Atrial fibrillation associated with chocolate intake abuse and chronic salbutamol inhalation abuse.

PubMed

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.

Structural modulation of gut microbiota in Bama minipigs in response to treatment with a "growth-promoting agent", salbutamol.

PubMed

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.

Comparison of the relative airways and systemic potencies of inhaled fenoterol and salbutamol in asthmatic patients.

PubMed Central

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

Quantitative determination of salbutamol sulfate impurities using achiral supercritical fluid chromatography.

PubMed

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.

Salbutamol sulfate suppositories: influence of formulation on physical parameters and stability.

PubMed

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.

Study on the determination and chiral inversion of R-salbutamol in human plasma and urine by liquid chromatography-tandem mass spectrometry.

PubMed

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.

Airway Peroxidases Catalyze Nitration of the β2-Agonist Salbutamol and Decrease Its Pharmacological Activity

PubMed Central

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

Treatment of acute asthma: salbutamol via jet nebuliser vs spacer and metered dose inhaler.

PubMed

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.

[Spectroscopic Study of Salbutamol Molecularly Imprinted Polymers].

PubMed

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

Relative bioavailability of salbutamol to the lung following inhalation via a novel dry powder inhaler and a standard metered dose inhaler

PubMed Central

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

Speed of onset of bronchodilator response to salbutamol inhaled via different devices in asthmatics: a bioassay based on functional antagonism

PubMed Central

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

Reversibility after inhaling salbutamol in different body postures in asthmatic children: a pilot study.

PubMed

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.

Paradoxical effect of salbutamol in a model of acute organophosphates intoxication in guinea pigs: role of substance P release.

PubMed

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

Response localization of the pharmacological agents histamine and salbutamol along the respiratory system by forced oscillations in asthmatic subjects.

PubMed

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.

Single dosing comparison of the relative cardiac beta 1/beta 2 activity of inhaled fenoterol and salbutamol in normal subjects.

PubMed Central

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

A cumulative dose comparison between salbutamol and fenoterol metered dose aerosols in asthmatic patients.

PubMed Central

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

Anti-inflammatory effects of theophylline, cromolyn and salbutamol in a murine model of pleurisy.

PubMed Central

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

Simultaneous spectrophotometric determination of salbutamol and bromhexine in tablets.

PubMed

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.

Isobaric Tags for Relative and Absolute Quantification (iTRAQ)-Based Untargeted Quantitative Proteomic Approach To Identify Change of the Plasma Proteins by Salbutamol Abuse in Beef Cattle.

PubMed

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.

Alcohol, indomethacin, and salbutamol. A comparative trial of their use in preterm labor.

PubMed

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.

Chiral liquid chromatography-mass spectrometry (LC-MS/MS) method development for the detection of salbutamol in urine samples.

PubMed

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.

Formulation Development and Evaluation of Fast Disintegrating Tablets of Salbutamol Sulphate for Respiratory Disorders

PubMed Central

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

Intern pharmacists as change agents to improve the practice of nonprescription medication supply: provision of salbutamol to patients with asthma.

PubMed

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

Simultaneous determination of ambroxol and salbutamol in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.

PubMed

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.

Non-invasive measurement of the haemodynamic effects of inhaled salbutamol, intravenous L-arginine and sublingual nitroglycerin

PubMed Central

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

Protection against severe hypokalemia but impaired cardiac repolarization after intense rowing exercise in healthy humans receiving salbutamol.

PubMed

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.

Distinct Metabolic Profile of Inhaled Budesonide and Salbutamol in Asthmatic Children during Acute Exacerbation.

PubMed

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

Floating capsules containing alginate-based beads of salbutamol sulfate: In vitro-in vivo evaluations.

PubMed

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.

Salbutamol in paediatrics: pharmacology, prescribing and controversies.

PubMed

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/

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.

In vitro dissolution and in vivo gamma scintigraphic evaluation of press-coated salbutamol sulfate tablets.

PubMed

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.

Agglomerated novel spray-dried lactose-leucine tailored as a carrier to enhance the aerosolization performance of salbutamol sulfate from DPI formulations.

PubMed

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.

Real-life effectiveness and safety of salbutamol Steri-Neb™ vs. Ventolin Nebules® for exacerbations in patients with COPD: Historical cohort study

PubMed Central

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

Acute systemic effects of inhaled salbutamol in asthmatic subjects expressing common homozygous beta2-adrenoceptor haplotypes at positions 16 and 27.

PubMed

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

The episode-free day as a composite measure of effectiveness: an illustrative economic evaluation of formoterol versus salbutamol in asthma therapy.

PubMed

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.

[Influence of CNTs on Photodegradation of Salbutamol in Water Environment].

PubMed

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.

Different mechanisms of action of beta2-adrenergic receptor agonists: a comparison of reproterol, fenoterol and salbutamol on monocyte cyclic-AMP and leukotriene B4 production in vitro.

PubMed

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.

A comparison between a combination of ipratropium bromide plus fenoterol in a single metered dose inhaler (Duovent) and salbutamol in asthma.

PubMed Central

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

Particle engineering using sonocrystallization: salbutamol sulphate for pulmonary delivery.

PubMed

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.

Effect of additives on eremomycin sorbent selectivity in separation of salbutamol enantiomers using supercritical fluid chromatography

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.

Size distribution of salbutamol/ipratropium aerosols produced by different nebulizers in the absence and presence of heat and humidification.

PubMed

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.

Formulation and Development of Metered Dose Inhalations of Salbutamol in Solution Form

PubMed Central

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

The effect of nebulized salbutamol or isotonic saline on exercise-induced bronchoconstriction in elite skaters following a 1,500-meter race: study protocol for a randomized controlled trial.

PubMed

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.

A Cost Analysis of Salbutamol Administration by Metered-Dose Inhalers with Spacers versus Nebulization for Patients with Wheeze in the Pediatric Emergency Department: Evidence from Observational Data in Nova Scotia.

PubMed

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.

Sustained delivery of salbutamol and beclometasone from spray-dried double emulsions.

PubMed

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.

Rapid analysis of clenbuterol, salbutamol, procaterol, and fenoterol in pharmaceuticals and human urine by capillary electrophoresis.

PubMed

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.

Analysis of Foreign Area Officer (FAO) Requirements

DTIC Science & Technology

2007-02-01

East jArabic (MS) Attache Atache NORTHCOM C~anada, Ottawa Ontario ALUSNA 10-6 jAn jFrech Afttche A.ttache N0RTHCOM IMaesc ALUSNA 0-8 S Amyerica...GOG jArabic [Pal-miI/sales Total billets: 15 58 UNCLASSIFIED The Naval Component Commands identified these unconstrained FAQ billets. 58 UNCLASSIFIED

Aquatic photolysis of β2-agonist salbutamol: kinetics and mechanism studies.

PubMed

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.

Effect of On-Demand vs Routine Nebulization of Acetylcysteine With Salbutamol on Ventilator-Free Days in Intensive Care Unit Patients Receiving Invasive Ventilation: A Randomized Clinical Trial.

PubMed

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

Development of analytical method for ultrasensitive detection of salbutamol utilizing DNA labeled-immunoprobe.

PubMed

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.

Formulation Development and Evaluation of Fast Disintegrating Tablets of Salbutamol Sulphate, Cetirizine Hydrochloride in Combined Pharmaceutical Dosage Form: A New Era in Novel Drug Delivery for Pediatrics and Geriatrics

PubMed Central

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

Production of salbutamol sulfate for inhalation by high-gravity controlled antisolvent precipitation.

PubMed

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.

Peroxidative Metabolism of β2-Agonists Salbutamol and Fenoterol and Their Analogs

PubMed Central

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

Peroxidative metabolism of beta2-agonists salbutamol and fenoterol and their analogues.

PubMed

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.

Doping dose of salbutamol and exercise training: impact on the skeleton of ovariectomized rats.

PubMed

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.

Effect of permeation enhancers in the mucoadhesive buccal patches of salbutamol sulphate for unidirectional buccal drug delivery

PubMed Central

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

Dry powder inhaler performance of spray dried mannitol with tailored surface morphologies as carrier and salbutamol sulphate.

PubMed

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.

Investigation of L-leucine in reducing the moisture-induced deterioration of spray-dried salbutamol sulfate power for inhalation.

PubMed

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.

Portable exhausters POR-004 SKID B, POR-005 SKID C, POR-006 SKID D storage plan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, O.D.

1997-09-04

This document provides a storage plan for portable exhausters POR-004 SKID B, POR-005 SKID C, AND POR-006 SKID D. The exhausters will be stored until they are needed by the TWRS (Tank Waste Remediation Systems) Saltwell Pumping Program. The storage plan provides criteria for portable exhauster storage, periodic inspections during storage, and retrieval from storage.

Discriminating Ability of Abbreviated Impactor Measurement Approach (AIM) to Detect Changes in Mass Median Aerodynamic Diameter (MMAD) of an Albuterol/Salbutamol pMDI Aerosol.

PubMed

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.

Portable exhauster POR-007/Skid E and POR-008/Skid F storage plan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, O.D.

1998-07-25

This document provides storage requirements for 1,000 CFM portable exhausters POR-O07/Skid E and POR-008/Skid F. These requirements are presented in three parts: preparation for storage, storage maintenance and testing, and retrieval from storage. The exhauster component identification numbers listed in this document contain the prefix POR-007 or POR-008 depending on which exhauster is being used.

Structural Insights into the PorK and PorN Components of the Porphyromonas gingivalis Type IX Secretion System.

PubMed

Gorasia, Dhana G; Veith, Paul D; Hanssen, Eric G; Glew, Michelle D; Sato, Keiko; Yukitake, Hideharu; Nakayama, Koji; Reynolds, Eric C

2016-08-01

The type IX secretion system (T9SS) has been recently discovered and is specific to Bacteroidetes species. Porphyromonas gingivalis, a keystone pathogen for periodontitis, utilizes the T9SS to transport many proteins including the gingipain virulence factors across the outer membrane and attach them to the cell surface via a sortase-like mechanism. At least 11 proteins have been identified as components of the T9SS including PorK, PorL, PorM, PorN and PorP, however the precise roles of most of these proteins have not been elucidated and the structural organization of these components is unknown. In this study, we purified PorK and PorN complexes from P. gingivalis and using electron microscopy we have shown that PorN and the PorK lipoprotein interact to form a 50 nm diameter ring-shaped structure containing approximately 32-36 subunits of each protein. The formation of these rings was dependent on both PorK and PorN, but was independent of PorL, PorM and PorP. PorL and PorM were found to form a separate stable complex. PorK and PorN were protected from proteinase K cleavage when present in undisrupted cells, but were rapidly degraded when the cells were lysed, which together with bioinformatic analyses suggests that these proteins are exposed in the periplasm and anchored to the outer membrane via the PorK lipid. Chemical cross-linking and mass spectrometry analyses confirmed the interaction between PorK and PorN and further revealed that they interact with the PG0189 outer membrane protein. Furthermore, we established that PorN was required for the stable expression of PorK, PorL and PorM. Collectively, these results suggest that the ring-shaped PorK/N complex may form part of the secretion channel of the T9SS. This is the first report showing the structural organization of any T9SS component.

Structural Insights into the PorK and PorN Components of the Porphyromonas gingivalis Type IX Secretion System

PubMed Central

Gorasia, Dhana G.; Veith, Paul D.; Hanssen, Eric G.; Glew, Michelle D.; Sato, Keiko; Yukitake, Hideharu; Nakayama, Koji; Reynolds, Eric C.

2016-01-01

The type IX secretion system (T9SS) has been recently discovered and is specific to Bacteroidetes species. Porphyromonas gingivalis, a keystone pathogen for periodontitis, utilizes the T9SS to transport many proteins including the gingipain virulence factors across the outer membrane and attach them to the cell surface via a sortase-like mechanism. At least 11 proteins have been identified as components of the T9SS including PorK, PorL, PorM, PorN and PorP, however the precise roles of most of these proteins have not been elucidated and the structural organization of these components is unknown. In this study, we purified PorK and PorN complexes from P. gingivalis and using electron microscopy we have shown that PorN and the PorK lipoprotein interact to form a 50 nm diameter ring-shaped structure containing approximately 32–36 subunits of each protein. The formation of these rings was dependent on both PorK and PorN, but was independent of PorL, PorM and PorP. PorL and PorM were found to form a separate stable complex. PorK and PorN were protected from proteinase K cleavage when present in undisrupted cells, but were rapidly degraded when the cells were lysed, which together with bioinformatic analyses suggests that these proteins are exposed in the periplasm and anchored to the outer membrane via the PorK lipid. Chemical cross-linking and mass spectrometry analyses confirmed the interaction between PorK and PorN and further revealed that they interact with the PG0189 outer membrane protein. Furthermore, we established that PorN was required for the stable expression of PorK, PorL and PorM. Collectively, these results suggest that the ring-shaped PorK/N complex may form part of the secretion channel of the T9SS. This is the first report showing the structural organization of any T9SS component. PMID:27509186

The PorX Response Regulator of the Porphyromonas gingivalis PorXY Two-Component System Does Not Directly Regulate the Type IX Secretion Genes but Binds the PorL Subunit

PubMed Central

Vincent, Maxence S.; Durand, Eric; Cascales, Eric

2016-01-01

The Type IX secretion system (T9SS) is a versatile multi-protein complex restricted to bacteria of the Bacteriodetes phylum and responsible for the secretion or cell surface exposition of diverse proteins that participate to S-layer formation, gliding motility or pathogenesis. The T9SS is poorly characterized but a number of proteins involved in the assembly of the secretion apparatus in the oral pathogen Porphyromonas gingivalis have been identified based on genome substractive analyses. Among these proteins, PorY, and PorX encode typical two-component system (TCS) sensor and CheY-like response regulator respectively. Although the porX and porY genes do not localize at the same genetic locus, it has been proposed that PorXY form a bona fide TCS. Deletion of porX in P. gingivalis causes a slight decrease of the expression of a number of other T9SS genes, including sov, porT, porP, porK, porL, porM, porN, and porY. Here, we show that PorX and the soluble cytoplasmic domain of PorY interact. Using electrophoretic mobility shift, DNA-protein co-purification and heterologous host expression assays, we demonstrate that PorX does not bind T9SS gene promoters and does not directly regulate expression of the T9SS genes. Finally, we show that PorX interacts with the cytoplasmic domain of PorL, a component of the T9SS membrane core complex and propose that the CheY-like PorX protein might be involved in the dynamics of the T9SS. PMID:27630829

Investigation of endothelial function by pulse contour analysis: a protocol for drug administration and timing of pulse contour assessment

PubMed Central

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

Development and comparison of immunochromatographic strips with three nanomaterial labels: Colloidal gold, nanogold-polyaniline-nanogold microspheres (GPGs) and colloidal carbon for visual detection of salbutamol.

PubMed

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.

Inhibition by fenoterol of human eosinophil functions including beta2-adrenoceptor-independent actions.

PubMed

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.

Novel method for the rapid and specific extraction of multiple β2 -agonist residues in food by tailor-made Monolith-MIPs extraction disks and detection by gas chromatography with mass spectrometry.

PubMed

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.

[Study of the clinical phenotype of symptomatic chronic airways disease by hierarchical cluster analysis and two-step cluster analyses].

PubMed

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

Inhibition by fenoterol of human eosinophil functions including β2-adrenoceptor-independent actions

PubMed Central

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

Long-Acting β2-Agonists in Asthma: Enantioselective Safety Studies are Needed.

PubMed

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.

Beta-Adrenergic Modulation of Tremor and Corticomuscular Coherence in Humans

PubMed Central

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

Predicting the behavior of novel sugar carriers for dry powder inhaler formulations via the use of a cohesive-adhesive force balance approach.

PubMed

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

Identification of Porphyromonas gingivalis proteins secreted by the Por secretion system.

PubMed

Sato, Keiko; Yukitake, Hideharu; Narita, Yuka; Shoji, Mikio; Naito, Mariko; Nakayama, Koji

2013-01-01

The Gram-negative bacterium Porphyromonas gingivalis possesses a number of potential virulence factors for periodontopathogenicity. In particular, cysteine proteinases named gingipains are of interest given their abilities to degrade host proteins and process other virulence factors such as fimbriae. Gingipains are translocated on the cell surface or into the extracellular milieu by the Por secretion system (PorSS), which consists of a number of membrane or periplasmic proteins including PorK, PorL, PorM, PorN, PorO, PorP, PorQ, PorT, PorU, PorV (PG27, LptO), PorW and Sov. To identify proteins other than gingipains secreted by the PorSS, we compared the proteomes of P. gingivalis strains kgp rgpA rgpB (PorSS-proficient strain) and kgp rgpA rgpB porK (PorSS-deficient strain) using two-dimensional gel electrophoresis and peptide-mass fingerprinting. Sixteen spots representing 10 different proteins were present in the particle-free culture supernatant of the PorSS-proficient strain but were absent or faint in that of the PorSS-deficient strain. These identified proteins possessed the C-terminal domains (CTDs), which had been suggested to form the CTD protein family. These results indicate that the PorSS is used for secretion of a number of proteins other than gingipains and that the CTDs of the proteins are associated with the PorSS-dependent secretion. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Suppression of Cytochrome P450 Reductase (POR) Expression in Hepatoma Cells Replicates the Hepatic Lipidosis Observed in Hepatic POR-Null Mice

PubMed Central

Banerjee, Subhashis; Stolarczyk, Elzbieta I.; Zou, Ling

2011-01-01

Cytochrome P450 reductase (POR) is a microsomal electron transport protein essential to cytochrome P450-mediated drug metabolism and sterol and bile acid synthesis. The conditional deletion of hepatic POR gene expression in mice results in a marked decrease in plasma cholesterol levels counterbalanced by the accumulation of triglycerides in lipid droplets in hepatocytes. To evaluate the role of cholesterol and bile acid synthesis in this hepatic lipidosis, as well as the possible role of lipid transport from peripheral tissues, we developed a stable, small interfering RNA (siRNA)-mediated cell culture model for the suppression of POR. POR mRNA and protein expression were decreased by greater than 50% in McArdle-RH7777 rat hepatoma cells 10 days after transfection with a POR-siRNA expression plasmid, and POR expression was nearly completely extinguished by day 20. Immunofluorescent analysis revealed a marked accumulation of lipid droplets in cells by day 15, accompanied by a nearly 2-fold increase in cellular triglyceride content, replicating the lipidosis seen in hepatic POR-null mouse liver. In contrast, suppression of CYP51A1 (lanosterol demethylase) did not result in lipid accumulation, indicating that loss of cholesterol synthesis is not the basis for this lipidosis. Indeed, addition of cholesterol to the medium appeared to augment the lipidosis in POR-suppressed cells, whereas removal of lipids from the medium reversed the lipidosis. Oxysterols did not accumulate in POR-suppressed cells, discounting a role for liver X receptor in stimulating triglyceride synthesis, but addition of chenodeoxycholate significantly repressed lipid accumulation, suggesting that the absence of bile acids and loss of farnesoid X receptor stimulation lead to excessive triglyceride synthesis. PMID:21368239

Suppression of cytochrome P450 reductase (POR) expression in hepatoma cells replicates the hepatic lipidosis observed in hepatic POR-null mice.

PubMed

Porter, Todd D; Banerjee, Subhashis; Stolarczyk, Elzbieta I; Zou, Ling

2011-06-01

Cytochrome P450 reductase (POR) is a microsomal electron transport protein essential to cytochrome P450-mediated drug metabolism and sterol and bile acid synthesis. The conditional deletion of hepatic POR gene expression in mice results in a marked decrease in plasma cholesterol levels counterbalanced by the accumulation of triglycerides in lipid droplets in hepatocytes. To evaluate the role of cholesterol and bile acid synthesis in this hepatic lipidosis, as well as the possible role of lipid transport from peripheral tissues, we developed a stable, small interfering RNA (siRNA)-mediated cell culture model for the suppression of POR. POR mRNA and protein expression were decreased by greater than 50% in McArdle-RH7777 rat hepatoma cells 10 days after transfection with a POR-siRNA expression plasmid, and POR expression was nearly completely extinguished by day 20. Immunofluorescent analysis revealed a marked accumulation of lipid droplets in cells by day 15, accompanied by a nearly 2-fold increase in cellular triglyceride content, replicating the lipidosis seen in hepatic POR-null mouse liver. In contrast, suppression of CYP51A1 (lanosterol demethylase) did not result in lipid accumulation, indicating that loss of cholesterol synthesis is not the basis for this lipidosis. Indeed, addition of cholesterol to the medium appeared to augment the lipidosis in POR-suppressed cells, whereas removal of lipids from the medium reversed the lipidosis. Oxysterols did not accumulate in POR-suppressed cells, discounting a role for liver X receptor in stimulating triglyceride synthesis, but addition of chenodeoxycholate significantly repressed lipid accumulation, suggesting that the absence of bile acids and loss of farnesoid X receptor stimulation lead to excessive triglyceride synthesis.

Importance of beta 2-adrenoceptor stimulation in the suppression of intradermal antigen challenge by adrenaline.

PubMed Central

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

Human-Health Pharmaceutical Compounds in Lake Mead, Nevada and Arizona, and Las Vegas Wash, Nevada, October 2000-August 2001

DTIC Science & Technology

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

The protective effect of a beta 2 agonist against excessive airway narrowing in response to bronchoconstrictor stimuli in asthma and chronic obstructive lung disease.

PubMed Central

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

Interaction between morphine and noradrenergic system of basolateral amygdala on anxiety and memory in the elevated plus-maze test based on a test-retest paradigm.

PubMed

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.

Selective stimulation and blockade of beta-adrenergic receptors in the mandibular gland of the red kangaroo, Macropus rufus.

PubMed

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.

Ipratropium bromide in patients with nocturnal asthma.

PubMed Central

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

Lung deposition and systemic bioavailability of different aerosol devices with and without humidification in mechanically ventilated patients.

PubMed

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.

Effect of educational and policy interventions on institutional utilization of wet nebulization respiratory drugs and portable inhalers.

PubMed

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.

Design of a device for simultaneous particle size and electrostatic charge measurement of inhalation drugs.

PubMed

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.

System design description for portable 1,000 CFM exhauster Skids POR-007/Skid E and POR-008/Skid F

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, O.D.

1998-07-25

The primary purpose of the two 1,000 CFM Exhauster Skids, POR-007-SKID E and POR-008-SKID F, is to provide backup to the waste tank primary ventilation systems for tanks 241-C-106 and 241-AY-102, and the AY-102 annulus in the event of a failure during the sluicing of tank 241-C-106 and subsequent transfer of sluiced waste to 241-AY-102. This redundancy is required since both of the tank ventilation systems have been declared as Safety Class systems.

The Effect of Mustard Gas on Salivary Trace Metals (Zn, Mn, Cu, Mg, Mo, Sr, Cd, Ca, Pb, Rb)

PubMed Central

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

Nebulisation of corticosteroid suspensions and solutions with a beta(2) agonist.

PubMed

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.

Acute bronchiolitis in a paediatric emergency department of Northern Greece. Comparisons between two decades

PubMed Central

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

New insight into the assessment of asthma using xenon ventilation computed tomography.

PubMed

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.

Budesonide/formoterol maintenance and reliever therapy in Asian patients (aged ≥16 years) with asthma: a sub-analysis of the COSMOS study.

PubMed

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

Association between respiratory prescribing, air pollution and deprivation, in primary health care.

PubMed

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.

β2 adrenergic receptor activation governs cardiac repolarization and arrhythmogenesis in a guinea pig model of heart failure.

PubMed

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.

β2 adrenergic receptor activation governs cardiac repolarization and arrhythmogenesis in a guinea pig model of heart failure

PubMed Central

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

Outer membrane vesicles from Neisseria gonorrhoeae target PorB to mitochondria and induce apoptosis

PubMed Central

Elgass, Kirstin D.; Gabriel, Kipros; Dougan, Gordon; Lithgow, Trevor; Heinz, Eva

2018-01-01

Neisseria gonorrhoeae causes the sexually transmitted disease gonorrhoea by evading innate immunity. Colonizing the mucosa of the reproductive tract depends on the bacterial outer membrane porin, PorB, which is essential for ion and nutrient uptake. PorB is also targeted to host mitochondria and regulates apoptosis pathways to promote infections. How PorB traffics from the outer membrane of N. gonorrhoeae to mitochondria and whether it modulates innate immune cells, such as macrophages, remains unclear. Here, we show that N. gonorrhoeae secretes PorB via outer membrane vesicles (OMVs). Purified OMVs contained primarily outer membrane proteins including oligomeric PorB. The porin was targeted to mitochondria of macrophages after exposure to purified OMVs and wild type N. gonorrhoeae. This was associated with loss of mitochondrial membrane potential, release of cytochrome c, activation of apoptotic caspases and cell death in a time-dependent manner. Consistent with this, OMV-induced macrophage death was prevented with the pan-caspase inhibitor, Q-VD-PH. This shows that N. gonorrhoeae utilizes OMVs to target PorB to mitochondria and to induce apoptosis in macrophages, thus affecting innate immunity. PMID:29601598

[An initiative to reduce the use of unnecessary medication in infants with bronchiolitis in primary care].

PubMed

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.

The Chocuhaler: sweet deliverance in asthma management.

PubMed

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.

Understanding the effects on constitutive activation and drug binding of a D130N mutation in the β2 adrenergic receptor via molecular dynamics simulation.

PubMed

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.

Safety and potential anticoagulant effects of nebulised heparin in burns patients with inhalational injury at Singapore General Hospital Burns Centre.

PubMed

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.

Gliding Motility and Por Secretion System Genes Are Widespread among Members of the Phylum Bacteroidetes

PubMed Central

Zhu, Yongtao

2013-01-01

The phylum Bacteroidetes is large and diverse, with rapid gliding motility and the ability to digest macromolecules associated with many genera and species. Recently, a novel protein secretion system, the Por secretion system (PorSS), was identified in two members of the phylum, the gliding bacterium Flavobacterium johnsoniae and the nonmotile oral pathogen Porphyromonas gingivalis. The components of the PorSS are not similar in sequence to those of other well-studied bacterial secretion systems. The F. johnsoniae PorSS genes are a subset of the gliding motility genes, suggesting a role for the secretion system in motility. The F. johnsoniae PorSS is needed for assembly of the gliding motility apparatus and for secretion of a chitinase, and the P. gingivalis PorSS is involved in secretion of gingipain protease virulence factors. Comparative analysis of 37 genomes of members of the phylum Bacteroidetes revealed the widespread occurrence of gliding motility genes and PorSS genes. Genes associated with other bacterial protein secretion systems were less common. The results suggest that gliding motility is more common than previously reported. Microscopic observations confirmed that organisms previously described as nonmotile, including Croceibacter atlanticus, “Gramella forsetii,” Paludibacter propionicigenes, Riemerella anatipestifer, and Robiginitalea biformata, exhibit gliding motility. Three genes (gldA, gldF, and gldG) that encode an apparent ATP-binding cassette transporter required for F. johnsoniae gliding were absent from two related gliding bacteria, suggesting that the transporter may not be central to gliding motility. PMID:23123910

Antigenic topology of chlamydial PorB protein and identification of targets for immune neutralization of infectivity.

PubMed

Kawa, Diane E; Stephens, Richard S

2002-05-15

The outer membrane protein PorB is a conserved chlamydial protein that functions as a porin and is capable of eliciting neutralizing Abs. A topological antigenic map was developed using overlapping synthetic peptides representing the Chlamydia trachomatis PorB sequence and polyclonal immune sera. To identify which antigenic determinants were surface accessible, monospecific antisera were raised to the PorB peptides and were used in dot-blot and ELISA-based absorption studies with viable chlamydial elementary bodies (EBs). The ability of the surface-accessible antigenic determinants to direct neutralizing Ab responses was investigated using standardized in vitro neutralization assays. Four major antigenic clusters corresponding to Phe(34)-Leu(59) (B1-2 and B1-3), Asp(112) -Glu(145) (B2-3 and B2-4), Gly(179)-Ala(225) (B3-2 to B3-4), and Val(261)-Asn(305) (B4-4 to B5-2) were identified. Collectively, the EB absorption and dot-blot assays established that the immunoreactive PorB Ags were exposed on the surface of chlamydial EBs. Peptide-specific antisera raised to the surface-accessible Ags neutralized chlamydial infectivity and demonstrated cross-reactivity to synthetic peptides representing analogous C. pneumoniae PorB sequences. Furthermore, neutralization of chlamydial infectivity by C. trachomatis PorB antisera was inhibited by synthetic peptides representing the surface-exposed PorB antigenic determinants. These findings demonstrate that PorB Ags may be useful for development of chlamydial vaccines.

Thin Layer Chromatographic Resolution of Some β-adrenolytics and a β2-Agonist Using Bovine Serum Albumin as Chiral Additive in Stationary Phase.

PubMed

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.

Determination of beta-agonists in swine hair by μFIA and chemiluminescence.

PubMed

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.

Do we really ponder about necessity of intravenous hydration in acute bronchiolitis?

PubMed

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.

Low oxygen environment facilitates embryo availability for older ovarian responders (PORs).

PubMed

Li, Mingzhao; Li, Zhibin; Shi, Juanzi

2018-04-18

We aimed to investigate the different effects of low oxygen (5% O 2 ) and atmospheric oxygen (20% O 2 ) on in vitro fertilization for older poor ovarian responders (PORs). We selected 1080 older PORs who met two criteria: (i) advanced maternal age (≥40) and (ii) an abnormal ovarian reserve test. All the patients used the ultra-short term protocols with GnRH agonist and recombinant FSH for controlled ovarian hyperstimulation (COH). About 506 cycles were performed in the incubators with 5% O 2 and 574 cycles were performed in the incubators with 20% O 2 . No significant differences were observed in normal fertilization rates (59.68 versus 60.25%; p = .691) and cancelation rates (18.97 versus 19.34%; p = .879) between two groups. The number of available embryos (1.77 ± 0.57 versus 1.52 ± 0.50; p = .041) and mean number of cells on Day 3 (7.49 ± 1.82 versus 7.16 ± 1.70; p = .032) were significantly higher in 5% O 2 group compared to that in 20% O 2 group. It showed no significant differences in the implantation rates (27.43 versus 24.11%; p = .803) and clinical pregnancy rates (36.34 versus 30.05%; p = .307) between two groups. The employ of low oxygen culture did not improve clinical pregnancy rate for older PORs. However, it benefited early embryonic development for older PORs.

Clinical application of inert gas Multiple Breath Washout in children and adolescents with asthma.

PubMed

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.

Steam inhalation or humidified oxygen for acute bronchiolitis in children up to three years of age.

PubMed

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

In vitro desensitization of beta-adrenoceptors in guinea pig trachea: interactions between beta-adrenoceptor agonists and influence of adenosine and other drugs.

PubMed

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

A cross-sectional questionnaire study of the rules governing pupils' carriage of inhalers for asthma treatment in secondary schools in North East England.

PubMed

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.

Chronic aerial exposure to glucorticoids or beta-agonists affects avoidance learning and exploratory motivation in rats.

PubMed

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.

The effect of chemical warfare on respiratory symptoms, pulmonary function tests and their reversibility 23-25 years after exposure.

PubMed

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.

Inversor Resonante de Tres Elementos L-LC con Caracteristica Cortocircuitable para Aplicaciones de Calentamiento por Induccion

NASA Astrophysics Data System (ADS)

Espi Huerta, Jose Miguel

Los generadores de calentamiento por induccion son puentes inversores con carga resonante, cuya mision es basicamente crear una corriente sinusoidal de gran amplitud sobre la "bobina de caldeo", que forma parte del tanque resonante. En el interior de esta bobina se introduce la pieza que se desea calentar. EI campo magnetico creado induce corrientes superficiales (corrientes de Foucault) sobre la pieza, que producen su calentamiento. Los tanques resonantes (tambien llamados osciladores) utilizados en la actualidad son el resonante serie y el resonante paralelo. Aunque ya desde hace algun tiempo se vienen construyendo generadores de alta potencia basados en estos dos osciladores, el exito nunca ha. sido completo en ninguno de los dos casos. Tal y como se explica en la introduccion de esta memoria, los puentes inversores utilizados deben operar sobre una carga inductiva (corriente retrasada) para evitar el fenomeno de la recuperacion inversa de sus diodos y la consiguiente ruptura de los transistores. De la restriccion topologica anterior se deduce que el generador paralelo debe conmutar a frecuencias inferiores a la resonancia, y el serie a frecuencias superiores. A esta restriccion topologica hay que unir otra que es exclusiva del calentamiento por induccion: La corriente por la bobina de caldeo debe ser sinusoidal. De no ser asi, resultaria imposible disponer toda la potencia de calentamiento sobre la pieza en el espesor requerido por la aplicacion. Como consecuencia, los inversores no pueden operar por debajo de la frecuencia de resonancia del oscilador, pues en ese caso se amplifican los armonicos de orden superior de la tension/corriente de entrada situados sobre la resonancia, con la consiguiente distorsion de la corriente de salida. La conjuncion de las dos restricciones anteriores obligan al inversor paralelo a funcionar a la frecuencia de resonancia del oscilador. Esto imposibilita un control por variacion de frecuencia, regulandose la potencia desde la

[Duration of bronchodilator effect of inhaled Salmeterol (dry powder x metered dose inhaler) in children with acute asthma attack].

PubMed

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.

Multiple active site residues are important for photochemical efficiency in the light-activated enzyme protochlorophyllide oxidoreductase (POR).

PubMed

Menon, Binuraj R K; Hardman, Samantha J O; Scrutton, Nigel S; Heyes, Derren J

2016-08-01

Protochlorophyllide oxidoreductase (POR) catalyzes the light-driven reduction of protochlorophyllide (Pchlide), an essential, regulatory step in chlorophyll biosynthesis. The unique requirement of the enzyme for light has provided the opportunity to investigate how light energy can be harnessed to power biological catalysis and enzyme dynamics. Excited state interactions between the Pchlide molecule and the protein are known to drive the subsequent reaction chemistry. However, the structural features of POR and active site residues that are important for photochemistry and catalysis are currently unknown, because there is no crystal structure for POR. Here, we have used static and time-resolved spectroscopic measurements of a number of active site variants to study the role of a number of residues, which are located in the proposed NADPH/Pchlide binding site based on previous homology models, in the reaction mechanism of POR. Our findings, which are interpreted in the context of a new improved structural model, have identified several residues that are predicted to interact with the coenzyme or substrate. Several of the POR variants have a profound effect on the photochemistry, suggesting that multiple residues are important in stabilizing the excited state required for catalysis. Our work offers insight into how the POR active site geometry is finely tuned by multiple active site residues to support enzyme-mediated photochemistry and reduction of Pchlide, both of which are crucial to the existence of life on Earth. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

VERA-CS User Support Activities for PoR 14

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kochunas, Brendan

2017-11-01

The purpose of this milestone is to document the user support activities that took place between 10/1/2016 and 3/31/2017 (PoR 14). In the normal PHI workflow, that also extends to several activities within RTM, a Kanban process is followed. This involves creating tickets for specific work items and track the progress to complete these specific work items.

Efficient preparation of α-ketoacetals.

PubMed

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.

Fenoterol inhibits superoxide anion generation by human polymorphonuclear leukocytes via beta-adrenoceptor-dependent and -independent mechanisms.

PubMed

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.

Improvement of the Prediction of Drugs Demand Using Spatial Data Mining Tools.

PubMed

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.

Reaction of β-blockers and β-agonist pharmaceuticals with aqueous chlorine. Investigation of kinetics and by-products by liquid chromatography quadrupole time-of-flight mass spectrometry.

PubMed

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.

A role for POR1, a Rac1-interacting protein, in ARF6-mediated cytoskeletal rearrangements.

PubMed Central

D'Souza-Schorey, C; Boshans, R L; McDonough, M; Stahl, P D; Van Aelst, L

1997-01-01

The ARF6 GTPase, the least conserved member of the ADP ribosylation factor (ARF) family, associates with the plasma membrane and intracellular endosome vesicles. Mutants of ARF6 defective in GTP binding and hydrolysis have a marked effect on endocytic trafficking and the gross morphology of the peripheral membrane system. Here we report that expression of the GTPase-defective mutant of ARF6, ARF6(Q67L), remodels the actin cytoskeleton by inducing actin polymerization at the cell periphery. This cytoskeletal rearrangement was inhibited by co-expression of ARF6(Q67L) with deletion mutants of POR1, a Rac1-interacting protein involved in membrane ruffling, but not with the dominant-negative mutant of Rac1, Rac1(S17N). A synergistic effect between POR1 and ARF6 for the induction of actin polymerization was detected. Furthermore, we observed that ARF6 interacts directly with POR1 and that this interaction was GTP dependent. These findings indicate that ARF6 and Rac1 function on distinct signaling pathways to mediate cytoskeletal reorganization, and suggest a role for POR1 as an important regulatory element in orchestrating cytoskeletal rearrangements at the cell periphery induced by ARF6 and Rac1. PMID:9312003

Effect of SPM-based cleaning POR on EUV mask performance

NASA Astrophysics Data System (ADS)

Choi, Jaehyuck; Lee, Han-shin; Yoon, Jinsang; Shimomura, Takeya; Friz, Alex; Montgomery, Cecilia; Ma, Andy; Goodwin, Frank; Kang, Daehyuk; Chung, Paul; Shin, Inkyun; Cho, H.

2011-11-01

EUV masks include many different layers of various materials rarely used in optical masks, and each layer of material has a particular role in enhancing the performance of EUV lithography. Therefore, it is crucial to understand how the mask quality and patterning performance can change during mask fabrication, EUV exposure, maintenance cleaning, shipping, or storage. The fact that a pellicle is not used to protect the mask surface in EUV lithography suggests that EUV masks may have to undergo more cleaning cycles during their lifetime. More frequent cleaning, combined with the adoption of new materials for EUV masks, necessitates that mask manufacturers closely examine the performance change of EUV masks during cleaning process. We have investigated EUV mask quality and patterning performance during 30 cycles of Samsung's EUV mask SPM-based cleaning and 20 cycles of SEMATECH ADT exposure. We have observed that the quality and patterning performance of EUV masks does not significantly change during these processes except mask pattern CD change. To resolve this issue, we have developed an acid-free cleaning POR and substantially improved EUV mask film loss compared to the SPM-based cleaning POR.

Detección y estudio mediante Fluorescencia Inducida por Láser de radicales libres formados por Disociación Multifotónica Infrarroja

NASA Astrophysics Data System (ADS)

Santos, M.; Díaz, L.; Torresano, J. A.; Rubio, L.; Samoudi, B.

Una de las principales aplicaciones actuales de los procesos de disociación multifotónica inducidos por radiación láser infrarroja (DMI) es la producción de radiales libres, con el fin de estudiar sus propiedades cinéticas y espectroscópicas. La disociación de moléculas poliatómicas en el IR con láseres de CO2 tiene lugar desde la superficie de energía molecular mas baja y conduce generalmente a la formación de fragmentos en el estado electrónico fundamental, con diversos grados de excitación vibracional. En el Grupo de Procesos Multifotónicos del Instituto de Estructura de la Materia del C.S.I.C. hemos puesto a punto la técnica de Fluorescencia Inducida por Láser (LIF) para la detección y análisis en tiempo real de los fragmentos producidos en la DMI inducida mediante uno o dos campos láseres de diferentes longitudes de onda. Objetivos de nuestro trabajo han sido el estudio de los canales de disociación mayoritarios y de las especies transitoria producidas, así como de la distribución de energía interna con que éstas son generadas. En particular hemos detectado mediante LIF las especies: C2, CF, CH, SiH2, CF2, CH2, SiHCl, y CF3 a partir de la disociación de, entre otras, las siguientes moléculas: C2H3Br, C3F6, C4H8Si, C2H5ClSi y CH5ClSi. En este trabajo presentamos algunos de los resultados obtenidos mediante el estudio por LIF de estos radicales: estudio temporal de la señal LIF obtenida con determinación de tiempos de vida, espectros de excitación y fluorescencia, temperaturas vibracionales de formación, variación de la intensidad LIF con el tiempo de retraso entre los láseres de disociación y prueba, etc.

Monitoring adverse drug reactions in children using community pharmacies: a pilot study

PubMed Central

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

Postmarketing surveillance study of a non-chlorofluorocarbon inhaler according to the safety assessment of marketed medicines guidelines

PubMed Central

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

Inhibition of basal and stimulated release of endothelin-1 from guinea pig tracheal epithelial cells in culture by beta 2-adrenoceptor agonists and cyclic AMP enhancers.

PubMed

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

Determinacion del error sistematico del momentum de muones producidos por interacciones neutrino-nucleon en el detector MINER$$\

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

Mapping the Laminin Receptor Binding Domains of Neisseria meningitidis PorA and Haemophilus influenzae OmpP2

PubMed Central

Mahdavi, Jafar; Oldfield, Neil J.; Wheldon, Lee M.; Wooldridge, Karl G.; Ala'Aldeen, Dlawer A. A.

2012-01-01

Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae are major bacterial agents of meningitis. They each bind the 37/67-kDa laminin receptor (LamR) via the surface protein adhesins: meningococcal PilQ and PorA, H. influenzae OmpP2 and pneumococcal CbpA. We have previously reported that a surface-exposed loop of the R2 domain of CbpA mediates LamR-binding. Here we have identified the LamR-binding regions of PorA and OmpP2. Using truncated recombinant proteins we show that binding is dependent on amino acids 171–240 and 91–99 of PorA and OmpP2, respectively, which are predicted to localize to the fourth and second surface-exposed loops, respectively, of these proteins. Synthetic peptides corresponding to the loops bound LamR and could block LamR-binding to bacterial ligands in a dose dependant manner. Meningococci expressing PorA lacking the apex of loop 4 and H. influenzae expressing OmpP2 lacking the apex of loop 2 showed significantly reduced LamR binding. Since both loops are hyper-variable, our data may suggest a molecular basis for the range of LamR-binding capabilities previously reported among different meningococcal and H. influenzae strains. PMID:23049988

Mapping the laminin receptor binding domains of Neisseria meningitidis PorA and Haemophilus influenzae OmpP2.

PubMed

Abouseada, Noha M; Assafi, Mahde Saleh A; Mahdavi, Jafar; Oldfield, Neil J; Wheldon, Lee M; Wooldridge, Karl G; Ala'Aldeen, Dlawer A A

2012-01-01

Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae are major bacterial agents of meningitis. They each bind the 37/67-kDa laminin receptor (LamR) via the surface protein adhesins: meningococcal PilQ and PorA, H. influenzae OmpP2 and pneumococcal CbpA. We have previously reported that a surface-exposed loop of the R2 domain of CbpA mediates LamR-binding. Here we have identified the LamR-binding regions of PorA and OmpP2. Using truncated recombinant proteins we show that binding is dependent on amino acids 171-240 and 91-99 of PorA and OmpP2, respectively, which are predicted to localize to the fourth and second surface-exposed loops, respectively, of these proteins. Synthetic peptides corresponding to the loops bound LamR and could block LamR-binding to bacterial ligands in a dose dependant manner. Meningococci expressing PorA lacking the apex of loop 4 and H. influenzae expressing OmpP2 lacking the apex of loop 2 showed significantly reduced LamR binding. Since both loops are hyper-variable, our data may suggest a molecular basis for the range of LamR-binding capabilities previously reported among different meningococcal and H. influenzae strains.

Generating monodisperse pharmacological aerosols using the spinning-top aerosol generator.

PubMed

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.

An Evaluation of the British Columbia Asthma Monitoring System (BCAMS) and PM2.5 Exposure Metrics during the 2014 Forest Fire Season

PubMed Central

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

Effects of high flavanol dark chocolate on cardiovascular function and platelet aggregation.

PubMed

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.

beta-Adrenoceptor agonists enhance 5-hydroxytryptamine-mediated behavioural responses.

PubMed Central

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

Trombocitopenia induzida por heparina em paciente com oclusão arterial aguda

PubMed Central

Pimenta, Rafael Elias Farres; Yoshida, Winston Bonetti; Rollo, Hamilton Almeida; Sobreira, Marcone Lima; Bertanha, Matheus; Mariúba, Jamil Victor de Oliveira; Jaldin, Rodrigo Gibin; de Camargo, Paula Angeleli Bueno

2016-01-01

Resumo A trombocitopenia induzida por heparina é uma complicação grave da terapêutica anticoagulante com heparina e está associada à formação de anticorpos antifator IV plaquetário. Costuma surgir a partir do quinto dia do tratamento, com queda de pelo menos 50% da contagem plaquetária. Em decorrência da ativação plaquetária concomitante, pode ocorrer quadro de trombose, venosa ou arterial, com repercussões clínicas graves. Apresentamos um caso de paciente portador de síndrome do anticorpo antifosfolípide, com quadro de oclusão arterial aguda, que foi tratado cirurgicamente e recebeu heparina não fracionada no intra e pós-operatório. No quinto dia de tratamento anticoagulante, apresentou queda maior de 50% da contagem de plaquetas em relação à contagem pré-heparina. A suspeita de trombocitopenia induzida por heparina e seus aspectos diagnósticos e terapêuticos serão abordados neste desafio terapêutico.

Prevalencia y tamizaje del Trastorno por Déficit de Atención con Hiperactividad en Costa Rica

PubMed Central

Weiss, Nicholas T.; Schuler, Jovita; Monge, Silvia; McGough, James J.; Chavira, Denise; Bagnarello, Monica; Herrera, Luis Diego; Mathews, Carol A.

2015-01-01

Resumen La investigación tuvo como propósito estimar la prevalencia del Trastorno por Déficit de Atención con Hiperactividad (TDAH) en Costa Rica y determinar si la versión en español del cuestionario Swanson Nolan and Pelham Scale IV (SNAP-IV) es un instrumento de tamizaje útil en una población de niños y niñas escolares costarricenses. El instrumento fue entregado a padres y maestros de 425 niños entre 5 y 13 años de edad (promedio = 8.8). Todos fueron evaluados con el instrumento Swanson, Kotkin, Agler, M-Flynn and Pelham Scale (SKAMP). Su diagnóstico fue confirmado con una entrevista clínica. La sensibilidad y la especificidad del SNAP-IV fueron evaluadas como predictores de criterios de diagnóstico según el DSM-IV. La prevalencia puntual en la muestra del TDAH fue del 5%. El tamizaje más preciso lo hizo el SNAP-IV completado por el maestro en un corte de 20%, con una sensibilidad de 96% y una especificidad de un 82%. La sensibilidad de los instrumentos completados por los padres fue más baja que aquella de los maestros. El SNAP-IV completado por las maestras con un corte aislando el 20% de los mayores puntajes categorizó correctamente a un 87% de los sujetos. PMID:22432094

Racism in digital era: Development and initial validation of the Perceived Online Racism Scale (PORS v1.0).

PubMed

Keum, Brian TaeHyuk; Miller, Matthew J

2017-04-01

The purpose of this study was to develop the Perceived Online Racism Scale (PORS) to assess perceived online racist interpersonal interactions and exposure to online racist content among people of color. Items were developed through a multistage process involving a comprehensive literature review, focus-groups, qualitative data collection, and survey of online racism experiences. Based on a sample of 1,023 racial minority participants, exploratory and confirmatory factor analyses provided support for a 30-item bifactor model accounted by the general factor and the following 3 specific factors: (a) personal experience of racial cyber-aggression, (b) vicarious exposure to racial cyber-aggression, and (c) online-mediated exposure to racist reality. The PORS demonstrated measurement invariance across racial/ethnic groups in our sample. Internal reliability estimates for the total and subscale scores of the PORS were above .88 and the 4-week test-retest reliability was adequate. Limitations and future directions for research are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

[Professor Frantisek Por MD and Professor Robert Klopstock MD, students at Budapest and Prague Faculties of Medicine].

PubMed

Mydlík, M; Derzsiová, K

2010-11-01

Professor Frantisek Por MD and Professor Robert Klopstock MD were contemporaries, both born in 1899, one in Zvolen, the other in Dombovar, at the time of Austro-Hungarian Monarchy. Prof. Por attended the Faculty of Medicine in Budapest from 1918 to 1920, and Prof. Klopstock studied at the same place between 1917 and 1919. From 1920 until graduation on 6th February 1926, Prof. Por continued his studies at the German Faculty of Medicine, Charles University in Prague. Prof. Klopstock had to interrupt his studies in Budapest due to pulmonary tuberculosis; he received treatment at Tatranske Matliare where he befriended Franz Kafka. Later, upon Kafka's encouragement, he changed institutions and continued his studies at the German Faculty of Medicine, Charles University in Prague, where he graduated the first great go. It is very likely that, during their studies in Budapest and Prague, both professors met repeatedly, even though their life paths later separated. Following his graduation, Prof. Por practiced as an internist in Prague, later in Slovakia, and from 1945 in Kosice. In 1961, he was awarded the title of university professor of internal medicine at the Faculty of Medicine, Pavol Jozef Safarik University in Kosice, where he practiced until his death in 1980. Prof. Klopstock continued his studies in Kiel and Berlin. After his graduation in 1933, he practiced in Berlin as a surgeon and in 1938 left for USA. In 1962, he was awarded the title of university professor of pulmonary surgery in NewYork, where he died in 1972.

Encefalitis por anticuerpos contra el receptor de NMDA: experiencia con seis pacientes pediátricos. Potencial eficacia del metotrexato

PubMed Central

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

Structural and functional probing of PorZ, an essential bacterial surface component of the type-IX secretion system of human oral-microbiomic Porphyromonas gingivalis.

PubMed Central

Lasica, Anna M.; Goulas, Theodoros; Mizgalska, Danuta; Zhou, Xiaoyan; de Diego, Iñaki; Ksiazek, Mirosław; Madej, Mariusz; Guo, Yonghua; Guevara, Tibisay; Nowak, Magdalena; Potempa, Barbara; Goel, Apoorv; Sztukowska, Maryta; Prabhakar, Apurva T.; Bzowska, Monika; Widziolek, Magdalena; Thøgersen, Ida B.; Enghild, Jan J.; Simonian, Mary; Kulczyk, Arkadiusz W.; Nguyen, Ky-Anh; Potempa, Jan; Gomis-Rüth, F. Xavier

2016-01-01

Porphyromonas gingivalis is a member of the human oral microbiome abundant in dysbiosis and implicated in the pathogenesis of periodontal (gum) disease. It employs a newly described type-IX secretion system (T9SS) for secretion of virulence factors. Cargo proteins destined for secretion through T9SS carry a recognition signal in the conserved C-terminal domain (CTD), which is removed by sortase PorU during translocation. Here, we identified a novel component of T9SS, PorZ, which is essential for surface exposure of PorU and posttranslational modification of T9SS cargo proteins. These include maturation of enzyme precursors, CTD removal and attachment of anionic lipopolysaccharide for anchorage in the outer membrane. The crystal structure of PorZ revealed two β-propeller domains and a C-terminal β-sandwich domain, which conforms to the canonical CTD architecture. We further documented that PorZ is itself transported to the cell surface via T9SS as a full-length protein with its CTD intact, independently of the presence or activity of PorU. Taken together, our results shed light on the architecture and possible function of a novel component of the T9SS. Knowledge of how T9SS operates will contribute to our understanding of protein secretion as part of host-microbiome interactions by dysbiotic members of the human oral cavity. PMID:27883039

Spatial analysis and source profiling of beta-agonists and sulfonamides in Langat River basin, Malaysia.

PubMed

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.

β2-adrenoceptor signaling reduction in dendritic cells is involved in the inflammatory response in adjuvant-induced arthritic rats

PubMed Central

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

The enhanced immune responses induced by Salmonella enteritidis ghosts loaded with Neisseria gonorrhoeae porB against Salmonella in mice.

PubMed

Jiao, Hongmei; Yang, Hui; Zhao, Dan; He, Li; Chen, Jin; Li, Guocai

2016-11-01

Human health has been seriously endangered by highly prevalent salmonellosis and multidrug-resistant Salmonella strains. Current vaccines suffer from variable immune-protective effects, so more effective ones are needed to control Salmonella infection : Bacterial ghosts have been produced by the expression of lysis gene E from bacteriophage PhiX174 and can be filled with considerable exogenous substances such as DNA or drugs as a novel platform. In this study, Salmonella enteritidis (SE) ghosts were developed and loaded with Neisseria gonorrhoeae porin B (porB) to construct a novel inactive vaccine. Our new studies show that SE ghosts loaded with porB displayed increased production of pro-inflammatory cytokines (IL-1β, IL-6, IL-10 and IL-12p70) in bone marrow-derived dendritic cells (BMDCs), and elicited significantly higher specific systemic and mucosal immune responses to Salmonella than SE ghosts alone. In addition, the novel porB-loaded ghosts conferred higher protective effects on virulent Salmonella challenge. For the first time, we demonstrate that N. gonorrhoeae porB, as a novel adjuvant, can increase the immunogenicity of SE ghosts. Our studies suggested that Salmonella enteritidis ghosts loaded with Neisseria gonorrhoeae porin B might be a useful mucosal Salmonella vaccine candidate for practical use in the future. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Diagnóstico diferencial en la encefalitis por anticuerpos contra el receptor NMDA

PubMed Central

González-Valcárcel, J.; Rosenfeld, M.R.; Dalmau, J.

2011-01-01

Resumen Introducción La encefalitis por anticuerpos contra el receptor de NMDA (NMDAR) suele desarrollarse como un síndrome característico de evolución multifásica y diagnóstico diferencial amplio. Pacientes Presentamos a 2 pacientes diagnosticadas de encefalitis por anticuerpos NMDAR con un cuadro clínico típico, pero que inicialmente señaló otras etiologías. Discusión La afectación frecuente de pacientes jóvenes con manifestaciones psiquiátricas prominentes indica frecuentemente otras consideraciones diagnósticas; las más frecuentes son las encefalitis virales, los procesos psiquiátricos y el síndrome neuroléptico maligno. Varios síndromes previamente definidos de manera parcial o descriptiva en adultos y pacientes pediátricos probablemente eran casos de encefalitis anti-NMDAR. Conclusiones La encefalitis anti-NMDAR debe considerarse en pacientes jóvenes con manifestaciones psiquiátricas subagudas, movimientos anormales y alteraciones autonómicas. La caracterización clínica e inmunológica de esta enfermedad ha llevado a la identificación de nuevos anticuerpos que afectan a procesos de memoria, aprendizaje, conducta y psicosis. PMID:20964986

Metabolomic analysis of swine urine treated with β2-agonists by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry.

PubMed

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.

Reconstrução tridimensional de arcos magnéticos por tomografia

NASA Astrophysics Data System (ADS)

Simões, P. J. A.; Costa, J. E. R.

2003-08-01

Uma explosão solar é uma variação súbita do brilho que ocorre nas regiões ativas da atmosfera solar. Estas regiões são constituídas por um plasma magnetizado com intensa indução magnética e em cenários bem complexos como visto recentemente através de experimentos embarcados em satélites operando instrumentos em raios X moles e ultra-violeta distante. A energia magnética, que pode ser armazenada por um período de horas até dias em configurações magnéticas estressadas, é subitamente lançada na atmosfera solar e transferida para partículas como elétrons, prótons e núcleos pesados, que são acelerados e/ou aquecidos, produzindo radiação eletromagnética. A proposta final deste projeto é determinar as características espaciais de alta resolução da emissão e polarização girossincrotrônica de explosões solares em ambientes complexos de campos magnéticos. Os recentes resultados da emissão difusa em EUV apresentado pelos satélites TRACE e SOHO dos arcos magnéticos conectando as diferentes polaridades magnéticas sobre as regiões ativas possibilitam novas abordagens sobre o papel do campo magnético na emissão em rádio. Nesta etapa apresentamos os resultados da reconstrução da geometria tridimensional das linhas de força destes arcos utilizando técnicas tomográficas, a partir de imagens de alta resolução espacial obtidas pelo instrumento EIT (Extreme ultraviolet Imaging Telescope), além da modelagem das induções magnéticas por um campo dipolar e as densidades de partículas aceleradas. Utilizamos para a reconstrução geométrica, imagens tomadas em vários ângulos dos arcos devido à rotacão solar. Com estes resultados, daremos continuidade ao projeto, com os cálculos da transferência radiativa nos modos ordinário e extraordinário de propagação da radiação girossincrotrônica de explosões solares.

The Acquisition of Lexical Meaning in a Study Abroad Context: The Spanish Prepositions "por" and "para."

ERIC Educational Resources Information Center

Lafford, Barbara A.; Ryan, John M.

1995-01-01

Examination of the development of form/function relations of the prepositions "por" and "para" at different levels of proficiency in the interlanguage of study-abroad students in Granada, Spain, revealed "noncanonical" as well as "canonical" uses of these prepositions. The most common noncanonical uses were…

Status asthmaticus in children: a one-year study.

PubMed Central

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

Improved purification of native meningococcal porin PorB and studies on its structure/function.

PubMed

Massari, Paola; King, Carol A; MacLeod, Heather; Wetzler, Lee M

2005-12-01

The outer membrane protein PorB of Neisseria meningitidis is a pore-forming protein which has various effects on eukaryotic cells. It has been shown to (1) up-regulate the surface expression of the co-stimulatory molecule CD86 and of MHC class II (which are TLR2/MyD88 dependent and related to the porin's immune-potentiating ability), (2) be involved in prevention of apoptosis by modulating the mitochondrial membrane potential, and (3) form pores in eukaryotic cells. As an outer membrane protein, its native trimeric form isolation is complicated by its insoluble nature, requiring the presence of detergent throughout the whole procedure, and by its tight association with other outer membrane components, such as neisserial LOS or lipoproteins. In this study, an improved chromatographic purification method to obtain an homogeneous product free of endotoxin and lipoprotein is described, without loss of any of the above-mentioned properties of the porin. Furthermore, we have investigated the requirement of the native trimeric structure for the porin's activity. Inactivation of functional PorB trimers into non-functional monomers was achieved by incubation on ice. Thus, routine long- and medium-term storage at low temperature may be a cause of porin inactivation.

Adjuvant Effects Elicited by Novel Oligosaccharide Variants of Detoxified Meningococcal Lipopolysaccharides on Neisseria meningitidis Recombinant PorA Protein: A Comparison in Mice

PubMed Central

Mehta, Ojas H.; Norheim, Gunnstein; Hoe, J . Claire; Rollier, Christine S.; Nagaputra, Jerry C.; Makepeace, Katherine; Saleem, Muhammad; Chan, Hannah; Ferguson, David J. P.; Jones, Claire; Sadarangani, Manish; Hood, Derek W.; Feavers, Ian; Derrick, Jeremy P.; Pollard, Andrew J.; Moxon, E . Richard

2014-01-01

Neisseria meningitidis lipopolysaccharide (LPS) has adjuvant properties that can be exploited to assist vaccine immunogenicity. The modified penta-acylated LPS retains the adjuvant properties of hexa-acylated LPS but has a reduced toxicity profile. In this study we investigated whether two modified glycoform structures (LgtE and IcsB) of detoxified penta-acylated LPS exhibited differential adjuvant properties when formulated as native outer membrane vesicles (nOMVs) as compared to the previously described LgtB variant. Detoxified penta-acylated LPS was obtained by disruption of the lpxL1 gene (LpxL1 LPS), and three different glycoforms were obtained by disruption of the lgtB, lgtE or icsB genes respectively. Mice (mus musculus) were immunized with a recombinant PorA P1.7-2,4 (rPorA) protein co-administered with different nOMVs (containing a different PorA serosubtype P1.7,16), each of which expressed one of the three penta-acylated LPS glycoforms. All nOMVs induced IgG responses against the rPorA, but the nOMVs containing the penta-acylated LgtB-LpxL1 LPS glycoform induced significantly greater bactericidal activity compared to the other nOMVs or when the adjuvant was Alhydrogel. Compared to LgtE or IcsB LPS glycoforms, these data support the use of nOMVs containing detoxified, modified LgtB-LpxL1 LPS as a potential adjuvant for future meningococcal protein vaccines. PMID:25545241

Global Microlending in Education Reform: Enseñá Por Argentina and the Neoliberalization of the Grassroots

ERIC Educational Resources Information Center

Friedrich, Daniel S.

2010-01-01

This article examines the workings and underlying assumptions behind Enseñá por Argentina (Teach for Argentina), one specific program that takes part in the larger and expanding network of Teach for All, by thinking about the ways in which a global push for redefining teaching and teacher education encounters local characteristics and histories,…

Concepciones y concepciones alternativas de estudiantes universitarios/as de biologia y futuros maestros/as de Ciencia de escuela secundaria sobre la teoria de evolucion biologica por seleccion natural

NASA Astrophysics Data System (ADS)

Morales Ramos, Egda M.

La teoria de evolucion biologica (TEB) por seleccion natural es uno de los conceptos unificadores mas importantes del curriculo de Biologia. En Puerto Rico se han hecho pocas investigaciones que abunden sobre las concepciones y concepciones alternativas (CA) que tienen los estudiantes universitarios/as de Biologia y los maestros/as de Ciencia del nivel secundario sobre esta teoria. La politica publica educativa actual establece mediante documentos normativos como los Estandares de contenido y Expectativas de grado del Programa de Ciencias [Puerto Rico Core Standards] la ensenanza de esta teoria. Sin embargo, no se encontraron preguntas sobre la seleccion natural en los ejercicios de practica provistos por el Departamento de Educacion para las pruebas estandarizadas lo cual puede influir para que no se ensene adecuadamente. Las preguntas de investigacion fueron 1. ¿Cuales son las concepciones y concepciones alternativas de estudiantes universitarios/as y de los futuros maestros y maestras de Ciencia sobre la TEB? 2. ¿Cuales conceptos que seleccionan los estudiantes universitarios/as y los futuros maestros y maestras de Ciencia sobre la TEB coinciden con lo aceptado como valido por la comunidad cientifica? y 3. ¿Como comparan las respuestas de la prueba original. v. Entendiendo el cambio biologico que mide concepciones y CA sobre la TEB por seleccion natural, con las de la traducida al idioma espanol? Se utilizo el metodo cuantitativo con un diseno de investigacion transversal por encuesta. La tecnica principal para recopilar los datos fue una prueba con doce items, que formo parte de un instrumento para el cual se recopilaron diversas fuentes de evidencia acerca de su validez. Las muestras estuvieron formadas por 69 estudiantes de Ciencias Naturales y por 16 estudiantes futuros maestros y maestras del nivel secundario de la UPR-RP. Se utilizaron estadisticas descriptivas, analisis de Ji cuadrado y se calcularon los coeficientes alfa de Cronbach y de Spearman

Flow-injection chemiluminescence method to detect a β2 adrenergic agonist.

PubMed

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.

Permanent effects of postnatal administration of beta-adrenergic ligands on the volume of sexually dimorphic nucleus of the preoptic area (SDN-POA) in rats.

PubMed

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

WITHDRAWN: Symptomatic treatment of the cough in whooping cough.

PubMed

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

Pincharse sin infectarse: estrategias para prevenir la infección por el VIH y el VHC entre usuarios de drogas inyectables

PubMed Central

MATEU-GELABERT, P.; FRIEDMAN, S.; SANDOVAL, M.

2011-01-01

Resumen Objetivo Desde principios de los noventa, en la ciudad de Nueva York se han implementado con éxito programas para reducir la incidencia del virus de la inmunodeficiencia humana (VIH) y, en menor medida, del virus de la hepatitis C (VHC). A pesar de ello, aproximadamente el 70% de los usuario de drogas inyectables (UDI) están infectados por el VHC. Queremos investigar cómo el 30% restante se las ha arreglado para no infectarse. El Staying safe (nombre original del estudio) explora los comportamientos y mecanismos que ayudan a evitar la infección por el VHC y el VIH a largo plazo. Material y métodos Hemos utilizado el concepto de «desviación positiva» aplicado en otros campos de salud pública. Estudiamos las estrategias, prácticas y tácticas de prevención de aquellos UDI que, viviendo en contextos de alta prevalencia, se mantienen sin infectar por VIH y el VHC, a pesar de haberse inyectado heroína durante años. Los resultados preliminares presentados en este artículo incluyen el análisis de las entrevistas realizadas a 25 UDI (17 doble negativos, 3 doble positivos y 5 con infección por el VHC y sin infección por el VIH). Se usaron entrevistas semiestructuradas que exploraban con detalle la historia de vida de los sujetos, incluyendo su consumo de drogas, redes sociales, contacto con instituciones, relaciones sexuales y estrategias de protección y vigilancia. Resultados La intencionalidad es importante para no infectarse, especialmente durante períodos de involución (períodos donde hay un deterioro económico y/o social que llevan al que se inyecta a situaciones de mayor riesgo). Presentamos tres dimensiones independientes de intencionalidad que conllevan comportamientos que pueden ayudar a prevenir la infección: a) evitar «el mono» (síntomas de abstención) asegurando el acceso a la droga; b) «llevarlo bien» para no convertirse en un junkie y así evitar la «muerte social» y la falta de acceso a los recursos, y c) seguir sin

Honey for acute cough in children.

PubMed

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

Acceptance test report for portable exhauster POR-007/Skid E

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kriskovich, J.R.

1998-07-24

This document describes Acceptance Testing performed on Portable Exhauster POR-007/Skid E. It includes measurements of bearing vibration levels, pressure decay testing, programmable logic controller interlocks, high vacuum, flow and pressure control functional testing. The purpose of Acceptance testing documented by this report was to demonstrate compliance of the exhausters with the performance criteria established within HNF-0490, Rev. 1 following a repair and upgrade effort at Hanford. In addition, data obtained during this testing is required for the resolution of outstanding Non-conformance Reports (NCR), and finally, to demonstrate the functionality of the associated software for the pressure control and high vacuummore » exhauster operating modes provided for by W-320. Additional testing not required by the ATP was also performed to assist in the disposition and close out of receiving inspection report and for application design information (system curve). Results of this testing are also captured within this document.« less

Study of the interaction mechanisms between absorbed NO{sub 2} and por-Si/SnO{sub x} nanocomposite layers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bolotov, V. V.; Kan, V. E., E-mail: kan@obisp.oscsbras.ru; Makushenko, R. K.

2013-10-15

The interaction mechanisms between NO{sub 2} molecules and the surface of por-Si/SnO{sub x} nanocomposites obtained by magnetron deposition and chemical vapor deposition (CVD) are studied by infrared absorption spectroscopy and electron paramagnetic resonance methods. The observed increase in the free carrier concentration in the por-Si/SnO{sub x} nanocomposite layers is explained by a change in the charge state of P{sub b} centers due to the formation of neutral 'surface defect-adsorbed NO{sub 2} molecule' complexes with free carrier generation in the crystallite bulk. In the nanocomposite layers grown by the CVD method, the increase in the free hole concentration during NO{sub 2}more » adsorption is much less pronounced in comparison with the composite grown by magnetron deposition, which is caused by the competing interaction channel of NO{sub 2} molecules with electrically neutral P{sub b} centers.« less

Btk Inhibitor RN983 Delivered by Dry Powder Nose-only Aerosol Inhalation Inhibits Bronchoconstriction and Pulmonary Inflammation in the Ovalbumin Allergic Mouse Model of Asthma.

PubMed

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.

Evaluation of a wildfire smoke forecasting system as a tool for public health protection.

PubMed

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.

Randomised controlled crossover trial of the effect on PtCO2 of oxygen-driven versus air-driven nebulisers in severe chronic obstructive pulmonary disease.

PubMed

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).

Comparison of capnovolumetry-derived dead space parameters with pulmonary function test in normal adults using histamine provocation.

PubMed

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.

Acceptance test report for portable exhauster POR-008/Skid F

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kriskovich, J.R.

1998-07-24

Portable Exhauster POR-008 was procured via HNF-0490, Specification for a Portable Exhausted System for Waste Tank Ventilation. Prior to taking ownership, acceptance testing was performed at the vendors. However at the conclusion of testing a number of issues remained that required resolution before the exhausters could be used by Project W-320. The purpose of acceptance testing documented by this report was to demonstrate compliance of the exhausters with the performance criteria established within HNF-O49O, Rev. 1 following a repair and upgrade effort at Hanford. In addition, data obtained during this testing is required for the resolution of outstanding Non-conformance Reportsmore » (NCR), and finally, to demonstrate the functionality of the associated software for the pressure control and high vacuum exhauster operating modes provided for by W-320. Additional testing not required by the ATP was also performed to assist in the disposition and close out of receiving inspection report and for application design information (system curve). Results of this testing are also captured within this document.« less

Análise dos Conceitos Astronômicos Apresentados por Professores de Algumas Escolas Estaduais Brasileiras

NASA Astrophysics Data System (ADS)

Voelzke, Marcos Rincon; Gonzaga, Edson Pereira

2011-12-01

A razão para o desenvolvimento deste trabalho baseia-se no fato de que muitos professores da Educação Básica (EB) não lidam com conceitos relacionados à astronomia, e quando o fazem eles simplesmente seguem livros didáticos que podem conter erros conceituais. Como é de conhecimento geral a astronomia é um dos conteúdos a serem ensinados na EB fazendo parte dos Parâmetros Curriculares Nacionais e das Propostas Curriculares do Estado de São Paulo, mas é um fato, que vários pesquisadores apontam, a existência de muitos problemas no ensino da astronomia. Com o propósito de minimizar algumas dessas deficiências foi realizado um trabalho de pesquisa com a utilização de questionários pré e pós pesquisa, para tanto foi desenvolvido um Curso de Extensão Universitária para professores da Diretoria de Ensino Regional (DE) que abrange Mauá, Ribeirão Pires e Rio Grande da Serra (no Estado de São Paulo) com os seguintes objetivos: levantar concepções alternativas; subsidiar os professores por meio de palestras, debates e workshops, e verificar o sucesso da aprendizagem após o curso, adotando-se como referência, para a análise dos resultados, os dicionários de Língua Portuguesa (FERREIRA, 2004) e Enciclopédico de Astronomia e Astronáutica (MOURĀO, 1995). Portanto, dezesseis questões foram aplicadas antes e após o curso, assim pode-se verificar após a pesquisa que 100,0% dos professores sabiam os nomes das fases da Lua, 97,0% entenderam que o Sistema Solar é composto por oito planetas, 78,1% foram capazes de explicar como ocorre um eclipse lunar, um eclipse solar e um solstício, 72,7% sabiam como explicar a ocorrência das estações do ano; 64,5% explicaram corretamente a ocorrência do equinócio, 89,7% foram capazes de definir adequadamente o termo cometa; 63,6% definiram asteróide, 54,5% meteoro, 58,1% galáxia, e 42,4% planeta. Os resultados obtidos indicam uma aprendizagem significativa por parte dos participantes.

Using the PORS Problems to Examine Evolutionary Optimization of Multiscale Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reinhart, Zachary; Molian, Vaelan; Bryden, Kenneth

2013-01-01

Nearly all systems of practical interest are composed of parts assembled across multiple scales. For example, an agrodynamic system is composed of flora and fauna on one scale; soil types, slope, and water runoff on another scale; and management practice and yield on another scale. Or consider an advanced coal-fired power plant: combustion and pollutant formation occurs on one scale, the plant components on another scale, and the overall performance of the power system is measured on another. In spite of this, there are few practical tools for the optimization of multiscale systems. This paper examines multiscale optimization of systemsmore » composed of discrete elements using the plus-one-recall-store (PORS) problem as a test case or study problem for multiscale systems. From this study, it is found that by recognizing the constraints and patterns present in discrete multiscale systems, the solution time can be significantly reduced and much more complex problems can be optimized.« less

Adult Student Retention and Achievement with Language-Based Modular Materials. POR FIN: Program Organizing Related Family Instruction in the Neighborhood.

ERIC Educational Resources Information Center

Bexar County School Board, San Antonio, TX.

The goal of the POR FIN research design was to develop a language-based curriculum emphasizing the audiolingual approach and integrating academic and social-functioning subject matter. The modular curriculum is designed so that each lesson is independent and complete in itself, and provides a high degree of motivation, retention, and achievement…

Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds

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

The availability, pricing and affordability of three essential asthma medicines in 52 low- and middle-income countries.

PubMed

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

Proliferation of the human urothelium is induced by atypical β1 -adrenoceptors.

PubMed

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.

Effects of vasoactive intestinal peptide, helodermin and galanin on responses of guinea-pig lung parenchyma to histamine, acetylcholine and leukotriene D4.

PubMed Central

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

Budesonide reduces hospital admission rates in preschool children with acute wheezing.

PubMed

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.

Btk Inhibitor RN983 Delivered by Dry Powder Nose-only Aerosol Inhalation Inhibits Bronchoconstriction and Pulmonary Inflammation in the Ovalbumin Allergic Mouse Model of Asthma

PubMed Central

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

Characterisation by multilocus sequence and porA and flaA typing of Campylobacter jejuni isolated from samples of dog faeces collected in one city in New Zealand.

PubMed

Mohan, V; Stevenson, M A; Marshall, J C; French, N P

2017-07-01

To investigate the prevalence of Campylobacter spp. and C. jejuni in dog faecal material collected from dog walkways in the city of Palmerston North, New Zealand, and to characterise the C. jejuni isolates by multilocus sequence typing (MLST) and porA and flaA antigen gene typing. A total of 355 fresh samples of dogs faeces were collected from bins provided for the disposal of dog faeces in 10 walkways in Palmerston North, New Zealand, between August 2008-July 2009. Presumptive Campylobacter colonies, cultured on modified charcoal cefoperazone deoxycholate plates, were screened for genus Campylobacter and C. jejuni by PCR. The C. jejuni isolates were subsequently characterised by MLST and porA and flaA typing, and C. jejuni sequence types (ST) were assigned. Of the 355 samples collected, 72 (20 (95% CI=16-25)%) were positive for Campylobacter spp. and 22 (6 (95% CI=4-9)%) were positive for C. jejuni. Of the 22 C. jejuni isolates, 19 were fully typed by MLST. Ten isolates were assigned to the clonal complex ST-45 and three to ST-52. The allelic combinations of ST-45/flaA 21/porA 44 (n=3), ST-45/flaA 22/porA 53 (n=3) and ST-52/ flaA 57/porA 905 (n=3) were most frequent. The successful isolation of C. jejuni from canine faecal samples collected from faecal bins provides evidence that Campylobacter spp. may survive outside the host for at least several hours despite requiring fastidious growth conditions in culture. The results show that dogs carry C. jejuni genotypes (ST-45, ST-50, ST-52 and ST-696) that have been reported in human clinical cases. Although these results do not provide any evidence either for the direction of infection or for dogs being a potential risk factor for human campylobacteriosis, dog owners are advised to practice good hygiene with respect to their pets to reduce potential exposure to infection.

One-Pot Synthesis of N-Substituted β-Amino Alcohols from Aldehydes and Isocyanides.

PubMed

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.

El proceso hacia la integracion de la equidad por genero al curriculo.(The Process of the Integration of Gender Equity in the Curriculum.)

ERIC Educational Resources Information Center

Rivera-Bermudez, Carmen D.

"El Proyecto Colaborativo de Equidad por Genero en la Educacion," or the Collaborative Project for Gender Equity in Education, was undertaken in Puerto Rico between 1990 and 1992 to study how to facilitate the integration of gender equity themes in the curriculum through the direct action of participating teachers. A study examined the…

Protection by meningococcal outer membrane protein PorA-specific antibodies and a serogroup B capsular polysaccharide-specific antibody in complement-sufficient and C6-deficient infant rats.

PubMed

Toropainen, Maija; Saarinen, Leena; Vidarsson, Gestur; Käyhty, Helena

2006-05-01

The relative contributions of antibody-induced complement-mediated bacterial lysis and antibody/complement-mediated phagocytosis to host immunity against meningococcal infections are currently unclear. Further, the in vivo effector functions of antibodies may vary depending on their specificity and Fc heavy-chain isotype. In this study, a mouse immunoglobulin G2a (mIgG2a) monoclonal antibody (MN12H2) to meningococcal outer membrane protein PorA (P1.16), its human IgG subclass derivatives (hIgG1 to hIgG4), and an mIgG2a monoclonal antibody (Nmb735) to serogroup B capsular polysaccharide (B-PS) were evaluated for passive protection against meningococcal serogroup B strain 44/76-SL (B:15:P1.7,16) in an infant rat infection model. Complement component C6-deficient (PVG/c-) rats were used to assess the importance of complement-mediated bacterial lysis for protection. The PorA-specific parental mIgG2a and the hIgG1 to hIgG3 derivatives all induced efficient bactericidal activity in vitro in the presence of human or infant rat complement and augmented bacterial clearance in complement-sufficient HsdBrlHan:WIST rats, while the hIgG4 was unable to do so. In C6-deficient PVG/c- rats, lacking complement-mediated bacterial lysis, the augmentation of bacterial clearance by PorA-specific mIgG2a and hIgG1 antibodies was impaired compared to that in the syngeneic complement-sufficient PVG/c+ rat strain. This was in contrast to the case for B-PS-specific mIgG2a, which conferred similar protective activity in both rat strains. These data suggest that while anti-B-PS antibody can provide protection in the infant rats without membrane attack complex formation, the protection afforded by anti-PorA antibody is more dependent on the activation of the whole complement pathway and subsequent bacterial lysis.

Effects of several potassium channel openers and glibenclamide on the uterus of the rat.

PubMed Central

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

Na+,K+-pump stimulation improves contractility in isolated muscles of mice with hyperkalemic periodic paralysis

PubMed Central

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

Evaluation of a Wildfire Smoke Forecasting System as a Tool for Public Health Protection

PubMed Central

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

β-adrenergic Receptor Blocker ICI 118,551 Selectively Increases Intermediate-Conductance Calcium-Activated Potassium Channel (IKCa )-Mediated Relaxations in Rat Main Mesenteric Artery.

PubMed

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

Physical stability of highly concentrated injectable drugs solutions used in intensive care units.

PubMed

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

Variability in delivered dose and respirable delivered dose from nebulizers: are current regulatory testing guidelines sufficient to produce meaningful information?

PubMed

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.

Aerosol Delivery Using Jet Nebulizer and Vibrating Mesh Nebulizer During High Frequency Oscillatory Ventilation: An In Vitro Comparison.

PubMed

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.

Beta 2 adrenergic receptor gene restriction fragment length polymorphism and bronchial asthma.

PubMed Central

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

Determination of the bioavailability of selected pharmaceutical residues in fish plasma using liquid chromatography coupled to tandem mass spectrometry.

PubMed

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 �

Seguridad del paciente en Radioterapia Intraoperatoria: Impacto de los elementos controlados por el Radiofisico

NASA Astrophysics Data System (ADS)

Tarjuelo, Juan Lopez

Introduccion: En la administracion de la radioterapia intervienen profesionales y equipos de tratamiento, por lo que existe el riesgo de error y se precisa que dicho equipamiento funcione conforme a lo esperado. A los radiofisicos les corresponde participar en las actividades de garantia o aseguramiento de la calidad, incluyendo el control de calidad de los equipos, y en la evaluacion de los riesgos asociados. La radioterapia intraoperatoria (RIO) es una tecnica radioterapica de intensificacion de dosis, altamente selectiva, dirigida a volumenes anatomicos restringidos durante el tratamiento quirurgico oncologico, basada en la administracion de una dosis absorbida alta por medio de un haz de electrones tras el examen visual directo del lecho tumoral. Como incorporar los ultimos avances en el refuerzo de la seguridad en radioterapia es una tarea ambiciosa y compleja, resulta mas concreta y de inmediata aplicacion su introduccion en la RIO. El objetivo es analizar los elementos que reducen los riesgos y aumentan la seguridad en la RIO y su dosimetria, y valorar la funcion del radiofisico en esta labor. Material y metodos: Se emplearon el planificador Radiance de GMV y el acelerador lineal de los tratamientos de RIO Elekta Precise, controlado con el verificador diario de haces Daily QA Check 1090 y medido con las camaras de ionizacion PPC 40, FC65-G y FC65-P de PTW-Freiburg, a su vez verificadas con fuentes radiactivas adecuadas de estroncio-90 modelos CDP y CDC de IBA Dosimetry. Se realizo un analisis de modos de fallo y efectos (failure mode and effect analysis, FMEA) con el fin de identificar los elementos que forman la RIO y aplicar las herramientas necesarias para la minimizacion de los riesgos y la mejora de la seguridad en la tecnica. Se estudiaron las verificaciones diarias de dicho acelerador Precise con el control estadistico de procesos (statistical process control, SPC) y se simularon intervenciones para devolverlo al estado llamado en control. El SPC

Fabrication of por-Si/SnO{sub x} nanocomposite layers for gas microsensors and nanosensors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bolotov, V. V., E-mail: bolotov@obisp.oscsbras.ru; Korusenko, P. M.; Nesov, S. N.

2011-05-15

Two-phase nanocomposite layers based on porous silicon and nonstoichiometric tin oxide were fabricated by various methods. The structure, as well as elemental and phase composition, of the obtained nanocomposites were studied using transmission and scanning electron microscopy, Raman spectroscopy, Auger electron spectroscopy, and X-ray photoelectron spectroscopy. The results obtained confirm the formation of nanocomposite layers with a thickness as large as 2 {mu}m thick and SnO{sub x} stoichiometry coefficients x = 1.0-2.0. Significant tin diffusion into the porous silicon matrix with D{sub eff} Almost-Equal-To 10{sup -14} cm{sup 2} s{sup -1} was observed upon annealing at 770 K. Test sensor structuresmore » based on por-Si/SnO{sub x} nanocomposite layers grown by magnetron deposition showed fairly high stability of properties and sensitivity to NO{sub 2}.« less

Being a mother and a por día domestic worker. Companionship and deprivation.

PubMed

Bernal, P; Meleis, A I

1995-08-01

This article presents qualitative findings concerning women's maternal roles, based on interviews conducted in a study on role integration and health, in a Colombian sample of 60 women who are "por día" domestic workers. The results describe the women's worldview as they discuss the stresses and the satisfactions of their mothering roles. The results also include the coping strategies used to deal with the stresses inherent in the maternal role. Women describe how the companionship of their children, watching their children grow, and the nurturing they give their children provides them with pride and deep satisfaction. These satisfying aspects of their role are burdened by the stress related to worry about children's bad behavior, their illness, and a pervasive generalized sense of constant worry. Being single parents adds more stress to these women's lives. Participants coped emotionally through distraction and through talking with friends. Other coping strategies included calming self, problem solving, talking with children, and substance use. The authors conclude with a discussion of the relationship between poverty and work situation as contexts for understanding maternal roles.

Nosema ceranae Winter Control: Study of the Effectiveness of Different Fumagillin Treatments and Consequences on the Strength of Honey Bee (Hymenoptera: Apidae) Colonies.

PubMed

Mendoza, Y; Diaz-Cetti, S; Ramallo, G; Santos, E; Porrini, M; Invernizzi, C

2017-02-01

ón y muchos emplean el antibiótico fumagilina para reducir el nivel de infección. El objetivo de este estudio fue comparar la eficacia de cuatro tratamientos diferentes con fumagilina y determinar cómo incide en la fortaleza de las colonias durante la invernada. Las colonias tratadas con fumagilina en julio presentaron una menor carga de esporas al terminar las aplicaciones, siendo los tratamientos más eficaces el de 4 aplicaciones mediante asperjado sobre las abejas de 30 mg de fumagilina en 100 ml de jarabe de azúcar 1:1, y el de 4 aplicaciones de 90 mg de fumagilina en 250 ml de jarabe de azúcar 1:1 utilizando un alimentador. Sin embargo, durante el período de experimentación, las colonias tratadas con antibiótico presentaron igual tamaño que las colonias no tratadas. En setiembre, las colonias tratadas y no tratadas con fumagilina no se diferenciaron en la intensidad de infección ni en su tamaño. En las condiciones en que se realizó el estudio, la aplicación de fumagilina disminuyó temporalmente la carga de esporas de N. ceranae pero esto no se reflejó en el tamaño de las colonias ni en la probabilidad de sobrevivir el invierno. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Swelling, erosion and drug release characteristics of salbutamol sulfate from hydroxypropyl methylcellulose-based matrix tablets.

PubMed

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.

Bronchodilators for the prevention and treatment of chronic lung disease in preterm infants.

PubMed

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

MAGNEsium Trial In Children (MAGNETIC): a randomised, placebo-controlled trial and economic evaluation of nebulised magnesium sulphate in acute severe asthma in children.

PubMed

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

Metabolic responses to BRL37344 and clenbuterol in soleus muscle and C2C12 cells via different atypical pharmacologies and β2-adrenoceptor mechanisms

PubMed Central

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

Maternal drug use and the risk of anorectal malformations: systematic review and meta-analysis.

PubMed

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

Risk factors of bronchial hyperresponsiveness in children with wheezing-associated respiratory infection.

PubMed

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

Aquisição fonológica do português brasileiro por crianças ouvintes bilíngues bimodais e surdas usuárias de implante coclear

PubMed Central

Cruz, Carina Rebello; Finger, Ingrid

2014-01-01

Resumo O presente estudo investiga a aquisição fonológica do Português Brasileiro (PB) por 24 crianças ouvintes bilíngues bimodais, com acesso irrestrito à Língua Brasileira de Sinais (Libras), e por 6 crianças surdas que utilizam implante coclear (IC), com acesso restrito ou irrestrito à Libras. Para a avaliação do sistema fonológico das crianças em PB, foi utilizada a Parte A, Prova de Nomeação, do ABFW – Teste de Linguagem Infantil (ANDRADE et al. 2004). Os resultados revelaram que as crianças ouvintes bilíngues bimodais e a criança surda usuária de IC com acesso irrestrito à Libras apresentaram processo de aquisição fonológica esperada (normal) para a sua faixa etária. Considera-se que a aquisição precoce e o acesso irrestrito à Libras podem ter sido determinantes para o desempenho dessas crianças no teste oral utilizado. PMID:25506105

The effects of drugs, other foreign compounds, and cigarette smoke on the synthesis of protein by lung slices

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

Highly stable aluminum-based metal-organic frameworks as biosensing platforms for assessment of food safety.

PubMed

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.

Nanospray mass spectrometry with indirect conductive graphite coating.

PubMed

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.

Analysis of antigen-induced changes in pulmonary mechanics in sensitized inbred rats.

PubMed

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.

Inhibition of artificially induced cough in man by bronchodilators.

PubMed Central

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

A brief history of inhaled asthma therapy over the last fifty years.

PubMed

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.

Resorcinol-, catechol- and saligenin-based bronchodilating β2-agonists as inhibitors of human cholinesterase activity.

PubMed

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.

Patterns of pregnancy exposure to prescription FDA C, D and X drugs in a Canadian population.

PubMed

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.

Use of complementary therapy by adolescents with asthma.

PubMed

Reznik, Marina; Ozuah, Philip O; Franco, Karen; Cohen, Robyn; Motlow, Ferrell

2002-10-01

About 40% of adult Americans use complementary or alternative medicine (CAM) for health problems. To determine the prevalence of reported use of CAM in a population of urban adolescents with asthma. We used a multistaged, stratified sample approach at an inner-city high school. An asthma screening survey was administered to 3800 registered students, aged 13 to 18 years. We identified a subset of 200 respondents who answered yes to each of the following questions: (1) Does your physician think that you have asthma? (2) Do your parents think that you have asthma? (3) Do you think that you have asthma? A self-completion questionnaire was administered to a sample drawn from this cohort. Differences in proportion were tested by chi( 2) analyses. Of the 160 participants, 63% were female, 68% were Hispanic, 26% were African American, 33% had weekly symptoms, and 14% had daily symptoms. Overall, 80% of participants reported using CAM for asthma. The most commonly reported CAM included rubs (74%), herbal teas (39%), prayer (37%), massage (36%), and Jarabe 7 syrup (24%). Subjects with daily or weekly symptoms were more likely to use CAM for each episode of asthma (72% vs 51%; P =.005). The 61% of subjects who had a family member who used CAM were more likely to use CAM again (84% vs 39%; P<.001). Of the respondents, 59% reported that CAM was effective. Subjects who perceived CAM to be effective were more likely to use it again (96% vs 22%; P<.001). Most adolescents with asthma in this study used CAM. The prevalence of CAM use in this study population was twice the national average for adults.

Pruritus Treatment in Viewpoints of Traditional Persian Medicine.

PubMed

Jazani, Arezoo Moini; Azgomi, Ramin Nasimi Doost; Shirbeigi, Leila

2016-05-01

Pruritus is an unpleasant feeling that can cause the desire of scratching in a person and can be the symptoms of systemic, infectious, and neurological diseases. Pruritus is the most common clinical manifestation of skin diseases. Pruritus prevalence is 8-38% in the general population. Causes and treatments of pruritus have been described by traditional Persian medicine scientists. The aim of this study was to derive general principles of the proposed treatment to reduce or relieve pruritus. This descriptive study, review traditional medicine books including Al canon fil tibb, Al-Hawi, Makhzan ul-adviyyah, Al-Abniyah an-Haghyegh el-adviyah, Tuhfat ul-Momineen and Exir-e-Azam. The above-mentioned documents were derived and classified by keywords such as pruritus, hakka, jarab and sherry. In traditional Persian medicine, there are different causes for pruritus such as accumulation of vapors or acute humors in subcutaneous tissue or weakness of expulsive (Dafi'a) faculty and its treatment is based on removing the causes. Proper nutrition, bathing, and removing pathogenic humors are involved in the treatment. According to this study, some plants such as Cassia fistula, Purslane, Violets, Fumaria, Barley, Coriander, Rose and Terminalia chebula are anti-itching. Proper nutrition is the most important point in health and treatment of humors production with appropriate quality and quantity. Pruritus can be treated by lifestyle modification and using medicinal plants. It could be concluded that traditional Persian medicine therapies can be effective in the treatment of pruritus with mild side effects. By further investigation and research, we can reach more effective treatment methods in the field of traditional Persian medicine along with other new medical therapies.

Prevalencia y factores de riesgo para infecciones del tracto urinario de inicio en la comunidad causadas por Escherichia coli productor de betalactamasas de espectro extendido en Colombia

PubMed Central

Blanco, Victor M.; Maya, Juan J.; Correa, Adriana; Perenguez, Marcela; Muñoz, Juan S.; Motoa, Gabriel; Pallares, Christian J.; Rosso, Fernando; Matta, Lorena; Celis, Yamile; Garzon, Martha; Villegas, y María V.

2016-01-01

RESUMEN Introducción Las infecciones del tracto urinario (ITU) son frecuentes en la comunidad. Sin embargo, la información de aislamientos resistentes en este contexto es limitada en Latinoamérica. Este estudio tiene como objetivo determinar la prevalencia y los factores de riesgo asociados con ITU de inicio en la comunidad (ITU-IC) causadas por Escherichia coli productor de betalactamasas de espectro extendido (BLEE) en Colombia. Materiales y métodos Entre agosto y diciembre de 2011 se realizó un estudio de casos y controles en 3 instituciones de salud de tercer nivel en Colombia. Se invitó a participar a todos los pacientes admitidos a urgencias con diagnóstico probable de ITU-IC, y se les pidió una muestra de orina. En los aislamien-tos de E. coli se realizaron pruebas confirmatorias para BLEE, susceptibilidad antibiótica, caracterización molecular (PCR en tiempo real para genes bla, repetitive element palindromic PCR [rep-PCR], multilocus sequence typing [MLST] y factores de virulencia por PCR). Se obtuvo información clínica y epidemiológica, y posteriormente se realizó el análisis estadístico. Resultados De los 2.124 pacientes seleccionados, 629 tuvieron un urocultivo positivo, en 431 de estos se aisló E. coli, 54 fueron positivos para BLEE y 29 correspondieron a CTX-M-15. La mayoría de los aislamientos de E. coli productor de BLEE fueron sensibles a ertapenem, fosfomicina y amikacina. La ITU complicada se asoció fuertemente con infecciones por E. coli productor de BLEE (OR = 3,89; IC 95%: 1,10–13,89; p = 0,03). E. coli productor de CTX-M-15 mostró 10 electroferotipos diferentes; de estos, el 65% correspondieron al ST131. La mayoría de estos aislamientos tuvieron 8 de los 9 factores de virulencia analizados. Discusión E. coli portador del gen blaCTX-M-15 asociado al ST131 sigue siendo frecuente en Colombia. La presencia de ITU-IC complicada aumenta el riesgo de tener E. coli productor de BLEE, lo cual debe tenerse en cuenta para ofrecer

La inserción en el mercado laboral de los inmigrantes latinos en España y en los Estados Unidos: Diferencias por país de origen y estatus legal

PubMed Central

Connor, Phillip; Massey, Douglas

2013-01-01

Resumen Este artículo compara los resultados económicos entre los inmigrantes latinoamericanos en España y Estados Unidos. Detectamos un efecto de selección por el que la mayoría de los inmigrantes latinoamericanos en España proceden de Sudamérica de un entorno de clases medias, mientras la mayoría de los inmigrantes que van a los Estados Unidos son centroamericanos de clase baja. Este efecto de selección explica las diferencias transnacionales en la probabilidad de empleo, logro ocupacional y salarios obtenidos. A pesar de las diferencias en los orígenes y las características de los latinoamericanos en ambos países, los factores demográficos, humanos y de capital social parecen operar de forma similar en ambos países; y cuando los modelos se estiman separadamente por estatus legal, descubrimos que los efectos se acentúan más entre los inmigrantes irregulares cuando se los compara con los regulares, especialmente en Estados Unidos. PMID:24532857

"Estudio tribologico de aceros para moldes. Aplicacion al moldeo por inyeccion de polibutilentereftalato reforzado con fibra de vidrio"

NASA Astrophysics Data System (ADS)

Martinez Mateo, Isidoro Jose

Mould materials for injection moulding of polymers and polymer-matrix composites represent a relevant industrial economic sector due to the large quantity of pieces and components processed. The material selection for mould manufacturing, its composition and heat treatment, the hardening procedures and machining and finishing processes determine the service performance and life of the mould. In the first part of the present study, the relationship between the hardness and microstructure and the wear resistance of mould steels from large blocks has been studied by pin-on-disc tests, studying the main wear mechanisms. In order to determine the surface damage on mould steels under real injection conditions, different commercial steels have been studied by measuring the variation of surface roughness with the number of injected pieces with different reinforcement percentages and different mould geometries, by using optical profilometry and scanning electron microscopy techniques. It was important to determine the variation of surface roughness of the moulded pieces with the number of injection operations. The materials used were polybutyleneterephthalate pure and reinforced with either 20% or 50% glass fibre. For the different mould designs, the evolution of the glass fibre orientation with injection flow has been determined by image analysis and related to roughness changes and surface damage, both of the composite parts and of the mould steel surface. Finally, the abrasion resistance of the composite parts has been studied by scratch tests as a function of the number of injected parts and of the scratch direction with respect to injection flow and glass fibre orientation. Los materiales para moldes de inyeccion de polimeros y materiales compuestos representan un sector economicamente muy relevante debido al gran aumento del numero de componentes fabricados a partir de materiales polimericos obtenidos mediante moldeo por inyeccion. La seleccion del material para la

Mujeres felices por ser saludables: a breast cancer risk reduction program for Latino women.

PubMed

Fitzgibbon, Marian L; Gapstur, Susan M; Knight, Sara J

2003-05-01

Breast cancer is the most commonly diagnosed cancer and the most common cause of cancer mortality among Latino women. Several behavioral factors such as early detection and dietary practices could help decrease morbidity and mortality associated with breast cancer in this population. Unfortunately, there are few data regarding the efficacy of health-related interventions for young Latino women. Mujeres Felices por ser Saludables is a randomized intervention project designed to assess breast cancer risk reduction behavior among Latino women ages 20-40 years. The primary objectives of the project were to determine whether an 8-month integrated dietary/breast health intervention could lead to a greater reduction in dietary fat, increase in dietary fiber, increase in the frequency and proficiency of breast self examination (BSE), and reduction in anxiety related to BSE compared to controls. Herein we describe the overall design of the project and present baseline characteristics of the 256 randomized women. Our results suggest that the average daily intake of dietary fat (percentage of total energy) was slightly below 30% (percentage of total energy) among the women randomized. While over half of these women reported that they practice BSE, and few reported anxiety related to BSE, less than 27% of women were proficient in the recommended BSE technique. There are few data on the dietary and breast health behaviors of young low-acculturated Latino women. This study documents the feasibility of recruiting, randomizing, and obtaining both baseline dietary and breast health data on this unique and underserved population.

Drug delivery to the human and mouse uterus using immunoliposomes targeted to the oxytocin receptor.

PubMed

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

Relación masa-radio para estrellas enanas blancas y la interpretación de recientes mediciones hechas por Hipparcos

NASA Astrophysics Data System (ADS)

Panei, J. A.; Althaus, L. G.; Benvenuto, O. G.

Recientes mediciones de la masa y el radio hechas por Hipparcos de las estrellas enanas blancas 40 Eri B y Procyon B (Shipman, H. & Provencal, J. - ApJ. 1998, 494, 759), sugieren un núcleo compuesto de hierro para dichas estrellas, en lugar de carbono y oxígeno como predice la teoría standard de evolución estelar. Para interpretar estas observaciones, presentamos aquí, relaciones masa-radio para configuraciones degeneradas a temperatura finita para distintas composiciones químicas centrales. Para tal fin hemos calculado secuencias evolutivas de enanas blancas utilizando el código de evolución estelar, desarrollado en el Observatorio de La Plata. Dicho código resuelve las ecuaciones de estructura y evolución estelar mediante la técnica de relajación de Henyey, y esta basado en una descripción física muy detallada y actualizada.

Relationship of CYP2D6, CYP3A, POR, and ABCB1 genotypes with galantamine plasma concentrations.

PubMed

Noetzli, Muriel; Guidi, Monia; Ebbing, Karsten; Eyer, Stephan; Zumbach, Serge; Giannakopoulos, Panteleimon; von Gunten, Armin; Csajka, Chantal; Eap, Chin B

2013-04-01

The frequently prescribed antidementia drug galantamine is extensively metabolized by the enzymes cytochrome P450 (CYP) 2D6 and CYP3A and is a substrate of the P-glycoprotein. We aimed to study the relationship between genetic variants influencing the activity of these enzymes and transporters with galantamine steady state plasma concentrations. In this naturalistic cross-sectional study, 27 older patients treated with galantamine were included. The patients were genotyped for common polymorphisms in CYP2D6, CYP3A4/5, POR, and ABCB1, and galantamine steady state plasma concentrations were determined. The CYP2D6 genotype seemed to be an important determinant of galantamine pharmacokinetics, with CYP2D6 poor metabolizers presenting 45% and 61% higher dose-adjusted galantamine plasma concentrations than heterozygous and homozygous CYP2D6 extensive metabolizers (median 2.9 versus 2.0 ng/mL · mg, P = 0.025, and 1.8 ng/mL · mg, P = 0.004), respectively. The CYP2D6 genotype significantly influenced galantamine plasma concentrations. The influence of CYP2D6 polymorphisms on the treatment efficacy and tolerability should be further investigated.

The Sangre Por Salud Biobank: Facilitating Genetic Research in an Underrepresented Latino Community.

PubMed

Shaibi, Gabriel; Singh, Davinder; De Filippis, Eleanna; Hernandez, Valentina; Rosenfeld, Bill; Otu, Essen; Montes de Oca, Gregorio; Levey, Sharon; Radecki Breitkopf, Carmen; Sharp, Richard; Olson, Janet; Cerhan, James; Thibodeau, Stephen; Winkler, Erin; Mandarino, Lawrence

2016-01-01

The Sangre Por Salud (Blood for Health; SPS) Biobank was created for the purpose of expanding precision medicine research to include underrepresented Latino patients. It is the result of a unique collaboration between Mayo Clinic and Mountain Park Health Center, a federally qualified community health center in Phoenix, Arizona. This report describes the rationale, development, implementation, and characteristics of the SPS Biobank. Latino adults (ages 18-85 years) who were active patients within Mountain Park Health Center's internal medicine practice in Phoenix, Ariz., and had no history of diabetes were eligible. Participants provided a personal and family history of chronic disease, completed a sociodemographic, psychosocial, and behavioral questionnaire, underwent a comprehensive cardiometabolic risk assessment (anthropometrics, blood pressure and labs), and provided blood samples for banking. Laboratory results of cardiometabolic testing were returned to the participants and their providers through the electronic health record. During the first 2 years of recruitment into the SPS Biobank, 2,335 patients were approached and 1,432 (61.3%) consented to participate; 1,354 (94.5%) ultimately completed all requisite questionnaires and medical evaluations. The cohort is primarily Spanish-speaking (72.9%), female (73.3%), with a mean age of 41.3 ± 12.5 years. Most participants were born outside of the US (77.9%) and do not have health insurance (77.5%). The prevalence of overweight (35.5%) and obesity (45.0%) was high, as was previously unidentified prediabetes (55.9%), type 2 diabetes (7.4%), prehypertension (46.8%), and hypertension (16.2%). The majority of participants rated their health as good to excellent (72.1%) and, as a whole, described their overall quality of life as high (7.9/10). Collaborative efforts such as the SPS Biobank are critical for ensuring that underrepresented minority populations are included in precision medicine initiatives and biomedical

The Sangre Por Salud Biobank: Facilitating Genetic Research in an Underrepresented Latino Community

PubMed Central

Shaibi, Gabriel; Singh, Davinder; De Filippis, Eleanna; Hernandez, Valentina; Rosenfeld, Bill; Otu, Essen; de Oca, Gregorio Montes; Levey, Sharon; Breitkopf, Carmen Radecki; Sharp, Richard; Olson, Janet; Cerhan, James; Thibodeau, Stephen; Winkler, Erin; Mandarino, Lawrence

2018-01-01

Background/Aims The Sangre Por Salud (Blood for Health; SPS) Biobank was created for the purpose of expanding precision medicine research to include underrepresented Latino patients. It is the result of a unique collaboration between Mayo Clinic and Mountain Park Health Center, a federally qualified community health center in Phoenix, Arizona. This report describes the rationale, development, implementation, and characteristics of the SPS Biobank. Methods Latino adults (ages 18–85 years) who were active patients within Mountain Park Health Center’s internal medicine practice in Phoenix, Ariz., and had no history of diabetes were eligible. Participants provided a personal and family history of chronic disease, completed a sociodemographic, psychosocial, and behavioral questionnaire, underwent a comprehensive cardiometabolic risk assessment (anthropometrics, blood pressure and labs), and provided blood samples for banking. Laboratory results of cardiometabolic testing were returned to the participants and their providers through the electronic health record. Results During the first 2 years of recruitment into the SPS Biobank, 2,335 patients were approached and 1,432 (61.3%) consented to participate; 1,354 (94.5%) ultimately completed all requisite questionnaires and medical evaluations. The cohort is primarily Spanish-speaking (72.9%), female (73.3%), with a mean age of 41.3 ± 12.5 years. Most participants were born outside of the US (77.9%) and do not have health insurance (77.5%). The prevalence of overweight (35.5%) and obesity (45.0%) was high, as was previously unidentified prediabetes (55.9%), type 2 diabetes (7.4%), prehypertension (46.8%), and hypertension (16.2%). The majority of participants rated their health as good to excellent (72.1%) and, as a whole, described their overall quality of life as high (7.9/10). Conclusion Collaborative efforts such as the SPS Biobank are critical for ensuring that underrepresented minority populations are included in

Rotifer neuropharmacology--III. Adrenergic drug effects on Brachionus plicatilis.

PubMed

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.

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

Simple semi-automated portable capillary electrophoresis instrument with contactless conductivity detection for the determination of β-agonists in pharmaceutical and pig-feed samples.

PubMed

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.

Fluorescence lifetime imaging of optically levitated aerosol: a technique to quantitatively map the viscosity of suspended aerosol particles.

PubMed

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.

A facile and efficient single-step approach for the fabrication of vancomycin functionalized polymer-based monolith as chiral stationary phase for nano-liquid chromatography.

PubMed

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.

Monitoring of PAEMs and beta-agonists in urine for a small group of experimental subjects and PAEs and beta-agonists in drinking water consumed by the same subjects.

PubMed

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.

Treatment of Cutaneous Lupus Erythematosus

PubMed Central

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

Astronomy in the Classroom: Why? (Spanish Title: Astronomía en la Clase: ¿Por Qué?) Astronomia na Sala de Aula: Por Quê?

NASA Astrophysics Data System (ADS)

Daros Gama, Leandro; Bagdonas Henrique, Alexandre

2010-07-01

There are many discussions about the relevance of the topics covered in classes. One subject in particular is the focus of this essay: astronomy. In what sense and to what extent it would be worth to teach it in science or other kind of classes? In this paper we discuss some aspects of the advantages of dealing with this area of knowledge in schools, taking into account the epistemological and axiological dimensions of astronomy, in light of the vision of science as an intelligent dialogue with the world (Bachelard), in addition to the "problematization" knowledge of Paulo Freire. We propose that in fact the Astronomy does not need to be seen as just a new set of contents to be taught, but appears as a set of motivational contents for historical-philosophical discussions, and permit the discussion of concepts of other disciplines. Numerosas discusiones se están llevando a cabo acerca de la pertinencia de los temas tradicionalmente tratados en las clases. Uno de los temas, en particular, es el foco de este ensayo: la astronomía. ¿En qué sentido y en qué medida sería conveniente tratarla en clase, ya sea en clases de ciencias naturales, específicamente en las de astronomía o asignaturas afines? Elaboramos en este artículo algunos aspectos de las ventajas de tratar esta área del conocimiento en las escuelas, teniendo en cuenta las dimensiones epistemológica y axiológica de la astronomía, a la luz de la visión de la ciencia como un diálogo inteligente con el mundo (Bachelard), además de la propuesta del conocimiento "problematizador" de Paulo Freire. Proponemos que en realidad la astronomía no tiene por qué ser vista sólo como un nuevo conjunto de contenidos que se enseñan, sino que aparece como un conjunto de temas de motivación para el debate histórico-filosófico y para permitir la discusión de los conceptos típicos de otras disciplinas. Muitas discussões vêm acontecendo sobre a relevância dos temas abordados em sala de aula. Um tema, em

Trayectoria de los tornillos pediculares lumbares y sacros: Comparación entre el abordaje por linea media versus el abordaje posterolateral tipo wiltse

PubMed Central

Gagliardi, Martín; Guiroy, Alfredo; Molina, Federico Fernández; Fasano, Francisco; Ciancio, Alejandro Morales; Mezzadri, Juan José; Jalón, Pablo

2017-01-01

Resumen Objetivos: El objetivo de este estudio fue comparar, en fusiones lumbosacras cortas, el ángulo de convergencia de los tornillos pediculares entre el abordaje posterolateral tipo Wiltse y el abordaje mediano convencional. Método: Se revisaron en forma retrospectiva los controles en tomografía axial computada (TAC) de 76 tornillos pediculares lumbares y sacros colocados por vía posterior, mediante un abordaje mediano convencional (n: 38) o por vía posterolateral transmuscular tipo Wiltse (n: 38). Se incluyeron fusiones lumbosacras cortas desde L3 a S1, en pacientes adultos, con patología degenerativa. Se excluyeron los tornillos con una brecha ósea >4 mm en cualquier dirección, los casos con instrumentaciones pediculares previas y aquellos con curvas en el plano coronal mayores de 20°. Resultados: Considerando la totalidad de los implantes, el ángulo de convergencia fue de 23,3° (+/- 15,82). La angulación promedio, en el grupo AW, fue de 29,3° (+/- 9,72). En el grupo AC, el grado de convergencia de los implantes fue de 17,2° (+/- 10,58). Esta diferencia fue estadísticamente significativa (P < 0,0001). Para el grupo AW, el grado de convergencia según nivel fue el siguiente: L3: 31,2° (+/- 1,9); L4: 31,4° (+/- 2,76); L5: 31,1° (+/- 5,62); S1: 24,2° (+/- 12,16). El promedio del ángulo del tornillo según nivel para el grupo AC fue: L3: 16° (+/- 7,16); L4: 20,3° (+/- 6,9) L5: 15,9° (+/- 13,38); S1: 15,2° (+/- 14,32). Los implantes del grupo AW tuvieron ángulos significativamente más convergentes que el grupo AC en todos los segmentos explorados. Conclusión: En las fusiones lumbosacras cortas, la utilización del abordaje tipo Wiltse permitió la colocación de tornillos pediculares con más convergencia que en el abordaje mediano convencional. La relevancia clínica de este hecho es desconocida y se requerirían trabajos prospectivos randomizados para determinar la misma. PMID:29142777

Estimaciones de Prevalencia del VIH por Género y Grupo de Riesgo en Tijuana, México: 2006

PubMed Central

Iñiguez-Stevens, Esmeralda; Brouwer, Kimberly C.; Hogg, Robert S.; Patterson, Thomas L.; Lozada, Remedios; Magis-Rodriguez, Carlos; Elder, John P.; Viani, Rolando M.; Strathdee, Steffanie A.

2010-01-01

OBJETIVO Estimar la prevalencia del VIH en adultos de 15-49 años de edad en Tijuana, México - en la población general y en subgrupos de riesgo en el 2006. METODOS Se obtuvieron datos demográficos del censo Mexicano del 2005, y la prevalencia del VIH se obtuvo de la literatura. Se construyó un modelo de prevalencia del VIH para la población general y de acuerdo al género. El análisis de sensibilidad consistió en estimar errores estándar del promedio-ponderado de la prevalencia del VIH y tomar derivados parciales con respecto a cada parámetro. RESULTADOS La prevalencia del VIH es 0.54%(N = 4,347) (Rango: 0.22%–0.86%, (N = 1,750–6,944)). Esto sugiere que 0.85%(Rango: 0.39%–1.31%) de los hombres y 0.22%(Rango: 0.04%–0.40%) de las mujeres podrían ser VIH-positivos. Los hombres que tienen sexo con hombres (HSH), las trabajadoras sexuales usuarias de drogas inyectables (MTS-UDI), MTS-noUDI, mujeres UDI, y los hombres UDI contribuyeron las proporciones más elevadas de personas infectadas por el VIH. CONCLUSIONES El número de adultos VIH-positivos entre subgrupos de riesgo en la población de Tijuana es considerable, marcando la necesidad de enforcar las intervenciones de prevención en sus necesidades específicas. El presente modelo estima que hasta 1 en cada 116 adultos podrían ser VIH-positivos. PMID:19685824

Oxygen as a driving gas for nebulisers: safe or dangerous?

PubMed

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.

Multi-residue screening of prioritised human pharmaceuticals, illicit drugs and bactericides in sediments and sludge.

PubMed

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.

Airway reactivity in chronic obstructive pulmonary disease. Failure of in vivo methacholine responsiveness to correlate with cholinergic, adrenergic, or nonadrenergic responses in vitro.

PubMed

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.

Adrenergic ligands that block oviposition in the cattle tick Rhipicephalus microplus affect ovary contraction

PubMed Central

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

Adrenergic ligands that block oviposition in the cattle tick Rhipicephalus microplus affect ovary contraction.

PubMed

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.

Notes on testing equality and interval estimation in Poisson frequency data under a three-treatment three-period crossover trial.

PubMed

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.

Hyperosmolar diabetic non-ketotic coma, hyperkalaemia and an unusual near death experience.

PubMed

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.

Predictors of bronchodilator responsiveness in infants with wheezing associated respiratory tract infection.

PubMed

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.

Comparison of the cohesion-adhesion balance approach to colloidal probe atomic force microscopy and the measurement of Hansen partial solubility parameters by inverse gas chromatography for the prediction of dry powder inhalation performance.

PubMed

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.

Recessive variants of MuSK are associated with late onset CMS and predominant limb girdle weakness.

PubMed

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.

Results of Mujeres Felices por ser Saludables: a dietary/breast health randomized clinical trial for Latino women.

PubMed

Fitzgibbon, Marian L; Gapstur, Susan M; Knight, Sara J

2004-10-01

Data are limited on the efficacy of health-focused interventions for young, low-acculturated Latino women. Because breast cancer is the most commonly diagnosed cancer and the most common cause of cancer mortality in this population, combined interventions that address both early detection and dietary patterns could help reduce both morbidity and mortality associated with breast cancer in this underserved population. Mujeres Felices por ser Saludables was randomized intervention study designed to assess the efficacy of an 8-month combined dietary and breast health intervention to reduce fat and increase fiber intake as well as to increase the frequency and proficiency of breast self-examination (BSE) and reduce anxiety related to BSE among Latinas. Blocked randomization in blocks of 6 was used to randomize 256 20- to 40-year-old Latinas to the intervention (n = 127) or control group (n = 129). The intervention group attended an 8-month multicomponent education program designed specifically for low-acculturated Latinas. The control group received mailed health education material on a schedule comparable to the intervention. A total of 195 women (76.2%) completed both the baseline and 8-month follow-up interviews. The intervention and control groups were similar on baseline sociodemographic characteristics. At the 8-month follow up, the intervention group reported lower dietary fat (P < .001) and higher fiber intake (p = .06); a higher proportion reported practicing BSE at the recommended interval (p < .001) and showed improved BSE proficiency (p < .001) compared to the control group. BSE-related anxiety was low for both groups at baseline, and no difference in reduction was observed. This project provides a successful model for achieving dietary change and improving breast health behavior in young, low-acculturated Latinas.

Bifurcación de las soluciones de vientos impulsados por radiación en estrellas Be: formación de líneas

NASA Astrophysics Data System (ADS)

Curé, M.; Rial, D.; Cidale, L.; Venero, R.

Se ha estudiado la topología de la ecuación hidrodinámica no-lineal que describe el perfil de velocidades de vientos impulsados por radiación en estrellas tempranas. Al aplicar este modelo a estrellas Be se encuentra que existen dos tipos De soluciones: la estándar, que describe el viento polar, y una nueva, que describe un viento más denso y lento y que explicaría el disco que se encuentra alrededor de estos objetos. Existe una región de transición en donde ambas soluciones coexisten (bifurcación}). Ambas soluciones satisfacen en esta región las mismas condiciones de borde. Para estas dos soluciones se han obtenido los perfiles de líneas de hidrógeno del visible y del IR, resolviendo el transporte de radiación en el ``comoving frame". Para la solución estándar, se obtienen perfiles con componentes en emisión, mientras que para la nueva solución se obtienen perfiles en absorción. Se comparan cualitativamente los resultados con las observaciones.

Characterization and pharmacodynamic properties of Arnica montana complex.

PubMed

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.

Salmeterol versus slow-release theophylline combined with ketotifen in nocturnal asthma: a multicentre trial. French Multicentre Study Group.

PubMed

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.

Effect of surface coating with magnesium stearate via mechanical dry powder coating approach on the aerosol performance of micronized drug powders from dry powder inhalers.

PubMed

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.

Acute respiratory failure revealing a multilocular thymic cyst in an infant: a case report.

PubMed

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.

Looking for immunotolerance: a case of allergy to baker's yeast (Saccharomyces cerevisiae).

PubMed

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.

Development and validation of an UHPLC-MS/MS method for β2-agonists quantification in human urine and application to clinical samples.

PubMed

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.

Influence of excipients in comilling on mitigating milling-induced amorphization or structural disorder of crystalline pharmaceutical actives.

PubMed

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.

Relaxant effect of superimposed length oscillation on sensitized airway smooth muscle.

PubMed

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.

Guidance on the diagnosis and management of asthma among adults in resource limited settings.

PubMed

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.

Principal findings of systematic reviews for the management of acute bronchiolitis in children.

PubMed

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.

THE CASE OF A 14-YEAR-OLD BOY WHO EXPERIENCED ANAPHYLAXIS DUE TO JELLYFISH (MASTIGIAS PAPUA) INGESTION.

PubMed

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.

The effect of different coating materials on the prevention of powder bounce in the next generation impactor

PubMed Central

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

The effect of different coating materials on the prevention of powder bounce in the next generation impactor.

PubMed

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.

Contaminación por mercurio de leche materna de madres lactantes de municipios de Antioquia con explotación minera de oro.

PubMed

Molina, Carlos Federico; Arango, Catalina María; Sepúlveda, Hernán

2018-05-01

Introducción. La leche materna es esencial para el desarrollo del ser humano, pero puede contener sustancias tóxicas provenientes de la contaminación ambiental, especialmente en las áreas mineras.Objetivo. Determinar la prevalencia de la contaminación con mercurio de la leche materna de mujeres lactantes residentes en los municipios con explotación minera de oro.Materiales y métodos. Se hizo un estudio transversal de 150 madres lactantes de cuatro municipios mineros de Antioquia (El Bagre, Segovia, Remedios y Zaragoza), a quienes se les hizo una encuesta sobre factores sociodemográficos, ocupacionales y ambientales relacionados con el mercurio, y se les tomaron muestras de leche materna, de orina y de cabello. Se calculó el promedio de la concentración de mercurio y las prevalencias municipales de contaminación.Resultados. El promedio de la concentración de mercurio en la leche materna fue de 2,5 (± desviación estándar 9,2) μg/L. La prevalencia de muestras de leche materna con niveles altos de mercurio fue de 11,7 %.Conclusión. En este estudio se evidencia un grave problema en las regiones mineras auríferas de Antioquia por el efecto de la contaminación con mercurio en sectores de la población más vulnerable.

Fuentes de variabilidad en el diagnóstico de gastritis atrófica multifocal asociada con la infección por Helicobacter pylori1

PubMed Central

Bravo, Luis Eduardo; Bravo, Juan Carlos; Realpe, José Luis; Zarama, Guillermo; Piazuelo, MarÍa Blanca; Correa, Pelayo

2014-01-01

RESUMEN Introducción El mapeo de las diferentes regiones del estómago y el número de fragmentos de mucosa gástrica disponibles para evaluación histopatológica son fuentes importantes de variación en el momento de clasificar y hacer la gradación de la gastritis crónica. Objetivos Estimar la sensibilidad del número de fragmentos de mucosa gástrica necesarios para establecer los diagnósticos de gastritis atrófica con metaplasia intestinal (MI), displasia y estado de infección por Helicobacter pylori. Además evaluar la variabilidad intra-observador en la clasificación de estas lesiones precursoras del cáncer gástrico. Materiales y métodos En una cohorte de 6 años de seguimiento se evaluaron 1,958 procedimientos de endoscopia realizados por dos gastroenterólogos. En cada procedimiento y de cada participante se obtuvieron 5 biopsias de mucosa gástrica que representaban antro, incisura angularis y cuerpo. Un único patólogo hizo la interpretación histológica de las 5 biopsias y proporcionó un diagnóstico definitivo global que se utilizó como patrón de referencia. Cada fragmento de mucosa gástrica examinado condujo a un diagnóstico individual para cada biopsia que se comparó con el patrón de referencia. La variabilidad intra-observador se evaluó en 127 personas que corresponden a una muestra aleatoria de 20% del total de endoscopias hechas a los 72 meses de seguimiento. Resultados La sensibilidad del diagnóstico de MI y displasia gástrica aumentó de manera significativa con el número de fragmentos de mucosa gástrica evaluados El sitio anatómico de mayor sensibilidad para el diagnóstico de MI y displasia fue la incisura angularis. Para descubrir H. pylori se logró alta sensibilidad con el estudio de un solo fragmento de mucosa gástrica (95.9%) y fue independiente del sitio de obtención de la biopsia. El acuerdo intra-observador para el diagnóstico de gastritis crónica fue 86.1% con valor kappa de 0.79 IC 95% (0.76-0.85). Las

Treatment of severe bronchiolitis: A survey of Canadian pediatric intensivists.

PubMed

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.

Bronchodilator responses after methacholine and adenosine 5'-monophosphate (AMP) challenges in children with asthma: their relationships with eosinophil markers.

PubMed

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.

Association between Selective Beta-adrenergic Drugs and Blood Pressure Elevation: Data Mining of the Japanese Adverse Drug Event Report (JADER) Database.

PubMed

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.

Cell-Free Expression, Purification, and Characterization of the Functional β2-Adrenergic Receptor for Multianalyte Detection of β-Agonists.

PubMed

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.

Beta2-adrenergic agonist use and the risk of multiple sclerosis: a total population-based case-control study.

PubMed

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.

Development and validation of chemometrics-assisted spectrophotometric and liquid chromatographic methods for the simultaneous determination of two multicomponent mixtures containing bronchodilator drugs.

PubMed

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.

Bifidobacterium mixture (B longum BB536, B infantis M-63, B breve M-16V) treatment in children with seasonal allergic rhinitis and intermittent asthma.

PubMed

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 .

Dissolution of fine particle fraction from truncated Anderson cascade impactor with an enhancer cell.

PubMed

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.

Evaluation of air-interfaced Calu-3 cell layers for investigation of inhaled drug interactions with organic cation transporters in vitro.

PubMed

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.

Multicomponent mesofluidic system for the detection of veterinary drug residues based on competitive immunoassay.

PubMed

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.

Central α- and β-adrenoceptors modifying arterial blood pressure and heart rate in conscious cats

PubMed Central

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

Potential of a cyclone prototype spacer to improve in vitro dry powder delivery.

PubMed

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.

Evaluation of Granulated Lactose as a Carrier for Dry Powder Inhaler Formulations 2: Effect of Drugs and Drug Loading.

PubMed

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.

Kinetic Study of Hydroxyl and Sulfate Radical-Mediated Oxidation of Pharmaceuticals in Wastewater Effluents.

PubMed

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.

A protein secretion system linked to bacteroidete gliding motility and pathogenesis

PubMed Central

Sato, Keiko; Naito, Mariko; Yukitake, Hideharu; Hirakawa, Hideki; Shoji, Mikio; McBride, Mark J.; Rhodes, Ryan G.; Nakayama, Koji

2009-01-01

Porphyromonas gingivalis secretes strong proteases called gingipains that are implicated in periodontal pathogenesis. Protein secretion systems common to other Gram-negative bacteria are lacking in P. gingivalis, but several proteins, including PorT, have been linked to gingipain secretion. Comparative genome analysis and genetic experiments revealed 11 additional proteins involved in gingipain secretion. Six of these (PorK, PorL, PorM, PorN, PorW, and Sov) were similar in sequence to Flavobacterium johnsoniae gliding motility proteins, and two others (PorX and PorY) were putative two-component system regulatory proteins. Real-time RT-PCR analysis revealed that porK, porL, porM, porN, porP, porT, and sov were down-regulated in P. gingivalis porX and porY mutants. Disruption of the F. johnsoniae porT ortholog resulted in defects in motility, chitinase secretion, and translocation of a gliding motility protein, SprB adhesin, to the cell surface, providing a link between a unique protein translocation system and a motility apparatus in members of the Bacteroidetes phylum. PMID:19966289

Differential Regulation of Duplicate Light-Dependent Protochlorophyllide Oxidoreductases in the Diatom Phaeodactylum tricornutum

PubMed Central

Hunsperger, Heather M.; Cattolico, Rose Ann

2016-01-01

Background Diatoms (Bacilliariophyceae) encode two light-dependent protochlorophyllide oxidoreductases (POR1 and POR2) that catalyze the penultimate step of chlorophyll biosynthesis in the light. Algae live in dynamic environments whose changing light levels induce photoacclimative metabolic shifts, including altered cellular chlorophyll levels. We hypothesized that the two POR proteins may be differentially adaptive under varying light conditions. Using the diatom Phaeodactylum tricornutum as a test system, differences in POR protein abundance and por gene expression were examined when this organism was grown on an alternating light:dark cycles at different irradiances; exposed to continuous light; and challenged by a significant decrease in light availability. Results For cultures maintained on a 12h light: 12h dark photoperiod at 200μE m−2 s−1 (200L/D), both por genes were up-regulated during the light and down-regulated in the dark, though por1 transcript abundance rose and fell earlier than that of por2. Little concordance occurred between por1 mRNA and POR1 protein abundance. In contrast, por2 mRNA and POR2 protein abundances followed similar diurnal patterns. When 200L/D P. tricornutum cultures were transferred to continuous light (200L/L), the diurnal regulatory pattern of por1 mRNA abundance but not of por2 was disrupted, and POR1 but not POR2 protein abundance dropped steeply. Under 1200μE m−2 s−1 (1200L/D), both por1 mRNA and POR1 protein abundance displayed diurnal oscillations. A compromised diel por2 mRNA response under 1200L/D did not impact the oscillation in POR2 abundance. When cells grown at 1200L/D were then shifted to 50μE m−2 s−1 (50L/D), por1 and por2 mRNA levels decreased swiftly but briefly upon light reduction. Thereafter, POR1 but not POR2 protein levels rose significantly in response to this light stepdown. Conclusion Given the sensitivity of diatom por1/POR1 to real-time light cues and adherence of por2/POR2 regulation to

Influenza A virus infection and cigarette smoke impair bronchodilator responsiveness to β-adrenoceptor agonists in mouse lung.

PubMed

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).

Simulations of Biased Agonists in the β2 Adrenergic Receptor with Accelerated Molecular Dynamics

PubMed Central

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

Chemical exposure and respiratory health of children in an industrial setting.

PubMed

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.

Subcutaneous adrenaline versus terbutaline in the treatment of acute severe asthma.

PubMed Central

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

Predicting the Fine Particle Fraction of Dry Powder Inhalers Using Artificial Neural Networks.

PubMed

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.

Binding kinetics of five drugs to beta2-adrenoceptor using peak profiling method and nonlinear chromatography.

PubMed

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.

Application of the piecewise rational quadratic interpolant to the AUC calculation in the bioavailability study.

PubMed

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.

Langerhans cells beta 2-adrenoceptors: role in migration, cytokine production, Th priming and contact hypersensitivity.

PubMed

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.

Nebulized perflubron and carbon dioxide rapidly dilate constricted airways in an ovine model of allergic asthma.

PubMed

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.

Performance indicators for carrier-based DPIs: Carrier surface properties for capsule filling and API properties for in vitro aerosolisation.

PubMed

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.

Oscillometric and spirometric bronchodilator response in preschool children with and without asthma

PubMed Central

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

Population pharmacokinetic approach to evaluate the effect of CYP2D6, CYP3A, ABCB1, POR and NR1I2 genotypes on donepezil clearance

PubMed Central

Noetzli, Muriel; Guidi, Monia; Ebbing, Karsten; Eyer, Stephan; Wilhelm, Laurence; Michon, Agnès; Thomazic, Valérie; Stancu, Ioana; Alnawaqil, Abdel-Messieh; Bula, Christophe; Zumbach, Serge; Gaillard, Michel; Giannakopoulos, Panteleimon; von Gunten, Armin; Csajka, Chantal; Eap, Chin B

2014-01-01

Aims A large interindividual variability in plasma concentrations has been reported in patients treated with donepezil, the most frequently prescribed antidementia drug. We aimed to evaluate clinical and genetic factors influencing donepezil disposition in a patient population recruited from a naturalistic setting. Methods A population pharmacokinetic study was performed including data from 129 older patients treated with donepezil. The patients were genotyped for common polymorphisms in the metabolic enzymes CYP2D6 and CYP3A, in the electron transferring protein POR and the nuclear factor NR1I2 involved in CYP activity and expression, and in the drug transporter ABCB1. Results The average donepezil clearance was 7.3 l h−1 with a 30% interindividual variability. Gender markedly influenced donepezil clearance (P < 0.01). Functional alleles of CYP2D6 were identified as unique significant genetic covariate for donepezil clearance (P < 0.01), with poor metabolizers and ultrarapid metabolizers demonstrating, respectively, a 32% slower and a 67% faster donepezil elimination compared with extensive metabolizers. Conclusion The pharmacokinetic parameters of donepezil were well described by the developed population model. Functional alleles of CYP2D6 significantly contributed to the variability in donepezil disposition in the patient population and should be further investigated in the context of individual dose optimization to improve clinical outcome and tolerability of the treatment. PMID:24433464

Population pharmacokinetic approach to evaluate the effect of CYP2D6, CYP3A, ABCB1, POR and NR1I2 genotypes on donepezil clearance.

PubMed

Noetzli, Muriel; Guidi, Monia; Ebbing, Karsten; Eyer, Stephan; Wilhelm, Laurence; Michon, Agnès; Thomazic, Valérie; Stancu, Ioana; Alnawaqil, Abdel-Messieh; Bula, Christophe; Zumbach, Serge; Gaillard, Michel; Giannakopoulos, Panteleimon; von Gunten, Armin; Csajka, Chantal; Eap, Chin B

2014-07-01

A large interindividual variability in plasma concentrations has been reported in patients treated with donepezil, the most frequently prescribed antidementia drug. We aimed to evaluate clinical and genetic factors influencing donepezil disposition in a patient population recruited from a naturalistic setting. A population pharmacokinetic study was performed including data from 129 older patients treated with donepezil. The patients were genotyped for common polymorphisms in the metabolic enzymes CYP2D6 and CYP3A, in the electron transferring protein POR and the nuclear factor NR1I2 involved in CYP activity and expression, and in the drug transporter ABCB1. The average donepezil clearance was 7.3 l h(-1) with a 30% interindividual variability. Gender markedly influenced donepezil clearance (P < 0.01). Functional alleles of CYP2D6 were identified as unique significant genetic covariate for donepezil clearance (P < 0.01), with poor metabolizers and ultrarapid metabolizers demonstrating, respectively, a 32% slower and a 67% faster donepezil elimination compared with extensive metabolizers. The pharmacokinetic parameters of donepezil were well described by the developed population model. Functional alleles of CYP2D6 significantly contributed to the variability in donepezil disposition in the patient population and should be further investigated in the context of individual dose optimization to improve clinical outcome and tolerability of the treatment. © 2014 The British Pharmacological Society.

Differential regulation of duplicate light-dependent protochlorophyllide oxidoreductases in the diatom Phaeodactylum tricornutum

DOE PAGES

Hunsperger, Heather M.; Ford, Christopher J.; Miller, James S.; ...

2016-07-01

Diatoms (Bacilliariophyceae) encode two light-dependent protochlorophyllide oxidoreductases (POR1 and POR2) that catalyze the penultimate step of chlorophyll biosynthesis in the light. Algae live in dynamic environments whose changing light levels induce photoacclimative metabolic shifts, including altered cellular chlorophyll levels. We hypothesized that the two POR proteins may be differentially adaptive under varying light conditions. Using the diatom Phaeodactylum tricornutum as a test system, differences in POR protein abundance and por gene expression were examined when this organism was grown on an alternating light:dark cycles at different irradiances; exposed to continuous light; and challenged by a significant decrease in light availability.more » As a result, for cultures maintained on a 12h light: 12h dark photoperiod at 200μEm –2 s –1 ( 200L/D), both por genes were up-regulated during the light and down-regulated in the dark, though por1 transcript abundance rose and fell earlier than that of por2. Little concordance occurred between por1 mRNA and POR1 protein abundance. In contrast, por2 mRNA and POR2 protein abundances followed similar diurnal patterns. When 200L/D P. tricornutum cultures were transferred to continuous light ( 200L/L), the diurnal regulatory pattern of por1 mRNA abundance but not of por2 was disrupted, and POR1 but not POR2 protein abundance dropped steeply. Under 1200μEm –2 s –1 ( 1200L/D), both por1 mRNA and POR1 protein abundance displayed diurnal oscillations. A compromised diel por2 mRNA response under 1200L/D did not impact the oscillation in POR2 abundance. When cells grown at 1200L/D were then shifted to 50μEm –2 s –1 (50L/D), por1 and por2 mRNA levels decreased swiftly but briefly upon light reduction. Thereafter, POR1 but not POR2 protein levels rose significantly in response to this light stepdown.« less

A study on the stability of O{sub 2} on oxometalloporphyrins by the first principles calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kubota, Yoshiyuki; Escano, Mary Clare Sison; Dy, Eben Sy

2007-05-21

The authors investigated the interaction of oxometalloporphyrins (MO(por))--specifically, MoO(por), WO(por), TiO(por), VO(por), and CrO(por)--with O{sub 2} by using first principles calculations. MoO(por) and WO(por) undergo reactions with O{sub 2}; on the other hand, TiO(por), VO(por), and CrO(por) do not. Next, they compared the interaction of MoO(por) and WO(por) with O{sub 2}. Activation barriers for the reactions of MoO(por) and WO(por) with a side-on O{sub 2} are small. For MoO(por)(O{sub 2}), the activation barrier for the reverse reaction that liberates O{sub 2} is also small; however, that for WO(por)(O{sub 2}) is large. The experimental results that photoirradiation with visible light ormore » heating of Mo {sup VI}O(tmp)(O{sub 2}) regenerates Mo {sup VI}O(tmp) by liberating O{sub 2} while W {sup VI}O(tmp)(O{sub 2}) does not [J. Tachibana, T. Imamura, and Y. Sasaki, Bull. Chem. Soc. Jpn. 71, 363 (1998)] are explained by the difference in activation barriers of the reverse reactions. This means that bonds formed between the W atom and O{sub 2} are stronger than those between the Mo atom and O{sub 2}. The bond strengths can be explained by differences in the energy levels between the highest occupied molecular orbital of MoO(por) and WO(por), which are mainly formed from the a orbitals of the central metal atom and {pi}{sup *} orbitals of O{sub 2}.« less

Pharmacological stress myocardial perfusion scintigraphy: use of a modified adenosine protocol in patients with asthma.

PubMed

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

Type IX secretion: the generation of bacterial cell surface coatings involved in virulence, gliding motility and the degradation of complex biopolymers.

PubMed

Veith, Paul D; Glew, Michelle D; Gorasia, Dhana G; Reynolds, Eric C

2017-10-01

The Type IX secretion system (T9SS) is present in over 1000 sequenced species/strains of the Fibrobacteres-Chlorobi-Bacteroidetes superphylum. Proteins secreted by the T9SS have an N-terminal signal peptide for translocation across the inner membrane via the SEC translocon and a C-terminal signal for secretion across the outer membrane via the T9SS. Nineteen protein components of the T9SS have been identified including three, SigP, PorX and PorY that are involved in regulation. The inner membrane proteins PorL and PorM and the outer membrane proteins PorK and PorN interact and a complex comprising PorK and PorN forms a large ring structure of 50 nm in diameter. PorU, PorV, PorQ and PorZ form an attachment complex on the cell surface of the oral pathogen, Porphyromonas gingivalis. P. gingivalis T9SS substrates bind to PorV suggesting that after translocation PorV functions as a shuttle protein to deliver T9SS substrates to the attachment complex. The PorU component of the attachment complex is a novel Gram negative sortase which catalyses the cleavage of the C-terminal signal and conjugation of the protein substrates to lipopolysaccharide, anchoring them to the cell surface. This review presents an overview of the T9SS focusing on the function of T9SS substrates and machinery components. © 2017 John Wiley & Sons Ltd.

The effect of β-saturated pyrrolic rings on the electronic structures and aromaticity of magnesium porphyrin derivatives: a density functional study.

PubMed

Wan, Liang; Qi, Dongdong; Zhang, Yuexing

2011-09-01

Density functional theory (DFT) calculation on the molecular structures, molecular orbitals, electronic absorption spectra, and magnetic properties of magnesium porphyrin (MgPor) and a series of five hydrogenated magnesium porphyrin complexes with different number of β-saturated pyrrolic rings, namely MgPor-β-1Hy, MgPor-β-opp-2Hy, MgPor-β-adj-2Hy, MgPor-β-3Hy, and MgPor-β-4Hy, clarifies the red-shift of the lowest energy absorption band from chlorophyll a to bacteriochlorophyll and reveals the strong chemical stability for both of them. The energy levels of highest occupied molecular orbitals (HOMO) and HOMO-1 for MgPor are reversed upon hydrogenation at β-positions (2 and 3, 7 and 8, 12 and 13, and 17 and 18) of porphyrin ring. Along with the increase of β-saturated pyrrolic rings from 1, 2, 3, to 4, the HOMO energy increases from -4.78 eV to -3.10 eV in a regular manner. In contrast, the lowest unoccupied molecular orbitals (LUMO) energy levels of MgPor, MgPor-β-1Hy, and MgPor-β-opp-2Hy are very similar with each other. As a result, the lowest energy absorption band involving main transition from HOMO to LUMO is red-shifted from MgPor-β-1Hy to MgPor-β-opp-2Hy which is representative of chlorophyll a and bacteriochlorophyll, respectively. Natural hydroporphyrins represented by MgPor, MgPor-β-1Hy, and MgPor-β-opp-2Hy have turned out to be aromatic and stable enough, in good accordance with the ubiquity of their derivatives in the nature. In contrast, MgPor-β-adj-2Hy, MgPor-β-3Hy, and MgPor-β-4Hy with relatively weak aromaticity seem to be unstable and therefore were not found in nature. Copyright © 2011 Elsevier Inc. All rights reserved.

Legal Knowledge as a Tool for Social Change: La Mesa por la Vida y la Salud de las Mujeres as an Expert on Colombian Abortion Law.

PubMed

González Vélez, Ana Cristina; Jaramillo, Isabel Cristina

2017-06-01

In May 2006, Colombia's Constitutional Court liberalized abortion, introducing three circumstances under which the procedure would not be considered a crime: (1) rape or incest; (2) a risk to the woman's health or life; and (3) fetal malformations incompatible with life. Immediately following the court's ruling, known as Sentence C-355, members of La Mesa por la Vida y Salud de las Mujeres (hereinafter La Mesa) began to mobilize to ensure the decision's implementation, bearing in mind the limited impact that the legal framework endorsed by the court has had in other countries in the region. We argue that La Mesa's strategy is an innovative one in the field of legal mobilization insofar as it presumes that law can be shaped not just by public officials and universities but also by social actors engaged in the creation and diffusion of legal knowledge. In this regard, La Mesa has become a legal expert on abortion by accumulating knowledge about the multiple legal rules affecting the practice of abortion and about the situations in which these rules are to be applied. In addition, by becoming a legal expert, La Mesa has been able to persuade health providers that they will not risk criminal prosecution or being fired if they perform abortions. We call this effect of legal mobilization a "pedagogical effect" insofar as it involves the production of expertise and appropriation of knowledge by health professionals. We conclude by discussing La Mesa's choice to become a legal expert on abortion as opposed to recruiting academics to do this work or encouraging women to produce and disseminate this knowledge.

Effect of Uruguay’s National 100% Smokefree Law on Emergency Visits for Bronchospasm

PubMed Central

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

Effect of Uruguay's National 100% Smokefree Law on Emergency Visits for Bronchospasm.

PubMed

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.

Use of heat of adsorption to quantify amorphous content in milled pharmaceutical powders.

PubMed

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.

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

The role of indacaterol for chronic obstructive pulmonary disease (COPD)

PubMed Central

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

The association between chronic airflow obstruction and poverty in 12 sites of the multinational BOLD study.

PubMed

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

Budesonide nebulization added to systemic prednisolone in the treatment of acute asthma in children: a double-blind, randomized, controlled trial.

PubMed

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

Beta 2 adrenergic receptor polymorphisms, at codons 16 and 27, and bronchodilator responses in adult Venezuelan asthmatic patients.

PubMed

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.

Development of Fluorescence Surrogates to Predict the Photochemical Transformation of Pharmaceuticals in Wastewater Effluents.

PubMed

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.

Understanding the effect of lactose particle size on the properties of DPI formulations using experimental design.

PubMed

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.

A clinical decision rule for triage of children under 5 years of age with hydrocarbon (kerosene) aspiration in developing countries.

PubMed

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.

Effect of smoking status on the efficacy of the SMART regimen in high risk asthma.

PubMed

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.

Sulfonated polystyrene magnetic nanobeads coupled with immunochromatographic strip for clenbuterol determination in pork muscle.

PubMed

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.

Proctalgia fugax, an evidence-based management pathway.

PubMed

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.

Efficacy of nebulised budesonide versus oral prednisolone in acute severe asthma.

PubMed

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.

Control of nasal vasculature and airflow resistance in the dog.

PubMed Central

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

Control of nasal vasculature and airflow resistance in the dog.

PubMed

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.

Audit of acute asthma management at the Paediatric Emergency Department at Wad Madani Children’s Hospital, Sudan

PubMed Central

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

Effect of P450 Oxidoreductase Polymorphisms on the Metabolic Activities of Ten Cytochrome P450s Varied by Polymorphic CYP Genotypes in Human Liver Microsomes.

PubMed

Fang, Yan; Gao, Na; Tian, Xin; Zhou, Jun; Zhang, Hai-Feng; Gao, Jie; He, Xiao-Pei; Wen, Qiang; Jia, Lin-Jing; Jin, Han; Qiao, Hai-Ling

2018-06-27

Background/ Aims: Little is known about the effect of P450 oxidoreductase (POR) gene polymorphisms on the activities of CYPs with multiple genotypes. We genotyped 102 human livers for 18 known POR single nucleotide polymorphisms (SNPs) with allelic frequencies greater than 1% as well as for 27 known SNPs in 10 CYPs. CYP enzyme activities in microsomes prepared from these livers were determined by measuring probe substrate metabolism by high performance liquid chromatograph. We found that the effects of the 18 POR SNPs on 10 CYP activities were CYP genotype-dependent. The POR mutations were significantly associated with decreased overall Km for CYP2B6 and 2E1, and specific genotypes within CYP1A2, 2A6, 2B6, 2C8, 2D6 and 2E1 were identified as being affected by these POR SNPs. Notably, the effect of a specific POR mutation on the activity of a CYP genotype could not be predicted from other CYP genotypes of even the same CYP. When combining one POR SNP with other POR SNPs, a hitherto unrecognized effect of multiple-site POR gene polymorphisms (MSGP) on CYP activity was uncovered, which was not necessarily consistent with the effect of either single POR SNP. The effects of POR SNPs on CYP activities were not only CYP-dependent, but more importantly, CYP genotype-dependent. Moreover, the effect of a POR SNP alone and in combination with other POR SNPs (MSGP) was not always consistent, nor predictable. Understanding the impact of POR gene polymorphisms on drug metabolism necessitates knowing the complete SNP complement of POR and the genotype of the relevant CYPs. © 2018 The Author(s). Published by S. Karger AG, Basel.

Evaluating Por Nuestra Salud: A Feasibility Study.

PubMed

Marshall, Brenda; Gonzales, Gustavo; Kernan, William

2016-01-01

This feasibility study evaluated the impact of a culturally consistent diabetes educational program, led by a Latino pastor, on Latino community diabetes knowledge levels. Latino adults were recruited from two churches serving Latino populations, one identified as intervention, the other as nonintervention. Both churches received the American Diabetes Association's booklets on diabetes education, "Four Steps to Control Your Diabetes for Life." The intervention group also received weekly reviews of the booklet's information from the church pastor, who was educated about diabetes by a Latino family nurse practitioner. Pre- and postintervention levels of diabetes knowledge were measured using the Diabetes Knowledge Questionnaire. Mean changes in the Diabetes Knowledge Questionnaire (DKQ-24) survey from pretest to posttest indicated a significant increase in knowledge in both groups. Only the grades for the participants from the pastor-led group, however, moved from failure in knowledge to high levels of passing. One hundred percent of intervention group participants reported having read the literature. This pilot study supports the feasibility of a local Latino pastor, as a culturally consistent diabetes educator, to increase Latino parishioner's knowledge of diabetes. © 2015 Society for Public Health Education.

Heterologous expression of equine CYP3A94 and investigation of a tunable system to regulate co-expressed NADPH P450 oxidoreductase levels.

PubMed

Dettwiler, Ramona; Schmitz, Andrea L; Plattet, Philippe; Zielinski, Jana; Mevissen, Meike

2014-01-01

The activity of cytochrome P450 enzymes depends on the enzyme NADPH P450 oxidoreductase (POR). The aim of this study was to investigate the activity of the equine CYP3A94 using a system that allows to regulate the POR protein levels in mammalian cells. CYP3A94 and the equine POR were heterologously expressed in V79 cells. In the system used, the POR protein regulation is based on a destabilizing domain (DD) that transfers its instability to a fused protein. The resulting fusion protein is therefore degraded by the ubiquitin-proteasome system (UPS). Addition of "Shield-1" prevents the DD fusion protein from degradation. The change of POR levels at different Shield-1 concentrations was demonstrated by cytochrome c reduction, Western immunoblot analysis, and immunocytochemistry. The alteration of CYP3A94 activity was investigated using a substrate (BFC) known to detect CYP3A4 activity. Equine CYP3A94 was demonstrated to be metabolically active and its activity could be significantly elevated by co-expression of POR. Cytochrome c reduction was significantly increased in V79-CYP3A94/DD-POR cells compared to V79-CYP3A94 cells. Surprisingly, incubation with different Shield-1 concentrations resulted in a decrease in POR protein shown by Western immunoblot analysis. Cytochrome c reduction did not change significantly, but the CYP3A94 activity decreased more than 4-fold after incubation with 500 nM and 1 µM Shield-1 for 24 hours. No differences were obtained when V79-CYP3A94 POR cells with and without Shield-1 were compared. The basal activity levels of V79-CYP3A94/DD-POR cells were unexpectedly high, indicating that DD/POR is not degraded without Shield-1. Shield-1 decreased POR protein levels and CYP3A94 activity suggesting that Shield-1 might impair POR activity by an unknown mechanism. Although regulation of POR with the pPTuner system could not be obtained, the cell line V79-CYP3A94/DD-POR system can be used for further experiments to characterize the equine CYP3A94

Primary language and cultural background as factors in resident burnout in medical specialties: a study in a bilingual US city.

PubMed

Afzal, Khalid I; Khan, Farhan M; Mulla, Zuber; Akins, Ralista; Ledger, Elizabeth; Giordano, Frank L

2010-07-01

The aim of this study was to identify the degree of burnout among resident physicians enrolled in seven postgraduate training programs at Texas Tech University Health Sciences Center (TTUHSC), Paul L. Foster School of Medicine, El Paso, Texas, as it related to residents' age, gender, marital status, number of hours worked per week, primary language, race/ethnicity, and cultural background. : The Maslach Burnout Inventory Human Service Survey (MBI) was administered to measure the level of burnout according to the prevalence of emotional exhaustion (EE), depersonalization (DP), and reduced personal accomplishment (PA). : Eighty-one percent of the residents at TTUHSC participated in the study. Residents raised in the United States or Canada comprised 28% and 35% of the study, and all reported English as their primary language. The EE scale was significant for obstetrics/gynecology (OB/GYN) residents (prevalence odds ratio [POR] = 13.55, P = 0.02) and psychiatry (PSY) residents (POR = 6.50, P = 0.03). Emergency medicine (EM) residents (POR = 23.35, P = 0.002), OB/GYN (POR = 10.89, P = 0.02), and general surgery (GS) (POR = 6.24, P = 0.03) residents had high DP. Internal medicine (IM) residents (primarily Spanish-speaking) reported significantly low EE (POR = 0.22, P = 0.03) and PA (POR = 0.09, P = 0.001) scores. Residents from the United States or Canada who reported English as their primary language and noted their race as white, had high EE (POR = 3.06, P = 0.03; POR = 5.61, P = 0.0001; POR = 2.91, P = 0.004), DP (POR = 3.19, P = 0.02; POR = 8.34, P < or = 0.0001; POR = 4.70, P < or = 0.0001) and PA (POR = 2.61, P = 0.02; POR = 2.35, P = 0.05, POR 0.29, P = 0.3) scores. Using valid measures, this pilot study identified a statistically significant relationship between burnout and residents' race/ethnicity, primary language, and cultural background. Larger studies with similar focus would be necessary to generalize these findings. At-risk residents in bilingual

Reduction in hepatic drug metabolizing CYP3A4 activities caused by P450 oxidoreductase mutations identified in patients with disordered steroid metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flueck, Christa E.; Mullis, Primus E.; Pandey, Amit V., E-mail: amit@pandeylab.org

2010-10-08

Research highlights: {yields} Cytochrome P450 3A4 (CYP3A4), metabolizes 50% of drugs in clinical use and requires NADPH-P450 reductase (POR). {yields} Mutations in human POR cause congenital adrenal hyperplasia from diminished activities of steroid metabolizing P450s. {yields} We are reporting that mutations in POR may reduce CYP3A4 activity. {yields} POR mutants Y181D, A457H, Y459H, V492E and R616X lost 99%, while A287P, C569Y and V608F lost 60-85% CYP3A4 activity. {yields} Reduction of CYP3A4 activity may cause increased risk of drug toxicities/adverse drug reactions in patients with POR mutations. -- Abstract: Cytochrome P450 3A4 (CYP3A4), the major P450 present in human liver metabolizesmore » approximately half the drugs in clinical use and requires electrons supplied from NADPH through NADPH-P450 reductase (POR, CPR). Mutations in human POR cause a rare form of congenital adrenal hyperplasia from diminished activities of steroid metabolizing P450s. In this study we examined the effect of mutations in POR on CYP3A4 activity. We used purified preparations of wild type and mutant human POR and in vitro reconstitution with purified CYP3A4 to perform kinetic studies. We are reporting that mutations in POR identified in patients with disordered steroidogenesis/Antley-Bixler syndrome (ABS) may reduce CYP3A4 activity, potentially affecting drug metabolism in individuals carrying mutant POR alleles. POR mutants Y181D, A457H, Y459H, V492E and R616X had more than 99% loss of CYP3A4 activity, while POR mutations A287P, C569Y and V608F lost 60-85% activity. Loss of CYP3A4 activity may result in increased risk of drug toxicities and adverse drug reactions in patients with POR mutations.« less

Altered heme catabolism by heme oxygenase-1 caused by mutations in human NADPH cytochrome P450 reductase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pandey, Amit V., E-mail: amit@pandeylab.org; Flueck, Christa E.; Mullis, Primus E.

2010-09-24

Research highlights: {yields} Mutations in POR identified from patients lead to reduced HO-1 activities. {yields} POR mutation Y181D affecting FMN binding results in total loss of HO-1 activity. {yields} POR mutations A287P, C569Y and V608F, lost 50-70% activity. {yields} Mutations in FAD binding domain, R457H, Y459H and V492E lost all HO-1 activity. {yields} POR polymorphisms P228L, R316W, G413S, A503V and G504R have normal activity. -- Abstract: Human heme oxygenase-1 (HO-1) carries out heme catabolism supported by electrons supplied from the NADPH through NADPH P450 reductase (POR, CPR). Previously we have shown that mutations in human POR cause a rare formmore » of congenital adrenal hyperplasia. In this study, we have evaluated the effects of mutations in POR on HO-1 activity. We used purified preparations of wild type and mutant human POR and in vitro reconstitution with purified HO-1 to measure heme degradation in a coupled assay using biliverdin reductase. Here we show that mutations in POR found in patients may reduce HO-1 activity, potentially influencing heme catabolism in individuals carrying mutant POR alleles. POR mutants Y181D, A457H, Y459H, V492E and R616X had total loss of HO-1 activity, while POR mutations A287P, C569Y and V608F lost 50-70% activity. The POR variants P228L, R316W and G413S, A503V and G504R identified as polymorphs had close to WT activity. Loss of HO-1 activity may result in increased oxidative neurotoxicity, anemia, growth retardation and iron deposition. Further examination of patients affected with POR deficiency will be required to assess the metabolic effects of reduced HO-1 activity in affected individuals.« less

Heterologous Expression of Equine CYP3A94 and Investigation of a Tunable System to Regulate Co-Expressed NADPH P450 Oxidoreductase Levels

PubMed Central

Dettwiler, Ramona; Schmitz, Andrea L.; Plattet, Philippe; Zielinski, Jana; Mevissen, Meike

2014-01-01

The activity of cytochrome P450 enzymes depends on the enzyme NADPH P450 oxidoreductase (POR). The aim of this study was to investigate the activity of the equine CYP3A94 using a system that allows to regulate the POR protein levels in mammalian cells. CYP3A94 and the equine POR were heterologously expressed in V79 cells. In the system used, the POR protein regulation is based on a destabilizing domain (DD) that transfers its instability to a fused protein. The resulting fusion protein is therefore degraded by the ubiquitin-proteasome system (UPS). Addition of “Shield-1” prevents the DD fusion protein from degradation. The change of POR levels at different Shield-1 concentrations was demonstrated by cytochrome c reduction, Western immunoblot analysis, and immunocytochemistry. The alteration of CYP3A94 activity was investigated using a substrate (BFC) known to detect CYP3A4 activity. Equine CYP3A94 was demonstrated to be metabolically active and its activity could be significantly elevated by co-expression of POR. Cytochrome c reduction was significantly increased in V79-CYP3A94/DD-POR cells compared to V79-CYP3A94 cells. Surprisingly, incubation with different Shield-1 concentrations resulted in a decrease in POR protein shown by Western immunoblot analysis. Cytochrome c reduction did not change significantly, but the CYP3A94 activity decreased more than 4-fold after incubation with 500 nM and 1 µM Shield-1 for 24 hours. No differences were obtained when V79-CYP3A94 POR cells with and without Shield-1 were compared. The basal activity levels of V79-CYP3A94/DD-POR cells were unexpectedly high, indicating that DD/POR is not degraded without Shield-1. Shield-1 decreased POR protein levels and CYP3A94 activity suggesting that Shield-1 might impair POR activity by an unknown mechanism. Although regulation of POR with the pPTuner system could not be obtained, the cell line V79-CYP3A94/DD-POR system can be used for further experiments to characterize the equine CYP3A

P450 oxidoreductase deficiency: a disorder of steroidogenesis with multiple clinical manifestations.

PubMed

Miller, Walter L

2012-10-23

Cytochrome P450 enzymes catalyze the biosynthesis of steroid hormones and metabolize drugs. There are seven human type I P450 enzymes in mitochondria and 50 type II enzymes in endoplasmic reticulum. Type II enzymes, including both drug-metabolizing and some steroidogenic enzymes, require electron donation from a two-flavin protein, P450 oxidoreductase (POR). Although knockout of the POR gene causes embryonic lethality in mice, we discovered human POR deficiency as a disorder of steroidogenesis associated with the Antley-Bixler skeletal malformation syndrome and found mild POR mutations in phenotypically normal adults with infertility. Assay results of mutant forms of POR using the traditional but nonphysiologic assay (reduction of cytochrome c) did not correlate with patient phenotypes; assays based on the 17,20 lyase activity of P450c17 (CYP17) correlated with clinical phenotypes. The POR sequence in 842 normal individuals revealed many polymorphisms; amino acid sequence variant A503V is encoded by ~28% of human alleles. POR A503V has about 60% of wild-type activity in assays with CYP17, CYP2D6, and CYP3A4, but nearly wild-type activity with P450c21, CYP1A2, and CYP2C19. Activity of a particular POR variant with one P450 enzyme will not predict its activity with another P450 enzyme: Each POR-P450 combination must be studied individually. Human POR transcription, initiated from an untranslated exon, is regulated by Smad3/4, thyroid receptors, and the transcription factor AP-2. A promoter polymorphism reduces transcription to 60% in liver cells and to 35% in adrenal cells. POR deficiency is a newly described disorder of steroidogenesis, and POR variants may account for some genetic variation in drug metabolism.

Antigen challenge induces pulmonary airway eosinophil accumulation and airway hyperreactivity in sensitized guinea-pigs: the effect of anti-asthma drugs.

PubMed Central

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

Clinical features of the myasthenic syndrome arising from mutations in GMPPB.

PubMed

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/

Quality of acute asthma care in two tertiary hospitals in a state in South Western Nigeria: A report of clinical audit.

PubMed

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.

Comparing dynamic hyperinflation and associated dyspnea induced by metronome-paced tachypnea versus incremental exercise.

PubMed

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.

Functional subcellular distribution of β1- and β2-adrenergic receptors in rat ventricular cardiac myocytes

PubMed Central

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

Dry powder inhalers: physicochemical and aerosolization properties of several size-fractions of a promising alterative carrier, freeze-dried mannitol.

PubMed

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.

A new method for examining the cost savings of reducing COPD exacerbations.

PubMed

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.

Association of MicroRNA-196a2 Variant with Response to Short-Acting β2-Agonist in COPD: An Egyptian Pilot Study

PubMed Central

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

Rational drug use for acute bronchiolitis in emergency care.

PubMed

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.

Effects of hydroxy pentacyclic triterpene acids from Forsythia viridissima on asthmatic responses to ovalbumin challenge in conscious guinea pigs.

PubMed

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.

Doping and respiratory system.

PubMed

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.

Early detection of changes in lung mechanics with oscillometry following bariatric surgery in severe obesity.

PubMed

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.

The electro-mechanical window in anaesthetized guinea pigs: a new marker in screening for Torsade de Pointes risk

PubMed Central

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

A randomised controlled trial evaluating the effect of potassium supplementation on vascular function and the renin-angiotensin-aldosterone system.

PubMed

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.

Access to essential medicines to treat chronic respiratory disease in low-income countries.

PubMed

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.

Airway Delivery of Soluble Factors from Plastic-Adherent Bone Marrow Cells Prevents Murine Asthma

PubMed Central

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

Airway delivery of soluble factors from plastic-adherent bone marrow cells prevents murine asthma.

PubMed

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.

Assessment and management of children aged 1-59 months presenting with wheeze, fast breathing, and/or lower chest indrawing; results of a multicentre descriptive study in Pakistan.

PubMed

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.

Differentiation of human bronchial epithelial cells: role of hydrocortisone in development of ion transport pathways involved in mucociliary clearance.

PubMed

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.

Patterns of coral disease across the Hawaiian Archipelago: Relating disease to environment

USGS Publications Warehouse

Aeby, G.S.; Williams, G.J.; Franklin, E.C.; Kenyon, J.; Cox, E.F.; Coles, S.; Work, Thierry M.

2011-01-01

In Hawaii, coral reefs occur across a gradient of biological (host abundance), climatic (sea surface temperature anomalies) and anthropogenic conditions from the human-impacted reefs of the main Hawaiian Islands (MHI) to the pristine reefs of the northwestern Hawaiian Islands (NWHI). Coral disease surveys were conducted at 142 sites from across the Archipelago and disease patterns examined. Twelve diseases were recorded from three coral genera (Porites, Montipora, Acropora) with Porites having the highest prevalence. Porites growth anomalies (PorGAs) were significantly more prevalent within and indicative of reefs in the MHI and Porites trematodiasis (PorTrm) was significantly more prevalent within and indicative of reefs in the NWHI. Porites tissue loss syndrome (PorTLS) was also important in driving regional differences but that relationship was less clear. These results highlight the importance of understanding disease ecology when interpreting patterns of disease occurrence. PorTrm is caused by a parasitic flatworm that utilizes multiple hosts during its life cycle (fish, mollusk and coral). All three hosts must be present for the disease to occur and higher host abundance leads to higher disease prevalence. Thus, a high prevalence of PorTrm on Hawaiian reefs would be an indicator of a healthy coral reef ecosystem. In contrast, the high occurrence of PorGAs within the MHI suggests that PorGAs are related, directly or indirectly, to some environmental co-factor associated with increased human population sizes. Focusing on the three indicator diseases (PorGAs, PorTrm, PorTLS) we used statistical modeling to examine the underlying associations between disease prevalence and 14 different predictor variables (biotic and abiotic). All three diseases showed positive associations with host abundance and negative associations with thermal stress. The association with human population density differed among disease states with PorGAs showing a positive and PorTrm showing

Patterns of Coral Disease across the Hawaiian Archipelago: Relating Disease to Environment

PubMed Central

Aeby, Greta S.; Williams, Gareth J.; Franklin, Erik C.; Kenyon, Jean; Cox, Evelyn F.; Coles, Steve; Work, Thierry M.

2011-01-01

In Hawaii, coral reefs occur across a gradient of biological (host abundance), climatic (sea surface temperature anomalies) and anthropogenic conditions from the human-impacted reefs of the main Hawaiian Islands (MHI) to the pristine reefs of the northwestern Hawaiian Islands (NWHI). Coral disease surveys were conducted at 142 sites from across the Archipelago and disease patterns examined. Twelve diseases were recorded from three coral genera (Porites, Montipora, Acropora) with Porites having the highest prevalence. Porites growth anomalies (PorGAs) were significantly more prevalent within and indicative of reefs in the MHI and Porites trematodiasis (PorTrm) was significantly more prevalent within and indicative of reefs in the NWHI. Porites tissue loss syndrome (PorTLS) was also important in driving regional differences but that relationship was less clear. These results highlight the importance of understanding disease ecology when interpreting patterns of disease occurrence. PorTrm is caused by a parasitic flatworm that utilizes multiple hosts during its life cycle (fish, mollusk and coral). All three hosts must be present for the disease to occur and higher host abundance leads to higher disease prevalence. Thus, a high prevalence of PorTrm on Hawaiian reefs would be an indicator of a healthy coral reef ecosystem. In contrast, the high occurrence of PorGAs within the MHI suggests that PorGAs are related, directly or indirectly, to some environmental co-factor associated with increased human population sizes. Focusing on the three indicator diseases (PorGAs, PorTrm, PorTLS) we used statistical modeling to examine the underlying associations between disease prevalence and 14 different predictor variables (biotic and abiotic). All three diseases showed positive associations with host abundance and negative associations with thermal stress. The association with human population density differed among disease states with PorGAs showing a positive and PorTrm showing

Evaluation of six nucleic acid amplification tests used for diagnosis of Neisseria gonorrhoeae in Russia compared with an international strictly validated real-time porA pseudogene polymerase chain reaction.

PubMed

Shipitsyna, E; Zolotoverkhaya, E; Hjelmevoll, S O; Maximova, A; Savicheva, A; Sokolovsky, E; Skogen, V; Domeika, M; Unemo, M

2009-11-01

In Russia, laboratory diagnosis of gonorrhoea has been mainly based on microscopy only and, in some settings, relatively rare suboptimal culturing. In recent years, Russian developed and manufactured nucleic acid amplification tests (NAAT) have been implemented for routine diagnosis of Neisseria gonorrhoeae. However, these NAATs have never been validated to any international well-recognized diagnostic NAAT. This study aims to evaluate the performance characteristics of six Russian NAATs for N. gonorrhoeae diagnostics. In total, 496 symptomatic patients were included. Five polymerase chain reaction (PCR) assays and one real-time nucleic acid sequence based amplification (NASBA) assay, developed by three Russian companies, were evaluated on urogenital samples, i.e. cervical and first voided urine (FVU) samples from females (n = 319), urethral and FVU samples from males (n = 127), and extragenital samples, i.e. rectal and pharyngeal samples, from 50 additional female patients with suspicion of gonorrhoea. As reference method, an international strictly validated real-time porA pseudogene PCR was applied. The prevalence of N. gonorrhoeae was 2.7% and 16% among the patients providing urogenital and extragenital samples, respectively. The Russian NAATs and the reference method displayed high level of concordance (99.4-100%). The sensitivities, specificities, positive predictive values and negative predictive values of the Russian tests in different specimens were 66.7-100%, 100%, 100%, and 99.4-100%, respectively. Russian N. gonorrhoeae diagnostic NAATs comprise relatively good performance characteristics. However, larger studies are crucial and, beneficially, the Russian assays should also be evaluated to other international highly sensitive and specific, and ideally Food and Drug Administration approved, NAATs such as Aptima Combo 2 (Gen-Probe).

Alerta De Insecto-Escarabajo asiatico de antenoas largas

Treesearch

Marco A. Fonseca; Ronald F. Billings

Hay probablemente una sola generacion de ALB por a'o. Los escarabajos adultos por lo general estan presentes de mayo a octubre, pero se pueden encontrar mas temprano en la primavera o mas tarde en el oto?o si las temperaturas son calidas. Los adultos por lo general permanecen en el arbol del que emergieron o se pueden desplazar por distancias cortas hacia un...

Geographical variation of overweight, obesity and related risk factors: Findings from the European Health Examination Survey in Luxembourg, 2013-2015.

PubMed

Samouda, Hanen; Ruiz-Castell, Maria; Bocquet, Valery; Kuemmerle, Andrea; Chioti, Anna; Dadoun, Frédéric; Kandala, Ngianga-Bakwin; Stranges, Saverio

2018-01-01

The analyses of geographic variations in the prevalence of major chronic conditions, such as overweight and obesity, are an important public health tool to identify "hot spots" and inform allocation of funding for policy and health promotion campaigns, yet rarely performed. Here we aimed at exploring, for the first time in Luxembourg, potential geographic patterns in overweight/obesity prevalence in the country, adjusted for several demographic, socioeconomic, behavioural and health status characteristics. Data came from 720 men and 764 women, 25-64 years old, who participated in the European Health Examination Survey in Luxembourg (2013-2015). To investigate the geographical variation, geo-additive semi-parametric mixed model and Bayesian modelisations based on Markov Chain Monte Carlo techniques for inference were performed. Large disparities in the prevalence of overweight and obesity were found between municipalities, with the highest rates of obesity found in 3 municipalities located in the South-West of the country. Bayesian approach also underlined a nonlinear effect of age on overweight and obesity in both genders (significant in men) and highlighted the following risk factors: 1. country of birth for overweight in men born in a non-European country (Posterior Odds Ratio (POR): 3.24 [1.61-8.69]) and women born in Portugal (POR: 2.44 [1.25-4.43]), 2. low educational level (secondary or below) for overweight (POR: 1.66 (1.06-2.72)] and obesity (POR:2.09 [1.05-3.65]) in men, 3. single marital status for obesity in women (POR: 2.20 [1.24-3.91]), 4.fair (men: POR: 3.19 [1.58-6.79], women: POR: 2.24 [1.33-3.73]) to very bad health perception (men: POR: 15.01 [2.16-98.09]) for obesity, 5. sleeping more than 6 hours for obesity in unemployed men (POR: 3.66 [2.02-8.03]). Protective factors highlighted were: 1. single marital status against overweight (POR: [0.60 (0.38-0.96)]) and obesity (POR: 0.39 [0.16-0.84]) in men, 2. the fact to be widowed against overweight in

The Understanding of Astronomy Concepts by Students from Basic Education of a Public School. (Spanish Title: El Entendimiento de Conceptos de Aastronmía Por Los Alumnos de Educación Básica en Una Escuela Pública.) O Entendimento de Conceitos de Astronomia Por Alunos da Educação Básica: O Caso de Uma Escola Pública Brasileira

NASA Astrophysics Data System (ADS)

Iria Machado, Daniel; dos Santos, Carlos

2011-07-01

We present the results obtained in a research on the comprehension of basic astronomical concepts, in which 561 students from fifth grade middle school to third grade high school of a public school of the city of Foz do Iguaçu (Brazil) took part. A test with 20 multiple-choice questions was applied to indentify the most common conceptions expressed by the students. This test was elaborated based on the literature about misconceptions and covered the following topics: the day-night cycle; the time zones; the seasons of the year; the phases of the Moon; the movement of the Moon; the apparent movement of the Sun in the celestial sphere; the eclipses; the dimensions and distances in the Universe; the brightness of the stars and its observation from Earth. Though a small progress was verified in the proportion of scientifically acceptable answers when comparing the eighth grade of middle school to the fifth, and the third grade of high school to the first, there was an overall predominance of alternative conceptions regarding most of the explored subjects, which persisted up to the last year of secondary school. The comparison to data found in this research made in other socio-cultural contexts revealed, in many aspects, similar notions and difficulties revealed by the students. Se presentan los resultados de una investigación sobre la comprensión de conceptos astronómicos básicos, en la cual participaron 561 estudiantes que cursaban entre el quinto grado de la enseñanza primaria y el tercer año de la enseñanza secundaria de una escuela pública de la ciudad de Foz do Iguaçu (Brasil). Se utilizó un test de 20 preguntas de opción múltiple para identificar las concepciones más comunes expresadas por los estudiantes. Este instrumento de recolección de datos se desarrolló en base a la literatura sobre las concepciones alternativas y trató los siguientes temas: el ciclo día-noche, los husos horarios, las estaciones del año, las fases de la Luna, el

Eficacia de la detección sistemática de la gripe en las fronteras en los viajeros que llegan por vía aérea*

PubMed Central

Priest, Patricia C.; Jennings, Lance C.; Duncan, Alasdair R.; Brunton, Cheryl R.; Baker, Michael G.

2015-01-01

Objetivos. Se midieron los síntomas y la prevalencia de la gripe (también llamada influenza), así como la eficacia del mecanismo de detección sistemática basado en los síntomas y la temperatura para diagnosticar la gripe en viajeros internacionales que llegaban por vía aérea. Métodos. El presente estudio transversal recopiló datos de viajeros que llegaron al aeropuerto internacional de Christchurch (Nueva Zelandia) en el invierno del 2008 mediante un cuestionario de salud, medición de la temperatura y toma de muestras de las vías respiratorias. Resultados. De los viajeros, 15 976 (68%) entregaron los formularios completos. De ellos, 17% notificaron al menos un síntoma de gripe; los síntomas más comunes fueron rinorrea o congestión nasal (10%) y tos (8%). Se tomaron muestras de las vías respiratorias de 3 769 viajeros. La prevalencia estimada de la gripe fue de 1,1% (4% en las personas sintomáticas, 0,2% en las asintomáticas). La sensibilidad de los criterios de detección varió de 84% para “cualquier síntoma” a 3% para la fiebre de 37,8 °C o mayor. El valor predictivo positivo fue bajo para todos los criterios. Conclusiones. El método de detección sistemática en las fronteras mediante la autonotificación de síntomas y la toma de la temperatura presenta limitaciones para impedir que una gripe pandémica entre en un país. Basarse en criterios como “cualquier síntoma” o la tos haría que se investigara a varias personas no infectadas, mientras que algunas personas infectadas pasarían inadvertidas. Si se usaran criterios más específicos como la fiebre, la mayoría de las personas infectadas entrarían en el país a pesar del mecanismo de detección.

Risk factors associated with human Rift Valley fever infection: systematic review and meta-analysis.

PubMed

Nicholas, Dennis E; Jacobsen, Kathryn H; Waters, Nigel M

2014-12-01

To identify risk factors for human Rift Valley fever virus (RVFV) infection. A systematic review identified 17 articles reporting on 16 studies examining risk factors for RVFV. Pooled odds ratios (pOR) were calculated for exposures examined in four or more studies. Being male [pOR = 1.4 (1.0, 1.8)], contact with aborted animal tissue [pOR = 3.4 (1.6, 7.3)], birthing an animal [pOR = 3.2 (2.4, 4.2)], skinning an animal [pOR = 2.5 (1.9, 3.2)], slaughtering an animal [pOR = 2.4 (1.4, 4.1)] and drinking raw milk [pOR = 1.8 (1.2, 2.6)] were significantly associated with RVF infection after meta-analysis. Other potential risk factors include sheltering animals in the home and milking an animal, which may both involve contact with animal body fluids. Based on the identified risk factors, use of personal protective equipment and disinfectants by animal handlers may help reduce RVFV transmission during outbreaks. Milk pasteurisation and other possible preventive methods require further investigation. © 2014 John Wiley & Sons Ltd.

Camina por Salud: Walking in Mexican-American Women

PubMed Central

Keller, Colleen S.; Gonzales, Adelita

2008-01-01

Forty-six percent of older Mexican-American women report no leisure time physical activity (PA); 38.1% are obese. This study (1) evaluated a PA intervention on reduction of risk for coronary heart disease (CHD) and (2) determined which variables affected adherence to PA. For 36 weeks, Group I walked 3 days/week; Group II walked 5 days/week. The investigators measured total body fat, regional fat, blood lipids, and adherence to PA The walking interventions favorably affected body fat, with significant differences in body mass index (BMI) reductions[F (2, 16) = 12.86, p = .001]. No statistical differences were noted in the anthropometric and blood lipid results from baseline to the 36-week measures. PMID:18457751

Desigualdad social y tendencias de mortalidad por diabetes.

PubMed

Medina-Gómez, Oswaldo; Medina-Reyes, E Ismael Seth

2017-01-01

To identify the trend of national diabetes mortality by level of marginality at the state and municipal levels. A descriptive study was conducted with records of deaths from diabetes in over 20 years from 1990 to 2013. The national mortality rate was calculated standardized by age according to the 2000 world population and the state level 2013 saw the projected naational population by join point analysis for trend analysis was performed. For the general population, the annual percentage change between 1990 and 1996 was 2.2, from 1996 to 2005 was 4.3, and from 2005 to 2013 was 0.1. The largest increase among women occurred between 1998 and 2005 while among men occurred between 1995 and 2006. At the state level was found higher annual percentage change between the towns with the highest degree of marginalization. The mortality of diabetes in women shows a significant decrease since 2004, among men, the mortality with a continuous upward trend, consistent with the trend that the disease has had in recent years. Copyright: © 2017 SecretarÍa de Salud

Disaster-related exposures and health effects among US Coast Guard responders to Hurricanes Katrina and Rita: a cross-sectional study.

PubMed

Rusiecki, Jennifer A; Thomas, Dana L; Chen, Ligong; Funk, Renée; McKibben, Jodi; Dayton, Melburn R

2014-08-01

Disaster responders work among poorly characterized physical and psychological hazards with little understood regarding health consequences of their work. A survey administered to 2834 US Coast Guard responders to Hurricanes Katrina and Rita provided data on exposures and health effects. Prevalence odds ratios (PORs) evaluated associations between baseline characteristics, missions, exposures, and health effects. Most frequent exposures were animal/insect vector (n = 1309; 46%) and floodwater (n = 817; 29%). Most frequent health effects were sunburn (n = 1119; 39%) and heat stress (n = 810; 30%). Significant positive associations were for mold exposure and sinus infection (POR = 10.39); carbon monoxide and confusion (POR = 6.27); lack of sleep and slips, trips, falls (POR = 3.34) and depression (POR = 3.01); being a Gulf-state responder and depression (POR = 3.22). Increasing protection for disaster responders requires provisions for adequate sleep, personal protective equipment, and access to medical and psychological support.

Making the invisible visible: improved electrospray ion formation of metalloporphyrins/-phthalocyanines by attachment of the formate anion (HCOO(-)).

PubMed

Hitzenberger, Jakob Felix; Dammann, Claudia; Lang, Nina; Lungerich, Dominik; García-Iglesias, Miguel; Bottari, Giovanni; Torres, Tomás; Jux, Norbert; Drewello, Thomas

2016-02-21

A protocol is developed for the coordination of the formate anion (HCOO(-)) to neutral metalloporphyrins (Pors) and -phthalocyanines (Pcs) containing divalent metals as a means to improve their ion formation in electrospray ionization (ESI). This method is particularly useful when the oxidation of the neutral metallomacrocycle fails. While focusing on Zn(II)Pors and Zn(II)Pcs, we show that formate is also readily attached to Mn(II), Mg(II) and Co(II)Pcs. However, for the Co(II)Pc secondary reactions can be observed. Upon collision-induced dissociation (CID), Zn(II)Por/Pc·formate supramolecular complexes can undergo the loss of CO2 in combination with transfer of a hydride anion (H(-)) to the zinc metal center. Further dissociation leads to electron transfer and hydrogen atom loss, generating a route to the radical anion of the Zn(II)Por/Pc without the need for electrochemical reduction, although the Zn(II)Por/Pc may have a too low electron affinity to allow electron transfer directly from the formate anion. In addition to single Por molecules, multi Por arrays were successfully analyzed by this method. In this case, multiple addition of formate occurs, giving rise to multiply charged species. In these multi Por arrays, complexation of the formate anion occurs by two surrounding Por units (sandwich). Therefore, the maximum attainment of formate anions in these arrays corresponds to the number of such sandwich complexes rather than the number of porphyrin moieties. The same bonding motif leads to dimers of the composition [(Zn(II)Por/Pc)2·HCOO](-). In these, the formate anion can act as a structural probe, allowing the distinction of isomeric ions with the formate bridging two macrocycles or being attached to a dimer of directly connected macrocycles.

Fecal Calprotectin Levels Are Closely Correlated with the Absence of Relevant Mucosal Lesions in Postoperative Crohn's Disease.

PubMed

Garcia-Planella, Esther; Mañosa, Míriam; Cabré, Eduard; Marín, Laura; Gordillo, Jordi; Zabana, Yamile; Boix, Jaume; Sáinz, Sergio; Domènech, Eugeni

2016-12-01

Fecal calprotectin (FC) is the best noninvasive biomarker of disease activity in inflammatory bowel disease. Its correlation with endoscopic mucosal lesions could save inconvenient, expensive, and repeated endoscopic examinations in particular clinical settings. To assess the correlation between FC and the existence and severity of endoscopic postoperative recurrence (POR), a group of clinically stable outpatients with Crohn's disease for whom an ileocolonoscopy was routinely planned to assess POR were invited to collect a stool sample before starting bowel cleansing to measure FC. POR was graded by means of Rutgeerts endoscopic score. One hundred nineteen ileocolonoscopies were included, 42% with endoscopic POR. FC was significantly lower in the absence of endoscopic POR and in the absence of any endoscopic lesion. The area under the receiver operating characteristic curve was 0.76 (95% confidence interval, 0.68-0.85) for the diagnosis of the absence of lesions and 0.75 (95% confidence interval, 0.66-0.84) for endoscopic POR. Better sensitivity and negative predictive value were observed when combining FC and serum C-reactive protein (CRP), leading to a sensitivity of 82%, a specificity of 53%, and negative and positive predictive values of 81% and 54%, respectively, for the prediction of endoscopic POR with a combination of FC 100 μg/g and CRP 5 mg/L cutoff values. FC correlates closely with endoscopic POR in clinically stable postoperative patients with Crohn's disease and, when used in combination with CRP, might save endoscopic examinations and allow for a high-grade suspicion of endoscopic POR in the long-term monitoring of these patients.

Anti-inflammatory, Analgesic and Antiulcer properties of Porphyra vietnamensis.

PubMed

Bhatia, Saurabh; Sharma, Kiran; Sharma, Ajay; Nagpal, Kalpana; Bera, Tanmoy

2015-01-01

Aim of the present work was to investigate the anti-inflammatory, analgesic and antiulcer effects of red seaweed Porphyra vietnamensis (P. vietnamenis). Aqueous (POR) and alcoholic (PE) fractions were successfully isolated from P. vietnamenis. Further biological investigations were performed using a classic test of paw edema induced by carrageenan, writhing induced by acetic acid, hot plate method and naproxen induced gastro-duodenal ulcer. Among the fractions POR showed better activity. POR and PE significantly (p < 0.05) reduced carrageenan induced paw edema in a dose dependent manner. In the writhing test POR significantly (p < 0.05) reduced abdominal writhes than PE. In hot plate method POR showed better analgesic activity than PE. POR showed comparable ulcers reducing potential (p<0.01) to that of omeprazole, and has more ulcer reducing potential then PE. The results of this study demonstrated that P. vietnamenis aqueous fraction possesses biological activity that is close to the standards taken for the treatment of peripheral painful or/and inflammatory and ulcer conditions.

Lipopolysaccharide does not alter small airway reactivity in mouse lung slices.

PubMed

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.

Assessment of Dry Powder Inhaler Carrier Targeted Design: A Comparative Case Study of Diverse Anomeric Compositions and Physical Properties of Lactose.

PubMed

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

Modulation of 3H-noradrenaline release by presynaptic opioid, cannabinoid and bradykinin receptors and β-adrenoceptors in mouse tissues

PubMed Central

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

Determination of chiral pharmaceuticals and illicit drugs in wastewater and sludge using microwave assisted extraction, solid-phase extraction and chiral liquid chromatography coupled with tandem mass spectrometry.

PubMed

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,

Case report of asthma associated with 3D printing.

PubMed

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

Lipopolysaccharide Does Not Alter Small Airway Reactivity in Mouse Lung Slices

PubMed Central

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

In Vitro Comparison of Aerosol Delivery Using Different Face Masks and Flow Rates With a High-Flow Humidity System.

PubMed

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.

Herbal medicine for adults with asthma: A systematic review.

PubMed

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.

Knowledge of oxygen administration, aerosol medicine, and chest physiotherapy among pediatric healthcare workers in Italy.

PubMed

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

The effects of lower than conventional doses of oral nadolol on relative beta 1/beta 2-adrenoceptor blockade.

PubMed

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)

Adrenoceptor function and expression in bladder urothelium and lamina propria.

PubMed

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.

Quantifying the Impoverishing Effects of Purchasing Medicines: A Cross-Country Comparison of the Affordability of Medicines in the Developing World

PubMed Central

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

Effect of beta2-adrenoceptor agonists and other cAMP-elevating agents on inflammatory gene expression in human ASM cells: a role for protein kinase A.

PubMed

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.

Laboratory Study Comparing Pharmacopeial Testing of Nebulizers with Evaluation Based on Nephele Mixing Inlet Methodology.

PubMed

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 salbutamol sulfate, simulating an adult tidal-breathing pattern (inspiratory to expiratory ratio = 1:1, tidal volume = 500 mL, 15 breaths per minute, peak inspiratory flow rate = 24 L/min). The two procedures were inequivalent, as FDD <5 μm by the MILS approach was 72% of that obtained using the compendial "combination" method. Since the MILS methodology more closely mimics clinical use, we infer that the compendial approach likely overestimates the dose reaching the human lung.

The β2 agonist terbutaline specifically decreases pulmonary arterial pressure under normoxia and hypoxia via α adrenoceptor antagonism.

PubMed

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.

Platelet-activating factor acether (PAF-acether) involvement in acute inflammatory and pain processes.

PubMed

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.

Pharmacological and histological examinations of regional differences of guinea-pig lung: a role of pleural surface smooth muscle in lung strip contraction.

PubMed Central

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

Exercise-Induced Changes in Exhaled NO Differentiates Asthma With or Without Fixed Airway Obstruction From COPD With Dynamic Hyperinflation.

PubMed

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.

Exercise-Induced Changes in Exhaled NO Differentiates Asthma With or Without Fixed Airway Obstruction From COPD With Dynamic Hyperinflation

PubMed Central

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

Influence of lung function on course of disease and response to antibiotic therapy in adult primary care patients with acute cough: a post hoc analysis of patients enrolled in a prospective multicentre study.

PubMed

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.

Treatment with endotracheal therapeutics after sarin microinstillation inhalation exposure increases blood cholinesterase levels in guinea pigs.

PubMed

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.

Uptake and effects of a mixture of widely used therapeutic drugs in Eruca sativa L. and Zea mays L. plants.

PubMed

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.

A cell-based assay to assess the persistence of action of agonists acting at recombinant human beta(2) adrenoceptors.

PubMed

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.

An inhibitory role for noradrenaline in the mouse vas deferens

PubMed Central

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

Congenital myasthenic syndromes in Turkey: Clinical clues and prognosis with long term follow-up.

PubMed

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.

Voltage-step pulsed electromembrane as a novel view of electrical field-induced liquid-phase microextraction.

PubMed

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.

Agonist-induced β2-adrenoceptor desensitization and downregulation enhance pro-inflammatory cytokine release in human bronchial epithelial cells.

PubMed

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.

Development of a highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) for the detection of phenylethanolamine A in tissue and feed samples and confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS).

PubMed

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.

76 FR 24857 - Fresh Garlic From the People's Republic of China: Preliminary Intent To Rescind New Shipper Reviews

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-03

... sales are not bona fide. As such, we are preliminarily rescinding the NSR for Shenzhen Bainong and... sale or entry during the original, unextended POR, and therefore we are preliminarily rescinding the...-annual NSR POR. When the sale of the subject merchandise occurs within the POR specified by the...

An ortholog of farA of Aspergillus nidulans is implicated in the transcriptional activation of genes involved in fatty acid utilization in the yeast Yarrowia lipolytica

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poopanitpan, Napapol; Kobayashi, Satoshi; Fukuda, Ryouichi

2010-11-26

Research highlights: {yields} POR1 is a Yarrowia lipolytica ortholog of farA involved in fatty acid response in A. nidulans. {yields} Deletion of POR1 caused growth defects on fatty acids. {yields} {Delta}por1 strain exhibited defects in the induction of genes involved in fatty acid utilization. -- Abstract: The yeast Yarrowia lipolytica effectively utilizes hydrophobic substrates such as fatty acids and n-alkanes. To identify a gene(s) regulating fatty acid utilization in Y. lipolytica, we first studied homologous genes to OAF1 and PIP2 of Saccharomyces cerevisiae, but their disruption did not change growth on oleic acid at all. We next characterized a Y.more » lipolytica gene, POR1 (primary oleate regulator 1), an ortholog of farA encoding a transcriptional activator that regulates fatty acid utilization in Aspergillus nidulans. The deletion mutant of POR1 was defective in the growth on various fatty acids, but not on glucose, glycerol, or n-hexadecane. It exhibited slight defect on n-decane. The transcriptional induction of genes involved in {beta}-oxidation and peroxisome proliferation by oleate was distinctly diminished in the {Delta}por1 strains. These data suggest that POR1 encodes a transcriptional activator widely regulating fatty acid metabolism in Y. lipolytica.« less

NADPH–Cytochrome P450 Oxidoreductase: Roles in Physiology, Pharmacology, and Toxicology

PubMed Central

Ding, Xinxin; Wolf, C. Roland; Porter, Todd D.; Pandey, Amit V.; Zhang, Qing-Yu; Gu, Jun; Finn, Robert D.; Ronseaux, Sebastien; McLaughlin, Lesley A.; Henderson, Colin J.; Zou, Ling; Flück, Christa E.

2013-01-01

This is a report on a symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the Experimental Biology 2012 meeting in San Diego, California, on April 25, 2012. The symposium speakers summarized and critically evaluated our current understanding of the physiologic, pharmacological, and toxicological roles of NADPH–cytochrome P450 oxidoreductase (POR), a flavoprotein involved in electron transfer to microsomal cytochromes P450 (P450), cytochrome b5, squalene mono-oxygenase, and heme oxygenase. Considerable insight has been derived from the development and characterization of mouse models with conditional Por deletion in particular tissues or partial suppression of POR expression in all tissues. Additional mouse models with global or conditional hepatic deletion of cytochrome b5 are helping to clarify the P450 isoform- and substrate-specific influences of cytochrome b5 on P450 electron transfer and catalytic function. This symposium also considered studies using siRNA to suppress POR expression in a hepatoma cell–culture model to explore the basis of the hepatic lipidosis phenotype observed in mice with conditional deletion of Por in liver. The symposium concluded with a strong translational perspective, relating the basic science of human POR structure and function to the impacts of POR genetic variation on human drug and steroid metabolism. PMID:23086197

Influence of cytochrome P450 oxidoreductase genetic polymorphisms on CYP1A2 activity and inducibility by smoking.

PubMed

Dobrinas, Maria; Cornuz, Jacques; Pedrido, Leticia; Eap, Chin B

2012-02-01

Cytochrome P4501A2 (CYP1A2) presents a high interindividual variability in its activity and also in its inducibility by smoking. Cytochrome P450 oxidoreductase (POR) is an electron transfer protein that catalyzes the activity of several cytochromes P450. We aimed to study the influence of POR genetic polymorphisms on CYP1A2 activity while smoking and after smoking cessation, as well as on CYP1A2 inducibility. CYP1A2 activity was determined by the paraxanthine/caffeine ratio in 184 smokers and in 113 of these smokers who were abstinent during a 4-week period. Participants were genotyped for POR rs17148944G>A, rs10239977C>T, rs3815455C>T, rs2286823G>A, rs2302429G>A, and rs1057868C>T (POR*28) polymorphisms. While smoking, none of the tested POR polymorphisms showed a significant influence on CYP1A2 activity. After smoking cessation, significantly higher CYP1A2 activity was found in POR rs2302429A carriers (P=0.038) and in carriers of rs17148944G-rs10239977C-rs3815455T-rs2286823G-rs2302429A-rs1057868T haplotype (P=0.038), whereas carriers of POR rs2286823A (P=0.031) and of the rs17148944G-rs10239977C-rs3815455C-rs2286823A-rs2302429G-rs1057868C haplotype (P=0.031) had decreased CYP1A2 activity. In the complete regression model, only POR rs2302429G>A showed a significant effect (P=0.017). No influence of POR genotypes or haplotypes was observed on the inducibility of CYP1A2. POR genetic polymorphisms influence CYP1A2 basal but not induced activity and do not seem to influence CYP1A2 inducibility. Future work is warranted to identify other clinical and genetic factors that may explain the variability in CYP1A2 activity and inducibility by smoking.

Deletion of P399{sub E}401 in NADPH cytochrome P450 oxidoreductase results in partial mixed oxidase deficiency

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flueck, Christa E., E-mail: christa.flueck@dkf.unibe.ch; Mallet, Delphine; Hofer, Gaby

2011-09-09

Highlights: {yields} Mutations in human POR cause congenital adrenal hyperplasia. {yields} We are reporting a novel 3 amino acid deletion mutation in POR P399{sub E}401del. {yields} POR mutation P399{sub E}401del decreased P450 activities by 60-85%. {yields} Impairment of steroid metabolism may be caused by multiple hits. {yields} Severity of aromatase inhibition is related to degree of in utero virilization. -- Abstract: P450 oxidoreductase (POR) is the electron donor for all microsomal P450s including steroidogenic enzymes CYP17A1, CYP19A1 and CYP21A2. We found a novel POR mutation P399{sub E}401del in two unrelated Turkish patients with 46,XX disorder of sexual development. Recombinant PORmore » proteins were produced in yeast and tested for their ability to support steroid metabolizing P450 activities. In comparison to wild-type POR, the P399{sub E}401del protein was found to decrease catalytic efficiency of 21-hydroxylation of progesterone by 68%, 17{alpha}-hydroxylation of progesterone by 76%, 17,20-lyase action on 17OH-pregnenolone by 69%, aromatization of androstenedione by 85% and cytochrome c reduction activity by 80%. Protein structure analysis of the three amino acid deletion P399{sub E}401 revealed reduced stability and flexibility of the mutant. In conclusion, P399{sub E}401del is a novel mutation in POR that provides valuable genotype-phenotype and structure-function correlation for mutations in a different region of POR compared to previous studies. Characterization of P399{sub E}401del provides further insight into specificity of different P450s for interaction with POR as well as nature of metabolic disruptions caused by more pronounced effect on specific P450s like CYP17A1 and aromatase.« less

"Spider"-shaped porphyrins with conjugated pyridyl anchoring groups as efficient sensitizers for dye-sensitized solar cells.

PubMed

Stangel, Christina; Bagaki, Anthi; Angaridis, Panagiotis A; Charalambidis, Georgios; Sharma, Ganesh D; Coutsolelos, Athanasios G

2014-11-17

Two novel "spider-shaped" porphyrins, meso-tetraaryl-substituted 1PV-Por and zinc-metalated 1PV-Zn-Por, bearing four oligo(p-phenylenevinylene) (oPPV) pyridyl groups with long dodecyloxy chains on the phenyl groups, have been synthesized. The presence of four pyridyl groups in both porphyrins, which allow them to act as anchoring groups upon coordination to various Lewis acid sites, the conjugated oPPV bridges, which offer the possibility of electronic communication between the porphyrin core and the pyridyl groups, and the dodecyloxy groups, which offer the advantage of high solubility in a variety of organic solvents of different polarities and could prevent porphyrin aggregation, renders porphyrins 1PV-Por and 1PV-Zn-Por very promising sensitizers for dye-sensitized solar cells (DSSCs). Photophysical measurements, together with electrochemistry experiments and density functional theory calculations, suggest that both porphyrins have frontier molecular orbital energy levels that favor electron injection and dye regeneration in DSSCs. Solar cells sensitized by 1PV-Por and 1PV-Zn-Por were fabricated, and it was found that they show power conversion efficiencies (PCEs) of 3.28 and 5.12%, respectively. Photovoltaic measurements (J-V curves) together with incident photon-to-electron conversion efficiency spectra of the two cells reveal that the higher PCE value of the DSSC based on 1PV-Zn-Por is ascribed to higher short-circuit current (Jsc), open-circuit voltage (Voc), and dye loading values. Emission spectra and electrochemistry experiments suggest a greater driving force for injection of the photogenerated electrons into the TiO2 conduction band for 1PV-Zn-Por rather than its free-base analogue. Furthermore, electrochemical impedance spectroscopy measurements prove that the utilization of 1PV-Zn-Por as a sensitizer offers a high charge recombination resistance and, therefore, leads to a longer electron lifetime.

Anti-inflammatory, Analgesic and Antiulcer properties of Porphyra vietnamensis

PubMed Central

Bhatia, Saurabh; Sharma, Kiran; Sharma, Ajay; Nagpal, Kalpana; Bera, Tanmoy

2015-01-01

Objectives: Aim of the present work was to investigate the anti-inflammatory, analgesic and antiulcer effects of red seaweed Porphyra vietnamensis (P. vietnamenis). Materials and Methods: Aqueous (POR) and alcoholic (PE) fractions were successfully isolated from P. vietnamenis. Further biological investigations were performed using a classic test of paw edema induced by carrageenan, writhing induced by acetic acid, hot plate method and naproxen induced gastro-duodenal ulcer. Results: Among the fractions POR showed better activity. POR and PE significantly (p < 0.05) reduced carrageenan induced paw edema in a dose dependent manner. In the writhing test POR significantly (p < 0.05) reduced abdominal writhes than PE. In hot plate method POR showed better analgesic activity than PE. POR showed comparable ulcers reducing potential (p<0.01) to that of omeprazole, and has more ulcer reducing potential then PE. Conclusions: The results of this study demonstrated that P. vietnamenis aqueous fraction possesses biological activity that is close to the standards taken for the treatment of peripheral painful or/and inflammatory and ulcer conditions. PMID:25767759

La Resonancia J/$$\\psi$$ y Sus Implicaciones Para La Masa Del W (in Spanish)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanchez-Hernandez, Alberto

Es un placer agradecer a mi asesor el doctor Heriberto Castilla Valdez por brindarme sus conocimientos, experiencia y paciencia en el desarrollo de esta tesis; tambien quiero agradecer al profesor H.E. Fisk, por su apoyo econemico en mi estancia en Fermilab. De igual forma agradezco a los doctores Arturo Fernandez Telles, Miguel Angel Perez Angen y Rebeca Juarez Wisozka quienes me introdujeron al campo de la fisica experimental de altas energfas. Agradezco tambien a Maribel Rios Cruz, Ruben Flores Mendieta, Juan Morales Corona, Fabiola Vazquez Valencia, Salvador Carrillo Moreno y Cecilia Uribe Estrada por su amistad y compaiierismo durante elmore » desarrollo de mi maestria. Un especial agradecimiento a Ian Adam y Kina Denisenko por su valiosa ayuda, comentarios y discusiones durante mi estancia en Fermilab. Por ultimo quisiera agradecer a mis profesores, amigos y familiares quienes siempre me apoyaron y alentaron y al Consejo N acional de Ciencia y Tecnologfa asf como al Departamento de Fisica de Cinvestav por su apoyo econemlco.« less

Influence of the doping type and level on the morphology of porous Si formed by galvanic etching

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pyatilova, O. V., E-mail: 5ilova87@gmail.com; Gavrilov, S. A.; Shilyaeva, Yu. I.

The formation of porous silicon (por-Si) layers by the galvanic etching of single-crystal Si samples (doped with boron or phosphorus) in an HF/C{sub 2}H{sub 5}OH/H{sub 2}O{sub 2} solution is investigated. The por-Si layers are analyzed by the capillary condensation of nitrogen and scanning electron microscopy (SEM). The dependences of the morphological characteristics of por-Si (pore diameter, specific surface area, pore volume, and thickness of the pore walls), which determine the por-Si combustion kinetics, on the dopant type and initial wafer resistivity are established.

Evidence for the bacterial origin of genes encoding fermentation enzymes of the amitochondriate protozoan parasite Entamoeba histolytica.

PubMed

Rosenthal, B; Mai, Z; Caplivski, D; Ghosh, S; de la Vega, H; Graf, T; Samuelson, J

1997-06-01

Entamoeba histolytica is an amitochondriate protozoan parasite with numerous bacterium-like fermentation enzymes including the pyruvate:ferredoxin oxidoreductase (POR), ferredoxin (FD), and alcohol dehydrogenase E (ADHE). The goal of this study was to determine whether the genes encoding these cytosolic E. histolytica fermentation enzymes might derive from a bacterium by horizontal transfer, as has previously been suggested for E. histolytica genes encoding heat shock protein 60, nicotinamide nucleotide transhydrogenase, and superoxide dismutase. In this study, the E. histolytica por gene and the adhE gene of a second amitochondriate protozoan parasite, Giardia lamblia, were sequenced, and their phylogenetic positions were estimated in relation to POR, ADHE, and FD cloned from eukaryotic and eubacterial organisms. The E. histolytica por gene encodes a 1,620-amino-acid peptide that contained conserved iron-sulfur- and thiamine pyrophosphate-binding sites. The predicted E. histolytica POR showed fewer positional identities to the POR of G. lamblia (34%) than to the POR of the enterobacterium Klebsiella pneumoniae (49%), the cyanobacterium Anabaena sp. (44%), and the protozoan Trichomonas vaginalis (46%), which targets its POR to anaerobic organelles called hydrogenosomes. Maximum-likelihood, neighbor-joining, and parsimony analyses also suggested as less likely E. histolytica POR sharing more recent common ancestry with G. lamblia POR than with POR of bacteria and the T. vaginalis hydrogenosome. The G. lamblia adhE encodes an 888-amino-acid fusion peptide with an aldehyde dehydrogenase at its amino half and an iron-dependent (class 3) ADH at its carboxy half. The predicted G. lamblia ADHE showed extensive positional identities to ADHE of Escherichia coli (49%), Clostridium acetobutylicum (44%), and E. histolytica (43%) and lesser identities to the class 3 ADH of eubacteria and yeast (19 to 36%). Phylogenetic analyses inferred a closer relationship of the E

First example of a modular porphyrinoid assembly capable of stabilizing different metal ions in a single molecular scaffold.

PubMed

Murugavel, Muthuchamy; Reddy, R V Ramana; Dey, Dhananjay; Sankar, Jeyaraman

2015-10-05

We report the synthesis and characterization of porphyrin-corrole-porphyrin (Por-Cor-Por) hybrids directly linked at the meso-meso positions for the first time. The stability and solubility of the trimer are carefully balanced by adding electron-withdrawing substituents to the corrole ring and sterically bulky groups on the porphyrins. The new hybrids are capable of stabilizing more than one metal ion in a single molecular scaffold. The versatility of the triad has been demonstrated by successfully stabilizing homo- (Ni) and heterotrinuclear (Ni-Cu-Ni) coordination motifs. The solid-state structure of the NiPor-CuCor-PorNi hybrid was revealed by single-crystal X-ray diffraction studies. The Ni(II) porphyrins are significantly ruffled and tilted by 83° from the plane of corrole. The robustness of the synthesized hybrids was reflected in the electrochemical investigations and the redox behaviour of the hybrids show that the oxidation processes are mostly corrole-centred. In particular it is worth noting that the Por-Cor-Por hybrid can further be manipulated due to the presence of substituent-free meso-positions on both the terminals. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Management of post-operative Crohn's disease in 2017: where do we go from here?

PubMed

Nguyen, Vu; Kanth, Rajan; Gazo, Joshua; Sorrentino, Dario

2016-11-01

Postoperative recurrence (POR) of Crohn's disease is common after surgical resection. How to best manage POR remains uncertain. Areas covered: In this review, we will first describe the natural course and the best modalities to diagnose this surgical sequela. We will then focus on the potential risk factors for relapse and highlight the main shortcomings in the current study designs and endoscopic and clinical scoring systems, which may partly explain the unexpected outcomes of recent clinical trials. Finally, we will propose a strategy to address the management of POR. Expert commentary: Anti-tumor necrosis factor (Anti-TNF) agents are the most effective therapy to prevent POR in Crohn's disease. Patient risk stratification and active monitoring with scheduled ileocolonoscopy are cornerstones of optimal POR management. Further studies are needed to address areas of uncertainty including timing and duration of therapy and the role of therapeutic drug monitoring in this setting.

Developing a military nurse scientist program of research: A military women's health exemplar.

PubMed

Trego, Lori Lyn

Developing a feasible, fundable, and sustainable program of research (POR) is an essential career goal in research. Nurse scientists can lay the foundation for a salient POR as early as during their doctoral studies. The ensuing years of postdoctoral experiences are informative as they expand their research skills and knowledge around their research area of interest. Following graduation from a doctoral research program, novice military nurse scientists (MNS) are placed in positions that are conducive to fostering a POR. Military organizational support and the rich experiences of peers and mentors facilitate early career development of MNS. The purpose of this article is to present a conceptual framework for research career development of the novice MNS. Using an exemplar POR in military women's health, the concepts are operationalized to illustrate how the military environment enhances the development of a successful POR. Copyright © 2017 Elsevier Inc. All rights reserved.

Association between arsenic exposure from drinking water and proteinuria: results from the Health Effects of Arsenic Longitudinal Study

PubMed Central

Chen, Yu; Parvez, Faruque; Liu, Mengling; Pesola, Gene R; Gamble, Mary V; Slavkovich, Vesna; Islam, Tariqul; Ahmed, Alauddin; Hasan, Rabiul; Graziano, Joseph H; Ahsan, Habibul

2011-01-01

Background Proteinuria has been recognized as a marker for an increased risk of chronic renal disease. It is unclear whether arsenic (As) exposure from drinking water is associated with proteinuria. Methods We evaluated the association between As exposure from drinking water and proteinuria in 11 122 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Proteinuria was detected by urinary dipstick tests at baseline and at 2-year intervals. As exposure variables included baseline well As and changes in urinary As during follow-up modelled as time-dependent variables in the analyses. Results At baseline, well As was positively related to prevalence of proteinuria; prevalence odds ratios (PORs) for proteinuria in increasing quintiles of well As (≤7, 8–39, 40–91, 92–179 and 180–864 µg/l) were 1.00 (ref), POR 0.99 [95% confidence interval (CI) 0.77–1.27], POR 1.23 (95% CI 0.97–1.57), POR 1.50 (95% CI 1.18–1.89) and POR 1.59 (95% CI 1.26–2.00) (P for trend <0.01). Hazard ratios for incidence of proteinuria were POR 0.83 (95% CI 0.67–1.03) and POR 0.91 (95% CI 0.74–1.12) for participants with a decreasing level of >70 and 17–70 µg/l in urinary As over time, respectively, and were POR 1.17 (95% CI 0.97–1.42) and POR 1.42 (95% CI 1.16–1.73) for participants with an increasing level of 16–68 and >68 µg/l in urinary As over time, respectively, compared with the group with relatively little changes in urinary As as the reference group (urinary As −16 to 15 µg/l). Conclusion The findings suggest that there are adverse effects of As exposure on the risk of proteinuria and the effects are modifiable by recent changes in As exposure. PMID:21343184

Recombinant Salivary Proteins of Phlebotomus orientalis are Suitable Antigens to Measure Exposure of Domestic Animals to Sand Fly Bites

PubMed Central

Sima, Michal; Ferencova, Blanka; Warburg, Alon; Rohousova, Iva; Volf, Petr

2016-01-01

Background Certain salivary proteins of phlebotomine sand flies injected into the host skin during blood-feeding are highly antigenic and elicit strong antibody-mediated immune responses in repeatedly-exposed hosts. These antibodies can be measured by enzyme-linked immuno sorbent assays (ELISAs) using salivary gland homogenates (SGHs) as the source of antigens and serve as a markers for exposure to biting sand flies. Large-scale screening for anti-sand fly saliva antibodies requires replacement of SGH with recombinant salivary proteins. In East Africa, Phlebotomus orientalis is the main vector of Leishmania donovani, a trypanosomatid parasite causing visceral leishmaniasis. We tested recombinant salivary proteins derived from Ph. orientalis saliva to study exposure of domestic animals to this sand fly species. Methodology/Principal Findings Antigenic salivary proteins from Ph. orientalis were identified by immunoblot and mass spectrometry. Recombinant apyrase rPorSP15, yellow-related protein rPorSP24, ParSP25-like protein rPorSP65, D7-related protein rPorSP67, and antigen 5-related protein rPorSP76 were tested using ELISA with sera of domestic animals from L. donovani foci in Ethiopia where Ph. orientalis is present. Our results highlighted recombinant yellow-related protein rPorSP24 as the most promising antigen, displaying a high positive correlation coefficient as well as good sensitivity and specificity when compared to SGH. This recombinant protein was the most suitable one for testing sera of dogs, sheep, and goats. In addition, a different antigen, rPorSP65 was found efficacious for testing canine sera. Conclusions/Significance Recombinant salivary proteins of Ph. orientalis, specifically rPorSP24, were shown to successfully substitute SGH in serological experiments to measure exposure of domestic animals to Ph. orientalis, the vector of L. donovani. The results suggest that rPorSP24 might be a suitable antigen for detecting anti-Ph. orientalis antibody

Recombinant Salivary Proteins of Phlebotomus orientalis are Suitable Antigens to Measure Exposure of Domestic Animals to Sand Fly Bites.

PubMed

Sima, Michal; Ferencova, Blanka; Warburg, Alon; Rohousova, Iva; Volf, Petr

2016-03-01

Certain salivary proteins of phlebotomine sand flies injected into the host skin during blood-feeding are highly antigenic and elicit strong antibody-mediated immune responses in repeatedly-exposed hosts. These antibodies can be measured by enzyme-linked immuno sorbent assays (ELISAs) using salivary gland homogenates (SGHs) as the source of antigens and serve as a markers for exposure to biting sand flies. Large-scale screening for anti-sand fly saliva antibodies requires replacement of SGH with recombinant salivary proteins. In East Africa, Phlebotomus orientalis is the main vector of Leishmania donovani, a trypanosomatid parasite causing visceral leishmaniasis. We tested recombinant salivary proteins derived from Ph. orientalis saliva to study exposure of domestic animals to this sand fly species. Antigenic salivary proteins from Ph. orientalis were identified by immunoblot and mass spectrometry. Recombinant apyrase rPorSP15, yellow-related protein rPorSP24, ParSP25-like protein rPorSP65, D7-related protein rPorSP67, and antigen 5-related protein rPorSP76 were tested using ELISA with sera of domestic animals from L. donovani foci in Ethiopia where Ph. orientalis is present. Our results highlighted recombinant yellow-related protein rPorSP24 as the most promising antigen, displaying a high positive correlation coefficient as well as good sensitivity and specificity when compared to SGH. This recombinant protein was the most suitable one for testing sera of dogs, sheep, and goats. In addition, a different antigen, rPorSP65 was found efficacious for testing canine sera. Recombinant salivary proteins of Ph. orientalis, specifically rPorSP24, were shown to successfully substitute SGH in serological experiments to measure exposure of domestic animals to Ph. orientalis, the vector of L. donovani. The results suggest that rPorSP24 might be a suitable antigen for detecting anti-Ph. orientalis antibody-mediated reactions also in other host species.

A Comparison Between PSRK and GERG-2004 Equation of State for Simulation of Non-Isothermal Compressible Natural Gases Mixed with Hydrogen in Pipelines / Porównanie równań stanu opracowanych według metody PSRK oraz GERG-2004 wykorzystanych do symulacji zachowania ściśliwych mieszanin gazu ziemnego i wodoru w rurociągach, w warunkach przepływów nie-izotermicznych

NASA Astrophysics Data System (ADS)

Uilhoorn, Frits E.

2013-06-01

In this work, the GERG-2004 equation of state based on a multi-fluid approximation explicit in the reduced Helmholtz energy is compared with the predictive Soave-Redlich-Kwong group contribution method. In the analysis, both equations of state are compared by simulating a non-isothermal transient flow of natural gas and mixed hydrogen-natural gas in pipelines. Besides the flow conditions also linepack-energy and energy consumption of the compressor station are computed. The gas flow is described by a set of partial differential equations resulting from the conservation of mass, momentum and energy. A pipeline section of the Yamal-Europe gas pipeline on Polish territory has been selected for the case study. W artykule dokonano porównania wyników uzyskanych przy wykorzystaniu równania stanu GERG- 2004 opartego na jawnym przybliżeniu wyników dla wielu cieczy w oparciu o zredukowaną energię Helmhotza oraz wyników uzyskanych w oparciu o metodę Soave-Redlich Kwonga. Obydwa równania stanu porównano poprzez przeprowadzenie symulacji stanów przejściowych przepływów gazu ziemnego oraz mieszanin gazu ziemnego i wodoru w rurociągach w warunkach przepływów nie-izotermicznych. Oprócz warunków przepływu, określono energię w napełnionym układzie oraz zużycie energii przez stację kompresora. Przepływ gazu opisano zbiorem równań różniczkowych cząstkowych, wyprowadzonych w oparciu o prawa zachowania masy, pędu i energii. Jako studium przypadku wybrano fragment rurociągu jamalskiego (Yamal- Europa) przebiegającego przez terytorium Polski.

Weathering resistance of thin plasma polymer films on pre-coated steel =

NASA Astrophysics Data System (ADS)

Serra, Ricardo Gil Henriques

O trabalho apresentado teve origem no projecto de investigacao “Tailored Thin Plasma Polymers Films for Surface Engineering of Coil Coated Steel”, financiado pelo Programa Europeu ECSC Steel Research. Sistemas de aco galvanizado pre-pintado em banda a base de poliester e poliuretano foram submetidos a um processo de polimerizacao por plasma onde um filme fino foi depositado de modo a modificar as propriedades de superficie. Foram usados reactores de catodo oco, microondas e radio frequencia para a deposicao do polimero fino. Os sistemas preparados foram analisados de modo a verificar a influencia do processo de polimerizacao por plasma na alteracao das propriedades barreira dos sistemas pre-pintados em banda. Foi estudado o efeito dos diferentes passos do processo de polimerizacao por plasma, bem como o efeito de diferentes variaveis operatorias. A mistura precursora foi variada de modo a modificar as propriedades da superficie de modo a poder vir a obter maior hidrofobicidade, maior resistencia a marcas digitais, bem como maior facilidade de limpeza. Os testes foram conduzidos em solucao de NaCl 0,5 M. Para o trabalho foram usadas tecnicas de analise da morfologia da superficie como Microscopia de Forca Atomica e Microscopia Electronica de Varrimento. As propriedades electroquimicas dos sistemas foram estudadas por Espectroscopia de Impedancia Electroquimica. A estrutura dos filmes gerados no processo de polimerizacao por plasma foi caracterizada por Microscopia de Transmissao Electronica. A modificacao das propriedades opticas devido ao processo de polimerizacao por plasma foi tambem obtida.

Prognosis and cost-effectiveness of IVF in poor responders according to the Bologna Criteria.

PubMed

Busnelli, Andrea; Somigliana, Edgardo

2018-02-01

Poor ovarian response (POR) to controlled ovarian hyperstimulation for in vitro fertilization (IVF) is one of the most challenging issue in the field of reproductive medicine. However, even if improving IVF outcome in poor responders (PORs) represents a main priority, the lack of a unique definition of POR has hampered research in this area. In order to overcome this impediment, an ESHRE Campus Workshop was organized in Bologna in 2010 and reached a consensus on the criteria for the diagnosis of POR ("Bologna Criteria"). In this review we aimed to estimate the prognostic potential of the ESHRE definition, to elucidate its possible weaknesses and to analyze the economic aspects of IVF in a population of poor responders (PORs). Available evidence confirmed that the Bologna criteria are able to select a population with a poor IVF prognosis thus supporting their validity. Nonetheless, different aspects of the definition have been criticized. The main points of debate concern the homogeneity of the population identified, the cut-off values chosen for the ovarian reserve tests and the risks factors other than age associated with POR. Data concerning the economic profile of IVF in PORs are scanty. The only published study on the argument showed that IVF in these cases is not cost-effective. However, considering the potential substantial impact of cost-effectiveness analyses on public health policies, there is the need for further and independent validations.

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.

El Estado de los Bosques de Puerto Rico, 2003

Treesearch

Thomas J. Brandeis; Eileen H. Helmer; Sonja N. Oswalt

2003-01-01

La cobertura forestal de Puerto Rico sigue aumentando y ahora asciende a un 57 por ciento en la isla de Puerto Rico, 85 por ciento en Vieques y 88 por ciento en Culebra. Los bosques subtropicales secos ocupan 50 346 ha, 6832 ha, 2591 ha y 6217 ha en las islas de Puerto Rico, Vieques, Culebra y Mona, respectivamente. El bosque subtropical húmedo, la zona de vida...

"Power-on resets" in cardiac implantable electronic devices during magnetic resonance imaging.

PubMed

Higgins, John V; Sheldon, Seth H; Watson, Robert E; Dalzell, Connie; Acker, Nancy; Cha, Yong-Mei; Asirvatham, Samuel J; Kapa, Suraj; Felmlee, Joel P; Friedman, Paul A

2015-03-01

Magnetic resonance imaging (MRI) has been safely performed in some patients with cardiac implantable electronic devices (CIEDs) under careful monitoring and prespecified conditions. Pacemaker-dependent patients are often excluded, partly because of the potential for "power-on reset" (PoR), which can lead to a change from asynchronous to inhibited pacing with consequent inhibition of pacing due to electromagnetic interference during MRI. The purpose of this study was to review risk factors for PoR during MRI. A prospective study was performed between January 2008 and May 2013 in patients with CIEDs undergoing clinically indicated MRI. Eligible patients were not pacemaker dependent. Devices were interrogated before and after MRI, programmed to an asynchronous mode or an inhibition mode with tachyarrhythmia therapies turned off, and reprogrammed to their original settings after MRI. MRI scans (n = 256) were performed in 198 patients with non-MRI-conditional CIEDs between 2008 and 2013 (median age 66 years; interquartile range 57-77 years; 59% men). PoR occurred during 9 MRI scans (3.5%) in 8 patients. PoR was more frequent with Medtronic devices than with other generator brands (n = 9/139 vs 0/117 [6% vs 0%]; P = .005). Devices with PoR were all released before 2002 and were implanted from 1999 to 2004. Effects of PoR included a decrease in heart rate during MRI (n = 4) and transient anomalous battery life indication (n = 1). All devices functioned normally after MRI. PoR occurs infrequently but can cause deleterious changes in pacing mode and heart rate. MRI should not be performed in pacemaker-dependent patients with older at-risk generators. Continuous monitoring during MRI is essential because unrecognized PoR may inhibit pacing or accelerate battery depletion due to high pacing output. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Hospitalization costs of severe bacterial pneumonia in children: comparative analysis considering different costing methods.

PubMed

Nunes, Sheila Elke Araujo; Minamisava, Ruth; Vieira, Maria Aparecida da Silva; Itria, Alexander; Pessoa, Vicente Porfirio; Andrade, Ana Lúcia Sampaio Sgambatti de; Toscano, Cristiana Maria

2017-01-01

To determine and compare hospitalization costs of bacterial community-acquired pneumonia cases via different costing methods under the Brazilian Public Unified Health System perspective. Cost-of-illness study based on primary data collected from a sample of 59 children aged between 28 days and 35 months and hospitalized due to bacterial pneumonia. Direct medical and non-medical costs were considered and three costing methods employed: micro-costing based on medical record review, micro-costing based on therapeutic guidelines and gross-costing based on the Brazilian Public Unified Health System reimbursement rates. Costs estimates obtained via different methods were compared using the Friedman test. Cost estimates of inpatient cases of severe pneumonia amounted to R$ 780,70/$Int. 858.7 (medical record review), R$ 641,90/$Int. 706.90 (therapeutic guidelines) and R$ 594,80/$Int. 654.28 (Brazilian Public Unified Health System reimbursement rates). Costs estimated via micro-costing (medical record review or therapeutic guidelines) did not differ significantly (p=0.405), while estimates based on reimbursement rates were significantly lower compared to estimates based on therapeutic guidelines (p<0.001) or record review (p=0.006). Brazilian Public Unified Health System costs estimated via different costing methods differ significantly, with gross-costing yielding lower cost estimates. Given costs estimated by different micro-costing methods are similar and costing methods based on therapeutic guidelines are easier to apply and less expensive, this method may be a valuable alternative for estimation of hospitalization costs of bacterial community-acquired pneumonia in children. Determinar e comparar custos hospitalares no tratamento da pneumonia bacteriana adquirida na comunidade por diferentes metodologias de custeio, na perspectiva do Sistema Único de Saúde. Estudo de custo, com coleta de dados primários de uma amostra de 59 crianças com 28 dias a 35 meses de idade

The role of galectin-1 in in vitro and in vivo photodynamic therapy with a galactodendritic porphyrin.

PubMed

Pereira, Patrícia M R; Silva, Sandrina; Ramalho, José S; Gomes, Célia M; Girão, Henrique; Cavaleiro, José A S; Ribeiro, Carlos A F; Tomé, João P C; Fernandes, Rosa

2016-11-01

Conventional photodynamic agents used in clinic are porphyrin-based photosensitizers. However, they have low tumour selectivity, which may induce unwanted side-effects and damage to healthy tissues. In this study, we used a porphyrin with dendritic units of galactose (PorGal 8 ) developed by us, which can target the galactose-binding protein, galectin-1, known to be overexpressed in many tumour tissues. In vitro and in vivo studies had been conducted for the validation of PorGal 8 effectiveness. We showed a specific uptake of PorGal 8 and induction of apoptotic cell death by generating oxidative stress and alterations in the cytoskeleton of bladder cancer cells overexpressing galectin-1. We further validated the photodynamic efficiency of PorGal 8 in athymic nude mice (Balb/c nu/nu) bearing subcutaneously implanted luciferase-positive bladder cancer xenografts, overexpressing galectin-1 protein. PorGal 8 (5 μmol/kg, intraperitoneal), injected 24 h before light delivery (50.4 J/cm 2 ), inhibited tumour growth. We conclude that the use of PorGal 8 enables selective target and cytotoxicity by photodynamic therapy in cancer cells overexpressing galectin-1, preventing undesired phototoxicity in the surrounding healthy tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

Empirical Analysis of Using Erasure Coding in Outsourcing Data Storage With Provable Security

DTIC Science & Technology

2016-06-01

the fastest encoding performance among the four tested schemes. We expected to observe that Cauchy Reed-Solomonwould be faster than Reed- Solomon for all...providing recoverability for POR. We survey MDS codes and select Reed- Solomon and Cauchy Reed- Solomon MDS codes to be implemented into a prototype POR...tools providing recoverability for POR. We survey MDS codes and select Reed- Solomon and Cauchy Reed- Solomon MDS codes to be implemented into a

Co-infection of classic swine H1N1 influenza virus in pigs persistently infected with porcine rubulavirus.

PubMed

Rivera-Benitez, José Francisco; De la Luz-Armendáriz, Jazmín; Saavedra-Montañez, Manuel; Jasso-Escutia, Miguel Ángel; Sánchez-Betancourt, Ivan; Pérez-Torres, Armando; Reyes-Leyva, Julio; Hernández, Jesús; Martínez-Lara, Atalo; Ramírez-Mendoza, Humberto

2016-02-29

Porcine rubulavirus (PorPV) and swine influenza virus infection causes respiratory disease in pigs. PorPV persistent infection could facilitate the establishment of secondary infections. The aim of this study was to analyse the pathogenicity of classic swine H1N1 influenza virus (swH1N1) in growing pigs persistently infected with porcine rubulavirus. Conventional six-week-old pigs were intranasally inoculated with PorPV, swH1N1, or PorPV/swH1N1. A mock-infected group was included. The co-infection with swH1N1 was at 44 days post-infection (DPI), right after clinical signs of PorPV infection had stopped. The pigs of the co-infection group presented an increase of clinical signs compared to the simple infection groups. In all infected groups, the most recurrent lung lesion was hyperplasia of the bronchiolar-associated lymphoid tissue and interstitial pneumonia. By means of immunohistochemical evaluation it was possible to demonstrate the presence of the two viral agents infecting simultaneously the bronchiolar epithelium. Viral excretion of PorPV in nasal and oral fluid was recorded at 28 and 52 DPI, respectively. PorPV persisted in several samples from respiratory tissues (RT), secondary lymphoid organs (SLO), and bronchoalveolar lavage fluid (BALF). For swH1N1, the viral excretion in nasal fluids was significantly higher in single-infected swH1N1 pigs than in the co-infected group. However, the co-infection group exhibited an increase in the presence of swH1N1 in RT, SLO, and BALF at two days after co-infection. In conclusion, the results obtained confirm an increase in the clinical signs of infection, and PorPV was observed to impact the spread of swH1N1 in analysed tissues in the early stage of co-infection, although viral shedding was not enhanced. In the present study, the interaction of swH1N1 infection is demonstrated in pigs persistently infected with PorPV. Copyright © 2016 Elsevier B.V. All rights reserved.

Management of phosgene-induced acute lung injury.

PubMed

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

Monóxido de carbono

EPA Pesticide Factsheets

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.

Genetic variations in NADPH-CYP450 oxidoreductase in a Czech Slavic cohort

PubMed Central

Tomková, Mária; Panda, Satya Prakash; Šeda, Ondřej; Baxová, Alice; Hůlková, Martina; Masters, Bettie Sue Siler; Martásek, Pavel

2015-01-01

Background Gene polymorphisms encoding the enzyme NADPH–cytochrome P450 oxidoreductase (POR) contribute to inter-individual differences in drug response. Aim To estimate polymorphic allele frequencies of the POR gene in a Czech Slavic population. Materials & Methods The gene POR was analyzed in 322 Czech Slavic individuals from a control cohort by sequencing and HRM analysis. Results Twenty-five SNP genetic variations were identified. Of these variants, 7 were new, unreported SNPs, including two SNPs in the 5´flanking region (g.4965 C>T and g.4994 G>T), one intronic variant (c.1899 −20C>T), one synonymous SNP (p.20Ala=) and three nonsynonymous SNPs (p.Thr29Ser, p.Pro384Leu and p.Thr529Met). The p.Pro384Leu variant exhibited reduced enzymatic activities compared to wild type. Conclusion New POR variant identification indicates that the number of uncommon variants might be specific for each subpopulation being investigated, particularly germane to the singular role that POR plays in providing reducing equivalents to all CYPs in the endoplasmic reticulum. PMID:25712184

Completing the surrogate motherhood process: parental order reporters' attitudes towards surrogacy arrangements, role ambiguity and role conflict.

PubMed

Purewal, Satvinder; Crawshaw, Marilyn; van den Akker, Olga

2012-06-01

This study investigated the attitudes of parental order reporters (PORs) towards their work with surrogacy arrangements and their experiences of role conflict and role ambiguity. A questionnaire was used to assess PORs' perceptions of their role in parental order [PO] applications, attitudes towards surrogacy arrangements and the legal process and the influence of role ambiguity or conflict. Questionnaires were distributed to all PORs employed by the Children and Family Court Advisory and Support Service in England. Thirty-three PORs participated (response rate 46%) who, on average, had each completed five PO applications (range 1-40). Positive attitudes towards surrogacy and the child's needs for openness about origins were found. Concerns about the inadequacy of preparation and assessment arrangements, overseas arrangements and non-regulation of surrogacy agencies were evident. PORs with high-role ambiguity were more likely to report less positive attitudes towards the emotional consequence of surrogacy on offspring. High scores on role ambiguity and role conflict were reflected in less positive attitudes towards the parties' preparation towards parenthood. These results have implications for training, policy and practice in this area.

Neuraminidase activity of blue eye disease porcine rubulavirus: Specificity, affinity and inhibition studies.

PubMed

Santos-López, Gerardo; Borraz-Argüello, María T; Márquez-Domínguez, Luis; Flores-Alonso, Juan Carlos; Ramírez-Mendoza, Humberto; Priem, Bernard; Fort, Sébastien; Vallejo-Ruiz, Verónica; Reyes-Leyva, Julio; Herrera-Camacho, Irma

2017-10-01

Porcine rubulavirus (PorPV), also known as La Piedad Michoacan Virus (LPMV) causes encephalitis and reproductive failure in newborn and adult pigs, respectively. The hemagglutinin-neuraminidase (HN) glycoprotein is the most exposed and antigenic of the virus proteins. HN plays central roles in PorPV infection; i.e., it recognizes sialic acid-containing cell receptors that mediate virus attachment and penetration; in addition, its neuraminidase (sialic acid releasing) activity has been proposed as a virulence factor. This work describes the purification and characterization of PorPV HN protein (isolate PAC1). The specificity of neuraminidase is restricted to sialyl(α2,3)lactose (3SL). HN showed typical Michaelis-Menten kinetics with fetuin as substrate (km=0.029μM, Vmax=522.8nmolmin -1 mg -1 ). When 3SL was used as substrate, typical cooperative kinetics were found (S 50 =0.15μM, Vmax=154.3nmolmin -1 mg -1 ). The influenza inhibitor zanamivir inhibited the PorPV neuraminidase with IC 50 of 0.24μM. PorPV neuraminidase was activated by Ca 2+ and inhibited by nucleoside triphosphates with the level of inhibition depending on phosphorylation level. The present results open possibilities to study the role of neuraminidase in the pathogenicity of PorPV infection and its potential inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prevalence of asthma and chronic obstructive pulmonary disease in Aboriginal and non-Aboriginal populations: A systematic review and meta-analysis of epidemiological studies

PubMed Central

Ospina, Maria B; Voaklander, Donald C; Stickland, Michael K; King, Malcolm; Senthilselvan, Ambikaipakan; Rowe, Brian H

2012-01-01

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) have considerable potential for inequities in diagnosis and treatment, thereby affecting vulnerable groups. OBJECTIVE: To evaluate differences in asthma and COPD prevalence between adult Aboriginal and non-Aboriginal populations. METHODS: MEDLINE, EMBASE, specialized databases and the grey literature up to October 2011 were searched to identify epidemiological studies comparing asthma and COPD prevalence between Aboriginal and non-Aboriginal adult populations. Prevalence ORs (PORs) and 95% CIs were calculated in a random-effects meta-analysis. RESULTS: Of 132 studies, eight contained relevant data. Aboriginal populations included Native Americans, Canadian Aboriginals, Australian Aboriginals and New Zealand Maori. Overall, Aboriginals were more likely to report having asthma than non-Aboriginals (POR 1.41 [95% CI 1.23 to 1.60]), particularly among Canadian Aboriginals (POR 1.80 [95% CI 1.68 to 1.93]), Native Americans (POR 1.41 [95% CI 1.13 to 1.76]) and Maori (POR 1.64 [95% CI 1.40 to 1.91]). Australian Aboriginals were less likely to report asthma (POR 0.49 [95% CI 0.28 to 0.86]). Sex differences in asthma prevalence between Aboriginals and their non-Aboriginal counterparts were not identified. One study compared COPD prevalence between Native and non-Native Americans, with similar rates in both groups (POR 1.08 [95% CI 0.81 to 1.44]). CONCLUSIONS: Differences in asthma prevalence between Aboriginal and non-Aboriginal populations exist in a variety of countries. Studies comparing COPD prevalence between Aboriginal and non-Aboriginal populations are scarce. Further investigation is needed to identify and account for factors associated with respiratory health inequalities among Aboriginal peoples. PMID:23248798

Disconnection of the Perirhinal and Postrhinal Cortices Impairs Recognition of Objects in Context But Not Contextual Fear Conditioning

PubMed Central

2017-01-01

The perirhinal cortex (PER) is known to process object information, whereas the rodent postrhinal cortex (POR), homolog to the parahippocampal cortex in primates, is thought to process spatial information. A number of studies, however, provide evidence that both areas are involved in processing contextual information. In this study, we tested the hypothesis that the rat POR relies on object information received from the PER to form complex representations of context. Using three fear-conditioning (FC) paradigms (signaled, unsignaled, and renewal) and two context-guided object recognition tasks (with 3D and 2D objects), we examined the effects of crossed excitotoxic lesions to the POR and the contralateral PER. Performance of rats with crossed lesions was compared with that of rats with ipsilateral POR plus PER lesions and sham-operated rats. We found that rats with contralateral PER–POR lesions were impaired in object–context recognition but not in contextual FC. Therefore, interaction between the POR and PER is necessary for context-guided exploratory behavior but not for associating fear with context. Our results provide evidence for the hypothesis that the POR relies on object and pattern information from the PER to encode representations of context. The association of fear with a context, however, may be supported by alternate cortical and/or subcortical pathways when PER–POR interaction is not available. Our results suggest that contextual FC may represent a special case of context-guided behavior. SIGNIFICANCE STATEMENT Representations of context are important for perception, memory, decision making, and other cognitive processes. Moreover, there is extensive evidence that the use of contextual representations to guide appropriate behavior is disrupted in neuropsychiatric and neurological disorders including developmental disorders, schizophrenia, affective disorders, and Alzheimer's disease. Many of these disorders are accompanied by changes in

Paleoenvironmental implications of taxonomic variation among δ 15 N values of chloropigments

NASA Astrophysics Data System (ADS)

Higgins, Meytal B.; Wolfe-Simon, Felisa; Robinson, Rebecca S.; Qin, Yelun; Saito, Mak A.; Pearson, Ann

2011-11-01

Natural variations in the ratios of nitrogen isotopes in biomass reflect variations in nutrient sources utilized for growth. In order to use δ 15N values of chloropigments of photosynthetic organisms to determine the corresponding δ 15N values of biomass - and by extension, surface waters - the isotopic offset between chlorophyll and biomass must be constrained. Here we examine this offset in various geologically-relevant taxa, grown using nutrient sources that may approximate ocean conditions at different times in Earth's history. Phytoplankton in this study include cyanobacteria (diazotrophic and non-diazotrophic), eukaryotic algae (red and green), and anoxygenic photosynthetic bacteria (Proteobacteria), as well as environmental samples from sulfidic lake water. Cultures were grown using N 2, NO 3-, and NH 4+ as nitrogen sources, and were examined under different light regimes and growth conditions. We find surprisingly high variability in the isotopic difference (δ 15N biomass - δ 15N chloropigment) for prokaryotes, with average values for species ranging from -12.2‰ to +11.7‰. We define this difference as ɛpor, a term that encompasses diagenetic porphyrins and chlorins, as well as chlorophyll. Negative values of ɛpor reflect chloropigments that are 15N-enriched relative to biomass. Notably, this enrichment appears to occur only in cyanobacteria. The average value of ɛpor for freshwater cyanobacterial species is -9.8 ± 1.8‰, while for marine cyanobacteria it is -0.9 ± 1.3‰. These isotopic effects group environmentally but not phylogenetically, e.g., ɛpor values for freshwater Chroococcales resemble those of freshwater Nostocales but differ from those of marine Chroococcales. Our measured values of ɛpor for eukaryotic algae (range = 4.7-8.7‰) are similar to previous reports for pure cultures. For all taxa studied, values of ɛpor do not depend on the type of nitrogen substrate used for growth. The observed environmental control of ɛpor

Disconnection of the Perirhinal and Postrhinal Cortices Impairs Recognition of Objects in Context But Not Contextual Fear Conditioning.

PubMed

Heimer-McGinn, Victoria R; Poeta, Devon L; Aghi, Krishan; Udawatta, Methma; Burwell, Rebecca D

2017-05-03

The perirhinal cortex (PER) is known to process object information, whereas the rodent postrhinal cortex (POR), homolog to the parahippocampal cortex in primates, is thought to process spatial information. A number of studies, however, provide evidence that both areas are involved in processing contextual information. In this study, we tested the hypothesis that the rat POR relies on object information received from the PER to form complex representations of context. Using three fear-conditioning (FC) paradigms (signaled, unsignaled, and renewal) and two context-guided object recognition tasks (with 3D and 2D objects), we examined the effects of crossed excitotoxic lesions to the POR and the contralateral PER. Performance of rats with crossed lesions was compared with that of rats with ipsilateral POR plus PER lesions and sham-operated rats. We found that rats with contralateral PER-POR lesions were impaired in object-context recognition but not in contextual FC. Therefore, interaction between the POR and PER is necessary for context-guided exploratory behavior but not for associating fear with context. Our results provide evidence for the hypothesis that the POR relies on object and pattern information from the PER to encode representations of context. The association of fear with a context, however, may be supported by alternate cortical and/or subcortical pathways when PER-POR interaction is not available. Our results suggest that contextual FC may represent a special case of context-guided behavior. SIGNIFICANCE STATEMENT Representations of context are important for perception, memory, decision making, and other cognitive processes. Moreover, there is extensive evidence that the use of contextual representations to guide appropriate behavior is disrupted in neuropsychiatric and neurological disorders including developmental disorders, schizophrenia, affective disorders, and Alzheimer's disease. Many of these disorders are accompanied by changes in

Porous silicon for drug delivery systems

NASA Astrophysics Data System (ADS)

Abramova, E. N.; Khort, A. M.; Yakovenko, A. G.; Kornilova, D. S.; Slipchenko, E. A.; Prokhorov, D. I.; Shvets, V. I.

2018-01-01

The article deals with main principles of the formation of porous silicon (por-Si) to produce containers for drug delivery systems. Most important por-Si characteristics to produce nanocontainers with required parameters are determined.

Moléculas orgánicas obtenidas en simulaciones experimentales del medio interestelar.

NASA Astrophysics Data System (ADS)

Muñoz-Caro, Guillermo Manuel

Las nubes moleculares son regiones de formación de estrellas, con temperaturas cinéticas entre 10-50 K y densidades de 103-106 átomos cm-3. Su materia está formada por gas y polvo interestelar. Estas partículas de polvo están cubiertas por una fina capa de hielo, de unos 0.01 μm, que contiene H2O y a menudo CO, CO2, CH3OH y NH3. El hielo es presumiblemente irradiado por fotones ultravioleta y rayos cósmicos en las zonas poco profundas de las nubes moleculares y las regiones circunestelares. En un sistema de vacío, P ˜ 10-7 mbar, simulamos la deposición de hielo a partir de 10 K y la irradiación ultravioleta por medio de una lámpara de descarga de hidrógeno activada con microondas. La evolución del hielo se observa por medio de un espectrómetro infrarrojo. De este modo es posible determinar la composición del hielo observado en el medio interestelar y predecir la presencia de moléculas aún no detectadas en el espacio, que han sido producto del procesamiento del hielo en nuestros experimentos. También es posible calentar el sistema hasta temperatura ambiente para sublimar el hielo depositado. Cuando el hielo ha sido previamente irradiado, se observa un residuo compuesto por moléculas orgánicas complejas, algunas prebióticas, como varios ácidos carboxílicos, aminas, amidas, ésteres y en menor proporción moléculas heterocíclicas y aminoácidos. Algunas de estas moléculas podrían detectarse en estado gaseoso por medio de observaciones milimétricas y de radio. También podrían estar presentes en el polvo cometario, cuyo análisis químico está planeado por las misiones Stardust y Rosetta. Mientras tanto, nuestro grupo está llevando a cabo el análisis de partículas de polvo interplanetario (IDPs), algunas de las cuales pueden ser de origen cometario. Al igual que ocurre con los productos obtenidos por irradiación del hielo en nuestros experimentos, algunas IDPs son ricas en material orgánico que contiene oxígeno.

PubMed

Scotta, Ana Verónica; Bongiovanni, Guillermina Azucena; Soria, Elio Andrés

2018-03-21

Antecedentes: Clorpirifos es un pesticida altamente tóxico, que puede producir inmunotoxicidad con efectos deletéreos sobre la salud a nivel mundial. Por otro lado, las plantas americanas pueden tener derivados con actividad protectora e inmunoestimulante. Por lo tanto, debe evaluarse el potencial de estas plantas frente a clorpirifos. Objetivo: Identificar extractos acuosos bioactivos de Lantana grisebachii (LG), Aspidosperma quebracho-blanco (AQ), Peumus boldus (PB), e Ilex paraguariensis (IP), contra la toxicidad de clorpirifos sobre esplenocitos de hembras Balb/c. Materiales y Métodos: Esplenocitos fueron tratados in vitro por 72 horas con 0-35 µg/mL de clorpirifos, 0-100 µg/mL de cada extracto (LG, AQ, PB, IP) y 0-5 µg/mL de concanavalina A. Luego, se midió y analizó estadísticamente viabilidad y muerte celular (tinciones de resazurina y yoduro de propidio), hidroperóxidos, lipoperóxidos (ensayos basados en naranja de xilenol), actividad de la ?-glutamiltranspeptidasa (método de Szasz). Resultados: Clorpirifos redujo la viabilidad celular de forma dosis dependiente, lo que fue contrarrestado por AQ e IP, los que fueron menos activos en las células inducibles por concanavalina A (p<0,05). La toxicidad por clorpirifos implicó la inducción de la ?-glutamiltranspeptidasa con la consecuente reducción de los peróxidos, mientras que AQ y principalmente IP antagonizaron dichas respuestas (p<0,05). Conclusiones: Los extractos de Ilex paraguariensis y Aspidosperma quebracho-blanco protegieron in vitro a los esplenocitos frente a clorpirifos. Este efecto dependió del tipo celular, dado que las células inducibles por concanavalina A fueron más susceptibles a este tóxico.

Sistemas de transporte inteligentes en cruces fronterizos internacionales : un estudio abarcador : facilitando el comercio y mejorando la seguridad en el transporte

DOT National Transportation Integrated Search

2001-04-01

El Programa de Permisosen Fronteras Internacionales (IBC por sus siglas en ingls) fue iniciado bajo la previsin del Acta de Eficiencia de Transporte Terrestre Intermodal (ISTEA por sus siglas en ingls) en 1991. El programa fue concebido origina...

Evaluation of a 3year intervention to increase adoption of safer nursery crop production practices.

PubMed

Chapman, Larry J; Newenhouse, Astrid C; Karsh, Ben-Tzion

2010-01-01

We conducted a 3year intervention to increase awareness and adoption of eight more profitable nursery crop production practices that reduced certain traumatic and musculoskeletal injury hazards. We disseminated information to nursery managers across seven states using information channels they were known to rely on (e.g. trade publications, public events, university Extension, other managers). We evaluated rolling, independent, probability samples (n=1200) with mail questionnaires before the intervention and after each of 3 intervention years. We also evaluated samples (n=250) from a comparison group of New Zealand nursery managers. The intervention was associated with increased awareness of four of the eight practices among US managers after year 3 compared to their baseline: zippers (20 vs. 32%, p=0.000), stools (11 vs. 22%, p=0.001), pruners (29 vs. 40%, p=0.014), and tarps (24 vs. 33%, p=0.009). There were no changes in adoption. New Zealand manager awareness was increased for hoes after year 2 compared to their baseline (35 vs. 52%, p=0.010). A modest, regionwide information dissemination intervention was associated with increased awareness, but not adoption.

Nuevos sistemas de frecuencia intermedia para el IAR

NASA Astrophysics Data System (ADS)

Olalde, J. C.; Perilli, D.; Larrarte, J. J.

Se presenta el diagrama en bloques de los nuevos sistemas de Frecuencia Intermedia para los dos radiómetros instalados en el IAR. Entre las características más importantes del sistema podemos mencionar la posibilidad de conectar cualquiera de las dos antenas a los ``backend" disponibles: analizador espectral de alta resolución (META II) de 0,05 Hz, autocorrelador de 1008 canales y contínuo. Se incorporan al sistema nuevos sintetizadores de frecuencia implementados con PLL y la moderna técnica de síntesis digital directa. Por último, el conjunto del sistema es susceptible de ser configurado por las computadoras de adquisición de datos, supervisadas por otra, que entrega el estado de funcionamiento actual y evita la selección de configuraciones incorrectas por parte del usuario.

Metabolic intervention in surgical patients. An assessment of the effect of somatostatin, ranitidine, naloxone, diclophenac, dipyridamole, or salbutamol infusion on energy and protein kinetics in surgical patients using stable and radioisotopes

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

Novel approach for III-N on Si (111) templates fabrication by low-temperature PA MBE using porous Si layer

NASA Astrophysics Data System (ADS)

Zolotukhin, D.; Seredin, P.; Lenshin, A.; Goloshchapov, D.; Mizerov, A.

2017-11-01

We report on successful growth of GaN nanorods by low-temperature plasma-assisted molecular beam epitaxy on a Si(111) substrate with and without preformed thin porous Si layer (por-Si). The deposited GaN initially forms islands which act as a seed for the wires. Porous structure of the por-Si layer helps to control nucleation islands sizes and achieve homogeneous distribution of the nanorods diameters. In addition 850 nm-thick crack-free GaN layer was formed on Si(111) substrate with preformed por-Si layer.

Measuring Access to Medicines: A Survey of Prices, Availability and Affordability in Shaanxi Province of China

PubMed Central

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

Measuring access to medicines: a survey of prices, availability and affordability in Shaanxi province of China.

PubMed

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

Comparison of conventional medicine, TCM treatment, and combination of both conventional medicine and TCM treatment for patients with chronic obstructive pulmonary disease: study protocol of a randomized comparative effectiveness research trial.

PubMed

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

Long-acting muscarinic antagonist use in adults with asthma: real-life prescribing and outcomes of add-on therapy with tiotropium bromide.

PubMed

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

Prescription drug use in pregnancy: a retrospective, population-based study in British Columbia, Canada (2001-2006).

PubMed

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

Access to Paediatric Essential Medicines: A Survey of Prices, Availability, Affordability and Price Components in Shaanxi Province, China

PubMed Central

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

Serelaxin Elicits Bronchodilation and Enhances β-Adrenoceptor-Mediated Airway Relaxation

PubMed Central

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

Understanding the Different Effects of Inhaler Design on the Aerosol Performance of Drug-Only and Carrier-Based DPI Formulations. Part 1: Grid Structure.

PubMed

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.

Response surface methodology for the determination of the design space of enantiomeric separations on cinchona-based zwitterionic chiral stationary phases by high performance liquid chromatography.

PubMed

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

Evaluation of partial beta-adrenoceptor agonist activity.

PubMed

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

Regional Ventilation Changes in the Lung: Treatment Response Mapping by Using Hyperpolarized Gas MR Imaging as a Quantitative Biomarker.

PubMed

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

Early use of noninvasive techniques for clearing respiratory secretions during noninvasive positive-pressure ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease and hypercapnic encephalopathy: A prospective cohort study.

PubMed

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

Human health risk assessment of pharmaceuticals and personal care products in plant tissue due to biosolids and manure amendments, and wastewater irrigation.

PubMed

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

ASM-024, a Piperazinium Compound, Promotes the In Vitro Relaxation of β2-Adrenoreceptor Desensitized Tracheas

PubMed Central

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

ASM-024, a piperazinium compound, promotes the in vitro relaxation of β2-adrenoreceptor desensitized tracheas.

PubMed

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

Electrostatic charge characteristics of jet nebulized aerosols.

PubMed

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

Access to paediatric essential medicines: a survey of prices, availability, affordability and price components in Shaanxi Province, China.

PubMed

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.

[Acute pancreatitis and acalculous cholecystitis associated with viral hepatitis A].

PubMed

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

Contribution of hospital effluents to the load of pharmaceuticals in urban wastewaters: identification of ecologically relevant pharmaceuticals.

PubMed

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

Determinants Of Oral corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY): protocol for a prospective multicentre cohort study of children with acute moderate-to-severe asthma exacerbations

PubMed Central

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

Microbicidas Metodo de Prevencion en VIH/SIDA Controlado por Mujeres

PubMed Central

Ruiz, Cindy; Torres, Viviana; Cianelli, Rosina; Ferrer, Lilian

2016-01-01

HIV/AIDS continues to expand throughout the world, and in recent times has had a severe impact on the number of women living with HIV. Access to methods of prevention for HIV/AIDS around the world is limited and for many women may not be feasible. Examples of such methods are sexual abstinence, which though recognized as an effective method of prevention is difficult for many women to achieve. Mutual fidelity is another option, but many women cannot control the sexual behavior of their partners. Finally, the male condom continues to be an available method of HIV prevention for sexually active people. However, in many places, gender inequality, social norms, and economic disparities severely limit women's capacity to negotiate the use of a condom with their partner. For this reason, an urgent need exists to develop a product for the prevention of HIV/AIDS that can be handled by women. Microbicides, products that can reduce HIV risk when applied intravaginally, hold promise for stopping the advance of HIV/AIDS, especially when considering that women can make their own decisions about whether to use them when other methods of prevention are not available. The objective of the current literature review was to understand the scientific advances related to microbicides in the prevention of HIV/AIDS in women through the analysis of available literature in this area. Interest in this topic emerged from the need to contribute to women's health and HIV/AIDS prevention. To achieve this review's objective, a search was carried out in multiple databases, including OVID, PUBMED, PROQUEST, and CINAHL, as well as published materials from organizations related to this area such as UNAIDS and CONASIDA, and literature available from the Internet. Upon completion of the literature review, it was concluded that microbicides are an effective method for preventing HIV/AIDS for women as well as their partners. Although they have a high level of acceptance among the female population, the majority of microbicides are still in clinical studies, requiring further evaluation for their safe use in humans. There are 3 microbicides in the final phases of clinical studies that will soon be available on the market. One of these was found to be 60% effective in protecting against the transmission of HIV and was used by women in 50% of their sexual activity, which resulted in avoiding approximately 2.5 million new HIV infections in men, women, and children over a 3-year period. PMID:28111528

Microbicidas Metodo de Prevencion en VIH/SIDA Controlado por Mujeres.

PubMed

Ruiz, Cindy; Torres, Viviana; Cianelli, Rosina; Ferrer, Lilian

2009-03-01

HIV/AIDS continues to expand throughout the world, and in recent times has had a severe impact on the number of women living with HIV. Access to methods of prevention for HIV/AIDS around the world is limited and for many women may not be feasible. Examples of such methods are sexual abstinence, which though recognized as an effective method of prevention is difficult for many women to achieve. Mutual fidelity is another option, but many women cannot control the sexual behavior of their partners. Finally, the male condom continues to be an available method of HIV prevention for sexually active people. However, in many places, gender inequality, social norms, and economic disparities severely limit women's capacity to negotiate the use of a condom with their partner. For this reason, an urgent need exists to develop a product for the prevention of HIV/AIDS that can be handled by women. Microbicides, products that can reduce HIV risk when applied intravaginally, hold promise for stopping the advance of HIV/AIDS, especially when considering that women can make their own decisions about whether to use them when other methods of prevention are not available. The objective of the current literature review was to understand the scientific advances related to microbicides in the prevention of HIV/AIDS in women through the analysis of available literature in this area. Interest in this topic emerged from the need to contribute to women's health and HIV/AIDS prevention. To achieve this review's objective, a search was carried out in multiple databases, including OVID, PUBMED, PROQUEST, and CINAHL, as well as published materials from organizations related to this area such as UNAIDS and CONASIDA, and literature available from the Internet. Upon completion of the literature review, it was concluded that microbicides are an effective method for preventing HIV/AIDS for women as well as their partners. Although they have a high level of acceptance among the female population, the majority of microbicides are still in clinical studies, requiring further evaluation for their safe use in humans. There are 3 microbicides in the final phases of clinical studies that will soon be available on the market. One of these was found to be 60% effective in protecting against the transmission of HIV and was used by women in 50% of their sexual activity, which resulted in avoiding approximately 2.5 million new HIV infections in men, women, and children over a 3-year period.

Decade of Venezuela’s President Hugo Chavez, Por Ahora

DTIC Science & Technology

2009-04-01

minor production source of opium and cocoa , Venezuela is important in the transit of narcotics between Columbia and the US. 60 61 Mindful of this, a...took over.91 To highlight the significance of oil to Venezuela , in 2006, oil represented 91% of its exports compared to 80% five years earlier.92...methodology to examine the last ten years of Venezuelas Hugo Chavez presidency and the significant aspects in terms of US security. The paper contents

On the Use of "Por" Plus Agent with "Se" Construction

ERIC Educational Resources Information Center

De Mello, George

1978-01-01

Two explanations for the role of "se" in such constructions as "Se construyen casas" are given by grammarians; one states that it is a passive interpretation ("Houses are built"), the other advocates an impersonal interpretation ("One builds houses"). Different views are presented and analyzed. (Author/NCR)

Time spent traveling in motor vehicles and its association with overweight and abdominal obesity in Colombian adults who do not own a car.

PubMed

Flórez Pregonero, Alberto; Gómez, Luis Fernando; Parra, Diana C; Cohen, Daniel D; Arango Paternina, Carlos Mario; Lobelo, Felipe

2012-06-01

This study examined associations between time spent traveling in motor vehicles per week (TSTMV) and BMI and abdominal obesity (AO) among Colombian adults residing in urban areas who do not own car. Secondary data analysis of the 2005 National Nutrition Survey of Colombia was conducted. TSTMV was assessed using the long International Physical Activity Questionnaire. Body composition was measured in 7900 adults. Polytomous and binary logistic regressions were conducted, stratified by gender and adjusted for confounders, including physical activity (PA). Forty-two percent of participants were either overweight or obese according to their BMI, and 22.4% had AO. Males in the middle (10 to 149 min) and highest (>150 min) TSTMV tertiles were more likely to be overweight (POR=1.58, 95% CI=1.13-2.21 and POR=1.55, 95% CI=1.12-2.15 respectively, p-trend=0.012), obese (POR=2.39, 95% CI=1.43-3.99 and POR=1.93, 95% CI=1.22-3.08 respectively, p trend=0.019) and to have AO (POR=1.81, 95% CI=1.18-2.78 and POR=1.73, 95% CI=1.18-2.54 respectively, p-trend=0.009). Associations were not significant in females. TSTMV was positively associated with overweight and AO in adult Colombian males even after adjusting for PA. These findings highlight the potential deleterious health effects of sedentary behaviors such as prolonged traveling time, independently of having met PA recommendations. Copyright © 2012 Elsevier Inc. All rights reserved.

[Not Available].

PubMed

San Mauro Martin, Ismael; Mendive Dubourdieu, Paula; Paredes Barato, Víctor; Garicano Vilar, Elena

2016-07-19

Introducción: la tradición de la comida picante desempeña un papel muy importante en el gusto por este tipo de comida y su tolerancia. Las preferencias alimentarias muestran influencia genética y ambiental.Objetivos: estudiar la tolerancia y el gusto por el picante de tres poblaciones, y la influencia hereditaria y del ambiente.Métodos:se realizó una encuesta a 522 sujetos, de tres continentes (Asia, Europa y Latinoamérica) en tres idiomas (español, inglés y chino) a través de Internet. Se realizaron preguntas acerca de la tolerancia al picante, el gusto por los alimentos picantes, su uso, la edad de comienzo de consumo, el gusto del padre y de la madre y si ella lo consumía durante el embarazo y/o lactancia.Resultados: existe diferencia entre el gusto por el picante del hijo y el sexo (p < 0,001), la tolerancia (p < 0,001) y, solo en el sexo femenino, el gusto de la madre por el picante (p < 0,001), su consumo durante el embarazo (p < 0,001) y la lactancia (p = 0,005) y el gusto del padre por el picante (p = 0,003). Existe correlación entre el continente de residencia (p = 0,007) y de nacimiento (p = 0,012) y la tolerancia a los alimentos picantes.Conclusión: la influencia de los progenitores, el género y la composición corporal se relacionaron con gustos y tolerancias diferentes.

Sunburn and sun-protective behaviors among adults with and without previous nonmelanoma skin cancer: a population-based study

PubMed Central

Fischer, Alexander H.; Wang, Timothy S.; Yenokyan, Gayane; Kang, Sewon; Chien, Anna L.

2016-01-01

Background Individuals with previous nonmelanoma skin cancer (NMSC) are at increased risk for subsequent skin cancer, and should therefore limit UV exposure. Objective To determine whether individuals with previous NMSC engage in better sun protection than those with no skin cancer history. Methods We pooled self-reported data (2005 and 2010 National Health Interview Surveys) from US non-Hispanic white adults (758 with and 34,161 without previous NMSC). We calculated adjusted prevalence odds ratios (aPOR) and 95% confidence intervals (95% CI), taking into account the complex survey design. Results Individuals with previous NMSC versus no history of NMSC had higher rates of frequent use of shade (44.3% versus 27.0%; aPOR=1.41; 1.16–1.71), long sleeves (20.5% versus 7.7%; aPOR=1.55; 1.21–1.98), a wide-brimmed hat (26.1% versus 10.5%; aPOR=1.52; 1.24–1.87), and sunscreen (53.7% versus 33.1%; aPOR=2.11; 95% CI=1.73–2.59), but did not have significantly lower odds of recent sunburn (29.7% versus 40.7%; aPOR=0.95; 0.77–1.17). Among subjects with previous NMSC, recent sunburn was inversely associated with age, sun avoidance, and shade but not sunscreen. Limitations Self-reported cross-sectional data and unavailable information quantifying regular sun exposure. Conclusion Physicians should emphasize sunburn prevention when counseling patients with previous NMSC, especially younger adults, focusing on shade and sun avoidance over sunscreen. PMID:27198078

Factors associated with anemia in refugee children.

PubMed

Hassan, K; Sullivan, K M; Yip, R; Woodruff, B A

1997-11-01

A nutrition survey was performed in 1990 among children 6 through 35 mo of age living in Palestinian refugee camps in Syria, Jordan, the West Bank, Gaza Strip and Lebanon. Overall, 67% [95% confidence interval (CI): 66, 68] were anemic (hemoglobin <110 g/L), ranging from 54% in the West Bank to 75% in Syria. The following factors were significantly associated with anemia in one or more of three age groups (6-11.9, 12-23.9 and 24-35.9 mo) by logistic regression: living in Syria, Lebanon, or Gaza [with prevalence odds ratios (POR) in the range of 1.4-2.6 depending on the age group and area, relative to children living in Jordan]; never having been breast-fed (POR = 1.7); male sex (POR = 1.2); maternal illiteracy (POR = 1.4 relative to those with >/=6 y of education); having a recent (within 2 wk) or current episode of fever or diarrhea; and stunting. Recent or current illness and stunting interacted in two age groups with the general trend of stunted children with recent or current illness having high POR. Early childhood anemia is associated with factors reflecting poor socioeconomic status and recent diarrheal and febrile illnesses in Palestinian refugee camps.

Risk of specific congenital abnormalities in offspring of women with diabetes.

PubMed

Nielsen, G L; Nørgard, B; Puho, E; Rothman, K J; Sørensen, H T; Czeizel, A E

2005-06-01

To assess the extent to which the increased risk of congenital abnormalities seen in women with pre-gestational insulin-treated diabetes mellitus is unspecific or related to the embryology of specific organs. Cases with congenital abnormalities were identified in the population-based Hungarian Congenital Abnormality Registry from 1980 to 1996 with two newborn children without congenital abnormality selected from the National Birth Registry as controls. We adjusted for parity, maternal age, and use of antipsychotic drugs. Among cases we found 63/22,843 babies with maternal diabetes compared with 50/38,151 in the control group [adjusted prevalence odds ratio (POR) 2.1; 95% CI 1.5-3.1]. The association was strongest for the following congenital abnormalities: renal agenesis (POR: 14.8; 95% CI, 3.5-62.1), obstructive congenital abnormalities of the urinary tract (POR: 4.3; 95% CI, 1.3-13.9), cardiovascular congenital abnormalities (POR: 3.4; 95% CI, 2.0-5.7), and multiple congenital abnormalities (POR: 5.0; 95% CI, 2.4-10.2). These data indicate that pre-gestational maternal diabetes is associated with strong teratogenic effects on the kidney, urinary tract, and heart, and strongly associated with multiple congenital abnormalities. We found no material association between diabetes and spinal congenital abnormalities and limb deficiencies.

Using MOMP typing as an epidemiological tool to investigate outbreaks caused by milkborne Campylobacter jejuni isolates in California

USDA-ARS?s Scientific Manuscript database

We describe using major outer membrane protein (MOMP) typing as a screen to compare the C. jejuni porA gene sequences of clinical outbreak strains from human stool with the porA sequences of dairy farm strains isolated during two milkborne campylobacteriosis outbreak investigations in California. Th...

Unidades generadoras de energía eléctrica para servicios públicos: Revocación del Plan de Energía Limpia: Propuesta

EPA Pesticide Factsheets

La EPA está proponiendo la revocación del Plan de Energía Limpia (CPP, por sus siglas en inglés) – después de completar una revisión minuciosa como fue dictaminada por la Orden Ejecutiva de Independencia Energética.

78 FR 29322 - Silicon Metal From the People's Republic of China: Final Results and Final No Shipments...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-20

... People's Republic of China: Final Results and Final No Shipments Determination of Antidumping Duty... the People's Republic of China (``PRC'').\\1\\ The period of review (``POR'') is June 1, 2011, through... any reviewable transactions during the POR. \\1\\ See Silicon Metal From the People's Republic of China...

77 FR 28570 - Honey From Argentina: Extension of Time Limit for the Final Results of Antidumping Duty...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-15

... DEPARTMENT OF COMMERCE International Trade Administration [A-357-812] Honey From Argentina... administrative review for the 2009-2010 period of review (POR) of honey from Argentina. See Honey From Argentina... producers/exporters of honey from Argentina during the POR.\\1\\ \\1\\ See Preliminary Results for a detailed...

El nuevo panorama de la Dinámica Galáctica

NASA Astrophysics Data System (ADS)

Pivovaroff, Michael James

En general, la tendencia imperante en Dinámica Galáctica ha sido considerar que los movimientos estelares son básicamente regulares y que el caos no tiene mayor relevancia en los sistemas estelares. Sin embargo, en el último lustro se vienen acumulando pruebas de la importancia del movimiento caótico en ciertos sistemas estelares que existen en la naturaleza. Por una parte, sobre todo el grupo de David Merritt, lo ha mostrado en los casos de galaxias elípticas con concentraciones centrales de materia; por otra parte, en nuestro propio grupo, lo hemos mostrado para el caso de los satélites galácticos. Las consecuencias de estos hallazgos son tanto de tipo técnico, por la necesidad de construir modelos que contengan órbitas caóticas, como astrofísico, por los efectos del caos sobre la estacionariedad y evolución de los sistemas estelares en los que se presenta.

Tyrosine oxidation in heme oxygenase: examination of long-range proton-coupled electron transfer.

PubMed

Smirnov, Valeriy V; Roth, Justine P

2014-10-01

Heme oxygenase is responsible for the degradation of a histidine-ligated ferric protoporphyrin IX (Por) to biliverdin, CO, and the free ferrous ion. Described here are studies of tyrosyl radical formation reactions that occur after oxidizing Fe(III)(Por) to Fe(IV)=O(Por(·+)) in human heme oxygenase isoform-1 (hHO-1) and the structurally homologous protein from Corynebacterium diphtheriae (cdHO). Site-directed mutagenesis on hHO-1 probes the reduction of Fe(IV)=O(Por(·+)) by tyrosine residues within 11 Å of the prosthetic group. In hHO-1, Y58· is implicated as the most likely site of oxidation, based on the pH and pD dependent kinetics. The absence of solvent deuterium isotope effects in basic solutions of hHO-1 and cdHO contrasts with the behavior of these proteins in the acidic solution, suggesting that long-range proton-coupled electron transfer predominates over electron transfer.

Genetic variations in NADPH-CYP450 oxidoreductase in a Czech Slavic cohort.

PubMed

Tomková, Mária; Panda, Satya Prakash; Šeda, Ondřej; Baxová, Alice; Hůlková, Martina; Siler Masters, Bettie Sue; Martásek, Pavel

2015-01-01

Estimating polymorphic allele frequencies of the NADPH-CYP450 oxidoreductase (POR) gene in a Czech Slavic population. The POR gene was analyzed in 322 individuals from a control cohort by sequencing and high resolution melting analysis. We identified seven unreported SNP genetic variations, including two SNPs in the 5' flanking region (g.4965C>T and g.4994G>T), one intronic variant (c.1899-20C>T), one synonymous SNP (p.20Ala=) and three nonsynonymous SNPs (p.Thr29Ser, p.Pro384Leu and p.Thr529Met). The p.Pro384Leu variant exhibited reduced enzymatic activities compared with wild-type. New POR variant identification indicates the number of uncommon variants might be specific for each subpopulation being investigated, particularly germane to the singular role that POR plays in providing reducing equivalents to all CYP450s in the endoplasmic reticulum. Original submitted 15 September 2014; Revision submitted 17 November 2014.

Observational study to calculate addictive risk to opioids: a validation study of a predictive algorithm to evaluate opioid use disorder.

PubMed

Brenton, Ashley; Richeimer, Steven; Sharma, Maneesh; Lee, Chee; Kantorovich, Svetlana; Blanchard, John; Meshkin, Brian

2017-01-01

Opioid abuse in chronic pain patients is a major public health issue, with rapidly increasing addiction rates and deaths from unintentional overdose more than quadrupling since 1999. This study seeks to determine the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated single-nucleotide polymorphisms (SNPs). The Proove Opioid Risk (POR) algorithm determines the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated SNPs. In a validation study with 258 subjects with diagnosed opioid use disorder (OUD) and 650 controls who reported using opioids, the POR successfully categorized patients at high and moderate risks of opioid misuse or abuse with 95.7% sensitivity. Regardless of changes in the prevalence of opioid misuse or abuse, the sensitivity of POR remained >95%. The POR correctly stratifies patients into low-, moderate-, and high-risk categories to appropriately identify patients at need for additional guidance, monitoring, or treatment changes.

Transmission scenarios of major vector-borne diseases in Colombia, 1990-2016.

PubMed

Padilla, Julio César; Lizarazo, Fredy Eberto; Murillo, Olga Lucía; Mendigaña, Fernando Antonio; Pachón, Edwin; Vera, Mauricio Javier

2017-03-29

Introducción. Las enfermedades transmitidas por vectores representan más de 17 % de todas las enfermedades infecciosas y causan anualmente un millón de defunciones a nivel mundial. En Colombia, la malaria, el dengue, la enfermedad de Chagas y las leishmaniasis son condiciones endemoepidémicas persistentes.Objetivo. Determinar el comportamiento epidemiológico de las enfermedades transmitidas por vectores en zonas urbanas y rurales de Colombia entre 1990 y 2016.Materiales y métodos. Se hizo un estudio descriptivo del comportamiento epidemiológico de las principales enfermedades transmitidas por vectores en zonas urbanas y rurales de Colombia entre 1990 y 2016, con la información proveniente de fuentes oficiales secundarias.Resultados. En el periodo estudiado se registraron 5'360.134 casos de enfermedades transmitidas por vectores, de los cuales 54,7 % fueron de malaria y 24,9 % de dengue. Estos casos concentraron el 80 % de la carga acumulada de casos de enfermedades transmitidas por vectores. Las medianas de las tasas de incidencia fueron 1.371 y 188 por 100.00 habitantes para malaria y dengue, respectivamente. Además, los casos de chikungunya fueron 774.831 desde su introducción en el 2014 y, los de Zika, 117.674 desde su aparición en 2015. En las zonas rurales predominaron las enfermedades parasitarias transmitidas por vectores como la malaria, las leishmaniasis y la enfermedad de Chagas. A nivel urbano, predominaron el dengue, el chikungunya y el Zika.Conclusiones. La transmisión en Colombia de estas enfermedades es persistente en las zonas urbanas y en las rurales, y de tipo endemoepidémico en los casos de malaria, dengue, leishmaniasis y enfermedad de Chagas. Dicha transmisión se ha dado de manera focalizada y con patrones variables de intensidad. Asimismo, se mantienen las condiciones que han favorecido la transmisión emergente de nuevas arbovirosis.

76 FR 26241 - Certain Frozen Warmwater Shrimp From Thailand: Notice of Court Decision Not in Harmony With Final...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-06

... Shrimp From Thailand: Notice of Court Decision Not in Harmony With Final Results of Administrative Review... Thailand covering the period of review (POR) of February 1, 2006, through January 31, 2007. DATES... administrative review of certain frozen warmwater shrimp from Thailand covering the POR of February 1, 2006...

Proyecto Energético Palmdale; Decisión del Permiso Final

EPA Pesticide Factsheets

Proyecto Energético Palmdale: EPA Región 9 por el presente emite aviso de su decisión final, el cumplimiento con la Ley Federal de Aire Limpio, para la construcción de una planta generadora de electricidad de ciclo combinado y alimentada por gas natural

PubMed

Escandón-Nagel, Neli

2016-11-29

Introducción: si bien el Trastorno por Atracón es un trastorno de la conducta alimentaria que  no se da exclusivamente en personas obesas, es más común en este grupo que en sujetos con normopeso, sin embargo no todas las personas con malnutrición por exceso presentan Trastorno por Atracón. Objetivo: identificar el conocimiento actual respecto a las diferencias y semejanzas existentes entre personas con malnutrición por exceso con y sin Trastorno por Atracón.Método: para lograr el objetivo anterior, se realizó una revisión de artículos científicos en torno al tema.Resultados: primero se analizó la comorbilidad psicopatológica en obesidad y después se detectaron similitudes y diferencias entre los grupos de interés, tanto en sintomatología general, como así también en sintomatología de la conducta alimentaria. Además, se identificaron algunos aspectos controversiales, en que existe evidencia contradictoria respecto a la comparación intergrupal.Conclusión: de esta revisión se concluye que en el estudio de la obesidad se hace necesario conocer en mayor profundidad las características del subgrupo de pacientes que además presenta Trastorno por Atracón,  ya que estas personas poseen características distintivas cuyo conocimiento permitirá ofrecer tratamientos integrales más adecuados a las necesidades de los pacientes, lo que posibilitará, en consecuencia, diseñar intervenciones más eficaces.

[Not Available].

PubMed

Latorre-Román, Pedro Ángel; Martínez-López, Emilio José; Ruiz-Ariza, Alberto; Izquierdo-Rus, Tomás; Salas-Sánchez, Jesús; García-Pinillos, Felipe

2016-06-30

Objetivo: el objetivo de este estudio es evaluar las propiedades psicométricas del cuestionario de disfrute por el ejercicio físico (PACES) en adolescentes con sobrepeso y obesidad.Métodos: participaron 139 adolescentes con sobrepeso y obesidad: 91 niñas (edad = 13,85 ± 1,92 años; índice de masa corporal [IMC] = 26,83 ± 3,16 kg/m2) y 48 niños (edad = 14,29 ± 1,62 años; IMC = 28,31 ± 3,74 kg/m2). Para analizar el disfrute por la actividad física se empleó el cuestionario Physical Activity Enjoyment Scale (PACES).Resultados: los resultados del análisis factorial exploratorio y confirmatorio han mostrado una estructura de dos factores; a su vez el PACES presenta una consistencia interna muy alta (alfa de Cronbach = 0,908). La fiabilidad test-retest indica una buena concordancia temporal (Spearman rho = 0,815, p < 0,001). Por último, el PACES en adolescentes con sobrepeso y obesidad manifiesta una validez convergente adecuada con la intencionalidad de ser activo (MIFA), la atracción por la actividad física (CAPA), la resistencia cardiorrespiratoria y los pliegues suprailiacoy subescapular.Conclusión: los resultados confirman que el PACES es una medida válida y fiable del disfrute por la actividad física en adolescentes con sobrepeso y obesidad. El disfrute por la actividad física puede ser relevante en la participación de los adolescentes con sobrepeso y obesidad en estas actividades.

LIL3, a Light-Harvesting Complex Protein, Links Terpenoid and Tetrapyrrole Biosynthesis in Arabidopsis thaliana1[OPEN

PubMed Central

Rothbart, Maxi; Herbst, Josephine; Wittmann, Daniel; Gruhl, Kirsten

2017-01-01

The LIL3 protein of Arabidopsis (Arabidopsis thaliana) belongs to the light-harvesting complex (LHC) protein family, which also includes the light-harvesting chlorophyll-binding proteins of photosystems I and II, the early-light-inducible proteins, PsbS involved in nonphotochemical quenching, and the one-helix proteins and their cyanobacterial homologs designated high-light-inducible proteins. Each member of this family is characterized by one or two LHC transmembrane domains (referred to as the LHC motif) to which potential functions such as chlorophyll binding, protein interaction, and integration of interacting partners into the plastid membranes have been attributed. Initially, LIL3 was shown to interact with geranylgeranyl reductase (CHLP), an enzyme of terpene biosynthesis that supplies the hydrocarbon chain for chlorophyll and tocopherol. Here, we show another function of LIL3 for the stability of protochlorophyllide oxidoreductase (POR). Multiple protein-protein interaction analyses suggest the direct physical interaction of LIL3 with POR but not with chlorophyll synthase. Consistently, LIL3-deficient plants exhibit substantial loss of POR as well as CHLP, which is not due to defective transcription of the POR and CHLP genes but to the posttranslational modification of their protein products. Interestingly, in vitro biochemical analyses provide novel evidence that LIL3 shows high binding affinity to protochlorophyllide, the substrate of POR. Taken together, this study suggests a critical role for LIL3 in the organization of later steps in chlorophyll biosynthesis. We suggest that LIL3 associates with POR and CHLP and thus contributes to the supply of the two metabolites, chlorophyllide and phytyl pyrophosphate, required for the final step in chlorophyll a synthesis. PMID:28432258

Sunburn and sun-protective behaviors among adults with and without previous nonmelanoma skin cancer (NMSC): A population-based study.

PubMed

Fischer, Alexander H; Wang, Timothy S; Yenokyan, Gayane; Kang, Sewon; Chien, Anna L

2016-08-01

Individuals with previous nonmelanoma skin cancer (NMSC) are at increased risk for subsequent skin cancer, and should therefore limit ultraviolet exposure. We sought to determine whether individuals with previous NMSC engage in better sun protection than those with no skin cancer history. We pooled self-reported data (2005 and 2010 National Health Interview Surveys) from US non-Hispanic white adults (758 with and 34,161 without previous NMSC). We calculated adjusted prevalence odds ratios (aPOR) and 95% confidence intervals (CI), taking into account the complex survey design. Individuals with previous NMSC versus no history of NMSC had higher rates of frequent use of shade (44.3% vs 27.0%; aPOR 1.41; 95% CI 1.16-1.71), long sleeves (20.5% vs 7.7%; aPOR 1.55; 95% CI 1.21-1.98), a wide-brimmed hat (26.1% vs 10.5%; aPOR 1.52; 95% CI 1.24-1.87), and sunscreen (53.7% vs 33.1%; aPOR 2.11; 95% CI 1.73-2.59), but did not have significantly lower odds of recent sunburn (29.7% vs 40.7%; aPOR 0.95; 95% CI 0.77-1.17). Among those with previous NMSC, recent sunburn was inversely associated with age, sun avoidance, and shade but not sunscreen. Self-reported cross-sectional data and unavailable information quantifying regular sun exposure are limitations. Physicians should emphasize sunburn prevention when counseling patients with previous NMSC, especially younger adults, focusing on shade and sun avoidance over sunscreen. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

LIL3, a Light-Harvesting Complex Protein, Links Terpenoid and Tetrapyrrole Biosynthesis in Arabidopsis thaliana.

PubMed

Hey, Daniel; Rothbart, Maxi; Herbst, Josephine; Wang, Peng; Müller, Jakob; Wittmann, Daniel; Gruhl, Kirsten; Grimm, Bernhard

2017-06-01

The LIL3 protein of Arabidopsis ( Arabidopsis thaliana ) belongs to the light-harvesting complex (LHC) protein family, which also includes the light-harvesting chlorophyll-binding proteins of photosystems I and II, the early-light-inducible proteins, PsbS involved in nonphotochemical quenching, and the one-helix proteins and their cyanobacterial homologs designated high-light-inducible proteins. Each member of this family is characterized by one or two LHC transmembrane domains (referred to as the LHC motif) to which potential functions such as chlorophyll binding, protein interaction, and integration of interacting partners into the plastid membranes have been attributed. Initially, LIL3 was shown to interact with geranylgeranyl reductase (CHLP), an enzyme of terpene biosynthesis that supplies the hydrocarbon chain for chlorophyll and tocopherol. Here, we show another function of LIL3 for the stability of protochlorophyllide oxidoreductase (POR). Multiple protein-protein interaction analyses suggest the direct physical interaction of LIL3 with POR but not with chlorophyll synthase. Consistently, LIL3-deficient plants exhibit substantial loss of POR as well as CHLP, which is not due to defective transcription of the POR and CHLP genes but to the posttranslational modification of their protein products. Interestingly, in vitro biochemical analyses provide novel evidence that LIL3 shows high binding affinity to protochlorophyllide, the substrate of POR. Taken together, this study suggests a critical role for LIL3 in the organization of later steps in chlorophyll biosynthesis. We suggest that LIL3 associates with POR and CHLP and thus contributes to the supply of the two metabolites, chlorophyllide and phytyl pyrophosphate, required for the final step in chlorophyll a synthesis. © 2017 American Society of Plant Biologists. All Rights Reserved.

Faecal calprotectin and magnetic resonance imaging in detecting Crohn's disease endoscopic postoperative recurrence.

PubMed

Baillet, Pierre; Cadiot, Guillaume; Goutte, Marion; Goutorbe, Felix; Brixi, Hedia; Hoeffel, Christine; Allimant, Christophe; Reymond, Maud; Obritin-Guilhen, Hélène; Magnin, Benoit; Bommelaer, Gilles; Pereira, Bruno; Hordonneau, Constance; Buisson, Anthony

2018-02-07

To assess magnetic resonance imaging (MRI) and faecal calprotectin to detect endoscopic postoperative recurrence in patients with Crohn's disease (CD). From two tertiary centers, all patients with CD who underwent ileocolonic resection were consecutively and prospectively included. All the patients underwent MRI and endoscopy within the first year after surgery or after the restoration of intestinal continuity [median = 6 mo (5.0-9.3)]. The stools were collected the day before the colonoscopy to evaluate faecal calprotectin level. Endoscopic postoperative recurrence (POR) was defined as Rutgeerts' index ≥ i2b. The MRI was analyzed independently by two radiologists blinded from clinical data. Apparent diffusion coefficient (ADC) was lower in patients with endoscopic POR compared to those with no recurrence (2.03 ± 0.32 vs 2.27 ± 0.38 × 10 -3 mm²/s, P = 0.032). Clermont score (10.4 ± 5.8 vs 7.4 ± 4.5, P = 0.038) and relative contrast enhancement (RCE) (129.4% ± 62.8% vs 76.4% ± 32.6%, P = 0.007) were significantly associated with endoscopic POR contrary to the magnetic resonance index of activity (MaRIA) (7.3 ± 4.5 vs 4.8 ± 3.7; P = 0.15) and MR scoring system ( P = 0.056). ADC < 2.35 × 10 -3 mm²/s [sensitivity = 0.85, specificity = 0.65, positive predictive value (PPV) = 0.85, negative predictive value (NPV) = 0.65] and RCE > 100% (sensitivity = 0.75, specificity = 0.81, PPV = 0.75, NPV = 0.81) were the best cut-off values to identify endoscopic POR. Clermont score > 6.4 (sensitivity = 0.61, specificity = 0.82, PPV = 0.73, NPV = 0.74), MaRIA > 3.76 (sensitivity = 0.61, specificity = 0.82, PPV = 0.73, NPV = 0.74) and a MR scoring system ≥ MR1 (sensitivity = 0.54, specificity = 0.82, PPV = 0.70, and NPV = 0.70) demonstrated interesting performances to detect endoscopic POR. Faecal calprotectin values were significantly higher in patients with endoscopic POR (114 ± 54.5 μg/g vs 354.8 ± 432.5 μg/g; P = 0.0075). Faecal calprotectin > 100 �

Faecal calprotectin and magnetic resonance imaging in detecting Crohn’s disease endoscopic postoperative recurrence

PubMed Central

Baillet, Pierre; Cadiot, Guillaume; Goutte, Marion; Goutorbe, Felix; Brixi, Hedia; Hoeffel, Christine; Allimant, Christophe; Reymond, Maud; Obritin-Guilhen, Hélène; Magnin, Benoit; Bommelaer, Gilles; Pereira, Bruno; Hordonneau, Constance; Buisson, Anthony

2018-01-01

AIM To assess magnetic resonance imaging (MRI) and faecal calprotectin to detect endoscopic postoperative recurrence in patients with Crohn’s disease (CD). METHODS From two tertiary centers, all patients with CD who underwent ileocolonic resection were consecutively and prospectively included. All the patients underwent MRI and endoscopy within the first year after surgery or after the restoration of intestinal continuity [median = 6 mo (5.0-9.3)]. The stools were collected the day before the colonoscopy to evaluate faecal calprotectin level. Endoscopic postoperative recurrence (POR) was defined as Rutgeerts’ index ≥ i2b. The MRI was analyzed independently by two radiologists blinded from clinical data. RESULTS Apparent diffusion coefficient (ADC) was lower in patients with endoscopic POR compared to those with no recurrence (2.03 ± 0.32 vs 2.27 ± 0.38 × 10-3 mm²/s, P = 0.032). Clermont score (10.4 ± 5.8 vs 7.4 ± 4.5, P = 0.038) and relative contrast enhancement (RCE) (129.4% ± 62.8% vs 76.4% ± 32.6%, P = 0.007) were significantly associated with endoscopic POR contrary to the magnetic resonance index of activity (MaRIA) (7.3 ± 4.5 vs 4.8 ± 3.7; P = 0.15) and MR scoring system (P = 0.056). ADC < 2.35 × 10-3 mm²/s [sensitivity = 0.85, specificity = 0.65, positive predictive value (PPV) = 0.85, negative predictive value (NPV) = 0.65] and RCE > 100% (sensitivity = 0.75, specificity = 0.81, PPV = 0.75, NPV = 0.81) were the best cut-off values to identify endoscopic POR. Clermont score > 6.4 (sensitivity = 0.61, specificity = 0.82, PPV = 0.73, NPV = 0.74), MaRIA > 3.76 (sensitivity = 0.61, specificity = 0.82, PPV = 0.73, NPV = 0.74) and a MR scoring system ≥ MR1 (sensitivity = 0.54, specificity = 0.82, PPV = 0.70, and NPV = 0.70) demonstrated interesting performances to detect endoscopic POR. Faecal calprotectin values were significantly higher in patients with endoscopic POR (114 ± 54.5 μg/g vs 354.8 ± 432.5 μg/g; P = 0.0075). Faecal

76 FR 34296 - Proposed Collection; Comment Request for Forms 1040-PR and 1040-SS

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-13

... Form 1040-PR, Planilla para la Declaraci[oacute]n de la Contribuci[oacute]n Federal sobre el Trabajo... Trabajo por Cuenta Propia (Incluyendo el Cr[eacute]dito Tributario Adicional por Hijos para Residentes... Subtitle A, and provide credit to the taxpayer's social security account. Anejo H-PR is used to compute...

77 FR 77017 - Certain Orange Juice From Brazil: Notice of Court Decision Not in Harmony With Final Results of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-31

..., International Trade Administration, Department of Commerce. SUMMARY: On October 24, 2012, the United States... juice (OJ) from Brazil covering the period of review (POR) of March 1, 2008, through February 28, 2009... administrative review of OJ from Brazil covering the POR of March 1, 2008, through February 28, 2009. See Certain...

La EPA ayuda a restaurar el laboratorio de ciencias de Puerto Rico y las capacidades de monitorear la calidad del aire

EPA Pesticide Factsheets

La EPA continúa ayudando a Puerto Rico a responder tras los daños causados por los huracanes Irma y María. La EPA, conforme a una misión asignada por FEMA, y en estrecha cooperación con el gobierno de Puerto Rico, se encuentra apoya

Two dimensional self-assembly zinc porphyrins and zinc phthalocyanines heterojunctions with record high power conversion efficiencies.

PubMed

Yu, Junting; Jiang, Zhou; Hao, Yifan; Zhu, Qianhong; Zhao, Mingliang; Jiang, Xue; Zhao, Jijun

2018-05-15

Compared to inorganic solar cells, the power conversion efficiencies (PCEs) of organic solar cells are much lower, but they are compensated by many merits such as lower cost, less weight, and tunable structures, making them prospective for further applications. Porphyrin and phthalocyanine are the two most significant materials for organic solar cells due to their strong light-absorbing properties and semiconductor characteristics. However, there is little research on the 2D heterojunction solar cells based on these two materials, meanwhile the PCEs of them are still low. Here we have self-assembled several 2D Zinc-porphyrins (ZnPors) and performed first-principles simulation to demonstrate their good stability, suitable light harvesting, and high charge carrier mobility. By perfectly matching lattice constants and band levels between those 2D ZnPors and our previous proposed ZnPcs, eleven type-II organic heterojunctions are constructed to further improve their charge separation capability. Those advantages endow 2D ZnPors and ZnPcs appreciable PCEs for solar cell. Among them, the theoretical PCE of 2D ZnPors/ZnPcs heterojunctions achieves as high as 19.84%, which prevails all reported organic solar cells, and even approaches the PCEs of inorganic solar cells. These results indicate that our 2D ZnPors and 2D ZnPcs are good candidate materials for future organic solar cells. © 2018 IOP Publishing Ltd.

Two dimensional self-assembly zinc porphyrin and zinc phthalocyanine heterojunctions with record high power conversion efficiencies

NASA Astrophysics Data System (ADS)

Yu, Junting; Jiang, Zhou; Hao, Yifan; Zhu, Qianhong; Zhao, Mingliang; Jiang, Xue; Zhao, Jijun

2018-06-01

Compared to inorganic solar cells, the power conversion efficiencies (PCEs) of organic solar cells are much lower, but they are compensated by many merits such as lower cost, less weight, and tunable structures, making them prospective for further applications. Porphyrin and phthalocyanine are the two most significant materials for organic solar cells due to their strong light-absorbing properties and semiconductor characteristics. However, there is little research on the 2D heterojunction solar cells based on these two materials, meanwhile the PCEs of them are still low. Here we have self-assembled several 2D zinc porphyrins (ZnPors) and performed first-principles simulation to demonstrate their good stability, suitable light harvesting, and high charge carrier mobility. By perfectly matching lattice constants and molecular energy levels between those 2D ZnPors and our previous proposed zinc phthalocyanines (ZnPcs), 11 type-II organic heterojunctions are constructed to further improve their charge separation capability. Those advantages endow 2D ZnPors and ZnPcs appreciable PCEs for solar cells. Among them, the theoretical PCE of 2D ZnPors/ZnPcs heterojunctions achieves as high as 19.84%, which exceeds all reported organic solar cells, and even approaches the PCEs of inorganic solar cells. These results indicate that our 2D ZnPors and 2D ZnPcs are good candidate materials for future organic solar cells.

78 FR 79665 - Welded Carbon Steel Standard Pipe and Tube Products From Turkey: Final Results of Antidumping...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-31

... Pipe and Tube Products From Turkey: Final Results of Antidumping Duty Administrative Review; 2011-2012... pipe and tube products (welded pipe and tube) from Turkey.\\1\\ The period of review (POR) is May 1, 2011... during the POR.\\2\\ \\1\\ See Welded Carbon Steel Standard Pipe and Tube Products from Turkey: Preliminary...

Differentiation‐associated urothelial cytochrome P450 oxidoreductase predicates the xenobiotic‐metabolizing activity of “luminal” muscle‐invasive bladder cancers

PubMed Central

Arlt, Volker M.; Indra, Radek; Joel, Madeleine; Stiborová, Marie; Eardley, Ian; Ahmad, Niaz; Otto, Wolfgang; Burger, Maximilian; Rubenwolf, Peter; Phillips, David H.; Southgate, Jennifer

2018-01-01

Extra‐hepatic metabolism of xenobiotics by epithelial tissues has evolved as a self‐defence mechanism but has potential to contribute to the local activation of carcinogens. Bladder epithelium (urothelium) is bathed in excreted urinary toxicants and pro‐carcinogens. This study reveals how differentiation affects cytochrome P450 (CYP) activity and the role of NADPH:P450 oxidoreductase (POR). CYP1A1 and CYP1B1 transcripts were inducible in normal human urothelial (NHU) cells maintained in both undifferentiated and functional barrier‐forming differentiated states in vitro. However, ethoxyresorufin O‐deethylation (EROD) activity, the generation of reactive BaP metabolites and BaP‐DNA adducts, were predominantly detected in differentiated NHU cell cultures. This gain‐of‐function was attributable to the expression of POR, an essential electron donor for all CYPs, which was significantly upregulated as part of urothelial differentiation. Immunohistology of muscle‐invasive bladder cancer (MIBC) revealed significant overall suppression of POR expression. Stratification of MIBC biopsies into “luminal” and “basal” groups, based on GATA3 and cytokeratin 5/6 labeling, showed POR over‐expression by a subgroup of the differentiated luminal tumors. In bladder cancer cell lines, CYP1‐activity was undetectable/low in basal PORlo T24 and SCaBER cells and higher in the luminal POR over‐expressing RT4 and RT112 cells than in differentiated NHU cells, indicating that CYP‐function is related to differentiation status in bladder cancers. This study establishes POR as a predictive biomarker of metabolic potential. This has implications in bladder carcinogenesis for the hepatic versus local activation of carcinogens and as a functional predictor of the potential for MIBC to respond to prodrug therapies. PMID:29323757

Association of low dietary intake of fiber and liquids with constipation: evidence from the National Health and Nutrition Examination Survey.

PubMed

Markland, Alayne D; Palsson, Olafur; Goode, Patricia S; Burgio, Kathryn L; Busby-Whitehead, Jan; Whitehead, William E

2013-05-01

Epidemiological studies support an association of self-defined constipation with fiber and physical activity, but not liquid intake. The aims of this study were to assess the prevalence and associations of dietary fiber and liquid intake to constipation. Analyses were based on data from 10,914 adults (≥20 years) from the 2005-2008 cycles of the National Health and Nutrition Examination Surveys. Constipation was defined as hard or lumpy stools (Bristol Stool Scale type 1 or 2) as the "usual or most common stool type." Dietary fiber and liquid intake from total moisture content were obtained from dietary recall. Co-variables included: age, race, education, poverty income ratio, body mass index, self-reported general health status, chronic illnesses, and physical activity. Prevalence estimates and prevalence odds ratios (POR) were analyzed in adjusted multivariable models using appropriate sampling weights. Overall, 9,373 (85.9%) adults (4,787 women and 4,586 men) had complete stool consistency and dietary data. Constipation rates were 10.2% (95% confidence interval (CI): 9.6, 10.9) for women and 4.0% (95% CI: 3.2, 5.0) for men (P<.001). After multivariable adjustment, low liquid consumption remained a predictor of constipation among women (POR: 1.3, 95% CI: 1.0, 1.6) and men (POR: 2.4, 95% CI: 1.5, 3.9); however, dietary fiber was not a predictor. Among women, African-American race/ethnicity (POR: 1.4, 95% CI: 1.0, 1.9), being obese (POR: 0.7, 95% CI: 0.5,0.9), and having a higher education level (POR: 0.8, 95% CI: 0.7, 0.9) were significantly associated with constipation. The findings support clinical recommendations to treat constipation with increased liquid, but not fiber or exercise.

Association of Low Dietary Intake of Fiber and Liquids with Constipation: Evidence from the National Health and Nutrition Examination Survey (NHANES)

PubMed Central

Markland, Alayne D.; Palsson, Olafur; Goode, Patricia S.; Burgio, Kathryn L.; Busby-Whitehead, Jan; Whitehead, William E.

2013-01-01

Objective Epidemiological studies support an association of self-defined constipation with fiber and physical activity, but not liquid intake. The aims of this study were to assess the prevalence and associations of dietary fiber and liquid intake to constipation. Methods Analyses were based on data from 10,914 adults (≥20 years) from the 2005-2008 cycles of the National Health and Nutrition Examination Surveys (NHANES). Constipation was defined as hard or lumpy stools (Bristol Stool Scale types 1 or 2) as the “usual or most common stool type.” Dietary fiber and liquid intake from total moisture content were obtained from dietary recall. Co-variables included: age, race, education, poverty income ratio, body mass index, self-reported general health status, chronic illnesses, and physical activity. Prevalence estimates and prevalence odds ratios (POR) were analyzed in adjusted multivariable models using appropriate sampling weights. Results Overall, 9,373 (85.9%) adults (4,787 women and 4,586 men) had complete stool consistency and dietary data. Constipation rates were 10.2% (95% CI: 9.6,10.9) for women and 4.0 (95% CI: 3.2,5.0) for men (p<.001). After multivariable adjustment, low liquid consumption remained a predictor of constipation among women (POR: 1.3, 95% CI: 1.0,1.6) and men (POR: 2.4, 95% CI: 1.5,3.9); however, dietary fiber was not a predictor. Among women, African-American race/ethnicity (POR: 1.4, 95% CI: 1.0,1.9), being obese (POR: 0.7, 95% CI: 0.5,0.9), and having a higher education level (POR: 0.8, 95% CI: 0.7,0.9) were significantly associated with constipation. Conclusions The findings support clinical recommendations to treat constipation with increased liquid, but not fiber or exercise. PMID:23567352

Factors associated with the incidence of pressure ulcer during hospital stay.

PubMed

Matozinhos, Fernanda Penido; Velasquez-Melendez, Gustavo; Tiensoli, Sabrina Daros; Moreira, Alexandra Dias; Gomes, Flávia Sampaio Latini

2017-05-25

Estimating the incidence rate of pressure ulcers and verifying factors associated with this occurrence in a cohort of hospitalized patients. This is a cohort study in which the considered outcome was the time until pressure ulcer occurrence. Estimated effect of the variables on the cumulative incidence ratio of the outcome was performed using the Cox proportional hazards model. Variable selection occurred via the Logrank hypothesis test. The sample consisted of 442 adults, with 25 incidents of pressure ulcers. Patients with high scores on the Braden scale presented a higher risk of pressure ulcer incidence when compared to those classified into the low score category. These results reinforce the importance of using the Braden Scale to assist in identifying patients more likely to develop pressure ulcers. Estimar a taxa de incidência de úlcera por pressão e verificar fatores associados a essa ocorrência em uma coorte de pacientes hospitalizados. Trata-se de estudo de coorte no qual o desfecho foi a ocorrência da úlcera por pressão. A estimativa do efeito das variáveis para a proporção de incidência acumulada do desfecho foi realizada utilizando o modelo de riscos proporcionais de Cox. A seleção das variáveis ocorreu por meio do teste de hipóteses Logrank. A amostra foi composta de 442 adultos, com 25 casos incidentes de úlcera por pressão. Pacientes com altos escores na escala de Braden apresentaram maior risco de incidência de úlcera por pressão quando comparados com aqueles classificados na categoria de baixo escore. Os resultados reforçam a importância do uso da Escala de Braden para auxiliar na identificação dos pacientes com maior probabilidade de desenvolver úlcera por pressão.

Missed Opportunities for Human Immunodeficiency Virus and Syphilis Testing Among Men Who Have Sex With Men in China: A Cross-Sectional Study.

PubMed

Ong, Jason J; Fu, Hongyun; Pan, Stephen; Smith, M Kumi; Wu, Dan; Wei, Chongyi; Cao, Bolin; Ma, Wei; Yang, Ligang; Tang, Weiming; Tucker, Joseph D

2018-06-01

Men who have sex with men (MSM) are at high risk of human immunodeficiency virus (HIV)/syphilis. To inform strategies for dual testing, we describe patterns of HIV/syphilis testing, and examine factors associated with never testing for HIV/syphilis in China. An online survey (2016) was completed by MSM from 8 cities: men born biologically male, 16 years or older, and had sex with another man at least once during their lifetime. Demographic, sexual behavioral, and HIV/syphilis testing data were collected. Multivariable multinomial logistic regression identified characteristics associated with men who never tested for HIV/syphilis compared with men who ever tested for both infections. Overall, 2105 men participated. Among them, 35.1% (738/2105) never tested for HIV/syphilis, and in those ever tested for HIV, only half (54.0%, 709/1312) had tested for syphilis. Relative to men who had ever tested for both infections, those with increased probability of never testing for HIV/syphilis include non-gay sexual identity (prevalence odds ratio [POR] 1.86; 95% confidence interval [CI], 1.45-2.37), not disclosed their sexuality/sexual history with men other than their regular partner (POR, 2.22; 95% CI, 1.75-2.78]) or with health professionals (POR, 11.11; 95% CI, 7.69-14.29), no condomless sex with casual partners in the last 3 months (POR, 1.89; 95% CI, 1.37-2.56), no community engagement in sexual health (POR, 15.16; 95% CI, 9.40-24.45), and mainly met partners offline (POR, 1.49; 95% CI, 1.16-1.92). There are significant gaps in lifetime testing for HIV/syphilis among Chinese MSM. Strategies to target never testers and integrate syphilis testing within HIV testing services are urgently needed. Future opportunities include point-of-care dual test kits, and testing in China's expanding primary healthcare system.

Does open-air exposure to volatile organic compounds near a plastic recycling factory cause health effects?

PubMed

Yorifuji, Takashi; Noguchi, Miyuki; Tsuda, Toshihide; Suzuki, Etsuji; Takao, Soshi; Kashima, Saori; Yanagisawa, Yukio

2012-01-01

After a plastic reprocessing factory began to operate in August 2004, the residents around the factory in Neyagawa, Osaka, Japan, began to complain of symptoms. Therefore, we conducted an exposure assessment and a population-based epidemiological study in 2006. To assess exposure, volatile organic compounds (VOCs) and total VOCs were measured at two locations in the vicinity of the factory. In the population-based study, a total of 3,950 residents were targeted. A self-administered questionnaire was used to collect information about subjects' mucocutaneous or respiratory symptoms. Using logistic regression models, we compared the prevalence of symptoms in July 2006 by employing the farthest area from the factory as a reference, and prevalence odds ratios (PORs) and their 95% confidence intervals (CIs) were estimated. The concentration of total VOCs was higher in the vicinity of the factory. The prevalence of mucocutaneous and respiratory symptoms was the highest among the residents in the closest area to the factory. Some symptoms were significantly increased among the residents within 500 m of the factory compared with residents of an area 2800 m from the factory: e.g., sore throat (POR=3.2, 95% CI: 1.3-8.0), eye itch (POR=3.0, 95% CI: 1.5-6.0), eye discharge (POR=6.0, 95% CI: 2.3-15.9), eczema (POR=3.0, 95% CI: 1.1-7.9) and sputum (POR=2.4, 95% CI: 1.1-5.1). Despite of the limitations of this study, these results imply a possible association of open-air VOCs with mucocutaneous and respiratory symptoms. Because this kind of plasticre cycling factory only recently came into operation, more attention should be paid to the operation of plastic recycling factories in the environment.

PubMed

Dipierri, José Edgardo; Bronberg, Rubén Adrian

2017-09-08

Debido al incremento de casos de microcefalia por virus Zika en Brasil el Ministerio de Salud de Argentina recomienda incrementar la vigilancia de esta malformación. A fin de profundizar el conocimiento del comportamiento epidemiológico de microcefalia en el país se analiza la mortalidad infantil por microcefalia entre 1998-2012. Los datos proceden de la Dirección de Estadísticas e Información de Salud (DEIS). Se calculó por provincias y regiones la tasa de mortalidad infantil por microcefalia (TMI-M) y se realizó un análisis de agrupamiento a nivel departamental. Las tasas más elevadas se observaron en las regiones y provincias del norte del país. La distribución espacial de la TMI-M guarda relación con las prevalencias de microcefalia en recién nacidos. Esta distribución se relaciona con la mayor pobreza y consanguinidad del norte de la Argentina, factores sinérgicos predisponentes de la ocurrencia de malformaciones congénitas en general y de microcefalia en particular.

Long-term follow-up of a female with congenital adrenal hyperplasia due to P450-oxidoreductase deficiency.

PubMed

Bonamichi, Beatriz D S F; Santiago, Stella L M; Bertola, Débora R; Kim, Chong A; Alonso, Nivaldo; Mendonca, Berenice B; Bachega, Tania A S S; Gomes, Larissa G

2016-10-01

P450 oxidoreductase deficiency (PORD) is a variant of congenital adrenal hyperplasia that is caused by POR gene mutations. The POR gene encodes a flavor protein that transfers electrons from nicotinamide adenine dinucleotide phosphate (NADPH) to all microsomal cytochrome P450 type II (including 21-hydroxylase, 17α-hydroxylase 17,20 lyase and aromatase), which is fundamental for their enzymatic activity. POR mutations cause variable impairments in steroidogenic enzyme activities that result in wide phenotypic variability ranging from 46,XX or 46,XY disorders of sexual differentiation, glucocorticoid deficiency, with or without skeletal malformations similar to Antley-Bixler syndrome to asymptomatic newborns diagnosed during neonatal screening test. Little is known about the PORD long-term evolution. We described a 46,XX patient with mild atypical genitalia associated with severe bone malformation, who was diagnosed after 13 years due to sexual infantilism. She developed large ovarian cysts and late onset adrenal insufficiency during follow-up, both of each regressed after hormone replacement therapies. We also described a late surgical approach for the correction of facial hypoplasia in a POR patient.

Observational study to calculate addictive risk to opioids: a validation study of a predictive algorithm to evaluate opioid use disorder

PubMed Central

Brenton, Ashley; Richeimer, Steven; Sharma, Maneesh; Lee, Chee; Kantorovich, Svetlana; Blanchard, John; Meshkin, Brian

2017-01-01

Background Opioid abuse in chronic pain patients is a major public health issue, with rapidly increasing addiction rates and deaths from unintentional overdose more than quadrupling since 1999. Purpose This study seeks to determine the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated single-nucleotide polymorphisms (SNPs). Patients and methods The Proove Opioid Risk (POR) algorithm determines the predictability of aberrant behavior to opioids using a comprehensive scoring algorithm incorporating phenotypic risk factors and neuroscience-associated SNPs. In a validation study with 258 subjects with diagnosed opioid use disorder (OUD) and 650 controls who reported using opioids, the POR successfully categorized patients at high and moderate risks of opioid misuse or abuse with 95.7% sensitivity. Regardless of changes in the prevalence of opioid misuse or abuse, the sensitivity of POR remained >95%. Conclusion The POR correctly stratifies patients into low-, moderate-, and high-risk categories to appropriately identify patients at need for additional guidance, monitoring, or treatment changes. PMID:28572737

[Not Available].

PubMed

Ortega, Rosa M

2016-07-19

El artículo de San Mauro y cols. profundiza en un tema de interés prioritario como es el estudio de los hábitos de ingesta de fluidos en personas de cuatro países: España, Portugal, México y Uruguay, para analizar si se cumplen (y si se conocen) las pautas de hidratación marcadas como adecuadas por organismos oficiales y, en concreto, por la EFSA. Es indudable la importancia de una correcta hidratación pues mientras que se puede vivir meses, o años, con una alimentación incorrecta, la deshidratación puede llevar a la muerte en un escaso periodo de tiempo. Por otra parte, un aporte ligeramente insuficiente de fluidos perjudica la salud, capacidad funcional y calidad de vida del individuo, por lo que debe ser evitada. Incluso algunos estudios encuentran hábitos y estilo de vida menos saludables en individuos con menor consumo de fluidos y pautas de hidratación más incorrectas.

Postinfectious bronchiolitis obliterans

PubMed

2018-06-01

La bronquiolitis obliterante es una enfermedad pulmonar crónica infrecuente y grave producto de una lesión del tracto respiratorio inferior. En nuestro país, es más frecuente observarla secundaria a una lesión viral grave, en especial, por adenovirus. La bronquiolitis obliterante se caracteriza por la oclusión parcial o total del lumen de los bronquiolos respiratorios y terminales por tejido inflamatorio y fibrosis, que produce la obstrucción crónica de la vía aérea. Este consenso discute el estado actual del conocimiento en las diferentes áreas de la bronquiolitis obliterante secundaria a una lesión infecciosa.