium-term effect on aldosterone levels and, if so, what the overall effect of this is on vascular function in patients at moderate cardiovascular disease risk. Forty patients at moderate cardiovascular disease risk were included in a randomised placebo-controlled crossover study. Patients were assigned to 64 mmol potassium chloride or placebo for 6 weeks. Vascular function was assessed using pulse-wave analysis including the detection of a change in augmentation index to salbutamol and nitroglycerine-induced vasodilation. There was no change in augmentation index with potassium vs placebo (25.2±1.4 vs. 26.0±1.3%, respectively). Potassium improved brachial systolic blood pressure (131.8±2.2 vs. 137.1±2.4 mm Hg; P=0.013), central systolic blood pressure (123.2±2.3 vs. 128.4±2.3 mm Hg; P=0.011) and central diastolic blood pressure (80.3±1.3 vs. 83.7±1.4 mm Hg; P=0.019). Plasma renin activity and serum aldosterone both increased with potassium (P=0.001 and P=0.048 respectively). We found that potassium supplementation had no effect on endothelial function or pulse-wave analysis. It lowered brachial systolic and central blood pressure. It was associated with increased plasma renin activity and serum aldosterone.
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Access to essential medicines to treat chronic respiratory disease in low-income countries.
Bissell, K; Perrin, C; Beran, D
2016-06-01
Chronic respiratory diseases (CRDs) affect hundreds of millions of people. The United Nations 2011 meeting on non-communicable diseases (NCDs) marked a turning point in addressing this burden. The targets established following this meeting incorporated specific measures to address the availability and affordability of essential medicines. These are aligned with the sustainable development goals (SDGs) and the push for universal health coverage. However, essential medicines for CRDs remain unaffordable and unavailable to many. For asthma, the availability of medicines was respectively 30.1% and 43.1% in the public and private sectors. The maximum annual costs of treatment were US$102.10 for beclometasone, US$82.99 for salbutamol and US$1501.79 for budesonide, representing respectively 40%, 15% and 209% of per capita income in Malawi, Burkina Faso and Guinea. Multiple factors contribute to poor availability and affordability. Experience from human immunodeficiency virus/acquired immune-deficiency syndrome shows that medicines and care can be delivered in low-income countries and among the NCDs. A unique example of an effective mechanism for providing access to affordable essential CRD medicines is the Asthma Drug Facility. Working on the six health system building blocks proposed by the World Health Organization can help countries address not only problems regarding access to medicines, but also those hampering adequate care. Improving medicine supply systems, training, national guidelines, financing, research, data utilisation and models of care at the primary health care level will help. A CRD target (e.g., 50% reduction in asthma hospitalisations) as well as the use of asthma as a measure for health system effectiveness and CRDs as a tracer for SDGs would help focus global, national and local leadership.
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Airway Delivery of Soluble Factors from Plastic-Adherent Bone Marrow Cells Prevents Murine Asthma
Ionescu, Lavinia I.; Alphonse, Rajesh S.; Arizmendi, Narcy; Morgan, Beverly; Abel, Melanie; Eaton, Farah; Duszyk, Marek; Vliagoftis, Harissios; Aprahamian, Tamar R.; Walsh, Kenneth
2012-01-01
Asthma affects an estimated 300 million people worldwide and accounts for 1 of 250 deaths and 15 million disability-adjusted life years lost annually. Plastic-adherent bone marrow–derived cell (BMC) administration holds therapeutic promise in regenerative medicine. However, given the low cell engraftment in target organs, including the lung, cell replacement cannot solely account for the reported therapeutic benefits. This suggests that BMCs may act by secreting soluble factors. BMCs also possess antiinflammatory and immunomodulatory properties and may therefore be beneficial for asthma. Our objective was to investigate the therapeutic potential of BMC-secreted factors in murine asthma. In a model of acute and chronic asthma, intranasal instillation of BMC conditioned medium (CdM) prevented airway hyperresponsiveness (AHR) and inflammation. In the chronic asthma model, CdM prevented airway smooth muscle thickening and peribronchial inflammation while restoring blunted salbutamol-induced bronchodilation. CdM reduced lung levels of the TH2 inflammatory cytokines IL-4 and IL-13 and increased levels of IL-10. CdM up-regulated an IL-10–induced and IL-10–secreting subset of T regulatory lymphocytes and promoted IL-10 expression by lung macrophages. Adiponectin (APN), an antiinflammatory adipokine found in CdM, prevented AHR, airway smooth muscle thickening, and peribronchial inflammation, whereas the effect of CdM in which APN was neutralized or from APN knock-out mice was attenuated compared with wild-type CdM. Our study provides evidence that BMC-derived soluble factors prevent murine asthma and suggests APN as one of the protective factors. Further identification of BMC-derived factors may hold promise for novel approaches in the treatment of asthma. PMID:21903873
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Airway delivery of soluble factors from plastic-adherent bone marrow cells prevents murine asthma.
Ionescu, Lavinia I; Alphonse, Rajesh S; Arizmendi, Narcy; Morgan, Beverly; Abel, Melanie; Eaton, Farah; Duszyk, Marek; Vliagoftis, Harissios; Aprahamian, Tamar R; Walsh, Kenneth; Thébaud, Bernard
2012-02-01
Asthma affects an estimated 300 million people worldwide and accounts for 1 of 250 deaths and 15 million disability-adjusted life years lost annually. Plastic-adherent bone marrow-derived cell (BMC) administration holds therapeutic promise in regenerative medicine. However, given the low cell engraftment in target organs, including the lung, cell replacement cannot solely account for the reported therapeutic benefits. This suggests that BMCs may act by secreting soluble factors. BMCs also possess antiinflammatory and immunomodulatory properties and may therefore be beneficial for asthma. Our objective was to investigate the therapeutic potential of BMC-secreted factors in murine asthma. In a model of acute and chronic asthma, intranasal instillation of BMC conditioned medium (CdM) prevented airway hyperresponsiveness (AHR) and inflammation. In the chronic asthma model, CdM prevented airway smooth muscle thickening and peribronchial inflammation while restoring blunted salbutamol-induced bronchodilation. CdM reduced lung levels of the T(H)2 inflammatory cytokines IL-4 and IL-13 and increased levels of IL-10. CdM up-regulated an IL-10-induced and IL-10-secreting subset of T regulatory lymphocytes and promoted IL-10 expression by lung macrophages. Adiponectin (APN), an antiinflammatory adipokine found in CdM, prevented AHR, airway smooth muscle thickening, and peribronchial inflammation, whereas the effect of CdM in which APN was neutralized or from APN knock-out mice was attenuated compared with wild-type CdM. Our study provides evidence that BMC-derived soluble factors prevent murine asthma and suggests APN as one of the protective factors. Further identification of BMC-derived factors may hold promise for novel approaches in the treatment of asthma.
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Hazir, T; Qazi, S; Nisar, Y B; Ansari, S; Maqbool, S; Randhawa, S; Kundi, Z; Asghar, R; Aslam, S
2004-11-01
Using current WHO guidelines, children with wheezing are being over prescribed antibiotics and bronchodilators are underutilised. To improve the WHO case management guidelines, more data is needed about the clinical outcome in children with wheezing/pneumonia overlap. In a multicentre prospective study, children aged 1-59 months with auscultatory/audible wheeze and fast breathing and/or lower chest indrawing were screened. Response to up to three cycles of inhaled salbutamol was recorded. The responders were enrolled and sent home on inhaled bronchodilators, and followed up on days 3 and 5. A total of 1622 children with wheeze were screened from May 2001 to April 2002, of which 1004 (61.8%) had WHO defined non-severe and 618 (38.2%) severe pneumonia. Wheeze was audible in only 595 (36.7%) of children. Of 1004 non-severe pneumonia children, 621 (61.8%) responded to up to three cycles of bronchodilator. Of 618 severe pneumonia children, only 166 (26.8%) responded. Among responders, 93 (14.9%) in the non-severe and 63 (37.9%) children in the severe pneumonia group showed subsequent deterioration on follow ups. No family history of wheeze, temperature >100 degrees F, and lower chest indrawing were identified as predictors of subsequent deterioration. Two third of children with wheeze are not identified by current WHO ARI (acute respiratory infections) guidelines. Antibiotics are over prescribed and bronchodilators under utilised in children with wheeze. Children with wheeze constitute a special ARI group requiring a separate management algorithm. In countries where wheeze is common it would be worthwhile to train health workers in use of the stethoscope to identify wheeze.
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Zaidman, Nathan A; Panoskaltsis-Mortari, Angela; O'Grady, Scott M
2016-08-01
Glucocorticoids strongly influence the mucosal-defense functions performed by the bronchial epithelium, and inhaled corticosteroids are critical in the treatment of patients with inflammatory airway diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. A common pathology associated with these diseases is reduced mucociliary clearance, a defense mechanism involving the coordinated transport of salt, water, and mucus by the bronchial epithelium, ultimately leading to retention of pathogens and particles in the airways and to further disease progression. In the present study we investigated the role of hydrocortisone (HC) in differentiation and development of the ion transport phenotype of normal human bronchial epithelial cells under air-liquid interface conditions. Normal human bronchial epithelial cells differentiated in the absence of HC (HC0) showed significantly less benzamil-sensitive short-circuit current than controls, as well as a reduced response after stimulation with the selective β2-adrenergic receptor agonist salbutamol. Apical membrane localization of epithelial Na(+) channel α-subunits was similarly reduced in HC0 cells compared with controls, supporting a role of HC in the trafficking and density of Na(+) channels in the plasma membrane. Additionally, glucocorticoid exposure during differentiation regulated the transcription of cystic fibrosis transmembrane conductance regulator and β2-adrenergic receptor mRNAs and appeared to be necessary for the expression of cystic fibrosis transmembrane conductance regulator-dependent anion secretion in response to β2-agonists. HC had no significant effect on surface cell differentiation but did modulate the expression of mucin mRNAs. These findings indicate that glucocorticoids support mucosal defense by regulating critical transport pathways essential for effective mucociliary clearance. Copyright © 2016 the American Physiological Society.
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Lipopolysaccharide does not alter small airway reactivity in mouse lung slices.
Donovan, Chantal; Royce, Simon G; Vlahos, Ross; Bourke, Jane E
2015-01-01
The bacterial endotoxin, lipopolysaccharide (LPS) has been associated with occupational airway diseases with asthma-like symptoms and in acute exacerbations of COPD. The direct and indirect effects of LPS on small airway reactivity have not been fully elucidated. We tested the hypothesis that both in vitro and in vivo LPS treatment would increase contraction and impair relaxation of mouse small airways. Lung slices were prepared from naïve Balb/C mice and cultured in the absence or presence of LPS (10 μg/ml) for up to 48 h for measurement of TNFα levels in conditioned media. Alternatively, mice were challenged with PBS or LPS in vivo once a day for 4 days for preparation of lung slices or for harvest of lungs for Q-PCR analysis of gene expression of pro-inflammatory cytokines and receptors involved in airway contraction. Reactivity of small airways to contractile agonists, methacholine and serotonin, and bronchodilator agents, salbutamol, isoprenaline and rosiglitazone, were assessed using phase-contrast microscopy. In vitro LPS treatment of slices increased TNFα release 6-fold but did not alter contraction or relaxation to any agonists tested. In vivo LPS treatment increased lung gene expression of TNFα, IL-1β and ryanodine receptor isoform 2 more than 5-fold. However there were no changes in reactivity in lung slices from these mice, even when also incubated with LPS ex vivo. Despite evidence of LPS-induced inflammation, neither airway hyperresponsiveness or impaired dilator reactivity were evident. The increase in ryanodine receptor isoform 2, known to regulate calcium signaling in vascular smooth muscle, warrants investigation. Since LPS failed to elicit changes in small airway reactivity in mouse lung slices following in vitro or in vivo treatment, alternative approaches are required to define the potential contribution of this endotoxin to altered small airway reactivity in human lung diseases.
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Pinto, Joana T; Zellnitz, Sarah; Guidi, Tomaso; Roblegg, Eva; Paudel, Amrit
2018-06-19
The pulmonary administration landscape has rapidly advanced in recent years. Targeted design of particles by spray-drying for dry powder inhaler development offers an invaluable tool for engineering of new carriers. In this work, different formulation and process aspects of spray-drying were exploited to produce new lactose carriers. Using an integrated approach, lactose was spray-dried in the presence of polyethylene glycol 200 (PEG 200), and the in vitro performance of the resulting particles was compared with other grades of lactose with varying anomeric compositions and/or physical properties. The anomeric composition of lactose in lactose-PEG 200 feed solutions of variable compositions was analyzed via polarimetry at different temperatures. These results were correlated with the solid-state and anomeric composition of the resulting spray-dried particles using modulated differential scanning calorimetry and wide-angle X-ray scattering. The distinct selected grades of lactose were characterized in terms of their micromeritic properties using laser diffraction, helium pycnometry, and gas adsorption, and their particle surface morphologies were evaluated via scanning electron microscopy. Adhesive mixtures of the different lactose carriers with inhalable-sized salbutamol sulfate, as a model drug, were prepared in low doses and evaluated for their blend homogeneity and aerodynamic performance using a Next Generation Impactor. Characterization of the spray-dried particles revealed that predominantly crystalline (in an anomeric ratio 0.8:1 of α to β) spherical particles with a mean size of 50.9 ± 0.4 μm could be produced. Finally, it was apparent that micromeritic, in particular, the shape, and surface properties (inherent to solid-state and anomeric composition) of carrier particles dominantly control DPI delivery. This provided an insight into the relatively inferior performance of the adhesive blends containing the spherical spray-dried lactose-PEG 200
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Trendelenburg, A U; Cox, S L; Schelb, V; Klebroff, W; Khairallah, L; Starke, K
2000-01-01
Release-modulating opioid and cannabinoid (CB) receptors, β-adrenoceptors and bradykinin receptors at noradrenergic axons were studied in mouse tissues (occipito-parietal cortex, heart atria, vas deferens and spleen) preincubated with 3H-noradrenaline. Experiments using the OP1 receptor-selective agonists DPDPE and DSLET, the OP2-selective agonists U50488H and U69593, the OP3-selective agonist DAMGO, the ORL1 receptor-selective agonist nociceptin, and a number of selective antagonists showed that the noradrenergic axons innervating the occipito-parietal cortex possess release-inhibiting OP3 and ORL1 receptors, those innervating atria OP1, ORL1 and possibly OP3 receptors, and those innervating the vas deferens all four opioid receptor types. Experiments using the non-selective CB agonists WIN 55,212-2 and CP 55,940 and the CB1-selective antagonist SR 141716A indicated that the noradrenergic axons of the vas deferens possess release-inhibiting CB1 receptors. Presynaptic CB receptors were not found in the occipito-parietal cortex, in atria or in the spleen. Experiments using the non-selective β-adrenoceptor agonist isoprenaline and the β2-selective agonist salbutamol, as well as subtype-selective antagonists, demonstrated the occurrence of release-enhancing β2-adrenoceptors at the sympathetic axons of atria and the spleen, but demonstrated their absence in the occipito-parietal cortex and the vas deferens. Experiments with bradykinin and the B2-selective antagonist Hoe 140 showed the operation of release-enhancing B2 receptors at the sympathetic axons of atria, the vas deferens and the spleen, but showed their absence in the occipito-parietal cortex. The experiments document a number of new presynaptic receptor locations. They confirm and extend the existence of marked tissue and species differences in presynaptic receptors at noradrenergic neurons. PMID:10807669
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Evans, Sian E; Davies, Paul; Lubben, Anneke; Kasprzyk-Hordern, Barbara
2015-07-02
This is the first study presenting a multi-residue method allowing for comprehensive analysis of several chiral pharmacologically active compounds (cPACs) including beta-blockers, antidepressants and amphetamines in wastewater and digested sludge at the enantiomeric level. Analysis of both the liquid and solid matrices within wastewater treatment is crucial to being able to carry out mass balance within these systems. The method developed comprises filtration, microwave assisted extraction and solid phase extraction followed by chiral liquid chromatography coupled with tandem mass spectrometry to analyse the enantiomers of 18 compounds within all three matrices. The method was successfully validated for 10 compounds within all three matrices (amphetamine, methamphetamine, MDMA, MDA, venlafaxine, desmethylvenlafaxine, citalopram, metoprolol, propranolol and sotalol), 7 compounds validated for the liquid matrices only (mirtazapine, salbutamol, fluoxetine, desmethylcitalopram, atenolol, ephedrine and pseudoephedrine) and 1 compound (alprenolol) passing the criteria for solid samples only. The method was then applied to wastewater samples; cPACs were found at concentration ranges in liquid matrices of: 1.7 ng L(-1) (metoprolol) - 1321 ng L(-1) (tramadol) in influent,
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Case report of asthma associated with 3D printing.
House, R; Rajaram, N; Tarlo, S M
2017-12-02
Three-dimensional (3D) printing is being increasingly used in manufacturing and by small business entrepreneurs and home hobbyists. Exposure to airborne emissions during 3D printing raises the issue of whether there may be adverse health effects associated with these emissions. We present a case of a worker who developed asthma while using 3D printers, which illustrates that respiratory problems may be associated with 3D printer emissions. The patient was a 28-year-old self-employed businessman with a past history of asthma in childhood, which had resolved completely by the age of eight. He started using 10 fused deposition modelling 3D printers with acrylonitrile-butadiene-styrene filaments in a small work area of approximately 3000 cubic feet. Ten days later, he began to experience recurrent chest tightness, shortness of breath and coughing at work. After 3 months, his work environment was modified by reducing the number of printers, changing to polylactic acid filaments and using an air purifier with an high-efficiency particulate air filter and organic cartridge. His symptoms improved gradually, although he still needed periodic treatment with a salbutamol inhaler. While still symptomatic, a methacholine challenge indicated a provocation concentration causing a 20% fall in FEV1 (PC20) of 4 mg/ml, consistent with mild asthma. Eventually, his symptoms resolved completely and a second methacholine challenge after symptom resolution was normal (PC20 > 16 mg/ml). This case indicates that workers may develop respiratory problems, including asthma when using 3D printers. Further investigation of the specific airborne emissions and health problems from 3D printing is warranted. © The Author 2017. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com
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Lipopolysaccharide Does Not Alter Small Airway Reactivity in Mouse Lung Slices
Donovan, Chantal; Royce, Simon G.; Vlahos, Ross; Bourke, Jane E.
2015-01-01
The bacterial endotoxin, lipopolysaccharide (LPS) has been associated with occupational airway diseases with asthma-like symptoms and in acute exacerbations of COPD. The direct and indirect effects of LPS on small airway reactivity have not been fully elucidated. We tested the hypothesis that both in vitro and in vivo LPS treatment would increase contraction and impair relaxation of mouse small airways. Lung slices were prepared from naïve Balb/C mice and cultured in the absence or presence of LPS (10 μg/ml) for up to 48 h for measurement of TNFα levels in conditioned media. Alternatively, mice were challenged with PBS or LPS in vivo once a day for 4 days for preparation of lung slices or for harvest of lungs for Q-PCR analysis of gene expression of pro-inflammatory cytokines and receptors involved in airway contraction. Reactivity of small airways to contractile agonists, methacholine and serotonin, and bronchodilator agents, salbutamol, isoprenaline and rosiglitazone, were assessed using phase-contrast microscopy. In vitro LPS treatment of slices increased TNFα release 6-fold but did not alter contraction or relaxation to any agonists tested. In vivo LPS treatment increased lung gene expression of TNFα, IL-1β and ryanodine receptor isoform 2 more than 5-fold. However there were no changes in reactivity in lung slices from these mice, even when also incubated with LPS ex vivo. Despite evidence of LPS-induced inflammation, neither airway hyperresponsiveness or impaired dilator reactivity were evident. The increase in ryanodine receptor isoform 2, known to regulate calcium signaling in vascular smooth muscle, warrants investigation. Since LPS failed to elicit changes in small airway reactivity in mouse lung slices following in vitro or in vivo treatment, alternative approaches are required to define the potential contribution of this endotoxin to altered small airway reactivity in human lung diseases. PMID:25822969
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Lin, Hui-Ling; Harwood, Robert J; Fink, James B; Goodfellow, Lynda T; Ari, Arzu
2015-09-01
Aerosol drug delivery to infants and small children is influenced by many factors, such as types of interface, gas flows, and the designs of face masks. The purpose of this in vitro study was to evaluate aerosol delivery during administration of gas flows across the range used clinically with high-flow humidity systems using 2 aerosol masks. A spontaneous lung model was used to simulate an infant/young toddler up to 2 y of age and pediatric breathing patterns. Nebulized salbutamol by a vibrating mesh nebulizer positioned at the inlet of a high-flow humidification system at gas flows of 3, 6, and 12 L/min was delivered via pediatric face masks to a pediatric face mannequin attached to a filter. Aerosol particle size distribution exiting the vibrating mesh nebulizer and at the mask position distal to the heated humidifier with 3 flows was measured with a cascade impactor. Eluted drug from the filters and the impactor was analyzed with a spectrophotometer (n = 3). Statistical analysis was performed by analysis of variance with a significant level of P < .05. The inhaled mass was between 2.8% and 8.1% among all settings and was significantly lower at 12 L/min (P = .004) in the pediatric model. Drug delivery with pediatric breathing was greater than with infant breathing (P = .004). The particle size distribution of aerosol emitted from the nebulizer was larger than the heated humidified aerosol exiting the tubing (P = .002), with no difference between the 3 flows (P = .10). The flows of gas entering the mask and breathing patterns influence aerosol delivery, independent of the face mask used. Aerosol delivery through a high-flow humidification system via mask could be effective with both infant and pediatric breathing patterns. Copyright © 2015 by Daedalus Enterprises.
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Herbal medicine for adults with asthma: A systematic review.
Shergis, Johannah L; Wu, Lei; Zhang, Anthony L; Guo, Xinfeng; Lu, Chuanjian; Xue, Charlie C
2016-08-01
Many people with asthma use herbal medicines to help reduce symptoms and improve asthma control. To update the systematic review and meta-analysis of randomised controlled trials of herbal medicine for adult asthma. Nine English and Chinese databases were searched (PubMed, Embase, CINAHL, CENTRAL, AMED, CBM, CNKI, CQVIP, Wanfang). Herbal medicines combined with routine pharmacotherapies compared with the same pharmacotherapies alone or placebo. Cochrane Risk of Bias Tool and GRADE Summary of Findings tables were used to evaluate methodological quality. Twenty-nine (29) studies involving 3,001 participants were included. Herbal interventions used multi-ingredients such as licorice root, crow-dipper, astragali, and angelica. Compared with routine pharmacotherapies alone, herbal medicines as add-on therapy improved lung function (FEV1: MD 7.81%, 95% CI 5.79, 9.83, I(2) = 63%; PEFR: MD 65.14 L/min, 95% CI 58.87, 71.41, I(2) = 21%); asthma control (MD 2.47 points, 95% CI 1.64, 3.29, I(2) = 55%); reduced salbutamol usage (MD -1.14 puffs/day, 95% CI -2.20, -0.09, I(2) = 92%); and reduced acute asthma exacerbations over one year (MD -1.20, 95% CI -1.82, -0.58, one study). Compared with placebo plus pharmacotherapies herbal medicines as add-on therapy improved lung function (FEV1: MD 15.83%, 95% CI 13.54, 18.12 and PEFR: MD 55.20 L/min, 95% CI 33.41, 76.99). Other outcomes were not reported in these placebo studies. Included studies were low to moderate quality. Adverse events were rare. Herbal medicines combined with routine pharmacotherapies improved asthma outcomes greater than pharmacotherapies alone. Included studies did not blind participants therefore more studies that address such weaknesses are warranted.
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Esposito, Susanna; Brivio, Anna; Tagliabue, Claudia; Galeone, Carlotta; Tagliaferri, Laura; Serra, Domenico; Foà, Michela; Patria, Maria Francesca; Marchisio, Paola; Principi, Nicola
2011-06-01
Oxygen administration, aerosol devices and drugs, or the use of chest physiotherapy are common practices in pediatrics; however, little is known about the knowledge of pediatric healthcare workers concerning the right utilization of these tools. The aim of this study was to fill this gap as a preliminary step in the implementation of appropriate educational programs. This cross-sectional survey of a nationally representative sample of Italian pediatricians and nurses was carried out between September 1 and October 8, 2008. A self-administered, anonymous questionnaire concerning the approach to respiratory disease in infants and children was distributed to all of the participants at the Annual Congress of the Italian Society of Pediatrics, together with a stamped envelope addressed to the trained study researchers. Of the 900 distributed questionnaires, 76.7% were completed and returned by 606 physicians (199 primary care pediatricians, 245 hospital pediatricians, and 162 pediatric residents) and 84 pediatric nurses. The vast majority of the respondents did not know the percentage of hemoglobin saturation indicating hypoxemia that requires oxygen administration. Most of the nurses admitted to overusing mucolytics and inhalatory corticosteroids, did not know the role of ipratropium bromide, were unable to indicate the first-line drug for respiratory distress, and did not know the correct dose of salbutamol. Only a minority of the respondents were able to specify the indications for chest physiotherapy. The nurses gave the fewest correct answers regardless of their age, gender, work setting, or the frequency with which they cared for children with respiratory distress in a year cared. The knowledge of primary care pediatricians, hospital pediatricians, and pediatric nurses in Italy concerning the use of pulse oximetry, aerosol devices and drugs, and chest physiotherapy is far from satisfactory and should be improved. Educational programs are therefore required for
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Wheeldon, N M; McDevitt, D G; Lipworth, B J
1994-08-01
1. The aim of the present study was to evaluate the relative beta 1/beta 2 antagonist selectivity of the beta-adrenoceptor blocker nadolol, in lower than conventional clinical doses. 2. Eight normal volunteers received single oral doses of either placebo (PL), nadolol 5 mg (N5), 20 mg (N20) or 80 mg (N80) in a single-blind, randomised crossover design. beta 1-adrenoceptor antagonism was assessed by attenuation of exercise tachycardia, and beta 2-adrenoceptor blockade by effects on salbutamol-induced chronotropic, hypokalaemic and finger tremor responses. The relative percentage attenuation of beta 2 and beta 1-mediated responses was calculated and expressed as beta 2:beta 1 selectivity ratios. 3. Nadolol produced dose-related reductions in exercise tachycardia in keeping with increasing beta 1-adrenoceptor blockade; mean % reduction (95% CI) compared with placebo: N5 10.7 (6.6 to 14.8), N20 21.4 (17.3 to 25.4), N80 38.9 (34.8 to 42.9). However, even the lowest dose of nadolol (5 mg) produced almost complete blunting of beta 2-mediated effects and significantly increase exercise hyperkalaemia; peak exercise hyperkalaemia (mmol l-1) (means and 95% CI): PL 4.88 (4.68 to 5.07), N5 5.36 (5.17 to 5.55), N20 5.48 (5.28 to 5.67), N80 5.42 (5.22 to 5.61). beta 2:beta 1 selectivity ratios significantly increased as the dose of nadolol was reduced. 4. These data suggest that whereas in the clinical dose range nadolol behaves as a non-selective beta-adrenoceptor antagonist, as the dose is reduced this drug demonstrates an increasing degree of selectivity for the beta 2-adrenoceptor.(ABSTRACT TRUNCATED AT 250 WORDS)
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Adrenoceptor function and expression in bladder urothelium and lamina propria.
Moro, Christian; Tajouri, Lotti; Chess-Williams, Russ
2013-01-01
To investigate the role of adrenoceptor subtypes in regulating the spontaneous contractile activity of the inner lining of the urinary bladder (urothelium/lamina propria). The responses of isolated strips of porcine urothelium/lamina propria to noradrenaline, phenylephrine, and isoprenaline were obtained in the absence and presence of receptor subtype-selective antagonists. Quantitative reverse-transcriptase polymerase chain reaction was undertaken to assess the expression of adrenoceptor genes. The tissues expressed all α1- and β-adrenoceptor subtypes, with the α1A-, α1B-, and β2-adrenoceptors the predominant receptors at the messenger RNA level. In the functional experiments, the rate of phasic contractions and the basal tension were increased by the α1-adrenoceptor agonists phenylephrine (100 μM) and A61603 (10 μM). The rate and tension responses to phenylephrine were reduced by low concentrations of tamsulosin (3 nM) and RS100329 (10 nM) but were unaffected by BMY7378 (100 nM), prazosin (10 nM), and RS17053 (1 μM). In contrast, isoprenaline and salbutamol (both 1 μM) induced a relaxation of tissues and slowing of phasic contractions. The rate and tension responses to isoprenaline were inhibited by propranolol (100 nM) or a combination of CGP20712A (30 nM) and ICI118551 (70 nM). The rate responses were also significantly inhibited by ICI118551 alone (70 nM). Although all α1- and β-adrenoceptor subtypes were expressed in the pig urothelium/lamina propria, the α1A/L-adrenoceptor appeared to mediate increases in the contractile rate and tension. The β-adrenoceptor induced inhibition of spontaneous contractile activity appears to be predominately mediated by β2-adrenoceptors, with β1- and β2-adrenoceptors possibly involved in the tension responses. Copyright © 2013 Elsevier Inc. All rights reserved.
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Niëns, Laurens M.; Cameron, Alexandra; Van de Poel, Ellen; Ewen, Margaret; Brouwer, Werner B. F.; Laing, Richard
2010-01-01
Background Increasing attention is being paid to the affordability of medicines in low- and middle-income countries (LICs and MICs) where medicines are often highly priced in relation to income levels. The impoverishing effect of medicine purchases can be estimated by determining pre- and postpayment incomes, which are then compared to a poverty line. Here we estimate the impoverishing effects of four medicines in 16 LICs and MICs using the impoverishment method as a metric of affordability. Methods and Findings Affordability was assessed in terms of the proportion of the population being pushed below US$1.25 or US$2 per day poverty levels because of the purchase of medicines. The prices of salbutamol 100 mcg/dose inhaler, glibenclamide 5 mg cap/tab, atenolol 50 mg cap/tab, and amoxicillin 250 mg cap/tab were obtained from facility-based surveys undertaken using a standard measurement methodology. The World Bank's World Development Indicators provided household expenditure data and information on income distributions. In the countries studied, purchasing these medicines would impoverish large portions of the population (up to 86%). Originator brand products were less affordable than the lowest-priced generic equivalents. In the Philippines, for example, originator brand atenolol would push an additional 22% of the population below US$1.25 per day, whereas for the lowest priced generic equivalent this demographic shift is 7%. Given related prevalence figures, substantial numbers of people are affected by the unaffordability of medicines. Conclusions Comparing medicine prices to available income in LICs and MICs shows that medicine purchases by individuals in those countries could lead to the impoverishment of large numbers of people. Action is needed to improve medicine affordability, such as promoting the use of quality assured, low-priced generics, and establishing health insurance systems. Please see later in the article for the Editors' Summary PMID:20824175
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Kaur, Manminder; Holden, Neil S; Wilson, Sylvia M; Sukkar, Maria B; Chung, Kian Fan; Barnes, Peter J; Newton, Robert; Giembycz, Mark A
2008-09-01
In diseases such as asthma, airway smooth muscle (ASM) cells play a synthetic role by secreting inflammatory mediators such as granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, or IL-8 and by expressing surface adhesion molecules, including ICAM-1. In the present study, PGE(2), forskolin, and short-acting (salbutamol) and long-acting (salmeterol and formoterol) beta(2)-adrenoceptor agonists reduced the expression of ICAM-1 and the release of GM-CSF evoked by IL-1beta in ASM cells. IL-1beta-induced IL-8 release was also repressed by PGE(2) and forskolin, whereas the beta(2)-adrenoceptor agonists were ineffective. In each case, repression of these inflammatory indexes was prevented by adenoviral overexpression of PKIalpha, a highly selective PKA inhibitor. These data indicate a PKA-dependent mechanism of repression and suggest that agents that elevate intracellular cAMP, and thereby activate PKA, may have a widespread anti-inflammatory effect in ASM cells. Since ICAM-1 and GM-CSF are highly NF-kappaB-dependent genes, we used an adenoviral-delivered NF-kappaB-dependent luciferase reporter to examine the effects of forskolin and the beta(2)-adrenoceptor agonists on NF-kappaB activation. There was no effect on luciferase activity measured in the presence of forskolin or beta(2)-adrenoceptor agonists. This finding is consistent with the observation that IL-1beta-induced expression of IL-6, a known NF-kappaB-dependent gene in ASM, was also unaffected by beta(2)-adrenoceptor agonists, forskolin, PGE(2), 8-bromo-cAMP, or rolipram. Collectively, these results indicate that repression of IL-1beta-induced ICAM-1 expression and GM-CSF release by cAMP-elevating agents, including beta(2)-adrenoceptor agonists, may not occur through a generic effect on NF-kappaB.
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Svensson, Mårten; Berg, Elna; Mitchell, Jolyon; Sandell, Dennis
2018-02-01
Determination of fine droplet dose with preparations for nebulization, currently deemed to be the metric most indicative of lung deposition and thus in vivo responses, involves combining two procedures following practice as described in the United States Pharmacopeia and the European Pharmacopeia. Delivered dose (DD) is established by simulating tidal breathing at the nebulizer, collecting the medication on a filter downstream of the nebulizer mouthpiece/facemask. Fine droplet fraction (FDF
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Neumann, Vanessa; Knies, Ralf; Seidinger, Alexander; Simon, Annika; Lorenz, Kristina; Matthey, Michaela; Breuer, Johannes; Wenzel, Daniela
2018-05-01
Pulmonary hypertension is a severe, incurable disease with a poor prognosis. Although treatment regimens have improved during the last 2 decades, current pharmacologic strategies are limited and focus on the modulation of only a few pathways related to endothelin, NO, and prostacyclin signaling. Therefore, the identification of novel molecular targets is urgently needed. We found that the β 2 adrenoceptor (AR) agonists terbutaline (TER) and salbutamol induced a dose-dependent vasorelaxation in large pulmonary arteries but not aortas of mouse. This effect was found to be independent of β ARs and the endothelium but was determined by the type of the preconstrictor. Vasodilation by β 2 AR agonists occurred after pretreatment of pulmonary arteries with phenylephrine and serotonin, both agonists of α 1 ARs, but was absent after preconstriction with the thromboxane analog U46619. These data indicated α-adrenolytic activity of β 2 AR agonists, which was confirmed by a right shift of the phenylephrine dose-response curve by TER. This effect was physiologically relevant because TER also relaxed small intrapulmonary arteries in lung slices and diminished pulmonary arterial pressure in an isolated perfused lung model under normoxia and hypoxia. Finally, TER applied as an aerosol also selectively decreased pulmonary arterial pressure without effects on systemic blood pressure and heart rate in mouse in vivo. Thus, β 2 AR agonists display α-adrenolytic activity in pulmonary arteries ex vivo and in vivo, and may provide a novel option to reduce pulmonary arterial pressure in pulmonary hypertension.-Neumann, V., Knies, R., Seidinger, A., Simon, A., Lorenz, K., Matthey, M., Breuer, J., Wenzel, D. The β 2 agonist terbutaline specifically decreases pulmonary arterial pressure under normoxia and hypoxia via α adrenoceptor antagonism.
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Bonnet, J; Loiseau, A M; Orvoen, M; Bessin, P
1981-12-01
PAF-acether is a potent aggregating agent released by various cells involved in acute inflammatory process. In this paper, exogenous PAF-acether has been investigated for its ability to generate signs of inflammation (edema measured by plethysmometry) and hyperalgesia (Randall-Sellito test) by standard subplantar injection in the rat paw. From 0.005 microgram. PAF-acether induced significant edema of the paw, maximal 1 hour after injection; it was dose-dependent from 0.1 to 5 microgram. Significant dose-dependent hyperalgesia occurred from 1.25 microgram; it reached a plateau from 2 to 4 hours after injection. Both phenomena were long-lasting (greater than 6 h). PAF-acether was 1.5 to 10 times stronger than PGI2 and PGE2 in inducing edema, pain, and in increasing vascular permeability. We investigated the interaction of miscellaneous drugs with the edema and the hyperalgesia caused by 2.5 microgram of PAF-acether. Non-steroidal anti-inflammatory (NSAI) drugs exerted only moderate effects on the edema without affecting hyperalgesia. Edema was highly reduced by various agents: prednisolone, L-cysteine, anti-calcic drugs, theophylline, PGI2, salbutamol, clonidine. All of them, except clonidine, and in contrast to NSAI drugs, were more potent on PAF-acether edema than on kaolin edema; a possible link between these agents is their ability to increase cyclic AMP levels in the cells and consequently to reduce lysosomal enzyme release. PAF-acether itself, injected intra-peritoneally, inhibited PAF-acether edema without preventing pain, at doses inactive on arterial pressure and hematocrit, but inducing marked gastric mucosal damage. Among the drugs tested, including analgesics, only PGI2 and imidazole improved PAF-induced hyperalgesia, showing a dissociation between edema and hyperalgesia not only in their induction (doses of PAF required, time course of the phenomena), but in the drugs able to antagonize their development too.
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Wong, W. S.; Bloomquist, S. L.; Bendele, A. M.; Fleisch, J. H.
1992-01-01
1. Parenchymal lung strip preparations have been widely used as an in vitro model of peripheral airway smooth muscle. The present study examined functional responses of 4 consecutive guinea-pig lung parenchymal strips isolated from the central region (segment 1) to the distal edge (segment 4) of the lower lung lobe. The middle two segments were designated as segments 2 and 3. 2. Lung segments 1 and 4 exhibited significantly greater contraction than the other 2 segments to KCl when responses were expressed as mg force per mg tissue weight. Contractile responses to bronchospastic agents including histamine, carbachol, endothelin-1, leukotrienes (LT) B4 and D4, and the thromboxane A2-mimetic U46619 demonstrated no significant difference in EC50 values among the 4 lung segments. 3. Contractile responses of segments 1 and 4 to antigen-challenge (ovalbumin), ionophore A23187 and substance P were significantly greater than the other 2 segments with respect to either sensitivity or maximum responsiveness. 4. U46619-induced contractions of the 4 lung segments were relaxed in similar manner by papaverine and theophylline up to 100%, salbutamol up to 80%, and sodium nitroprusside by only 20%. In contrast, sodium nitroprusside markedly reversed U46619-induced contraction of pulmonary arterial rings and bronchial rings. 5. Histological studies identified 2-4 layers of smooth muscle cells underlying the lung pleural surface. Mast cells were prominent in this area. Moreover, morphometric studies showed that segment 4 possessed the least amount of smooth muscle structures from bronchial/bronchiolar wall and vasculatures as compared to the other 3 segments, and a significant difference in this respect was evident between segment 1 and segment 4.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1 Figure 6 PMID:1378341
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Huang, Shu-Yi; Chou, Pai-Chien; Wang, Tsai-Yu; Lo, Yu-Lun; Joa, Wen-Ching; Chen, Li-Fei; Sheng, Te-Fang; Chung, Kian Fan; Wang, Chun-Hua; Kuo, Han-Pin
2016-04-01
Asthmatic patients with fixed airway obstruction (FAO) and patients with chronic obstructive pulmonary disease (COPD) share similarities in terms of irreversible pulmonary function impairment. Exhaled nitric oxide (eNO) has been documented as a marker of airway inflammation in asthma, but not in COPD. To examine whether the basal eNO level and the change after exercise may differentiate asthmatics with FAO from COPD, 27 normal subjects, 60 stable asthmatics, and 62 stable COPD patients were studied. Asthmatics with FAO (n = 29) were defined as showing a postbronchodilator FEV1/forced vital capacity (FVC) ≤70% and FEV1 less than 80% predicted after inhaled salbutamol (400 μg). COPD with dynamic hyperinflation (n = 31) was defined as a decrease in inspiratory capacity (ΔIC%) after a 6 minute walk test (6MWT). Basal levels of eNO were significantly higher in asthmatics and COPD patients compared to normal subjects. The changes in eNO after 6MWT were negatively correlated with the percent change in IC (r = -0.380, n = 29, P = 0.042) in asthmatics with FAO. Their levels of basal eNO correlated with the maximum mid-expiratory flow (MMEF % predicted) before and after 6MWT. In COPD patients with air-trapping, the percent change of eNO was positively correlated to ΔIC% (rs = 0.404, n = 31, P = 0.024). We conclude that asthma with FAO may represent residual inflammation in the airways, while dynamic hyperinflation in COPD may retain NO in the distal airspace. eNO changes after 6MWT may differentiate the subgroups of asthma or COPD patients and will help toward delivery of individualized therapy for airflow obstruction.
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Huang, Shu-Yi; Chou, Pai-Chien; Wang, Tsai-Yu; Lo, Yu-Lun; Joa, Wen-Ching; Chen, Li-Fei; Sheng, Te-Fang; Chung, Kian Fan; Wang, Chun-Hua; Kuo, Han-Pin
2016-01-01
Abstract Asthmatic patients with fixed airway obstruction (FAO) and patients with chronic obstructive pulmonary disease (COPD) share similarities in terms of irreversible pulmonary function impairment. Exhaled nitric oxide (eNO) has been documented as a marker of airway inflammation in asthma, but not in COPD. To examine whether the basal eNO level and the change after exercise may differentiate asthmatics with FAO from COPD, 27 normal subjects, 60 stable asthmatics, and 62 stable COPD patients were studied. Asthmatics with FAO (n = 29) were defined as showing a postbronchodilator FEV1/forced vital capacity (FVC) ≤70% and FEV1 less than 80% predicted after inhaled salbutamol (400 μg). COPD with dynamic hyperinflation (n = 31) was defined as a decrease in inspiratory capacity (ΔIC%) after a 6 minute walk test (6MWT). Basal levels of eNO were significantly higher in asthmatics and COPD patients compared to normal subjects. The changes in eNO after 6MWT were negatively correlated with the percent change in IC (r = −0.380, n = 29, P = 0.042) in asthmatics with FAO. Their levels of basal eNO correlated with the maximum mid-expiratory flow (MMEF % predicted) before and after 6MWT. In COPD patients with air-trapping, the percent change of eNO was positively correlated to ΔIC% (rs = 0.404, n = 31, P = 0.024). We conclude that asthma with FAO may represent residual inflammation in the airways, while dynamic hyperinflation in COPD may retain NO in the distal airspace. eNO changes after 6MWT may differentiate the subgroups of asthma or COPD patients and will help toward delivery of individualized therapy for airflow obstruction. PMID:27082615
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van Erp, Nicole; Little, Paul; Stuart, Beth; Moore, Michael; Thomas, Mike; Butler, Chris C; Hood, Kerenza; Coenen, Samuel; Goossens, Herman; Leven, Margareta; Verheij, Theo J M
2014-09-25
In acute cough patients, impaired lung function as present in chronic lung conditions like asthma and chronic obstructive pulmonary disease (COPD) are often thought to negatively influence course of disease, but clear evidence is lacking. To investigate the influence of lung function abnormalities on course of disease and response to antibiotic therapy in primary care patients with acute cough. A total of 3,104 patients with acute cough (⩽28 days) were included in a prospective observational study with a within-nested trial, of which 2,427 underwent spirometry 28-35 days after inclusion. Influence of the lung function abnormalities fixed obstruction (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7) and bronchodilator responsiveness (FEV1 increase of ⩾12% or 200 ml after 400 μg salbutamol) on symptom severity, duration and worsening were evaluated using uni- and multivariable regression models. Antibiotic use was defined as the reported use of antibiotics ⩾5 days in the first week. Interaction terms were calculated to investigate modifying effects of lung function on antibiotic effect. The only significant association was the effect of severe airway obstruction on symptom severity on days 2-4 (difference=0.31, 95% confidence interval (CI)=0.03-0.60, P=0.03). No evidence of a differential effect of lung function on the effect of antibiotics was found. Prior use of inhaled steroids was associated with a 30% slower resolution of symptoms rated 'moderately bad' or worse (hazard ratio=0.75, 95% CI=0.63-0.90, P=0.00). In adult patients with acute cough, lung function abnormalities were neither significantly associated with course of disease nor did they modify the effect of antibiotics.
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Che, Magnus M; Song, Jian; Oguntayo, Samuel; Doctor, Bhupendra P; Rezk, Peter; Perkins, Michael W; Sciuto, Alfred M; Nambiar, Madhusoodana P
2012-05-01
Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were measured in the blood and tissues of animals that are treated with a number of endotracheally aerosolized therapeutics for protection against inhalation toxicity to sarin. Therapeutics included, aerosolized atropine methyl bromide (AMB), scopolamine or combination of AMB with salbutamol, sphingosine 1-phosphate, keratinocyte growth factor, adenosine A1 receptor antisense oligonucleotide (EPI2010), 2,3-diacetyloxybenzoic acid (2,3 DABA), oxycyte, and survanta. Guinea pigs exposed to 677.4 mg/m(3) or 846.5 mg/m(3) (1.2 LCt(50)) sarin for 4 min using a microinstillation inhalation exposure technique and treated 1 min later with the aerosolized therapeutics. Treatment with all therapeutics significantly increased the survival rate with no convulsions throughout the 24 h study period. Blood AChE activity determined using acetylthiocholine as substrate showed 20% activity remaining in sarin-exposed animals compare to controls. In aerosolized AMB and scopolamine-treated animals the remaining AChE activity was significantly higher (45-60%) compared to sarin-exposed animals (p < 0.05). Similarly, treatment with all the combination therapeutics resulted in significant increase in blood AChE activity in comparison to sarin-exposed animals although the increases varied between treatments (p < 0.05). BChE activity was increased after treatment with aerosolized therapeutics but was lesser in magnitude compared to AChE activity changes. Various tissues showed elevated AChE activity after therapeutic treatment of sarin-exposed animals. Increased AChE and BChE activities in animals treated with nasal therapeutics suggest that enhanced breathing and reduced respiratory toxicity/lung injury possibly contribute to rapid normalization of chemical warfare nerve agent inhibited cholinesterases.
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Marsoni, Milena; De Mattia, Fabrizio; Labra, Massimo; Bruno, Antonia; Bracale, Marcella; Vannini, Candida
2014-10-01
Pharmaceutically active compounds (PACs) are continuously dispersed into the environment due to human and veterinary use, giving rise to their potential accumulation in edible plants. In this study, Eruca sativa L. and Zea mays L. were selected to determine the potential uptake and accumulation of eight different PACs (Salbutamol, Atenolol, Lincomycin, Cyclophosphamide, Carbamazepine, Bezafibrate, Ofloxacin and Ranitidine) designed for human use. To mimic environmental conditions, the plants were grown in pots and irrigated with water spiked with a mixture of PACs at concentrations found in Italian wastewaters and rivers. Moreover, 10× and 100× concentrations of these pharmaceuticals were also tested. The presence of the pharmaceuticals was tested in the edible parts of the plants, namely leaves for E. sativa and grains for Z. mays. Quantification was performed by liquid chromatography mass spectroscopy (LC/MS/MS). In the grains of 100× treated Z. mays, only atenolol, lincomycin and carbamazepine were above the limit of detection (LOD). At the same concentration in E. sativa plants the uptake of all PACs was >LOD. Lincomycin and oflaxacin were above the limit of quantitation in all conditions tested in E. sativa. The results suggest that uptake of some pharmaceuticals from the soil may indeed be a potential transport route to plants and that these environmental pollutants can reach different edible parts of the selected crops. Measurements of the concentrations of these pharmaceuticals in plant materials were used to model potential adult human exposure to these compounds. The results indicate that under the current experimental conditions, crops exposed to the selected pharmaceutical mixture would not have any negative effects on human health. Moreover, no significant differences in the growth of E. sativa or Z. mays plants irrigated with PAC-spiked vs. non-spiked water were observed. Copyright © 2014 Elsevier Inc. All rights reserved.
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Summerhill, Susan; Stroud, Timothy; Nagendra, Roshini; Perros-Huguet, Christelle; Trevethick, Michael
2008-01-01
The aim was to establish a robust, 96-well, cell-based assay to assess the potency and persistence of action of agonists acting at human recombinant beta(2) adrenoceptors expressed in CHO (Chinese Hamster Ovary) cells and to compare this with published duration of action data in guinea pig isolated trachea and human bronchus. Cells were treated with either: (i) beta-adrenoceptor agonist for 30 min, washed and cyclicAMP (cAMP) measured 30 min later-termed 'washed' cells or, (ii) treated with solvent for 30 min, washed, and then treated with beta-adrenoceptor agonist for 30 min and cAMP measured-termed 'unwashed' cells. The 'washed' EC(50) was divided by the 'unwashed' EC(50) to determine a rightward shift concentration ratio, which was indicative of the persistence of action at the receptor. At the beta(2) adrenoceptor salmeterol, carmoterol and indacaterol were resistant to washing with a concentration ratio of <5, indicating a long persistence of action, whereas formoterol, isoprenaline and salbutamol were washed out with a ratio of 32, >294 and >800 respectively, suggesting a shorter persistence of action. At beta(1) and beta(3) adrenoceptors all compounds washed out. The persistent effects of salmeterol at beta(2) following washing could be reversed by the selective beta(2) antagonist ICI 118551, suggesting continued receptor activation. The data presented agree well with published data assessing duration of action of beta(2) agonists in human isolated bronchus and guinea pig isolated trachea. Key features are: (a) it is a 96-well format which can be used to assess many compounds in a single experiment, (b) both potency and persistence of agonist action are assessed in the same assay, (c) any effects of concentration on the persistence of action can be highlighted, and (d) it allows triage of compounds prior to tissue bath studies thus reducing the use of animal tissue.
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An inhibitory role for noradrenaline in the mouse vas deferens
Jenkins, D.A.; Marshall, I.; Nasmyth, P.A.
1977-01-01
1 Noradrenaline (0.1-3.0 μM) inhibited the twitch responses to single pulse field stimulation of the isolated vas deferens of the mouse. The higher concentrations of noradrenaline (ca. 0.3-3.0 μM) were required to make the tissue contract. 2 Phentolamine (10 μM) abolished the contractor response to higher concentrations of noradrenaline and antagonized the inhibitory effect of lower concentrations on the twitch response. 3 Propranolol (10 μM) potentiated both the contractor and the inhibitory effect of noradrenaline on the twitch response. 4 Isoprenaline (0.1-3.0 μM) and salbutamol (1.0-3.0 μM) both inhibited the twitch response. Their effects were antagonized by propranolol (10 μM), but not by practolol (10 μM). 5 The effects of uptake1 and uptake2 blocking agents were determined. Cocaine (10 μM) reduced the size of the twitch response in 2 out of 4 experiments. Imipramine (0.18 μM) also reduced the size of the twitch, as did oestradiol (3.7 μM) and a combination of cocaine and oestradiol. 6 Contractor responses to exogenous noradrenaline showed tachyphylaxis, but when this was not very marked, the response could be shown to be potentiated by uptake blocking agents. 7 The inhibitory effect of noradrenaline on the twitch response was greatly potentiated by cocaine (10 μM) and much less so by oestradiol (3.7 μM). 8 It is concluded that the transmitter responsible for the twitch response is either an unknown substance released from the sympathetic neurone, or noradrenaline acting upon a receptor with none of the characteristics of known α- or β-adrenoceptors. In either case, noradrenaline can inhibit the output, probably by stimulation of presynaptic α-adrenoceptors. PMID:202361
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Congenital myasthenic syndromes in Turkey: Clinical clues and prognosis with long term follow-up.
Durmus, Hacer; Shen, Xin-Ming; Serdaroglu-Oflazer, Piraye; Kara, Bulent; Parman-Gulsen, Yesim; Ozdemir, Coskun; Brengman, Joan; Deymeer, Feza; Engel, Andrew G
2018-04-01
Congenital myasthenic syndromes (CMS) are a group of hereditary disorders affecting the neuromuscular junction. Here, we present clinical, electrophysiological and genetic findings of 69 patients from 51 unrelated kinships from Turkey. Genetic tests of 60 patients were performed at Mayo Clinic. Median follow-up time was 9.8 years (range 1-22 years). The most common CMS was primary acetylcholine receptor (AChR) deficiency (31/51) and the most common mutations in AChR were c.1219 + 2T > G (12/51) and c.1327delG (6/51) in CHRNE. Four of our 5 kinships with AChE deficiency carried p.W148X that truncates the collagen domain of COLQ, and was previously reported only in patients from Turkey. These were followed by GFPT1 deficiency (4/51), DOK7 deficiency (3/51), slow channel CMS (3/51), fast channel CMS (3/51), choline acetyltransferase deficiency (1/51) and a CMS associated with desmin deficiency (1/51). Distribution of muscle weakness was sometimes useful in giving a clue to the CMS subtype. Presence of repetitive compound muscle action potentials pointed to AChE deficiency or slow channel CMS. Our experience confirms that one needs to be cautious using pyridostigmine, since it can worsen some types of CMS. Ephedrine/salbutamol were very effective in AChE and DOK7 deficiencies and were useful as adjuncts in other types of CMS. Long follow-up gave us a chance to assess progression of the disease, and to witness 12 mainly uneventful pregnancies in 8 patients. In this study, we describe some new phenotypes and detail the clinical features of the well-known CMS. Copyright © 2017 Elsevier B.V. All rights reserved.
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Rezazadeh, Maryam; Yamini, Yadollah; Seidi, Shahram; Arjomandi-Behzad, Leila
2014-01-10
In the present work, the effect of application of voltage steps on extraction efficiency of pulsed electromembrane extraction (PEME) was investigated for the first time. The effects of voltage variations including initial and final voltages, number of steps between the initial and final voltages as well as their time durations were studied on the extraction efficiencies of three different classes of analytes. These classes include amitriptyline (AMI) and nortriptyline (NOR) as more hydrophobic analytes, diclofenac (DIC) and mefenamic acid (MEF) as acidic drugs and salbutamol (SB) and terbutaline (TB) as hydrophilic compounds. It was anticipated that the application of high voltages is not necessary at the beginning of the extraction, since large amounts of target analytes exist around the supported liquid membrane (SLM)/sample solution interface. So, they could be easily transferred into the acceptor phase utilizing lower voltages. Results showed that the benefits of voltage-step PEME (VS-PEME) are more obvious in systems with low electrical resistance (regarding the SLM composition). Efficiencies of VS-PEME for extraction of AMI and NOR (96% and 89% for AMI and NOR, respectively) were comparable with those achieved from applying a constant voltage (95% for AMI and 83% for NOR). However, recoveries from the VS-PEME of DIC and MEF (53% and 44% for DIC and MEF, respectively) were significantly higher than those from the application of a constant voltage (33% for DIC and 31% for MEF). Also, recoveries obtained from the VS-PEME for SB and TB were approximately 3 orders of magnitude greater than those from a constant voltage. Moreover, it was demonstrated that in all cases analytes could effectively be extracted at the beginning of extraction by applying low voltages. Copyright © 2013 Elsevier B.V. All rights reserved.
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Oehme, Susanne; Mittag, Anja; Schrödl, Wieland; Tarnok, Attila; Nieber, Karen; Abraham, Getu
2015-02-01
It is not clear whether increased asthma severity associated with long-term use of β2-adrenoceptor (β2-AR) agonists can be attributed to receptor degradation and increased inflammation. We investigated the cross-talk between β-AR agonist-mediated effects on β2-AR function and expression and cytokine release in human bronchial epithelial cells. In 16HBE14o(-) cells grown in the presence and absence of β-AR agonists and/or antagonists, the β2-AR density was assessed by radioligand binding; the receptor protein and mRNA was determined using laser scanning cytometer and RT-PCR; cAMP generation, the cytokines IL-6 and IL-8 release were determined using AlphaScreen Assay and ELISA, respectively. Isoprenaline (ISO) and salbutamol (Salbu) induced a concentration- and time-dependent significant decrease in β2-AR density. Both Salbu and ISO reduced cAMP generation in a concentration-dependent manner while in same cell culture the IL-6 and IL-8 release was significantly enhanced. These effects were antagonized to a greater extent by ICI 118.551 than by propranolol, but CGP 20712A had no effect. Reduction of the β2-AR protein and mRNA could be seen when cells were treated with ISO for 24 h. Our findings indicate a direct link between cytokine release and altered β2-AR expression and function in airway epithelial cells. β2-AR desensitization and downregulation induced by long-term treatment with β2-AR agonists during asthma may account for adverse reactions also due to enhanced release of pro-inflammatory mediators and should, thus, be considered in asthma therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Cao, Biyun; He, Guangzhao; Yang, Hong; Chang, Huafang; Li, Shuqun; Deng, Anping
2013-10-15
Phenylethanolamine A (PA) is a new emerged β-adrenergic agonist illegally used as feed additives for growth promotion. In this study, a highly sensitive and specific indirect competitive enzyme-linked immunosorbent assay (ELISA) for the detection of PA in tissue and feed samples was developed and confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS). By reduction of nitryl group to amino group, the PA derivative was synthesized and coupled to carrier proteins with diazobenzidine method. The antisera obtained from four immunized rabbits were characterized in terms of sensitivity and specificity. All antisera displayed high sensitivity with IC50 values lower than 0.48 ng mL(-1). The most sensitive ELISA was established with IC50 and limit of detection (LOD) values of 0.049 ng mL(-1) and 0.003 ng mL(-1), respectively. The cross-reactivity (CR) values of the antisera with three frequently used β-adrenergic agonists (clenbuterol, salbutamol and ractopamine) were lesser than 0.39%; there was no CR of the antisera with other six compounds including two structurally related substances (isoproterenol, phenylephrine). To investigate the accuracy and precision of the assay, swine kidney, liver, meat and feed samples were fortified with PA at different content and analyzed by ELISA. Acceptable recovery rates of 92.2-113.7% and intra-assay coefficients of variation of 3.8-10.9% (n=3) were achieved. Seven spiked samples were simultaneously analyzed by ELISA and LC-MS/MS. There was a high correlation coefficient of 0.9956 (n=7) between the two methods. The proposed ELISA proven to be a feasible quantitative/screening method for PA analysis in tissue and feed samples with the properties of high sensitivity and specificity, high sample throughput and low expensive. © 2013 Elsevier B.V. All rights reserved.
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Materials Data on CoMo (SG:221) by Materials Project
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kristin Persson
Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations
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Como reembolsar sus prestamos para estudiantes (Repaying Your Student Loans).
ERIC Educational Resources Information Center
Office of Federal Student Aid (ED), Washington, DC.
This guide, written in Spanish, discusses how to repay student loans. Following a general introduction, the guide discusses the grace period before repayment and repayment requirements. Repayment plans are described for Perkins Loans, Direct Loans, and Federal Family Education Loans. Repayment options are discussed, including consolidation,…
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El Espanol como Idioma Universal (Spanish as a Universal Language)
ERIC Educational Resources Information Center
Mijares, Jose
1977-01-01
A proposal to transform Spanish into a universal language because it possesses the prerequisites: it is a living language, spoken in several countries; it is a natural language; and it uses the ordinary alphabet. Details on simplification and standardization are given. (Text is in Spanish.) (AMH)
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Múltiples estados de desorden en el etanol sólido
NASA Astrophysics Data System (ADS)
Fernández-Perea, R.
El diagrama de fases del etanol por debajo de los 169 K será presentado. Se mostrará que el etanol puede solidificarse en tres fases con diversos niveles de desorden,(como un vidrio(G), como un vidrio orientacional (OG) y como un cristal de fase rotora (RP)) además de en una fase totalmente cristalina. Las estructuras de estas tres fases serán presentadas tal y como se deducen a partir de diversas medidas de difracción de neutrones al igual que las proporciones de los isómeros de dicho material en las fases desordenadas y se compararán con los resultados de la fase cristalina y del líquido superenfriado. Igualmente diversas medidas sobre su dinámica serán presentadas, tanto de dispersión de neutrones, como de capacidad calorífica y de medidas dieléctricas y comparadas con modelos teóricos y simulaciones para tratar de explicar los procesos de relajación observados y las transiciones entre las diversas fases.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Dugulan, A.I.; Overweg, A.R.; Craje, M.W.J.
2005-04-26
The behavior of CoMo/Al2O3 catalysts sulfided in H2S/H2 gas mixture, under industrial conditions, was investigated using Moessbauer emission spectroscopy (MES). An intermediate Co-Mo phase is formed after increasing the sulfidation pressure to 4 MPa, favoring the Co-Mo-S phase formation. An increase in the quadrupole splitting value of the Co-sulfide species after treatment at 573 K is proposed as a prerequisite for the formation of ideal Co-Mo-S structures.
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Silva, Cristiane Gonçalves da; Santos, Alessandro Oliveira; Licciardi, Daniele Carli; Paiva, Vera; Parker, Richard
2008-01-01
Esse artigo descreve como jovens religiosos e autoridades religiosas de sua comunidade compreendem a sexualidade, considerando suas experiências pessoais e como membros de comunidades religiosas. A análise pretende contribuir para que políticas públicas dedicadas à promoção da saúde sexual da juventude considerem a religiosidade, no contexto de um estado laico e da promoção do direito à prevenção. Foram realizadas 26 entrevistas abertas e semidirigidas em diferentes comunidades da região metropolitana da cidade de São Paulo (comunidades católicas, da umbanda, do candomblé e de diferentes denominações evangélicas) sobre iniciação sexual, casamento, gravidez, contracepção e prevenção das DST/Aids, homossexualidade, aborto e direitos humanos. Observou-se como jovens e autoridades religiosas convivem com a tensão entre tradição e modernidade e os distintos discursos sobre a sexualidade. Como sujeitos religiosos (do discurso religioso) e sujeitos sexuais (de discursos sobre sexualidade), devem ser incorporados pelos programas como sujeitos de direito nos termos de sua religiosidade.
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Religiosidade, juventude e sexualidade: entre a autonomia e a rigidez1
Silva, Cristiane Gonçalves da; Santos, Alessandro Oliveira; Licciardi, Daniele Carli; Paiva, Vera; Parker, Richard
2009-01-01
Esse artigo descreve como jovens religiosos e autoridades religiosas de sua comunidade compreendem a sexualidade, considerando suas experiências pessoais e como membros de comunidades religiosas. A análise pretende contribuir para que políticas públicas dedicadas à promoção da saúde sexual da juventude considerem a religiosidade, no contexto de um estado laico e da promoção do direito à prevenção. Foram realizadas 26 entrevistas abertas e semidirigidas em diferentes comunidades da região metropolitana da cidade de São Paulo (comunidades católicas, da umbanda, do candomblé e de diferentes denominações evangélicas) sobre iniciação sexual, casamento, gravidez, contracepção e prevenção das DST/Aids, homossexualidade, aborto e direitos humanos. Observou-se como jovens e autoridades religiosas convivem com a tensão entre tradição e modernidade e os distintos discursos sobre a sexualidade. Como sujeitos religiosos (do discurso religioso) e sujeitos sexuais (de discursos sobre sexualidade), devem ser incorporados pelos programas como sujeitos de direito nos termos de sua religiosidade. PMID:21886456
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Sistema Solar: de la observación de La Tierra a los planetas gigantes y sus lunas
NASA Astrophysics Data System (ADS)
Rodrigo, R.
La fotoquímica tiene un papel principal en la composición de las atmósferas planetarias. Se examinan diferentes procesos fotoquímicos tanto para atmósferas oxidadas como reductoras, poniendo un especial énfasis en los ciclos químicos más importantes. En este sentido, se presentan diferentes ciclos químicos capaces de producir hidrocarbonos y nitrilos en atmósferas reductoras, así como aquellos capaces de mantener las proporciones de mezcla de las moléculas que contienen oxígeno, tales como CO2, O2 y H2O. También se analizan otros procesos importantes tales como la condensación y procesos de sputtering y de sublimación que han de tenerse en cuenta cuando se realizan modelos sobre la composición atmosférica.
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El dicloruro de paraquat, comúnmente conocido como “paraquat,” es uno de los herbicidas registrados de mayor uso en los Estados Unidos. El paraquat también se conoce como Gramaxone (un producto popular de uso final
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Como pagar to educacion, 2004-2005 (Funding Your Education, 2004-2005).
ERIC Educational Resources Information Center
Office of Federal Student Aid (ED), Washington, DC.
This publication, written in Spanish, describes financial aid programs of the U.S. Department of Education and advises students about paying for college. It outlines things a student should ask about college and how to obtain financial aid, whether grants, work-study, or loans. Chapters provide information on: (1) "Education after High School";…
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"Las Charlas" como expresion oral diaria ["Chats" as Daily Oral Practice].
ERIC Educational Resources Information Center
Borden, Matt
2002-01-01
An oral practice system of "chats" in the classroom functions as an extemporaneous speaking exercise or chat (without notes or prompt sheets), occurring between two students for a minute or so at the beginning of class, following which the presenters respond to other students' questions. (CNP)
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Management of phosgene-induced acute lung injury.
Grainge, Christopher; Rice, Paul
2010-07-01
administration of nebulized acetylcysteine 1-2 g, though there is no substantive evidence of benefit outside a small animal, isolated lung model and there is a possibility of adverse effects. If the oxygen saturation falls below 94%, patients should receive the lowest concentration of supplemental oxygen to maintain their SaO(2) in the normal range. Once patients require oxygen, nebulized β-agonists [e.g., salbutamol (albuterol) 5 mg by nebulizer every 4 h] may reduce lung inflammation if administered within 1 h of exposure. Elective intubation should be considered early using an ARDSnet protective ventilation strategy. Management of a large-scale, non-confirmed exposure. In the circumstances of a large-scale industrial or urban release, not all patients presenting will have been exposed and health services are likely to be highly stretched. In this situation, patients should not be treated immediately as there is no evidence that delaying therapy causes harm, rather they should be rested and observed with regular physical examination and measurement of peripheral oxygen saturations. Once a patient's oxygen saturation falls below 94%, treatment with the lowest concentration of oxygen required to maintain their oxygen saturations in the normal range should be started. Once oxygen has been started, nebulized β-agonists [e.g., salbutamol (albuterol) 5 mg by nebulizer every 4 h] may reduce lung inflammation if administered within 1 h of exposure, though delayed administration which is likely following a large-scale release has not been tested formally. There is no benefit from nebulized steroid even when administered 1 h after exposure, or high-dose corticosteroid if administered intravenously ≥6 h after exposure. Although there are no experimental data to support this recommendation, an intravenous bolus of high-dose corticosteroid (e.g., methylprednisolone 1 g) may be considered if presentation is <6 h and resources allow. Depending on the numbers of casualties presenting
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NASA Astrophysics Data System (ADS)
Damasio, Felipe; Allain, Olivier; Antunes Rodrigues, Adriano
2013-07-01
The study reported in this work takes place since 2009 at the Federal Institute of Education, Science and Technology of Santa Catarina, Campus Araranguá. Our main goal is to help form teachers, training undergraduate students in Natural Sciences with specialization in Physics as science communicators, as well as to promote actions of broader scientific popularization in the region of the town of Araranguá through an Astronomy Club called CA2. Among the actions of scientific popularization that the students promote are: video production, radio broadcasts, lectures, nightly observations, preparation and exhibition of posters, physics teaching for children, continuing education activities for teachers and regular physics teaching using Astronomy as a theme. The Club's teacher education and scientific dissemination work is based on the Theory of Meaningful Learning, always trying to reach the student's predisposition to learn and produce potentially meaningful material, the two essential conditions for meaningful learning to occur. O estudo que este trabalho relata ocorre desde 2009 no Instituto Federal de Educação, Ciência e Tecnologia de Santa Catarina, campus Araranguá. Nele procura-se formar divulgadores científicos durante a formação inicial de docentes do curso de Licenciatura em Ciências da Natureza com habilitação em Física, além de promover ações de divulgação científica para o público geral da região da cidade de Araranguá por meio de um Clube de Astronomia chamado CA² (Clube de Astronomia de Araranguá). Entre as ações de divulgação científica que os licenciandos promovem estão: produção de vídeos, programas de rádio, palestras, observações noturnas, confecção e exposição de pôsteres, ensino de física para crianças, formação continuada de professores em atividades e ensino de Física regular utilizando a Astronomia como tema gerador. O trabalho de formação docente e divulgação científica do Clube fundamenta
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ERIC Educational Resources Information Center
Mansfield, Gillian; Poppi, Franca
2012-01-01
The function of English as a lingua franca for communication needs rethinking in the teaching of English as a foreign language classroom as a consequence of globalisation. The present contribution is an empirical study carried out in an Italian university environment which aims to show how teachers should take on board awareness raising activities…
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Shaw, J.H.; Wolfe, R.R.
1988-03-01
We have assessed the effect of a variety of forms of metabolic intervention on both energy and protein metabolism in 44 severely ill surgical patients. The patients were studied either in the basal state or while receiving total parenteral nutrition (TPN), and the metabolic effects were assessed using the primed-constant infusion of a combination of stable isotopes and radioisotopes. Somatostatin infusion, either in the basal state or in the TPN, did not change glucose kinetics, but there was a significant decrease in the rate of net protein catabolism (NPC). In the basal studies the rate of NPC decreased from 3.4more » +/- 0.7 g/kg/d to 2.9 +/- 0.7 g/kg/d (p less than 0.002), while in the TPN patients the corresponding values were 1.48 +/- 0.61 g/kg/d and 1.10 +/- 0.50 g/kg/d, respectively (p less than 0.005). Histamine type 2 blockade with ranitidine did not significantly alter glucose kinetics, but in both the TPN patients and in the basal state ranitidine was associated with a significant decrease in the rate of NPC. In the basal state rate of NPC was 2.44 +/- 0.53 g/kg/d and during ranitidine infusion the value was 2.08 +/- 0.42 g/kg/d (p less than 0.04). Naloxone infusion did not alter glucose kinetics, but there was a significant decrease in the rate of NPC from a basal value of 2.6 +/- 0.6 g/kg/d to 2.3 +/- 0.5 g/kg/d (p less than 0.04). The infusion of the prostaglandin antagonists diclofenac or dipyridamole resulted in increases in the plasma insulin level, and as a result glucose turnover decreased in both groups. In the diclofenac group the rate of glucose turnover decreased from 14.4 +/- 1.7 mumol/kg/min to 12.6 +/- 1.3 mumol/kg/min (p less than 0.02). Neither prostaglandin antagonist resulted in any significant change in the rate of NPC.« less
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Jiang, Minghuan; Yang, Shimin; Yan, Kangkang; Liu, Jun; Zhao, Jun; Fang, Yu
2013-01-01
Objective To measure the prices and availability of selected medicines in Shaanxi Province after the implementation of new healthcare reform in 2009. Methods Data on the prices and availability of 47 medicines were collected from 50 public and 36 private sector medicine outlets in six regions of Shaanxi Province, Western China using a standardized methodology developed by the World Health Organization and Health Action International from September to October 2010. Medicine prices were compared with international reference prices to obtain a median price ratio. Affordability was measured as the number of days’ wages required for the lowest-paid unskilled government worker to purchase standard treatments for common conditions. Findings The mean availabilities of originator brands and lowest-priced generics were 8.9% and 26.5% in the public sector, and 18.1% and 43.6% in the private sector, respectively. The public sector procured generics and originator brands at median price ratios of 0.75 and 8.49, respectively, while patients paid 0.97 and 10.16. Final patient prices for lowest-priced generics and originator brands in the private sector were about 1.53 and 8.36 times their international retail prices, respectively. Public sector vendors applied high markups of 30.4% to generics, and 19.6% to originator brands. In the private sector, originator brands cost 390.7% more, on average, than their generic equivalents. Generic medicines were priced 17.3% higher in the private sector than the public sector. The lowest-paid government worker would need 0.1 day’s wages to purchase captopril for lowest-priced generics from private sector, while 6.6 days’ wages for losartan. For originator brands, the costs rise to 1.2 days’ wages for salbutamol inhaler and 15.6 days’ wages for omeprazole. Conclusions The prices, availability and affordability of medicines in China should be improved to ensure equitable access to basic medical treatments, especially for the poor
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Jiang, Minghuan; Yang, Shimin; Yan, Kangkang; Liu, Jun; Zhao, Jun; Fang, Yu
2013-01-01
To measure the prices and availability of selected medicines in Shaanxi Province after the implementation of new healthcare reform in 2009. Data on the prices and availability of 47 medicines were collected from 50 public and 36 private sector medicine outlets in six regions of Shaanxi Province, Western China using a standardized methodology developed by the World Health Organization and Health Action International from September to October 2010. Medicine prices were compared with international reference prices to obtain a median price ratio. Affordability was measured as the number of days' wages required for the lowest-paid unskilled government worker to purchase standard treatments for common conditions. The mean availabilities of originator brands and lowest-priced generics were 8.9% and 26.5% in the public sector, and 18.1% and 43.6% in the private sector, respectively. The public sector procured generics and originator brands at median price ratios of 0.75 and 8.49, respectively, while patients paid 0.97 and 10.16. Final patient prices for lowest-priced generics and originator brands in the private sector were about 1.53 and 8.36 times their international retail prices, respectively. Public sector vendors applied high markups of 30.4% to generics, and 19.6% to originator brands. In the private sector, originator brands cost 390.7% more, on average, than their generic equivalents. Generic medicines were priced 17.3% higher in the private sector than the public sector. The lowest-paid government worker would need 0.1 day's wages to purchase captopril for lowest-priced generics from private sector, while 6.6 days' wages for losartan. For originator brands, the costs rise to 1.2 days' wages for salbutamol inhaler and 15.6 days' wages for omeprazole. The prices, availability and affordability of medicines in China should be improved to ensure equitable access to basic medical treatments, especially for the poor. This requires multi-faceted interventions, as well
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Li, Jian-Sheng; Xie, Yang; Li, Su-Yun; Yu, Xue-Qing
2014-05-01
Chronic obstructive pulmonary disease (COPD) affects millions worldwide. Although many therapies exist and are being developed to relieve symptoms and reduce mortality, few data are available to understand which of the therapeutic alternatives is the most cost-effective for COPD patients in everyday clinical practice, especially for traditional Chinese medicine (TCM). Comparative effectiveness research can help patients, clinicians, and decision-makers make best informed treatment decisions where such evidence was previously lacking. This study aims to compare the effectiveness and economic evaluation of three treatments: (1) conventional Western medicine; (2) TCM treatments, which have been evaluated and have certain effect; and (3) a combination of both conventional Western medicine and TCM treatments, and then determine which treatment is the most suitable for COPD patients. A multicenter, pragmatic, randomized, controlled trial is adopted. A total of 360 patients will be recruited and randomly assigned to one of the three treatments group, with 120 in each group. Patients in the conventional Western medicine group will be given Salbutamol, Formoterol, Salmeterol/fluticasone, respectively, according to the guidelines. For the TCM group, patients will be given Bufei granule, Bu-Fei Jian-Pi granule, Bu-Fei Yi-Shen granule, and Yi-Qi Zi-Shen granule based on their corresponding TCM syndrome patterns, respectively. For the combination of conventional medicine and TCM treatments group, patients will be given a combination of conventional Western medicine and TCM granules. Treatments in each group are recognized as a whole comprehensive intervention. After the 26-week treatment, another 26 weeks will be followed up. The outcome measures including the frequency and duration of acute exacerbations, lung function, dyspnea, exercise capacity, quality of life, and economic evaluation will be assessed. It is hypothesized that each of the three treatments will have
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Price, David; Kaplan, Alan; Jones, Rupert; Freeman, Daryl; Burden, Anne; Gould, Shuna; von Ziegenweidt, Julie; Ali, Muzammil; King, Christine; Thomas, Mike
2015-01-01
Randomized controlled trials indicate that addition of a long-acting muscarinic antagonist (LAMA) such as tiotropium may improve asthma control and reduce exacerbation risk in patients with poorly controlled asthma, but broader clinical studies are needed to investigate the effectiveness of LAMA in real-life asthma care. Medical records of adults with asthma (aged ≥18 years) prescribed tiotropium were obtained from the UK Optimum Patient Care Research Database for the period 2001-2013. Patients diagnosed with chronic obstructive pulmonary disease were excluded, but no other clinical exclusions were applied. Two primary outcomes were compared in the year before (baseline) and the year after (outcome) addition of tiotropium: exacerbations (asthma-related hospital emergency department attendance or inpatient admission, or acute oral corticosteroid course) and acute respiratory events (exacerbation or antibiotic prescription with lower respiratory consultation). Secondary outcomes included lung function test results and short-acting β2 agonist usage. The Wilcoxon signed-rank test was used for variables measured on the interval scale, the marginal homogeneity test for categorized variables, and the paired t-test for lung function indices. Of the 2,042 study patients, 83% were prescribed an inhaled corticosteroid and 68% a long-acting β2 agonist during the baseline year; 67% were prescribed both. Comparing baseline and outcome years, the percentage of patients having at least one exacerbation decreased from 37% to 27% (P<0.001) and the percentage having at least one acute respiratory event decreased from 58% to 47% (P<0.001). There were no significant changes in lung function, and usage of short-acting β2 agonists (in salbutamol/albuterol equivalents) increased from a median (interquartile range) of 274 (110, 548) to 329 (110, 603) μg/day (P=0.01). In this real-life asthma population, addition of LAMA therapy was associated with significant decreases in the
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Daw, Jamie R; Mintzes, Barbara; Law, Michael R; Hanley, Gillian E; Morgan, Steven G
2012-01-01
Owing to the paucity of evidence available on the risks and benefits of drug use in pregnancy, the use of prescription medicines is a concern for both pregnant women and their health care providers. The aim of this study was to measure the frequency, timing, and type of medicines used before, during, and after pregnancy in a Canadian population. This retrospective cohort analysis used population-based health care data from all pregnancies ending in live births in hospitals in British Columbia from April 2001 to June 2006 (n = 163,082). Data from hospital records were linked to those in outpatient prescription-drug claims. Data from prescriptions filled from 6 months before pregnancy to 6 months postpartum were analyzed. Drugs were classified by therapeutic category and US Food and Drug Administration (FDA) pregnancy risk categories. Prescriptions were filled in 63.5% of pregnancies. Evidence on safety is limited for many of the medicines most frequently filled in pregnancy, including codeine, salbutamol, and betamethasone. At least 1 prescription for a category D or X medicine was filled in 7.8% of pregnancies (5.5% category D; 2.5% category X). The most frequently filled prescriptions for category D drugs were benzodiazepines and antidepressants. The most frequently filled prescriptions for category X drugs were oral contraceptives and ovulation stimulants filled in the first trimester. The majority of pregnant women in British Columbia filled at least 1 prescription, and ~1 in 13 filled a prescription for a drug categorized as D or X by the FDA. The prevalence of maternal prescription drug use emphasizes the need for postmarketing evaluation of the risk-benefit profiles of pharmaceuticals in pregnancy. Future research on prenatal drug use based on administrative databases should examine maternal treatment adherence and the determinants of maternal drug use, considering maternal health status, sociodemographics, and the characteristics and providers of prenatal
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Wang, Xiao; Fang, Yu; Yang, Shimin; Jiang, Minghuan; Yan, Kangkang; Wu, Lina; Lv, Bing; Shen, Qian
2014-01-01
Objective To evaluate the prices and availability of paediatric essential medicines in Shaanxi Province, China. Methods Price and availability data for 28 paediatric essential medicines were collected from 60 public hospitals and 60 retail pharmacies in six areas of Shaanxi Province using a standardised methodology developed by the World Health Organization and Health Action International, during November to December 2012. Affordability was measured as the number of days’ wages required for the lowest-paid unskilled government worker to purchase standard treatments for common conditions. Data on medicine price components were collected from hospitals, wholesalers and distributors to obtain price mark-ups. Findings The mean availabilities of originator brands (OBs) and lowest-priced generics (LPGs) were 10.8% and 27.3% in the public hospitals and 11.9% and 20.6% in the private pharmacies. The public procurement and retail prices were 2.25 and 2.59 times the international reference prices (IRPs) for three OBs, and 0.52 and 0.93 times for 20 LPGs. In the private sector, the final prices for OBs and LPGs were 3.89 and 1.25 times their IRPs. The final price in the private sector was 2.7% lower than in the public sector for OBs, and 14.1% higher for LPGs. Generally, standard treatments cost less than 1 day’s wages in both sectors. Distribution mark-ups applied to brand salbutamol in Xi'an was 65.5%, and up to 185.3% for generic. Cumulative mark-ups for LPGs in Ankang were also high, from 33% to 50%. The manufacturer’s selling price is the largest contributor to the final price in both areas. Conclusions The government should approve a list of national paediatric essential medicines. The availability, price and affordability of these should be improved in both public hospitals and private pharmacies to enable children to obtain effective treatment. Measures should be taken to improve the efficiency of the centralised medicine purchasing system. PMID:24595099
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Serelaxin Elicits Bronchodilation and Enhances β-Adrenoceptor-Mediated Airway Relaxation
Lam, Maggie; Royce, Simon G.; Donovan, Chantal; Jelinic, Maria; Parry, Laura J.; Samuel, Chrishan S.; Bourke, Jane E.
2016-01-01
Treatment with β-adrenoceptor agonists does not fully overcome the symptoms associated with severe asthma. Serelaxin elicits potent uterine and vascular relaxation via its cognate receptor, RXFP1, and nitric oxide (NO) signaling, and is being clinically evaluated for the treatment of acute heart failure. However, its direct bronchodilator efficacy has yet to be explored. Tracheal rings were prepared from male Sprague-Dawley rats (250–350 g) and tricolor guinea pigs, and precision cut lung slices (PCLSs) containing intrapulmonary airways were prepared from rats only. Recombinant human serelaxin (rhRLX) alone and in combination with rosiglitazone (PPARγ agonist; recently described as a novel dilator) or β-adrenoceptor agonists (isoprenaline, salbutamol) were added either to pre-contracted airways, or before contraction with methacholine or endothelin-1. Regulation of rhRLX responses by epithelial removal, indomethacin (cyclooxygenase inhibitor), L-NAME (nitric oxide synthase inhibitor), SQ22536 (adenylate cyclase inhibitor) and ODQ (guanylate cyclase inhibitor) were also evaluated. Immunohistochemistry was used to localize RXFP1 to airway epithelium and smooth muscle. rhRLX elicited relaxation in rat trachea and PCLS, more slowly than rosiglitazone or isoprenaline, but potentiated relaxation to both these dilators. It markedly increased β-adrenoceptor agonist potency in guinea pig trachea. rhRLX, rosiglitazone, and isoprenaline pretreatment also inhibited the development of rat tracheal contraction. Bronchoprotection by rhRLX increased with longer pre-incubation time, and was partially reduced by epithelial removal, indomethacin and/or L-NAME. SQ22536 and ODQ also partially inhibited rhRLX-mediated relaxation in both intact and epithelial-denuded trachea. RXFP1 expression in the airways was at higher levels in epithelium than smooth muscle. In summary, rhRLX elicits large and small airway relaxation via epithelial-dependent and -independent mechanisms, likely
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Leung, Cassandra Ming Shan; Tong, Zhenbo; Zhou, Qi Tony; Chan, John Gar Yan; Tang, Patricia; Sun, Siping; Yang, Runyu; Chan, Hak-Kim
2016-09-01
The design of a dry powder inhaler device has significant influence on aerosol performance; however, such influence may be different between the drug-only and carrier-based formulations. The present study aims to examine the potential difference on the dispersion between these distinct types of formulations, using Aerolizer(®) as a model inhaler with the original or modified (cross-grid) designs. A coupled CFD-discrete element method analysis was employed to determine the flow characteristics and particle impaction. Micronized salbutamol sulphate as a drug-only formulation and three lactose carrier-based formulations with various drug-to-carrier weight ratios 1:5, 1:10 and 1:100 were used. The in vitro aerosolization performance was assessed by a next-generation impactor operating at 100 L/min. Using the original device, FPFloaded was reduced from 47.5 ± 3.8% for the drug-only formulation to 31.8 ± 0.7%, 32.1 ± 0.7% and 12.9 ± 1.0% for the 1:5, 1:10 and 1:100 formulations, respectively. With the cross-grid design, powder-mouthpiece impaction was increased, which caused not only powder deagglomeration but also significant drug retention (doubling or more) in the mouthpiece, and the net result is a significant decrease in FPFloaded to 36.8 ± 1.2%, 20.9 ± 2.6% and 21.9 ± 1.5% for the drug-only, 1:5 and 1:10 formulations, respectively. In contrast, the FPFloaded of the 1:100 formulation remained the same at 12.1 ± 1.3%, indicating the increased mouthpiece drug retention was compensated by increased drug detachment from carriers caused by increased powder-mouthpiece impaction. In conclusion, this study has elucidated different effects and the mechanism on the aerosolization of varied dry powder inhaler formulations due to the grid design.
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Hanafi, Rasha Sayed; Lämmerhofer, Michael
2018-01-26
Quality-by-Design approach for enantioselective HPLC method development surpasses Quality-by-Testing in offering the optimal separation conditions with the least number of experiments and in its ability to describe the method's Design Space visually which helps to determine enantiorecognition to a significant extent. Although some schemes exist for enantiomeric separations on Cinchona-based zwitterionic stationary phases, the exact design space and the weights by which each of the chromatographic parameters influences the separation have not yet been statistically studied. In the current work, a screening design followed by a Response Surface Methodology optimization design were adopted for enantioseparation optimization of 3 model drugs namely the acidic Fmoc leucine, the amphoteric tryptophan and the basic salbutamol. The screening design proved that the acid/base additives are of utmost importance for the 3 chiral drugs, and that among 3 different pairs of acids and bases, acetic acid and diethylamine is the couple able to provide acceptable resolution at variable conditions. Visualization of the response surface of the retention factor, separation factor and resolution helped describe accurately the magnitude by which each chromatographic factor (% MeOH, concentration and ratio of acid base modifiers) affects the separation while interacting with other parameters. The global optima compromising highest enantioresolution with the least run time for the 3 chiral model drugs varied extremely, where it was best to set low % methanol with equal ratio of acid-base modifiers for the acidic drug, very high % methanol and 10-fold higher concentration of the acid for the amphoteric drug while 20 folds of the base modifier with moderate %methanol were needed for the basic drug. Considering the selected drugs as models for many series of structurally related compounds, the design space defined and the optimum conditions computed are the key for method development on
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Evaluation of partial beta-adrenoceptor agonist activity.
Lipworth, B J; Grove, A
1997-01-01
A partial beta-adrenoceptor (beta-AR) agonist will exhibit opposite agonist and antagonist activity depending on the prevailing degree of adrenergic tone or the presence of a beta-AR agonist with higher intrinsic activity. In vivo partial beta-AR agonist activity will be evident at rest with low endogenous adrenergic tone, as for example with chronotropicity (beta 1/beta 2), inotropicity (beta 1) or peripheral vasodilatation and finger tremor (beta 2). beta-AR blocking drugs which have partial agonist activity may exhibit a better therapeutic profile when used for hypertension because of maintained cardiac output without increased systemic vascular resistance, along with an improved lipid profile. In the presence of raised endogenous adrenergic tone such as exercise or an exogenous full agonist, beta-AR subtype antagonist activity will become evident in terms of effects on exercise induced heart rate (beta 1) and potassium (beta 2) responses. Reduction of exercise heart rate will occur to a lesser degree in the case of a beta-adrenoceptor blocker with partial beta 1-AR agonist activity compared with a beta-adrenoceptor blocker devoid of partial agonist activity. This may result in reduced therapeutic efficacy in the treatment of angina on effort when using beta-AR blocking drugs with partial beta 1-AR agonist activity. Effects on exercise hyperkalaemia are determined by the balance between beta 2-AR partial agonist activity and endogenous adrenergic activity. For predominantly beta 2-AR agonist such as salmeterol and salbutamol, potentiation of exercise hyperkalaemia occurs. For predominantly beta 2-AR antagonists such as carteolol, either potentiation or attenuation of exercise hyperkalaemia occurs at low and high doses respectively. beta 2-AR partial agonist activity may also be expressed as antagonism in the presence of an exogenous full agonist, as for example attenuation of fenoterol induced responses by salmeterol. Studies are required to investigate whether
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Horn, Felix C; Marshall, Helen; Collier, Guilhem J; Kay, Richard; Siddiqui, Salman; Brightling, Christopher E; Parra-Robles, Juan; Wild, Jim M
2017-09-01
Purpose To assess the magnitude of regional response to respiratory therapeutic agents in the lungs by using treatment response mapping (TRM) with hyperpolarized gas magnetic resonance (MR) imaging. TRM was used to quantify regional physiologic response in adults with asthma who underwent a bronchodilator challenge. Materials and Methods This study was approved by the national research ethics committee and was performed with informed consent. Imaging was performed in 20 adult patients with asthma by using hyperpolarized helium 3 ( 3 He) ventilation MR imaging. Two sets of baseline images were acquired before inhalation of a bronchodilating agent (salbutamol 400 μg), and one set was acquired after. All images were registered for voxelwise comparison. Regional treatment response, ΔR(r), was calculated as the difference in regional gas distribution (R[r] = ratio of inhaled gas to total volume of a voxel when normalized for lung inflation volume) before and after intervention. A voxelwise activation threshold from the variability of the baseline images was applied to ΔR(r) maps. The summed global treatment response map (ΔR net ) was then used as a global lung index for comparison with metrics of bronchodilator response measured by using spirometry and the global imaging metric percentage ventilated volume (%VV). Results ΔR net showed significant correlation (P < .01) with changes in forced expiratory volume in 1 second (r = 0.70), forced vital capacity (r = 0.84), and %VV (r = 0.56). A significant (P < .01) positive treatment effect was detected with all metrics; however, ΔR net showed a lower intersubject coefficient of variation (64%) than all of the other tests (coefficient of variation, ≥99%). Conclusion TRM provides regional quantitative information on changes in inhaled gas ventilation in response to therapy. This method could be used as a sensitive regional outcome metric for novel respiratory interventions. © RSNA, 2017 Online supplemental material is
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Wang, Jinrong; Cui, Zhaobo; Liu, Shuhong; Gao, Xiuling; Gao, Pan; Shi, Yi; Guo, Shufen; Li, Peipei
2017-03-01
Noninvasive positive-pressure ventilation (NPPV) might be superior to conventional mechanical ventilation (CMV) in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPDs). Inefficient clearance of respiratory secretions provokes NPPV failure in patients with hypercapnic encephalopathy (HE). This study compared CMV and NPPV combined with a noninvasive strategy for clearing secretions in HE and AECOPD patients.The present study is a prospective cohort study of AECOPD and HE patients enrolled between October 2013 and August 2015 in a critical care unit of a major university teaching hospital in China.A total of 74 patients received NPPV and 90 patients received CMV. Inclusion criteria included the following: physician-diagnosed AECOPD, spontaneous airway clearance of excessive secretions, arterial blood gas analysis requiring intensive care, moderate-to-severe dyspnea, and a Kelly-Matthay scale score of 3 to 5. Exclusion criteria included the following: preexisting psychiatric/neurological disorders unrelated to HE, upper gastrointestinal bleeding, upper airway obstruction, acute coronary syndromes, preadmission tracheostomy or endotracheal intubation, and urgent endotracheal intubation for cardiovascular, psychomotor agitation, or severe hemodynamic conditions.Intensive care unit participants were managed by NPPV. Participants received standard treatment consisting of controlled oxygen therapy during NPPV-free periods; antibiotics, intravenous doxofylline, corticosteroids (e.g., salbutamol and ambroxol), and subcutaneous low-molecular-weight heparin; and therapy for comorbidities if necessary. Nasogastric tubes were inserted only in participants who developed gastric distension. No pharmacological sedation was administered.The primary and secondary outcome measures included comparative complication rates, durations of ventilation and hospitalization, number of invasive devices/patient, and in-hospital and 1-year mortality rates
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Prosser, R S; Sibley, P K
2015-02-01
Amending soil with biosolids or livestock manure provides essential nutrients in agriculture. Irrigation with wastewater allows for agriculture in regions where water resources are limited. However, biosolids, manure and wastewater have all been shown to contain pharmaceuticals and personal care products (PPCPs). Studies have shown that PPCPs can accumulate in the tissues of plants but the risk that accumulated residues may pose to humans via consumption of edible portions is not well documented. This study reviewed the literature for studies that reported residues of PPCPs in the edible tissue of plants grown in biosolids- or manure-amended soils or irrigated with wastewater. These residues were used to determine the estimated daily intake of PPCPs for an adult and toddler. Estimated daily intake values were compared to acceptable daily intakes to determine whether PPCPs in plant tissue pose a hazard to human health. For all three amendment practices, the majority of reported residues resulted in hazard quotients <0.1. Amendment with biosolids or manure resulted in hazard quotients ≥0.1 for carbamazepine, diphenhydramine, salbutamol, triclosan, and sulfamethazine. Irrigation with wastewater resulted in hazard quotients of ≥0.1 for ambrettolid, carbamazepine, diclofenac, flunixin, lamotrigine, metoprolol, naproxen, sildenafil and tonalide. [corrected]. Many of the residues that resulted in hazard quotients ≥0.1 were due to exposing plants to concentrations of PPCPs that would not be considered relevant based on concentrations reported in biosolids and manure or unrealistic methods of exposure, which lead to artificially elevated plant residues. Our assessment indicates that the majority of individual PPCPs in the edible tissue of plants due to biosolids or manure amendment or wastewater irrigation represent a de minimis risk to human health. Assuming additivity, the mixture of PPCPs could potentially present a hazard. Further work needs to be done to assess
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Israël-Assayag, Evelyne; Beaulieu, Marie-Josée; Cormier, Yvon
2015-01-01
Inhaled β2-adrenoreceptor agonists are widely used in asthma and chronic obstructive pulmonary disease (COPD) for bronchoconstriction relief. β2-adrenoreceptor agonists relax airway smooth muscle cells via cyclic adenosine monophosphate (cAMP) mediated pathways. However, prolonged stimulation induces functional desensitization of the β2-adrenoreceptors (β2-AR), potentially leading to reduced clinical efficacy with chronic or prolonged administration. ASM-024, a small synthetic molecule in clinical stage development, has shown activity at the level of nicotinic receptors and possibly at the muscarinic level and presents anti-inflammatory and bronchodilator properties. Aerosolized ASM-024 reduces airway resistance in mice and promotes in-vitro relaxation of tracheal and bronchial preparations from animal and human tissues. ASM-024 increased in vitro relaxation response to maximally effective concentration of short—acting beta-2 agonists in dog and human bronchi. Although the precise mechanisms by which ASM-024 promotes airway smooth muscle (ASM) relaxation remain unclear, we hypothesized that ASM-024 will attenuate and/or abrogate agonist-induced contraction and remain effective despite β2-AR tachyphylaxis. β2-AR tachyphylaxis was induced with salbutamol, salmeterol and formoterol on guinea pig tracheas. The addition of ASM-024 relaxed concentration-dependently intact or β2-AR desensitized tracheal rings precontracted with methacholine. ASM-024 did not induce any elevation of intracellular cAMP in isolated smooth muscle cells; moreover, blockade of the cAMP pathway with an adenylate cyclase inhibitor had no significant effect on ASM-024-induced guinea pig trachea relaxation. Collectively, these findings show that ASM-024 elicits relaxation of β2-AR desensitized tracheal preparations and suggest that ASM-024 mediates smooth muscle relaxation through a different target and signaling pathway than β2-adrenergic receptor agonists. These findings suggest ASM-024
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Israël-Assayag, Evelyne; Beaulieu, Marie-Josée; Cormier, Yvon
2015-01-01
Inhaled β2-adrenoreceptor agonists are widely used in asthma and chronic obstructive pulmonary disease (COPD) for bronchoconstriction relief. β2-Adrenoreceptor agonists relax airway smooth muscle cells via cyclic adenosine monophosphate (cAMP) mediated pathways. However, prolonged stimulation induces functional desensitization of the β2-adrenoreceptors (β2-AR), potentially leading to reduced clinical efficacy with chronic or prolonged administration. ASM-024, a small synthetic molecule in clinical stage development, has shown activity at the level of nicotinic receptors and possibly at the muscarinic level and presents anti-inflammatory and bronchodilator properties. Aerosolized ASM-024 reduces airway resistance in mice and promotes in-vitro relaxation of tracheal and bronchial preparations from animal and human tissues. ASM-024 increased in vitro relaxation response to maximally effective concentration of short-acting beta-2 agonists in dog and human bronchi. Although the precise mechanisms by which ASM-024 promotes airway smooth muscle (ASM) relaxation remain unclear, we hypothesized that ASM-024 will attenuate and/or abrogate agonist-induced contraction and remain effective despite β2-AR tachyphylaxis. β2-AR tachyphylaxis was induced with salbutamol, salmeterol and formoterol on guinea pig tracheas. The addition of ASM-024 relaxed concentration-dependently intact or β2-AR desensitized tracheal rings precontracted with methacholine. ASM-024 did not induce any elevation of intracellular cAMP in isolated smooth muscle cells; moreover, blockade of the cAMP pathway with an adenylate cyclase inhibitor had no significant effect on ASM-024-induced guinea pig trachea relaxation. Collectively, these findings show that ASM-024 elicits relaxation of β2-AR desensitized tracheal preparations and suggest that ASM-024 mediates smooth muscle relaxation through a different target and signaling pathway than β2-adrenergic receptor agonists. These findings suggest ASM-024
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Electrostatic charge characteristics of jet nebulized aerosols.
Kwok, Philip Chi Lip; Trietsch, Sebastiaan J; Kumon, Michiko; Chan, Hak-Kim
2010-06-01
Liquid droplets can be spontaneously charged in the absence of applied electric fields by spraying. It has been shown by computational simulation that charges may influence particle deposition in the airways. The electrostatic properties of jet nebulized aerosols and their potential effects on lung deposition have hardly been studied. A modified electrical low pressure impactor (ELPI) was employed to characterize the aerosol charges generated from jet nebulized commercial products. The charge and size measurements were conducted at 50% RH and 22 degrees C with a modified ELPI. Ventolin, Bricanyl, and Atrovent were nebulized using PARI LC Plus jet nebulizers coupled to a DeVilbiss Pulmo-Aide compressor. The aerosols were sampled in 30-sec durations. The drug deposits on the impactor stages were assayed chemically using high-performance liquid chromatography (HPLC). The charges of nebulized deionized water, isotonic saline, and the three commercial products diluted with saline were also measured to analyze the contributions of the major nebule ingredients on charging. No mass assays were performed on these runs. All three commercial nebules generated net negative charges. The magnitude of the charges reduced over the period of nebulization. Ventolin and Bricanyl yielded similar charge profiles. Highly variable charges were produced from deionized water. On the other hand, nebulized saline reproducibly generated net positive charges. Diluted commercial nebules showed charge polarity inversion. The charge profiles of diluted salbutamol and terbutaline solutions resembled those of saline, while the charges from diluted ipratropium solutions fluctuated near neutrality. The charge profiles were shown to be influenced by the concentration and physicochemical properties of the drugs, as well as the history of nebulization. The drugs may have unique isoelectric concentrations in saline at which the nebulized droplets would carry near-zero charges. According to results from
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Wang, Xiao; Fang, Yu; Yang, Shimin; Jiang, Minghuan; Yan, Kangkang; Wu, Lina; Lv, Bing; Shen, Qian
2014-01-01
To evaluate the prices and availability of paediatric essential medicines in Shaanxi Province, China. Price and availability data for 28 paediatric essential medicines were collected from 60 public hospitals and 60 retail pharmacies in six areas of Shaanxi Province using a standardised methodology developed by the World Health Organization and Health Action International, during November to December 2012. Affordability was measured as the number of days' wages required for the lowest-paid unskilled government worker to purchase standard treatments for common conditions. Data on medicine price components were collected from hospitals, wholesalers and distributors to obtain price mark-ups. The mean availabilities of originator brands (OBs) and lowest-priced generics (LPGs) were 10.8% and 27.3% in the public hospitals and 11.9% and 20.6% in the private pharmacies. The public procurement and retail prices were 2.25 and 2.59 times the international reference prices (IRPs) for three OBs, and 0.52 and 0.93 times for 20 LPGs. In the private sector, the final prices for OBs and LPGs were 3.89 and 1.25 times their IRPs. The final price in the private sector was 2.7% lower than in the public sector for OBs, and 14.1% higher for LPGs. Generally, standard treatments cost less than 1 day's wages in both sectors. Distribution mark-ups applied to brand salbutamol in Xi'an was 65.5%, and up to 185.3% for generic. Cumulative mark-ups for LPGs in Ankang were also high, from 33% to 50%. The manufacturer's selling price is the largest contributor to the final price in both areas. The government should approve a list of national paediatric essential medicines. The availability, price and affordability of these should be improved in both public hospitals and private pharmacies to enable children to obtain effective treatment. Measures should be taken to improve the efficiency of the centralised medicine purchasing system.
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[Acute pancreatitis and acalculous cholecystitis associated with viral hepatitis A].
Arcana, Ronald; Frisancho, Oscar
2011-01-01
We report the case of a 14 year-old male from Lima. He is a student with a history of bronchial asthma since age 4 receives conditional salbutamol, corticosteroids used for asthma attacks (a crisis in 2010, 1 month ago) Refuses surgery or transfusions. He presented with a two weeks for abdominal pain, nausea, fever, and jaundice. Epigastric pain is colicky and radiated back to righ upper quadrant, refers in addition to nausea and fever, for ten days notice jaundice of skin and sclera. On examen he was lucid, with jaundice of skin and mucous membranes. There was no palpable lymph nodes, abdomen with bowel sounds, soft, depressible, liver span of 15cm, positive Murphy, no peritonitis. The laboratory findings showed hemoglobin 13gr, MCV 90, platelets 461.000/mm3, WBC 4320/mm, lymphocytes 1700 (39%). total bilirubin: 8.8, B Direct: 7.6, ALT (alanine aminotransferase): 3016, AST (aspartate aminotransferase): 984, alkaline phosphatase: 250, albumin: 3.34gr%, globulin: 2.8, amylase: 589 (high serum amylase), TP: 17, INR: 1.6, VHA IgM positive. 89 mg glucose, urea 19 mg%, creatinine 0.5 mg Hemoglobin 13gr, MCV 90 Platelet 461000/mm3, WBC 4320/mm, Lymphocytes 1700 (39%). The nuclear magnetic resonance showed hepatomegaly associated with thickening of gallbladder wall without stones up to 11mm inside. No bile duct dilatation, bile duct 4mm, pancreas increased prevalence of body size. Mild splenomegaly and free fluid in the space of Morrison and right flank. Abdominal ultrasound revealed a gallbladder wall thickness (11mm), without stones in his light. Pancreas to increase volume with peripancreatic fluid free perivesicular with a volume of 430 cc. Findings consistent with acute acalculous cholecystitis and acute pancreatitis. CT-scan showed enlarged pancreas with predominance of body and tail with peripancreatic edema; the gallbladder was thickening. We report this case because the extrahepatic manifestations of viral hepatitis A infection are uncommon, specially the
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Santos, Lúcia H M L M; Gros, Meritxell; Rodriguez-Mozaz, Sara; Delerue-Matos, Cristina; Pena, Angelina; Barceló, Damià; Montenegro, M Conceição B S M
2013-09-01
The impact of effluent wastewaters from four different hospitals: a university (1456 beds), a general (350 beds), a pediatric (110 beds) and a maternity hospital (96 beds), which are conveyed to the same wastewater treatment plant (WWTP), was evaluated in the receiving urban wastewaters. The occurrence of 78 pharmaceuticals belonging to several therapeutic classes was assessed in hospital effluents and WWTP wastewaters (influent and effluent) as well as the contribution of each hospital in WWTP influent in terms of pharmaceutical load. Results indicate that pharmaceuticals are widespread pollutants in both hospital and urban wastewaters. The contribution of hospitals to the input of pharmaceuticals in urban wastewaters widely varies, according to their dimension. The estimated total mass loadings were 306 g d(-1) for the university hospital, 155 g d(-1) for the general one, 14 g d(-1) for the pediatric hospital and 1.5 g d(-1) for the maternity hospital, showing that the biggest hospitals have a greater contribution to the total mass load of pharmaceuticals. Furthermore, analysis of individual contributions of each therapeutic group showed that NSAIDs, analgesics and antibiotics are among the groups with the highest inputs. Removal efficiency can go from over 90% for pharmaceuticals like acetaminophen and ibuprofen to not removal for β-blockers and salbutamol. Total mass load of pharmaceuticals into receiving surface waters was estimated between 5 and 14 g/d/1000 inhabitants. Finally, the environmental risk posed by pharmaceuticals detected in hospital and WWTP effluents was assessed by means of hazard quotients toward different trophic levels (algae, daphnids and fish). Several pharmaceuticals present in the different matrices were identified as potentially hazardous to aquatic organisms, showing that especial attention should be paid to antibiotics such as ciprofloxacin, ofloxacin, sulfamethoxazole, azithromycin and clarithromycin, since their hazard quotients
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Ducharme, F M; Zemek, R; Gravel, J; Chalut, D; Poonai, N; Laberge, S; Quach, C; Krajinovic, M; Guimont, C; Lemière, C; Guertin, M C
2014-01-01
Introduction Oral corticosteroids are the cornerstone of acute asthma management in the emergency department. Recent evidence has raised doubts about the efficacy of this treatment in preschool-aged children with viral-induced wheezing and in smoking adults. The aims of the study were to: (1) document the magnitude of response to oral corticosteroids in children presenting to the emergency department with moderate or severe asthma; (2) quantify potential determinants of response to corticosteroids and (3) explore the role of gene polymorphisms associated with the responsiveness to corticosteroids. Methods and analysis The design is a prospective cohort study of 1008 children aged 1–17 years meeting a strict definition of asthma and presenting with a clinical score of ≥4 on the validated Pediatric Respiratory Assessment Measure. All children will receive standardised severity-specific treatment with prednisone/prednisolone and cointerventions (salbutamol with/without ipratropium bromide). Determinants, namely viral aetiology, environmental tobacco smoke and single nucleotide polymorphism, will be objectively documented. The primary efficacy endpoint is the failure of emergency department (ED) management within 72 h of the ED visit. Secondary endpoints include other measures of asthma severity and time to recovery within 7 days of the index visit. The study has 80% power for detecting a risk difference of 7.5% associated with each determinant from a baseline risk of 21%, at an α of 0.05. Ethics and dissemination Ethical approval has been obtained from all participating institutions. An impaired response to systemic steroids in certain subgroups will challenge the current standard of practice and call for the immediate search for better approaches. A potential host–environment interaction will broaden our understanding of corticosteroid responsiveness in children. Documentation of similar effectiveness of corticosteroids across determinants will provide
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Martín Álvarez, Estefanía; Jiménez Cabanillas, María Victoria; Peña Caballero, Manuela; Serrano López, Laura; Kajarabille, Naroa; Díaz Castro, Javier; Ochoa Herrera, Julio José; Maldonado Lozano, José
2016-03-25
Introducción: el recién nacido prematuro de muy bajo peso (RNMBP) es inmunológicamente inmaduro y además presenta una alteración de las barreras naturales de defensa. Objetivo: evaluar los efectos que pueda tener la administración de calostro orofaríngeo, administrado durante los primeros 15 días posnatales, sobre los niveles de inmunoglobulina A (IgA) sérica en recién nacidos prematuros de muy bajo peso durante el primer mes de vida. Material y métodos: se desarrolló un estudio de intervención no aleatorizado con grupo control, en el que se incluyeron 38 recién nacidos con ≤ 32 + 6 semanas de gestación y/o menores de 1.500 g de peso. Los sujetos recibieron 0,2 ml de calostro de su madre cada 4 h, iniciándose el procedimiento en las primeras 24 h de vida hasta el 15.o día postnatal. Se midieron los niveles de IgA en la sangre al nacimiento, 3. er , 15.o y 30.o días de vida. Se registraron datos perinatales al nacimiento y durante el periodo de seguimiento. Resultados: IgA sérica aumentó de forma estadísticamente significativa en el grupo de intervención (M1 15,84 μg/ml, M2 20,07 μg/ml, M3 23,65 μg/ml, M4 30,34 μg/ml, p 0,001) y en el grupo control (M1 12,48 μg/ml, M2 16,48 μg/ml, p 0,018; M3 19,41 μg/ml, M4 22,48 μg/ml, p 0,001). Al mes de vida, los niveles de IgA sérica fueron significativamente mayores en el grupo de intervención que en el grupo control (p 0,026). Conclusiones: este estudio sugiere que la administración de calostro orofarínge.
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Acceptability of an Embodied Conversational Agent-based Computer Application for Hispanic Women
Wells, Kristen J.; Vázquez-Otero, Coralia; Bredice, Marissa; Meade, Cathy D.; Chaet, Alexis; Rivera, Maria I.; Arroyo, Gloria; Proctor, Sara K.; Barnes, Laura E.
2015-01-01
There are few Spanish language interactive, technology-driven health education programs. Objectives of this feasibility study were to: 1) learn more about computer and technology usage among Hispanic women living in a rural community; and 2) evaluate acceptability of the concept of using an embodied conversational agent (ECA) computer application among this population. A survey about computer usage history and interest in computers was administered to a convenience sample of 26 women. A sample video prototype of a hospital discharge ECA was administered followed by questions to gauge opinion about the ECA. Data indicate women exhibited both a high level of computer experience and enthusiasm for the ECA. Feedback from community is essential to ensure equity in state of the art dissemination of health information. Hay algunos programas interactivos en español que usan la tecnología para educar sobre la salud. Los objetivos de este estudio fueron: 1) aprender más sobre el uso de computadoras y tecnología entre mujeres Hispanas que viven en comunidades rurales y 2) evaluar la aceptabilidad del concepto de usar un programa de computadora utilizando un agente de conversación encarnado (ECA) en esta población. Se administro una encuesta sobre el historial de uso y del interés de aprender sobre computadoras fue a 26 mujeres por muestreo de conveniencia. Un ejemplo del prototipo ECA en forma de video de un alta hospitalaria fue administrado y fue seguido por preguntas sobre la opinión que tenían del ECA. Los datos indican que las mujeres mostraron un alto nivel de experiencia con las computadoras y un alto nivel de entusiasmo sobre el ECA. La retroalimentación de la comunidad es esencial para asegurar equidad en la diseminación de información sobre la salud con tecnología de punta. PMID:26671558
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Helenistic Encomium: A Reflection on Comics and Rhetoric
ERIC Educational Resources Information Center
Helms, Jason
2009-01-01
This video reflection starts in a presentation on comics at the Thomas R. Watson Conference last October, which prompted the author to explore the etymology of cosmos and comos through an alternate reading of Gorgias' "Encomium of Helen". The author then works with comos, as revelry, to offer thoughts on comics as a form of multimodal composition…
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Cuauhtemoc Saenz-Romero; Gerald E. Rehfeldt; Nicholas L. Crookston; Pierre Duval; Jean Beaulieu
2009-01-01
El cambio climatico, conocido comunmente como calentamiento global, es el incremento de la temperatura a nivel mundial y los cambios que de ello derivan, causados por el "efecto invernadero" del bioxido de carbono (CO2) y otros gases emitidos a la atmosfera. El uso de combustibles fosiles (carbon y derivados del petroleo, como gasolina, diesel, combustoleo y...
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Uso de terreno urbano y rural en Puerto Rico
Sebastian Martinuzzi; William A. Gould; Olga M. Ramos Gonzalez; Maya Quinones; Michael E. Jimenez
2008-01-01
El Proyecto de Analisis de Gap de Puerto Rico (PRGAP) (Gould et al. 2008) desarrollo tres usos de terrenos para Puerto Rico: Urbano, Suburbano, y Rural (Martinuzzi et al. 2007). Estas regiones tambien pueden ser consideradas como urbano, densamente-poblado rural, y escasamente-poblado rural, o como urbano y area silvestre con una interfase de area silvestre-urbana. La...
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Contributions of local knowledge to the physical limnology of Lake Como, Italy.
Laborde, Sarah; Imberger, Jörg; Toussaint, Sandy
2012-04-24
This article shows how local knowledge may be valuably integrated into a scientific approach in the study of large and complex hydrological systems where data collection at high resolution is a challenge. This claim is supported through a study of the hydrodynamics of a large lake where qualitative data collected from professional fishers was combined with theory to develop a hypothesis that was then verified by numerical modeling. First the fishermen's narratives were found to describe with accuracy internal wave motions that were evident in water column temperature records, which revealed their practical knowledge of the lake's hydrodynamics. Second, local knowledge accounts emphasized the recurrent formation of mesoscale gyres and return flows in certain zones of the lake in stratified conditions, which did not appear in the physical data because of limitations of sampling resolution. We hypothesized that these features developed predominantly because of the interaction of wind-driven internal motions with the lake's bathymetry, and the Earth's rotation in the widest areas of the basin. Numerical simulation results corroborated the fishers' descriptions of the flow paths and supported the hypothesis about their formation. We conclude that the collaboration between scientific and local knowledge groups, although an unusual approach for a physical discipline of the geosciences, is worth exploring in the pursuit of a more comprehensive understanding of complex geophysical systems such as large lakes.
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Management, Maintenance, and Upkeep of the Baseline COMO III Air Defense Model.
1986-10-20
weapon subsystems. The sensor subsystems include passive, infrared (IR), television, and a nonimaging sensor and observer, typically the vehicle driver...initially scheduled from the enter game event (DGO) and is rescheduled on a cyclic basis. When radar target detection occurs, the optical search process (DG9...one search cycle in elevation by the track radar/gunner’s optics . DG1 constantly monitors the radar surveillance search volume and when a higher
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Como Lo Hago Yo: Defectos Del Cierre Del Tubo Neural En Nicaragua
Gonzalez, Juan Bosco
2014-01-01
En Nicaragua no hay un plan de forltificación de alimentos con ácido fólico. Las madres son muy jóvenes. En La Mascota operamos mas de cuarenta niños por año. Derivación tardía es un problema. La infección preoperatoria tiene que ser descartada. Vancomicina y Ceftriaxone estan indicadas. Estricta regla de asepsia operatoria. Suturamos la plaqueta para asemejar su forma al cilindro normal de la médula. No ceramos la capa de músculo. PMID:24791221
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DESAFÍOS ÉTICOS DE LA INVESTIGACIÓN CON ANIMALES, MANIPULACIÓN GENÉTICA
Yunta, Eduardo Rodríguez
2012-01-01
En la investigación con animales existen cuestionamientos éticos tanto en el uso como modelos de enfermedades humanas y requisito previo para ensayos en humanos como en la introducción de modificaciones genéticas. Algunos de estos cuestionamientos son: no representar exactamente la condición humana como modelos, realizar pruebas de toxicidad con grave daño para los animales, alterar su naturaleza mediante modificaciones genéticas, riesgos de la introducción de organismos genéticamente modificados. El uso de animales en investigación para beneficio humano, impone al ser humano la responsabilidad moral de respetarlo, no haciéndoles sufrir innecesariamente, al estar trabajando con seres vivientes y sentientes. PMID:23338641
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Reis, Mario S; Moreira Dos Santos, Antonio F
Por s culos, acreditou-se que o magnetismo s se manifestava em metais, como aqueles contendo ferro; hoje, a imagem mais comum de um m talvez seja a daquelas plaquinhas flex veis coladas geladeira com propagandas dos mais diversos tipos. O leitor conseguiria imaginar um material puramente org nico daqueles que formam os seres vivos como magn tico? E m s do tamanho de mol culas? fato: ambos existem. Esses novos materiais, conhecidos como magnetos moleculares, descobertos e desenvolvidos em v rios laborat rios do mundo, j re nem longa lista de aplica es, do tratamento do c ncer a refrigeradoresmore » ecol gicos, passando pela transmiss o de eletricidade sem perda de calor e a fabrica o de computadores extremamente velozes.« less
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"Como Si Nada": Enduring Violence and Diabetes among Rural Women in Southern Mexico.
Montesi, Laura
2018-04-01
Rural women in Southern Mexico link their diabetes to distressful life experiences rooted in ordinary violence. While much has been written on the use that diabetes sufferers make of their morbid condition as an idiom of distress, I investigate the personal and social effects that such an idiom has on women. As I illustrate, diabetes reflects an ambivalence that helps women to speak about the unspeakable and, at the same time, reinforces their ideas of culpability, namely that they are to blame for both the gendered violence that they endure and the diabetes from which they suffer.
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Como Ayudar a sus Hijos a Aprender Ciencia (Helping Your Child Learn Science).
ERIC Educational Resources Information Center
Paulu, Nancy; Martin, Margery
Because most parents say they do not or cannot help their children with science, this booklet was designed to help them do so, easily and with pleasure for both parent and child. The introduction presents information on why and how parents should help their children and provides a general orientation to the ideas and activities offered in the…
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Berton, Danilo Cortozi; Santos, Álvaro Huber Dos; Bohn, Ivo; Lima, Rodrigo Quevedo de; Breda, Vanderléia; Teixeira, Paulo José Zimermann
2016-01-01
longa duração administrado uma vez por dia (indacaterol 150 µg) a um anticolinérgico de longa duração administrado uma vez por dia (tiotrópio 5 µg) quanto a seus efeitos na resistência ao exercício (limite de tolerância, Tlim) em pacientes com DPOC moderada. Os desfechos secundários foram seus efeitos na hiperinsuflação pulmonar, na dispneia causada pelo exercício e na dispneia na vida diária. Estudo piloto randomizado cruzado e simples cego com 20 pacientes (média de idade: 60,9 ± 10,0 anos; média do VEF1: 69 ± 7% do previsto). Parâmetros espirométricos, pontuação no Transition Dyspnea Index, Tlim e dispneia aos esforços foram comparados após três semanas de cada tratamento (com uma semana de intervalo entre os tratamentos). Dezenove pacientes completaram o estudo - um foi excluído por causa de exacerbação da DPOC. A melhora no Tlim tendeu a ser maior com tiotrópio do que com indacaterol (96 ± 163 s vs. 8 ± 82 s; p = 0,06). Em comparação com os valores basais, o Tlim melhorou significativamente com tiotrópio (aumentando de 396 ± 319 s para 493 ± 347 s; p = 0,010), mas não com indacaterol (aumentando de 393 ± 246 para 401 ± 254 s; p = 0,678). Não houve diferença entre os tratamentos quanto à melhora na pontuação na escala de dispneia de Borg e na insuflação pulmonar no "isotempo" e no pico do exercício. Também não houve diferenças significativas entre os tratamentos quanto à pontuação no Transition Dyspnea Index (1,5 ± 2,1 vs. 0,9 ± 2,3; p = 0,39). Em pacientes com DPOC moderada, o tiotrópio tende a melhorar o Tlim em comparação com o indacaterol. Não houve diferenças significativas entre os tratamentos quanto a seus efeitos na insuflação pulmonar, na dispneia durante o exercício e na dispneia na vida diária. São necessários mais estudos, com um número maior de pacientes, para confirmar nossos achados e explorar explicações mecanicistas. (ClinicalTrials.gov identifier: NCT01693003 [http://www.clinicaltrials.gov/]).
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Populações estelares do bojo galáctico
NASA Astrophysics Data System (ADS)
Escudero, A. V.; Costa, R. D. D.; Maciel, W. J.
2003-08-01
Os estudos mais recentes do bojo galáctico têm enfocado essencialmente as abundâncias químicas de elementos pesados, como o ferro, obtidos a partir das estrelas nas regiões centrais da galáxia. Elementos leves, como hélio, nitrogênio, oxigênio e argônio ainda são pouco estudados nestas regiões, devido à difícil determinação de suas abundâncias a partir de estrelas. Nestas condições as nebulosas planetárias desempenham um importante papel, pois permitem a determinação de abundâncias destes elementos usando técnicas de espectroscopia nebular. Neste trabalho, reportamos a análise das abundâncias químicas de uma nova amostra de nebulosas planetárias do bojo, bem como os resultados preliminares de um código numérico destinado a modelar a evolução química desta região. Usamos como vínculos observacionais os resultados obtidos das nebulosas planetárias, bem como de abundâncias estelares da região do bojo, obtidas da literatura. A partir deste modelo da evolução química e dos vínculos observacionais foi possível fazer um diagnóstico mais preciso das populações que constituem o bojo galáctico. O estudo destas populações que compõem a região central de nossa galáxia é de extrema importância para o maior entendimento da evolução química e dinâmica da galáxia como um todo. Por isto, verificamos a importância dos modelos de formação simples e mista utilizados para explicar características da população da região central da galáxia. Algumas destas características são: uma grande dispersão nos valores das abundâncias químicas e um grande espalhamento nas correlações entre as abundâcias de nitrogênio e oxigênio. Estas peculiaridades são dificilmente reproduzidas por modelos de formação simples, e portanto são importantes indícios da validade dos modelos de formação mista, tais como um rápido colapso do bojo seguido de uma evolução secular. (FAPESP, CNPq)
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Percepção Astronômica de Alunos do Ensino Médio da Rede Estadual de São Paulo
NASA Astrophysics Data System (ADS)
de Oliveira, E. F.; Voelzke, M. R.; Amaral, L. H.
2005-08-01
Embora a astronomia seja uma das ciências mais antigas da humanidade e muitos dos conceitos astronômicos serem populares, principalmente nesta época de alta globalização do conhecimento por intermédio de eficientes meios de comunicação e de obtenção da informação, notadamente através da internet, observa-se que uma parcela significativa dos estudantes encontra-se à margem dessas informações. O presente trabalho visa analisar o nível de conhecimento básico dos alunos de Ensino Médio da rede estadual da cidade de Suzano quanto aos fenômenos astronômicos que os rodeiam, tais como a sucessão dos dias e das estações do ano, além de questioná-los sobre fatos genéricos tais como: quais são os astros que se encontram mais próximos do planeta Terra, o que vem a ser o Sol, o Big Bang, um ano-luz, uma estrela cadente, a estrela de Bélem e o que ocasionou a extinção dos dinossauros. Para tanto foi elaborado um formulário constando de questões de múltipla escolha, o qual foi aplicado no primeiro colegial noturno da Escola Estadual Batista Renzi. Num espaço amostral de 34 alunos constatou-se que apenas 29,4% compreendiam a sucessão dos dias da semana, que apenas 20,6% explicaram corretamente as estações do ano, que apenas 20,6% tinham idéia de quais são os objetos celestes mais próximos da Terra, em contraposição 67,6% sabiam classificar corretamente o Sol como estrela, 55,9% relacionavam o Big Bang à origem do universo, apenas 20,6% identificavam um ano-luz como unidade de distância, 32,4% reconheciam uma estrela cadente como meteoro, 41,2% consideravam a estrela de Belém como um cometa e 50,0% explicaram corretamente a extinção dos dinossauros. A presente análise será expandida para as demais classes de primeiro colegial, não somente do período noturno, mas também do diurno da Escola Estadual Batista Renzi, bem como o formulário será devidamente ampliado. Já nesta primeira fase nota-se claramente o pequeno discernimento
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Conhecimento Científico e Cotidiano em Astronomia: Uma Investigação com Alunos da Educação Básica
NASA Astrophysics Data System (ADS)
Vieira, J. B.; Longhini, M. D.
2011-12-01
Este texto apresenta resultados de uma investigação que teve como objetivo, investigar como os conhecimentos científicos e do cotidiano relacionados a essa área de conhecimento apresentam na escola de Educação Básica, especialmente, em alunos do Ensino Médio prestes a deixar Educação Básica. Para realização da pesquisa, utilizamos como recurso metodológico a aplicação de um questionário estruturado contendo 47 questões, organizadas em duas categorias: Conhecimento Cotidiano e Conhecimento Científico. As questões da categoria “Conhecimento Cotidiano” possuíam afirmações relacionadas a crendices, contos populares, especulações e temáticas do gênero, as quais, geralmente, estão fora do círculo de discussão da comunidade científica, talvez por não serem consideradas como objeto de estudo da ciência. As questões da categoria “Conhecimento Científico” são relacionadas a conteúdos específicos de Astronomia, as quais são compartilhadas pela comunidade científica e aceitas, pelo menos provisoriamente, como possuindo fundamentação científica. Concluímos que, possuem ainda concepções de temas Astronômicos persistentes à mudança, por exemplo, fases da Lua relacionadas à melhor período para corte de cabelo e também para plantio; estrela cadente e ocasião perfeita para se fazer um pedido. Entretanto, podemos observar no que diz respeito a mitos e superstições, que quase não existe influência destes entre os alunos. Portanto, ao trabalharmos com os alunos determinados conceitos científicos, é importante lembrarmos que o professor não opera no vazio; os alunos são sujeitos de saberes, práticas e, dessa forma constroem e reconstroem saberes. Cabe ao professor ouvir os estudantes reconstruindo junto deles conceitos científicos. Acreditamos que o ensino de Ciências na Educação Básica deve lidar criticamente com o conhecimento cotidiano e científico e, assim, efetivar a Ciência como disciplina educativa
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On Ensino de Astronomia: Desafios para Implantação
NASA Astrophysics Data System (ADS)
Faria, R. Z.; Voelzke, M. R.
2008-09-01
Em 2002 o ensino de Astronomia foi proposto como um dos temas estruturadores pelos Parâmetros Curriculares Nacionais e sugerido como facilitador para que o aluno compreendesse a Física como construção humana e parte do seu mundo vivencial, mas raramente seus conceitos foram ensinados. A presente pesquisa discute dois aspectos relacionados à abordagem de Astronomia. O primeiro aspecto é se ela está sendo abordada pelos professores do Ensino Médio e o segundo, aborda a maneira como ela está sendo ensinada. Optou-se pela aplicação de um questionário a partir do 2° semestre de 2006 e durante o ano de 2007 com professores que ministram a disciplina de Física, os quais trabalham em escolas estaduais em Rio Grande da Serra, Ribeirão Pires e Mauá no estado São Paulo. Dos 66,2% dos professores que responderam ao questionário nos municípios de Rio Grande da Serra, Ribeirão Pires e Mauá, 57,4% não aplicaram nenhum tópico de astronomia, 70,2% não utilizaram laboratório, 89,4% não utilizaram qualquer tipo de programa computacional, 83,0% nunca fizeram visitas com alunos a museus e planetários e 38,3% não indicaram qualquer tipo de livro ou revista referente à astronomia aos seus alunos. Mesmo considerando a Astronomia um conteúdo potencialmente significativo, esta não fez parte dos planejamentos escolares. Portanto são necessárias propostas que visem estratégias para a educação continuada dos professores como, por exemplo, cursos específicos sobre o ensino em Astronomia.
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Desaphy, Jean-François; Dipalma, Antonella; Costanza, Teresa; Carbonara, Roberta; Dinardo, Maria Maddalena; Catalano, Alessia; Carocci, Alessia; Lentini, Giovanni; Franchini, Carlo; Camerino, Diana Conte
2011-01-01
We previously showed that the β-adrenoceptor modulators, clenbuterol and propranolol, directly blocked voltage-gated sodium channels, whereas salbutamol and nadolol did not (Desaphy et al., 2003), suggesting the presence of two hydroxyl groups on the aromatic moiety of the drugs as a molecular requisite for impeding sodium channel block. To verify such an hypothesis, we synthesized five new mexiletine analogs by adding one or two hydroxyl groups to the aryloxy moiety of the sodium channel blocker and tested these compounds on hNav1.4 channels expressed in HEK293 cells. Concentration–response relationships were constructed using 25-ms-long depolarizing pulses at −30 mV applied from an holding potential of −120 mV at 0.1 Hz (tonic block) and 10 Hz (use-dependent block) stimulation frequencies. The half-maximum inhibitory concentrations (IC50) were linearly correlated to drug lipophilicity: the less lipophilic the drug, minor was the block. The same compounds were also tested on F1586C and Y1593C hNav1.4 channel mutants, to gain further information on the molecular interactions of mexiletine with its receptor within the sodium channel pore. In particular, replacement of Phe1586 and Tyr1593 by non-aromatic cysteine residues may help in the understanding of the role of π–π or π–cation interactions in mexiletine binding. Alteration of tonic block suggests that the aryloxy moiety of mexiletine may interact either directly or indirectly with Phe1586 in the closed sodium channel to produce low-affinity binding block, and that this interaction depends on the electrostatic potential of the drug aromatic tail. Alteration of use-dependent block suggests that addition of hydroxyl groups to the aryloxy moiety may modify high-affinity binding of the drug amine terminal to Phe1586 through cooperativity between the two pharmacophores, this effect being mainly related to drug lipophilicity. Mutation of Tyr1593 further impaired such cooperativity. In conclusion
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Exploring pharmacists' opinions regarding PHARMAC's interventions in promoting brand changes.
Babar, Z U; Polwin, A; Kan, S W; Amerasinghe, N; McCarthy, S; Rasheed, F; Stewart, J; Lessing, C; Ragupathy, R; Scahill, S L
2015-01-01
availability when a brand change occurs. Over one-third of respondents were satisfied with brand change information provided by PHARMAC. Cilazapril was the least difficult medicine to substitute, while omeprazole and salbutamol changes were the most difficult. Claims about effectiveness, quality and side effects were the main factors identified as barriers to generic substitution. Copyright © 2015 Elsevier Inc. All rights reserved.
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Malerba, M; Boni, E; Tantucci, C; Filippi, B; Romagnoni, G; Grassi, V
1996-01-01
The effects on exercise tolerance after acute administration of beta 2-agonists were investigated in 11 patients with partly reversible chronic airway obstruction after 400 micrograms of salbutamol (S) given intravenously (i.v.) and after 400 micrograms i.v. of a new selective beta 2-agonist, broxaterol (B), by a cardiopulmonary incremental exercise test. At rest, while VE increased in respect to basal conditions (C) after S (from 13.3 +/- 2.2 to 14.4 +/- 2.8 l/min; p < 0.05) and after B (from 13.6 +/- 3.1 to 15.5 +/- 3.6 l/min; p < 0.05), VO2, VCO2 and VO2/HR showed no substantial variations. A small, not significant reduction of PaO2 was observed both after S (from 82.7 +/- 11.7 to 79.1 +/- 16.7 mm Hg) and B (from 81.6 +/- 10.5 to 78.0 +/- 11.0 mm Hg). The maximum workload increased neither after S (from 67.5 +/- 39.1 to 66.6 +/- 37.0 W) nor after B (from 65.7 +/- 39.3 to 60.0 +/- 35.8 W). At peak of exercise, VO2, VCO2 and VO2/HR did not change after S and B as compared with C, whereas VE remained higher after both beta 2-agonists throughout the effort. VO2 at ventilatory anaerobic threshold (AT) was significantly greater either after S (from 744 +/- 378 to 815 +/- 302 ml/min; p < 0.05) and after B (from 756 +/- 290 to 842 +/- 292 ml/min; p < 0.05). The PaO2 increase shown by these patients during effort was greater after beta 2-agonists administration, delta PaO2 from rest to peak of exercise amounting to 14.9 +/- 14.3 vs. 7.8 +/- 8.2 mm Hg after S and to 17.8 +/- 15.1 vs. 8.8 +/- 10.9 mm Hg after B, in respect to relative baseline (p < 0.05). We conclude that beta 2-agonists, when given acutely, do not improve exercise tolerance in patients with reversible chronic airflow obstruction, although these drugs can induce a small increment of ventilatory AT. In addition, arterial blood gases do not deteriorate at rest and are better preserved during exercise after beta 2-agonists.
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The effect of respiratory disorders on clinical pharmacokinetic variables.
Taburet, A M; Tollier, C; Richard, C
1990-12-01
Respiratory disorders induce several pathophysiological changes involving gas exchange and acid-base balance, regional haemodynamics, and alterations of the alveolocapillary membrane. The consequences for the absorption, distribution and elimination of drugs are evaluated. Drug absorption after inhalation is not significantly impaired in patients. With drugs administered by this route, an average of 10% of the dose reaches the lungs. It is not completely clear whether changes in pulmonary endothelium in respiratory failure enhance lung absorption. The effects of changes in blood pH on plasma protein binding and volume of distribution are discussed, but relevant data are not available to explain the distribution changes observed in acutely ill patients. Lung diffusion of some antimicrobial agents is enhanced in patients with pulmonary infections. Decreased cardiac output and hepatic blood flow in patients under mechanical ventilation cause an increase in the plasma concentration of drugs with a high hepatic extraction ratio, such as lidocaine (lignocaine). On a theoretical basis, hypoxia should lead to decreased biotransformation of drugs with a low hepatic extraction ratio, but in vivo data with phenazone (antipyrine) or theophylline are conflicting. The effects of disease on the lung clearance of drugs are discussed but clinically relevant data are lacking. The pharmacokinetics of drugs in patients with asthma or chronic obstructive pulmonary disease are reviewed. Stable asthma and chronic obstructive pulmonary disease do not appear to affect the disposition of theophylline or beta 2-agonists such as salbutamol (albuterol) or terbutaline. Important variations in theophylline pharmacokinetics have been reported in critically ill patients, the causes of which are more likely to be linked to the poor condition of the patients than to a direct effect of hypoxia or hypercapnia. Little is known regarding the pharmacokinetics of cromoglycate, ipratropium, corticoids or
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Awasthi, Shally; Agarwal, Girdhar; Kabra, Sushil K.; Singhi, Sunit; Kulkarni, Madhuri; More, Vaishali; Niswade, Abhimanyu; Pillai, Raj Mohan; Luke, Ravi; Srivastava, Neeraj M.; Suresh, Saradha; Verghese, Valsan P.; Raghupathy, P.; Lodha, R.; Walter, Stephen D.
2008-01-01
Background WHO-defined pneumonias, treated with antibiotics, are responsible for a significant proportion of childhood morbidity and mortality in the developing countries. Since substantial proportion pneumonias have a viral etiology, where children are more likely to present with wheeze, there is a concern that currently antibiotics are being over-prescribed for it. Hence the current trial was conducted with the objective to show the therapeutic equivalence of two treatments (placebo and amoxycillin) for children presenting with non-severe pneumonia with wheeze, who have persistent fast breathing after nebulisation with salbutamol, and have normal chest radiograph. Methodology This multi-centric, randomised placebo controlled double blind clinical trial intended to investigate equivalent efficacy of placebo and amoxicillin and was conducted in ambulatory care settings in eight government hospitals in India. Participants were children aged 2–59 months of age, who received either oral amoxycillin (31–54 mg/Kg/day, in three divided doses for three days) or placebo, and standard bronchodilator therapy. Primary outcome was clinical failure on or before day- 4. Principal Findings We randomized 836 cases in placebo and 835 in amoxycillin group. Clinical failures occurred in 201 (24.0%) on placebo and 166 (19.9%) on amoxycillin (risk difference 4.2% in favour of antibiotic, 95% CI: 0.2 to 8.1). Adherence for both placebo and amoxycillin was >96% and 98.9% subjects were followed up on day- 4. Clinical failure was associated with (i) placebo treatment (adjusted OR = 1.28, 95% CI: 1.01 to1.62), (ii) excess respiratory rate of >10 breaths per minute (adjusted OR = 1.51, 95% CI: 1.19, 1.92), (iii) vomiting at enrolment (adjusted OR = 1.49, 95% CI: 1.13, 1.96), (iv) history of use of broncho-dilators (adjusted OR = 1.71, 95% CI: 1.30, 2.24) and (v) non-adherence (adjusted OR = 8.06, 95% CI: 4.36, 14.92). Conclusions Treating children with non
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Right middle lobe atelectasis in children with asthma and prognostic factors.
Soyer, Ozge; Ozen, Cinar; Cavkaytar, Ozlem; Senyücel, Cagri; Dallar, Yildiz
2016-07-01
Although right middle lobe (RML)-atelectasis of the lungs is a common complication of asthma, the relevant data is limited. The aim of this study is to define the characteristics of RML atelectasis in asthma during childhood. Children with asthma who had recently developed RML atelectasis were included; anti-inflammatory medications, clarithromycin, and inhaled salbutamol were prescribed, chest-physiotherapy (starting on the sixth day) was applied. Patients were reevaluated on the sixth, fourteenth, thirtieth, and ninetieth days, chest X-rays were taken if the atelectasis had not resolved at the time of the previous visit. Twenty-seven patients (6.8 (4.8-8.3) years, 48.1% male) with RML atelectasis were included. Symptoms started 15 (7-30) days before admission. The thickness of the atelectasis was 11.8 ± 5.8 mm; FEV1% was 75.9 ± 14.2 and Childhood Asthma Control Test scores were 11.8 ± 5.6 at the time of admission. The atelectasis had been resolved by the sixth (n = 3), fourteenth (n = 9), thirtieth (n = 10), and ninetieth days (n = 3). The treatment response of the patients whose atelectasis resolved in fourteen days was better on the sixth-day (atelectasis thickness: 4.7 ± 1.7 vs. 11.9 ± 7.3 mm, p = 0.021) compared to those whose atelectasis resolved later. Nearly half (54.5%) of the patients whose atelectasis had resolved by fourteen days were using controller medications at the time of admission. However, only two patients (13.3%) were on controller treatment in the latter group (p = 0.032). Regression analysis didn't reveal any prognostic factors for the early resolution of atelectasis. Early diagnosis and treatment of RML atelectasis prevents complications. Patients who had early resolution of atelectasis had already been on anti-inflammatory medications, and responded better to aggressive treatment within the first week. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights
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Labor, Marina; Vrbica, Žarko; Gudelj, Ivan; Labor, Slavica; Plavec, Davor
2016-08-19
COPD-6™ is a lung function testing device for a rapid pre-spirometry testing to screen-out at-risk individuals not having COPD and indicating those at risk. The aim of this study was to validate COPD-6™ lung function testing (index test) in general practice in discriminating patients with COPD out of the population at risk - smokers/ex-smokers with no previous diagnosis of COPD, using measurements at tertiary care as reference standard. Consecutive 227 subjects (115 women, 185 smokers/42 ex-smokers, ≥20 pack-years) with no previous diagnosis of COPD, aged 52.5 (SD 6.8) years from 26 general practitioners (GPs) were recruited, lung function tested with COPD-6™, referred to the tertiary institution for repeated COPD-6™ testing followed by spirometry with a bronchodilator (salbutamol), examination, and pulmonologist consultation for the diagnosis and severity of COPD. COPD was diagnosed in 43 subjects (18.9 %), with an AUC of 0.827 (95 % CI 0.769-0.875, P < 0.001) for the diagnosis of COPD when lung function was measured using COPD-6™ in GP's office with a specificity of 100 % (95 % CI, 97.95-100 %) but a very low sensitivity of 32.56 % (95 % CI, 20.49-47.48 %). Significant agreement for forced expiratory volume in 1 s measured at GP's office and at lung function lab was found (mean difference 0.01 L, p = 0.667) but not for other measured parameters (p < 0.001 for all). Our study results point out that active case finding in a population at risk for COPD should be instituted (almost 20 % of undiagnosed COPD). Based on our results lung function testing with COPD-6™ can substitute spirometry testing in cases where it is not readily available to the patient/physician taken into account that the traditional FEV1/FEV6 cutoff value of <0.7 is not the only criterion for diagnosis and/or further referral. ClinicalTrials.gov Identifier NCT01550679 Registered 28 September 2014, retrospectively registered.
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Economic evaluation of nebulized magnesium sulphate in acute severe asthma in children.
Petrou, Stavros; Boland, Angela; Khan, Kamran; Powell, Colin; Kolamunnage-Dona, Ruwanthi; Lowe, John; Doull, Iolo; Hood, Kerry; Williamson, Paula
2014-10-01
The aim of this study was to estimate the cost-effectiveness of nebulized magnesium sulphate (MgSO4) in acute asthma in children from the perspective of the UK National Health Service and personal social services. An economic evaluation was conducted based on evidence from a randomized placebo controlled multi-center trial of nebulized MgSO4 in severe acute asthma in children. Participants comprised 508 children aged 2-16 years presenting to an emergency department or a children's assessment unit with severe acute asthma across thirty hospitals in the United Kingdom. Children were randomly allocated to receive nebulized salbutamol and ipratropium bromide mixed with either 2.5 ml of isotonic MgSO4 or 2.5 ml of isotonic saline on three occasions at 20-min intervals. Cost-effectiveness outcomes were constructed around the Yung Asthma Severity Score (ASS) after 60 min of treatment; whilst cost-utility outcomes were constructed around the quality-adjusted life-year (QALY) metric. The nonparametric bootstrap method was used to present cost-effectiveness acceptability curves at alternative cost-effectiveness thresholds for either: (i) a unit reduction in ASS; or (ii) an additional QALY. MgSO4 had a 75.1 percent probability of being cost-effective at a GBP 1,000 (EUR 1,148) per unit decrement in ASS threshold, an 88.0 percent probability of being more effective (in terms of reducing the ASS) and a 36.6 percent probability of being less costly. MgSO4 also had a 67.6 percent probability of being cost-effective at a GBP 20,000 (EUR 22,957) per QALY gained threshold, an 8.5 percent probability of being more effective (in terms of generating increased QALYs) and a 69.1 percent probability of being less costly. Sensitivity analyses showed that the results of the economic evaluation were particularly sensitive to the methods used for QALY estimation. The probability of cost-effectiveness of nebulized isotonic MgSO4, given as an adjuvant to standard treatment of severe acute
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Kotwani, Anita
2013-07-25
Inequitable access to medicines is a major weakness in the Indian health care system. Baseline data needed to develop effective public health policy and provide equitable access to essential medicines. The present survey was conducted to investigate the price, availability, and affordability of fifty essential medicines in the public and private sector in Delhi, India using standardized WHO/HAI methodology. Data on procurement price and availability was collected (July-October 2011) from three public healthcare providers: the federal (central) government, state government and Municipal Corporation of Delhi (MCD). Data on price and availability of medicines was collected from private retail and chain pharmacies of a leading corporate house. Prices were compared to an international reference price (expressed as median price ratio-MPR). The procurement price of surveyed medicines was 0.53-0.82 times the international reference price-IRP. However, the overall mean availability of surveyed medicines in facilities under state government and MCD was 41.3% and 23.2%, respectively. The overall mean availability of medicines in three tertiary care facilities operated by the federal government was 49.3%. Availability of generic medicines was much higher in the private sector. Off-patented medicines, like diazepam, diclofenac, and doxycycline had the highest MPRs. The price ratio between procurement and retail was as high as 28 (range 11-28) for certain medicines. Seven-day treatment with a popular brand of amoxicillin+clavulanic acid or one inhaler each of budesonide and salbutamol cost 2.3 and 1.4 days' wages for the lowest paid government worker. A majority of India's population cannot afford these prices. This study revealed that procurement prices of surveyed medicines were reasonable in comparison to IRP. However, variation in procurement prices of certain medicines by different public procurement agencies was noted. Availability of medicines was very poor in public
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2013-01-01
Background Inequitable access to medicines is a major weakness in the Indian health care system. Baseline data needed to develop effective public health policy and provide equitable access to essential medicines. The present survey was conducted to investigate the price, availability, and affordability of fifty essential medicines in the public and private sector in Delhi, India using standardized WHO/HAI methodology. Methods Data on procurement price and availability was collected (July-October 2011) from three public healthcare providers: the federal (central) government, state government and Municipal Corporation of Delhi (MCD). Data on price and availability of medicines was collected from private retail and chain pharmacies of a leading corporate house. Prices were compared to an international reference price (expressed as median price ratio-MPR). Results The procurement price of surveyed medicines was 0.53-0.82 times the international reference price-IRP. However, the overall mean availability of surveyed medicines in facilities under state government and MCD was 41.3% and 23.2%, respectively. The overall mean availability of medicines in three tertiary care facilities operated by the federal government was 49.3%. Availability of generic medicines was much higher in the private sector. Off-patented medicines, like diazepam, diclofenac, and doxycycline had the highest MPRs. The price ratio between procurement and retail was as high as 28 (range 11–28) for certain medicines. Seven-day treatment with a popular brand of amoxicillin+clavulanic acid or one inhaler each of budesonide and salbutamol cost 2.3 and 1.4 days’ wages for the lowest paid government worker. A majority of India’s population cannot afford these prices. Conclusions This study revealed that procurement prices of surveyed medicines were reasonable in comparison to IRP. However, variation in procurement prices of certain medicines by different public procurement agencies was noted
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Mitchell, Jolyon; Copley, Mark; Sizer, Yvonne; Russell, Theresa; Solomon, Derek
2012-08-01
The Abbreviated Impactor Measurement (AIM) concept simplifies determination of aerodynamic size metrics for inhaler quality control testing. A similar approach is needed to compare in vitro particle size distribution metrics with human respiratory tract (HRT) deposition. An abbreviated impactor based on the Andersen eight-stage cascade impactor (ACI) was developed having two size-fractionating stages with cut-points at 4.7 and 1.1 μm aerodynamic diameter at 28.3 L/min, to distinguish between coarse (CPM), fine (FPM), and extra-fine (EPM) mass fractions likely to deposit in the oropharynx, airways of the lungs, or be exhaled, respectively. In vitro data were determined for pressurized metered dose inhaler (pMDI)-delivered salbutamol (100 μg/actuation ex valve) with an "Alberta" idealized adult upper airway (throat) inlet (AIM-pHRT). Corresponding benchmark data for a full resolution Andersen eight-stage cascade impactor with "Alberta" idealized throat (ACI-AIT) and ACI-Ph.Eur./USP inlet were obtained with the same product. Mass recoveries (μg/actuation; mean ± SD) were equivalent at 100.5 ± 0.7; 97.2 ± 4.9 and 101.5 ± 9.5 for the AIM-pHRT, ACI-AIT, and ACI-Ph.Eur./USP induction port, respectively [one-way analysis of variance (ANOVA), p=0.64]. Corresponding values of CPM were 59.2 ± 4.2; 58.4 ± 2.4, and 65.6 ± 5.8; the AIT captured larger particles more efficiently than the Ph.Eur./USP induction port, so that less large particle mass was apparent in the upper stages of the ACI-AIT (p ≤ 0.037). Equivalent values of FPM were similar regardless of inlet/abbreviation at 41.3 ± 4.2; 38.7 ± 3.0, and 35.9 ± 3.8 (p=0.054), and EPM measures (1.7 ± 0.3; 2.0 ± 0.5; 2.1 ± 0.3) were also comparable (p=0.32). The AIT inlet significantly increased the capture of the coarse fraction compared with that collected by the Ph.Eur./USP induction port. Measures obtained using the AIM-pHRT apparatus were comparable with those obtained with the ACI-AIT.
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Farr, S. J.; Rowe, A. M.; Rubsamen, R.; Taylor, G.
1995-01-01
BACKGROUND--Gamma scintigraphy was employed to assess the deposition of aerosols emitted from a pressurised metered dose inhaler (MDI) contained in a microprocessor controlled device (SmartMist), a system which analyses an inspiratory flow profile and automatically actuates the MDI when predefined conditions of flow rate and cumulative inspired volume coincide. METHODS--Micronised salbutamol particles contained in a commercial MDI (Ventolin) were labelled with 99m-technetium using a method validated by the determination of (1) aerosol size characteristics of the drug and radiotracer following actuation into an eight stage cascade impactor and (2) shot potencies of these non-volatile components as a function of actuation number. Using nine healthy volunteers in a randomised factorial interaction design the effect of inspiratory flow rate (slow, 30 l/min; medium, 90 l/min; fast, 270 l/min) combined with cumulative inspired volume (early, 300 ml; late, 3000 ml) was determined on total and regional aerosol lung deposition using the technique of gamma scintigraphy. RESULTS--The SmartMist firing at the medium/early setting (medium flow and early in the cumulative inspired volume) resulted in the highest lung deposition at 18.6 (1.42)%. The slow/early setting gave the second highest deposition at 14.1 (2.06)% with the fast/late setting resulting in the lowest (7.6 (1.15)%). Peripheral lung deposition obtained for the medium/early (9.1 (0.9)%) and slow/early (7.5 (1.06)%) settings were equivalent but higher than those obtained with the other treatments. This reflected the lower total lung deposition at these other settings as no difference in regional deposition, expressed as a volume corrected central zone:peripheral zone ratio, was apparent for all modes of inhalation studied. CONCLUSIONS--The SmartMist device allowed reproducible actuation of an MDI at a preprogrammed point during inspiration. The extent of aerosol deposition in the lung is affected by a change in
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Reimberg, Mariana Mazzuca; Castro, Rejane Agnelo Silva; Selman, Jessyca Pachi Rodrigues; Meneses, Aline Santos; Politti, Fabiano; Mallozi, Márcia Carvalho; Wandalsen, Gustavo Falbo; Solé, Dirceu; De Angelis, Kátia; Dal Corso, Simone; Lanza, Fernanda Cordoba
2015-08-13
Individuals with chronic lung disease are more susceptible to present reduction in exercise tolerance and muscles strength not only due to pulmonary limitations but also due systemic repercussions of the pulmonary disease. The aim of this study is to assess the physical capacity, peripheral muscle function, physical activity in daily life, and the inflammatory markers in children and adolescents with asthma after pulmonary rehabilitation program. This is a study protocol of randomized controlled trial in asthmatic patients between 6 to 18 years old. The assessments will be conducted in three different days and will be performed at the beginning and at the end of the protocol. First visit: quality of life questionnaire, asthma control questionnaire, pre- and post-bronchodilator spirometry (400 μcg salbutamol), inflammatory assessment (blood collection), and cardiopulmonary exercise test on a cycle ergometer to determine aerobic capacity. Second visit: assessment of strength and endurance of the quadriceps femoris and biceps brachii muscles with concomitant electromyography to assess peripheral muscle strength. Third visit: incremental shuttle walk test (ISWT) and accelerometer to evaluate functional capacity and physical activity in daily life during 7 days. Then, the volunteers will be randomized to receive pulmonary rehabilitation program (intervention group) or chest physiotherapy + stretching exercises (control group). Both groups will have a supervised session, twice a week, each session will have 60 minutes duration, with minimum interval of 24 hours, for a period of 8 weeks. Intervention group: aerobic training (35 minutes) intensity between 60 to 80 % of the maximum workload of cardiopulmonary exercise testing or of ISWT; strength muscle training will be applied to the quadriceps femoris, biceps brachii and deltoid muscles (intensity: 40 to 70 % of maximal repetition, 3 x 8 repetition); finally the oral high-frequency oscillation device (Flutter®) will be
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Diaz Bautista, Gonzalo A.
El Modelo Estandar describe todas las partculas observadas en el naturaleza hasta el momento as como las caractersticas que gobiernan a las interacciones fundamentales entre ellas. En especial es posible identicar a las interacciones electromagnetica y debil, las cuales bajo determinadas condiciones de temperatura y energa pueden ser descritas a traves de una sola teora que engloba a ambas. A esta teora se le denomina electrodebil y tiene como nalidad caracterizar las propiedades de la interaccion maniesta a partir de la mezcla de las interacciones electromagnetica y debil, la que tambien lleva como nombre interaccion electrodebil. Particularmente, los neutrinos sonmore » de especial interes ya que, por un lado, interactuan por medio de la interaccion debil muy raramente en comparacion con otras partculas y, por el otro, no son acertadamente descritos por el Modelo Estandar. Por medio de observaciones experimentales que demostraban que los neutrinos cambian de sabor al propagarse, fenomeno llamado oscilaciones de neutrinos, se pudo llegar a la conclusion de que la implicancia de este fenomeno da como consecuencia que los neutrinos efectivamente s tienen masa, algo que entra en contradiccion con la descripcion inicial del Modelo Estandar, el cual los describe como partculas sin masa. Es de esta manera que las oscilaciones de neutrinos han sido y siguen siendo en la actualidad objeto de interes en la Fsica de Altas Energas tanto teorica como experimental. A n de poder realizar mediciones precisas de oscilaciones de neutrinos, los experimentos encargados de estas mediciones deben tratar de reducir sus incertidumbres en lo posible. Una de estas proviene de la caracterizacion de las secciones de choque de los neutrinos cuando interactuan con la materia, particularmente los nucleones al interior de los nucleos atomicos. El experimento MINERA esta orientado, entre otras cosas, a hacer una correcta caracterizacion de secciones de choque neutrino-nucleon por medio del
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Neurobiología del autismo y TDAH mediante técnicas de neuroimagen: divergencias y convergencias
Proal, Erika; Olvera, Jorge González; Blancas, Aurea S.; Chalita, Pablo J.; Castellanos, F. Xavier
2013-01-01
En el área clínica algunos síntomas del trastorno por déficit de atención e hiperactividad (TDAH), se presentan en los pacientes con trastorno del espectro autista (TEA). Se ha demostrado que existen alteraciones en circuitos cerebrales que impactan en fallas cognitivas y de comportamiento específicas de cada uno de estos trastornos. Sin embargo, han sido poco estudiados los correlatos cerebrales que hay detrás tanto de las similitudes como de las diferencias sintomatológicas. En la presente revisión se analizaron los estudios meta-analíticos existentes estructurales y funcionales en TDAH y TEA. Por un lado, se observaron convergencias en circuitos como el dorsal atencional, de funciones ejecutivas, visual, somatomotor y circuito de activación por defecto. Estas similitudes posiblemente explican las manifestaciones comórbidas entre los trastornos como la falla en la integración de información, motricidad fina y procesos atencionales específicos. Por otro lado, específicamente en el TDAH se observan déficits en el circuito de recompensa y ventral atencional, sistemas involucrados en la medición de efectos de reforzamiento y monitoreo atencional. En TEA los circuitos más afectados fueron los implicados en procesos de cognición social y lenguaje. En conclusión, existen correlatos neuronales en TEA que explican las manifestaciones clínicas tanto convergentes como divergentes presentes en TDAH. PMID:23897144
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Raízes pós-mitológicas da Astronomia Clássica
NASA Astrophysics Data System (ADS)
di Bartolo, L.; Villas da Rocha, J. F.
2004-02-01
Apresentamos como a invenção de um modelo astronômico e cosmológico fundado em causas naturais foi um processo gestado num ambiente cultural específico, o do advento do pensamento pós-mitológico, que tem como sua raiz mais funda a trajetória particular da Grécia Antiga, com ênfase na resolução de uma grave crise social e a evolução do mundo clássico para o contexto espiritual de um império universal.
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Cosmic ray soil moisture observing systems comos in cap fields at El Reno Oklahoma
USDA-ARS?s Scientific Manuscript database
Soil water content (SWC) partitions rainfall into runoff and infiltration, modulates surface and atmospheric exchanges of water and energy, affects plant growth and crop yields, and impacts chemical and biological activities of soil, among other things. Thus, SWC, especially over large scales, is a...
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Escuelas sin Drogas. Como Actuar. Edicion 1992. (Schools without Drugs. What Works. 1992 Edition).
ERIC Educational Resources Information Center
Department of Education, Washington, DC.
Across the United States, schools and communities have found ways to turn the tide in the battle against drugs. This guidebook describes the methods they have used and the actions they have taken. The first section, "Children and Drugs" outlines the nature and extent of the drug problem and summarizes the latest research on the effects of drugs on…
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ERIC Educational Resources Information Center
Corbell, Gloria; And Others
This teacher's guide to Spanish language at the kindergarten level includes a recommended subject presentation sequence for the Spanish curriculum, a sample schedule, a grouping of students using three stations, and a classroom layout. The grouping would be effective when at least one-third of the children are Spanish-speaking or bilingual. The…
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Las líneas de aluminio neutro como diagnóstico cromosférico
NASA Astrophysics Data System (ADS)
Fernández Borda, R.; Mauas, P. J. D.
Se presenta un modelo atómico para el cálculo de las lí neas del Aluminio neutro que se forman en la cromósfera solar. En particular, se estudia la línea λ 3961 Å, que, por estar muy próxima a la lí nea H del Ca II y a Hɛ es muy frecuentemente observada. Observaciones en esta lí nea obtenidas con el espectrógrafo a instalarse en el CASLEO, serán utilizadas para el estudio de fulguraciones solares.
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NASA Astrophysics Data System (ADS)
Cordova-Santiago, Lizzette Astrid
La investigacion---accion que se llevo a cabo en la sala de clases tenia como punto de partida las creencias de la cultura de la ciencia de un grupo de estudiantes universitarios para luego examinar sus implicaciones en el proceso de aprendizaje de las Ciencias Biologicas. ¿Que se supone que hagan las creencias en relacion con el aprendizaje? ¿En que consiste incorporar este aspecto a la practica educativa universitaria? Utilizando el modelo de Kemmis y McTaggart (1987) la investigacion-accion se planteo como un proceso dinamico en cuatro momentos en espiral constituidos por la planificacion, la accion, la observacion y la reflexion. Cada una de las fases tuvo una intencion retrospectiva y prospectiva formando una espiral de autorreflexion del conocimiento y la accion. Se llevaron a cabo audio grabaciones en clases y analisis de documentos. Ademas, la profesora-investigadora hizo un portafolio para reflexionar sobre las creencias de la cultura de la ciencia que tienen los estudiantes y las creencias del aprendizaje que tiene la profesora y sobre como la comprension de estos elementos ayudo a mejorar su practica educativa a traves del tiempo. Los resultados obtenidos apuntan a que las creencias de la cultura de la ciencia que tiene el grupo de estudiantes son diversas. Ellos si creen que la ciencia tiene una cultura la cual describieron como: complicada y desconocida que evoluciona constantemente, que es un conjunto de metodos, que es altamente tecnologica, que resuelve problemas de salud, ayuda a interpretar la realidad del mundo que los rodea y su origen y que existen unas intersecciones entre la ciencia y el poder. Sobre las creencias del proceso de aprendizaje de la profesora-investigadora, estas senalan que el modelaje de actores, la vision de la academia que tiene ella asi como la participacion y negociacion entre todos los involucrados en el proceso educativo, son factores que inciden en el proceso de aprendizaje.
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Sobrevivendo a un tsunami: lecciones de Chile, Hawai y Japon
Compilado por Atwater, Brian F.; Cisternas V., Marco; Bourgeois, Joanne; Dudley, Walter C.; Hendley, James W.; Stauffer, Peter H.
1999-01-01
Este folleto contiene historias veridicas que ilustran como sobrevivir, y como no sobrevivir, a un tsunami. Esta publicacion esta dirigida a las personas que viven, trabajan o, simplemente, se divierten a lo largo de las costas que pueden ser afectadas por un tsunami. Tales costas rodean la mayor parte del Oceano Pacifico pero tambien incluyen algunas areas costeras de los Oceanos Atlantico e Indico. Aunque mucha gente llama a los tsunamis 'olas de marea', estos no estan relacionados a las mareas, sino son una serie de olas, o 'tren de olas', generalmente causadas por cambios en el nivel del fondo marino durante los terremotos. Los tsunamis tambien pueden ser generados por la erupcion de volcanes costeros, islas volconicas, deslizamientos submarinos e impactos de grandes meteoritos en el mar. Como sucedio en Sumatra en el 2004, los tsunamis pueden alcanzar alturas de 15 metros, no tan solo en la costa sino tambien kilometros tierra adentro. Los relatos presentados en este folleto fueron seleccionados de entrevistas realizadas a personas que sobrevivieron al tsunami del Oceano Pacifico de 1960. Muchas de estas personas, incluyendo a la enfermera de la foto, se enfrento a las olas generadas a poca distancia, en la costa chilena. En cambio, otros debieron hacer frente al tsunami muchas horas despues, en Hawai y Japon. La mayoria de las entrevistas fueron realizadas a fines de los anos ochenta y en los noventa. Las historias ofrecen una mezcla de lecciones de supervivencia a un tsunami. En algunos casos se presentan las acciones que confiablemente salvaron vidas: poner atencion a los avisos de la naturaleza, abandonar los bienes, dirigirse rapidamente a un sector alto y permanecer alli hasta que el tsunami realmente haya terminado. Otras historias describen como se encontro refugio al subir a construcciones y arboles o flotar sobre desechos, tacticas que tuvieron diferentes resultados y que pueden ser recomendadas solo como actos desesperados de personas atrapadas en
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Astronomia Motivadora no Ensino Fundamental
NASA Astrophysics Data System (ADS)
Melo, J.; Voelzke, M. R.
2008-09-01
O objetivo principal deste trabalho é procurar desenvolver o interesse dos alunos pelas ciências através da Astronomia. Uma pesquisa com perguntas sobre Astronomia foi realizada junto a 161 alunos do Ensino Fundamental, com o intuito de descobrir conhecimentos prévios dos alunos sobre o assunto. Constatou-se, por exemplo, que 29,3% da 6ª série responderam corretamente o que é eclipse, 30,0% da 8ª série acertaram o que a Astronomia estuda, enquanto 42,3% dos alunos da 5ª série souberam definir o Sol. Pretende-se ampliar as turmas participantes e trabalhar, principalmente de forma prática com: dimensões e escalas no Sistema Solar, construção de luneta, questões como dia e noite, estações do ano e eclipses. Busca-se abordar, também, outros conteúdos de Física tais como a óptica na construção da luneta, e a mecânica no trabalho com escalas e medidas, e ao utilizar uma luminária para representar o Sol na questão do eclipse, e de outras disciplinas como a Matemática na transformação de unidades, regras de três; Artes na modelagem ou desenho dos planetas; a própria História com relação à busca pela origem do universo, e a Informática que possibilita a busca mais rápida por informações, além de permitir simulações e visualizações de imagens importantes. Acredita-se que a Astronomia é importante no processo ensino aprendizagem, pois permite a discussão de temas curiosos como, por exemplo, a origem do universo, viagens espaciais a existência ou não de vida em outros planetas, além de temas atuais como as novas tecnologias.
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Gustinelli, Andrea; Menconi, Vasco; Prearo, Marino; Caffara, Monica; Righetti, Marzia; Scanzio, Tommaso; Raglio, Annibale; Fioravanti, Maria Letizia
2016-10-17
In recent years there has been a re-emergence of diphyllobothriasis by Diphyllobothrium latum (Cestoda: Diphyllobothriidae) in Italy, France and Switzerland, where in the past this fish-borne zoonosis was widespread and then virtually disappeared. A change in eating habits such as the consumption of raw/undercooked freshwater fish, has led to an increased risk for consumers of ingesting infective larvae of D. latum. A survey on the factors responsible for the re-emergence of human diphyllobothriasis in Italy was carried out from March 2013 to December 2014. The aim of this study was to assess the diffusion of D. latum plerocercoids in the fish populations of the sub-alpine lakes of Maggiore, Como, Iseo and Garda, updating the scarce historical data and assessing a preliminary "risk level" of the lacustrine environments and fish species under investigation. A total of 2228 fish belonging to 5 species, 690 from Lake Maggiore, 500 from Lake Como, 655 from Lake Iseo and 383 from Lake Garda were submitted to parasitological examination. The presence of D. latum plerocercoid larvae was detected in 6.6%, 25.4% and 7.6% of perch (Perca fluviatilis) from Lakes Maggiore, Como and Iseo respectively. The parasite was also present in pike (Esox lucius) with prevalence values ranging from 71.4 to 84.2% and in 3.6-3.8% of burbot (Lota lota) from Lakes Iseo and Como. Fish from Lake Garda were negative as well as sampled whitefish (Coregonus lavaretus) and shad (Alosa fallax lacustris). The results of this survey showed a widespread presence of D. latum plerocercoid larvae in Maggiore, Como and Iseo fish populations. Urban fecal contamination of water is still a key issue to be resolved, together with the improvement of communication with consumers regarding the best dietary habits and the most effective processes of parasite inactivation, required for the consumption of raw/undercooked fish caught in high-risk areas. Copyright © 2016 Elsevier B.V. All rights reserved.
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NASA Astrophysics Data System (ADS)
de Oliveira, E. F.; Voelzke, M. R.; Amaral, L. H.
2007-08-01
Embora os Parâmetros Curriculares Nacionais do Ensino Médio (PCN-EM) e as orientações complementares a esses Parâmetros (PCN+) apontem a importância de uma abordagem significativa de conceitos relacionados à astronomia nas aulas de Física, muitos estudantes terminam o Ensino Médio (EM) sem compreender a razão de certos acontecimentos de origem celeste, ainda que estes façam parte de seu cotidiano. Este trabalho tem por objetivo analisar os conhecimentos básicos em astronomia dos alunos de EM da escola estadual Batista Renzi, bem como investigar os meios através dos quais estes conhecimentos foram adquiridos. Para tanto foi elaborado um questionário de múltipla escolha aplicado a 310 alunos distribuídos entre as três séries do EM dos períodos matutino e noturno. Dessa forma, observou-se que apenas 34,5% relacionaram as estações do ano à inclinação do eixo de rotação da Terra, 21,3% indicaram a influência gravitacional da Lua e do Sol como responsáveis pelo fenômeno das marés, 24,5% indicaram corretamente quais são os objetos celestes mais próximos da Terra, 36,1% identificaram ano-luz como uma medida de distância e 34,2% reconheceram uma estrela cadente como meteoro. Em contrapartida, 67,1% compreendiam a sucessão entre dia e noite, 73,9% identificaram o Sol como estrela e 52,3% relacionaram o Big Bang à origem do Universo. Além disso, foram comparadas as respostas de alunos de diferentes séries e períodos, observando-se, dentre outras coisas, que os estudantes do terceiro ano apresentam um percentual de acertos semelhante ao dos alunos do primeiro, caracterizando que a abordagem de tópicos relacionados à astronomia no EM não tem contribuído para uma maior compreensão dos fenômenos e conceitos.
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NASA Astrophysics Data System (ADS)
dos Santos Leão, Demetrius
2013-07-01
The aim of this article is to present part of the results obtained by the intervention made from the author's Master degree project, which consisted in the development of a set of Astronomy classes for first year of High School students from a private school in the "Distrito Federal", Brasilia, Brazil, making use of a didactical material called mini-planetarium (MP) as the main resource. Using Paulo Freire's contextualization and dialogicity ideas as a theoretical framework guided by these lessons, it was proposed to the students the assembly and application of that resource in a planetarium session. During the project, some subjects such as the apparent trajectory of stars through Brasilia's sky, the location of the cardinal points beginning from the Southern Cross constellation, the color of stars and the stars being seen from a particular place were emphasized. It was found that the students showed an improvement of their understanding about these subjects, as well as a significant excitement with the developed methodology. El objetivo de este trabajo es presentar algunos de los resultados obtenidos en el proyecto de la tesis de maestría del autor, que incluyó el desarrollo de algunas clases de Astronomía, con estudiantes del primer año del bachillerato de una escuela privada del Distrito Federal (Brasilia, Brasil), utilizando como materia prima didáctica el recurso llamado miniplanetario (MP). Utilizando como base teórica orientadora de esas clases las ideas de contextualización y dialógica de Paulo Freire, fue propuesto a los estudiantes el montaje y la utilización de este recurso en una función de planetario. Durante el proyecto, se enfatizaron asuntos tales como la trayectoria aparente de las estrellas del cielo de Brasilia, la ubicación de los puntos cardinales a partir de la constelación de la Cruz del Sur, los colores de las estrellas y las estrellas vistas desde una localidad determinada. Se constató que los estudiantes mostraron una mejora
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NASA Astrophysics Data System (ADS)
Dias, Claudio André C. M.; Santa Rita, Josué R.
2008-12-01
Astronomy is considered among the first sciences that man dominated, however, the basic skills for the construction of knowledge, relatively to the contents "Earth and the Universe" are not being developed properly for the majority of students concluding the high school level. The students are concluding this teaching cycle without proper knowledge of several subjects in the area of Astronomy, which are mandatory in the national Curricular National Parameters (PCN). Because of this discrepancy, this work stresses the need of the incorporation of a specific subject of Astronomy in the high school, in order to reduce the gap between what is taught and which should be taught. La Astronomía es considerada una de las primeras ciencias que el hombre dominó. Sin embargo, las habilidades básicas para la construcción del conocimento, relativo al eje temático "Tierra y Universo", no vienen siendo trabajadas adecuadamente con la mayoría de los alumnos que concluyen el ciclo escolar medio. Los alumnos están concluyendo este nivel de enseñanza sin conocimentos de varios temas en el área de Astronomía, que son obligatorios según los Parámetros Curriculares Nacionales (PCN). En virtud de esta discrepancia, este trabajo enfatiza la necesidad de incorporar una disciplina específica de Astronomía em el ciclo medio, em pro de la reducción de las distorsiones entre lo que es enseñado y lo que se debe enseñar. A Astronomia é considerada uma das primeiras ciências que o homem dominou, porém as competências básicas para a construção do conhecimento, relativo ao eixo temático "Terra e Universo", não vêm sendo trabalhadas a contento com a maioria dos alunos que concluem o ensino médio. Os alunos estão concluindo este nível de ensino sem conhecimento de vários temas na área de Astronomia, que são obrigatórios nos Parâmetros Curriculares Nacionais (PCN). Em virtude desta discrepância, este trabalho vem evidenciar a necessidade da incorporação de uma disciplina específica de Astronomia, no ensino médio, em prol da redução das distorções entre o que é ensinado e o que se deve ensinar.
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A Visão do Universo Segundo a Concepção de um Grupo de Alunos do Ensino Médio de São Paulo
NASA Astrophysics Data System (ADS)
Araújo, M. A. A.; Elias, D. C. N.; Amaral, L. H.; Araújo, M. S. T.; Voelzke, M. R.
2005-12-01
Nesse trabalho foi identificada por meio de um questionário a visão de mundo sobre o Universo espaço e tempo entre 270 estudantes de Ensino Médio de três escolas de São Paulo. Constatou-se pouco conhecimento dos temas investigados sendo que apenas 20% dos alunos relacionaram as semanas com as fases da lua enquanto 28% associaram as estações do ano à inclinação do eixo de rotação da Terra e 23% tinham noções das distâncias entre objetos celestes próximos da Terra. Enquanto 56% conseguiram relacionar o Big Bang com a origem do Universo verificou-se que 37% reconheciam ano-luz como unidade de distância e 60% reconheciam o Sol como uma estrela. Apesar de 60% dos alunos indicarem a escola como principal fonte dos conhecimentos de astronomia seus conceitos ainda são inadequados havendo necessidade de aprimoramento da abordagem desses conteúdos pois apesar de popular a astronomia é veiculada de maneira pouco esclarecedora e com imprecissões.
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Walker, Janiece L.; Harrison, Tracie C.; Hendrickson, Sherry G.
2012-01-01
There is a dearth of literature examining how adversity shapes the experiences of pain and/or suffering in a middle aged Mexican American women. The purpose of this qualitative descriptive study was to understand pain and suffering from a life course perspective as described by a Mexican American woman aging with early onset mobility impairment. This Hispanic woman experienced episodes of abuse and rejection over the life course, which may have significantly influenced her pain and suffering experience in adulthood. This adds to the literature on how adversity influences later life pain experience and provides insight on why pharmacological treatment alone may not be as successful as a holistic intervention. Hay escasez de literatura que examine cómo la adversidad da forma a las experiencias de dolor y / o sufrimiento en mujeres mexicana-americana mayores de edad. El propósito de este estudio descriptivo cualitativo fue comprender el dolor y el sufrimiento desde una perspectiva de ciclo de vida como descrito por una mujer mexicana-americana envejeciendo con inicio temprano de deterioro de movilidad. Esta Latina experimentó episodios de maltrato y rechazo, que se percibió haber afectado su experiencia de dolor y sufrimiento luego como adulta. Este estudio aumenta la literatura sobre cómo la adversidad influya la experiencia de dolor más tarde en la vida, y nos permite comprender mejor como el tratamiento farmacológico por sí solo no es tan exitoso como pueda ser una intervención integral. PMID:24830728
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Domínguez, Raúl; Garnacho-Castaño, Manuel Vicente; Maté-Muñoz, José Luis
2016-06-30
La fuerza influye directamente en el estado de salud y en la capacidad de fitness, motivo por el que el entrenamiento contra resistencias o resistance training (RT) se incluye dentro de aquellos programas de ejercicio encaminados a mejorar la salud y calidad de vida. Debido a que muchasenfermedades cursan con alteración de la masa y funcionalidad muscular y a que el RT es la principal modalidad de ejercicio encaminada a mejorar la función muscular, el objetivo de la presente revisión bibliográfica ha sido exponer las evidencias actuales sobre las adaptaciones delRT, así como su posible aplicación en patologías como la obesidad, diabetes, dislipemia, hipertensión, cáncer, Parkinson, esclerosis múltiple o fibromialgia. El RT en estas enfermedades puede aumentar los niveles de masa muscular, disminuyendo los niveles de masa grasa, los nivelesde ácidos grasos en sangre y la glucemia, incrementando la sensibilidad a la insulina, y disminuyendo los niveles de citokinas inflamatorias. El RT, además, mejora el gasto cardiaco y la funcionalidad endotelial, regulando la tensión arterial e incrementando el consumo de oxígeno. Las ganancias de fuerza muscular mejoran la funcionalidad y la calidad de vida, especialmente en población con una afectación neuromuscular grave, como pudieran ser los enfermos de esclerosis múltiple, fibromialgia o Parkinson. Por ello, el RT debe ser incorporado como parte del tratamiento en las personas que presentan determinado tipo de patologías.
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Zubiaga, Lorea; Ruiz-Tovar, Jaime; Giner, Lorena; González, Juan; Aguilar, María Del Mar; García, Alejandro; Calpena, Rafael; Durán, Manuel
2016-07-19
Introducción y objetivo: el IMC puede resultar engañoso para ciertas complexiones corporales, por lo que se han propuesto otros parámetros como la adiposidad (calculada a través de fórmula CUN-BAE,) el índice de Framingham de riesgo cardiovascular (IF) y el índice aterogénico (IA) (rCT/HDL-c) como predictores de riesgo cardiovascular. Se propone comparar estos factores como marcadores de éxito terapéutico tras cirugía en pacientes obesos sometidos a gastrectomía vertical laparoscópica (GVL) como procedimiento de cirugía bariátrica.Material y métodos: realizamos un estudio observacional prospectivo de pacientes sometidos a GVL y con un periodo de seguimiento mínimo de 1 año. Analizamos la evolución de IMC, adiposidad, IF e IA.Resultados: analizamos 140 pacientes. El IMC preoperatorio fue de 49,1 kg/m2, con una adiposidad del 54,8%, un IF 7,54% y un IA de 4,2. A los 12 meses el IMC era de 28,4 kg/m2, con una adiposidad del 39,4%, un IF del 3,7% y un IA de 1,64. En función de estos resultados, a los 12 meses el IMC medio está en rango de sobrepeso, la adiposidad en niveles de obesidad (obesidad: > 25% en hombres y > 35% en mujeres), el IF en rango de riesgo cardiovascular bajo (< 5%) y el IA dentro del rango de normalidad (< 3). Correlacionando estos parámetros observamos que el IMC se correlaciona con la adiposidad tanto en valores preoperatorios (Pearson 0,486; p = 0,004), posoperatorios (Pearson 0,957; p < 0,001), como en la diferencia entre ambos (Pearson 0,606; p = 0,017), lo cual es lógico, porque el IMC se incluye en la fórmula CUN-BAE para el cálculo de la adiposidad. En los valores posoperatorios se objetiva una correlación de la adiposidad con el IF (Pearson 0,814, p = 0,036) y con el IA (Pearson 0,517; p = 0,049). En los valores preoperatorios no se objetivan dichas correlaciones. El IMC no se correlacionó con la adiposidad.Conclusión: la adiposidad se correlaciona con índices de riesgo cardiovascular, como el índice de
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NASA Astrophysics Data System (ADS)
Rosado Olivieri, Wilda Y.
Gran parte de la investigacion acerca de la ensenanza de las ciencias se dedica a estudiar la forma o manera en que los estudiantes visualizan los conceptos cientificos. Para Driver (1983) esas ideas o concepciones se conocen como concepciones alternativas; las cuales pueden ocasionar dificultad para comprender los conceptos de las diferentes areas del conocimiento. El proposito de este estudio fue: (a) indagar como las distintas etapas del ABP permiten explorar las concepciones alternativas que poseen los estudiantes de nivel elemental acerca de los estados de agregacion de la materia y, (b) explorar en que medida el ABP permite identificar e incorporar las concepciones alternativas que poseen los estudiantes de nivel elemental con relacion al concepto de estados de agregacion de la materia para facilitar su aprendizaje. Con el fin de explorar las concepciones alternativas en el tema de los estados agregados de la materia se implanto la estrategia de Aprendizaje Basado en Problemas (ABP) con estudiantes de quinto grado de nivel elemental. Se utilizo la metodologia mixta con varias estrategias de recopilacion de datos, como una pre y pos prueba para elucidar el conocimiento previo y al mismo tiempo las concepciones alternativas sobre el tema bajo estudio y luego verificar el aprendizaje en los estudiantes. Asimismo, el uso de mapas conceptuales para determinar la profundidad del tema estudiado y el entrelazamiento de los conceptos Una tercera estrategia fue el grupo focal para tomar en cuenta la impresion de los estudiantes acerca del proyecto ABP. El aspecto colaborativo y cooperativo fue un factor fundamental, ya que el aprendizaje ocurrio en ese contexto educativo. Para los hallazgos de esta investigacion fue tan importante el conocimiento previo como los procesos que se generaban para que la adquisicion del mismo fuera de forma significativa y funcional (Escribano & Del Valle, 2010). La estrategia de ABP constituyo en este estudio una forma para indagar las
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Resultados do desenvolvimento de um propulsor à plasma no Brasil
NASA Astrophysics Data System (ADS)
Ferreira, I. S.; Ferreira, J. L.
2003-08-01
Uma das partes mais importantes de um satélite é o controle de atitude do mesmo. E se tratando de um satélite científico, a atenção para este sistema deve ser redobrada. Uma possibilidade atraente para executar esta tarefa é a propulsão elétrica. Aqui, mostraremos resultados obtidos pelo propulsor à plasma PHALL-01, desenvolvido na Universidade de Brasília entre 2000 e 2003. Este é derivado do propulsor russo SPT-100 (Stationary Plasma Thruster), mas com o emprego inovador de um arranjo de imãs permanentes como fonte do campo magnético, este último o agente da aceleração do plasma. Esta alteração foi motivada pelo objetivo de que o mesmo operasse com o mínimo de potência elétrica. A partir da formulação teórica do mecanismo de aceleração, tendo como base as equações da magnetohidrodinâmica, pode-se obter vínculos sob os quais o propulsor pudesse ser construído. O mais forte destes é o que dita a topologia do campo magnético. Sendo assim, foram realizadas simulações computacionais, que definiram a geometria do propulsor. Após construído, este foi diagnosticado usando-se sondas de Langmuir e analisadores de energia. Como resultados, obtivemos a distribuição espacial da temperatura, densidade e potencial do plasma, bem como a distribuição angular do feixe produzido pelo mesmo em vários regimes de operação. O espectro de energia do feixe de plasma também foi medido, indicando íons de até 560eV. Combinando estes resultados, calculou-se o empuxo do propulsor: 84mN; e o impulso específico: 1083s. Estes demonstram que o mesmo estará qualificado, num futuro próximo, para o emprego no controle de atitude de satélites científicos, ou até mesmo como parte do conjunto propulsor primário, responsáveis pela transferência de órbitas.
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NASA Astrophysics Data System (ADS)
Delgado, Isabel C.
Los modelos de eensenanza y aprendizaje constructivistas conceptualizan el aprendizaje como un proceso activo. El modelo de Aprendizaje Basado en Proyectos (ABPr) se distingue por una serie de componentes, entre los cuales se destaca el aspecto colaborativo y cooperativo como un reto al momento de su implantacion. Son pocas las investigaciones que se concentran en este aspecto del modelo. En este estudio, se analizaron las diversas interacciones que surgen durante la implantacion de una unidad curricular sobre el tema de Geologia de Puerto Rico, la cual se diseno con el modelo ABPr cuyo enfoque es orientacion a proyectos. Particularmente, se examinaron las interacciones sociales que surgen entre los pares y entre pares y docente durante el proceso de planificacion y desarrollo de los productos finales, al igual que las interacciones entre los estudiantes y el material didactico en estas etapas del modelo. La investigacion es de tipo cualitativo e incorpora como diseno el estudio de caso. Las diversas interacciones constituyen la unidad de analisis. En el estudio participaron 19 estudiantes de 9no grado, a quienes se organizaron en 5 grupos colaborativos por temas de interes (Pangea, Placas tectonicas, Volcanes, Tsunamis y Terremotos). Las tecnicas que se utilizaron para recopilar los datos fueron: observaciones participativas, grupos focales y analisis de documentos (cuadernos reflexivos y respuestas de los estudiantes a la pregunta central del proyecto). Para el analisis de los datos se aplico la teoria de actividad (CHAT) que concentra la unidad de analisis en la actividad humana en un contexto particular. Los resultados del estudio senalan que las interacciones entre pares, entre pares y docente, asi como entre estudiantes y material didactico son fundamentales en el proceso de aprendizaje. Una mayor interaccion entre pares durante las etapas de planificar y desarrollar los productos finales de la unidad, promueve una mejor comprension de los conceptos de la
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NASA Astrophysics Data System (ADS)
Ballesteros Benavides, Maria Elvira
Para este trabajo utilizamos el estudio de casos cualitativo que se llevo a cabo en una universidad privada de Puerto Rico. Empleamos como unidad de analisis el concepto de enlace quimico, ionico y covalente. Los participantes fueron los estudiantes de la seccion nocturna del curso de Quimica General I. La investigacion se desarrollo por medio de dos entrevistas de persona a persona, observaciones de las expresiones no verbales y la hoja de identificacion de conceptos. Para la triangulacion tomamos en consideracion las preconcepciones erroneas, las concepciones alternativas y el mapa de conceptos de cada participante. Preparamos un mapa de conceptos para el enlace quimico validado por un comite de expertos. Tambien, elaboramos los mapas de conceptos de los participantes que sirvieron para varios propositos: conocer la estructura conceptual, expresar los logros, hacer comparaciones e identificar la presencia de concepciones alternativas. Entre los hallazgos encontramos que todos los participantes poseen conocimiento previo de los enlaces quimicos ionico y covalente y dentro de ese conocimiento existen preconcepciones erroneas mas numerosas para el enlace ionico. Al principio del semestre el 50% de los participantes demostraron tener "carencia fuerte de conceptos" tanto para el enlace ionico como para el covalente. Al finalizar el semestre encontramos en el 40% de los participantes concepciones alternativas tanto para el enlace ionico como para el covalente y el 90% no lograron distinguir un enlace del otro. Nuestras conclusiones fueron que los participantes sin distincion del aprovechamiento academico demostraron tener la tendencia de "carencia fuerte de conceptos" tanto para el enlace ionico como para el covalente, presentaron dificultad al integrar los conceptos de los enlaces quimicos ionico y covalente que se pusieron de manifiesto al dar los ejemplos. Las preconcepciones erroneas contribuyen en el desarrollo de las concepciones alternativas. Ademas, los
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Determinação de regiões de órbitas diretas estáveis ao redor da Lua
NASA Astrophysics Data System (ADS)
de Melo, C. F.; Winter, O. C.; Vieira Neto, E.
2003-08-01
Neste Trabalho estamos investigando regiões do sistema Terra-Lua que contêm órbitas diretas estáveis ao redor da Lua visando a utilização destas órbitas em futuras missões de veículos espaciais como alternativas de trajetórias com baixo custo de manutenção. Adotando-se o problema restrito de três corpos, Terra-Lua-partícula, a localização e a extensão destas regiões de estabilidade foram investigadas numericamente considerando como estável toda órbita que permanece ao redor a Lua por, no mínimo, 1000 dias com energia de dois corpos da partícula em relação à Lua negativa. A estabilidade de tais regiões está associada a duas famílias de órbitas periódicas simples H1 e H2 e a órbitas quase-periódicas associadas a elas. Uma vez identificadas as regiões de estabilidade passamos a analisá-las introduzindo, paulatinamente, outras interações relevantes ao sistema como as perturbações do Sol (via problema restrito de quatro corpos), das marés, da pressão de radiação e do achatamento terrestre. Os resultados encontrados até o momento mostram que a perturbação do Sol é a única que reduz significativamente o tamanho das regiões de estabilidade. Também estamos investigando o comportamento de tais regiões quando características intrínsecas do sistema como as excentricidades das órbitas da Terra e da Lua e a inclinação da órbita Lua são consideradas. Com este estudo estamos reunindo informações que nos permitirão compreender a evolução das regiões de estabilidade no sistema Terra-Lua, bem como estabelecer parâmetros adequados para a utilização das trajetórias estáveis em futuras missões espaciais. Agradecimentos: Este projeto conta com o apoio do CNPq, da Capes e da Fapesp.
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Camporro, Fernando Astur; Gutierrez Magaldi, Ignacio; Bulacio, Exequiel
2017-09-08
Introducción: El tabaquismo es la primera causa evitable de muerte en el mundo. El cigarrillo electrónico (CE), es un dispositivo que simula a los cigarrillos convencionales y permite inhalar nicotina y otras sustancias de forma vaporizada, sin combustión de tabaco. Su conocimiento por parte de la población general, así como su comercialización y consumo viene en constante aumento. Es utilizado en todo el mundo con el objetivo de disminuir el consumo de tabaco, lograr su abandono o poder utilizarlo en lugares públicos donde el consumo de cigarrillos convencionales está prohibido. Efectos nocivos sobre la salud: Su utilización se ha asociado a neumonía lipoidea e irritación de la vía aérea superior y toxicidad por nicotina. Presenta sustancias cancerígenas como nitrosaminas, formaldeido y metales como el niquel, cromo y plomo. Aumenta la resistencia de la vía aérea, efecto que es similar al que se produce después de la inhalación del humo del tabaco. Eficacia para dejar de fumar: No hay hasta el momento trabajos que demuestren con poder estadístico y buena metodología que este producto sea eficaz para dejar de fumar. Conclusiones: De acuerdo a la evidencia disponible, no podemos descartar que el uso del cigarrillo electrónico no tenga riesgos para la salud. La seguridad y eficacia de los cigarrillos electrónicos como ayuda para el abandono del hábito tabáquico no han sido demostradas.
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Zea-Vera, Alonso; Turin, Christie G.; Ochoa, Theresa J.
2015-01-01
Las infecciones constituyen una de las principales causas de muerte en el periodo neonatal. El diagnóstico de sepsis neonatal representa un gran desafío ya que los recién nacidos presentan signos clínicos muy inespecíficos y los exámenes auxiliares tienen una baja sensibilidad. Con el objetivo de mejorar el diagnóstico correcto de esta patología proponemos un algoritmo de vigilancia diagnóstica para sepsis neonatal tardía en el Perú y países de la región. El algoritmo permite clasificar a los episodios como sepsis confirmada, probable o posible, y sobretodo busca identificar aquellos episodios que no corresponden a sepsis, evitando calificar otras patologías como “sepsis”. Un mejor diagnóstico permitiría tener tasas más reales de sepsis neonatal, mejorar el uso de antibióticos y evitar sus efectos negativos en el recién nacido, así como una visión más exacta de su impacto en la salud pública. PMID:25123879
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Del sujeto que ha intentado suicidarse y el Otro: la Institución Psiquiátrica
Liliana, Mondragón B.; Miguel Ángel, Caballero G.
2009-01-01
El hospital psiquiátrico se ha constituido como un lugar donde se posibilita legitimar la exclusión y la radicalidad de ese otro “que no es igual”, como es el caso del sujeto que atenta contra su propia vida. En consecuencia, el intento de suicidio desde el pensamiento foucaultiano, es una resistencia que desmantela la estructura de dominación a través de un acto de poder, el cual se ejerce sobre el propio cuerpo. Así, la intención de este texto es mostrar que la relación Otro-otro es un lugar en la estructura subjetiva, que se deposita en la institución psiquiátrica, la cual representa el poder, la ley, y es aquello a lo que se le quiere agredir, resistir, abatir con un intento de suicidio. Para demostrar como se materializan estos hechos, se exponen los testimonios de tres adolescentes atendidas en un hospital psiquiátrico por intentos suicidas, en los cuales se señalan los diferentes significados que le atribuyen a la institución psiquiátrica en tanto que representa un Otro en sus actos autoinfligidos. PMID:25400324
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Nota sobre el "Se" como Sujeto Indefinido (A Note on "Se" as an Indefinite Subject)
ERIC Educational Resources Information Center
Lujan, Marta
1975-01-01
Contradicts Pablo Jordan's theory that certain "se" constructions in Spanish are neither passive nor reflexive. It is claimed that syntactic evidence reveals two types of impersonal structures, the impersonal active and the passive reflexive. (Text is in Spanish.) (CK)
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Como ayudar a sus hijos a usar la biblioteca (Helping Your Child Use the Library).
ERIC Educational Resources Information Center
Perkinson, Kathryn
Focusing on the cooperative role of parents and public libraries in stimulating reading interests in children of all ages, this booklet addresses the following issues: (1) getting children interested in reading (reading aloud to children; encouraging children to read to you; starting a home library; showing children that you enjoy reading;…
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ERIC Educational Resources Information Center
Office of Federal Student Aid (ED), Washington, DC.
This guide, written in Spanish, discusses reasons for going to college, how to pay for college, and how to apply for federal student aid in a series of brief, clear illustrations. Following outlines of financial benefits of college, college costs, and space to note costs for the student's area, the guide outlines these steps in the application…
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ERIC Educational Resources Information Center
Rockefeller Foundation, New York, NY.
This volume presents nine papers read at a conference on affirmative action, sponsored by the Rockefeller Foundation and held at Columbia University in August 1982; a preface, summary paper, and list of participants are also included. Each paper addresses the issue of affirmative action within a different country and describes: (1) the policies…
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Distribución del continuo ultravioleta e infrarrojo en estrellas Be
NASA Astrophysics Data System (ADS)
Cruzado, A.; Ringuelet, A.; di Rocco, H.
Estamos interesados en interpretar los excesos de flujo infrarrojo y/o ultravioleta observados en estrellas Be con respecto al de estrellas B normales, así como su posible correlación. Una envoltura rodeando la estrella distingue una estrella Be de una B normal; para explicar las observaciones es necesario entonces tener en cuenta todos los posibles procesos físicos que en ella tienen lugar. Adoptando un modelo atmosférico específico, hemos estudiado el proceso de recombinación dielectrónica de metales como MgII y FeII, teniendo en cuenta la posible influencia de la opacidad del medio en el flujo emitido.
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Cálculos ab initio con correlación electrónica
NASA Astrophysics Data System (ADS)
Merchán Bonete, M.
Estamos entrando en una era donde la ortogonalidad entre las investigaciones de carácter experimental y de naturaleza teórica se irá difuminando progresivamente y la problemática a resolver quedará en escena como el único actor principal de la obra. Como premisa para una cooperación teórico-experimental de igual a igual, la metodología químico-cuántica utilizada debe ser capaz de ofrecer resultados de carácter predictivo. Sin duda, esta madurez en la metodología químico-cuántica ya la hemos alcanzado hace algunos años, tal y como muestra entre otras muchas, la labor que nuestro grupo ha realizado en el transcurso de la última década, dentro del campo de la Espectroscopía Teórica. Los estudios realizados comprenden una amplia gama de sistemas, variando tanto en tamaño como en complejidad, abordando problemáticas espectroscópicas consideradas tradicionalmente como especialmente controvertidas. Nuestra contribución científica más relevante reside en el carácter cuantitativo de las asignaciones espectroscópicas que hemos propuesto en base a resultados ab initio. Recordemos que en los años noventa los resultados ab initio solían presentar para las energías de excitación de sistemas de tamaño molecular moderado, como el benceno, errores de más de 1 eV. En comparación con el éxito relativo de los métodos semiempíricos, la frustración de la metodología ab initio quedaba todavía más patente. Los estudios que hemos presentado representan una comprensión profunda de los espectros electrónicos en sistemas orgánicos claves, mostrando el camino a seguir para obtener asignaciones espectroscópicas precisas (entre 0.1-0.2 eV). La naturaleza del método CASPT2 junto al diseño de estrategias computacionales nos ha permitido alcanzar el carácter cuantitativo con el que se caracterizan nuestras contribuciones[1,2]. Por todo ello, algunos de los trabajos publicados se consideran clásicos dentro del campo, pues en cierto modo definen el
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NASA Astrophysics Data System (ADS)
Leite, Cristina; Hosoume, Yassuko
2007-12-01
The research presented in this article is about the way science teachers from Elementary School think about astronomical elements. Its methodology is based on semi-structured interviews, which were video recorded. The research is centered in a three-dimensional perspective of astronomical Earth, the Sun, the Moon, the planets and the stars, and also the conceptions about sky and Universe. The esults indicate a Universe that contains: Sun, stars, planets and Moon; where the Solar System is a little part of the whole. Sometimes they think that the Solar System is the Universe. The objects are in the sky or in the Universe, which, for many of them, is only the space above the Earth. The flat shape of astronomical objects and the spatial structure of the Universe are striking features. Many of them think that Sun and stars are different: the Sun is a hot object and the stars are cold ones. These results worry us and they certainly indicate how urgent it is to plan Professional Development in Astronomy for teachers, after all the PCN's emphasize that this subject is important to be taught. El objeto de investigación de este artículo es la manera de pensar sobre los elementos de la Astronomía de los profesores de Ciencias en la enseñanza fundamental. La metodología consiste en entrevistas semi-estructuradas, filmadas en video y centradas en la tridimensionalidad de los elementos astronómicos, para posibilitar un mapeamiento de las concepciones sobre las formas y dimensiones de la Tierra, del Sol, de la Luna, de los planetas y de las estrellas, como también de la concepción de cielo y de Universo en su totalidad. Los resultados indican un Universo conteniendo: Sol, estrellas, planetas y Luna, donde el Sistema Solar se ubica como parte. Algunas veces, el Universo es concebido como el propio Sistema Solar. Los objetos están en el cielo o en el Universo, que, para muchos, se restringe al espacio que está arriba de la Tierra. La forma plana de los objetos astron
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Patient safety and nursing: interface with stress and Burnout Syndrome.
Rodrigues, Cláudia Cristiane Filgueira Martins; Santos, Viviane Euzébia Pereira; Sousa, Paulo
2017-01-01
To analyze studies on stress, Burnout Syndrome, and patient safety in the scope of nursing care in the hospital environment. This was an integrative literature review. Data collection was performed in February 2016 in the following databases: Medical Literature Analysis and Retrieval System Online - PubMed/MEDLINE, Latin American and Caribbean Literature in Health Sciences - LILACS. Ten scientific productions were selected, which listed that factors contributing to stress and Burnout Syndrome of nursing professionals are the work environment as a source of stress, and excessive workload as a source of failures. The analysis found that the stress and Burnout Syndrome experienced by these professionals lead to greater vulnerability and development of unsafe care, and factors such as lack of organizational support can contribute to prevent these failures. Analisar estudos que versam sobre o estresse e Síndrome de Burnout, bem como a segurança do paciente no âmbito da assistência de enfermagem no ambiente hospitalar. Tratou-se de uma revisão integrativa de literatura. O levantamento dos dados foi efetuado nas bases de dados Medical Literature Analysis and Retrieval System Online - PubMed / MEDLINE, Literatura Latino-Americana e do Caribe em Ciências da Saúde -LILACS em fevereiro de 2016. Foram selecionadas10 produções científicas que apontaram que os fatores que contribuem para o estresse e a Síndrome de Burnout dos profissionais de enfermagem são o ambiente de trabalho como fonte de estresse e a carga de trabalho excessiva como geradora de falhas. A análise apontou que o estresse e a Síndrome de Burnout vivenciada por esses profissionais acarretam maior vulnerabilidade ao desenvolvimento de uma assistência insegura e que fatores como a falta de apoio organizacional podem contribuir para dirimir essas falhas.
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Bravo-Oro, Antonio; Abud-Mendoza, Carlos; Quezada-Corona, Arturo; Dalmau, Josep; Campos-Guevara, Verónica
2016-01-01
Introducción La encefalitis por anticuerpos contra el receptor de N-metil-D-aspartato (NMDA) es una entidad cada vez más diagnosticada en edad pediátrica. A diferencia de los adultos, en muchos casos no se asocia a tumores y las manifestaciones iniciales en niños más frecuentes son crisis convulsivas y trastornos del movimiento, mientras que en los adultos predominan las alteraciones psiquiátricas. Casos clínicos Presentamos seis casos pediátricos confirmados con anticuerpos contra la subunidad NR1 del receptor de NMDA en suero y líquido cefalorraquídeo. Cinco de los casos comenzaron con crisis convulsivas como manifestación clínica inicial antes de desarrollar el cuadro clásico de esta entidad. En todos los casos se utilizaron esteroides como primera línea de tratamiento, con los que sólo se observó control de las manifestaciones en uno, por lo que el resto de los pacientes requirió inmunomoduladores de segunda línea. Todos los pacientes recibieron metotrexato como tratamiento inmunomodulador para evitar recaídas y la evolución fue a la mejoría en todos ellos. Conclusiones En nuestra serie de pacientes con encefalitis por anticuerpos contra el receptor de NMDA, ninguno se asoció a tumores. Todos los casos recibieron metotrexato por lo menos durante un año, no observamos eventos adversos clínicos ni por laboratorio, ni hubo secuelas neurológicas ni recaídas durante el tratamiento. Aunque es una serie pequeña y es deseable incrementar el número y tiempo de evolución, consideramos el metotrexato una excelente alternativa como tratamiento inmunomodulador para esta patología. PMID:24150952
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NASA Astrophysics Data System (ADS)
Balan, Catalin
Na ultima decada, foram feitos grandes progressos no desenvolvimento dos detetores de detecao direta das particulas que constituem a materia negra. Com estrategias do aumento gradual do volume do alvo e, simultaneamente, de reducao dos niveis de fundo, a experiencia XENON obteve resultados muito bons e perspetivas promissoras para a detecao de materia negra. Tarefas relativas a analise de dados experimentais adquiridos com o detetor de dupla fase em uso, assim como as simulacoes do campo eletrico, desenvolvimento, montagem e testes para o proximo detetor XENON1T, assim como a participacao regular na manutencao geral e monitorizacao do prototipo atual XENON100 no LNGS, constituiram o plano de trabalhos para as atividades de investigacao do presente doutoramento e a minha contribuicao para a otimizacao da detecao de cintilacao nos detetores da experiencia XENON. A necessidade de alcancar niveis elevados de sensibilidade, requer inovacao em todos os aspetos fisicos do detetor, assim como a reducao de todas as fontes de radioatividade que contribuem para o fundo. O modo mais indicado de operacao para os detetores com enchimento a Xe no estado liquido e gasoso envolve a medicao da cintilacao primaria e da secundaria provenientes da interacao das particulas no Xe liquido. A razao entre estes dois sinais permite diferenciar claramente a maior parte dos eventos correspondentes as fundo dos eventos correspondentes a WIMPs. Deste modo, a leitura dos sinais correspondentes a cintilacao e de extrema importancia. A amplitude do sinal de cintilacao antes dos fotossensores e maximizada atraves da otimizacao de varios parametros, tais como a geometria do alvo do detetor, a transparencia das grelhas dos eletrodos, a uniformidade do ganho em cintilacao secundaria e a utilizacao de material reflectivo para cobrir as superficies que nao sao fotossensiveis.
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Arístegui, Inés; Dorigo, Analía; Bofill, Lina; Bordatto, Alejandra; Lucas, Mar; Cabanillas, Graciela Fernández; Sued, Omar; Cahn, Pedro; Cassetti, Isabel; Weiss, Stephen; Jones., Deborah
2016-01-01
Resumen Introducción el Programa Nacional de Sida garantiza el acceso universal a los antirretrovirales, aun así las personas que reciben medicamentos a través del sistema público no logran obtener una carga viral indetectable en la misma proporción que los pacientes del sistema privado. Este estudio cualitativo tiene como objeto identificar los factores asociados a la adherencia y retención en la cascada de atención de VIH de los sistemas de salud público y privado de Buenos Aires, según las percepciones de pacientes y del personal de salud. Métodos se registraron datos cualitativos de 12 entrevistas semi-estructuradas a informantes clave y 4 grupos focales de pacientes y personal de salud tanto del sistema público como privado. Se codificaron y analizaron temas predeterminados sobre adherencia, utilizando el software QRS Nvivo9® de análisis de datos cualitativos. Resultados pacientes y personal de salud de ambos sistemas coinciden en la importancia del estigma asociado al VIH, la relación médicopaciente, la comunicación entre ambos y la división de responsabilidades en relación al tratamiento como aspectos fundamentales para la adherencia y retención en la cascada de atención. Se observan diferencias entre los sistemas en la forma en que algunos de estos aspectos actúan. Las barreras estructurales se presentan como principales obstáculos del sistema público. Discusión se resalta la necesidad de intervenciones focalizadas en la díada médico-paciente que considere las particularidades de cada sistema de atención para facilitar el compromiso del paciente en la adherencia. PMID:26878024
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Jiménez-Castro, Lorena; Raventós-Vorst, Henriette; Escamilla, Michael
2012-01-01
El interés por comprender la co-morbilidad de la esquizofrenia y el trastorno en el uso de sustancias, ha aumentado debido al incremento de este diagnóstico, a los efectos negativos observados en el sujeto y a los costos en los servicios de salud. Este trastorno dual puede tener efectos dramáticos en el curso clínico del trastorno psicótico tales como: mayores recaídas, re-hospitalizaciones, síntomas más severos, no adherencia al tratamiento antipsicótico, cambios marcados del humor, aumento en el grado de hostilidad e ideación suicida, así como alteraciones en otras áreas del funcionamiento incluyendo violencia, victimización, indigencia y problemas legales. La literatura proveniente en particular de Estados Unidos y Europa sugiere que el rango de prevalencia para este diagnóstico puede oscilar entre el 10% hasta el 70%. En este estudio, revisamos la prevalencia del diagnóstico dual de esquizofrenia y trastorno en el uso sustancias, así como sus características sociodemográficas, con base en la literatura disponible alrededor del mundo dando énfasis en la poblacion latina. A pesar de que este diagnóstico es ampliamente aceptado, se conoce poco sobre su prevalencia en la población latina, sobre los factores ambientales, demográficos, clínicos y otras características de estos individuos. Un mejor conocimiento sobre este diagnóstico permitiría mejorar los métodos para la detección y adecuada valoración del trastorno en el uso de sustancias en personas con trastornos metales severos como la esquizofrenia. PMID:21404151
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Trippe, Zahra Anita; Brendani, Bruno; Meier, Christoph; Lewis, David
2017-04-01
. This resulted in an output of 23 potential SSMs. The literature search identified two communications issued to health professionals concerning a substandard rivastigmine patch, which validated our initial findings. Furthermore, we identified excess reporting of product quality issues with an ethinyl estradiol/norgestrel combination and with salbutamol. These were categorized as confirmed clusters of substandard/spurious/falsely labelled/falsified/counterfeit (SSFFC) medical products by the UMC in 2014. This study illustrates the value of data mining of spontaneous adverse event reports and the applicability of disproportionality analysis to identify potential SSMs.
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Symptomatic treatment of the cough in whooping cough.
Bettiol, Silvana; Thompson, Matthew J; Roberts, Nia Wyn; Perera, Rafael; Heneghan, Carl J; Harnden, Anthony
2010-01-20
.5). One study on pertussis immunoglobulin reported a possible mean reduction of -3.1 whoops per 24 hours (95% CI -6.2 to 0.02) but no change in hospital stay (-0.7 days) (95% CI -3.8 to 2.4). Dexamethasone did not show a clear decrease in length of hospital stay (-3.5 days) (95% CI -15.3 to 8.4) and salbutamol showed no change in coughing paroxysms per 24 hours (-0.22) (95% CI -4.13 to 3.69). Insufficient evidence exists to draw conclusions about the effects of interventions for the cough in whooping cough.
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Echinacea complex--chemical view and anti-asthmatic profile.
Šutovská, Martina; Capek, Peter; Kazimierová, Ivana; Pappová, Lenka; Jošková, Marta; Matulová, Mária; Fraňová, Soňa; Pawlaczyk, Izabela; Gancarz, Roman
2015-12-04
Echinacea purpurea (L.) Moench is one of the mostly used herbs in the traditional medicine for the treatment of respiratory diseases. Modern interest in Echinacea is directed to its immunomodulatory activity. Recent studies have shown that secretion of asthma-related cytokines in the bronchial epithelial cells can be reversed by Echinacea preparations. To examine the pharmacodynamics profile of Echinacea active principles, a complex has been isolated from its flowers by alkaline extraction and has been tested using an animal model of allergic asthma. The structural features of Echinacea purpurea complex was determined using chemical and spectroscopic methods. Allergic inflammation of the airways was induced by repetitive exposure of guinea pigs to ovalbumin. Echinacea complex was then administered 14 days in 50mg/kg b.w. daily dose perorally. Bronchodilatory effect was verified as decrease in the specific airway resistance (sRaw) in vivo and by reduced contraction amplitude (mN) of tracheal and pulmonary smooth muscle to cumulative concentrations of acetylcholine and histamine in vitro. The impact on mucociliary clearance evaluated measurement of ciliary beat frequency (CBF) in vitro using LabVIEW™ Software. Anti-inflammatory effect of Echinacea complex was verified by changes in exhaled NO levels and by Bio-Plex® assay of Th2 cytokine concentrations (IL-4, IL-5, IL-13 and TNF-alpha) in serum and bronchoalveolar lavage fluid (BALF). Chemical and spectroscopic studies confirmed the presence of carbohydrates, phenolic compounds and proteins, as well as the dominance of rhamnogalacturonan and arabinogalactan moieties in Echinacea complex. The significant decrease in sRaw values and suppressed histamine and acetylcholine-induced contractile amplitude of isolated airways smooth muscle that were similar to effects of control drug salbutamol confirmed Echinacea complex bronchodilatory activity. The anti-inflammatory effect was comparable with that of control agent
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The Douro estuarine plume: Detection, processes and dynamics =
NASA Astrophysics Data System (ADS)
Mendes, Renato Paulo dos Santos
O Douro e um dos maiores rios da Peninsula Iberica, constituindo a maior descarga de agua doce para o Oceano Atlântico na costa noroeste portuguesa. A sua pluma estuarina tem particular relevância na dinâmica costeira e na modulacao de fenomenos biogeoquimicos. Sao objetivos desta dissertacao contribuir para a compreensao dos processos fisicos associados a geracao e propagacao da pluma estuarina do Rio Douro no oceano, assim como para o conhecimento dos seus padroes de dispersao e da forma como estes alteram a hidrologia e a circulacao costeira, considerando os agentes forcadores tipicos deste fenomeno (caudal fluvial, vento e mare) e indices climaticos relevantes. Para concretizacao destes objetivos foram desenvolvidas e aplicadas metodologias inovadoras de processamento de dados de detecao remota, assim como novas implementacoes estuarinas e costeiras de modelos numericos. Atraves de imagens MODIS, otimizadas para o estudo de fenomenos costeiros, efetuou-se uma detecao rigorosa da pluma. Identificou-se uma relacao entre o sinal turbido nLw555 e o caudal, demonstrando-se este produto como um bom proxy para a observacao da pluma no oceano. As escalas temporais e espaciais da pluma foram caraterizadas atraves destas imagens, combinadas com dados de caudal fluvial, mare, vento e precipitacao, e tambem com indices climaticos relevantes. Para compreender a propagacao da pluma e caracterizar a sua dinâmica e impacto na circulacao costeira, foi desenvolvida uma aplicacao 3D de modelos estuarinos e costeiros com malhas aninhadas de resolucao variavel. Definiramse e analisaram-se diferentes cenarios de vento e descarga fluvial. A interacao da pluma do Rio Douro e do Minho foi ainda analisada atraves dos resultados de simulacoes baseadas num evento de inverno. Os compositos turbidos mostraram que a pluma e facilmente detetada quando o caudal e maior que 500 m3 s??1. A descarga fluvial e o vento sao os principais forcadores da sua propagacao, enquanto a mare e apenas
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Perspectivas Futuras para o Observatório do Pico dos Dias
NASA Astrophysics Data System (ADS)
Bruch, Albert
2004-02-01
Com o Observatório Gemini plenamente operacional e o telescópio SOAR iniciando suas operações em breve, a astronomia observacional brasileira encontra-se no auge de uma transformação profunda que terá um impacto grave no Observatório do Pico dos Dias - OPD. Refletimos aqui sobre a natureza desse impacto e estratégias para manter a competitividade do OPD. Não queremos apresentar receitas prontas, mas idéias que poderão servir como base de discussão sobre o uso inteligente dos telescópios do OPD como parte do conjunto de instrumentos disponíveis à comunidade astronômica brasileira.
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Conceptos Basicos Sobre el Gas Natural (in Spanish)
DOE Office of Scientific and Technical Information (OSTI.GOV)
El gas natural abastece cerca de 150.000 vehiculos en los Estados Unidos y aproximadamente 22 millones de vehiculos en todo el mundo. Los vehiculos de gas natural (NGV, por sus siglas en ingles) son una buena opcion para las flotas de vehiculos de alto kilometraje, tales como autobuses, taxis, vehiculos de recoleccion de basura, los cuales son alimentados centralmente u operan dentro de un area limitada o a lo largo de una ruta con estaciones de servicio de gas natural. Las ventajas del gas natural como combustible alternativo incluyen su disponibilidad interna, la red de distribucion establecida, un costo relativamentemore » bajo, y los beneficios de las emisiones.« less
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Lana, Francisco C. F.; Malvárez, Silvina
2012-01-01
Resumen La BVS Enfermeria constituye un nuevo paradigma en enfermería una vez que o modelo representa una expansión de la cooperación técnica y ha como objetivos centrales promover la ampliación del acceso la información sobre enfermería la través del acceso universal equitativo y construir un patrimonio informacional en enfermería, ayudando la mejorar la formación y práctica de enfermería a actuar con compromiso ético-social en el área de educación, investigación y atención a la salud. Como resultado del proceso de sensibilización, verifica-se la construcción de Bibliotecas Virtuales de Enfermería en varios países (Brasil, Argentina, Bolívia y Uruguay). La expectativa es que las BVS’s nacionais convergen a un gran portal que se está construyendo en una colaboración con BIREME/OPS/OMS, de la Asesoría Regional de Enfermería de la OPS-Washington y de Ministerio de Salud del Brasil, así como instituciones líderes en la producción del conocimiento en enfermería Iberoamérica. PMID:24199093
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Neurobiología de la impulsividad y los trastornos de la conducta alimentaria*
Orozco-Cabal, Luis Felipe; Herin, David
2009-01-01
Resumen Introducción La impulsividad es un rasgo de personalidad multidimensional relacionado con el control del comportamiento y las emociones. Está presente de manera diversa en los trastornos de la conducta alimentaria, particularmente, en la bulimia nerviosa (BN). Aunque la relación entre la impulsividad y BN ha sido objeto de numerosas investigaciones, en la actualidad se desconocen los sustratos neurobiológicos de esta relación. Objetivos Discutir críticamente la evidencia que sugiere que las alteraciones en los sistemas neuronales relacio-nados con las funciones ejecutivas, con la formación de preferencias y con la regulación de los estados emocionales sirven como base para el rasgo de personalidad impulsiva, así como su estado en subgrupos de pacientes con BN. Métodos Búsqueda selectiva de la literatura relevante. Resultados y conclusiones Esta discusión ilustra la complejidad de la relación entre la impulsividad y BN, donde la impulsividad actúa como un factor de vulnerabilidad que puede sensibilizar al sujeto con BN a estados emocionales negativos, durante los cuales modifica el impacto de estímulos internos y externos sobre el comportamiento y su regulación, favoreciendo así patrones de comportamiento maladaptativos e inflexibles. PMID:19838321
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Torres Díaz, Cristina V; Martín Peña, Gonzalo; Ezquiaga, Elena; Navas García, Marta; García de Sola, Rafael
2016-07-19
Gracias a los avances técnicos en técnicas neuroquirúrgicas, y debido a que el diagnóstico y la clasificación de las enfermedades psiquiátricas han evolucionado significativamente a lo largo de las últimas décadas, se están desarrollando tratamientos a nivel experimental para aquellos pacientes resistentes al manejo conservador.La anorexia nerviosa es una enfermedad de prevalencia creciente, con la tasa de mortalidad más elevada dentro de los trastornos psiquiátricos, y con aproximadamente un 20% de pacientes que presentan una evolución tórpida. Para estos pacientes que no responden a manejo conservador, la estimulación cerebral profunda ha surgido como una alternativa terapéutica, si bien la literatura especializada al respecto es escasa.A continuación presentamos una revisión de la fisiopatología de la anorexia nerviosa, así como de los distintos tratamientos neuroquirúrgicos realizados a lo largo de la historia. Se detalla la perspectiva de tratamiento quirúrgico actual, así como los aspectos éticos que se han de considerar en relación con el surgimiento de estas nuevas terapias.
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2013-01-01
índrome de pérdida reproductiva en dromedarios transmitido por orugas y observado por pastores nómadas saharauis del Sáhara Occidental. Antecedentes Los conocimientos tradicionales de las comunidades locales de todo el mundo son una valiosa fuente de nuevas ideas e información para la ciencia. En este estudio, se utilizaron los conocimientos de etnoveterinaria de pastores saharauis del Sáhara Occidental con el fin de proponer una hipótesis científica sobre las interacciones competitivas entre los camellos y las orugas en el ecosistema del Sáhara. Métodos Entre los años 2005 y 2009, se realizaron 44 entrevistas semi-estructuradas a los pastores saharauis en los territorios administrados por la República Árabe Saharaui Democrática, Sáhara Occidental, mediante un diseño de muestreo por bola de nieve. Resultados Los pastores nómadas saharauis describieron un síndrome reproductivo transmitido por orugas, llamado duda, entre sus camellas. Sobre la base de los conocimientos saharauis sobre el duda y una revisión literaria exhaustiva, se propuso la siguiente hipótesis: 1) brotes esporádico de orugas de la familia Lasiocampidae (géneros Lasiocampa, Psilogaster o Streblote) en árboles de Acacia se pueden presentar después de fuertes lluvias en el ecosistema del Sáhara Occidental; 2) durante estos brotes, los camellos ingieren las orugas durante el pastoreo; 3) como consecuencia de esta ingestión, se producen abortos repentinos o partos de crías debilitadas. Apoyamos esta hipótesis mediante razonamiento inductivo basado en evidencia circunstancial y razonamiento analógico con síndromes similares en yeguas de los Estados Unidos y Australia. Conclusiones Este es el primer reporte de la posible existencia de un síndrome de pérdida reproductiva en camellos, transmitido por orugas. Se insinúa que estos síndromes son más comunes que lo que actualmente se conoce. Se sugieren investigaciones adicionales para poner a prueba nuestra hipótesis. Finalmente, se
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USE OF TRANEXAMIC ACID IN TRAUMA PATIENTS: AN ANALYSIS OF COST-EFFECTIVENESS FOR USE IN BRAZIL.
Pinto, Marcelo A; Silva, Jair G da; Chedid, Aljamir D; Chedid, Marcio F
2016-01-01
parte de pesquisadores e profissionais de saúde. No entanto, seus benefícios ainda não foram completamente definidos. Os pontos de divergência entre especialistas incluem questões como: quais pacientes devem receber TXA no trauma? O tratamento deve ser realizado em ambiente pré-hospitalar? Há necessidade de exames laboratoriais para indicar o tratamento? Qual o perfil de segurança da droga? A principal questão para a qual ainda não existe qualquer embasamento na literatura é: qual a indicação do tratamento dentro de protocolos de transfusão maciça? Responder às questões propostas, com base em avaliação crítica da evidência reunida até o momento e realizar estudo de custo-efetividade do uso do TXA no trauma adaptado à realidade brasileira. Foi realizada revisão da literatura através de estratégia de busca: PubMed.com, Embase e no Cab Abstract pelos descritores "tranexamic AND trauma", em todos idiomas, resultando em 426 artigos. Foram excluídos aqueles relativos às operações eletivas, restando 79 artigos. Cinquenta e cinco foram selecionados e avaliados criticamente com vistas a responder às questões em estudo. A avaliação de custo-efetividade foi realizada utilizando dados do estudo CRASH-2 e populacionais oficiais brasileiros. Através da análise da evidência disponível chegou-se à conclusão de que o ácido tranexâmico é tratamento eficaz e efetivo, devendo ser administrado à ampla gama de pacientes, incluindo todos aqueles com indicação já avaliada nos protocolos de pesquisa publicados e provavelmente devam-se expandir os critérios de indicação. Quanto à avaliação de custo-efetividade, o TXA mostrou-se bastante custo-eficaz com gasto médio de R$ 61,35 por ano de vida salvo. O uso do ácido tranexâmico no trauma parece ser eficaz, efetivo e custo-eficaz nos diversos grupos de pacientes politraumatizados. Seu uso em protocolos de transfusão maciça ainda deve ser objeto de futuras investigações.
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NASA Astrophysics Data System (ADS)
Rodriguez Ramos, Teresita
Se llevó a cabo una investigación en acción con los propósitos de 1) documentar las relaciones de las tecnologías de la información y la comunicación en las clases de ciencias de escuela intermedia como elemento de apoyo cuando se aborda el tema ambiental y sus conceptos pertinentes, a partir de las observaciones de la investigadora, así como las entrevistas y diarios reflexivos de los estudiantes de una escuela intermedia en la zona metropolitana, y luego 2) diseñar una unidad instruccional sobre el tema ambiental que integre actividades tecnologías para el curso de ciencias de la escuela intermedia según el modelo PROCIC y las observaciones que hayan iniciado los estudiantes participantes. Finalmente, se plantearon las implicaciones educativas para el currículo del Programa de Ciencias al instrumentar este modelo de unidad mediante PROCIC, e integrado la tecnología y el tema ambiental. Los hallazgos se analizaron y se categorizaron de acuerdo con las preguntas de investigación. El hallazgo principal de la investigación aborda las cuatro relaciones centrales en las que se articula la utilización de las tecnologías y sus aplicaciones en la clase de ciencias. Estas cuatro relaciones que recogen la posición de los estudiantes son: 1) Perspectiva de los estudiantes hacia la tecnología. 2) Participación de los estudiantes en los aspectos docentes. 3) Aprendizaje estudiantil sobre el ambiente, y 4) Conciencia ambiental en relación con la vida diaria. Estas relaciones ponen de manifiesto,cómo se plantea en las implicaciones, la necesidad de más investigación en acción en la sala de clases, la importancia—como tema transversal—de la conciencia ambiental mediante la tecnología al construir conocimientos significativos dentro y fuera de la escuela, asó como, valorar la investigación y la dialogicidad en la sala de clases como actividades que obligan al reexamen de la práctica didáctica en su formas curriculares de objetivos, recursos
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Myocardial Viability on Cardiac Magnetic Resonance.
Souto, Ana Luiza Mansur; Souto, Rafael Mansur; Teixeira, Isabella Cristina Resende; Nacif, Marcelo Souto
2017-05-01
The study of myocardial viability is of great importance in the orientation and management of patients requiring myocardial revascularization or angioplasty. The technique of delayed enhancement (DE) is accurate and has transformed the study of viability into an easy test, not only for the detection of fibrosis but also as a binary test detecting what is viable or not. On DE, fibrosis equal to or greater than 50% of the segmental area is considered as non-viable, whereas that below 50% is considered viable. During the same evaluation, cardiac magnetic resonance (CMR) may also use other techniques for functional and perfusion studies to obtain a global evaluation of ischemic heart disease. This study aims to highlight the current concepts and broadly emphasize the use of CMR as a method that over the last 20 years has become a reference in the detection of infarction and assessment of myocardial viability. Resumo O estudo de viabilidade miocárdica é de grande importância para a orientação e manejo de pacientes que necessitam de cirurgia de revascularização miocárdica ou angioplastia. A técnica de realce tardio (RT) é precisa e transformou o estudo de viabilidade em um teste fácil, não só para a detecção de fibrose, mas também como um modelo binário para a detecção do que é ou não é viável. Uma fibrose identificada pelo RT é considerada como não viável quando igual ou maior do que 50% da área segmentar e como viável quando menor que 50%. A ressonância magnética cardíaca (RMC) também pode lançar mão de outras técnicas para estudo funcional e de perfusão para uma avaliação global da doença isquêmica do coração no mesmo exame. Este estudo tem como objetivo destacar os conceitos atuais e enfatizar amplamente o uso da RMC como um método que nos últimos 20 anos se tornou referência na detecção de infarto e avaliação de viabilidade miocárdica.
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Spin-Transfer-Torque Nano-Oscillators: Fabrication, Characterization and Dynamics
NASA Astrophysics Data System (ADS)
Costa, Jose Diogo Teixeira Barbosa
Este trabalho aborda algumas propriedades magneticas e estruturais de nanoparticulas de oxidos e oxidos-hidroxidos de ferro crescidos em matrizes hibridas orgânicas-inorgânicas. As matrizes hibridas, denominadas di-ureasils e obtidas pelo processo sol-gel, sao compostas por uma rede siliciosa ligada covalentemente por pontes ureia a cadeias orgânicas de diferente peso molecular. A estrutura local dos di-ureasils nao dopados esta modelada como grupos de dominios siliciosos com dimensoes nanometricas, estruturalmente correlacionados no seio de uma matriz rica em polimero. Neste trabalho mostra-se que os di-ureasils permitem o crescimento controlado de oxidos e oxidos-hidroxidos de ferro, incluindo a magnetite, maguemite, oxihidroxinitrato de ferro e ferrihidrite. O crescimento das nanoparticulas de ferrihidrite da-se em condicoes acidas a superficie dos dominios siliciosos, junto aos grupos carbonilo, que funcionam como pontos de nucleacao. Desse modo da-se uma nucleacao heterogenea, onde o tamanho das nanoparticulas depende da concentracao de ferro (entre 1 e 6% em massa), sendo a concentracao de particulas constante. As propriedades magneticas das nanoparticulas de ferrihidrite revelam a existencia de interaccoes antiferromagneticas e de momentos descompensados. A contribuicao destas duas componentes nas curvas de magnetizacao em funcao do campo magnetico pode ser separada usando um metodo aqui proposto, o que permite um adequado estudo da evolucao do momento magnetico com a temperatura. O estudo das propriedades magneticas dinâmicas das particulas de ferrihidrite, atraves de susceptibilidade ac, medidas de relaxacao e medidas de efeito Mossbauer, permitiu estudar a evolucao das interaccoes dipolares em funcao da concentracao de ferro, bem como determinar a distribuicao de barreiras de energia de anisotropia no caso em que essas interaccoes sao desprezaveis. E apresentado um novo metodo para comparacao desta distribuicao com a distribuicao de tamanhos, que
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Structural and Magnetic Studies on Iron Oxide Nanoparticles in Hybrid Matrices =
NASA Astrophysics Data System (ADS)
Silva, Nuno Joao de Oliveira
Este trabalho aborda algumas propriedades magneticas e estruturais de nanoparticulas de oxidos e oxidos-hidroxidos de ferro crescidos em matrizes hibridas orgânicas-inorgânicas. As matrizes hibridas, denominadas di-ureasils e obtidas pelo processo sol-gel, sao compostas por uma rede siliciosa ligada covalentemente por pontes ureia a cadeias orgânicas de diferente peso molecular. A estrutura local dos di-ureasils nao dopados esta modelada como grupos de dominios siliciosos com dimensoes nanometricas, estruturalmente correlacionados no seio de uma matriz rica em polimero. Neste trabalho mostra-se que os di-ureasils permitem o crescimento controlado de oxidos e oxidos-hidroxidos de ferro, incluindo a magnetite, maguemite, oxihidroxinitrato de ferro e ferrihidrite. O crescimento das nanoparticulas de ferrihidrite da-se em condicoes acidas a superficie dos dominios siliciosos, junto aos grupos carbonilo, que funcionam como pontos de nucleacao. Desse modo da-se uma nucleacao heterogenea, onde o tamanho das nanoparticulas depende da concentracao de ferro (entre 1 e 6% em massa), sendo a concentracao de particulas constante. As propriedades magneticas das nanoparticulas de ferrihidrite revelam a existencia de interaccoes antiferromagneticas e de momentos descompensados. A contribuicao destas duas componentes nas curvas de magnetizacao em funcao do campo magnetico pode ser separada usando um metodo aqui proposto, o que permite um adequado estudo da evolucao do momento magnetico com a temperatura. O estudo das propriedades magneticas dinâmicas das particulas de ferrihidrite, atraves de susceptibilidade ac, medidas de relaxacao e medidas de efeito Mossbauer, permitiu estudar a evolucao das interaccoes dipolares em funcao da concentracao de ferro, bem como determinar a distribuicao de barreiras de energia de anisotropia no caso em que essas interaccoes sao desprezaveis. E apresentado um novo metodo para comparacao desta distribuicao com a distribuicao de tamanhos, que
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A proposed contents astronomy for basic education
NASA Astrophysics Data System (ADS)
Albrecht, E.; Voelzke, M. R.
2014-08-01
A Astronomia é um tema que sempre exerceu fascínio sobre as pessoas de um modo geral. Conhecer e estudar o que há nos “céus”, além de nossos olhos, continua sendo instigador e de grande interesse. Baseado nestas justificativas desenvolveu-se uma pesquisa de Doutorado, na qual, o objetivo principal foi investigar sobre a presença dos conteúdos de Astronomia nas Propostas Curriculares da região Sul do Brasil, a saber, os estados de Paraná, Rio Grande do Sul e Santa Catarina e, posterior comparação com os Parâmetros Curriculares Nacionais (PCN) que trazem propostas de conteúdos para toda a Educação Básica brasileira. Tal investigação pautou-se na abordagem de caráter qualitativo e utilizouse para tal da Análise de Conteúdos (Bardin, 2011), que possibilitou a construção de quatro categorias, nas quais os conteúdos astronômicos foram agrupados: Terra, Sistema Solar, Via Láctea e Universo. Após a leitura, coleta de dados, construção de categorias, observou-se a dicotomia na apresentação destes conteúdos. As propostas curriculares analisadas foram as de Geografia, Ciências e Física dos estados do Paraná (2008), Rio Grande do Sul (2009) e de Santa Catarina (1998), responsáveis pelo trabalho com Astronomia nestes estados. No Ensino Fundamental, a proposta curricular do estado do Paraná apresenta conteúdos ligados à Astronomia desde o sexto ano até o nono ano, como conteúdo do primeiro bimestre, o que também é apresentado na proposta curricular do estado do Rio Grande do Sul, porém, este, não divide os conteúdos por bimestre e nem por ano, mas por ciclos, sexto e sétimo anos como primeiro ciclo e oitavo e nono anos como segundo ciclo, deixando livre para o professor estruturar sua sequência de conteúdos. A proposta curricular de Santa Catarina não apresenta estes conteúdos de maneira explícita, não divide dos conteúdos nem por ano, nem por série, traz uma sequência de conteúdos para serem trabalhados ao longo dos
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ERIC Educational Resources Information Center
Dodge, Diane Trister
Many typical classroom behavior problems--running in the classroom, inability to make choices, failure to stick with activities, fighting over toys, and poor use of materials-- can be traced to how the room is arranged and how materials are displayed. By making a few changes in the classroom environment, early childhood teachers can create a…
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ERIC Educational Resources Information Center
de la Piedra, Maria Teresa
2011-01-01
This paper presents part of the results of a qualitative study about literacy practices of Mexican transnational mothers, who live in and frequently cross the border between two countries (the United States and Mexico). Drawing on sociocultural approaches to literacy and literature on transnationalism, I analyze one practice: "leer…
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[Rabdomiosarcoma primario de corazón como causa de síncope recurrente en el adulto].
Díaz-Pérez, Julio Alexander; Gómez-Arbeláez, Diego; Hurtado-Gomez, Gabriel Alexander
2011-01-01
Primary or secondary neoplasms can affect the heart. Secondary are more common. However, primary neoplasms are relevant because is a group with diverse genesis, behavior, treatment and clinical manifestations. We present a case of a 45 year-old woman, with recurrent syncope started 1 year before her first consult. She had palpitations and chest pain. Echocardiography identified a left atrium mass of 2.1x1.8 cm. Endomyocardial biopsy document a primary rhabdomyosarcoma of the heart. The patient dies after a overall-survival of 22 months. This case presented had a good study of its symptoms with an accurate diagnosis and early treatment, which provided prolonged survival of this rare and aggressive neoplasm.
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Enhanced hydrogen evolution reaction on hybrids of cobalt phosphide and molybdenum phosphide
NASA Astrophysics Data System (ADS)
Fang, Si-Ling; Chou, Tsu-Chin; Samireddi, Satyanarayana; Chen, Kuei-Hsien; Chen, Li-Chyong; Chen, Wei-Fu
2017-03-01
Production of hydrogen from water electrolysis has stimulated the search of sustainable electrocatalysts as possible alternatives. Recently, cobalt phosphide (CoP) and molybdenum phosphide (MoP) received great attention owing to their superior catalytic activity and stability towards the hydrogen evolution reaction (HER) which rivals platinum catalysts. In this study, we synthesize and study a series of catalysts based on hybrids of CoP and MoP with different Co/Mo ratio. The HER activity shows a volcano shape and reaches a maximum for Co/Mo = 1. Tafel analysis indicates a change in the dominating step of Volmer-Hyrovský mechanism. Interestingly, X-ray diffraction patterns confirmed a major ternary interstitial hexagonal CoMoP2 crystal phase is formed which enhances the electrochemical activity.
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Sandoval-Gutiérrez, José Luis
2017-01-01
Según la Real Academia Española, el término «líder» significa «persona que dirige u orienta a un grupo, que reconoce su autoridad». Es importante este término ya que es muy ambiguo, porque no reconoce el nivel moral o la empatía que puede ejercer una persona en determinado grupo al reconocerlo como líder, y no solo con la autoridad que este puede ejercer en el mismo, siendo este último concepto algo muy común en el mundo anglosajón, denominándose líder a alguien que tiene un puesto de autoridad, lo cual se puede confundir con lo que conocemos como «jefe».
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Estructura orbital en el Problema Restringido Rectilíneo Isósceles
NASA Astrophysics Data System (ADS)
Orellana, R. B.
Para definir problemas en Mecánica Celeste se utilizan diferentes parámetros. El conocimiento de la dinámica del problema para valores particulares de estos parámetros nos permite entender el comportamiento en casos más generales. El Problema Restringido Rectilíneo Isósceles puede ser considerado como el caso límite del Problema de Sitnikov cuando la excentricidad tiende a uno o como el Problema Isósceles cuando la masa central tiende a cero. Se ha compactificado el espacio de fases y analizado la dinámica en el límite. Esto ha permitido separar el espacio de fases en diferentes regiones dependiendo de las clases de órbitas.
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Investigación del USGS sobre el ecosistema de arrecifes de coral en el Atlántico
Kuffner, Ilsa B.; Yates, Kimberly K.; Zawada, David G.; Richey, Julie N.; Kellogg, Christina A.; Toth, Lauren T.; Torres-Garcia, Legna M.
2015-10-23
Los arrecifes de coral son estructuras sólidas, biomineralizadas que protegen comunidades costeras actuando como barreras protectoras de peligros tales como los huracanes y los tsunamis. Estos proveen arena a las playas a través de procesos naturales de erosión, fomentan la industria del turismo, las actividades recreacionales y proveen hábitats pesqueros esenciales. La conti-nua degradación mundial de ecosistemas de arrecifes de coral está bien documentada. Existe la necesidad de enfoque y organización de la ciencia para entender los procesos complejos físicos y biológicos e interacciones que están afectando el estado de los arrecifes coralinos y su capacidad para responder a un entorno cambiante.
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Low temperature growth of ultra-high mass density carbon nanotube forests on conductive supports
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sugime, Hisashi; Esconjauregui, Santiago; Yang, Junwei
2013-08-12
We grow ultra-high mass density carbon nanotube forests at 450 °C on Ti-coated Cu supports using Co-Mo co-catalyst. X-ray photoelectron spectroscopy shows Mo strongly interacts with Ti and Co, suppressing both aggregation and lifting off of Co particles and, thus, promoting the root growth mechanism. The forests average a height of 0.38 μm and a mass density of 1.6 g cm{sup −3}. This mass density is the highest reported so far, even at higher temperatures or on insulators. The forests and Cu supports show ohmic conductivity (lowest resistance ∼22 kΩ), suggesting Co-Mo is useful for applications requiring forest growth onmore » conductors.« less
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La mayoria de los accidentes causados por envenenamiento por monoxido de carbono (CO) se producen en los hogares y estan relacionados a nuestras actividades diarias como cocinar y usar la calefaccion.
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NASA Astrophysics Data System (ADS)
Ferreres Sabater, Agustin
Cualquier sistema electronico que incluya un procesado o tratamiento de la senal, y ademas, algun tipo de actuador mecanico generalmente necesita, como minimo, dos tensiones diferentes de alimentacion. Excluyendo los sistemas de alimentacion distribuida, la solucion tecnica mas utilizada para proporcionar dos o mas tensiones consiste en las fuentes de alimentacion multisalida. En una fuente de alimentacion multisalida los diferentes circuitos que conforman cada salida comparten un mismo transformador de potencia optimizando coste, masa, y volumen. Las ventajas obtenidas con este procedimiento tienen en su contra el efecto que sobre cada salida individual provocan las demas en su conjunto debido, principalmente, a los efectos de los elementos parasitos de los componentes. Un cambio de carga en una de las salidas produce un transitorio que es visto por todas las demas como un efecto de impedancia cruzada, y al final del transitorio, la tension de cada salida es diferente respecto a la que tenian antes del transitorio. Este ultimo resultado se conoce como regulacion cruzada. La disminucion de los efectos de la regulacion cruzada ha sido objeto de estudio durante los ultimos anos. El objetivo ha sido el desarrollo de distintas estrategias que permiten, desde disminuir los efectos de la regulacion cruzada hasta los niveles deseables, a eliminarla completamente. El resultado final suele suponer una penalizacion sobre el diseno del sistema directamente proporcional al grado de regulacion a conseguir en las distintas salidas. Entre las soluciones propuestas para eliminar la regulacion cruzada las tecnicas de post-regulacion se han consolidado como la opcion mas aceptada ya que, pueden aplicarse a cualquier convertidor y no suponen ninguna complejidad adicional a la hora de plantear el diseno. En esta Tesis Doctoral se abordara el estudio de la tecnica conocida como postregulacion mediante transformador controlado, que si bien se ha empleado en convertidores resonantes, su
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NASA Astrophysics Data System (ADS)
Espinosa Rodriguez, Tulia
tribocorrosion processes. The formation of a coating layer on magnesium alloys from phosphonate imidazolium ionic liquids by immersion and by chronoamperometry has been described. The new coatings reduce the abrasive wear in the magnesium-aluminium alloy but they are not effective in the magnesium-zinc alloy, which prevent the formation of continuous coatings. Los liquidos ionicos son sales liquidas a temperatura ambiente o bajas temperaturas que presentan excelentes propiedades fisico-quimicas. En el presente trabajo se estudian como lubricantes en problemas tribologicos complejos como la lubricacion de metales contra si mismos, el desarrollo de lubricantes base agua y de nuevas superficies autolubricadas. Cuando no es posible reducir la friccion y desgaste mediante lubricacion, como en las aleaciones de magnesio, los liquidos ionicos se han estudiado como precursores de recubrimientos protectores. Se han determinado las interacciones superficiales y los procesos de corrosion sobre cobre y sobre acero con diferentes liquidos ionicos proticos y aproticos para desarrollar nuevos lubricantes y aditivos. En el contacto cobre/cobre, excepto el liquido ionico protico derivado del oleato, todos los liquidos ionicos estudiados presentan mejor comportamiento tribologico que el lubricante comercial Polialfaolefina 6. En el contacto acero/zafiro, los nuevos liquidos ionicos proticos son buenos lubricantes cuando se utilizan en estado puro, y, como aditivos en agua, generan peliculas adsorbidas sobre la superficie del metal reduciendo la friccion y el desgaste tras la evaporacion del agua. Para evitar el periodo de alta friccion inicial en presencia de agua, se han generado peliculas superficiales de liquido ionico sobre el acero en condiciones estaticas. El mejor comportamiento lubricante tanto en el contacto cobre/cobre como en el contacto acero/zafiro se obtiene para el liquido ionico protico derivado del anion adipato, con dos grupos carboxilicos. Las interacciones de los grupos
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[80 years of soial service in medicine].
Hace 80 años, la Escuela de Medicina de la Universidad Nacional, en voz de su director, Gustavo Baz Prada, hizo una propuesta que pronto se convirtió en realidad y finalmente en norma, la que desde entonces se conoce como SS. Esta iniciativa se vio como una manera para que los estudiantes de medicina del último año retribuyeran a la sociedad una parte de lo que esta invirtió en su educación, consolidaran su formación mediante la exposición a las realidades de todos los días en los medios más necesitados, se pusieran a prueba sobre sus verdaderas capacidades para atender pacientes y participaran en la solución de un problema de atención sanitaria que en ese entonces era mucho más apremiante que ahora. Unos años después, los recién egresados de otras licenciaturas (pasantes) también fueron incorporados a esta estrategia y, al fin, se reconoció formalmente como una responsabilidad de las instituciones educativas. Las aportaciones del SS a la salud de las personas y a la formación de los médicos han sido incuestionables, y la experiencia humana que ha representado para quienes lo han vivido ha dejado marcas indelebles.
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Resposta do detector de ondas gravitacionais Mario Schenberg ao "ringdown" de buraco negros
NASA Astrophysics Data System (ADS)
Costa, C. A.; Aguiar, O. D.; Magalhães, N. S.
2003-08-01
Acredita-se que quando duas estrelas de nêutrons coalescem, elas, eventualmente, formam um buraco negro com massa igual a soma das massas dos objetos originais. Durante a formação do buraco negro, o espaço-tempo em torno do sistema sofre perturbações que se propagam na forma de radiação gravitacional. A forma de onda associada a radiação gravitacional, durante este estágio, aproxima-se a uma senóide exponencialmente amortecida. Este tipo de sinal é conhecido como "ringdown", e seu comportamento e parametrização são muito bem conhecidos. Neste trabalho, simulamos computacionalmente sinais provenientes do "ringdown" de buracos negros, com a finalidade de testar o desempenho do detector de ondas gravitacionais Mario Schenberg em observá-los, quando entrar em funcionamento. Este primeiro teste teórico ajudou-nos a criar estratégias de detecção de sinais imersos no ruído instrumental. Calculamos a relação sinal-ruído como uma função da frequência, bem como sua integral dentro da faixa de sensibilidade do detector. Os resultados obtidos mostraram que o detector Schenberg terá sensibilidade suficiente para detectar este tipo de sinal, proveniente de fontes astrofísicas localizadas dentro de um raio de ~100kpc.
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Estudio teórico de moléculas de interés en Astrofísica: compuestos binarios policarbonados
NASA Astrophysics Data System (ADS)
Largo-Cabrerizo, A.
Se han detectado en el espacio distintos compuestos binarios policarbonados (que se pueden formular como CnX), algunos de ellos con elementos de la primera fila del sistema periódico, pero también existen otros que contienen elementos de la segunda fila, como azufre o silicio. La información experimental sobre estos últimos compuestos es escasa, por lo que los estudios teóricos son especialmente valiosos en este campo. En esta comunicación presentaremos los avances mas recientes que sobre el tema ha realizado nuestro grupo. Incidiremos particularmente en dos aspectos. En primer lugar resumiremos los estudios en los que hemos intentado proporcionar información estructural sobre carburos metálicos formados por sodio, magnesio, aluminio o calcio, que pueda ser de ayuda a la hora de caracterizar estas moléculas en laboratorio como paso previo a su eventual detección en el espacio. Un aspecto importante dentro de este primer apartado es el análisis de las propiedades moleculares en función del tamaño del sistema (cuantificado en el numero de átomos de carbono) con el objeto de intentar sistematizar su estudio. En segundo lugar comentaremos brevemente algunos de los estudios realizados sobre posibles reacciones que pueden ser vías de síntesis de este tipo de compuestos en el medio interestelar.
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Hernández Mosqueira, Claudio; Hernández Vasquez, Dagoberto; Caniuqueo Vargas, Alexis; Castillo Quezada, Humberto; Fernandes Da Silva, Sandro; Pavez-Adasme, Gustavo; Martínez Salazar, Cristian; Cárcamo-Oyarzún, Jaime; Fernandes Filho, José
2016-11-29
Introducción: Chile en las últimas décadas ha experimentado un cambio en su perfil epidemiológico nutricional, pasando de una situación caracterizada por una elevada prevalencia de desnutrición y enfermedades infecciosas/parasitarias a otro completamente distinto, en donde las enfermedades crónicas y degenerativas presentan una elevada prevalencia.Objetivo: el objetivo del estudio es elaborar tablas de referencia de aspectos antropométricos y de condición física en estudiantes varones de 10 a 14 años de la ciudad de Chillán.Método: estudio descriptivo de corte transversal. La muestra se compone de 1250 varones con edades entre los 10 y 14 años. Para la confección de las tablas de referencia se utilizó estadística descriptiva y estas fueron divididas en cinco clasificaciones desde muy malo, malo, media, bueno y muy bueno, teniendo como parámetro la edad.Resultados: observamos niveles importantes de sobrepeso que se asociaron con bajo desempeño físico, lo que plantea la urgencia de realizar un seguimiento en el tiempo con herramientas de fácil aplicación como la presente batería; con el fin de detectar a tiempo a los niños que tienen bajos niveles de condición física y tomar medidas orientadas a estimular o mejorar la capacidad física como factores protectores de promoción de la salud y como ayuda en la prevención de enfermedades crónicas relacionadas con el sobrepeso u obesidad.Conclusión: en este trabajo se han establecido valores de referencia para posteriores estudios en cuanto a la condición física orientada a la salud en estudiantes varones de 10 a 14 años de la ciudad de Chillán, que permitirán evaluar e interpretar correctamente la condición física orientada a la salud de este grupo etario.
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Oyarce Merino, Karina; Valladares Vega, Macarena; Elizondo-Vega, Roberto; Obregón, Ana María
2016-11-29
Introducción: cambios socioculturales como el incremento en el sedentarismo y el consumo de alimentos ricos en grasas y azúcares, sumado a características genéticas, han producido un aumento en las cifras de obesidad a nivel mundial. La evaluación temprana en niños, mediante el establecimiento de perfi les genéticos asociados a obesidad y a la regulación metabólica y hedónica de la alimentación, complementado con estudios de la conducta alimentaria, nos permitiría predecir la predisposición a la obesidad en etapas adultas.Objetivo: revisar los conceptos asociados a la conducta alimenticia, enfocándose en la regulación hedónica, que puede convertirse en un parámetro predictivo de obesidad en niños.Material y métodos: se revisó la bibliografía asociada a obesidad infantil y a la regulación homeostática y hedónica de la obesidad, como también parámetros génicos asociados a la obesidad. En la búsqueda de artículos se incluyó el trabajo en animales y humanos (adultos y niños, pero con énfasis en niños).Resultados: se analizaron los mecanismos celulares de la regulación de la ingesta, así como los estudios de conducta alimentaria en niños, entregando antecedentes y carencias en el desarrollo investigativo para la predicción de la obesidad infantil.Conclusión: la regulación hedónica de la ingesta alimenticia en niños, como perfi les genéticos asociados a receptores de dopamina, puede convertirse en un importante predictor de la obesidad. Es necesario incrementar el número de estudios que permitan defi nir de mejor forma, cuáles son los mejores parámetros para predecir el desarrollo de la obesidad adulta.
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NASA Astrophysics Data System (ADS)
Chiesa Bartelmebs, Roberta; Batista Siqueira Harres, João; da Silva, João Alberto
2014-12-01
This work is presented as a theoretical essay on some facts from the history of astronomy analyzed according to the theory of reflective abstraction developed by Jean Piaget and collaborators (1970). Its aim is to understand the reasons that led to different astronomers, at the same historical period and culture, to "see" quite different evidences about the same phenomenon. In addition, we intend to facilitate the understanding of science as a human construction, subject to a time epoch and the ways of understanding of each scientist. Este trabajo se presenta como un ensayo teórico sobre algunos hechos históricos de la astronomía, analizados según la teoría de la abstracción reflexionante de Jean Piaget y sus colaboradores (1970). Se trata de comprender los motivos que llevaran a distintos astrónomos, de una misma época histórica y cultural, a "ver" diferentes evidencias sobre un mismo fenómeno. Además, se intenta posibilitar la comprensión de la ciencia como construcción humana, la cual es condicionada por su momento histórico y por las creencias y las formas de entender de los científicos. Este trabalho configura-se como um ensaio teórico a respeito de alguns fatos da história da astronomia analisados segundo a teoria da abstração reflexionante elaborada por Jean Piaget e seus colaboradores (1970). Trata-se de compreender os motivos que levaram diferentes astrônomos, da mesma época histórica e cultural, a "enxergarem" evidências tão diferentes sobre um mesmo fenômeno. Além disso, pretendemos possibilitar a compreensão das Ciências como construção humana, condicionadas a uma época e às crenças e os modos de compreender de cada cientista.
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NASA Astrophysics Data System (ADS)
Alves, Mauro A.; Lyra, Cássia S.
2008-12-01
The Newcomb-Benford's Law (LNB) of first digits is introduced to high school students in an extracurricular activity through the study of sunspots. The LNB establishes that the first digits of various sets of data describing natural occurrences are not distributed uniformly, but according to a logarithmic distribution of probability. The LNB is counter-intuitive and is a good example of how mathematics applied to the study of natural phenomena can provide surprising and unexpected results serving also as a motivating agent in the study of physical sciences. En este trabajo se describe una actividad extracurricular donde se presenta a los estudiantes la ley de los primeros dígitos de Newcomb-Benford (LNB) con el estudio de manchas solares. La LNB establece que los primeros dígitos de algunos tipos de dados de ocurrencia natural no están distribuidos en manera uniforme, pero sí de acuerdo con una distribución logarítmica de probabilidad. La LNB es contra-intuitiva y es un excelente ejemplo de como las matemáticas aplicadas al estudio de fenómenos naturales pueden sorprender al estudiante, sirviendo también como elemento motivador en la educación de ciencias y de matemáticas. Este trabalho descreve uma atividade extracurricular na qual a lei dos primeiros dígitos de Newcomb-Benford (LNB) é introduzida a estudantes através do estudo de manchas solares. A LNB estabelece que os primeiros dígitos de vários tipos de conjunto de dados de ocorrência natural não são distribuídos de maneira uniforme, mas sim de acordo com uma distribuição logarítmica de probabilidade. A LNB é contra-intuitiva e é um ótimo exemplo de como a matemática aplicada ao estudo de fenômenos naturais pode fornecer resultados surpreendentes e inesperados, servindo também como um agente motivador no ensino de ciências e matemática.
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Domínguez, Vanihamín; Aguiñiga, Itzen; Moreno, Leticia; Torres, Beatriz; Santiago-Osorio, Edelmiro
2017-12-01
Introducción. El caseinato de sodio, una sal de la caseína utilizada como agente proinflamatorio en ratones, es capaz de inducir granulopoyesis en vivo e incrementar la producción de citocinas esenciales en dicho evento.Objetivo. Evaluar si el caseinato de sodio es capaz de inducir un efecto biológico en células de origen linfoide y la producción de citocinas involucradas con este linaje.Materiales y métodos: Se utilizaron ratones hembra BALB/c de 8 a 12 semanas de edad. Los animales se inyectaron cuatro veces, con intervalos de 48 horas, por vía intraperitoneal con 1 ml de caseinato de sodio (10 % de SFB p/v). La población de linfocitos B y la incorporación de bromodesoxiuridina (BrdU) se analizaron mediante citometría de flujo. La detección de la interleucina 7 se evaluó mediante la técnica de ELISA.Resultados. Tras la inyección por vía intraperitoneal, el número de linfocitos B 220+ provenientes del bazo de ratones tratados con caseinato de sodio aumentó comparados con los que solo recibieron el vehículo como tratamiento (89,01±1,03 Vs. 75,66±2,08), así como la incorporación de BrdU en células B220+ (38,59±4,48 Vs. 11,82±1,04). Se evidenció, asimismo, el incremento en la concentración de la interleucina 7 (IL-7) en el suero de los ratones tratados con caseinato de sodio, comparados con los que solo recibieron el vehículo (62,1±17,5 Vs. 26,9±4,4 pg/ml).Conclusión. El caseinato de sodio fue capaz de aumentar el número de linfocitos B en bazo de ratones, así como inducir la producción de IL-7, citocina clave para la linfopoyesis B.
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Variación temporal de las constantes fundamentales
NASA Astrophysics Data System (ADS)
Landau, S. J.; Vucetich, H.
La variación temporal de las constantes fundamentales es un problema que ha motivado numerosos trabajos teóricos y experimentales desde la hipótesis de los grandes números de Dirac en 1937. Entre los métodos experimentales y observacionales para establecer restricciones sobre la variación de las constantes fundamentes es importante mencionar: comparación entre relojes atómicos[1], métodos geofísicos[2][3], análisis de sistemas de absorción en quasares[4][5][6] y cotas provenientes de la nucleosíntesis primordial[7]. En un trabajo reciente[5], se reportó una significativa variación en la constante de estructura fina. Intentos de unificar las cuatro interacciones fundamentales dieron como resultado teorías con múltiples dimensiones como las teorías de Kaluza-Klein y teorías de supercuerdas. Estas teorías proporcionan un marco teórico natural para el estudio de la variación temporal de las constantes fundamentales. A su vez, un modelo sencillo para estudiar la variación de la constante de estructura fina, fue propuesto en [8], a partir de premisas muy generales como ser covarianza, invarianza de gauge, causalidad y invarianza ante reversiones temporales en el electromagnetismo. Diferentes versiones de las teorías antes mencionadas coinciden en predecir variaciones temporales de las constantes fundamentales pero difieren en la forma de esta variación[9][10]. De esta manera, las restricciones establecidas experimentalmente sobre la variación de las constantes fundamentales pueden ser una herramienta importante para testear estas diferentes teorías. En este trabajo, utilizamos las cotas provenientes de diversas técnicas experimentales, para testear si las mismas son consistentes con alguna de las teorías antes mencionadas. En particular, establecemos cotas sobre la variación de los parámentros libres de las diferentes teorías como por ejemplo el radio de las dimensiones extras en las teorías tipo Kaluza-Klein.
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Abundâncias químicas de estrelas T Tauri fracas
NASA Astrophysics Data System (ADS)
Rojas, G. A.; Gregorio-Hetem, J.
2003-08-01
Apresentamos resultados do estudo de 44 estrelas pré-seqüência principal, para as quais buscamos realizar uma classificação espectroscópica e determinar parâmetros estelares e abundâncias químicas. A amostra foi escolhida da seguinte maneira : 21 objetos selecionados a partir de catálogos de objetos jovens, como o Pico dos Dias Survey e o Herbig Bell Catalogue, e 23 objetos selecionados a partir de contrapartidas ópticas de fontes de raios X detectadas pelo satélite ROSAT. Dentre 24 objetos previamente classificados como estrelas T Tauri Fracas, apenas 7 revelaram ser realmente pertencentes à essa classe, sendo os demais objetos T Tauri Clássicas ou estrelas evoluídas da pré-seqüência principal. Esse resultado demonstra que o critério mais utilizado para distinguir as T Tauri Clássicas das T Tauri Fracas, baseado na largura equivelente da emissão Ha, não é suficiente para determinar o estágio evolutivo desses objetos. Para o cálculo de parâmetros estelares e abundâncias, foram escolhidas as estrelas que apresentam características ideais para esse tipo de estudo, como ausência de velamento, baixa velocidade de rotação e espectros com razão sinal-ruído adequada. Os parâmetros estelares como temperatura efetiva e gravidade foram determinados através do equilíbrio de excitação e ionização das linhas de Ferro, e as abundâncias químicas foram calculadas utilizando o método de síntese espectral. Serão apresentados os parâmetros estelares e as abundâncias de Lítio para toda a amostra, e abundâncias de vários elementos quimicos para 7 estrelas estudadas em maior detalhe
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Conceptos Basicos Sobre el Propano (in Spanish)
DOE Office of Scientific and Technical Information (OSTI.GOV)
El propano provee energia a mas de 143.000 vehiculos en los Estados Unidos y 23 millones en todo el mundo. Flotas de todos los Estados Unidos han implementado con exito el uso de vehiculos que funcionan con gas propano, y en la actualidad varios funcionan gracias a este gas, incluyendo autobuses escolares, lanzaderas y autobuses publicos, asi como tambien furgonetas, taxis, vehiculos utilizados por las fuerzas del orden, barredoras de calles y camiones para uso profesional. El propano tambien se utiliza con frecuencia en aplicaciones fuera de la carretera, tales como montacargas, podadoras y equipos de uso profesional y otrosmore » equipos agricolas. Las ventajas del propano incluyen la disponibilidad interna, su rendimiento y el hecho de que genera menos emisiones de gases contaminantes que otras alternativas energeticas.« less
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Spanish Summary (Nuevos meteoritos encountrados en lmilac)
NASA Astrophysics Data System (ADS)
1987-03-01
Desde tiempos prehistoricos han sido coleccionadas piedras que caen dei cielo. Hasta hace poco eran la unica fuente para hacer estudios de laboratorio de la materia extragal, ktica, e incluso en nuestra era espacial, siguen siendo una valiosa fuente de investigacion de la temprana historia dei sistema solar. Se estima que como termine medio cada kilometro cuadrado de la superficie terrestre es golpeada cada millon de aiios por un meteorito con un pese superior a 500 gramos. La mayoria se pierden en los oceanos 0 caen en regiones con escasa poblacion. Como resultado, los museos en el munda reciben anualmente tan solo alrededor de 6 meteoritos cuya caida fuera atestiguada. Otros llegan por hallazgos casuales que en la mayoria de los casos son meteoritos que han cardo en tiempos prehistoricos.