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Sample records for airway resistance increased

  1. Mouth leak with nasal continuous positive airway pressure increases nasal airway resistance.

    PubMed

    Richards, G N; Cistulli, P A; Ungar, R G; Berthon-Jones, M; Sullivan, C E

    1996-07-01

    Nasal congestion, dry nose and throat, and sore throat affect approximately 40% of patients using nasal continuous positive airway pressure (CPAP). The mechanisms causing nasal symptoms are unclear, but mouth leaks causing high unidirectional nasal airflow may be important. We conducted a study to investigate the effects of mouth leak and the influence of humidification on nasal resistance in normal subjects. Nasal resistance was measured with posterior rhinomanometry in six normal subjects who deliberately produced a mouth leak for 10 min while using nasal CPAP. Nasal resistance was measured regularly for 20 min after the challenge. A series of tests were performed using air at differing temperatures and humidities. There was no change in nasal resistance when subjects breathed through their noses while on CPAP, but a mouth leak caused a large increase in resistance (at a flow of 0.5 L/s) from a baseline mean of 2.21 cm H2O/L/s to a maximum mean of 7.52 cm H2O/L/s at 1 min after the challenge. Use of a cold passover humidifier caused little change in the response (maximum mean: 8.27 cm H2O/L/s), but a hot water bath humidifier greatly attenuated the magnitude (maximum mean: 4.02 cm H2O/L/s) and duration of the response. Mouth leak with nasal CPAP leads to high unidirectional nasal airflow, which causes a large increase in nasal resistance. This response can be largely prevented by fully humidifying the inspired air.

  2. Mouth-opening increases upper-airway collapsibility without changing resistance during midazolam sedation.

    PubMed

    Ayuse, T; Inazawa, T; Kurata, S; Okayasu, I; Sakamoto, E; Oi, K; Schneider, H; Schwartz, A R

    2004-09-01

    Sedative doses of anesthetic agents affect upper-airway function. Oral-maxillofacial surgery is frequently performed on sedated patients whose mouths must be as open as possible if the procedures are to be accomplished successfully. We examined upper-airway pressure-flow relationships in closed mouths, mouths opened moderately, and mouths opened maximally to test the hypothesis that mouth-opening compromises upper-airway patency during midazolam sedation. From these relationships, upper-airway critical pressure (Pcrit) and upstream resistance (Rua) were derived. Maximal mouth-opening increased Pcrit to -3.6 +/- 2.9 cm H2O compared with -8.7 +/- 2.8 (p = 0.002) for closed mouths and -7.2 +/- 4.1 (p = 0.038) for mouths opened moderately. In contrast, Rua was similar in all three conditions (18.4 +/- 6.6 vs. 17.7 +/- 7.6 vs. 21.5 +/- 11.6 cm H2O/L/sec). Moreover, maximum mouth-opening produced an inspiratory airflow limitation at atmosphere that was eliminated when nasal pressure was adjusted to 4.3 +/- 2.7 cm H2O. We conclude that maximal mouth-opening increases upper-airway collapsibility, which contributes to upper-airway obstruction at atmosphere during midazolam sedation.

  3. Vitamin A Deficiency Increases Airway Resistance Following C-fiber Stimulation

    PubMed Central

    McGowan, S.E.

    2009-01-01

    Vitamin A deficiency (VAD) remains an important problem in the developing world where environmental air pollution is increasing. Because the coincidence of these factors could increase the prevalence of asthma in these regions, airway reactivity to methacholine, capsaicin, and sulfur dioxide was studied in VAD rats. The impedance to a small volume oscillation was analyzed to determine airway resistance (Raw) and lung elastance (H). VAD rats demonstrated larger increases in Raw and H after the administration of methacholine, and in Raw after administration of capsaicin or sulfur-dioxide. The muscarinic receptor-2 (M2R) selective antagonist AFDX-116 enhanced the effect of capsaicin in vitamin A sufficient (VAS) but not VAD rats and retinoic acid administration partially restored this enhancement. These data indicate that diminished auto-inhibitory muscarinic receptor-2 (M2R) function contributed to this increased airway responsiveness to pulmonary C-fiber stimulation in VAD rats. If children with VAD also have diminished M2R function, they may be more prone to develop asthma, particularly in the presence of environmental co-factors such as sulfur dioxide. PMID:17321224

  4. [The syndrome of increased upper airways resistance: What are the clinical features and diagnostic procedures?].

    PubMed

    M'saad, S; Yangui, I; Feki, W; Abid, N; Bahloul, N; Marouen, F; Chakroun, A; Kammoun, S

    2015-12-01

    The upper airway resistance syndrome "UARS" is a poorly defined entity, often described as a moderate variant of the obstructive sleep apnea syndrome. It is associated with respiratory effort-related arousal, absence of obstructive sleep apnea, and absence of significant desaturation. It is a relatively common condition that predominantly affects non-obese young adults, with no predominance in either sex. The degree of upper airway collapsibility during sleep of patients with UARS is intermediate between that of normal subjects and that of patients with mild-to-moderate sleep apnea syndrome. Craniofacial and palatal abnormalities are often noted. Patients frequently complain of a functional somatic syndrome, especially daytime sleepiness and chronic fatigue. Polysomnography with esophageal pressure measurements remains the gold standard diagnostic test. The absence of any neurological abnormality gives UARS a good prognosis and it is potentially reversible if treated early. However, some studies suggest that untreated UARS has an increased risk of arterial hypertension. It can also evolve into obstructive sleep apnea.

  5. What does airway resistance tell us about lung function?

    PubMed

    Kaminsky, David A

    2012-01-01

    Spirometry is considered the primary method to detect the air flow limitation associated with obstructive lung disease. However, air flow limitation is the end-result of many factors that contribute to obstructive lung disease. One of these factors is increased airway resistance. Airway resistance is traditionally measured by relating air flow and driving pressure using body plethysmography, thus deriving airway resistance (R(aw)), specific airway resistance (sR(aw)), and specific airway conductance (sG(aw)). Other methods to measure airway resistance include the forced oscillation technique (FOT), which allows calculation of respiratory system resistance (R(RS)) and reactance (X(RS)), and the interrupter technique, which allows calculation of interrupter resistance (R(int)). An advantage of these other methods is that they may be easier to perform than spirometry, making them particularly suited to patients who cannot perform spirometry, such as young children, patients with neuromuscular disorders, or patients on mechanical ventilation. Since spirometry also requires a deep inhalation, which can alter airway resistance, these alternative methods may provide more sensitive measures of airway resistance. Furthermore, the FOT provides unique information about lung mechanics that is not available from analysis using spirometry, body plethysmography, or the interrupter technique. However, it is unclear whether any of these measures of airway resistance contribute clinically important information to the traditional measures derived from spirometry (FEV(1), FVC, and FEV(1)/FVC). The purpose of this paper is to review the physiology and methodology of these measures of airway resistance, and then focus on their clinical utility in relation to each other and to spirometry.

  6. Deposition of aerosol particles and flow resistance in mathematical and experimental airway models.

    PubMed

    Kim, C S; Brown, L K; Lewars, G G; Sackner, M A

    1983-07-01

    Aerosol deposition and flow resistance in obstructed airways were determined from five mathematical and experimental airway models. The first three models were theoretical and based upon Weibel's symmetrical lung model with 1) uniform reduction of airway diameter in various groups of airway generations; 2) obstruction of a few major airways such that a severe uneven flow distribution occurs in the lung; 3) focal constriction of selected large airways. In model 3, an empirical formula was utilized to assess deposition and resistance in the constricted airways. The remaining two models were tested experimentally; 4) oscillation of a compliant wall in a straight tube and 5) two-phase gas-liquid flow utilizing human sputum in a rigid branching tube. In models 1, 2, and 3, airway resistance increased to a greater extent than did the increase of aerosol deposition except when small airways were obstructed in model 1. Here, the increase of aerosol deposition was slightly higher than the rise in airway resistance. A sharp increase of aerosol deposition with a minimal increase of flow resistance was demonstrated in models 4 and 5. These data indicate that aerosol deposition may be a more sensitive indicator of airway abnormalities than overall airway resistance in small airways obstruction, during oscillation of large and medium airway walls, and when excessive secretions within the airways move with a wave or slug motion.

  7. Upper airway resistance: species-related differences.

    PubMed

    Kirschvink, N; Reinhold, P

    2010-07-01

    In veterinary medicine, upper airway resistance deserves a particular attention in equines athletes and brachycephalic dogs. Due to the anatomical peculiarities of the upper airway and/or pathological conditions, significant alterations of performance and/or well being might occur in horses and dogs. Physiological specificities and pathological changes of the lower respiratory tract deserve a major attention in other species.

  8. Firefighting acutely increases airway responsiveness.

    PubMed

    Sherman, C B; Barnhart, S; Miller, M F; Segal, M R; Aitken, M; Schoene, R; Daniell, W; Rosenstock, L

    1989-07-01

    The acute effects of the products of combustion and pyrolysis on airway responsiveness among firefighters are poorly documented. To study this relationship, spirometry and methacholine challenge testing (MCT) were performed on 18 active Seattle firefighters before and 5 to 24 h after firefighting. Body plethysmography was used to measure changes in specific airway conductance (SGaw), and results of MCT were analyzed using PD35-SGaw, the cumulative dose causing a 35% decrease in SGaw. Subjects who did not react by the end of the protocol were assigned a value of 640 inhalational units, the largest cumulative dose. Fire exposure was defined as the total time (hours) spent without a self-contained breathing apparatus at the firesite and was categorized as mild (less than 1 h, n = 7), moderate (1 to 2 h, n = 5), or severe (greater than 2 h, n = 6). Mean age of the 18 firefighters was 36.7 +/- 6.7 yr (range, 25 to 51), with a mean of 9.1 +/- 7.9 active years in the trade (range, zero to 22). None was known to be asthmatic. After firefighting, FEV1 % predicted (%pred) and FEF25-75 %pred significantly decreased by means of 3.4 +/- 1.1% and 5.6 +/- 2.6%, respectively. The mean decline in PD35-SGaw after firefighting was 184.5 +/- 53.2 units (p = 0.003). This observed decline in PD35-SGaw could not be explained by decrements in prechallenge SGaw, FEV1, or FVC.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Exploratory study into the effect of abdominal mass loading on airways resistance and ventilatory failure

    PubMed Central

    Dattani, Raj S; Swerner, Casey B; Stradling, John R; Manuel, Ari RG

    2016-01-01

    Objective We hypothesised that the airway resistance during tidal breathing would correlate with a particular pattern of increasing obesity, particularly when supine, and would differ between participants with and without ventilatory failure. Methods In our cross-sectional cohort study, 72 morbidly obese patients (40 males, 32 females, mean body mass index (BMI) 47.2) had measurements of both airways resistance (by impulse oscillometry (IOS)) and adiposity (by dual-energy X-ray absorptiometry (DXA)). Results All measures of airways resistance increased in the supine position: total airways resistance (R5) +37% (p<0.0005); large airways resistance (R20) +29% (p<0.0005); and small airways resistance (R5–R20) +52% (p<0.0005). BMI was correlated with seated R5, seated R5–R20, supine R5 and supine R5–R20 (r=0.33 p<0.006, r=0.32 p<0.004, r=0.30 p<0.02 and r=0.36 p<0.04, respectively). Visceral adipose tissue mass was correlated with supine R5–20 (r=0.46 p<0.05). Supine measures of total airways resistance (R5) and large airways resistance (R20) differed between those with and without ventilatory failure, as did mean weight and BMI. Conclusions Our study identifies a potentially detrimental effect of the supine posture on tidal breathing airways resistance in obese patients. This change is correlated most with visceral adipose tissue mass and the small airways. We were able to demonstrate that supine increases in airways resistance during tidal breathing, within obese patients, are different between those with and without ventilatory failure. Trial registration number NCT01380418; pre-results. PMID:27335651

  10. Modeling airway resistance dynamics after tidal and deep inspirations.

    PubMed

    Thorpe, C William; Salome, Cheryl M; Berend, Norbert; King, Gregory G

    2004-11-01

    Using the forced oscillation technique, we tracked airway resistance continuously during quiet breathing (QB) and deep inspiration (DI), thus observing fluctuations in resistance that may reflect mechanisms of airway stretch and renarrowing. After DI, however, the resistance may be depressed for a period not related to volume changes. We hypothesized that this gradual increase in resistance after DI-induced dilation was determined by a simple time constant. Furthermore, to the extent that this effect reflects dynamic characteristics of airway renarrowing, the resistance change after each tidal inspiration should also be constrained by this temporal limit. A model relating resistance fluctuations to the breathing pattern, including both instantaneous and delayed effects, was developed and applied to data from 14 nonasthmatic and 17 asthmatic subjects (forced expiratory volume in 1 s = 103 +/- 13 and 83 +/- 12%, respectively, means +/- SD) after methacholine challenge (dose 145 +/- 80 and 3.0 +/- 3.4 micromol, respectively) that resulted in respective forced expiratory volume in 1 s reductions of 16 +/- 7 and 24 +/- 6% from baseline. Resistance was measured continuously for 1 min of QB, a DI, followed by a further minute of QB. Resistance values at end expiration (Ree) and end inspiration were calculated. We found that the sequence of Ree after DI was best modeled by a power-law function of time rather than an exponential decay (r2 = 0.82 +/- 0.18 compared with 0.63 +/- 0.16; P < 0.01). Furthermore, the coefficient characterizing this "renarrowing function" was close to equal to the coefficient characterizing the equivalent function of resistance change between each resistance value at end inpiration and subsequent Ree during QB, particularly in the nonasthmatic subjects for whom the intraclass correlation was 0.66. This suggests that the same time-dependent factors determine renarrowing after both large and small breaths.

  11. Maternal Diesel Inhalation Increases Airway Hyperreactivity in Ozone Exposed Offspring

    EPA Science Inventory

    Air pollutant exposure is linked with childhood asthma incidence and exacerbations, and maternal exposure to airborne pollutants during pregnancy increases airway hyperreactivity (ARR) in offspring. To determine if exposure to diesel exhaust during pregnancy worsened postnatal oz...

  12. Cigarette smoke extract inhibits expression of peroxiredoxin V and increases airway epithelial permeability.

    PubMed

    Serikov, Vladimir B; Leutenegger, Christian; Krutilina, Raisa; Kropotov, Andrei; Pleskach, Nadezhda; Suh, Jung H; Tomilin, Nikolay V

    2006-01-01

    Inhaled cigarette smoke induces oxidative stress in the epithelium of airways. Peroxiredoxin V (PRXV) is a potent antioxidant protein, highly expressed in cells of the airway epithelium. The goal of our study was to determine whether cigarette smoke extract (CSE) influenced expression of this protein in airway epithelia in vivo and in vitro. In Sprague-Dawley rats, we determined effects of CSE on airway epithelial permeability, mRNA levels and expression of PRXV protein. Exposure of isolated tracheal segment in vitro to 20% CSE for 4 h resulted in development of increased permeability to albumin, significantly reduced mRNA levels for PRXV, and reduced amounts of PRXV protein in the epithelium. In cultures of the airway epithelial cell lines (Calu-3, JME), primary airway cell culture (cow), and alveolar epithelial cells A549, CSE also significantly decreased transepithelial electrical resistance and expression of PRXV protein, and induced glutathione and protein oxidation. To demonstrate functional importance of PRXV, we exposed clones of HeLa cells with siRNA-downregulated PRXV to hydrogen peroxide, which resulted in increased rate of cell death and protein oxidation. CSE directly downregulates expression of functionally important antioxidant enzyme PRXV in the epithelial cells of airways, which represents one pathophysiological mechanism of cigarette smoke toxicity.

  13. Effects of hypercapnia and inspiratory flow-resistive loading on respiratory activity in chronic airways obstruction.

    PubMed Central

    Altose, M D; McCauley, W C; Kelsen, S G; Cherniack, N S

    1977-01-01

    The respiratory responses to hypercapnia alone and to hypercapnia and flow-resistive loading during inspiration were studied in normal individuals and in eucapnic and hypercapnic patients with chronic airways obstruction. Responses were assessed in terms of minute ventilation and occlusion pressure (mouth pressure during airway occlusion 100 ms after the onset of inspiration). Ventilatory responses to CO2 (deltaV/deltaPCO2) were distinctly subnormal in both groups of patients with airways obstruction. The two groups of patients, however, showed different occlusion pressure responses to CO2 (deltaP100/deltaPCO2): deltaP100/deltaPCO2 was normal in the eucapnic patients but subnormal in the hypercapnic patients. Flow-resistive loading during inspiration reduced deltaV/deltaPCO2 both in normal subjects and in patients with airways obstruction. The occlusion pressure response to CO2 increased in normal subjects during flow-resistive loading but remained unchanged in both groups of patients with chronic airways obstruction. These results indicate that while chemosensitivity as determined by deltaP100/deltaPCO2 is impaired only in hypercapnic patients with chronic airways obstruction, an acute increase in flow resistance elicits a subnormal increase in respiratory efferent activity in both eucapnic and hypercapnic patients. PMID:838862

  14. Effect of aerosol propellants and surfactants on airway resistance

    PubMed Central

    Sterling, G. M.; Batten, J. C.

    1969-01-01

    The effects on the airways of inhalation of the vehicles used in two commercial pressurized bronchodilator aerosols were studied in 20 normal and seven asthmatic subjects. Changes in bronchial calibre due to bronchoconstriction were measured as changes in airway resistance using a constant volume whole body plethysmograph, and results were expressed as changes in the ratio Airway conductance/Thoracic gas volume (=specific airway conductance). The aerosols caused very slight bronchoconstriction in the normal subjects, with a mean decrease of 5·3% in specific airway conductance after inhalation of a spray containing sorbitol trioleate as a surface tension lowering agent, and of 9·7% after inhalation of a spray containing lecithin. This effect was prevented by prior inhalation of atropine methonitrate, and its mechanism was therefore probably a vagally mediated reflex. The bronchoconstriction was also reversed by the addition of isoprenaline to the aerosol. The asthmatic subjects showed larger mean reductions in specific airway conductance of 13% and 21% after sorbitol and lecithin respectively: the response was again prevented by atropine. We conclude that, although the aerosol vehicles cause slight bronchoconstriction, this is unlikely to be a clinical danger since it is insufficient to cause symptoms of wheezing, and is less than that caused by inhalation of a single cigarette. Moreover, the constriction is regularly converted to dilatation in both normal and asthmatic subjects by the addition of atropine or isoprenaline to the aerosol. PMID:5821624

  15. The effect of Le Fort I maxillary impaction on nasal airway resistance.

    PubMed

    Guenthner, T A; Sather, A H; Kern, E B

    1984-04-01

    To evaluate the effect of maxillary superior movement via Le Fort I osteotomy on nasal airway resistance, eleven Caucasian patients whose surgical orthodontic treatment included Le Fort I impaction (range 2 to 8 mm, mean 5.3 mm) were selected. Nasal airway resistance in these patients was determined a few days before and approximately 8 weeks after the Le Fort I surgical procedure. Nasal airway resistance was determined by means of a uninasal active mask rhinomanometric technique. Contrary to the predicted negative effects of maxillary superior movement on nasal airway function, there was a statistically significant improvement in nasal airway resistance (P less than 0.01) after maxillary superior movement. This rather unexpected finding can be explained by examining the effect of maxillary superior movement on the nasal valve area in the anterior nose. The nasal valve area is a teardrop-shaped area bordered by the nasal septum, the caudal end of the upper lateral nasal cartilage, the floor of the nose, and the soft fibrofatty tissue on the lateral aspect of the nose. The apex of the teardrop-shaped area (the angle between the nasal septum and the upper lateral cartilage) is called the nasal valve. In the Caucasian type of nose, the nasal valve accounts for most of the inspiratory resistance to airflow. Maxillary superior movement increases the alar width. It is proposed that this increase in alar width is transmitted at least partially to the nasal valve angle, causing it to widen slightly, paradoxically reducing nasal airway resistance while reducing skeletal intranasal dimensions.

  16. Airway wall stiffening increases peak wall shear stress: a fluid-structure interaction study in rigid and compliant airways.

    PubMed

    Xia, Guohua; Tawhai, Merryn H; Hoffman, Eric A; Lin, Ching-Long

    2010-05-01

    The airflow characteristics in a computed tomography (CT) based human airway bifurcation model with rigid and compliant walls are investigated numerically. An in-house three-dimensional (3D) fluid-structure interaction (FSI) method is applied to simulate the flow at different Reynolds numbers and airway wall stiffness. As the Reynolds number increases, the airway wall deformation increases and the secondary flow becomes more prominent. It is found that the peak wall shear stress on the rigid airway wall can be five times stronger than that on the compliant airway wall. When adding tethering forces to the model, we find that these forces, which produce larger airway deformation than without tethering, lead to more skewed velocity profiles in the lower branches and further reduced wall shear stresses via a larger airway lumen. This implies that pathologic changes in the lung such as fibrosis or remodeling of the airway wall-both of which can serve to restrain airway wall motion-have the potential to increase wall shear stress and thus can form a positive feed-back loop for the development of altered flow profiles and airway remodeling. These observations are particularly interesting as we try to understand flow and structural changes seen in, for instance, asthma, emphysema, cystic fibrosis, and interstitial lung disease.

  17. Accumulating evidence for increased velocity of airway smooth muscle shortening in asthmatic airway hyperresponsiveness.

    PubMed

    Ijpma, Gijs; Matusovsky, Oleg; Lauzon, Anne-Marie

    2012-01-01

    It remains unclear whether airway smooth muscle (ASM) mechanics is altered in asthma. While efforts have originally focussed on contractile force, some evidence points to an increased velocity of shortening. A greater rate of airway renarrowing after a deep inspiration has been reported in asthmatics compared to controls, which could result from a shortening velocity increase. In addition, we have recently shown in rats that increased shortening velocity correlates with increased muscle shortening, without increasing muscle force. Nonetheless, establishing whether or not asthmatic ASM shortens faster than that of normal subjects remains problematic. Endobronchial biopsies provide excellent tissue samples because the patients are well characterized, but the size of the samples allows only cell level experiments. Whole human lungs from transplant programs suffer primarily from poor patient characterization, leading to high variability. ASM from several animal models of asthma has shown increased shortening velocity, but it is unclear whether this is representative of human asthma. Several candidates have been suggested as responsible for increased shortening velocity in asthma, such as alterations in contractile protein expression or changes in the contractile apparatus structure. There is no doubt that more remains to be learned about the role of shortening velocity in asthma.

  18. Respiratory syncytial virus infection increases chlorine-induced airway hyperresponsiveness

    PubMed Central

    Song, Weifeng; Yu, Zhihong; Doran, Stephen F.; Ambalavanan, Namasivayam; Steele, Chad; Garantziotis, Stavros

    2015-01-01

    Exposure to chlorine (Cl2) damages airway and alveolar epithelia resulting in acute lung injury and reactive airway hyperresponsiveness (AHR) to methacholine. However, little is known about the effect of preexisting respiratory disease on Cl2-induced lung injury. By using a murine respiratory syncytial virus (RSV) infection model, we found that preexisting RSV infection increases Cl2 (187 ppm for 30 min)-induced lung inflammation and airway AHR at 24 h after exposure (5 days after infection). RSV infection and Cl2 exposure synergistically induced oxygen desaturation and neutrophil infiltration and increased MCP-1, MIP-1β, IL-10, IFN-γ, and RANTES concentrations in the bronchoalveolar lavage fluid (BALF). In contrast, levels of type 2 cytokines (i.e., IL-4, IL-5, IL-9, and IL-13) were not significantly affected by either RSV infection or Cl2 exposure. Cl2 exposure, but not RSV infection, induced AHR to methacholine challenge as measured by flexiVent. Moreover, preexisting RSV infection amplified BALF levels of hyaluronan (HA) and AHR. The Cl2-induced AHR was mitigated by treatment with inter-α-trypsin inhibitor antibody, which inhibits HA signaling, suggesting a mechanism of HA-mediated AHR from exacerbated oxidative injury. Our results show for the first time that preexisting RSV infection predisposes the lung to Cl2-induced injury. These data emphasize the necessity for further research on the effects of Cl2 in vulnerable populations and the development of appropriate treatments. PMID:26071553

  19. Effect of sleep and sighing on upper airway resistance in mongrel dogs.

    PubMed

    Issa, F G; Porostocky, S; Feroah, T

    1994-08-01

    We investigated the effect of sleep and sighing on supratracheal resistance in unrestrained mongrel dogs breathing through the nose by comparing within-breath changes in upper airway pressure-flow relationship in control, sigh, and five postsigh breaths recorded during wakefulness and during non-rapid-eye-movement and rapid-eye-movement sleep. A sigh breath was characterized by a high tidal volume and was typically followed by an apnea of a variable duration. Sleep had little or no effect on supratracheal resistance, measured at peak flow rates, during quiet breathing (awake 7.3 +/- 0.4, non-rapid eye movement 8.3 +/- 0.4, and rapid eye movement 6.8 +/- 0.4 cmH2O.l-1.s). The resistance was identical in the early part of inspiration in control and sigh breaths but increased during the augmented phase of sigh breaths. Resistance at peak inspiratory flow was higher in sigh breaths than in control breaths in all sleep states. The flow-pressure profile of postsigh breaths was identical to that of control breaths in all sleep states. We conclude that upper airway resistance is essentially unaffected by sleep state in the mongrel dog and that sighing increases upper airway resistance regardless of sleep state.

  20. Could an increase in airway smooth muscle shortening velocity cause airway hyperresponsiveness?

    PubMed

    Bullimore, Sharon R; Siddiqui, Sana; Donovan, Graham M; Martin, James G; Sneyd, James; Bates, Jason H T; Lauzon, Anne-Marie

    2011-01-01

    Airway hyperresponsiveness (AHR) is a characteristic feature of asthma. It has been proposed that an increase in the shortening velocity of airway smooth muscle (ASM) could contribute to AHR. To address this possibility, we tested whether an increase in the isotonic shortening velocity of ASM is associated with an increase in the rate and total amount of shortening when ASM is subjected to an oscillating load, as occurs during breathing. Experiments were performed in vitro using 27 rat tracheal ASM strips supramaximally stimulated with methacholine. Isotonic velocity at 20% isometric force (Fiso) was measured, and then the load on the muscle was varied sinusoidally (0.33 ± 0.25 Fiso, 1.2 Hz) for 20 min, while muscle length was measured. A large amplitude oscillation was applied every 4 min to simulate a deep breath. We found that: 1) ASM strips with a higher isotonic velocity shortened more quickly during the force oscillations, both initially (P < 0.001) and after the simulated deep breaths (P = 0.002); 2) ASM strips with a higher isotonic velocity exhibited a greater total shortening during the force oscillation protocol (P < 0.005); and 3) the effect of an increase in isotonic velocity was at least comparable in magnitude to the effect of a proportional increase in ASM force-generating capacity. A cross-bridge model showed that an increase in the total amount of shortening with increased isotonic velocity could be explained by a change in either the cycling rate of phosphorylated cross bridges or the rate of myosin light chain phosphorylation. We conclude that, if asthma involves an increase in ASM velocity, this could be an important factor in the associated AHR.

  1. Role of Autonomic Nervous System and the Cough Reflex in the Increased Responsiveness of Airways in Patients with Obstructive Airway Disease*

    PubMed Central

    Simonsson, B. G.; Jacobs, F. M.; Nadel, J. A.

    1967-01-01

    Inhalation of aerosols of citric acid, histamine phosphate, or carbon dust, or air cooled to - 20°C or rapid respiratory maneuvers (inspiration or expiration) results in an increase in airway resistance in some patients with asthma or bronchitis. It has been shown previously in animals that stimulation of cough receptors results in bronchoconstriction through efferent cholinergic pathways. In the patients studied, the administration of atropine sulfate, which would block such pathways, abolished the bronchoconstrictor effects of all the stimuli except large doses of histamine, which may exert a direct effect on airway smooth muscle. These data suggest that sensitized cough receptors may be involved in triggering reflex airway constriction in such patients. PMID:6070326

  2. Validation of airway resistance models for predicting pressure loss through anatomically realistic conducting airway replicas of adults and children.

    PubMed

    Borojeni, Azadeh A T; Noga, Michelle L; Martin, Andrew R; Finlay, Warren H

    2015-07-16

    This work describes in vitro measurement of the total pressure loss at varying flow rate through anatomically realistic conducting airway replicas of 10 children, 4 to 8 years old, and 5 adults. Experimental results were compared with analytical predictions made using published airway resistance models. For the adult replicas, the model proposed by van Ertbruggen et al. (2005. J. Appl. Physiol. 98, 970-980) most accurately predicted central conducting airway resistance for inspiratory flow rates ranging from 15 to 90 L/min. Models proposed by Pedley et al. (1970. J. Respir. Physiol. 9, 371-386) and by Katz et al. (2011. J. Biomech. 44, 1137-1143) also provided reasonable estimates, but with a tendency to over predict measured pressure loss for both models. For child replicas, the Pedley and Katz models both provided good estimation of measured pressure loss at flow rates representative of resting tidal breathing, but under predicted measured values at high inspiratory flow rate (60 L/min). The van Ertbruggen model, developed based on flow simulations performed in an adult airway model, tended to under predict measured pressure loss through the child replicas across the range of flow rates studied (2 to 60 L/min). These results are intended to provide guidance for selection of analytical pressure loss models for use in predicting airway resistance and ventilation distribution in adults and children.

  3. Effects of cigarette smoke and chronic hypoxia on airways remodeling and resistance. Clinical significance.

    PubMed

    Olea, Elena; Ferrer, Elisabet; Prieto-Lloret, Jesus; Gonzalez-Martin, Carmen; Vega-Agapito, Victoria; Gonzalez-Obeso, Elvira; Agapito, Teresa; Peinado, Victor; Obeso, Ana; Barbera, Joan Albert; Gonzalez, Constancio

    2011-12-15

    Previously we have reported that association of cigarette smoke (CS) and chronic hypoxia (CH) interact positively to physiopathologically remodel pulmonary circulation. In present study we have exposed guinea pigs to CS smoke (four cigarettes/day; 3 months; CS) and to chronic hypoxia (12% O(2), 15 days; CH) alone or in combination (CSCH animals) and evaluated airways remodeling and resistance assessed as Penh (enhance pause). We measured Penh while animals breathe air, 10% O(2) and 5% CO(2) and found that CS and CH animals have higher Penh than controls; Penh was even larger in CSCH animals. A rough parallelism between Penh and thickness of bronchiolar wall and muscular layer and Goblet cell number was noticed. We conclude that CS and CH association accelerates CS-induced respiratory system damage, evidenced by augmented airway resistance, bronchial wall thickness and muscularization and Goblet cell number. Our findings would suggest that appearance of hypoxia would aggravate any preexisting pulmonary pathology by increasing airways resistance and reactivity.

  4. Vitamin D deficiency causes airway hyperresponsiveness, increases airway smooth muscle mass, and reduces TGF-β expression in the lungs of female BALB/c mice.

    PubMed

    Foong, Rachel E; Shaw, Nicole C; Berry, Luke J; Hart, Prue H; Gorman, Shelley; Zosky, Graeme R

    2014-01-01

    Abstract Vitamin D deficiency is associated with disease severity in asthma. We tested whether there is a causal association between vitamin D deficiency, airway smooth muscle (ASM) mass, and the development of airway hyperresponsiveness (AHR). A physiologically relevant mouse model of vitamin D deficiency was developed by raising BALB/c mice on vitamin D-deficient or -replete diets. AHR was assessed by measuring lung function responses to increasing doses of inhaled methacholine. Five-micron sections from formalin-fixed lungs were used for ASM measurement and assessment of lung structure using stereological methods. Transforming growth factor (TGF)-β levels were measured in bronchoalveolar lavage fluid (BALF). Lungs were dissected from embryonic day (E) 17.5 vitamin D-deficient and -replete fetal mice for quantification of ASM density and relative gene expression of TGF-β signaling pathway molecules. Eight-week-old adult vitamin D-deficient female mice had significantly increased airway resistance and ASM in the large airways compared with controls. Vitamin D-deficient female mice had a smaller lung volume, volume of parenchyma, and alveolar septa. Both vitamin D-deficient male and female mice had reduced TGF-β levels in BALF. Vitamin D deficiency did not have an effect on ASM density in E17.5 mice, however, expression of TGF-β1 and TGF-β receptor I was downregulated in vitamin D-deficient female fetal mice. Decreased expression of TGF-β1 and TGF-β receptor I during early lung development in vitamin D-deficient mice may contribute to airway remodeling and AHR in vitamin D-deficient adult female mice. This study provides a link between vitamin D deficiency and respiratory symptoms in chronic lung disease.

  5. Cigarette smoke increases the penetration of asbestos fibers into airway walls.

    PubMed Central

    McFadden, D.; Wright, J.; Wiggs, B.; Churg, A.

    1986-01-01

    For study of the penetration of asbestos fibers into airway walls, guinea pigs were given amosite asbestos by intratracheal instillation. Half of the animals were also exposed to cigarette smoke. Animals were sacrificed at 1 week and 1 month, and numbers of fibers in airway walls were counted in histologic sections. In both smoke-exposed and nonexposed groups, numbers of fibers per square millimeter of airway wall increased from 1 week to 1 month in the respiratory bronchioles. At each time period, smoke-exposed animals had significantly higher numbers of fibers in the airway walls, compared with nonexposed animals. It is concluded that 1) continued transport of fibers into interstitial tissues may be the reason that asbestosis can progress after cessation of exposure; 2) cigarette smoke increases the penetration of fibers into airway walls. This effect may play a role in the increased incidence of disease seen in smoking, compared with nonsmoking, asbestos workers. PMID:3963152

  6. Relationship between Pulmonary Airflow and Resistance in Patients with Airway Narrowing Using An 1-D Network Resistance and Compliance Model

    NASA Astrophysics Data System (ADS)

    Choi, Sanghun; Choi, Jiwoong; Hoffman, Eric; Lin, Ching-Long

    2016-11-01

    To predict the proper relationship between airway resistance and regional airflow, we proposed a novel 1-D network model for airway resistance and acinar compliance. First, we extracted 1-D skeletons at inspiration images, and generated 1-D trees of CT unresolved airways with a volume filling method. We used Horsfield order with random heterogeneity to create diameters of the generated 1-D trees. We employed a resistance model that accounts for kinetic energy and viscous dissipation (Model A). The resistance model is further coupled with a regional compliance model estimated from two static images (Model B). For validation, we applied both models to a healthy subject. The results showed that Model A failed to provide airflows consistent with air volume change, whereas Model B provided airflows consistent with air volume change. Since airflows shall be regionally consistent with air volume change in patients with normal airways, Model B was validated. Then, we applied Model B to severe asthmatic subjects. The results showed that regional airflows were significantly deviated from air volume change due to airway narrowing. This implies that airway resistance plays a major role in determining regional airflows of patients with airway narrowing. Support for this study was provided, in part, by NIH Grants U01 HL114494, R01 HL094315, R01 HL112986, and S10 RR022421.

  7. Modelling resistance and reactance with heterogeneous airway narrowing in mild to severe asthma.

    PubMed

    Bhatawadekar, Swati A; Leary, Del; Maksym, Geoffrey N

    2015-03-01

    Ventilation heterogeneity is an important marker of small airway dysfunction in asthma. The frequency dependence of respiratory system resistance (Rrs) from oscillometry is used as a measure of this heterogeneity. However, this has not been quantitatively assessed or compared with other outcomes from oscillometry, including respiratory system reactance (Xrs) and the associated elastance (Ers). Here, we used a multibranch model of the human lung, including an upper airway shunt, to match previously reported respiratory mechanics in mild to severe asthma. We imposed heterogeneity by narrowing a proportion of the peripheral airways to account for patient Ers at 5 Hz, and then narrowed central airways to account for the remaining Rrs at 18 Hz. The model required >75% of the small airways to be occluded to reproduce severe asthma. While the model produced frequency dependence in Rrs, it was upward-shifted below 5 Hz compared with in-vivo results, indicating that other factors, including more distributed airway narrowing or central airway wall compliance, are required. However, Ers quantitatively reflected the imposed heterogeneity better than the frequency dependence of Rrs, independent of the frequency range for the estimation, and thus was a more robust measure of small-airway function. Thus, Ers appears to have greater potential as a clinical measure of early small-airway disease in asthma.

  8. Novel insights into the aetiology and pathophysiology of increased airway inflammation during COPD exacerbations.

    PubMed

    Tsoumakidou, Maria; Siafakas, Nikolaos M

    2006-05-22

    Airway inflammation increases during acute exacerbations of COPD. Extrinsic factors, such as airway infections, increased air pollution, and intrinsic factors, such as increased oxidative stress and altered immunity may contribute to this increase. The evidence for this and the potential mechanisms by which various aetiological agents increase inflammation during COPD exacerbations is reviewed. The pathophysiologic consequences of increased airway inflammation during COPD exacerbations are also discussed. This review aims to establish a cause and effect relationship between etiological factors of increased airway inflammation and COPD exacerbations based on recently published data. Although it can be speculated that reducing inflammation may prevent and/or treat COPD exacerbations, the existing anti-inflammatory treatments are modestly effective.

  9. The Effects of Hyper- and Hypocapnia on Phonatory Laryngeal Airway Resistance in Women

    PubMed Central

    Slivka, William; Atwood, Charles W.; Verdolini Abbott, Katherine

    2015-01-01

    Purpose The larynx has a dual role in the regulation of gas flow into and out of the lungs while also establishing resistance required for vocal fold vibration. This study assessed reciprocal relations between phonatory functions—specifically, phonatory laryngeal airway resistance (Rlaw)—and respiratory homeostasis during states of ventilatory gas perturbations. Method Twenty-four healthy women performed phonatory tasks while exposed to induced hypercapnia (high CO2), hypocapnia (low CO2), and normal breathing (eupnea). Effects of gas perturbations on Rlaw were investigated as were the reciprocal effects of Rlaw modulations on respiratory homeostasis. Results Rlaw remained stable despite manipulations of inspired gas concentrations. In contrast, end-tidal CO2 levels increased significantly during all phonatory tasks. Thus, for the conditions tested, Rlaw did not adjust to accommodate ventilatory needs as predicted. Rather, stable Rlaw was spontaneously accomplished at the cost of those needs. Conclusions Findings provide support for a theory of regulation wherein Rlaw may be a control parameter in phonation. Results also provide insight into the influence of phonation on respiration. The work sets the foundation for future studies on laryngeal function during phonation in individuals with lower airway disease and other patient populations. PMID:25764093

  10. The Effects of Hyper- and Hypocapnia on Phonatory Laryngeal Airway Resistance in Women

    ERIC Educational Resources Information Center

    Gillespie, Amanda I.; Slivka, William; Atwood, Charles W., Jr.; Abbott, Katherine Verdolini

    2015-01-01

    Purpose: The larynx has a dual role in the regulation of gas flow into and out of the lungs while also establishing resistance required for vocal fold vibration. This study assessed reciprocal relations between phonatory functions--specifically, phonatory laryngeal airway resistance (R[subscript law])--and respiratory homeostasis during states of…

  11. Relationship between pre-anesthetic and intra-anesthetic airway resistance in patients undergoing general anesthesia: A prospective observational study.

    PubMed

    Ikeda, Takamitsu; Uchida, Kanji; Yamauchi, Yasuhiro; Nagase, Takahide; Oba, Koji; Yamada, Yoshitsugu

    2017-01-01

    Surgery patients in Japan undergo routine spirometry testing prior to general anesthesia. The use of a flow sensor during general anesthesia has recently become common. However, it is not certain whether the information derived from flow-volume curves is being adequately used for mechanical ventilation management during general anesthesia. So far, there have been no attempts to calculate airway resistance using flow-volume curves. Therefore, we performed a prospective, observational study to investigate the relationship between pre-anesthetic and intra-anesthetic airway resistance in patients scheduled for surgery under general anesthesia. We calculated pre-anesthetic and intra-anesthetic airway resistance in each patient, based on the slopes of flow-volume curves obtained prior to and during general anesthesia. We also calculated endotracheal tube resistance to correct the intra-anesthetic airway resistance values calculated. A total of 526 patients were included in the study, and 98 patients had a forced expiratory volume in the first second/forced vital capacity ratio of < 70%. Pre-anesthetic airway resistance was significantly higher in patients with airflow obstruction than in those without airflow obstruction (p < 0.001), whereas no significant difference in intra-anesthetic airway resistance was found between patients with and without airflow obstruction during mechanical ventilation (p = 0.48). Pre-anesthetic and intra-anesthetic airway resistance values were closer to each other in patients without airflow obstruction, with a mean difference < 1.0 cmH2O L-1s-1, than in those with airflow obstruction, although these respiratory parameters were significantly different (p < 0.001). Intra-anesthetic airway resistance was not related to the FEV1/FVC ratio, regardless of the degree to which the FEV1/FVC ratio reflected pre-anesthetic airway resistance. As compared with patients with airflow obstruction, the mean difference between pre-anesthetic and intra

  12. Relationship between pre-anesthetic and intra-anesthetic airway resistance in patients undergoing general anesthesia: A prospective observational study

    PubMed Central

    Ikeda, Takamitsu; Uchida, Kanji; Yamauchi, Yasuhiro; Nagase, Takahide; Oba, Koji; Yamada, Yoshitsugu

    2017-01-01

    Surgery patients in Japan undergo routine spirometry testing prior to general anesthesia. The use of a flow sensor during general anesthesia has recently become common. However, it is not certain whether the information derived from flow-volume curves is being adequately used for mechanical ventilation management during general anesthesia. So far, there have been no attempts to calculate airway resistance using flow-volume curves. Therefore, we performed a prospective, observational study to investigate the relationship between pre-anesthetic and intra-anesthetic airway resistance in patients scheduled for surgery under general anesthesia. We calculated pre-anesthetic and intra-anesthetic airway resistance in each patient, based on the slopes of flow-volume curves obtained prior to and during general anesthesia. We also calculated endotracheal tube resistance to correct the intra-anesthetic airway resistance values calculated. A total of 526 patients were included in the study, and 98 patients had a forced expiratory volume in the first second/forced vital capacity ratio of < 70%. Pre-anesthetic airway resistance was significantly higher in patients with airflow obstruction than in those without airflow obstruction (p < 0.001), whereas no significant difference in intra-anesthetic airway resistance was found between patients with and without airflow obstruction during mechanical ventilation (p = 0.48). Pre-anesthetic and intra-anesthetic airway resistance values were closer to each other in patients without airflow obstruction, with a mean difference < 1.0 cmH2O L-1s-1, than in those with airflow obstruction, although these respiratory parameters were significantly different (p < 0.001). Intra-anesthetic airway resistance was not related to the FEV1/FVC ratio, regardless of the degree to which the FEV1/FVC ratio reflected pre-anesthetic airway resistance. As compared with patients with airflow obstruction, the mean difference between pre-anesthetic and intra

  13. Injury Induces Localized Airway Increases in Pro-Inflammatory Cytokines in Humans and Mice

    PubMed Central

    Jonker, Mark A.; Hermsen, Joshua L.; Gomez, F. Enrique; Sano, Yoshifumi

    2011-01-01

    Abstract Background Secretory immunoglobulin A (sIgA) increases in the airways of humans and mice after injury to protect against infection. The pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 are linked molecularly to sIgA production and secretion and are required for sIgA increases in the airway after injury in a mouse model. We investigated the injury effect on airway and serum concentrations to determine the source of the cytokines involved in the airway IgA response. Methods In the first experiment, TNF-α, IL-1β, and IL-6 concentrations in bronchoalveolar lavage (BAL) fluid and serum obtained from 11 ventilated trauma patients within 30 h of admission were compared with those in eight elective surgical patients. In the second experiment, male ICR mice received no injury (n = 7) or injury with sham celiotomy and neck incisions (n = 8) with sacrifice of all animals at 8 h for BAL fluid and serum cytokine measurements by enzyme-linked immunosorbent assay. Results Injured patients had significantly higher BAL fluid and serum TNF-α, IL-1β, and IL-6 concentrations, with greater increases in the BAL fluid than in the serum. Injured mice had significantly increased BAL fluid concentrations of TNF-α, IL-1β, and IL-6 without significant changes in serum TNF-α or IL-1β. Serum IL-6 increased significantly. Conclusions Injury significantly increases human and mouse airway TNF-α, IL-1β, and IL-6. Increases are greater in the airway than in serum, implying a local rather than a systemic stress response to injury. PMID:21166596

  14. Treatment of upper airway resistance syndrome in adults: Where do we stand?☆

    PubMed Central

    de Godoy, Luciana B.M.; Palombini, Luciana O.; Guilleminault, Christian; Poyares, Dalva; Tufik, Sergio; Togeiro, Sonia M.

    2015-01-01

    Objective: To evaluate the available literature regarding Upper Airway Resistance Syndrome (UARS) treatment. Methods: Keywords “Upper Airway Resistance Syndrome,” “Sleep-related Breathing Disorder treatment,” “Obstructive Sleep Apnea treatment” and “flow limitation and sleep” were used in main databases. Results: We found 27 articles describing UARS treatment. Nasal continuous positive airway pressure (CPAP) has been the mainstay therapy prescribed but with limited effectiveness. Studies about surgical treatments had methodological limitations. Oral appliances seem to be effective but their efficacy is not yet established. Conclusion: Randomized controlled trials with larger numbers of patients and long-term follow-up are important to establish UARS treatment options. PMID:26483942

  15. Increased airway responsiveness and decreased alveolar attachment points following in utero smoke exposure in the guinea pig.

    PubMed

    Elliot, J; Carroll, N; Bosco, M; McCrohan, M; Robinson, P

    2001-01-01

    Maternal smoking during pregnancy has been shown to result in abnormalities in lung function in newborn infants, including reduced expiratory flow and increased airway responsiveness to inhaled agonists. The mechanisms by which this occurs remain unclear. Using a guinea pig model of in utero smoke exposure, we measured airway responsiveness and lung morphology in a group of neonatal guinea pigs 21 d after delivery. Pregnant guinea pigs were exposed to cigarette smoke from Day 28 to term (Day 68 of gestation). After delivery newborn animals did not receive any smoke exposure. Airway wall thickness, smooth muscle area, and the number of points where the alveoli attached to the airway adventitia were measured. Airway responsiveness was increased (p < 0.05) and the mean distance between alveolar attachment points was increased (mean 0.052 +/- SE 0.001 mm versus 0.046 +/- 0.001, p = 0.001) in animals exposed to cigarette smoke in utero compared with nonexposed animals. Although not statistically significant, both the inner and outer airway wall and the smooth muscle area were greater in exposed animals compared with nonexposed animals. The increased mean distance between alveolar attachments in the smoke-exposed group was the result of a reduction in the number of attachments and an increase in the outer airway wall perimeter. These findings suggest that the increased airway responsiveness observed in postnatal animals, subsequent to in utero cigarette smoke exposure, may be the result of decreased alveolar attachment points to the airways and changes in airway dimensions.

  16. Comparison of effects of spreader grafts and flaring sutures on nasal airway resistance in rhinoplasty.

    PubMed

    Jalali, Mir Mohammad

    2015-09-01

    Cephalic resection of the lateral crura of the alar cartilages, lateral osteotomies, and removal of the nasal hump during rhinoplasty may cause collapse of the internal nasal valve angle. This study was performed to compare preventive effects of two techniques (spreader grafts and flaring sutures) on rhinoplasty by rhinomanometry. Two hundred and forty-eight patients participated in this semi-experimental study. The patients were assigned into two groups. 28 of them were not available for follow-up. All patients had a straight nose in the midline and no severe septal deviations. 87 of 220 patients underwent the spreader grafts technique and the flaring sutures technique was performed in 133 patients. The nasal airway resistance was calculated by active anterior rhinomanometry on admission to hospital and again between 3 and 6 months following surgery. The mean of follow-up was 20.9 ± 2.9 weeks. After rhinoplasty, nasal airway resistance decreased in 46 patients (52.9 percent) of spreader grafts group and in 84 patients (63.2 percent) of flaring sutures group. The median nasal airway resistance difference (before-after surgery) of spreader grafts and flaring sutures groups was 0.027 Pa/ml/s (range -110 to 130) and 0.017 Pa/ml/s (range -0.690 to 0.790), respectively. The difference of nasal airway resistance between before and after rhinoplasty in two groups was insignificance (Mann-Whitney U test, P = 0.5). The spreader grafts and flaring sutures move the dorsal border of the upper lateral cartilage in a lateral direction and had similar preventive effect on nasal airway resistance after rhinoplasty.

  17. Nose-only water-pipe smoking effects on airway resistance, inflammation, and oxidative stress in mice.

    PubMed

    Nemmar, Abderrahim; Raza, Haider; Yuvaraju, Priya; Beegam, Sumaya; John, Annie; Yasin, Javed; Hameed, Rasheed S; Adeghate, Ernest; Ali, Badreldin H

    2013-11-01

    Water-pipe smoking (WPS) is a common practice in the Middle East and is now gaining popularity in Europe and the United States. However, there is a limited number of studies on the respiratory effects of WPS. More specifically, the underlying pulmonary pathophysiological mechanisms related to WPS exposure are not understood. Presently, we assessed the respiratory effects of nose-only exposure to mainstream WPS generated by commercially available honey flavored "moasel" tobacco. The duration of the session was 30 min/day and 5 days/wk for 1 mo. Control mice were exposed to air only. Here, we measured in BALB/c mice the airway resistance using forced-oscillation technique. Lung inflammation was assessed histopathologically and by biochemical analysis of bronchoalveolar lavage (BAL) fluid, and oxidative stress was evaluated biochemically by measuring lipid peroxidation, reduced glutathione and several antioxidant enzymes. Pulmonary inflammation assessment showed an increase in neutrophil and lymphocyte numbers. Likewise, airway resistance was significantly increased in the WPS group compared with controls. Tumor necrosis factor α and interleukin 6 concentrations were significantly increased in BAL fluid. Lipid peroxidation in lung tissue was significantly increased whereas the level and activity of antioxidants including reduced glutathione, glutathione S transferase, and superoxide dismutase were all significantly decreased following WPS exposure, indicating the occurrence of oxidative stress. Moreover, carboxyhemoglobin levels were significantly increased in the WPS group. We conclude that 1-mo nose-only exposure to WPS significantly increased airway resistance, inflammation, and oxidative stress. Our results provide a mechanistic explanation for the limited clinical studies that reported the detrimental respiratory effects of WPS.

  18. Using Drugs to Probe the Variability of Trans-Epithelial Airway Resistance

    PubMed Central

    Tosoni, Kendra; Cassidy, Diane; Kerr, Barry; Land, Stephen C.; Mehta, Anil

    2016-01-01

    Background Precision medicine aims to combat the variability of the therapeutic response to a given medicine by delivering the right medicine to the right patient. However, the application of precision medicine is predicated on a prior quantitation of the variance of the reference range of normality. Airway pathophysiology provides a good example due to a very variable first line of defence against airborne assault. Humans differ in their susceptibility to inhaled pollutants and pathogens in part due to the magnitude of trans-epithelial resistance that determines the degree of epithelial penetration to the submucosal space. This initial ‘set-point’ may drive a sentinel event in airway disease pathogenesis. Epithelia differentiated in vitro from airway biopsies are commonly used to model trans-epithelial resistance but the ‘reference range of normality’ remains problematic. We investigated the range of electrophysiological characteristics of human airway epithelia grown at air-liquid interface in vitro from healthy volunteers focusing on the inter- and intra-subject variability both at baseline and after sequential exposure to drugs modulating ion transport. Methodology/Principal Findings Brushed nasal airway epithelial cells were differentiated at air-liquid interface generating 137 pseudostratified ciliated epithelia from 18 donors. A positively-skewed baseline range exists for trans-epithelial resistance (Min/Max: 309/2963 Ω·cm2), trans-epithelial voltage (-62.3/-1.8 mV) and calculated equivalent current (-125.0/-3.2 μA/cm2; all non-normal, P<0.001). A minority of healthy humans manifest a dramatic amiloride sensitivity to voltage and trans-epithelial resistance that is further discriminated by prior modulation of cAMP-stimulated chloride transport. Conclusions/Significance Healthy epithelia show log-order differences in their ion transport characteristics, likely reflective of their initial set-points of basal trans-epithelial resistance and sodium

  19. Corticosteroid administration modifies ozone-induced increases in sheep airway blood flow

    SciTech Connect

    Gunther, R.A.; Yousef, M.A.; Schelegle, E.S.; Cross, C.E. )

    1992-09-01

    Recently, we have shown that exposure of intubated conscious sheep to 3 to 4 ppm ozone (O3) for 3 h increases bronchial blood flow (Qbr). The purpose of the present study was to assess the potential role of corticosteroids in modulating this increase. Six nasally intubated sheep were exposed to filtered room air, 3.5 ppm O3 on two separate occasions, and 3.5 ppm O3 plus methyl-prednisone, for 3 h. Qbr was measured using a chronically implanted 20 MHz pulsed Doppler flow probe. Qbr, mean aortic pressure, cardiac output, pulmonary artery pressure, arterial blood gases, and core temperature were monitored. After 3 h of 3.5 ppm O3, Qbr increased from 3.2 +/- 0.5 (mean +/- SEM) to 8.5 +/- 1.6 KHz, whereas bronchial vascular resistance (BVR) decreased from the baseline value of 43.6 +/- 8.0 to 15.0 +/- 3 mm Hg/KHz. With corticosteroids, baseline Qbr was 3.2 +/- 0.6 and BVR was 44.2 +/- 9.7; after 3 h of 3.5 ppm O3, Qbr was 3.3 +/- 0.5 KHz and BVR was 39.0 +/- 8.0 mm Hg/KHz. The two 3.5-ppm O3 exposures without corticosteroids were impressively reproducible. Except for Qbr and BVR, no other measured cardiovascular parameters were affected by O3. The results indicate that corticosteroids are capable of interfering with mediator, neurohumoral, or inflammatory cell mechanisms responsible for vasodilation of the airway microcirculation after O3 exposure, but do not specifically address the specific processes whereby this attenuation occurs.

  20. Treatment resistant adolescent depression with upper airway resistance syndrome treated with rapid palatal expansion: a case report

    PubMed Central

    2012-01-01

    Introduction To the best of our knowledge, this is the first report of a case of treatment-resistant depression in which the patient was evaluated for sleep disordered breathing as the cause and in which rapid palatal expansion to permanently treat the sleep disordered breathing produced a prolonged symptom-free period off medication. Case presentation An 18-year-old Caucasian man presented to our sleep disorders center with chronic severe depression that was no longer responsive to medication but that had recently responded to electroconvulsive therapy. Ancillary, persistent symptoms included mild insomnia, moderate to severe fatigue, mild sleepiness and severe anxiety treated with medication. Our patient had no history of snoring or witnessed apnea, but polysomnography was consistent with upper airway resistance syndrome. Although our patient did not have an orthodontic indication for rapid palatal expansion, rapid palatal expansion was performed as a treatment of his upper airway resistance syndrome. Following rapid palatal expansion, our patient experienced a marked improvement of his sleep quality, anxiety, fatigue and sleepiness. His improvement has been maintained off all psychotropic medication and his depression has remained in remission for approximately two years following his electroconvulsive therapy. Conclusions This case report introduces the possibility that unrecognized sleep disordered breathing may play a role in adolescent treatment-resistant depression. The symptoms of upper airway resistance syndrome are non-specific enough that every adolescent with depression, even those responding to medication, may have underlying sleep disordered breathing. In such patients, rapid palatal expansion, by widening the upper airway and improving airflow during sleep, may produce a prolonged improvement of symptoms and a tapering of medication. Psychiatrists treating adolescents may benefit from having another treatment option for treatment-resistant

  1. Ambroxol suppresses influenza-virus proliferation in the mouse airway by increasing antiviral factor levels.

    PubMed

    Yang, B; Yao, D F; Ohuchi, M; Ide, M; Yano, M; Okumura, Y; Kido, H

    2002-05-01

    The protective effect of ambroxol, a mucolytic agent which has antioxidant properties and stimulates the release of pulmonary surfactant, against influenza-virus proliferation in the airway was investigated in mice. Ambroxol or the vehicle was administered intraperitoneally twice a day for 5-7 days to mice shortly after intranasal infection with a lethal dose of influenza A/Aichi/68 (H3N2) virus, and the survival rate, virus titre and levels of factors regulating virus proliferation in the airway fluid were analysed. Ambroxol significantly suppressed virus multiplication and improved the survival rate of mice. The effect of ambroxol reached a peak at 10 mg x kg(-1) x day(-1), higher doses being less effective. Ambroxol stimulated the release of suppressors of influenza-virus multiplication, such as pulmonary surfactant, mucus protease inhibitor, immunoglobulin (Ig)-A and IgG, although it stimulated the release of a trypsin-type protease that potentiates virus proliferation. In addition, ambroxol transiently suppressed release of the cytokines, tumour necrosis factor-alpha, interferon-gamma and interleukin-12, into airway fluid. Although ambroxol had several negative effects on the host defence system, overall it strikingly increased the concentrations of suppressors of influenza-virus multiplication in the airway.

  2. Increased Epicardial Adipose Tissue Is Associated with the Airway Dominant Phenotype of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Higami, Yuichi; Ogawa, Emiko; Ryujin, Yasushi; Goto, Kenichi; Seto, Ruriko; Wada, Hiroshi; Tho, Nguyen Van; Lan, Le Thi Tuyet; Paré, Peter D.; Nakano, Yasutaka

    2016-01-01

    Background Epicardial adipose tissue (EAT) has been shown to be a non-invasive marker that predicts the progression of cardiovascular disease (CVD). It has been reported that the EAT volume is increased in patients with chronic obstructive pulmonary disease (COPD). However, little is known about which phenotypes of COPD are associated with increased EAT. Methods One hundred and eighty smokers who were referred to the clinic were consecutively enrolled. A chest CT was used for the quantification of the emphysematous lesions, airway lesions, and EAT. These lesions were assessed as the percentage of low attenuation volume (LAV%), the square root of airway wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) and the EAT area, respectively. The same measurements were made on 225 Vietnamese COPD patients to replicate the results. Results Twenty-six of the referred patients did not have COPD, while 105 were diagnosed as having COPD based on a FEV1/FVC<0.70. The EAT area was significantly associated with age, BMI, FEV1 (%predicted), FEV1/FVC, self-reported hypertension, self-reported CVD, statin use, LAV%, and √Aaw at Pi10 in COPD patients. The multiple regression analyses showed that only BMI, self-reported CVD and √Aaw at Pi10 were independently associated with the EAT area (R2 = 0.51, p<0.0001). These results were replicated in the Vietnamese population. Conclusions The EAT area is independently associated with airway wall thickness. Because EAT is also an independent predictor of CVD risk, these data suggest a mechanistic link between the airway predominant form of COPD and CVD. PMID:26866482

  3. TNFα Affects Ciliary Beat Response to Increased Viscosity in Human Pediatric Airway Epithelium.

    PubMed

    González, Claudia; Droguett, Karla; Rios, Mariana; Cohen, Noam A; Villalón, Manuel

    2016-01-01

    In airway epithelium, mucociliary clearance (MCC) velocity depends on the ciliary beat frequency (CBF), and it is affected by mucus viscoelastic properties. Local inflammation induces secretion of cytokines (TNFα) that can alter mucus viscosity; however airway ciliated cells have an autoregulatory mechanism to prevent the collapse of CBF in response to increase in mucus viscosity, mechanism that is associated with an increment in intracellular Ca(+2) level ([Ca(2+)]i). We studied the effect of TNFα on the autoregulatory mechanism that regulates CBF in response to increased viscosity using dextran solutions, in ciliated cells cultured from human pediatric epithelial adenoid tissue. Cultures were treated with TNFα, before and after the viscous load was changed. TNFα treatment produced a significantly larger decrease in CBF in cultures exposed to dextran. Furthermore, an increment in [Ca(2+)]i was observed, which was significantly larger after TNFα treatment. In conclusion, although TNFα has deleterious effects on ciliated cells in response to maintaining CBF after increasing viscous loading, it has a positive effect, since increasing [Ca(2+)]i may prevent the MCC collapse. These findings suggest that augmented levels of TNFα associated with an inflammatory response of the nasopharyngeal epithelium may have dual effects that contribute to maintaining the effectiveness of MCC in the upper airways.

  4. TNFα Affects Ciliary Beat Response to Increased Viscosity in Human Pediatric Airway Epithelium

    PubMed Central

    Droguett, Karla; Rios, Mariana; Cohen, Noam A.

    2016-01-01

    In airway epithelium, mucociliary clearance (MCC) velocity depends on the ciliary beat frequency (CBF), and it is affected by mucus viscoelastic properties. Local inflammation induces secretion of cytokines (TNFα) that can alter mucus viscosity; however airway ciliated cells have an autoregulatory mechanism to prevent the collapse of CBF in response to increase in mucus viscosity, mechanism that is associated with an increment in intracellular Ca+2 level ([Ca2+]i). We studied the effect of TNFα on the autoregulatory mechanism that regulates CBF in response to increased viscosity using dextran solutions, in ciliated cells cultured from human pediatric epithelial adenoid tissue. Cultures were treated with TNFα, before and after the viscous load was changed. TNFα treatment produced a significantly larger decrease in CBF in cultures exposed to dextran. Furthermore, an increment in [Ca2+]i was observed, which was significantly larger after TNFα treatment. In conclusion, although TNFα has deleterious effects on ciliated cells in response to maintaining CBF after increasing viscous loading, it has a positive effect, since increasing [Ca2+]i may prevent the MCC collapse. These findings suggest that augmented levels of TNFα associated with an inflammatory response of the nasopharyngeal epithelium may have dual effects that contribute to maintaining the effectiveness of MCC in the upper airways. PMID:28025644

  5. Loss of anion transport without increased sodium absorption characterizes newborn porcine cystic fibrosis airway epithelia

    PubMed Central

    Chen, Jeng-Haur; Stoltz, David A.; Karp, Philip H.; Ernst, Sarah E.; Pezzulo, Alejandro A.; Moninger, Thomas O.; Rector, Michael V.; Reznikov, Leah R.; Launspach, Janice L.; Chaloner, Kathryn; Zabner, Joseph; Welsh, Michael J.

    2011-01-01

    SUMMARY Defective transepithelial electrolyte transport is thought to initiate cystic fibrosis (CF) lung disease. Yet, how loss of CFTR affects electrolyte transport remains uncertain. CFTR−/− pigs spontaneously develop lung disease resembling human CF. At birth, their airways exhibit a bacterial host defense defect, but are not inflamed. Therefore, we studied ion transport in newborn nasal and tracheal/bronchial epithelia in tissue, cultures, and in vivo. CFTR−/− epithelia showed markedly reduced Cl− and HCO3− transport. However, in contrast to a widely held view, lack of CFTR did not increase transepithelial Na+ or liquid absorption or reduce periciliary liquid depth. Like human CF, CFTR−/− pigs showed increased amiloride-sensitive voltage and current, but lack of apical Cl− conductance caused the change, not increased Na+ transport. These results indicate that CFTR provides the predominant transcellular pathway for Cl− and HCO3− in porcine airway epithelia, and reduced anion permeability may initiate CF airway disease. PMID:21145458

  6. Exposure to Ozone Modulates Human Airway Protease/Antiprotease Balance Contributing to Increased Influenza A Infection

    PubMed Central

    Kesic, Matthew J.; Meyer, Megan; Bauer, Rebecca; Jaspers, Ilona

    2012-01-01

    Exposure to oxidant air pollution is associated with increased respiratory morbidities and susceptibility to infections. Ozone is a commonly encountered oxidant air pollutant, yet its effects on influenza infections in humans are not known. The greater Mexico City area was the primary site for the spring 2009 influenza A H1N1 pandemic, which also coincided with high levels of environmental ozone. Proteolytic cleavage of the viral membrane protein hemagglutinin (HA) is essential for influenza virus infectivity. Recent studies suggest that HA cleavage might be cell-associated and facilitated by the type II transmembrane serine proteases (TTSPs) human airway trypsin-like protease (HAT) and transmembrane protease, serine 2 (TMPRSS2), whose activities are regulated by antiproteases, such as secretory leukocyte protease inhibitor (SLPI). Based on these observations, we sought to determine how acute exposure to ozone may modulate cellular protease/antiprotease expression and function, and to define their roles in a viral infection. We utilized our in vitro model of differentiated human nasal epithelial cells (NECs) to determine the effects of ozone on influenza cleavage, entry, and replication. We show that ozone exposure disrupts the protease/antiprotease balance within the airway liquid. We also determined that functional forms of HAT, TMPRSS2, and SLPI are secreted from human airway epithelium, and acute exposure to ozone inversely alters their expression levels. We also show that addition of antioxidants significantly reduces virus replication through the induction of SLPI. In addition, we determined that ozone-induced cleavage of the viral HA protein is not cell-associated and that secreted endogenous proteases are sufficient to activate HA leading to a significant increase in viral replication. Our data indicate that pre-exposure to ozone disrupts the protease/antiprotease balance found in the human airway, leading to increased influenza susceptibility. PMID

  7. Oxidation increases mucin polymer cross-links to stiffen airway mucus gels.

    PubMed

    Yuan, Shaopeng; Hollinger, Martin; Lachowicz-Scroggins, Marrah E; Kerr, Sheena C; Dunican, Eleanor M; Daniel, Brian M; Ghosh, Sudakshina; Erzurum, Serpel C; Willard, Belinda; Hazen, Stanley L; Huang, Xiaozhu; Carrington, Stephen D; Oscarson, Stefan; Fahy, John V

    2015-02-25

    Airway mucus in cystic fibrosis (CF) is highly elastic, but the mechanism behind this pathology is unclear. We hypothesized that the biophysical properties of CF mucus are altered because of neutrophilic oxidative stress. Using confocal imaging, rheology, and biochemical measures of inflammation and oxidation, we found that CF airway mucus gels have a molecular architecture characterized by a core of mucin covered by a web of DNA and a rheological profile characterized by high elasticity that can be normalized by chemical reduction. We also found that high levels of reactive oxygen species in CF mucus correlated positively and significantly with high concentrations of the oxidized products of cysteine (disulfide cross-links). To directly determine whether oxidation can cross-link mucins to increase mucus elasticity, we exposed induced sputum from healthy subjects to oxidizing stimuli and found a marked and thiol-dependent increase in sputum elasticity. Targeting mucin disulfide cross-links using current thiol-amino structures such as N-acetylcysteine (NAC) requires high drug concentrations to have mucolytic effects. We therefore synthesized a thiol-carbohydrate structure (methyl 6-thio-6-deoxy-α-D-galactopyranoside) and found that it had stronger reducing activity than NAC and more potent and fast-acting mucolytic activity in CF sputum. Thus, oxidation arising from airway inflammation or environmental exposure contributes to pathologic mucus gel formation in the lung, which suggests that it can be targeted by thiol-modified carbohydrates.

  8. Abdominal adiposity and obstructive airway disease: testing insulin resistance and sleep disordered breathing mechanisms

    PubMed Central

    2012-01-01

    Background This study examined associations of abdominal adiposity with lung function, asthma symptoms and current doctor-diagnosed asthma and mediation by insulin resistance (IR) and sleep disordered breathing (SDB). Methods A random sample of 2500 households was drawn from the community of Whyalla, South Australia (The Whyalla Intergenerational Study of Health, WISH February 2008 - July 2009). Seven-hundred twenty-two randomly selected adults (≥18 years) completed clinical protocols (32.2% response rate). Lung function was measured by spirometry. Post-bronchodilator FEV1/FVC was used to measure airway obstruction and reversibility of FEV1 was calculated. Current asthma was defined by self-reported doctor-diagnosis and evidence of currently active asthma. Symptom scores for asthma (CASS) and SDB were calculated. Intra-abdominal fat (IAF) was estimated using dual-energy x-ray absorptiometry (DXA). IR was calculated from fasting glucose and insulin concentrations. Results The prevalence of current doctor-diagnosed asthma was 19.9% (95% CI 16.7 – 23.5%). The ratio of observed to expected cases given the age and sex distribution of the population was 2.4 (95%CI 2.1, 2.9). IAF was not associated with current doctor-diagnosed asthma, FEV1/FVC or FEV1 reversibility in men or women but was positively associated with CASS independent of IR and SDB in women. A 1% increase in IAF was associated with decreases of 12 mL and 20 mL in FEV1 and FVC respectively in men, and 4 mL and 7 mL respectively in women. SDB mediated 12% and 26% of these associations respectively in men but had minimal effects in women. Conclusions In this population with an excess of doctor-diagnosed asthma, IAF was not a major factor in airway obstruction or doctor-diagnosed asthma, although women with higher IAF perceived more severe asthma symptoms which did not correlate with lower FEV1. Higher IAF was significantly associated with lower FEV1 and FVC and in men SDB mechanisms may

  9. Acidic pH increases airway surface liquid viscosity in cystic fibrosis

    PubMed Central

    Tang, Xiao Xiao; Ostedgaard, Lynda S.; Hoegger, Mark J.; Moninger, Thomas O.; Karp, Philip H.; McMenimen, James D.; Choudhury, Biswa; Varki, Ajit; Stoltz, David A.; Welsh, Michael J.

    2016-01-01

    Cystic fibrosis (CF) disrupts respiratory host defenses, allowing bacterial infection, inflammation, and mucus accumulation to progressively destroy the lungs. Our previous studies revealed that mucus with abnormal behavior impaired mucociliary transport in newborn CF piglets prior to the onset of secondary manifestations. To further investigate mucus abnormalities, here we studied airway surface liquid (ASL) collected from newborn piglets and ASL on cultured airway epithelia. Fluorescence recovery after photobleaching revealed that the viscosity of CF ASL was increased relative to that of non-CF ASL. CF ASL had a reduced pH, which was necessary and sufficient for genotype-dependent viscosity differences. The increased viscosity of CF ASL was not explained by pH-independent changes in HCO3– concentration, altered glycosylation, additional pH-induced disulfide bond formation, increased percentage of nonvolatile material, or increased sulfation. Treating acidic ASL with hypertonic saline or heparin largely reversed the increased viscosity, suggesting that acidic pH influences mucin electrostatic interactions. These findings link loss of cystic fibrosis transmembrane conductance regulator–dependent alkalinization to abnormal CF ASL. In addition, we found that increasing Ca2+ concentrations elevated ASL viscosity, in part, independently of pH. The results suggest that increasing pH, reducing Ca2+ concentration, and/or altering electrostatic interactions in ASL might benefit early CF. PMID:26808501

  10. Acidic pH increases airway surface liquid viscosity in cystic fibrosis.

    PubMed

    Tang, Xiao Xiao; Ostedgaard, Lynda S; Hoegger, Mark J; Moninger, Thomas O; Karp, Philip H; McMenimen, James D; Choudhury, Biswa; Varki, Ajit; Stoltz, David A; Welsh, Michael J

    2016-03-01

    Cystic fibrosis (CF) disrupts respiratory host defenses, allowing bacterial infection, inflammation, and mucus accumulation to progressively destroy the lungs. Our previous studies revealed that mucus with abnormal behavior impaired mucociliary transport in newborn CF piglets prior to the onset of secondary manifestations. To further investigate mucus abnormalities, here we studied airway surface liquid (ASL) collected from newborn piglets and ASL on cultured airway epithelia. Fluorescence recovery after photobleaching revealed that the viscosity of CF ASL was increased relative to that of non-CF ASL. CF ASL had a reduced pH, which was necessary and sufficient for genotype-dependent viscosity differences. The increased viscosity of CF ASL was not explained by pH-independent changes in HCO3- concentration, altered glycosylation, additional pH-induced disulfide bond formation, increased percentage of nonvolatile material, or increased sulfation. Treating acidic ASL with hypertonic saline or heparin largely reversed the increased viscosity, suggesting that acidic pH influences mucin electrostatic interactions. These findings link loss of cystic fibrosis transmembrane conductance regulator-dependent alkalinization to abnormal CF ASL. In addition, we found that increasing Ca2+ concentrations elevated ASL viscosity, in part, independently of pH. The results suggest that increasing pH, reducing Ca2+ concentration, and/or altering electrostatic interactions in ASL might benefit early CF.

  11. Reduced levels of maternal progesterone during pregnancy increase the risk for allergic airway diseases in females only.

    PubMed

    Hartwig, Isabel R V; Bruenahl, Christian A; Ramisch, Katherina; Keil, Thomas; Inman, Mark; Arck, Petra C; Pincus, Maike

    2014-10-01

    Observational as well as experimental studies support that prenatal challenges seemed to be associated with an increased risk for allergic airway diseases in the offspring. However, insights into biomarkers involved in mediating this risk are largely elusive. We here aimed to test the association between endogenous and exogenous factors documented in pregnant women, including psychosocial, endocrine, and life style parameters, and the risk for allergic airway diseases in the children later in life. We further pursued to functionally test identified factors in a mouse model of an allergic airway response. In a prospectively designed pregnancy cohort (n = 409 families), women were recruited between the 4th and 12th week of pregnancy. To investigate an association between exposures during pregnancy and the incidence of allergic airway disease in children between 3 and 5 years of age, multiple logistic regression analyses were applied. Further, in prenatally stressed adult offspring of BALB/c-mated BALB/c female mice, asthma was experimentally induced by ovalbumin (OVA) sensitization. In addition to the prenatal stress challenge, some pregnant females were treated with the progesterone derivative dihydrodydrogesterone (DHD). In humans, we observed that high levels of maternal progesterone in early human pregnancies were associated with a decreased risk for an allergic airway disease (asthma or allergic rhinitis) in daughters (adjusted OR 0.92; 95% confidence interval [CI] 0.84 to 1.00) but not sons (aOR 1.02, 95% CI 0.94-1.10). In mice, prenatal DHD supplementation of stress-challenged dams attenuated prenatal stress-induced airway hyperresponsiveness exclusively in female offspring. Reduced levels of maternal progesterone during pregnancy-which can result from high stress perception-increase the risk for allergic airway diseases in females but not in males. Key messages: Lower maternal progesterone during pregnancy increases the risk for allergic airway disease

  12. Lung volumes and airway resistance in patients with a possible restrictive pattern on spirometry

    PubMed Central

    Schultz, Kenia; D'Aquino, Luiz Carlos; Soares, Maria Raquel; Gimenez, Andrea; Pereira, Carlos Alberto de Castro

    2016-01-01

    ABSTRACT Objective: Many patients with proportional reductions in FVC and FEV1 on spirometry show no reduction in TLC. The aim of this study was to evaluate the role that measuring lung volumes and airway resistance plays in the correct classification of patients with a possible restrictive pattern on spirometry. Methods: This was a prospective study involving adults with reduced FVC and FEV1, as well as an FEV1/FV(C) ratio within the predicted range. Restrictive lung disease (RLD) was characterized by TLC below the 5th percentile, as determined by plethysmography. Obstructive lung disease (OLD) was characterized by high specific airway resistance, significant changes in post-bronchodilator FEV1, or an FEF25-75% < 50% of predicted, together with a high RV/TLC ratio. Nonspecific lung disease (NLD) was characterized by TLC within the predicted range and no obstruction. Combined lung disease (CLD) was characterized by reduced TLC and findings indicative of airflow obstruction. Clinical diagnoses were based on clinical suspicion, a respiratory questionnaire, and the review of tests of interest. Results: We included 300 patients in the study, of whom 108 (36%) were diagnosed with RLD. In addition, 120 (40%) and 72 (24%) were diagnosed with OLD/CLD and NLD, respectively. Among the latter, 24 (33%) were clinically diagnosed with OLD. In this sample, 151 patients (50.3%) were obese, and obesity was associated with all patterns of lung disease. Conclusions: Measuring lung volumes and airway resistance is often necessary in order to provide an appropriate characterization of the pattern of lung disease in patients presenting with a spirometry pattern suggestive of restriction. Airflow obstruction is common in such cases. PMID:27812633

  13. Increased phosphatidylcholine concentration in saliva reduces surface tension and improves airway patency in obstructive sleep apnoea.

    PubMed

    Kawai, M; Kirkness, J P; Yamamura, S; Imaizumi, K; Yoshimine, H; Oi, K; Ayuse, T

    2013-10-01

    Surface tension may have important role for maintaining upper airway patency in patients with obstructive sleep apnoea. It has been demonstrated that elevated surface tension increases the pharyngeal pressures required to reopen the upper airway following collapse. The aim of the study was to evaluate the associations between the concentrations of endogenous surfactants in saliva with indices of upper airway patency in obstructive sleep apnoea. We studied 20 male patients with obstructive sleep apnoea (age: 60·3 ± 10·3 years; BMI: 25·9 ± 4·6 kg m(-2); AHI: 41·5 ± 18·6 events h(-1)). We obtained 100-μL samples of saliva prior to overnight polysomnographic sleep study. The surface tension was determined using the pull-off force technique. The concentration of phosphatidylcholine (PC) was evaluated by liquid chromatography-mass spectrometry (LC-MS/MS). Regression analysis between apnoea, hypopnoea and apnoea/hypopnoea indices and the ratio of hypopnoea time/total disordered breathing time (HT/DBT) with surface tension and PC were performed. P < 0·05 was considered significant. The mean saliva surface tension was 48·8 ± 8·0 mN m(-1) and PC concentration was 15·7 ± 11·1 nM. The surface tension was negatively correlated with the PC concentration (r = -0·48, P = 0·03). There was a significant positive correlation between surface tension with hypopnoea index (r = 0·50, P = 0·03) and HT/DBT (r = 0·6, P = 0·006), but not apnoea or apnoea/hypopnoea index (P > 0·11). Similarly, PC concentration negatively correlated with hypopnoea index (r = -0·45, P = 0·04) and HT/DBT (r = -0·6, P = 0·004), but not with apnoea index or AHI (P > 0·08). An increase in salivary PC concentration may increase upper airway patency in obstructive sleep apnoea through a reduction in surface tension.

  14. Chlorzoxazone or 1-EBIO increases Na(+) absorption across cystic fibrosis airway epithelial cells.

    PubMed

    Gao, L; Yankaskas, J R; Fuller, C M; Sorscher, E J; Matalon, S; Forman, H J; Venglarik, C J

    2001-11-01

    Previous studies demonstrated that chlorzoxazone or 1-ethyl-2-benzimidazolinone (1-EBIO) enhances transepithelial Cl(-) secretion by increasing basolateral K(+) conductance (G(K)) (Singh AK, Devor DC, Gerlach AC, Gondor M, Pilewski JM, and Bridges RJ. J Pharmacol Exp Ther 292: 778-787, 2000). Hence these compounds may be useful to treat cystic fibrosis (CF) airway disease. The goal of the present study was to determine whether chlorzoxazone or 1-EBIO altered ion transport across Delta F508-CF transmembrane conductance regulator homozygous CFT1 airway cells. CFT1 monolayers exhibited a basal short-circuit current that was abolished by apical amiloride (inhibition constant 320 nM) as expected for Na(+) absorption. The addition of chlorzoxazone (400 microM) or 1-EBIO (2 mM) increased the amiloride-sensitive I(sc) approximately 2.5-fold. This overlapping specificity may preclude use of these compounds as CF therapeutics. Assaying for changes in the basolateral G(K) with a K(+) gradient plus the pore-forming antibiotic amphotericin B revealed that chlorzoxazone or 1-EBIO evoked an approximately 10-fold increase in clotrimazole-sensitive G(K). In contrast, chlorzoxazone did not alter epithelial Na(+) channel-mediated currents across basolateral-permeabilized monolayers or in Xenopus oocytes. These data further suggest that alterations in basolateral G(K) alone can modulate epithelial Na(+) transport.

  15. Cationic Amphiphiles Increase Activity of Aminoglycoside Antibiotic Tobramycin in the Presence of Airway Polyelectrolytes

    SciTech Connect

    Purdy Drew, Kirstin R.; Sanders, Lori K.; Culumber, Zachary W.; Zribi, Olena; Wong, Gerard C.L.

    2009-06-17

    It is empirically known that anionic polyelectrolytes present in cystic fibrosis (CF) airways due to bacterial infection significantly decrease the activity of cationic antimicrobials via electrostatic binding. In this work, we use synchrotron small-angle X-ray scattering to investigate the interaction between tobramycin, an aminoglycoside antibiotic commonly administered to CF patients via inhalation, with DNA, which is found in high concentrations in the CF airway. We find that interactions between DNA and tobramycin are significantly modified by the presence of mixtures of amphiphilic molecules. We measure a hierarchy of self-assembled structures formed between tobramycin, DNA, and the amphiphile mixtures and show how interactions between these components can be controlled. Results indicate that mixtures of cationic and negative curvature amphiphiles optimized for DNA binding via charge matching and curvature matching can competitively displace bound tobramycin from DNA and thereby drastically suppress tobramycin-DNA binding and resultant antimicrobial inactivation. Growth inhibition assays confirm the increased activity of tobramycin in the presence of DNA with the addition of the amphiphiles. These results suggest that optimized cationic amphiphile solutions have the potential to enhance antimicrobial function in highly infected environments that contain increased concentrations of anionic inflammatory polymers.

  16. Cationic Amphiphiles Increase Activity of Aminoglycoside Antibiotic Tobramycin in the Presence of Airway Polyelectrolytes

    SciTech Connect

    Drew, K.R.Purdy; Sanders, L.K.; Culumber, Z.W.; Zribi, O.; Wong, G.C.L.

    2009-05-21

    It is empirically known that anionic polyelectrolytes present in cystic fibrosis (CF) airways due to bacterial infection significantly decrease the activity of cationic antimicrobials via electrostatic binding. In this work, we use synchrotron small-angle X-ray scattering to investigate the interaction between tobramycin, an aminoglycoside antibiotic commonly administered to CF patients via inhalation, with DNA, which is found in high concentrations in the CF airway. We find that interactions between DNA and tobramycin are significantly modified by the presence of mixtures of amphiphilic molecules. We measure a hierarchy of self-assembled structures formed between tobramycin, DNA, and the amphiphile mixtures and show how interactions between these components can be controlled. Results indicate that mixtures of cationic and negative curvature amphiphiles optimized for DNA binding via charge matching and curvature matching can competitively displace bound tobramycin from DNA and thereby drastically suppress tobramycin-DNA binding and resultant antimicrobial inactivation. Growth inhibition assays confirm the increased activity of tobramycin in the presence of DNA with the addition of the amphiphiles. These results suggest that optimized cationic amphiphile solutions have the potential to enhance antimicrobial function in highly infected environments that contain increased concentrations of anionic inflammatory polymers.

  17. Reference equations for specific airway resistance in children: the Asthma UK initiative.

    PubMed

    Kirkby, J; Stanojevic, S; Welsh, L; Lum, S; Badier, M; Beardsmore, C; Custovic, A; Nielsen, K; Paton, J; Tomalak, W; Stocks, J

    2010-09-01

    Plethysmographic specific airway resistance (sR(aw)) is a useful research method for discriminating lung disease in young children. Its use in clinical management has, however, been limited by lack of consensus regarding equipment, methodology and reference data. The aim of our study was to collate reference data from healthy children (3-10 yrs), document methodological differences, explore the impact of these differences and construct reference equations from the collated dataset. Centres were approached to contribute sR(aw) data as part of the Asthma UK initiative. A random selection of pressure-flow plots were assessed for quality and site visits elucidated data collection and analysis protocols. Five centres contributed 2,872 measurements. Marked variation in methodology and analysis excluded two centres. sR(aw) over-read sheets were developed for quality control. Reference equations and recommendations for recording and reporting both specific effective and total airway resistance (sR(eff) and sR(tot), respectively) were developed for White European children from 1,908 measurements made under similar conditions. Reference sR(aw) data collected from a single centre may be misleading, as methodological differences exist between centres. These preliminary reference equations can only be applied under similar measurement conditions. Given the potential clinical usefulness of sR(aw), particularly with respect to sR(eff), methodological guidelines need to be established and used in prospective data collection.

  18. Lipoxin A4 Stimulates Calcium-Activated Chloride Currents and Increases Airway Surface Liquid Height in Normal and Cystic Fibrosis Airway Epithelia

    PubMed Central

    Al-Alawi, Mazen; Costello, Richard W.; McNally, Paul; Chiron, Raphaël; Harvey, Brian J.; Urbach, Valérie

    2012-01-01

    Cystic Fibrosis (CF) is a genetic disease characterised by a deficit in epithelial Cl− secretion which in the lung leads to airway dehydration and a reduced Airway Surface Liquid (ASL) height. The endogenous lipoxin LXA4 is a member of the newly identified eicosanoids playing a key role in ending the inflammatory process. Levels of LXA4 are reported to be decreased in the airways of patients with CF. We have previously shown that in normal human bronchial epithelial cells, LXA4 produced a rapid and transient increase in intracellular Ca2+. We have investigated, the effect of LXA4 on Cl− secretion and the functional consequences on ASL generation in bronchial epithelial cells obtained from CF and non-CF patient biopsies and in bronchial epithelial cell lines. We found that LXA4 stimulated a rapid intracellular Ca2+ increase in all of the different CF bronchial epithelial cells tested. In non-CF and CF bronchial epithelia, LXA4 stimulated whole-cell Cl− currents which were inhibited by NPPB (calcium-activated Cl− channel inhibitor), BAPTA-AM (chelator of intracellular Ca2+) but not by CFTRinh-172 (CFTR inhibitor). We found, using confocal imaging, that LXA4 increased the ASL height in non-CF and in CF airway bronchial epithelia. The LXA4 effect on ASL height was sensitive to bumetanide, an inhibitor of transepithelial Cl− secretion. The LXA4 stimulation of intracellular Ca2+, whole-cell Cl− currents, conductances and ASL height were inhibited by Boc-2, a specific antagonist of the ALX/FPR2 receptor. Our results provide, for the first time, evidence for a novel role of LXA4 in the stimulation of intracellular Ca2+ signalling leading to Ca2+-activated Cl− secretion and enhanced ASL height in non-CF and CF bronchial epithelia. PMID:22662206

  19. Inspiratory high frequency airway oscillation attenuates resistive loaded dyspnea and modulates respiratory function in young healthy individuals.

    PubMed

    Morris, Theresa; Sumners, David Paul; Green, David Andrew

    2014-01-01

    Direct chest-wall percussion can reduce breathlessness in Chronic Obstructive Pulmonary Disease and respiratory function may be improved, in health and disease, by respiratory muscle training (RMT). We tested whether high-frequency airway oscillation (HFAO), a novel form of airflow oscillation generation can modulate induced dyspnoea and respiratory strength and/or patterns following 5 weeks of HFAO training (n = 20) compared to a SHAM-RMT (conventional flow-resistive RMT) device (n = 15) in healthy volunteers (13 males; aged 20-36 yrs). HFAO causes oscillations with peak-to-peak amplitude of 1 cm H2O, whereas the SHAM-RMT device was identical but created no pressure oscillation. Respiratory function, dyspnoea and ventilation during 3 minutes of spontaneous resting ventilation, 1 minute of maximal voluntary hyperventilation and 1 minute breathing against a moderate inspiratory resistance, were compared PRE and POST 5-weeks of training (2 × 30 breaths at 70% peak flow, 5 days a week). Training significantly reduced NRS dyspnoea scores during resistive loaded ventilation, both in the HFAO (p = 0.003) and SHAM-RMT (p = 0.005) groups. Maximum inspiratory static pressure (cm H2O) was significantly increased by HFAO training (vs. PRE; p<0.001). Maximum inspiratory dynamic pressure was increased by training in both the HFAO (vs. PRE; p<0.001) and SHAM-RMT (vs. PRE; p = 0.021) groups. Peak inspiratory flow rate (L.s(-1)) achieved during the maximum inspiratory dynamic pressure manoeuvre increased significantly POST (vs. PRE; p = 0.001) in the HFAO group only. HFAO reduced inspiratory resistive loading-induced dyspnoea and augments static and dynamic maximal respiratory manoeuvre performance in excess of flow-resistive IMT (SHAM-RMT) in healthy individuals without the respiratory discomfort associated with RMT.

  20. Ethanologenic bacteria with increased resistance to furfural

    DOEpatents

    Miller, Elliot Norman; Jarboe, Laura R.; Yomano, Lorraine P.; York, Sean W.; Shanmugam, Keelnatham; Ingram, Lonnie O'Neal

    2015-10-06

    The invention relates to bacterium that have increased resistance to furfural and methods of preparation. The invention also relates to methods of producing ethanol using the bacterium and corresponding kits.

  1. Novel method for conscious airway resistance and ventilation estimation in neonatal rodents using plethysmography and a mechanical lung.

    PubMed

    Zhang, Boyang; McDonald, Fiona B; Cummings, Kevin J; Frappell, Peter B; Wilson, Richard J A

    2014-09-15

    In unrestrained whole body plethysmography, tidal volume is commonly determined using the barometric method, which assumes that temperature and humidity changes (the 'barometric component') are solely responsible for breathing-related chamber pressure fluctuations. However, in small animals chamber pressure is also influenced by a 'mechanical component' dependent on airway resistance and airflow. We devised a novel 'mechanical lung' capable of simulating neonatal mouse breathing in the absence of temperature or humidity changes. Using this device, we confirm that the chamber pressure fluctuations produced by breathing of neonatal mice are dominated by the mechanical component, precluding direct quantitative assessment of tidal volume. Recognizing the importance of airway resistance to the chamber pressure signal and the ability of our device to simulate neonatal breathing at different frequencies and tidal volumes, we invented a novel in vivo, non-invasive method for conscious airway resistance and ventilation estimation (CARVE) in neonatal rodents. This technique will allow evaluation of developmental, pathological and pharmaceutical effects on airway resistance.

  2. SUBCHRONIC ENDOTOXIN INHALATION CAUSES CHRONIC AIRWAY DISEASE IN ENDOTOXIN-SENSITIVE BUT NOT ENDOTOXIN-RESISTANT MICE

    EPA Science Inventory

    SUBCHRONIC ENDOTOXIN INHALATION CAUSES CHRONIC AIRWAY DISEASE IN ENDOTOXIN-SENSITIVE BUT NOT ENDOTOXIN-RESISTANT MICE. D. M. Brass, J. D. Savov, *S. H. Gavett, ?C. George, D. A. Schwartz. Duke Univ Medical Center Durham, NC, *U.S. E.P.A. Research Triangle Park, NC, ?Univ of Iowa,...

  3. Acid and organic aerosol coatings on magnetic nanoparticles increase iron concentrations in human airway epithelial cells.

    PubMed

    Ghio, Andrew J; Dailey, Lisa A; Richards, Judy H; Jang, Myoseon

    2009-07-01

    Numerous industrial applications for man-made nanoparticles have been proposed. Interactions of nanoparticles with agents in the atmosphere may impact human health. We tested the postulate that in vitro exposures of respiratory epithelial cells to airborne magnetic nanoparticles (MNP; Fe(3)O(4)) with and without a secondary organic aerosol (SOA) and an inorganic acid could affect iron homeostasis, oxidative stress, and interleukin (IL)-8 release. Cell iron concentrations were increased after exposures to MNP and values were further elevated with co-exposures to either SOA or inorganic acid. Increased expression of ferritin and elevated levels of RNA for DMT1, proteins for iron storage and transport respectively, followed MNP exposures, but values were significant for only those with co-exposures to inorganic acid and organic aerosols. Cell iron concentration corresponded to a measure of oxidative stress in the airway epithelial cells; MNP with co-exposures to SOA and inorganic acid increased both available metal and indices of oxidant generation. Finally, the release of a proinflammatory cytokine (i.e. IL-8) by the exposed cells similarly increased with cell iron concentration. We conclude that MNP can interact with a SOA and an inorganic acid to present metal in a catalytically reactive state to cultured respiratory cells. This produces an oxidative stress to affect a release of IL-8.

  4. Changes in airway permeability and responsiveness after exposure to ozone. [Sheep

    SciTech Connect

    Abraham, W.M.; Delehunt, J.C.; Yerger, L.; Marchette, B.; Oliver, W. Jr.

    1984-06-01

    The relationship between airway responsiveness and the permeability of histamine through the airways in conscious sheep after exposure to ozone (O/sub 3/ was examined). Airway responsiveness was assessed by measuring the change from baseline in mean pulmonary flow resistance following a controlled 2-min inhalation challenge with 1% histamine, containing 200 ..mu..Ci/ml of (/sup 3/H)histamine. The rate of appearance of the (/sup 3/H)histamine in the plasma during inhalation challenge was used to estimate airway permeability. To perturb the airways, conscious sheep were exposed to either 0.5 or 1.0 ppm O/sub 3/ for 2 hr via an endotracheal tube. Airway responsiveness and airway permeability were measured prior to and 1 day after exposure. In six sheep exposed to 0.5 ppm O/sub 3/, increased airway responsiveness and airway permeability were obseved 1 day after exposure. Four of seven sheep exposed to 1.0 ppm O/sub 3/ had enhanced airway responsiveness and airway permeability, while the remaining three sheep showed corresponding decreases in airway responsiveness and airway permeability. Since the O/sub 3/-induced directional changes in airway responsiveness paralleled the directional changes in airway permeability in both the positive and negative directions, it was concluded that changes in airway responsiveness to inhaled histamine following exposure to O/sub 3/ may be related to concomitant changes in airway permeability to this agent.

  5. The effect of increased lung volume in chronic obstructive pulmonary disease on upper airway obstruction during sleep

    PubMed Central

    Biselli, Paolo; Grossman, Peter R.; Kirkness, Jason P.; Patil, Susheel P.; Smith, Philip L.; Schwartz, Alan R.

    2015-01-01

    Patients with chronic obstructive pulmonary disease (COPD) exhibit increases in lung volume due to expiratory airflow limitation. Increases in lung volumes may affect upper airway patency and compensatory responses to inspiratory flow limitation (IFL) during sleep. We hypothesized that COPD patients have less collapsible airways inversely proportional to their lung volumes, and that the presence of expiratory airflow limitation limits duty cycle responses to defend ventilation in the presence of IFL. We enrolled 18 COPD patients and 18 controls, matched by age, body mass index, sex, and obstructive sleep apnea disease severity. Sleep studies, including quantitative assessment of airflow at various nasal pressure levels, were conducted to determine upper airway mechanical properties [passive critical closing pressure (Pcrit)] and for quantifying respiratory timing responses to experimentally induced IFL. COPD patients had lower passive Pcrit than their matched controls (COPD: −2.8 ± 0.9 cmH2O; controls: −0.5 ± 0.5 cmH2O, P = 0.03), and there was an inverse relationship of subject's functional residual capacity and passive Pcrit (−1.7 cmH2O/l increase in functional residual capacity, r2 = 0.27, P = 0.002). In response to IFL, inspiratory duty cycle increased more (P = 0.03) in COPD patients (0.40 to 0.54) than in controls (0.41 to 0.51) and led to a marked reduction in expiratory time from 2.5 to 1.5 s (P < 0.01). COPD patients have a less collapsible airway and a greater, not reduced, compensatory timing response during upper airway obstruction. While these timing responses may reduce hypoventilation, it may also increase the risk for developing dynamic hyperinflation due to a marked reduction in expiratory time. PMID:26048975

  6. Airway wall thickness is increased in COPD patients with bronchodilator responsiveness

    PubMed Central

    2014-01-01

    Rationale Bronchodilator responsiveness (BDR) is a common but variable phenomenon in COPD. The CT characteristics of airway dimensions that differentiate COPD subjects with BDR from those without BDR have not been well described. We aimed to assess airway dimensions in COPD subjects with and without BDR. Methods We analyzed subjects with GOLD 1–4 disease in the COPDGene® study who had CT airway analysis. We divided patients into two groups: BDR + (post bronchodilator ΔFEV1 ≥ 10%) and BDR-(post bronchodilator ΔFEV1 < 10%). The mean wall area percent (WA%) of six segmental bronchi in each subject was quantified using VIDA. Using 3D SLICER, airway wall thickness was also expressed as the square root wall area of an airway of 10 mm (Pi10) and 15 mm (Pi15) diameter. %Emphysema and %gas trapping were also calculated. Results 2355 subjects in the BDR-group and 1306 in the BDR + group formed our analysis. The BDR + group had a greater Pi10, Pi15, and mean segmental WA% compared to the BDR-group. In multivariate logistic regression using gender, race, current smoking, history of asthma, %emphysema, %gas trapping, %predicted FEV1, and %predicted FVC, airway wall measures remained independent predictors of BDR. Using a threshold change in FEV1 ≥ 15% and FEV1 ≥ 12% and 200 mL to divide patients into groups, the results were similar. Conclusion BDR in COPD is independently associated with CT evidence of airway pathology. This study provides us with greater evidence of changes in lung structure that correlate with physiologic manifestations of airflow obstruction in COPD. PMID:25248436

  7. Perivascular fluid cuffs decrease lung compliance by increasing tissue resistance

    PubMed Central

    Lowe, Kevin; Alvarez, Diego F.; King, Judy A.; Stevens, Troy

    2010-01-01

    Objective Lung inflammation causes perivascular fluid cuffs to form around extra-alveolar blood vessels; however, the physiologic consequences of such cuffs remain poorly understood. Herein, we tested the hypothesis that perivascular fluid cuffs, without concomitant alveolar edema, are sufficient to decrease lung compliance. Design Prospective, randomized, controlled study. Setting Research laboratory. Subjects One hundred twenty male CD40 rats. Interventions To test this hypothesis, the plant alkaloid thapsigargin was used to activate store-operated calcium entry and increase cytosolic calcium in endothelium. Thapsigargin was infused into a central venous catheter of intact, sedated, and mechanically ventilated rats. Measurements Static and dynamic lung mechanics and hemodynamics were measured continuously. Main Results Thapsigargin produced perivascular fluid cuffs along extra-alveolar vessels but did not cause alveolar flooding or blood gas abnormalities. Lung compliance dose-dependently decreased after thapsigargin infusion, attributable to an increase in tissue resistance that was attributed to increased tissue damping and tissue elastance. Airway resistance was not changed. Neither central venous pressure nor left ventricular end diastolic pressure was altered by thapsigargin. Heart rate did not change, although thapsigargin decreased pressure over time sufficient to reduce cardiac output by 50%. Infusion of the type 4 phosphodiesterase inhibitor, rolipram, prevented thapsigargin from inducing perivascular cuffs and decreasing lung compliance. Rolipram also normalized pressure over time and corrected the deficit in cardiac output. Conclusions Our findings resolve for the first time that perivascular cuff formation negatively impacts mechanical coupling between the bronchovascular bundle and the lung parenchyma, decreasing lung compliance without impacting central venous pressure. PMID:20400904

  8. Increased CCL24/eotaxin-2 with postnatal ozone exposure in allergen-sensitized infant monkeys is not associated with recruitment of eosinophils to airway mucosa

    SciTech Connect

    Chou, Debbie L.; Gerriets, Joan E.; Schelegle, Edward S.; Hyde, Dallas M.; Miller, Lisa A.

    2011-12-15

    Epidemiology supports a causal link between air pollutant exposure and childhood asthma, but the mechanisms are unknown. We have previously reported that ozone exposure can alter the anatomic distribution of CD25+ lymphocytes in airways of allergen-sensitized infant rhesus monkeys. Here, we hypothesized that ozone may also affect eosinophil trafficking to allergen-sensitized infant airways. To test this hypothesis, we measured blood, lavage, and airway mucosa eosinophils in 3-month old monkeys following cyclical ozone and house dust mite (HDM) aerosol exposures. We also determined if eotaxin family members (CCL11, CCL24, CCL26) are associated with eosinophil location in response to exposures. In lavage, eosinophil numbers increased in animals exposed to ozone and/or HDM. Ozone + HDM animals showed significantly increased CCL24 and CCL26 protein in lavage, but the concentration of CCL11, CCL24, and CCL26 was independent of eosinophil number for all exposure groups. In airway mucosa, eosinophils increased with exposure to HDM alone; comparatively, ozone and ozone + HDM resulted in reduced eosinophils. CCL26 mRNA and immunofluorescence staining increased in airway mucosa of HDM alone animals and correlated with eosinophil volume. In ozone + HDM animal groups, CCL24 mRNA and immunofluorescence increased along with CCR3 mRNA, but did not correlate with airway mucosa eosinophils. Cumulatively, our data indicate that ozone exposure results in a profile of airway eosinophil migration that is distinct from HDM mediated pathways. CCL24 was found to be induced only by combined ozone and HDM exposure, however expression was not associated with the presence of eosinophils within the airway mucosa. -- Highlights: Black-Right-Pointing-Pointer Ozone can modulate the localization of eosinophils in infant allergic airways. Black-Right-Pointing-Pointer Expression of eotaxins within the lung is affected by ozone and allergen exposure. Black-Right-Pointing-Pointer CCL24 induction by

  9. Coal fly ash impairs airway antimicrobial peptides and increases bacterial growth.

    PubMed

    Borcherding, Jennifer A; Chen, Haihan; Caraballo, Juan C; Baltrusaitis, Jonas; Pezzulo, Alejandro A; Zabner, Joseph; Grassian, Vicki H; Comellas, Alejandro P

    2013-01-01

    Air pollution is a risk factor for respiratory infections, and one of its main components is particulate matter (PM), which is comprised of a number of particles that contain iron, such as coal fly ash (CFA). Since free iron concentrations are extremely low in airway surface liquid (ASL), we hypothesize that CFA impairs antimicrobial peptides (AMP) function and can be a source of iron to bacteria. We tested this hypothesis in vivo by instilling mice with Pseudomonas aeruginosa (PA01) and CFA and determine the percentage of bacterial clearance. In addition, we tested bacterial clearance in cell culture by exposing primary human airway epithelial cells to PA01 and CFA and determining the AMP activity and bacterial growth in vitro. We report that CFA is a bioavailable source of iron for bacteria. We show that CFA interferes with bacterial clearance in vivo and in primary human airway epithelial cultures. Also, we demonstrate that CFA inhibits AMP activity in vitro, which we propose as a mechanism of our cell culture and in vivo results. Furthermore, PA01 uses CFA as an iron source with a direct correlation between CFA iron dissolution and bacterial growth. CFA concentrations used are very relevant to human daily exposures, thus posing a potential public health risk for susceptible subjects. Although CFA provides a source of bioavailable iron for bacteria, not all CFA particles have the same biological effects, and their propensity for iron dissolution is an important factor. CFA impairs lung innate immune mechanisms of bacterial clearance, specifically AMP activity. We expect that identifying the PM mechanisms of respiratory infections will translate into public health policies aimed at controlling, not only concentration of PM exposure, but physicochemical characteristics that will potentially cause respiratory infections in susceptible individuals and populations.

  10. Bromodomain and Extra Terminal (BET) Inhibitor Suppresses Macrophage-Driven Steroid-Resistant Exacerbations of Airway Hyper-Responsiveness and Inflammation

    PubMed Central

    Nguyen, Thi Hiep; Maltby, Steven; Eyers, Fiona; Foster, Paul S.; Yang, Ming

    2016-01-01

    Background Exacerbations of asthma are linked to significant decline in lung function and are often poorly controlled by corticosteroid treatment. Clinical investigations indicate that viral and bacterial infections play crucial roles in the onset of steroid-resistant inflammation and airways hyperresponsiveness (AHR) that are hallmark features of exacerbations. We have previously shown that interferon γ (IFNγ) and lipopolysaccharide (LPS) cooperatively activate pulmonary macrophages and induce steroid-resistant airway inflammation and AHR in mouse models. Furthermore, we have established a mouse model of respiratory syncytial virus (RSV)-induced exacerbation of asthma, which exhibits macrophage-dependent, steroid-resistant lung disease. Emerging evidence has demonstrated a key role for bromo- and extra-terminal (BET) proteins in the regulation of inflammatory gene expression in macrophages. We hypothesised that BET proteins may be involved in the regulation of AHR and airway inflammation in our steroid-resistant exacerbation models. Methodology/Principal Findings We investigated the effects of a BET inhibitor (I-BET-762) on the development of steroid-resistant AHR and airway inflammation in two mouse models. I-BET-762 administration decreased macrophage and neutrophil infiltration into the airways, and suppressed key inflammatory cytokines in both models. I-BET treatment also suppressed key inflammatory cytokines linked to the development of steroid-resistant inflammation such as monocyte chemoattractant protein 1 (MCP-1), keratinocyte-derived protein chemokine (KC), IFNγ, and interleukin 27 (IL-27). Attenuation of inflammation was associated with suppression of AHR. Conclusions/Significance Our results suggest that BET proteins play an important role in the regulation of steroid-resistant exacerbations of airway inflammation and AHR. BET proteins may be potential targets for the development of future therapies to treat steroid-resistant inflammatory components

  11. Upper Airway Resistance Syndrome Patients Have Worse Sleep Quality Compared to Mild Obstructive Sleep Apnea

    PubMed Central

    de Godoy, Luciana Balester Mello; Luz, Gabriela Pontes; Palombini, Luciana Oliveira; e Silva, Luciana Oliveira; Hoshino, Wilson; Guimarães, Thaís Moura; Tufik, Sergio; Bittencourt, Lia; Togeiro, Sonia Maria

    2016-01-01

    Purpose To compare sleep quality and sustained attention of patients with Upper Airway Resistance Syndrome (UARS), mild Obstructive Sleep Apnea (OSA) and normal individuals. Methods UARS criteria were presence of excessive daytime sleepiness (Epworth Sleepiness Scale—ESS—≥ 10) and/or fatigue (Modified Fatigue Impact Scale—MFIS—≥ 38) associated to Apnea/hypopnea index (AHI) ≤ 5 and Respiratory Disturbance Index (RDI) > 5 events/hour of sleep or more than 30% of total sleep time with flow limitation. Mild OSA was considered if the presence of excessive daytime sleepiness (ESS ≥ 10) and/or fatigue (MFIS ≥ 38) associated to AHI ≥ 5 and ≤ 15 events/hour. “Control group” criteria were AHI < 5 events/hour and RDI ≤ 5 events/hour and ESS ≤ 9, without any sleep, clinical, neurological or psychiatric disorder. 115 individuals (34 UARS and 47 mild OSA patients and 34 individuals in “control group”), adjusted for age, gender, body mass index (BMI) and schooling years, performed sleep questionnaires and sustained attention evaluation. Psychomotor Vigilance Task (PVT) was performed five times (each two hours) from 8 a.m. to 4 p.m. Results UARS patients had worse sleep quality (Functional Outcomes of Sleep Questionnaire—FOSQ—and Pittsburgh Sleep Quality Index—PSQI: p < 0.05) and more fatigue than mild OSA patients (p = 0.003) and scored significantly higher in both Beck inventories than “control group” (p < 0.02). UARS patients had more lapses early in the morning (in time 1) compared to the results in the afternoon (time 5) than mild OSA (p = 0.02). Mild OSA patients had more lapses in times 2 than in time 5 compared to “control group” (p = 0.04). Conclusions UARS patients have a worse sleep quality, more fatigue and a worse early morning sustained attention compared to mild OSA. These last had a worse sustained attention than controls. PMID:27228081

  12. Myeloid cell HIF-1α regulates asthma airway resistance and eosinophil function

    PubMed Central

    Akong-Moore, Kathryn; Feldstein, Stephanie; Johansson, Per; Nyugen, Anh; McEachern, Elisa K.; Nicatia, Shari; Cowburn, Andrew S.; Olson, Joshua; Cho, Jae Youn; Isaacs, Hart; Johnson, Randall S.; Broide, David H.; Nizet, Victor

    2013-01-01

    Hypoxia-inducible factor (HIF)-1α is a master regulator of inflammatory activities of myeloid cells, including neutrophils and macrophages. These studies examine the role of myeloid cell HIF-1α in regulating asthma induction and pathogenesis, and for the first time, evaluate the roles of HIF-1α and HIF-2α in the chemotactic properties of eosinophils, the myeloid cells most associated with asthma. Wild-type (WT) and myeloid cell-specific HIF-1α knockout (KO) C57BL/6 mice were studied in an ovalbumin (OVA) model of asthma. Administration of the pharmacological HIF-1α antagonist YC-1 was used to corroborate findings from the genetic model. WT, HIF-1α, and HIF-2α KO eosinophils underwent in vitro chemotaxis assays. We found that deletion of HIF-1α in myeloid cells and systemic treatment with YC-1 during asthma induction decreased airway hyperresponsiveness (AHR). Deletion of HIF-1α in myeloid cells in OVA-induced asthma also reduced eosinophil infiltration, goblet cell hyperplasia, and levels 34 of cytokines IL-4, IL-5, and IL-13 in the lung. HIF-1α inhibition with YC-1 during asthma induction decreased eosinophilia in bronchoalveolar lavage, lung parenchyma, and blood, as well as decreased total lung inflammation, IL-5, and serum OVA-specific IgE levels. Deletion of HIF-1α in eosinophils decreased their chemotaxis, while deletion of the isoform HIF-2α led to increased chemotaxis. This work demonstrates that HIF-1α in myeloid cells plays a role in asthma pathogenesis, particularly in AHR development. Additionally, treatment with HIF-1α inhibitors during asthma induction decreases AHR and eosinophilia. Finally, we show that HIF- 1α and HIF-2α regulate eosinophil migration in opposing ways. PMID:23250618

  13. [Therapeutic effects of histone deacetylase inhibitor givinostat on air inflammation and high airway resistance in a murine asthma model].

    PubMed

    Su, X M; Ren, Y; Kong, L F; Kang, J

    2017-02-01

    Objective: To investigate the therapeutic effects of givinostat, a histone deacetylase inhibitor (HDACI), on the development of chronic asthma with airway inflammation, airway remodeling and airway hyperresponsiveness (AHR). Methods: BALB/C mice were randomly divided into control group, asthma group, dexamethasone group and givinostat group (n=12 per group). AHR was assessed. Total cell numbers and differential counts, interleukin-4(IL-4), interleukin-5(IL-5) and interferon-γ (IFNγ) levels in the bronchoalveolar lavage fluid (BALF) were measured in the above 4 groups. The pathology of lung tissue was evaluated. Immunohistochemical (IHC) staining and Western blot were used to detect α smooth muscle actin(α-SMA) and transforming growth factor-β1(TGFβ1). Results: Compared with the asthma only group, givinostat treatment relieved airway resistance (2.96±1.01 vs 6.50±0.79, P<0.05). Total inflammatory cells [(33.04±5.62)×10(4)/ml vs (98.04±9.27)×10(4)/ml, P<0.01], eosinophil cells [(9.17±2.33)×10(4)/ml vs(37.64±6.98)×10(4)/ml, P<0.01], IL-4 [(10.12±2.98)ng/ml vs (16.88±2.78)ng/ml, P<0.05] and IL-5 [(27.09±3.62)ng/ml vs (37.86±7.34)ng/ml, P<0.05] levels were all reduced in givinostat group, while IFNγ [(91.86±23.73)pg/ml vs (60.49±11.88)pg/ml, P>0.05] was enhanced in BALF. Inflammatory cell infiltration around the airway was reduced, with decreased inflammatory cell score[(1.60±0.69)points vs (3.40±0.68) points, P<0.01] and inflammatory cell number (111.65±31.41 vs 601.25±186.85, P<0.01). The goblet cell metaplasia [(26.36±2.33)% vs (57.21±11.56)%] and collagen deposition area [(52.77±7.58)μm(2)/μm vs (111.81±12.40)μm(2)/μm] were obviously reduced (P<0.01). The expressions of α-SMA and TGFβ1 in the lung tissue were both significantly decreased (P<0.01). Conclusion: Givinostat treatment can reduce airway inflammation, airway remodeling and airway hyperresponsiveness in chronic asthma. Its effect is comparable to that of glucocorticoid

  14. Effect of a single dose of salmeterol on the increase in airway eosinophils induced by allergen challenge in asthmatic subjects

    PubMed Central

    Dente, F.; Bancalari, L.; Bacci, E.; Bartoli, M.; Carnevali, S.; Cianchetti, S.; Di, F; Giannini, D.; Vagaggini, B.; Testi, R.; Paggiaro, P.

    1999-01-01

    BACKGROUND—The long acting β2 agonist salmeterol is very effective in preventing asthmatic responses to specific stimuli, and this effect could theoretically be due to some anti-inflammatory property in addition to bronchodilator property.
METHODS—The protective effect of a single dose of salmeterol (50 µg) on allergen induced early and late responses and on the associated airway inflammation was investigated in a double blind, placebo controlled, crossover study in 11 atopic asthmatic subjects. Eosinophil percentages and concentrations of eosinophil cationic protein (ECP) in peripheral blood and in hypertonic saline induced sputum were measured 24 hours after allergen inhalation.
RESULTS—Salmeterol effectively inhibited both early and late asthmatic responses in comparison with placebo. Salmeterol also inhibited the increase in the percentage of eosinophils in the sputum 24hours after allergen inhalation (median (range) baseline 6% (1-36), after placebo 31% (5-75), after salmeterol 12% (1-63)). However, the increase in both sputum and serum ECP concentrations 24 hours after allergen challenge was not affected by pretreatment with salmeterol.
CONCLUSIONS—A single dose of salmeterol inhibits the allergen induced airway responses and the increase in sputum eosinophils after allergen challenge.

 PMID:10377209

  15. Bactericidal/Permeability-Increasing Protein Fold–Containing Family Member A1 in Airway Host Protection and Respiratory Disease

    PubMed Central

    Britto, Clemente J.

    2015-01-01

    Bactericidal/permeability-increasing protein fold–containing family member A1 (BPIFA1), formerly known as SPLUNC1, is one of the most abundant proteins in respiratory secretions and has been identified with increasing frequency in studies of pulmonary disease. Its expression is largely restricted to the respiratory tract, being highly concentrated in the upper airways and proximal trachea. BPIFA1 is highly responsive to airborne pathogens, allergens, and irritants. BPIFA1 actively participates in host protection through antimicrobial, surfactant, airway surface liquid regulation, and immunomodulatory properties. Its expression is modulated in multiple lung diseases, including cystic fibrosis, chronic obstructive pulmonary disease, respiratory malignancies, and idiopathic pulmonary fibrosis. However, the role of BPIFA1 in pulmonary pathogenesis remains to be elucidated. This review highlights the versatile properties of BPIFA1 in antimicrobial protection and its roles as a sensor of environmental exposure and regulator of immune cell function. A greater understanding of the contribution of BPIFA1 to disease pathogenesis and activity may clarify if BPIFA1 is a biomarker and potential drug target in pulmonary disease. PMID:25265466

  16. Targeted expression of IL-11 in the murine airway causes lymphocytic inflammation, bronchial remodeling, and airways obstruction.

    PubMed Central

    Tang, W; Geba, G P; Zheng, T; Ray, P; Homer, R J; Kuhn, C; Flavell, R A; Elias, J A

    1996-01-01

    Interleukin-11 is a pleotropic cytokine produced by lung stromal cells in response to respiratory viruses, cytokines, and histamine. To further define its potential effector functions, the Clara cell 10-kD protein promoter was used to express IL-11 and the airways of the resulting transgene mice were characterized. In contrast to transgene (-) littermates, the airways of IL-11 transgene (+) animals manifest nodular peribronchiolar mononuclear cell infiltrates and impressive airways remodeling with subepithelial fibrosis. The inflammatory foci contained large numbers of B220(+) and MHC Class II(+) cells and lesser numbers of CD3(+), CD4(+), and CD8(+) cells. The fibrotic response contained increased amounts of types III and I collagen, increased numbers of alpha smooth muscle actin and desmin-containing cells and a spectrum of stromal elements including fibroblasts, myofibroblasts, and smooth muscle cells. Physiologic evaluation also demonstrated that 2-mo-old transgene (+) mice had increased airways resistance and non-specific airways hyperresponsiveness to methacholine when compared with their transgene (-) littermates. These studies demonstrate that the targeted expression of IL-11 in the mouse airway causes a B and T cell-predominant inflammatory response, airway remodeling with increased types III and I collagen, the local accumulation of fibroblasts, myofibroblasts, and myocytes, and obstructive physiologic dysregulation. IL-11 may play an important role in the inflammatory and fibrotic responses in viral and/or nonviral human airway disorders. PMID:8981933

  17. GPCRs and arrestins in airways: implications for asthma

    PubMed Central

    Penn, Raymond B.; Bond, Richard A.; Walker, Julia K. L.

    2015-01-01

    The obstructive lung disease asthma is treated by drugs that target, either directly or indirectly, G protein-coupled receptors (GPCRs). GPCRs coupled to Gq are the primary mediators of airway smooth muscle (ASM) contraction and increased airway resistance, whereas the Gs-coupled beta-2-adrenoceptor (β2AR) promotes pro-relaxant signaling in and relaxation of ASM resulting in greater airway patency and reversal of life-threatening bronchoconstriction. In additions, GPCR-mediated functions in other cell types, including airway epithelium and hematopoietic cells, are involved in control of lung inflammation that causes most asthma. The capacity of arrestins to regulate GPCR signaling, via either control of GPCR desensitization/resensitization, or via G protein-independent signaling, renders arrestins an intriguing therapeutic target for asthma and other obstructive lung diseases. This review will focus on the potential role of arrestins in those GPCR-mediated airway cell functions that are dysregulated in asthma. PMID:24292841

  18. Exposure to ozone modulates human airway protease/antiprotease balance contributing to increased influenza A infection

    EPA Science Inventory

    Exposure to oxidant air pollution is associated with Increased respiratory morbiditses and susceptibility to Infections Ozone is a commonly encountered oxidant air pollutant, yet Its effects on influenza infections in humans are not known ‘the greater Mexico City area was the pri...

  19. Efficiency of bimaxillary advancement surgery in increasing the volume of the upper airways: a systematic review of observational studies and meta-analysis.

    PubMed

    Rosário, Henrique Damian; Oliveira, Gustavo Mussi Stefan; Freires, Irlan Almeida; de Souza Matos, Felipe; Paranhos, Luiz Renato

    2017-01-01

    Postsurgical changes of the airways have become a great point of interest because it has been reported that maxillomandibular advancement surgery can improve or eliminate obstructive sleep apnea; however, its treatment effectiveness is still controversial. The purpose of this systematic review and meta-analysis was to assess the effectiveness of maxillomandibular advancement surgery to increase upper airway volume in adults, comparing before and after treatment. Bibliographic searches of observational studies with no restriction of year or language were performed in the electronic databases PubMed, Scopus, ScienceDirect and SciELO for articles published up to April 2015. After verification of duplicate records, 1860 articles were examined. Of these, ten met the eligibility criteria, of which three were excluded for having poor methodological quality. The other seven articles were included in the systematic review and six in the meta-analysis, representing 83 patients. One study whose data were not given in absolute values was excluded from the meta-analysis. The meta-analysis showed a statistically significant difference between the averages of upper airway volume before and after surgery {7.86 cm(3) [95 % CI (6.22, 9.49), p = 1.00)}. Clinical evidence suggests that the upper airway volume is increased after maxillomandibular advancement surgery.

  20. Pre-treatment with α-hederin increases β-adrenoceptor mediated relaxation of airway smooth muscle.

    PubMed

    Wolf, Anne; Gosens, Reinoud; Meurs, Herman; Häberlein, Hanns

    2011-01-15

    Preparations of ivy leaves dry extract with secretolytic and bronchiolytic efficacy are widely used for the treatment of acute and chronic obstructive airway diseases. The mechanism by which ivy preparations improve lung functions is not fully understood. Here, we tested the influence of the three main saponins of ivy, α-hederin, hederacoside C and hederagenin, on the contraction and relaxation behaviour of isolated bovine tracheal smooth muscle strips by isometric tension measurements. None of the tested compounds altered histamine or methacholine-induced contraction of the smooth muscle strips. In contrast, the isoprenaline-induced relaxation of 100μM methacholine precontracted muscle strips was significantly enhanced when pre-treated with 1μM of α-hederin for 18h. The pre-treatment with hederacoside C or hederagenin had no effect on isoprenaline-induced relaxation. For the first time the bronchiolytic effect of α-hederin was demonstrated by isometric tension measurements using bovine tracheal smooth muscle strips. α-Hederin increases isoprenaline-induced relaxation indirectly, probably by inhibiting heterologous desensitization induced by high concentrations of muscarinic ligands like methacholine.

  1. A new paradigm in respiratory hygiene: increasing the cohesivity of airway secretions to improve cough interaction and reduce aerosol dispersion

    PubMed Central

    Zayas, Gustavo; Dimitry, John; Zayas, Ana; O'Brien, Darryl; King, Malcolm

    2005-01-01

    Background Infectious respiratory diseases are transmitted to non-infected subjects when an infected person expels pathogenic microorganisms to the surrounding environment when coughing or sneezing. When the airway mucus layer interacts with high-speed airflow, droplets are expelled as aerosol; their concentration and size distribution may each play an important role in disease transmission. Our goal is to reduce the aerosolizability of respiratory secretions while interfering only minimally with normal mucus clearance using agents capable of increasing crosslinking in the mucin glycoprotein network. Methods We exposed mucus simulants (MS) to airflow in a simulated cough machine (SCM). The MS ranged from non-viscous, non-elastic substances (water) to MS of varying degrees of viscosity and elasticity. Mucociliary clearance of the MS was assessed on the frog palate, elasticity in the Filancemeter and the aerosol pattern in a "bulls-eye" target. The sample loaded was weighed before and after each cough maneuver. We tested two mucomodulators: sodium tetraborate (XL"B") and calcium chloride (XL "C"). Results Mucociliary transport was close to normal speed in viscoelastic samples compared to non-elastic, non-viscous or viscous-only samples. Spinnability ranged from 2.5 ± 0.6 to 50.9 ± 6.9 cm, and the amount of MS expelled from the SCM increased from 47 % to 96 % adding 1.5 μL to 150 μL of XL "B". Concurrently, particles were inversely reduced to almost disappear from the aerosolization pattern. Conclusion The aerosolizability of MS was modified by increasing its cohesivity, thereby reducing the number of particles expelled from the SCM while interfering minimally with its clearance on the frog palate. An unexpected finding is that MS crosslinking increased "expectoration". PMID:16138926

  2. The influence of gender and upper airway resistance on the ventilatory response to arousal in obstructive sleep apnoea in humans

    PubMed Central

    Jordan, Amy S; McEvoy, R Doug; Edwards, Jill K; Schory, Karen; Yang, Chang-Kook; Catcheside, Peter G; Fogel, Robert B; Malhotra, Atul; White, David P

    2004-01-01

    The termination of obstructive respiratory events is typically associated with arousal from sleep. The ventilatory response to arousal may be an important determinant of subsequent respiratory stability/instability and therefore may be involved in perpetuating obstructive respiratory events. In healthy subjects arousal is associated with brief hyperventilation followed by more prolonged hypoventilation on return to sleep. This study was designed to assess whether elevated sleeping upper airway resistance (RUA) alters the ventilatory response to arousal and subsequent breathing on return to sleep in patients with obstructive sleep apnoea (OSA). Inspired minute ventilation (VI), RUA and end-tidal CO2 pressure (PET,CO2) were measured in 22 patients (11 men, 11 women) with OSA (mean ±s.e.m., apnoea–hypopnoea index (AHI) 48.9 ± 5.9 events h−1) during non-rapid eye movement (NREM) sleep with low RUA (2.8 ± 0.3 cmH2O l−1 s; optimal continuous positive airway pressure (CPAP) = 11.3 ± 0.7 cmH2O) and with elevated RUA (17.6 ± 2.8 cmH2O l−1 s; sub-optimal CPAP = 8.4 ± 0.8 cmH2O). A single observer, unaware of respiratory data, identified spontaneous and tone-induced arousals of 3–15 s duration preceded and followed by stable NREM sleep. VI was compared between CPAP levels before and after spontaneous arousal in 16 subjects with tone-induced arousals in both conditions. During stable NREM sleep at sub-optimal CPAP, PET,CO2 was mildly elevated (43.5 ± 0.8 versus 42.5 ± 0.8 Torr). However, baseline VI (7.8 ± 0.3 versus 8.0 ± 0.3 l min−1) was unchanged between CPAP conditions. For the first three breaths following arousal, VI was higher for sub-optimal than optimal CPAP (first breath: 11.2 ± 0.9 versus 9.3 ± 0.6 l min−1). The magnitude of hypoventilation on return to sleep was not affected by the level of CPAP and both obstructive and central respiratory events were rare following arousal. Similar results occurred after tone-induced arousals which led to

  3. A Comparison of Personality Characteristics and Psychiatric Symptomatology between Upper Airway Resistance Syndrome and Obstructive Sleep Apnea Syndrome

    PubMed Central

    So, Soo-Jung; Kang, Seung-Gul; Cho, Chul-Hyun; Yoon, Ho-Kyoung; Kim, Leen

    2015-01-01

    Objective To investigate the personality characteristics of patients with upper airway resistance syndrome (UARS) and those of patients with obstructive sleep apnea syndrome (OSAS). Methods Eighty-eight patients with UARS and 365 patients with OSAS participated. All patients had a diagnostic full-night attended polysomnography (PSG) and completed the Athens Insomnia Scale (AIS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Symptom Checklist-90-Revision (SCL-90-R) and Eysenck Personality Questionnaire (EPQ). Results The UARS group scored significantly higher than the OSAS group on the ESS, AIS, and PSQI (p<0.001). The scores of all SCL-90-R subscales in the UARS group were significantly higher than those in the OSA group (all p<0.001, except for somatization, p=0.016). Patients with UARS scored lower on EPQ-E (extroversion/introversion) (p=0.006) and EPQ-L (lie) (p<0.001) than those with OSA. UARS patients also showed higher scores on EPQ-P (psychoticism) (p=0.002) and EPQ-N (neuroticism) (p<0.001) than OSAS patients. Conclusion Our results suggest that patients with UARS have worse subjective sleep quality than OSAS patients in spite of their better PSG findings. UARS patients tend to have more neurotic and sensitive personalities than patients with OSAS, which may be a cause of the clinical features of UARS. PMID:25866518

  4. Effects of continuous positive airway pressure treatment on clinic and ambulatory blood pressures in patients with obstructive sleep apnea and resistant hypertension: a randomized controlled trial.

    PubMed

    Muxfeldt, Elizabeth S; Margallo, Victor; Costa, Leonardo M S; Guimarães, Gleison; Cavalcante, Aline H; Azevedo, João C M; de Souza, Fabio; Cardoso, Claudia R L; Salles, Gil F

    2015-04-01

    The effect of continuous positive airway pressure (CPAP) on blood pressures (BPs) in patients with resistant hypertension and obstructive sleep apnea is not established. We aimed to evaluate it in a randomized controlled clinical trial, with blinded assessment of outcomes. Four hundred thirty-four resistant hypertensive patients were screened and 117 patients with moderate/severe obstructive sleep apnea, defined by an apnea-hypopnea index ≥15 per hour, were randomized to 6-month CPAP treatment (57 patients) or no therapy (60 patients), while maintaining antihypertensive treatment. Clinic and 24-hour ambulatory BPs were obtained before and after 6-month treatment. Primary outcomes were changes in clinic and ambulatory BPs and in nocturnal BP fall patterns. Intention-to-treat and per-protocol (limited to those with uncontrolled ambulatory BPs) analyses were performed. Patients had mean (SD) 24-hour BP of 129(16)/75(12) mm Hg, and 59% had uncontrolled ambulatory BPs. Mean apnea-hypopnea index was 41 per hour and 58.5% had severe obstructive sleep apnea. On intention-to-treat analysis, there was no significant difference in any BP change, neither in nocturnal BP fall, between CPAP and control groups. The best effect of CPAP was on night-time systolic blood pressure in per-protocol analysis, with greater reduction of 4.7 mm Hg (95% confidence interval, -11.3 to +3.1 mm Hg; P=0.24) and an increase in nocturnal BP fall of 2.2% (95% confidence interval, -1.6% to +5.8%; P=0.25), in comparison with control group. In conclusion, CPAP treatment had no significant effect on clinic and ambulatory BPs in patients with resistant hypertension and moderate/severe obstructive sleep apnea, although a beneficial effect on night-time systolic blood pressure and on nocturnal BP fall might exist in patients with uncontrolled ambulatory BP levels.

  5. Modified developer increases line resolution in photosensitive resist

    NASA Technical Reports Server (NTRS)

    1965-01-01

    Standard developer solution is mixed with dipropyl carbonate. This reduces swelling in the photosensitive resist and permits application of relatively thick films with minimal pinhole formation and increased line resolution.

  6. Biodiversity increases the resistance of ecosystem productivity to climate extremes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It remains unclear whether biodiversity buffers ecosystems against extreme climate events, which are becoming increasingly frequent worldwide. Although early results suggested that biodiversity might provide both resistance and resilience (sensu rapid recovery) of ecosystem productivity to drought, ...

  7. Multidrug-Resistant Acinetobacter spp.: Increasingly Problematic Nosocomial Pathogens

    PubMed Central

    Lee, Kyungwon; Yong, Dongeun; Jeong, Seok Hoon

    2011-01-01

    Pathogenic bacteria have increasingly been resisting to antimicrobial therapy. Recently, resistance problem has been relatively much worsened in Gram-negative bacilli. Acinetobacter spp. are typical nosocomial pathogens causing infections and high mortality, almost exclusively in compromised hospital patients. Acinetobacter spp. are intrinsically less susceptible to antibiotics than Enterobacteriaceae, and have propensity to acquire resistance. A surveillance study in Korea in 2009 showed that resistance rates of Acinetobacter spp. were very high: to fluoroquinolone 67%, to amikacin 48%, to ceftazidime 66% and to imipenem 51%. Carbapenem resistance was mostly due to OXA type carbapenemase production in A. baumannii isolates, whereas it was due to metallo-β-lactamase production in non-baumannii Acinetobacter isolates. Colistin-resistant isolates were rare but started to be isolated in Korea. Currently, the infection caused by multidrug-resistant A. baumannii is among the most difficult ones to treat. Analysis at tertiary care hospital in 2010 showed that among the 1,085 isolates of Acinetobacter spp., 14.9% and 41.8% were resistant to seven, and to all eight antimicrobial agents tested, respectively. It is known to be difficult to prevent Acinetobacter spp. infection in hospitalized patients, because the organisms are ubiquitous in hospital environment. Efforts to control resistant bacteria in Korea by hospitals, relevant scientific societies and government agencies have only partially been successful. We need concerted multidisciplinary efforts to preserve the efficacy of currently available antimicrobial agents, by following the principles of antimicrobial stewardship. PMID:22028150

  8. Loss-of-function of inositol polyphosphate-4-phosphatase reversibly increases the severity of allergic airway inflammation.

    PubMed

    Aich, Jyotirmoi; Mabalirajan, Ulaganathan; Ahmad, Tanveer; Agrawal, Anurag; Ghosh, Balaram

    2012-06-06

    Inositol polyphosphate phosphatases regulate the magnitude of phosphoinositide-3 kinase signalling output. Although inositol polyphosphate-4-phosphatase is known to regulate phosphoinositide-3 kinase signalling, little is known regarding its role in asthma pathogenesis. Here we show that modulation of inositol polyphosphate-4-phosphatase alters the severity of asthma. Allergic airway inflammation in mice led to calpain-mediated degradation of inositol polyphosphate-4-phosphatase. In allergic airway inflammation models, preventing inositol polyphosphate-4-phosphatase degradation by inhibiting calpain activity, or overexpression of inositol polyphosphate-4-phosphatase in mouse lungs, led to attenuation of the asthma phenotype. Conversely, knockdown of inositol polyphosphate-4-phosphatase severely aggravated the allergic airway inflammation and the asthma phenotype. Interestingly, inositol polyphosphate-4-phosphatase knockdown in lungs of naive mice led to spontaneous airway hyper-responsiveness, suggesting that inositol polyphosphate-4-phosphatase could be vital in maintaining the lung homeostasis. We suggest that inositol polyphosphate-4-phosphatase has an important role in modulating inflammatory response in asthma, and thus, uncover a new understanding of the complex interplay between inositol signalling and asthma, which could provide alternative strategies in asthma management.

  9. Urinary Phthalates and Increased Insulin Resistance in Adolescents

    PubMed Central

    Spanier, Adam J.; Sathyanarayana, Sheela; Attina, Teresa M.; Blustein, Jan

    2013-01-01

    BACKGROUND Di-2-ethylhexylphthalate (DEHP) is an environmental chemical commonly found in processed foods. Phthalate exposures, in particular to DEHP, have been associated with insulin resistance in adults, but have not been studied in adolescents. METHODS: Using cross-sectional data from 766 fasting 12- to 19-year-olds in the 2003–2008 NHANES, we examined associations of phthalate metabolites with continuous and categorical measures of homeostatic model assessment of insulin resistance (HOMA-IR). RESULTS: Controlling for demographic and behavioral factors, diet, continuous age, BMI category, and urinary creatinine, for each log (roughly threefold) increase in DEHP metabolites, a 0.27 increase (95% confidence interval 0.14–0.40; P < .001) in HOMA-IR was identified. Compared with the first tertile of DEHP metabolite in the study population (14.5% insulin resistant), the third tertile had 21.6% prevalence (95% confidence interval 17.2%–26.0%; P = .02). Associations persisted despite controlling for bisphenol A, another endocrine-disrupting chemical commonly found in foods, and HOMA-IR and insulin resistance were not significantly associated with metabolites of lower molecular weight phthalates commonly found in cosmetics and other personal care products. CONCLUSIONS: Urinary DEHP concentrations were associated with increased insulin resistance in this cross-sectional study of adolescents. This study cannot rule out the possibility that insulin-resistant children ingest food with higher phthalate content, or that insulin-resistant children excrete more DEHP. PMID:23958772

  10. Biodiversity increases the resistance of ecosystem productivity to climate extremes.

    PubMed

    Isbell, Forest; Craven, Dylan; Connolly, John; Loreau, Michel; Schmid, Bernhard; Beierkuhnlein, Carl; Bezemer, T Martijn; Bonin, Catherine; Bruelheide, Helge; de Luca, Enrica; Ebeling, Anne; Griffin, John N; Guo, Qinfeng; Hautier, Yann; Hector, Andy; Jentsch, Anke; Kreyling, Jürgen; Lanta, Vojtěch; Manning, Pete; Meyer, Sebastian T; Mori, Akira S; Naeem, Shahid; Niklaus, Pascal A; Polley, H Wayne; Reich, Peter B; Roscher, Christiane; Seabloom, Eric W; Smith, Melinda D; Thakur, Madhav P; Tilman, David; Tracy, Benjamin F; van der Putten, Wim H; van Ruijven, Jasper; Weigelt, Alexandra; Weisser, Wolfgang W; Wilsey, Brian; Eisenhauer, Nico

    2015-10-22

    It remains unclear whether biodiversity buffers ecosystems against climate extremes, which are becoming increasingly frequent worldwide. Early results suggested that the ecosystem productivity of diverse grassland plant communities was more resistant, changing less during drought, and more resilient, recovering more quickly after drought, than that of depauperate communities. However, subsequent experimental tests produced mixed results. Here we use data from 46 experiments that manipulated grassland plant diversity to test whether biodiversity provides resistance during and resilience after climate events. We show that biodiversity increased ecosystem resistance for a broad range of climate events, including wet or dry, moderate or extreme, and brief or prolonged events. Across all studies and climate events, the productivity of low-diversity communities with one or two species changed by approximately 50% during climate events, whereas that of high-diversity communities with 16-32 species was more resistant, changing by only approximately 25%. By a year after each climate event, ecosystem productivity had often fully recovered, or overshot, normal levels of productivity in both high- and low-diversity communities, leading to no detectable dependence of ecosystem resilience on biodiversity. Our results suggest that biodiversity mainly stabilizes ecosystem productivity, and productivity-dependent ecosystem services, by increasing resistance to climate events. Anthropogenic environmental changes that drive biodiversity loss thus seem likely to decrease ecosystem stability, and restoration of biodiversity to increase it, mainly by changing the resistance of ecosystem productivity to climate events.

  11. An improved murine model of asthma: selective airway inflammation, epithelial lesions and increased methacholine responsiveness following chronic exposure to aerosolised allergen

    PubMed Central

    Temelkovski, J.; Hogan, S.; Shepherd, D.; Foster, P.; Kumar, R.

    1998-01-01

    BACKGROUND—Existing murine models of asthma lack many of the inflammatory and epithelial changes that are typical of the human disease. Moreover, these models are frequently complicated by allergic alveolitis.
METHODS—High IgE responder BALB/c mice were systemically sensitised to ovalbumin and chronically challenged with low particle mass concentrations of aerosolised ovalbumin. Titres of anti-ovalbumin IgE in serum were measured at two weekly intervals by enzyme immunoassay, accumulation of inflammatory cells and histopathological abnormalities of the epithelium were quantified morphometrically in the trachea and the lungs, and airway reactivity was assessed by measuring bronchoconstriction following intravenous administration of methacholine.
RESULTS—Mice sensitised by two intraperitoneal injections of ovalbumin developed high titres of IgE antibodies to ovalbumin. Following exposure to low concentrations of aerosolised antigen for up to eight weeks these animals developed a progressive inflammatory response in the airways, characterised by the presence of intraepithelial eosinophils and by infiltration of the lamina propria with lymphoid/mononuclear cells, without associated alveolitis. Goblet cell hyperplasia/metaplasia was induced in the intrapulmonary airways, while epithelial thickening and subepithelial fibrosis were evident following chronic exposure. In parallel, the mice developed increased sensitivity to induction of bronchospasm, as well as increased maximal reactivity. Non-immunised mice exposed to aerosolised ovalbumin had low or absent anti-ovalbumin IgE and did not exhibit inflammatory or epithelial changes, but developed airway hyperreactivity.
CONCLUSIONS—This experimental model replicates many of the features of human asthma and should facilitate studies of pathogenetic mechanisms and of potential therapeutic agents. 

 PMID:10193371

  12. An imbalance in C/EBPs and increased mitochondrial activity in asthmatic airway smooth muscle cells: novel targets in asthma therapy?

    PubMed

    Roth, Michael; Black, Judith L

    2009-06-01

    The asthma prevalence was increasing over the past two decades worldwide. Allergic asthma, caused by inhaled allergens of different origin or by food, is mediated by inflammatory mechanisms. The action of non-allergic asthma, induced by cold air, humidity, temperature or exercise, is not well understood. Asthma affects up to 15% of the population and is treated with anti-inflammatory and muscle relaxing drugs which allow symptom control. Asthma was first defined as a malfunction of the airway smooth muscle, later as an imbalanced immune response of the lung. Recent studies placed the airway smooth muscle again into the focus. Here we summarize the molecular biological basis of the deregulated function of the human airway smooth muscle cell as a cause or important contributor to the pathology of asthma. In the asthmatic human airway smooth muscle cells, there is: (i) a deregulation of cell differentiation due to low levels of maturation-regulating transcription factors such as CCAAT/enhancer binding proteins and peroxisome proliferator-activated receptors, thereby reducing the cells threshold to proliferate and to secrete pro-inflammatory cytokines under certain conditions; (ii) a higher basal energy turnover that is due to increased number and activity of mitochondria; and (iii) a modified feedback mechanism between cells and the extracellular matrix they are embedded in. All these cellular pathologies are linked to each other and to the innate immune response of the lung, but the sequence of events is unclear and needs further investigation. However, these findings may present the basis for the development of novel curative asthma drugs.

  13. Increased metacyclogenesis of antimony-resistant Leishmania donovani clinical lines.

    PubMed

    Ouakad, M; Vanaerschot, M; Rijal, S; Sundar, S; Speybroeck, N; Kestens, L; Boel, L; De Doncker, S; Maes, I; Decuypere, S; Dujardin, J-C

    2011-09-01

    Mathematical models predict that the future of epidemics of drug-resistant pathogens depends in part on the competitive fitness of drug-resistant strains. Considering metacyclogenesis (differentiation process essential for infectivity) as a major contributor to the fitness of Leishmania donovani, we tested its relationship with pentavalent antimony (SbV) resistance in clinical lines. Different methods for the assessment of metacyclogenesis were cross-validated: gene expression profiling (META1 and SHERP), morphometry (microscopy and FACS), in vitro infectivity to macrophages and resistance to complement lysis. This was done on a model constituted by 2 pairs of reference strains cloned from a SbV-resistant and -sensitive isolate. We selected the most adequate parameter and extended the analysis of metacyclogenesis diversity to a sample of 20 clinical lines with different in vitro susceptibility to the drug. The capacity of metacyclogenesis, as measured by the complement lysis test, was shown to be significantly higher in SbV-resistant clinical lines of L. donovani than in SbV-sensitive lines. Together with other lines of evidence, it is concluded that L. donovani constitutes a unique example and model of drug-resistant pathogens with traits of increased fitness. These findings raise a fundamental question about the potential risks of selecting more virulent pathogens through massive chemotherapeutic interventions.

  14. Increasing antimicrobial resistance and narrowing therapeutics in typhoidal salmonellae.

    PubMed

    Kaurthe, Jaspal

    2013-03-01

    Multidrug-resistant typhoid fever (MDRTF) is a major public health problem in developing countries and is an emerging problem in the developed world. Because of the difficulties in preventing typhoid by public health measures or immunization in developing countries, great reliance is placed on antimicrobial chemotherapy. The treatment should commence as soon as the clinical diagnosis is made rather than after the results of antimicrobial susceptibility tests but the existence of MDRTF poses a serious clinical dilemma in the selection of empiric antimicrobial therapy. With the widespread emergence and spread of strains resistant to chloramphenicol, ampicillin and trimethoprim, ciprofloxacin became the drug of choice for the treatment of typhoid fever. However, of late the efficacy of fluoroquinolones too has been questioned, mainly due to increasing reports of increasing defervescence time and poor patient response. This indicates that the organism has begun to develop resistance to fluoroquinolones, and is corroborated by a steady increase in Minimum Inhibitory Concentration (MIC) of ciprofloxacin. The therapeutics of ciprofloxacin-resistant enteric fever narrows down to third- and fourth-generation cephalosporins and azithromycin. However, the emergence of extended-spectrum b-lactamases (ESBLs) in typhoidal Salmonellae poses a new challenge and would greatly limit the therapeutic options leaving only tigecycline and carbepenems as secondary antimicrobial drugs. This increasing resistance is alarming and emphasizes the need of effective preventive measures to control typhoid and to limit the unnecessary use of antibiotics.

  15. Effects of propranolol inhalation on the diurnal increase in FEV1 and on propranolol airways responsiveness in atopic subjects with asthma.

    PubMed Central

    Oosterhoff, Y.; Koëter, G. H.; Postma, D. S.

    1995-01-01

    BACKGROUND--Propranolol inhalation provocation tests are used to measure indirect airways responsiveness in the investigation of asthma. In this study the effects of repeated propranolol inhalation provocation tests within the same day on normal diurnal variation in the forced expiratory volume in one second (FEV1) and subsequent propranolol airways responsiveness were investigated. METHODS--Fifteen atopic asthmatic subjects were challenged with doubling concentrations of propranolol at 08.00 and 16.00 hours on the same study day and at 16.00 hours on a control day to exclude changes related to normal diurnal variation. RESULTS--Mean (SD) baseline FEV1 at 16.00 hours on the study day was 3.38 (0.23) 1, significantly lower than the value at 16.00 hours on the control day of 3.70 (0.24) 1 (p = 0.001). No differences were found between the geometric mean provocative concentration of propranolol causing a 20% fall in FEV1 (PC20) measured on the study day (08.00 hours, 9.3 mg/ml; 16.00 hours, 11.3 mg/ml) and on the control day (16.00 hours 9.3 mg/ml). CONCLUSIONS--The results suggest that propranolol provocation at 08.00 hours has a long lasting effect on FEV1, thereby counteracting the normal diurnal increase in diameter of the airways. This makes propranolol challenge tests less suitable for studying indirect airways responsiveness in the course of one day. Because the FEV1 does not return to control values, it is not possible to determine whether tachyphylaxis to repeated propranolol challenge with a time interval of up to eight hours occurs. PMID:8539672

  16. Does the length dependency of airway smooth muscle force contribute to airway hyperresponsiveness?

    PubMed

    Lee-Gosselin, Audrey; Pascoe, Chris D; Couture, Christian; Paré, Peter D; Bossé, Ynuk

    2013-11-01

    Airway wall remodeling and lung hyperinflation are two typical features of asthma that may alter the contractility of airway smooth muscle (ASM) by affecting its operating length. The aims of this study were as follows: 1) to describe in detail the "length dependency of ASM force" in response to different spasmogens; and 2) to predict, based on morphological data and a computational model, the consequence of this length dependency of ASM force on airway responsiveness in asthmatic subjects who have both remodeled airway walls and hyperinflated lungs. Ovine tracheal ASM strips and human bronchial rings were isolated and stimulated to contract in response to increasing concentrations of spasmogens at three different lengths. Ovine tracheal strips were more sensitive and generated greater force at longer lengths in response to acetylcholine (ACh) and K(+). Equipotent concentrations of ACh were approximately a log less for ASM stretched by 30% and approximately a log more for ASM shortened by 30%. Similar results were observed in human bronchi in response to methacholine. Morphometric and computational analyses predicted that the ASM of asthmatic subjects may be elongated by 6.6-10.4% (depending on airway generation) due to remodeling and/or hyperinflation, which could increase ACh-induced force by 1.8-117.8% (depending on ASM length and ACh concentration) and enhance the increased resistance to airflow by 0.4-4,432.8%. In conclusion, elongation of ASM imposed by airway wall remodeling and/or hyperinflation may allow ASM to operate at a longer length and to consequently generate more force and respond to lower concentration of spasmogens. This phenomenon could contribute to airway hyperresponsiveness.

  17. Role of leukotrienes in airway hyperresponsiveness in guinea-pigs.

    PubMed Central

    Ishida, K.; Thomson, R. J.; Schellenberg, R. R.

    1993-01-01

    1. Repeated aerosolization of leukotriene C4 (LTC4) to guinea-pigs produced leftward shift in their pulmonary resistance (RL) dose-response curves to inhaled acetylcholine (ACh) without increasing the maximum responses. 2. Repeated LTC4 aerosolization did not increase airway eosinophils. 3. The 5-lipoxygenase-activating protein (FLAP) inhibitor, MK-886, prevented the leftward shift in RL dose-response curves to ACh following repeated antigen challenge in guinea-pigs. 4. MK-886 did not inhibit the increased maximal RL produced by repeated antigen challenge, nor inhibit the airway eosinophilia induced by repeated antigen challenge. 5. Our findings suggest that leukotrienes may account for the leftward shift in pulmonary resistance responses caused by antigen but do not cause the airway eosinophilia nor enhanced maximum broncho-constrictor response to antigen. PMID:8467358

  18. Breathing resistance and ultrafine particle deposition in nasal-laryngeal airways of a newborn, an infant, a child, and an adult.

    PubMed

    Xi, Jinxiang; Berlinski, Ariel; Zhou, Yue; Greenberg, Bruce; Ou, Xiawei

    2012-12-01

    As a human grows from birth to adulthood, both airway anatomy and breathing conditions vary, altering the deposition rate and pattern of inhaled aerosols. However, deposition studies have typically focused on adult subjects, results of which may not be readily extrapolated to children. This study numerically evaluated the age-related effects on the airflow and aerosol dynamics in image-based nose-throat models of a 10-day-old newborn, a 7-month-old infant, a 5-year-old child, and a 53-year-old adult. Differences in airway physiology, breathing resistance, and aerosol filtering efficiency among the four models were quantified and compared. A high-fidelity fluid-particle transport model was employed to simulate the multi-regime airflows and particle transport within the nasal-laryngeal airways. Ultrafine particles were evaluated under breathing conditions ranging from sedentary to heavy activities. Results of this study indicate that the nasal-laryngeal airways at different ages, albeit differ significantly in morphology and dimension, do not significantly affect the total deposition fractions or maximum local deposition enhancement for ultrafine aerosols. Further, the deposition partitioning in the sub-regions of interest is different among the four models. Results of this study corroborate the use of the in vivo-based diffusion parameter (D(0.5)Q(-0.28)) over the replica-based parameter in correlating nasal-laryngeal depositions of ultrafine aerosols. Improved correlations have been developed for the four age groups by implementing this in vivo-based diffusion parameter as well as the Cunningham correction factor.

  19. Long-term exposure of adults to outdoor air pollution is associated with increased airway obstruction and higher prevalence of bronchial hyperresponsiveness

    SciTech Connect

    Jammres, Y.; Delpierre, S.; Burnet, H.; Delvolgo, M.J.; Humbert-Tena, C.

    1998-11-01

    The authors studied the association between long-term exposure to outdoor air pollution and the severity of obstructive pulmonary disease and prevalence of bronchial hyperreactivity to {beta}2 agonists in two groups of adult patients who were of similar ages and who had similar smoking habits. The subjects lived in downtown districts or in the outer suburbs of Marseilles, the neighborhood that contained air samplers. The regions were similar with respect to sulfur dioxide levels, but levels of nitric oxides and particulate matter were higher in the downtown area than the suburbs. The authors assessed airway obstruction, as determined by a decrease in forced expiratory volume in 1 s, mean forced expiratory flow measured between 25% and 75% of vital capacity, and an elevated value of central airway resistance. The authors tested the changes in these variables induced by inhalation of a {beta}2 agonist. Baseline lung function was altered more significantly in both male and female patients who lived in downtown Marseilles than in those who resided in the suburbs, and the differences persisted regardless of the season during which the study occurred. Prevalence of bronchial hyperreactivity and symptoms of asthma were higher in the downtown than suburban male subjects. The results of this study suggest that an association exists between actual environmental exposure to outdoor air pollution and respiratory effects in sensitive adults represented by patients with chronic obstructive pulmonary disease or asthma.

  20. Airway-parenchyma uncoupling in nocturnal asthma.

    PubMed

    Irvin, C G; Pak, J; Martin, R J

    2000-01-01

    Airway flow resistance is well known to be dependent upon lung volume. The rise in lung volume that occurs in asthma is therefore thought to be an important mechanism that defends airway patency. The purpose of the current study was to investigate the interdependence or mechanical coupling between airways and lung parenchyma during the inflammatory processes that occur in the patient with nocturnal asthma. Five patients with documented nocturnal asthma were studied in both a vertical and a horizontal body plethysmograph. Lung volume was altered with continuous negative pressure as applied to the chest wall with a poncho cuirass in different postures and during sleep. We found during the awake phase that an increase in lung volume decreased lower pulmonary resistance (Rlp); however, within 30 min of sleep onset, functional residual capacity (FRC) fell and Rlp rose more than would be expected for the fall in FRC. Restoring FRC to presleep values either at an early (half-hour) or a late (3-h) time point did not cause Rlp to significantly fall. A second phase of the study showed that the loss of Rlp dependence on lung volume was not due to the assumption of the supine posture. Indirect measurements of lung compliance were consistent with a stiffening of the lung. We conclude that with sleep there is an immediate uncoupling of the parenchyma to the airway, resulting in a loss of interdependence that persists throughout sleep and may contribute to the morbidity and mortality associated with nocturnal asthma.

  1. Plant adaptogens increase lifespan and stress resistance in C. elegans.

    PubMed

    Wiegant, F A C; Surinova, S; Ytsma, E; Langelaar-Makkinje, M; Wikman, G; Post, J A

    2009-02-01

    Extracts of plant adaptogens such as Eleutherococcus senticosus (or Acanthopanax senticosus) and Rhodiola rosea can increase stress resistance in several model systems. We now show that both extracts also increase the mean lifespan of the nematode C. elegans in a dose-dependent way. In at least four independent experiments, 250 microg/ml Eleutherococcus (SHE-3) and 10-25 microg/ml Rhodiola (SHR-5) significantly increased life span between 10 and 20% (P < 0.001), increased the maximum lifespan with 2-3 days and postponed the moment when the first individuals in a population die, suggesting a modulation of the ageing process. With higher concentrations, less effect was observed, whereas at the highest concentrations tested (2500 microg/ml Eleutherococcus and 250 microg/ml Rhodiola) a lifespan shortening effect was observed of 15-25% (P < 0.001). Both adaptogen extracts were also able to increase stress resistance in C. elegans: against a relatively short heat shock (35 degrees C during 3 h) as well as chronic heat treatment at 26 degrees C. An increase against chronic oxidative stress conditions was observed in mev-1 mutants, and during exposure of the wild type nematode to paraquat (10 mM) or UV stress, be it less efficiently. Concerning the mode of action: both adaptogens induce translocation of the DAF-16 transcription factor from the cytoplasm into the nucleus, suggesting a reprogramming of transcriptional activities favoring the synthesis of proteins involved in stress resistance (such as the chaperone HSP-16) and longevity. Based on these observations, it is suggested that adaptogens are experienced as mild stressors at the lifespan-enhancing concentrations and thereby induce increased stress resistance and a longer lifespan.

  2. Accumulation of Phosphatidic Acid Increases Vancomycin Resistance in Escherichia coli

    PubMed Central

    Sutterlin, Holly A.; Zhang, Sisi

    2014-01-01

    In Gram-negative bacteria, lipopolysaccharide (LPS) contributes to the robust permeability barrier of the outer membrane, preventing entry of toxic molecules such as antibiotics. Mutations in lptD, the beta-barrel component of the LPS transport and assembly machinery, compromise LPS assembly and result in increased antibiotic sensitivity. Here, we report rare vancomycin-resistant suppressors that improve barrier function of a subset of lptD mutations. We find that all seven suppressors analyzed mapped to the essential gene cdsA, which is responsible for the conversion of phosphatidic acid to CDP-diacylglycerol in phospholipid biosynthesis. These cdsA mutations cause a partial loss of function and, as expected, accumulate phosphatidic acid. We show that this suppression is not confined to mutations that cause defects in outer membrane biogenesis but rather that these cdsA mutations confer a general increase in vancomycin resistance, even in a wild-type cell. We use genetics and quadrupole time of flight (Q-TOF) liquid chromatography-mass spectrometry (LC-MS) to show that accumulation of phosphatidic acid by means other than cdsA mutations also increases resistance to vancomycin. We suggest that increased levels of phosphatidic acid change the physical properties of the outer membrane to impede entry of vancomycin into the periplasm, hindering access to its target, an intermediate required for the synthesis of the peptidoglycan cell wall. PMID:24957626

  3. High glucose induces dysfunction of airway epithelial barrier through down-regulation of connexin 43.

    PubMed

    Yu, Hongmei; Yang, Juan; Zhou, Xiangdong; Xiao, Qian; Lü, Yang; Xia, Li

    2016-03-01

    The airway epithelium is a barrier to the inhaled antigens and pathogens. Connexin 43 (Cx43) has been found to play critical role in maintaining the function of airway epithelial barrier and be involved in the pathogenesis of the diabetic retinal vasculature, diabetes nephropathy and diabetes skin. Hyperglycemia has been shown to be an independent risk factor for respiratory infections. We hypothesize that the down-regulation of Cx43 induced by HG alters the expression of tight junctions (zonula occludens-1 (ZO-1) and occludin) and contributes to dysfunction of airway epithelial barrier, and Cx43 plays a critical role in the process in human airway epithelial cells (16 HBE). We show that high glucose (HG) decreased the expression of ZO-1 and occludin, disassociated interaction between Cx43 and tight junctions, and then increased airway epithelial transepithelial electrical resistance (TER) and permeability by down-regulation of Cx43 in human airway epithelial cells. These observations demonstrate an important role for Cx43 in regulating HG-induced dysfunction of airway epithelial barrier. These findings may bring new insights into the molecular pathogenesis of pulmonary infection related to diabetes mellitus and lead to novel therapeutic intervention for the dysfunction of airway epithelial barrier in chronic inflammatory airway diseases.

  4. Increased Vascular Resistance with Hemoglobin-Based Oxygen Carriers

    DTIC Science & Technology

    1993-01-01

    vascular resistance. Swine resuscitated with otofHb exhibited the rapid onset of marked systemic hypertension . The blood pressure rose within seconds...virtual absence of red blood cells (3), hemoglobin solutions have produced hypertension irn animals or have not supported an increase in cardiac output...with blood volume expansion. Half of all the humans administered hemoglobin in published trials demonstrated hypertension (4), and a recent human

  5. Increasing pesticide-resistant ectoparasitic infections may increase pesticide poisoning risks in children.

    PubMed

    Diaz, James H

    2008-01-01

    Head louse and scabies mite infestations are common among pre-school and school-age children, and topical pesticides are frequently prescribed to treat such conditions. Ectoparasite resistance to the safest and most commonly prescribed pyrethrin/pyrethroid pesticides for ectoparasitic infections has, however, been increasing since the 1980s. The increasing resistance of these arthropods to the safest pesticides may lead to greater use of more toxic, alternative pesticides to control infestations and to prevent institutional outbreaks. MEDLINE and Cochrane searches, 1966-2008, were conducted to assess the impact of increasing pesticide resistance on prescribing practices for ectoparasitic infections and to describe the evolving global epidemiology of pediatric poisonings by more toxic pediculicides and miticides, including carbamates, organochlorines, and organophosphates. Pharmacists, physicians, and poison control personnel should be fully informed about increasing pesticide resistance among the most commonly encountered ectoparasites of children and the institutionalized and be prepared to prevent and to treat accidental home and institutional pesticide poisonings with more toxic pesticides.

  6. Cystic Fibrosis Transmembrane Conductance Regulator in Sarcoplasmic Reticulum of Airway Smooth Muscle. Implications for Airway Contractility

    PubMed Central

    Cook, Daniel P.; Rector, Michael V.; Bouzek, Drake C.; Michalski, Andrew S.; Gansemer, Nicholas D.; Reznikov, Leah R.; Li, Xiaopeng; Stroik, Mallory R.; Ostedgaard, Lynda S.; Abou Alaiwa, Mahmoud H.; Thompson, Michael A.; Prakash, Y. S.; Krishnan, Ramaswamy; Meyerholz, David K.; Seow, Chun Y.

    2016-01-01

    Rationale: An asthma-like airway phenotype has been described in people with cystic fibrosis (CF). Whether these findings are directly caused by loss of CF transmembrane conductance regulator (CFTR) function or secondary to chronic airway infection and/or inflammation has been difficult to determine. Objectives: Airway contractility is primarily determined by airway smooth muscle. We tested the hypothesis that CFTR is expressed in airway smooth muscle and directly affects airway smooth muscle contractility. Methods: Newborn pigs, both wild type and with CF (before the onset of airway infection and inflammation), were used in this study. High-resolution immunofluorescence was used to identify the subcellular localization of CFTR in airway smooth muscle. Airway smooth muscle function was determined with tissue myography, intracellular calcium measurements, and regulatory myosin light chain phosphorylation status. Precision-cut lung slices were used to investigate the therapeutic potential of CFTR modulation on airway reactivity. Measurements and Main Results: We found that CFTR localizes to the sarcoplasmic reticulum compartment of airway smooth muscle and regulates airway smooth muscle tone. Loss of CFTR function led to delayed calcium reuptake following cholinergic stimulation and increased myosin light chain phosphorylation. CFTR potentiation with ivacaftor decreased airway reactivity in precision-cut lung slices following cholinergic stimulation. Conclusions: Loss of CFTR alters porcine airway smooth muscle function and may contribute to the airflow obstruction phenotype observed in human CF. Airway smooth muscle CFTR may represent a therapeutic target in CF and other diseases of airway narrowing. PMID:26488271

  7. Linoleic acid supplementation results in increased arachidonic acid and eicosanoid production in CF airway cells and in cftr−/− transgenic mice

    PubMed Central

    Zaman, Munir M.; Martin, Camilia R.; Andersson, Charlotte; Bhutta, Abdul Q.; Cluette-Brown, Joanne E.; Laposata, Michael

    2010-01-01

    Cystic fibrosis (CF) patients display a fatty acid imbalance characterized by low linoleic acid levels and variable changes in arachidonic acid. This led to the recommendation that CF patients consume a high-fat diet containing >6% linoleic acid. We hypothesized that increased conversion of linoleic acid to arachidonic acid in CF leads to increased levels of arachidonate-derived proinflammatory metabolites and that this process is exacerbated by increasing linoleic acid levels in the diet. To test this hypothesis, we determined the effect of linoleic acid supplementation on downstream proinflammatory biomarkers in two CF models: 1) in vitro cell culture model using 16HBE14o− sense [wild-type (WT)] and antisense (CF) human airway epithelial cells; and 2) in an in vivo model using cftr−/− transgenic mice. Fatty acids were analyzed by gas chromatography-mass spectrometry (GC/MS), and IL-8 and eicosanoids were measured by ELISA. Neutrophils were quantified in bronchoalveolar lavage fluid from knockout mice following linoleic acid supplementation and exposure to aerosolized Pseudomonas LPS. Linoleic acid supplementation increased arachidonic acid levels in CF but not WT cells. IL-8, PGE2, and PGF2α secretion were increased in CF compared with WT cells, with a further increase following linoleic acid supplementation. cftr−/− Mice supplemented with 100 mg of linoleic acid had increased arachidonic acid levels in lung tissue associated with increased neutrophil infiltration into the airway compared with control mice. These findings support the hypothesis that increasing linoleic acid levels in the setting of loss of cystic fibrosis transmembrane conductance regulator (CFTR) function leads to increased arachidonic acid levels and proinflammatory mediators. PMID:20656894

  8. Development of allergic airway disease in mice following antibiotic therapy and fungal microbiota increase: role of host genetics, antigen, and interleukin-13.

    PubMed

    Noverr, Mairi C; Falkowski, Nicole R; McDonald, Rod A; McKenzie, Andrew N; Huffnagle, Gary B

    2005-01-01

    Lending support to the hygiene hypothesis, epidemiological studies have demonstrated that allergic disease correlates with widespread use of antibiotics and alterations in fecal microbiota ("microflora"). Antibiotics also lead to overgrowth of the yeast Candida albicans, which can secrete potent prostaglandin-like immune response modulators, from the microbiota. We have recently developed a mouse model of antibiotic-induced gastrointestinal microbiota disruption that is characterized by stable increases in levels of gastrointestinal enteric bacteria and Candida. Using this model, we have previously demonstrated that microbiota disruption can drive the development of a CD4 T-cell-mediated airway allergic response to mold spore challenge in immunocompetent C57BL/6 mice without previous systemic antigen priming. The studies presented here address important questions concerning the universality of the model. To investigate the role of host genetics, we tested BALB/c mice. As with C57BL/6 mice, microbiota disruption promoted the development of an allergic response in the lungs of BALB/c mice upon subsequent challenge with mold spores. In addition, this allergic response required interleukin-13 (IL-13) (the response was absent in IL-13(-/-) mice). To investigate the role of antigen, we subjected mice with disrupted microbiota to intranasal challenge with ovalbumin (OVA). In the absence of systemic priming, only mice with altered microbiota developed airway allergic responses to OVA. The studies presented here demonstrate that the effects of microbiota disruption are largely independent of host genetics and the nature of the antigen and that IL-13 is required for the airway allergic response that follows microbiota disruption.

  9. Immobilisation increases yeast cells' resistance to dehydration-rehydration treatment.

    PubMed

    Borovikova, Diana; Rozenfelde, Linda; Pavlovska, Ilona; Rapoport, Alexander

    2014-08-20

    This study was performed with the goal of revealing if the dehydration procedure used in our new immobilisation method noticeably decreases the viability of yeast cells in immobilised preparations. Various yeasts were used in this research: Saccharomyces cerevisiae cells that were rather sensitive to dehydration and had been aerobically grown in an ethanol-containing medium, a recombinant strain of S. cerevisiae grown in aerobic conditions which were completely non-resistant to dehydration and an anaerobically grown bakers' yeast strain S. cerevisiae, as well as a fairly resistant Pichia pastoris strain. Experiments performed showed that immobilisation of all these strains essentially increased their resistance to a dehydration-rehydration treatment. The increase of cells' viability (compared with control cells dehydrated in similar conditions) was from 30 to 60%. It is concluded that a new immobilisation method, which includes a dehydration stage, does not lead to an essential loss of yeast cell viability. Correspondingly, there is no risk of losing the biotechnological activities of immobilised preparations. The possibility of producing dry, active yeast preparations is shown, for those strains that are very sensitive to dehydration and which can be used in biotechnology in an immobilised form. Finally, the immobilisation approach can be used for the development of efficient methods for the storage of recombinant yeast strains.

  10. Positive correlation of airway resistance and serum asymmetric dimethylarginine level in COPD patients with systemic markers of low-grade inflammation

    PubMed Central

    Tajti, Gabor; Gesztelyi, Rudolf; Pak, Krisztian; Papp, Csaba; Keki, Sandor; Szilasi, Magdolna Emma; Mikaczo, Angela; Fodor, Andrea; Szilasi, Maria; Zsuga, Judit

    2017-01-01

    The major feature of COPD is a progressive airflow limitation caused by chronic airway inflammation and consequent airway remodeling. Modified arginase and nitric oxide synthase (NOS) pathways are presumed to contribute to the inflammation and fibrosis. Asymmetric dimethylarginine (ADMA) may shunt L-arginine from the NOS pathway to the arginase one by uncoupling and competitive inhibition of NOS and by enhancing arginase activity. To attest the interplay of these pathways, the relationship between ADMA and airflow limitation, described by airway resistance (Raw), was investigated in a cohort of COPD patients. Every COPD patient willing to give consent to participate (n=74) was included. Case history, laboratory parameters, serum arginine and ADMA, pulmonary function (whole-body plethysmography), and disease-specific quality of life (St George’s Respiratory Questionnaire) were determined. Multiple linear regression was used to identify independent determinants of Raw. The final multiple model was stratified based on symptom control. The log Raw showed significant positive correlation with log ADMA in the whole sample (Pearson’s correlation coefficient: 0.25, P=0.03). This association remained significant after adjusting for confounders in the whole data set (β: 0.42; confidence interval [CI]: 0.06, 0.77; P=0.022) and in the worse-controlled stratum (β: 0.84; CI: 0.25, 1.43; P=0.007). Percent predicted value of forced expiratory flow between 25% and 75% of forced vital capacity showed that significant negative, elevated C-reactive protein exhibited significant positive relationship with Raw in the final model. Positive correlation of Raw with ADMA in COPD patients showing evidence of a systemic low-grade inflammation implies that ADMA contributes to the progression of COPD, probably by shunting L-arginine from the NOS pathway to the arginase one. PMID:28352168

  11. Increased oxidative DNA damage and decreased expression of base excision repair proteins in airway epithelial cells of women who cook with biomass fuels.

    PubMed

    Mukherjee, Bidisha; Bindhani, Banani; Saha, Hirak; Ray, Manas Ranjan

    2014-09-01

    To investigate whether biomass burning causes oxidative DNA damage and alters the expression of DNA base excision repair (BER) proteins in airway cells, sputum samples were collected from 80 premenopausal rural biomass-users and 70 age-matched control women who cooked with liquefied petroleum gas. Compared with control the airway cells of biomass-users showed increased DNA damage in alkaline comet assay. Biomass-users showed higher percentage of cells expressing oxidative DNA damage marker 8-oxoguanine and lower percentages of BER proteins OGG1 and APE1 by immunocytochemical staining. Reactive oxygen species (ROS) generation was doubled and level of superoxide dismutase was depleted significantly among biomass-users. The concentrations of particulate matters were higher in biomass-using households which positively correlated with ROS generation and negatively with BER proteins expressions. ROS generation was positively correlated with 8-oxoguanine and negatively with BER proteins suggesting cooking with biomass is a risk for genotoxicity among rural women in their child-bearing age.

  12. Advanced Wear-resistant Nanocomposites for Increased Energy Efficiency

    SciTech Connect

    Cook, B. A.; Harringa, J. L.; Russel, A. M.

    2012-12-01

    This report summarizes the work performed by an Ames-led project team under a 4-year DOE-ITP sponsored project titled, 'Advanced Wear-resistant Nanocomposites for Increased Energy Efficiency.' The Report serves as the project deliverable for the CPS agreement number 15015. The purpose of this project was to develop and commercialize a family of lightweight, bulk composite materials that are highly resistant to degradation by erosive and abrasive wear. These materials, based on AlMgB{sub 14}, are projected to save over 30 TBtu of energy per year when fully implemented in industrial applications, with the associated environmental benefits of eliminating the burning of 1.5 M tons/yr of coal and averting the release of 4.2 M tons/yr of CO{sub 2} into the air. This program targeted applications in the mining, drilling, machining, and dry erosion applications as key platforms for initial commercialization, which includes some of the most severe wear conditions in industry. Production-scale manufacturing of this technology has begun through a start-up company, NewTech Ceramics (NTC). This project included providing technical support to NTC in order to facilitate cost-effective mass production of the wear-resistant boride components. Resolution of issues related to processing scale-up, reduction in energy intensity during processing, and improving the quality and performance of the composites, without adding to the cost of processing were among the primary technical focus areas of this program. Compositional refinements were also investigated in order to achieve the maximum wear resistance. In addition, synthesis of large-scale, single-phase AlMgB{sub 14} powder was conducted for use as PVD sputtering targets for nanocoating applications.

  13. Sensitivity of global climate model simulations to increased stomatal resistance and CO{sub 2} increases

    SciTech Connect

    Henderson-Sellers, A.; McGuffie, K.; Gross, C.

    1995-07-01

    Increasing levels of atmospheric CO{sub 2} will not only modify climate, they will also likely increase the water-use efficiency of plants by decreasing stomatal openings. The effect of the imposition of {open_quotes}doubled stomatal resistance{close_quotes} on climate is investigated in off-line simulations with the Biosphere-Atmosphere Transfer Scheme (BATS) and in two sets of global climate model simulations: for present-day and doubled atmospheric CO{sub 2} concentrations. The anticipated evapotranspiration decrease is seen most clearly in the boreal forests in the summer although, for the present-day climate (but not at 2 x CO{sub 2}), there are also noticeable responses in the tropical forests in South America. In the latitude zone 44{degrees}N to 58{degrees}N, evapotranspiration decreases by -15 W m{sup 2}, temperatures increase by =2 K, and the sensible heat flux by +15 W m{sup {minus}2}. Soil moisture is often, but less extensively, increased, which can cause increases in runoff. The responses at 2 x CO{sub 2} are larger in the 44{degrees}N to 58{degrees}N zone than elsewhere. Globally, the impact of imposing a doubled stomatal resistance in the present-day climate is an increase in the annually averaged surface air temperature of 0.13 K and a reduction in total precipitation of -0.82%. If both the atmospheric CO{sub 2} content and the stomatal resistance are doubled, the global response in surface air temperature and precipitation are +2.72 K and +5.01% compared with +2.67 K and + 7.73% if CO{sub 2} is doubled but stomatal resistance remains unchanged as in the usual {open_quotes}greenhouse{close_quotes} experiment. Doubling stomatal resistance as well as atmospheric CO{sub 2} results in increased soil moisture in northern midlatitudes in summer. 40 refs.. 17 figs., 5 tabs.

  14. Induction of periodic breathing during sleep causes upper airway obstruction in humans.

    PubMed

    Onal, E; Burrows, D L; Hart, R H; Lopata, M

    1986-10-01

    To test the hypothesis that occlusive apneas result from sleep-induced periodic breathing in association with some degree of upper airway compromise, periodic breathing was induced during non-rapid-eye-movement (NREM) sleep by administering hypoxic gas mixtures with and without applied external inspiratory resistance (9 cmH2O X l-1 X s) in five normal male volunteers. In addition to standard polysomnography for sleep staging and respiratory pattern monitoring, esophageal pressure, tidal volume (VT), and airflow were measured via an esophageal catheter and pneumotachograph, respectively, with the latter attached to a tight-fitting face mask, allowing calculation of total pulmonary system resistance (Rp). During stage I/II NREM sleep minimal period breathing was evident in two of the subjects; however, in four subjects during hypoxia and/or relief from hypoxia, with and without added resistance, pronounced periodic breathing developed with waxing and waning of VT, sometimes with apneic phases. Resistive loading without hypoxia did not cause periodicity. At the nadir of periodic changes in VT, Rp was usually at its highest and there was a significant linear relationship between Rp and 1/VT, indicating the development of obstructive hypopneas. In one subject without added resistance and in the same subject and in another during resistive loading, upper airway obstruction at the nadir of the periodic fluctuations in VT was observed. We conclude that periodic breathing resulting in periodic diminution of upper airway muscle activity is associated with increased upper airway resistance that predisposes upper airways to collapse.

  15. Airway smooth muscle growth in asthma: proliferation, hypertrophy, and migration.

    PubMed

    Bentley, J Kelley; Hershenson, Marc B

    2008-01-01

    Increased airway smooth muscle mass is present in fatal and non-fatal asthma. However, little information is available regarding the cellular mechanism (i.e., hyperplasia vs. hypertrophy). Even less information exists regarding the functional consequences of airway smooth muscle remodeling. It would appear that increased airway smooth muscle mass would tend to increase airway narrowing and airflow obstruction. However, the precise effects of increased airway smooth muscle mass on airway narrowing are not known. This review will consider the evidence for airway smooth muscle cell proliferation and hypertrophy in asthma, potential functional effects, and biochemical mechanisms.

  16. Oral airway flow dynamics in healthy humans.

    PubMed

    Amis, T C; O'Neill, N; Wheatley, J R

    1999-02-15

    1. Oral airway resistance (RO) is an important determinant of oro-nasal partitioning of airflow (e.g. during exercise and sleep); however, little is known of factors influencing its magnitude and measurement. 2. We developed a non-invasive standardized technique for measuring RO (based on a modification of posterior rhinomanometry) and examined inspiratory RO in 17 healthy male subjects (age, 36 +/- 2 years (mean +/- s.e.m.); height, 177 +/- 2 cm; weight, 83 +/- 3 kg). 3. Inspiratory RO (at 0.4 l s-1) was 0.86 +/- 0.23 cmH2O l-1 s-1 during resting mouthpiece breathing in the upright posture. RO was unaffected by assumption of the supine posture, tended to decrease with head and neck extension and increased to 1.22 +/- 0.19 cmH2O l-1 s-1 (n = 10 subjects, P < 0.01) with 40-45 deg of head and neck flexion. When breathing via a mouth-mask RO was 2.98 +/- 0.42 cmH2O l-1 s-1 (n = 7) and not significantly different from nasal airway resistance. 4. Thus, in awake healthy male subjects with constant jaw position, RO is unaffected by body posture but increases with modest degrees of head and neck flexion. This influence on upper airway patency may be important when oral route breathing is associated with alterations in head and neck position, e.g. during sleep.

  17. Mucoidy, Quorum Sensing, Mismatch Repair and Antibiotic Resistance in Pseudomonas aeruginosa from Cystic Fibrosis Chronic Airways Infections

    PubMed Central

    Feliziani, Sofía; Sola, Claudia; Bocco, José L.; Montanaro, Patricia; Canigia, Liliana Fernández; Argaraña, Carlos E.; Smania, Andrea M.

    2010-01-01

    Survival of Pseudomonas aeruginosa in cystic fibrosis (CF) chronic infections is based on a genetic adaptation process consisting of mutations in specific genes, which can produce advantageous phenotypic switches and ensure its persistence in the lung. Among these, mutations inactivating the regulators MucA (alginate biosynthesis), LasR (quorum sensing) and MexZ (multidrug-efflux pump MexXY) are the most frequently observed, with those inactivating the DNA mismatch repair system (MRS) being also highly prevalent in P. aeruginosa CF isolates, leading to hypermutator phenotypes that could contribute to this adaptive mutagenesis by virtue of an increased mutation rate. Here, we characterized the mutations found in the mucA, lasR, mexZ and MRS genes in P. aeruginosa isolates obtained from Argentinean CF patients, and analyzed the potential association of mucA, lasR and mexZ mutagenesis with MRS-deficiency and antibiotic resistance. Thus, 38 isolates from 26 chronically infected CF patients were characterized for their phenotypic traits, PFGE genotypic patterns, mutations in the mucA, lasR, mexZ, mutS and mutL gene coding sequences and antibiotic resistance profiles. The most frequently mutated gene was mexZ (79%), followed by mucA (63%) and lasR (39%) as well as a high prevalence (42%) of hypermutators being observed due to loss-of-function mutations in mutL (60%) followed by mutS (40%). Interestingly, mutational spectra were particular to each gene, suggesting that several mechanisms are responsible for mutations during chronic infection. However, no link could be established between hypermutability and mutagenesis in mucA, lasR and mexZ, indicating that MRS-deficiency was not involved in the acquisition of these mutations. Finally, although inactivation of mucA, lasR and mexZ has been previously shown to confer resistance/tolerance to antibiotics, only mutations in MRS genes could be related to an antibiotic resistance increase. These results help to unravel the

  18. Decreasing SMPD1 activity in BEAS-2B bronchial airway epithelial cells results in increased NRF2 activity, cytokine synthesis and neutrophil recruitment.

    PubMed

    MacFadden-Murphy, Elyse; Roussel, Lucie; Martel, Guy; Bérubé, Julie; Rousseau, Simon

    2017-01-22

    Niemann-Pick disease (NPD) type B is a rare autosomal recessive disease characterized by variable levels of impairment in sphingomyelin phosphodiesterase 1 (SMPD1) activity. Lung involvement is the most important prognostic factor in NPD-B, with recurrent respiratory infections starting in infancy being the major cause of morbidity and mortality. We hypothesized that decreased SMPD1 activity impaired airway epithelium host defense response. SMPD1 activity was reduced using inducible shRNA. Surprisingly, decreasing SMPD1 activity by 50%, resulted in increased neutrophil recruitment, both at baseline and in response to bacterial stimulation. This correlated with elevated levels of cytokine mRNA shown to contribute to neutrophil recruitment in unstimulated (e.g. IL-8 and GRO-α) and infected cells (e.g. IL-8, GRO-α, GM-CSF and CCL20). Instead of preventing the host defence responses, decreased SMPD1 activity results in an inflammatory response even in the absence of infection. Moreover, decreasing SMPD1 activity resulted in a pro-oxidative shift. Accordingly, expression of an inactive mutant, SMPD1[L225P] but not the WT enzyme increased activation of the antioxidant transcription factor NRF2. Therefore, decreasing SMPD1 activity by 50% in airway epithelial cells, the equivalent of the loss of one allele, results in the accumulation of oxidants that activates NRF2 and a concomitant increased cytokine production as well as neutrophil recruitment. This can result in a chronic inflammatory state that impairs host defence similar to scenarios observe in other chronic inflammatory lung disease such as Chronic Obstructive Pulmonary Disease or Cystic Fibrosis.

  19. Low-salt diet increases insulin resistance in healthy subjects.

    PubMed

    Garg, Rajesh; Williams, Gordon H; Hurwitz, Shelley; Brown, Nancy J; Hopkins, Paul N; Adler, Gail K

    2011-07-01

    Low-salt (LS) diet activates the renin-angiotensin-aldosterone and sympathetic nervous systems, both of which can increase insulin resistance (IR). We investigated the hypothesis that LS diet is associated with an increase in IR in healthy subjects. Healthy individuals were studied after 7 days of LS diet (urine sodium <20 mmol/d) and 7 days of high-salt (HS) diet (urine sodium >150 mmol/d) in a random order. Insulin resistance was measured after each diet and compared statistically, unadjusted and adjusted for important covariates. One hundred fifty-two healthy men and women, aged 39.1 ± 12.5 years (range, 18-65) and with body mass index of 25.3 ± 4.0 kg/m(2), were included in this study. Mean (SD) homeostasis model assessment index was significantly higher on LS compared with HS diet (2.8 ± 1.6 vs 2.4 ± 1.7, P < .01). Serum aldosterone (21.0 ± 14.3 vs 3.4 ± 1.5 ng/dL, P < .001), 24-hour urine aldosterone (63.0 ± 34.0 vs 9.5 ± 6.5 μg/d, P < .001), and 24-hour urine norepinephrine excretion (78.0 ± 36.7 vs 67.9 ± 39.8 μg/d, P < .05) were higher on LS diet compared with HS diet. Low-salt diet was significantly associated with higher homeostasis model assessment index independent of age, sex, blood pressure, body mass index, serum sodium and potassium, serum angiotensin II, plasma renin activity, serum and urine aldosterone, and urine epinephrine and norepinephrine. Low-salt diet is associated with an increase in IR. The impact of our findings on the pathogenesis of diabetes and cardiovascular disease needs further investigation.

  20. Adropin deficiency is associated with increased adiposity and insulin resistance.

    PubMed

    Ganesh Kumar, K; Zhang, Jingying; Gao, Su; Rossi, Jari; McGuinness, Owen P; Halem, Heather H; Culler, Michael D; Mynatt, Randall L; Butler, Andrew A

    2012-07-01

    Adropin is a secreted peptide that improves hepatic steatosis and glucose homeostasis when administered to diet-induced obese mice. It is not clear if adropin is a peptide hormone regulated by signals of metabolic state. Moreover, the significance of a decline in adropin expression with obesity with respect to metabolic disease is also not clear. We investigated the regulation of serum adropin by metabolic status and diet. Serum adropin levels were high in chow-fed conditions and were suppressed by fasting and diet-induced obesity (DIO). High adropin levels were observed in mice fed a high-fat low carbohydrate diet, whereas lower levels were observed in mice fed a low-fat high carbohydrate diet. To investigate the role of adropin deficiency in metabolic homeostasis, we generated adropin knockout mice (AdrKO) on the C57BL/6J background. AdrKO displayed a 50%-increase in increase in adiposity, although food intake and energy expenditure were normal. AdrKO also exhibited dyslipidemia and impaired suppression of endogenous glucose production (EndoR(a)) in hyperinsulinemic-euglycemic clamp conditions, suggesting insulin resistance. While homo- and heterozygous carriers of the null adropin allele exhibited normal DIO relative to controls, impaired glucose tolerance associated with weight gain was more severe in both groups. In summary, adropin is a peptide hormone regulated by fasting and feeding. In fed conditions, adropin levels are regulated dietary macronutrients, and increase with dietary fat content. Adropin is not required for regulating food intake, however, its functions impact on adiposity and are involved in preventing insulin resistance, dyslipidemia, and impaired glucose tolerance.

  1. Adropin Deficiency Is Associated With Increased Adiposity and Insulin Resistance

    PubMed Central

    Kumar, K. Ganesh; Zhang, Jingying; Gao, Su; Rossi, Jari; McGuinness, Owen P.; Halem, Heather H.; Culler, Michael D.; Mynatt, Randall L.; Butler, Andrew A.

    2014-01-01

    Adropin is a secreted peptide that improves hepatic steatosis and glucose homeostasis when administered to diet-induced obese mice. It is not clear if adropin is a peptide hormone regulated by signals of metabolic state. Moreover, the significance of a decline in adropin expression with obesity with respect to metabolic disease is also not clear. We investigated the regulation of serum adropin by metabolic status and diet. Serum adropin levels were high in chow-fed conditions and were suppressed by fasting and diet-induced obesity (DIO). High adropin levels were observed in mice fed a high-fat low carbohydrate diet, whereas lower levels were observed in mice fed a low-fat high carbohydrate diet. To investigate the role of adropin deficiency in metabolic homeostasis, we generated adropin knockout mice (AdrKO) on the C57BL/6J background. AdrKO displayed a 50%-increase in increase in adiposity, although food intake and energy expenditure were normal. AdrKO also exhibited dyslipidemia and impaired suppression of endogenous glucose production (EndoRa) in hyperinsulinemic–euglycemic clamp conditions, suggesting insulin resistance. While homo- and heterozygous carriers of the null adropin allele exhibited normal DIO relative to controls, impaired glucose tolerance associated with weight gain was more severe in both groups. In summary, adropin is a peptide hormone regulated by fasting and feeding. In fed conditions, adropin levels are regulated dietary macronutrients, and increase with dietary fat content. Adropin is not required for regulating food intake, however, its functions impact on adiposity and are involved in preventing insulin resistance, dyslipidemia, and impaired glucose tolerance. PMID:22318315

  2. Airflow behavior changes in upper airway caused by different head and neck positions: Comparison by computational fluid dynamics.

    PubMed

    Wei, Wei; Huang, Shi-Wei; Chen, Lian-Hua; Qi, Yang; Qiu, Yi-Min; Li, Shi-Tong

    2017-02-08

    The feasibility of computational fluid dynamics (CFD) to evaluate airflow characteristics in different head and neck positions has not been established. This study compared the changes in volume and airflow behavior of the upper airway by CFD simulation to predict the influence of anatomical and physiological airway changes due to different head-neck positions on mechanical ventilation. One awake volunteer with no risk of difficult airway underwent computed tomography in neutral position, extension position (both head and neck extended), and sniffing position (head extended and neck flexed). Three-dimensional airway models of the upper airway were reconstructed. The total volume (V) and narrowest area (Amin) of the airway models were measured. CFD simulation with an Spalart-Allmaras model was performed to characterize airflow behavior in neutral, extension, and sniffing positions of closed-mouth and open-mouth ventilation. The comparison result for V was neutral increasing were more obvious in neutral than sniffing or extension position at the same airflow rate. In sniffing position, pressure differences decreased and velocity remained almost constant. Recirculation airflow was generated near the subglottic region in neutral and extension positions. Sniffing position improves airway patency by increasing airway volume and decreasing airway resistance, suggesting that sniffing position may be the optimal choice for mask ventilation.

  3. Potato tuber herbivory increases resistance to aboveground lepidopteran herbivores.

    PubMed

    Kumar, Pavan; Ortiz, Erandi Vargas; Garrido, Etzel; Poveda, Katja; Jander, Georg

    2016-09-01

    Plants mediate interactions between aboveground and belowground herbivores. Although effects of root herbivory on foliar herbivores have been documented in several plant species, interactions between tuber-feeding herbivores and foliar herbivores are rarely investigated. We report that localized tuber damage by Tecia solanivora (Guatemalan tuber moth) larvae reduced aboveground Spodoptera exigua (beet armyworm) and Spodoptera frugiperda (fall armyworm) performance on Solanum tuberosum (potato). Conversely, S. exigua leaf damage had no noticeable effect on belowground T. solanivora performance. Tuber infestation by T. solanivora induced systemic plant defenses and elevated resistance to aboveground herbivores. Lipoxygenase 3 (Lox3), which contributes to the synthesis of plant defense signaling molecules, had higher transcript abundance in T. solanivora-infested leaves and tubers than in equivalent control samples. Foliar expression of the hydroxycinnamoyl-CoA quinate hydroxycinnamoyl transferase (HQT) and 3-hydroxy-3-methylglutaryl CoA reductase I (HMGR1) genes, which are involved in chlorogenic acid and steroidal glycoalkaloid biosynthesis, respectively, also increased in response to tuber herbivory. Leaf metabolite profiling demonstrated the accumulation of unknown metabolites as well as the known potato defense compounds chlorogenic acid, α-solanine, and α-chaconine. When added to insect diet at concentrations similar to those found in potato leaves, chlorogenic acid, α-solanine, and α-chaconine all reduced S. exigua larval growth. Thus, despite the fact that tubers are a metabolic sink tissue, T. solanivora feeding elicits a systemic signal that induces aboveground resistance against S. exigua and S. frugiperda by increasing foliar abundance of defensive metabolites.

  4. Effects of continuous negative airway pressure-related lung deflation on upper airway collapsibility.

    PubMed

    Sériès, F; Marc, I

    1993-09-01

    Continuous negative airway pressure (CNAP) causes a decrease in lung volume, which is known to increase upper airway resistance by itself. We studied how this lung volume change could modify upper airway collapsibility with five normal awake subjects. In a first trial, pressure in a nasal mask (Pm) was progressively decreased in 3- to 5-cmH2O steps (CNAP). In a second trial, changes in lung volumes resulting from CNAP were prevented by applying simultaneously an equivalent level of negative extrathoracic pressure into a poncho-type respirator [isovolumetric CNAP (CNAPisovol)]. For each trial, we examined the relationship between the maximal inspiratory airflow of each flow-limited inspiratory cycle and the corresponding Pm by least-squares linear regression analysis and determined the critical pressure. We also determined the Pm threshold corresponding to the first Pm value below which flow limitation occurred. Flow limitation was observed in each subject with CNAP but in only two subjects with CNAPisovol. In these two subjects, the Pm threshold values were -20 and -9 cmH2O with CNAP and -39 and -16 cmH2O with CNAPisovol, respectively. Critical pressures for the same two subjects were -161 and -96 cmH2O with CNAP and -202 and -197 cmH2O with CNAPisovol, respectively. We conclude that CNAP-induced decreases in lung volume increase upper airway collapsibility.

  5. Apoptosis and the Airway Epithelium

    PubMed Central

    White, Steven R.

    2011-01-01

    The airway epithelium functions as a barrier and front line of host defense in the lung. Apoptosis or programmed cell death can be elicited in the epithelium as a response to viral infection, exposure to allergen or to environmental toxins, or to drugs. While apoptosis can be induced via activation of death receptors on the cell surface or by disruption of mitochondrial polarity, epithelial cells compared to inflammatory cells are more resistant to apoptotic stimuli. This paper focuses on the response of airway epithelium to apoptosis in the normal state, apoptosis as a potential regulator of the number and types of epithelial cells in the airway, and the contribution of epithelial cell apoptosis in important airways diseases. PMID:22203854

  6. Respiratory and upper airways impedance responses to methacholine inhalation in spontaneously breathing cats.

    PubMed

    Loos, N; Peslin, R; Marchal, F

    2000-06-01

    The upper airways may contribute to the increase in respiratory resistance induced by methacholine (Mch). The aim of this study was to simultaneously assess the Mch response of upper airways and lower respiratory resistances (Rua, Rrs,lo) and reactances (Xua, Xrs,lo), and to test whether the change of total respiratory resistance and reactance after Mch were affected by upper airways mechanisms. Seven cats breathing spontaneously were studied under chloralose, urethane anaesthesia. Forced oscillations were generated at 20 Hz by a loud-speaker connected to the pharyngeal cavity. A pneumotachograph was placed between rostral and caudal extremities of the severed cervical trachea. Pressure drops were measured across the upper airways and across the lower respiratory system. Rua, Xua, Rrs,lo and Xrs,lo were obtained after nebulized normal saline and Mch administered directly through the tracheostomy. The analysis focused on Mch tests showing clear positive upper airways response. Volume and flow dependence of Rrs,lo and Rua were assessed during tidal inspiration using multiple linear regression analysis. After Mch, Rrs,lo increased and became negatively volume dependent, while the increase in Rua was associated with no significant change in volume dependence; Xrs,lo became negative while Xua did not change. The upper airways response to methacholine may thus contribute to the increase in total respiratory resistance but may not account for either its negative volume dependence or the decrease in total resistance. It is surmised that these features more specifically reflect alterations in respiratory mechanics occurring at the level of the intrathoracic airways.

  7. Investigating the geometry of pig airways using computed tomography

    NASA Astrophysics Data System (ADS)

    Mansy, Hansen A.; Azad, Md Khurshidul; McMurray, Brandon; Henry, Brian; Royston, Thomas J.; Sandler, Richard H.

    2015-03-01

    Numerical modeling of sound propagation in the airways requires accurate knowledge of the airway geometry. These models are often validated using human and animal experiments. While many studies documented the geometric details of the human airways, information about the geometry of pig airways is scarcer. In addition, the morphology of animal airways can be significantly different from that of humans. The objective of this study is to measure the airway diameter, length and bifurcation angles in domestic pigs using computed tomography. After imaging the lungs of 3 pigs, segmentation software tools were used to extract the geometry of the airway lumen. The airway dimensions were then measured from the resulting 3 D models for the first 10 airway generations. Results showed that the size and morphology of the airways of different animals were similar. The measured airway dimensions were compared with those of the human airways. While the trachea diameter was found to be comparable to the adult human, the diameter, length and branching angles of other airways were noticeably different from that of humans. For example, pigs consistently had an early airway branching from the trachea that feeds the superior (top) right lung lobe proximal to the carina. This branch is absent in the human airways. These results suggested that the human geometry may not be a good approximation of the pig airways and may contribute to increasing the errors when the human airway geometric values are used in computational models of the pig chest.

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

    EPA Science Inventory

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

  9. The Phillips airway.

    PubMed

    Haridas, R P; Wilkinson, D J

    2012-07-01

    The Phillips airway was developed by George Ramsay Phillips. There is no known original description of the airway and the earliest known reference to it is from 1919. The airway and its modifications are described.

  10. Blockage of upper airway

    MedlinePlus

    ... Airway obstruction - acute upper Images Throat anatomy Choking Respiratory system References Cukor J, Manno M. Pediatric respiratory emergencies: upper airway obstruction and infections. In: Marx ...

  11. Airway malacia in children with achondroplasia.

    PubMed

    Dessoffy, Kimberly E; Modaff, Peggy; Pauli, Richard M

    2014-02-01

    This study was undertaken to assess the frequency of airway malacia in infants and young children with achondroplasia, a population well known to be at risk for a variety of respiratory problems. We also wished to evaluate what, if any, contribution airway malacia makes to the complex respiratory issues that may be present in those with achondroplasia. Retrospective chart review of all infants and young children with achondroplasia who were assessed through the Midwest Regional Bone Dysplasia Clinics from 1985 through 2012 (n = 236) was completed. Records of comprehensive clinical examinations, polysomnographic assessments, and airway visualization were reviewed and abstracted using a data collection form. Analyses were completed comparing the group with and those without evidence for airway malacia. Thirteen of 236 patients (5.5%) were found to have airway malacia. Most of those affected had lower airway involvement (9/13). The presence of airway malacia was correlated with an increased occurrence of obstructive sleep apnea as well as need for oxygen supplementation, airway surgeries and tracheostomy placement. Although estimates of the frequency of airway malacia in the general population are limited, its frequency in children with achondroplasia appears to be much higher than any published general population estimate. The presence of airway malacia appears to confound other breathing abnormalities in this population and results in the need for more invasive airway treatments.

  12. Pharmacodynamics of Itraconazole against Aspergillus fumigatus in an In Vitro Model of the Human Alveolus: Perspectives on the Treatment of Triazole-Resistant Infection and Utility of Airway Administration

    PubMed Central

    Al-Nakeeb, Zaid; Sudan, Ajay; Jeans, Adam R.; Gregson, Lea; Goodwin, Joanne; Warn, Peter A.; Felton, Timothy W.; Howard, Susan J.

    2012-01-01

    Itraconazole is used for the prevention and treatment of infections caused by Aspergillus fumigatus. An understanding of the pharmacodynamics of itraconazole against wild-type and triazole-resistant strains provides a basis for innovative therapeutic strategies for treatment of infections. An in vitro model of the human alveolus was used to define the pharmacodynamics of itraconazole. Galactomannan was used as a biomarker. The effect of systemic and airway administration of itraconazole was assessed, as was a combination of itraconazole administered to the airway and systemically administered 5FC. Systemically administered itraconazole against the wild type induced a concentration-dependent decline in galactomannan in the alveolar and endothelial compartments. No exposure-response relationships were apparent for the L98H, M220T, or G138C mutant. The administration of itraconazole to the airway resulted in comparable exposure-response relationships to those observed with systemic therapy. This was achieved without detectable concentrations of drug within the endothelial compartment. The airway administration of itraconazole resulted in a definite but submaximal effect in the endothelial compartment against the L98H mutant. The administration of 5FC resulted in a concentration-dependent decline in galactomannan in both the alveolar and endothelial compartments. The combination of airway administration of itraconazole and systemically administered 5FC was additive. Systemic administration of itraconazole is ineffective against Cyp51 mutants. The airway administration of itraconazole is effective for the treatment of wild-type strains and appears to have some activity against the L98H mutants. Combination with other agents, such as 5FC, may enable the attainment of near-maximal antifungal activity. PMID:22615280

  13. Activation of muscarinic receptors in porcine airway smooth muscle elicits a transient increase in phospholipase D activity.

    PubMed

    Mamoon, A M; Smith, J; Baker, R C; Farley, J M

    1999-01-01

    Phospholipase D (PLD) is a phosphodiesterase that catalyses hydrolysis of phosphatidylcholine to produce phosphatidic acid and choline. In the presence of ethanol, PLD also catalyses the formation of phosphatidylethanol, which is a unique characteristic of this enzyme. Muscarinic receptor-induced changes in the activity of PLD were investigated in porcine tracheal smooth muscle by measuring the formation of [3H]phosphatidic acid ([3H]PA) and [3H]phosphatidylethanol ([3H]PEth) after labeling the muscle strips with [3H]palmitic acid. The cholinergic receptor agonist acetylcholine (Ach) significantly but transiently increased formation of both [3H]PA and [3H]PEth in a concentration-dependent manner (>105-400% vs. controls in the presence of 10(-6) to 10(-4) M Ach) when pretreated with 100 mM ethanol. The Ach receptor-mediated increase in PLD activity was inhibited by atropine (10(-6) M), indicating that activation of PLD occurred via muscarinic receptors. Activation of protein kinase C (PKC) by phorbol-12-myristate-13-acetate (PMA) increased PLD activity that was effectively blocked by the PKC inhibitors calphostin C (10(-8) to 10(-6) M) and GFX (10(-8) to 10(-6) M). Ach-induced increases in PLD activity were also significantly, but incompletely, inhibited by both GFX and calphostin C. From the present data, we conclude that in tracheal smooth muscle, muscarinic acetylcholine receptor-induced PLD activation is transient in nature and coupled to these receptors via PKC. However, PKC activation is not solely responsible for Ach-induced activation of PLD in porcine tracheal smooth muscle.

  14. Exposure to multi-walled carbon nanotubes results in aggravation of airway inflammation and remodeling and in increased production of epithelium-derived innate cytokines in a mouse model of asthma.

    PubMed

    Ronzani, Carole; Casset, Anne; Pons, Françoise

    2014-02-01

    With the development of nanotechnologies, the potential adverse effects of nanomaterials such as multi-walled carbon nanotubes (MWCNT) on the respiratory tract of asthmatics are questioned. Furthermore, investigations are necessary to understand how these effects might arise. In the present study, we hypothesized that epithelium-derived innate cytokines that are considered as important promoting factors in allergy may contribute to an aggravating effect of MWCNT on asthma. We investigated in the mouse the effect of MWCNT on systemic immune response and airway inflammation and remodeling induced by the most frequent allergen so far associated with asthma, house dust mite (HDM), and we examined the production of the innate cytokines thymic stromal lymphopoietin (TSLP), IL-25, IL-33, and GM-CSF. Mice exposed to HDM exhibited specific IgG1 in serum and inflammatory cell infiltration, and increased Th2 cytokine production, mucus hyperproduction, and collagen deposition in the airways when compared to naïve animals. Levels of total IgG1 and HDM-specific IgG1, influx of macrophages, eosinophils and neutrophils, production of collagen, TGF-β1, and mucus, as well as levels of IL-13, eotaxin, and TARC, were dose-dependently increased in mice exposed to HDM and MWCNT compared to HDM alone. These effects were associated with an increased production of TSLP, IL-25, IL-33, and GM-CSF in the airways. Our data demonstrate that MWCNT increase in a dose-dependent manner systemic immune response, as well as airway allergic inflammation and remodeling induced by HDM in the mouse. Our data suggest also a role for airway epithelium and innate cytokines in these effects.

  15. Functional characterization of muscarinic receptors in murine airways.

    PubMed Central

    Garssen, J.; Van Loveren, H.; Gierveld, C. M.; Van der Vliet, H.; Nijkamp, F. P.

    1993-01-01

    1. The effects of muscarinic receptor antagonists considered to be selective for M1 receptors (pirenzepine; PZ), M2 receptors (AFDX-116), and for M3 receptors (4-diphenyl acetoxy N-methyl-piperidine (4-DAMP)) were used to investigate the existence of muscarinic receptors subtypes in murine airways. Atropine was used as a nonselective antagonist. The effects of these antagonists were studied upon tracheal contractions induced either by EFS (electric field stimulation) or by application of an exogenous cholinoceptor agonist (arecoline). 2. The muscarinic receptor antagonists tested inhibited arecoline-induced tracheal contractions with the following rank order of potency: 4-DAMP = atropine > pirenzepine = AFDX-116. The rank order of potency of the muscarinic antagonists used in inhibiting EFS-induced tracheal contractions was: 4-DAMP = atropine > PZ > AFDX-116. The pA2 values for these antagonists were similar when compared to the pA2 values determined in guinea-pig and bovine airway smooth muscle. 3. In addition to in vitro studies, the effects of inhalation of the different muscarinic antagonists on lung function parameters in vivo were investigated. Inhalation of 4-DAMP induced a decrease in airway resistance and an increase in lung compliance. In contrast, inhalation of AFDX-116 induced an increase in airway resistance and almost no change in lung compliance. Apart from some minor effects of atropine on airway resistance, atropine, PZ, and pilocarpine failed to induce changes in lung mechanics as determined by in vivo lung function measurements. 4. The results provide evidence for the existence of M3 receptors on murine tracheae that are involved in the contraction of tracheal smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 6 Figure 7 PMID:8495246

  16. Pets and cockroaches: two increasing causes of respiratory allergy in indoor environments. Characteristics of airways sensitization and prevention strategies.

    PubMed

    Liccardi, G; Cazzola, M; D'Amato, M; D'Amato, G

    2000-11-01

    The increasing prevalence of allergic sensitization to indoor allergens such as dust mites, pets and cockroaches is the result of the changes in indoor environments induced by human activities. The Westernized lifestyle and the increasing time spent indoors determine a reduction in natural air ventilation and, consequently, higher levels of allergen concentrations and longer exposure to allergens. The major cat allergen Fel d 1 is carried by small-dimension particles (< 5 microm diameter) that readily become airborne and persist immodified for a long time. Fel d 1 must be considered a ubiquitous allergen because it has been found in indoor environments and even in public places where a cat has never been kept. Recent research has demonstrated that clothing of cat owners may contribute to the dispersal of Fel d 1 in cat-free environments. Therefore, washing Fel d 1-contaminated clothes should be considered a simple and effective method for removing this allergen from clothing and, consequently, reducing the risk of Fel d 1 dispersion. Cockroach allergens constitute another important cause of environment-related respiratory allergy and may trigger asthma exacerbations in sensitized individuals. In the prevention of cockroach allergy, the use of chemical agents associated with an intensive vacuum cleaning of indoor environments is an important tool in removing cockroach material containing allergenic proteins. Early recognition of allergy-predisposed babies, monitoring indoor allergens and adequate strategies of allergen avoidance are likely to be important means for reducing the prevalence of bronchial asthma.

  17. A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-kappaB and hypoxia-inducible factor-1alpha.

    PubMed

    Lee, Kyung Sun; Kim, So Ri; Park, Hee Sun; Park, Seoung Ju; Min, Kyung Hoon; Lee, Ka Young; Choe, Yeong Hun; Hong, Sang Hyun; Han, Hyo Jin; Lee, Young Rae; Kim, Jong Suk; Atlas, Daphne; Lee, Yong Chul

    2007-12-31

    Reactive oxygen species (ROS) play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AD4 decreased the increases of the NF-kappaB and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-kappaB and HIF-1alpha as well as reducing ROS generation in allergic airway disease.

  18. Methods of increasing the erosion resistance of powder metallurgy steel

    SciTech Connect

    Kulu, P.A.

    1987-09-01

    The authors comparatively assess the effects of a variety of surface hardening methods--including carburizing, boriding, chromizing, and carbochromizing, as well as the flame, plasma arc, and detonation spraying of nickel and molybdenum coatings--on the wear, corrosion resistance, and pore structure of steel 45, and outline testing procedures used to arrive at their results.

  19. The role of depressed metabolism in increased radio resistance

    NASA Technical Reports Server (NTRS)

    Musacchia, X. J.

    1972-01-01

    Studies are presented of the physiology of depressed metabolism, radio-resistance in depressed metabolic states, comparative aspects of depressed metabolism, and gastrointestinal responses to ionizing radiation. Specific data cover helium-cold induced hypothermia in white rats and hamsters, and radiation responses and intestinal absorption in the gerbil.

  20. Anatomic Optical Coherence Tomography of Upper Airways

    NASA Astrophysics Data System (ADS)

    Chin Loy, Anthony; Jing, Joseph; Zhang, Jun; Wang, Yong; Elghobashi, Said; Chen, Zhongping; Wong, Brian J. F.

    The upper airway is a complex and intricate system responsible for respiration, phonation, and deglutition. Obstruction of the upper airways afflicts an estimated 12-18 million Americans. Pharyngeal size and shape are important factors in the pathogenesis of airway obstructions. In addition, nocturnal loss in pharyngeal muscular tone combined with high pharyngeal resistance can lead to collapse of the airway and periodic partial or complete upper airway obstruction. Anatomical optical coherence tomography (OCT) has the potential to provide high-speed three-dimensional tomographic images of the airway lumen without the use of ionizing radiation. In this chapter we describe the methods behind endoscopic OCT imaging and processing to generate full three dimensional anatomical models of the human airway which can be used in conjunction with numerical simulation methods to assess areas of airway obstruction. Combining this structural information with flow dynamic simulations, we can better estimate the site and causes of airway obstruction and better select and design surgery for patients with obstructive sleep apnea.

  1. Hyaluronan mediates airway hyperresponsiveness in oxidative lung injury

    PubMed Central

    Lazrak, Ahmed; Creighton, Judy; Yu, Zhihong; Komarova, Svetlana; Doran, Stephen F.; Aggarwal, Saurabh; Emala, Charles W.; Stober, Vandy P.; Trempus, Carol S.; Garantziotis, Stavros

    2015-01-01

    Chlorine (Cl2) inhalation induces severe oxidative lung injury and airway hyperresponsiveness (AHR) that lead to asthmalike symptoms. When inhaled, Cl2 reacts with epithelial lining fluid, forming by-products that damage hyaluronan, a constituent of the extracellular matrix, causing the release of low-molecular-weight fragments (L-HA, <300 kDa), which initiate a series of proinflammatory events. Cl2 (400 ppm, 30 min) exposure to mice caused an increase of L-HA and its binding partner, inter-α-trypsin-inhibitor (IαI), in the bronchoalveolar lavage fluid. Airway resistance following methacholine challenge was increased 24 h post-Cl2 exposure. Intratracheal administration of high-molecular-weight hyaluronan (H-HA) or an antibody against IαI post-Cl2 exposure decreased AHR. Exposure of human airway smooth muscle (HASM) cells to Cl2 (100 ppm, 10 min) or incubation with Cl2-exposed H-HA (which fragments it to L-HA) increased membrane potential depolarization, intracellular Ca2+, and RhoA activation. Inhibition of RhoA, chelation of intracellular Ca2+, blockade of cation channels, as well as postexposure addition of H-HA, reversed membrane depolarization in HASM cells. We propose a paradigm in which oxidative lung injury generates reactive species and L-HA that activates RhoA and Ca2+ channels of airway smooth muscle cells, increasing their contractility and thus causing AHR. PMID:25747964

  2. In Utero Estrogen Exposure Increases Antiestrogen Resistance by Inducing EMT

    DTIC Science & Technology

    2015-02-01

    line therapy in in utero EE2 exposed rats can prevent the development of TAM resistance. Briefly, pregnant Sprague Dawley dams (Harlan, USA) were fed ...day 10 and 20; after that all dams were fed control AIN93G diet. Pregnant dams gave birth to an average of 8 pups each in both treatment groups. All...year 2) from each of the treatment groups and treatment outcomes. Upon sacrifice, mammary glands, tumors, blood, liver , spleen, brain, ovary

  3. Failure of synthetic muramyl dipeptide to increase antibacterial resistance.

    PubMed Central

    Finger, H; Wirsing von König, C H

    1980-01-01

    Synthetic muranyl dipeptide, which potentiates antibody production and cellular immune responses at a dosage of 100 to 500 micrograms, did not enhance resistance to intravenous infection with a sublethal dose of 2 X 10(3) to 4 X 10(3) viable Listeria monocytogenes cells in mice when intraperitoneally injected either 20 min or 5 days before infection. Similarly, blockade of the mononuclear phagocyte system by dextran sulfate 500 could not be overcome by pretreatment with muramyl dipeptide. In contrast, dextran sulfate 500-induced loss of antibacterial resistance was found to be completely abolished by intraperitoneal injection of 3 X 10(9) killed Bordetella pertussis organisms when given 4 days before injection of dextran sulfate 500, i.e., 5 days before infection. B. pertussis were also effective in enhancing antibacterial resistance when administered 5 days before infection. The different behavior of the two adjuvants tested is assumed to be due to their different nonspecific proliferative capacities. Thus, B. pertussis are assumed to act by direct stimulation of the mononuclear phagocyte system whereas muramyl dipeptide does not. PMID:6155329

  4. A new removable airway stent

    PubMed Central

    Amundsen, Tore; Sørhaug, Sveinung; Leira, Håkon Olav; Tyvold, Stig Sverre; Langø, Thomas; Hammer, Tommy; Manstad-Hulaas, Frode; Mattsson, Erney

    2016-01-01

    Background Malignant airway obstruction is a feared complication and will most probably occur more frequently in the future because of increasing cancer incidence and increased life expectancy in cancer patients. Minimal invasive treatment using airway stents represents a meaningful and life-saving palliation. We present a new removable airway stent for improved individualised treatment. Methods To our knowledge, the new airway stent is the world's first knitted and uncovered self-expanding metal stent, which can unravel and be completely removed. In an in vivo model using two anaesthetised and spontaneously breathing pigs, we deployed and subsequently removed the stents by unravelling the device. The procedures were executed by flexible bronchoscopy in an acute and a chronic setting – a ‘proof-of-principle’ study. Results The new stent was easily and accurately deployed in the central airways, and it remained fixed in its original position. It was easy to unravel and completely remove from the airways without clinically significant complications. During the presence of the stent in the chronic study, granulation tissue was induced. This tissue disappeared spontaneously with the removal. Conclusions The new removable stent functioned according to its purpose and unravelled easily, and it was completely removed without significant technical or medical complications. Induced granulation tissue disappeared spontaneously. Further studies on animals and humans are needed to define its optimal indications and future use. PMID:27608269

  5. Molecular and physiological strategies to increase aluminum resistance in plants.

    PubMed

    Inostroza-Blancheteau, Claudio; Rengel, Zed; Alberdi, Miren; de la Luz Mora, María; Aquea, Felipe; Arce-Johnson, Patricio; Reyes-Díaz, Marjorie

    2012-03-01

    Aluminum (Al) toxicity is a primary limitation to plant growth on acid soils. Root meristems are the first site for toxic Al accumulation, and therefore inhibition of root elongation is the most evident physiological manifestation of Al toxicity. Plants may resist Al toxicity by avoidance (Al exclusion) and/or tolerance mechanisms (detoxification of Al inside the cells). The Al exclusion involves the exudation of organic acid anions from the root apices, whereas tolerance mechanisms comprise internal Al detoxification by organic acid anions and enhanced scavenging of free oxygen radicals. One of the most important advances in understanding the molecular events associated with the Al exclusion mechanism was the identification of the ALMT1 gene (Al-activated malate transporter) in Triticum aestivum root cells, which codes for a plasma membrane anion channel that allows efflux of organic acid anions, such as malate, citrate or oxalate. On the other hand, the scavenging of free radicals is dependent on the expression of genes involved in antioxidant defenses, such as peroxidases (e.g. in Arabidopsis thaliana and Nicotiana tabacum), catalases (e.g. in Capsicum annuum), and the gene WMnSOD1 from T. aestivum. However, other recent findings show that reactive oxygen species (ROS) induced stress may be due to acidic (low pH) conditions rather than to Al stress. In this review, we summarize recent findings regarding molecular and physiological mechanisms of Al toxicity and resistance in higher plants. Advances have been made in understanding some of the underlying strategies that plants use to cope with Al toxicity. Furthermore, we discuss the physiological and molecular responses to Al toxicity, including genes involved in Al resistance that have been identified and characterized in several plant species. The better understanding of these strategies and mechanisms is essential for improving plant performance in acidic, Al-toxic soils.

  6. Elevated Mutagenesis Does Not Explain the Increased Frequency of Antibiotic Resistant Mutants in Starved Aging Colonies

    PubMed Central

    Katz, Sophia; Hershberg, Ruth

    2013-01-01

    The frequency of mutants resistant to the antibiotic rifampicin has been shown to increase in aging (starved), compared to young colonies of Eschierchia coli. These increases in resistance frequency occur in the absence of any antibiotic exposure, and similar increases have also been observed in response to additional growth limiting conditions. Understanding the causes of such increases in the frequency of resistance is important for understanding the dynamics of antibiotic resistance emergence and spread. Increased frequency of rifampicin resistant mutants in aging colonies is cited widely as evidence of stress-induced mutagenesis (SIM), a mechanism thought to allow bacteria to increase mutation rates upon exposure to growth-limiting stresses. At the same time it has been demonstrated that some rifampicin resistant mutants are relatively fitter in aging compared to young colonies, indicating that natural selection may also contribute to increased frequency of rifampicin resistance in aging colonies. Here, we demonstrate that the frequency of mutants resistant to both rifampicin and an additional antibiotic (nalidixic-acid) significantly increases in aging compared to young colonies of a lab strain of Escherichia coli. We then use whole genome sequencing to demonstrate conclusively that SIM cannot explain the observed magnitude of increased frequency of resistance to these two antibiotics. We further demonstrate that, as was previously shown for rifampicin resistance mutations, mutations conferring nalidixic acid resistance can also increase fitness in aging compared to young colonies. Our results show that increases in the frequency of antibiotic resistant mutants in aging colonies cannot be seen as evidence of SIM. Furthermore, they demonstrate that natural selection likely contributes to increases in the frequency of certain antibiotic resistance mutations, even when no selection is exerted due to the presence of antibiotics. PMID:24244205

  7. Increase in larval gut proteolytic activities and Bti resistance in the Dengue fever mosquito.

    PubMed

    Tetreau, Guillaume; Stalinski, Renaud; David, Jean-Philippe; Després, Laurence

    2013-02-01

    The bioinsecticide Bacillus thuringiensis var. israelensis (Bti) is increasingly used worldwide for mosquito control. Although no established resistance to Bti has been described in the field so far, a resistant Aedes aegypti strain (LiTOX strain) was selected in the laboratory using field-collected leaf litter containing Bti toxins. This selected strain exhibits a moderate resistance level to Bti, but a high resistance level to individual Cry toxins. As Bti contains four different toxins, generalist resistance mechanisms affecting mosquito tolerance to different toxins were expected in the resistant strain. In the present work, we show that the resistant strain exhibits an increase of various gut proteolytic activities including trypsins, leucine-aminopeptidases, and carboxypeptidase A activities. These elevated proteolytic activities resulted in a faster activation of Cry4Aa protoxins while Cry4Ba or Cry11Aa were not affected. These results suggest that changes in proteolytic activities may contribute to Bti resistance in mosquitoes together with other mechanisms.

  8. Triggers of airway inflammation.

    PubMed

    Kerrebijn, K F

    1986-01-01

    Most asthmatics have hyperresponsive airways. This makes them more sensitive than non-asthmatics to bronchoconstricting environmental exposures which, in their turn, may enhance responsiveness. Airway inflammation is considered to be a key determinant of airway hyperresponsiveness: the fact that chronic airway inflammation in cystic fibrosis does not lead to airway hyperresponsiveness of any importance indicates, however, that the role of airway inflammation is complex and incompletely elucidated. The main inducers of airway inflammation are viral infections, antigens, occupational stimuli and pollutants. Although exercise, airway cooling and hyper- or hypotonic aerosols are potent stimuli of bronchoconstriction, it is questionable if airway inflammation is involved in their mode of action. Each of the above-mentioned stimuli is discussed, with emphasis laid on the relation of symptoms to mechanisms.

  9. Airway and tissue mechanics during physiological breathing and bronchoconstriction in dogs.

    PubMed

    Lutchen, K R; Suki, B; Zhang, Q; Peták, F; Daróczy, B; Hantos, Z

    1994-07-01

    In five open-chest dogs and with four to five alveolar capsules we used an optimal ventilator waveform (OVW) to follow frequency and tidal volume (VT) dependence of lung, airway, and tissue resistance (R) and elastance (E) before and during constant infusion of histamine (16 micrograms.kg-1.min-1). OVW contains sufficient flow energy between 0.234 and 4.7 Hz, avoids nonlinear harmonic interactions, and simultaneously ventilates with physiological VT. Each OVW breath permits a smooth estimate of frequency dependence of R and E for the whole lung. A constant-phase model analysis provided estimates of purely viscous resistance (Rvis), which represents the sum of airway resistance (Raw) and any purely newtonian component of tissue resistance (Rti), and parameters G and H, which govern frequency dependence of Rti and tissue elastance (Eti), respectively. Tissue structural damping (eta) is calculated as G/H. This model was applied to the whole lung and tissue impedance as estimated from each capsule. We found a small but inconsequential purely newtonian component of Rti, even during constriction. Four dogs showed a peak response at approximately 4 min in lung Rvis coupled (in time) to initial increases in G, H, eta, and airway inhomogeneities. In two of these dogs the response was severe. Tissue properties estimated from whole lung impedance (G, H, and eta) were nearly identical to values estimated from unobstructed capsules throughout infusion. By using a technique independent of alveolar capsules, our results indicate that a major if not dominant response to a constrictive agonist occurs in lung tissues, resulting in a large increase in Rti and Eti. With severe constriction, significant increases occur in Raw and airway inhomogeneities as well. Finally, separation of airway and tissue properties using input impedance estimated from the frequency-rich OVW avoids use of alveolar capsules and may prove an effective tool for partitioning airway and tissue properties in

  10. Fitness Cost of Resistance to Bt Cotton Linked with Increased Gossypol Content in Pink Bollworm Larvae

    PubMed Central

    Williams, Jennifer L.; Ellers-Kirk, Christa; Orth, Robert G.; Gassmann, Aaron J.; Head, Graham; Tabashnik, Bruce E.; Carrière, Yves

    2011-01-01

    Fitness costs of resistance to Bacillus thuringiensis (Bt) crops occur in the absence of Bt toxins, when individuals with resistance alleles are less fit than individuals without resistance alleles. As costs of Bt resistance are common, refuges of non-Bt host plants can delay resistance not only by providing susceptible individuals to mate with resistant individuals, but also by selecting against resistance. Because costs typically vary across host plants, refuges with host plants that magnify costs or make them less recessive could enhance resistance management. Limited understanding of the physiological mechanisms causing fitness costs, however, hampers attempts to increase costs. In several major cotton pests including pink bollworm (Pectinophora gossypiella), resistance to Cry1Ac cotton is associated with mutations altering cadherin proteins that bind this toxin in susceptible larvae. Here we report that the concentration of gossypol, a cotton defensive chemical, was higher in pink bollworm larvae with cadherin resistance alleles than in larvae lacking such alleles. Adding gossypol to the larval diet decreased larval weight and survival, and increased the fitness cost affecting larval growth, but not survival. Across cadherin genotypes, the cost affecting larval growth increased as the gossypol concentration of larvae increased. These results suggest that increased accumulation of plant defensive chemicals may contribute to fitness costs associated with resistance to Bt toxins. PMID:21738799

  11. Difficult Airway Response Team: A Novel Quality Improvement Program for Managing Hospital-Wide Airway Emergencies

    PubMed Central

    Mark, Lynette J.; Herzer, Kurt R.; Cover, Renee; Pandian, Vinciya; Bhatti, Nasir I.; Berkow, Lauren C.; Haut, Elliott R.; Hillel, Alexander T.; Miller, Christina R.; Feller-Kopman, David J.; Schiavi, Adam J.; Xie, Yanjun J.; Lim, Christine; Holzmueller, Christine; Ahmad, Mueen; Thomas, Pradeep; Flint, Paul W.; Mirski, Marek A.

    2015-01-01

    Background Difficult airway cases can quickly become emergencies, increasing the risk of life-threatening complications or death. Emergency airway management outside the operating room is particularly challenging. Methods We developed a quality improvement program—the Difficult Airway Response Team (DART)—to improve emergency airway management outside the operating room. DART was implemented by a team of anesthesiologists, otolaryngologists, trauma surgeons, emergency medicine physicians, and risk managers in 2005 at The Johns Hopkins Hospital in Baltimore, Maryland. The DART program had three core components: operations, safety, and education. The operations component focused on developing a multidisciplinary difficult airway response team, standardizing the emergency response process, and deploying difficult airway equipment carts throughout the hospital. The safety component focused on real-time monitoring of DART activations and learning from past DART events to continuously improve system-level performance. This objective entailed monitoring the paging system, reporting difficult airway events and DART activations to a web-based registry, and using in situ simulations to identify and mitigate defects in the emergency airway management process. The educational component included development of a multispecialty difficult airway curriculum encompassing case-based lectures, simulation, and team building/communication to ensure consistency of care. Educational materials were also developed for non-DART staff and patients to inform them about the needs of patients with difficult airways and ensure continuity of care with other providers after discharge. Results Between July 2008 and June 2013, DART managed 360 adult difficult airway events comprising 8% of all code activations. Predisposing patient factors included body mass index > 40, history of head and neck tumor, prior difficult intubation, cervical spine injury, airway edema, airway bleeding, and previous

  12. Airway adequacy, head posture, and craniofacial morphology.

    PubMed

    Solow, B; Siersbaek-Nielsen, S; Greve, E

    1984-09-01

    Previous studies of different samples have demonstrated associations between craniocervical angulation and craniofacial morphology, between airway obstruction by adenoids and craniofacial morphology, and between airway obstruction and craniocervical angulation. A hypothesis to account for the different sets of associations was suggested by Solow and Kreiborg in 1977. In the present study, the three sets of associations were examined in a single group of nonpathologic subjects with no history of airway obstruction. Cephalometric radiographs taken in the natural head position and rhinomanometric recordings were obtained from twenty-four children 7 to 9 years of age. Correlations were calculated between twenty-seven morphologic, eight postural, and two airway variables. A large craniocervical angle was, on the average, seen in connection with small mandibular dimensions, mandibular retrognathism, and a large mandibular inclination. Obstructed nasopharyngeal airways (defined as a small pm-ad 2 radiographic distance and a large nasal respiratory resistance, NRR, determined rhinomanometrically) were, on the average, seen in connection with a large craniocervical angle and with small mandibular dimensions, mandibular retrognathism, a large mandibular inclination, and retroclination of the upper incisors. The observed correlations were in agreement with the predicted pattern of associations between craniofacial morphology, craniocervical angulation, and airway resistance, thus suggesting the simultaneous presence of such associations in the sample of nonpathologic subjects with no history of airway obstruction.

  13. Immunoglobulin E anaphylaxis in rabbits: mechanisms of pulmonary resistance and compliance changes.

    PubMed

    Habib, M P; Dunn, A M; Sobonya, R E; Baumgartener, C C; Newell, J D; Halonen, M

    1988-03-01

    Factors causing changes in pulmonary resistance and dynamic compliance with immunoglobulin (Ig) E anaphylaxis in spontaneously breathing rabbits were assessed in ventilated rabbits using tantalum bronchography and wet-to-dry wt ratios. Ventilated rabbits demonstrated changes in resistance and compliance similar to spontaneously breathing rabbits. Chlorpheniramine pretreatment prevented increases in resistance but not decreases in compliance. Anaphylaxis constricted small (less than 1 mm) airways 20.9 +/- 16.0% (mean +/- SD) and intermediate (between 1 and 3 mm) airways 21.8 +/- 19.8%. Chlorpheniramine (10 mg/kg) prevented small airway changes and attenuated those in intermediate airways. Chlorpheniramine prevented histamine-induced constriction of small (23.6 +/- 15.7%) and intermediate (17.6 +/- 15.0%) airways. Lung wet-to-dry wt ratios were unchanged. Changes in resistance and compliance during rabbit IgE anaphylaxis are not due to changes in tidal volume or frequency. Histamine, via H1 receptors, is the principal mediator of pulmonary resistance increases but not dynamic compliance reductions. Chlorpheniramine-sensitive increases in resistance are caused by constrictions of intermediate and small airways, whereas the chlorpheniramine-resistant decrease in compliance is not caused directly by constriction of the smallest measurable airways (0.25 mm) or changes in lung water.

  14. Genetic engineering for increasing fungal and bacterial disease resistance in crop plants.

    PubMed

    Wally, Owen; Punja, Zamir K

    2010-01-01

    We review the current and future potential of genetic engineering strategies used to make fungal and bacterial pathogen-resistant GM crops, illustrating different examples of the technologies and the potential benefits and short-falls of the strategies. There are well- established procedures for the production of transgenic plants with resistance towards these pathogens and considerable progress has been made using a range of new methodologies. There are no current commercially available transgenic plant species with increased resistance towards fungal and bacterial pathogens; only plants with increased resistance towards viruses are available. With an improved understanding of plant signaling pathways in response to a range of other pathogens, such as fungi, additional candidate genes for achieving resistance are being investigated. The potential for engineering plants for resistance against individual devastating diseases or for plants with resistance towards multiple pathogens is discussed in detail.

  15. Composites for Increased Wear Resistance: Current Achievements and Future Prospects

    NASA Technical Reports Server (NTRS)

    Lancaster, J. K.

    1984-01-01

    The various ways in which reductions in wear and/or friction can be achieved by the use of composite materials are reviewed. Reinforced plastics are emphasized and it is shown that fillers and fibers reduce wear via several mechanisms additional to their role of increasing overall mechanical strength, preferential transfer, counter face abrasion, preferential load support, or third-body formation on either the composite or its counterface. Examples are given from recent work on thin layer composites of the type widely used as dry bearings in aircraft flight control mechanisms. Developments in metal based composites and carbon-carbon composites for high energy brakes are discussed. The aspects which could benefit by increased fundamental understanding identified and the types of composites which appear to have greatest potential for further growth are indicated.

  16. NDRG1 is important to maintain the integrity of airway epithelial barrier through claudin-9 expression.

    PubMed

    Gon, Yasuhiro; Maruoka, Shuichiro; Kishi, Hiroyuki; Kozu, Yutaka; Kazumichi, Kuroda; Nomura, Yasuyuki; Takeshita, Ikuko; Oshima, Takeshi; Hashimoto, Shu

    2017-02-13

    Impairment of epithelial barrier integrity caused by environmental triggers is associated with the pathogenesis of airway inflammation. Using human airway epithelial cells, we attempted to identify molecule(s) that promote airway epithelial barrier integrity. Microarray analyses were conducted using the Affimetrix human whole genome gene chip, and we identified the N-myc downstream-regulated gene 1 (NDRG1) gene, which was induced during the development of the epithelial cell barrier. Immunohistochemical analysis revealed strong NDRG1 expression in ciliated epithelial cells in nasal tissues sampled from patients with chronic rhinosinusitis (CRS), and the low expression of NDRG1 was observed in goblet cells or damaged epithelial cells. NDRG1 gene knockdown with its specific siRNA decreased the transepithelial electrical resistance and increased the dextran permeability. Immunocytochemistry revealed that NDRG1 knockdown disrupted tight junctions of airway epithelial cells. Next, we analyzed the effects of NDRG1 knockdown on the expression of tight and adhesion junction molecules. NDRG1 knockdown significantly decreased only claudin-9 expression, but did not decrease other claudin family molecules, such as E-cadherin, and ZO-1, -2, or -3. Knockdown of claudin-9 markedly impaired the barrier function in airway epithelial cells. These results suggest that NDRG1 is important for the barrier integrity in airway epithelial cells.

  17. Airway management in emergency situations.

    PubMed

    Dörges, Volker

    2005-12-01

    Securing and monitoring the airway are among the key requirements of appropriate therapy in emergency patients. Failures to secure the airways can drastically increase morbidity and mortality of patients within a very short time. Therefore, the entire range of measures needed to secure the airway in an emergency, without intermediate ventilation and oxygenation, is limited to 30-40 seconds. Endotracheal intubation is often called the 'gold standard' for airway management in an emergency, but multiple failed intubation attempts do not result in maintaining oxygenation; instead, they endanger the patient by prolonging hypoxia and causing additional trauma to the upper airways. Thus, knowledge and availability of alternative procedures are also essential in every emergency setting. Given the great variety of techniques available, it is important to establish a well-planned, methodical protocol within the framework of an algorithm. This not only facilitates the preparation of equipment and the training of personnel, it also ensures efficient decision-making under time pressure. Most anaesthesia-related deaths are due to hypoxaemia when difficulty in securing the airway is encountered, especially in obstetrics during induction of anaesthesia for caesarean delivery. The most commonly occurring adverse respiratory events are failure to intubate, failure to recognize oesophageal intubation, and failure to ventilate. Thus, it is essential that every anaesthesiologist working on the labour and delivery ward is comfortable with the algorithm for the management of failed intubation. The algorithm for emergency airway management describing the sequence of various procedures has to be adapted to internal standards and to techniques that are available.

  18. Nebulized lidocaine blunts airway hyper-responsiveness in experimental feline asthma.

    PubMed

    Nafe, Laura A; Guntur, Vamsi P; Dodam, John R; Lee-Fowler, Tekla M; Cohn, Leah A; Reinero, Carol R

    2013-08-01

    Nebulized lidocaine may be a corticosteroid-sparing drug in human asthmatics, reducing airway resistance and peripheral blood eosinophilia. We hypothesized that inhaled lidocaine would be safe in healthy and experimentally asthmatic cats, diminishing airflow limitation and eosinophilic airway inflammation in the latter population. Healthy (n = 5) and experimentally asthmatic (n = 9) research cats were administered 2 weeks of nebulized lidocaine (2 mg/kg q8h) or placebo (saline) followed by a 2-week washout and crossover to the alternate treatment. Cats were anesthetized to measure the response to inhaled methacholine (MCh) after each treatment. Placebo and doubling doses of methacholine (0.0625-32.0000 mg/ml) were delivered and results were expressed as the concentration of MCh increasing baseline airway resistance by 200% (EC200Raw). Bronchoalveolar lavage was performed after each treatment and eosinophil numbers quantified. Bronchoalveolar lavage fluid (BALF) % eosinophils and EC200Raw within groups after each treatment were compared using a paired t-test (P <0.05 significant). No adverse effects were noted. In healthy cats, lidocaine did not significantly alter BALF eosinophilia or the EC200Raw. There was no difference in %BALF eosinophils in asthmatic cats treated with lidocaine (36±10%) or placebo (33 ± 6%). However, lidocaine increased the EC200Raw compared with placebo 10 ± 2 versus 5 ± 1 mg/ml; P = 0.043). Chronic nebulized lidocaine was well-tolerated in all cats, and lidocaine did not induce airway inflammation or airway hyper-responsiveness in healthy cats. Lidocaine decreased airway response to MCh in asthmatic cats without reducing airway eosinophilia, making it unsuitable for monotherapy. However, lidocaine may serve as a novel adjunctive therapy in feline asthmatics with beneficial effects on airflow obstruction.

  19. Emergency airway puncture

    MedlinePlus

    ... support for only a very short period of time. Alternative Names Needle cricothyrotomy Images Emergency airway puncture Cricoid cartilage Emergency airway puncture - series References Hebert RB, Bose S, Mace SE. Cricothyrotomy and ...

  20. Upper airway biopsy

    MedlinePlus

    ... upper airway Images Upper airway test Bronchoscopy Throat anatomy References Yung RC, Boss EF. Tracheobronchial endoscopy. In: Flint PW, Haughey BH, Lund LJ, et al, eds. Cummings Otolaryngology: Head & Neck Surgery. 5th ed. Philadelphia, PA: Elsevier Mosby; ...

  1. Alpha 4-integrins mediate antigen-induced late bronchial responses and prolonged airway hyperresponsiveness in sheep.

    PubMed Central

    Abraham, W M; Sielczak, M W; Ahmed, A; Cortes, A; Lauredo, I T; Kim, J; Pepinsky, B; Benjamin, C D; Leone, D R; Lobb, R R

    1994-01-01

    Eosinophils and T lymphocytes are thought to be involved in allergic airway inflammation. Both cells express the alpha 4 beta 1-integrin, very late antigen-4 (VLA-4, CD49d/CD29); alpha 4-integrins can promote cellular adhesion and activation. Therefore, we examined the in vivo effects of a blocking anti-alpha 4 monoclonal antibody, HP 1/2, on antigen-induced early and late bronchial responses, airway hyperresponsiveness, inflammatory cell influx, and peripheral leukocyte counts in allergic sheep. Sheep blood lymphocytes, monocytes, and eosinophils expressed alpha 4 and bound HP 1/2. In control sheep, Ascaris antigen challenge produced early and late increases in specific lung resistance of 380 +/- 42% and 175 +/- 16% over baseline immediately and 7 h after challenge, respectively, as well as airway hyperresponsiveness continuing for 14 d after antigen challenge. Treatment with HP 1/2 (1 mg/kg, i.v.) 30 min before antigen challenge did not affect the early increase in specific lung resistance but inhibited the late-phase increase at 5-8 h by 75% (P < 0.05) and inhibited the post-antigen-induced airway hyperresponsiveness at 1, 2, 7, and 14 d (P < 0.05, for each time). Intravenous HP 1/2 given 2 h after antigen challenge likewise blocked late-phase airway changes and postchallenge airway hyperresponsiveness. Airway administration of HP 1/2 (16-mg dose) was also effective in blocking these antigen-induced changes. Response to HP 1/2 was specific since an isotypic monoclonal antibody, 1E6, was ineffective by intravenous and aerosol administration. Inhibition of leukocyte recruitment did not totally account for the activity of anti-alpha 4 antibody since HP 1/2 neither diminished the eosinopenia or lymphopenia that followed antigen challenge nor consistently altered the composition of leukocytes recovered by bronchoalveolar lavage. Because airway administration of HP 1/2 was also active, HP 1/2 may have inhibited cell activation. Reduction of platelet-activating factor

  2. The Effect of Lung Stretch during Sleep on Airway Mechanics in Overweight and Obese Asthma

    PubMed Central

    Campana, L.M.; Malhotra, A.; Suki, B.; Hess, L.; Israel, E.; Smales, E.; DeYoung, P.; Owens, R.L.

    2012-01-01

    Both obesity and sleep reduce lung volume and limit deep breaths, possibly contributing to asthma. We hypothesize that increasing lung volume dynamically during sleep would reduce airway resistance in asthma. Asthma (n=10) and control (n=10) subjects were studied during sleep at baseline and with increased lung volume via bi-level positive airway pressure (BPAP). Using forced oscillations, respiratory system resistance (Rrs) and reactance (Xrs) were measured during sleep and Rrs was partitioned to upper and lower airway resistance (Rup, Rlow) using an epiglottic pressure catheter. Rrs and Rup increased with sleep (p<0.01) and Xrs was decreased in REM (p=0.02) as compared to wake. Rrs, Rup, and Rlow, were larger (p<0.01) and Xrs was decreased (p<0.02) in asthma. On BPAP, Rrs and Rup were decreased (p<0.001) and Xrs increased (p<0.01), but Rlow was unchanged. High Rup was observed in asthma, which reduced with BPAP. We conclude that the upper airway is a major component of Rrs and larger lung volume changes may be required to alter Rlow. PMID:23041446

  3. A Computational Study of the Respiratory Airflow Characteristics in Normal and Obstructed Human Airways

    DTIC Science & Technology

    2014-01-01

    normal and three different obstructed airway geometries, consisting of symmetric, asym- metric, and random obstructions. Fig. 2 shows the geometric ...normal and obstructed airways Airway resistance is a measure of the opposition to the airflow caused by geometric properties, such as airway obstruction...pressure drops. Resistance values were dependent on the degree and geometric distribution of the obstruction sites. In the symmetric obstruction model

  4. Repeated hyperventilation causes peripheral airways inflammation, hyperreactivity, and impaired bronchodilation in dogs.

    PubMed

    Davis, M S; Freed, A N

    2001-09-01

    Winter athletes have an increased incidence of asthma, suggesting that repetitive hyperventilation with cold air may predispose individuals to airways disease. We used a canine model of exercise-induced hyperpnea to examine the effects of repeated hyperventilation with cool, dry air (i.e., dry air challenge [DAC]) on peripheral airway resistance (Rp), reactivity, and inflammation. Specific bronchi were exposed to a single DAC on five consecutive days. Rp and Delta Rp to aerosolized histamine, intravenous histamine, or hypocapnia were measured daily. Bronchoalveolar lavage fluid (BALF) was obtained on the fifth day. Rp increased from 0.70 +/- 0.08 to 1.13 +/- 0.22 cm H(2)O/ml/s (n = 25) 24 h after the first DAC, rose to 1.49 +/- 0.24 cm H(2)O/ml/s by Day 3, and remained elevated throughout the remainder of the protocol. Repeated DAC increased reactivity to hypocapnia and intravenous histamine. Intravenous salbutamol failed to reduce Rp as effectively in challenged airways (111% of Day 1 baseline) as in naive airways (54% of baseline). Repeated DAC caused increased BALF neutrophils, eosinophils, and sulfidopeptide leukotrienes. We conclude that repeated DAC causes peripheral airways inflammation, obstruction, hyperreactivity, and impaired beta-agonist-induced relaxation. This suggests that other mechanisms in addition to increased smooth muscle tone may contribute to the development of repetitive hyperventilation-induced bronchial obstruction and hyperreactivity.

  5. Bortezomib-resistance is associated with increased levels of proteasome subunits and apoptosis-avoidance

    PubMed Central

    Wu, Yi-Xin; Yang, Jia-Hua; Saitsu, Hirotomo

    2016-01-01

    Bortezomib (BTZ), a proteasome inhibitor, is the first proteasome inhibitor to be used in clinical practice. Here we investigated the mechanisms underlying acquired bortezomib resistance in hepatocellular carcinoma (HCC) cells. Using stepwise selection, we established two acquired bortezomib-resistant HCC cell lines, a bortezomib-resistant HepG2 cell line (HepG2/BTZ) and bortezomib-resistant HuH7 cell line (HuH7/BTZ). The 50% inhibitory concentration values of HepG2/BTZ and HuH7/BTZ were respectively 15- and 39-fold higher than those of parental cell lines. Sequence analysis of the bortezomib-binding pocket in the β5-subunit showed no mutation. However, bortezomib-resistant HCC cells had increased expression of β1 and β5 proteasome subunits. These alterations of proteasome expression were accompanied by a weak degree of proteasome inhibition in bortezomib-resistant cells than that in wild-type cells after bortezomib exposure. Furthermore, bortezomib-resistant HCC cells acquired resistance to apoptosis. Bortezomib up-regulated pro-apoptotic proteins of the Bcl-2 protein family, Bax and Noxa in wild-type HCC cells. However, in bortezomib-resistant HCC cells, resistance to apoptosis was accompanied by loss of the ability to stabilize and accumulate these proteins. Thus, increased expression and increased activity of proteasomes constitute an adaptive and auto regulatory feedback mechanism to allow cells to survive exposure bortezomib. PMID:27769058

  6. Careers in Airway Science.

    ERIC Educational Resources Information Center

    Federal Aviation Administration (DOT), Washington, DC.

    The Federal Aviation Administration (FAA) has initiated the Airway Science curriculum as a method of preparing the next generation of aviation technicians and managers. This document: (1) discusses the FAA's role in the Airway Science program; (2) describes some of the career fields that FAA offers to Airway Science graduates (air traffic control…

  7. Resisting sarcolemmal rupture: dystrophin repeats increase membrane-actin stiffness.

    PubMed

    Sarkis, Joe; Vié, Véronique; Winder, Steve J; Renault, Anne; Le Rumeur, Elisabeth; Hubert, Jean-François

    2013-01-01

    Dystrophin is an essential part of a membrane protein complex that provides flexible support to muscle fiber membranes. Loss of dystrophin function leads to membrane fragility and muscle-wasting disease. Given the importance of cytoskeletal interactions in strengthening the sarcolemma, we have focused on actin-binding domain 2 of human dystrophin, constituted by repeats 11 to 15 of the central domain (DYS R11-15). We previously showed that DYS R11-15 also interacts with membrane lipids. We investigated the shear elastic constant (μ) and the surface viscosity (η(s)) of Langmuir phospholipid monolayers mimicking the inner leaflet of the sarcolemma in the presence of DYS R11-15 and actin. The initial interaction of 100 nM DYS R11-15 with the monolayers slightly modifies their rheological properties. Injection of 0.125 μM filamentous actin leads to a strong increase of μ and η(s,) from 0 to 5.5 mN/m and 2.4 × 10(-4) N · s/m, respectively. These effects are specific to DYS R11-15, require filamentous actin, and depend on phospholipid nature and lateral surface pressure. These findings suggest that the central domain of dystrophin contributes significantly to the stiffness and the stability of the sarcolemma through its simultaneous interactions with the cytoskeleton and lipid membrane. This mechanical link is likely to be a major contributing factor to the shock absorber function of dystrophin and muscle sarcolemmal integrity on mechanical stress.

  8. Involvement of inflammatory mediators in the airway responses to trimellitic anhydride in sensitized guinea-pigs.

    PubMed Central

    Hayes, J. P.; Lotvall, J. O.; Barnes, P. J.; Newman Taylor, A. J.; Chung, K. F.

    1992-01-01

    1. We examined the effect of various pharmacological agents on the acute bronchoconstrictor response and airway microvascular leakage in a model of guinea-pig sensitization to trimellitic anhydride (TMA) a cause of low molecular weight occupational asthma in man. 2. Guinea-pigs were given intradermal injections of 0.1 ml of 0.3% TMA in corn oil; 21-28 days later, anaesthetized guinea-pigs were challenged with TMA conjugated to guinea-pig albumin by tracheal instillation. Changes in lung resistance were measured and airway microvascular leakage was quantified by measuring the extravasation of Evans blue dye into the airway tissue. 3. Sensitized guinea-pig (n = 9 in each group) were pretreated with chlorpheniramine (2.5 mg kg-1, i.v.), WEB 2086 (10 micrograms kg-1, i.v.), BW 4AC (50 mg kg-1, i.p.), nedocromil sodium (2% aerosol for 60 s) or vehicle alone. 4. Pretreatment with chlorpheniramine inhibited both the acute bronchoconstrictor response and the increase in airway microvascular leakage. WEB 2086 and nedocromil sodium partially inhibited the bronchoconstrictor response but had no significant effect on airway microvascular leakage. BW 4AC caused a non-significant reduction of the bronchoconstrictor response and airway microvascular leakage. 5. These results indicate that both the bronchoconstrictor response and the airway microvascular response in this model of sensitization is mediated to a large extent by histamine. PAF but not 5-lipoxygenase products also partially mediates the bronchoconstrictor response but not the airway microvascular leakage. Nedocromil sodium partially inhibits the bronchoconstrictor response only. PMID:1382788

  9. Involvement of superoxide in ozone-induced airway hyperresponsiveness in anesthetized cats

    SciTech Connect

    Takahashi, T.; Miura, M.; Katsumata, U.; Ichinose, M.; Kimura, K.; Inoue, H.; Takishima, T.; Shirato, K. )

    1993-07-01

    To determine whether oxygen radical scavengers inhibit ozone-induced airway hyperresponsiveness, we examined the protective effect of polyethylene glycol-superoxide dismutase (PEG-SOD) and PEG-catalase (PEG-CAT) on ozone-induced airway hyperresponsiveness in cat airways. Twenty-five cats divided into five groups were anesthetized and mechanically ventilated. There was no difference between the groups in baseline airway responsiveness to inhaled acetylcholine (ACh). In the control group, AChPC, the concentration required to produce a doubling increase in baseline pulmonary resistance, was significantly reduced by ozone exposure (2.0 ppm for 2 h); the ratios of AChPC before ozone exposure to after ozone exposure (AChPC ratio) were 14.8 +/- 5.7 (p < 0.001) and 4.80 +/- 1.6 (p < 0.01) 30 and 120 min after exposure, respectively. Local administration of PEG-SOD (2,000 U/kg) into airways partially but significantly prevented ozone-induced airway hyperresponsiveness. The AChPC ratios were 6.2 +/- 1.4 and 1.5 +/- 0.2 30 and 120 min after exposure, respectively, which were significantly different from those of the control group (p < 0.05), whereas PEG-CAT pretreatment (6,000 U/kg) was without effect. Combined pretreatment with PEG-SOD and PEG-CAT had no additional protective effect compared with PEG-SOD alone. PEG-SOD had no direct effect on airway responsiveness to ACh. These results suggest that superoxide may be involved in ozone-induced airway hyperresponsiveness.

  10. A study of the deposition of carbide coatings on graphite fibers. [to increase electrical resistance

    NASA Technical Reports Server (NTRS)

    Suplinskas, R. J.; Henze, T. W.

    1979-01-01

    The chemical vapor deposition of boron carbide and silicon carbide on graphite fibers to increase their electrical resistance was studied. Silicon carbide coatings were applied without degradation of the mechanical properties of the filaments. These coatings typically added 1000 ohms to the resistance of a filament as measured between two mercury pools. When SiC-coated filaments were oxidized by refluxing in boiling phosphoric acid, average resistance increased by an additional 1000 ohms; in addition resistance increases as high as 150 K ohms and breakdown voltages as high as 17 volts were noted. Data on boron carbide coatings indicated that such coatings would not be effective in increasing resistance, and would degrade the mechanical properties.

  11. Chitosan Microparticles Exert Broad-Spectrum Antimicrobial Activity against Antibiotic-Resistant Micro-organisms without Increasing Resistance.

    PubMed

    Ma, Zhengxin; Kim, Donghyeon; Adesogan, Adegbola T; Ko, Sanghoon; Galvao, Klibs; Jeong, Kwangcheol Casey

    2016-05-04

    Antibiotic resistance is growing exponentially, increasing public health concerns for humans and animals. In the current study, we investigated the antimicrobial features of chitosan microparticles (CM), engineered from chitosan by ion gelation, seeking potential application for treating infectious disease caused by multidrug resistant microorganisms. CM showed excellent antimicrobial activity against a wide range of microorganisms, including clinically important antibiotic-resistant pathogens without raising resistant mutants in serial passage assays over a period of 15 days, which is a significantly long passage compared to tested antibiotics used in human and veterinary medicine. In addition, CM treatment did not cause cross-resistance, which is frequently observed with other antibiotics and triggers multidrug resistance. Furthermore, CM activity was examined in simulated gastrointestinal fluids that CM encounter when orally administered. Antimicrobial activity of CM was exceptionally strong to eliminate pathogens completely. CM at a concentration of 0.1 μg/mL killed E. coli O157:H7 (5 × 10(8) CFU/mL) completely in synthetic gastric fluid within 20 min. Risk assessment of CM, in an in vitro animal model, revealed that CM did not disrupt the digestibility, pH or total volatile fatty acid production, indicating that CM likely do not affect the functionality of the rumen. Given all the advantages, CM can serve as a great candidate to treat infectious disease, especially those caused by antibiotic-resistant pathogens without adverse side effects.

  12. Mixed-Methods Resistance Training Increases Power and Strength of Young and Older Men.

    ERIC Educational Resources Information Center

    Newton, Robert U.; Hakkinen, Keijo; Hakkinen, Arja; McCormick, Matt; Volek, Jeff; Kraemer, William J.

    2002-01-01

    Examined the effects of a 10-week, mixed-methods resistance training program on young and older men. Although results confirmed some age-related reductions in muscle strength and power, the older men demonstrated similar capacity to the younger men for increases in muscle strength and power via an appropriate, periodized resistance training…

  13. The non-neuronal cholinergic system as novel drug target in the airways.

    PubMed

    Pieper, Michael Paul

    2012-11-27

    The parasympathetic nervous system is a key regulator of the human organism involved in the pathophysiology of various disorders through cholinergic mechanisms. In the lungs, acetylcholine (ACh) released by vagal nerve endings stimulates muscarinic receptors thereby increasing airway smooth muscle tone. Contraction of airway smooth muscle cells leads to increased respiratory resistance and dyspnea. An additional branch of the cholinergic system is the non-neuronal cholinergic system expressed in nearly all cell types present in the airways. Activation of this system may contribute to an increased cholinergic tone in the lungs, inducing pathophysiological processes like inflammation, remodeling, mucus hypersecretion and chronic cough. Selective muscarinic receptor antagonists specifically inhibit acetylcholine at the receptor inducing bronchodilation in patients with obstructive airway diseases. This paper reviews preclinical pharmacological research activities on anticholinergics including experimental models of asthma and chronic obstructive pulmonary disease, COPD. It discloses various options to follow up the non-neuronal cholinergic system as a novel drug target for the treatment of key aspects of obstructive airway diseases, in particular those of a chronic nature.

  14. Novel Effects of Azithromycin on Tight Junction Proteins in Human Airway Epithelia

    PubMed Central

    Asgrimsson, Valthor; Gudjonsson, Thorarinn; Gudmundsson, Gudmundur Hrafn; Baldursson, Olafur

    2006-01-01

    The macrolide antibiotic azithromycin improves lung function and prognosis among patients with cystic fibrosis or diffuse panbronchiolitis, independently of bacterial eradication. Anti-inflammatory effects have been implicated, but data from in vivo studies are scarce, and the link between abnormal electrolyte content in airway surface liquid and bronchial infections remains uncertain. In the present study, we treated human airway epithelia on filter supports with azithromycin and monitored transepithelial electrical resistance. We found that azithromycin increased transepithelial electrical resistance of airway epithelia in a dose-dependent manner. Immunocytochemistry and Western blotting showed that addition of azithromycin changed the locations of proteins in cell cultures and induced processing of the tight junction proteins claudin-1 and claudin-4, occludin, and junctional adhesion molecule-A. These effects were reversible, and no effect was seen when cells were treated with penicillin or erythromycin. The data indicate that azithromycin increases the transepithelial electrical resistance of human airway epithelia by changing the processing of tight junction proteins. The results are novel and may help explain the beneficial effects of azithromycin in patients with cystic fibrosis, diffuse panbronchiolitis, and community-acquired pneumonia. PMID:16641453

  15. A highly potent agonist to protease-activated receptor-2 reveals apical activation of the airway epithelium resulting in Ca2+-regulated ion conductance

    PubMed Central

    Sherwood, Cara L.; Daines, Michael O.; Price, Theodore J.; Vagner, Josef

    2014-01-01

    The airway epithelium provides a barrier that separates inhaled air and its various particulates from the underlying tissues. It provides key physiological functions in both sensing the environment and initiating appropriate innate immune defenses to protect the lung. Protease-activated receptor-2 (PAR2) is expressed both apically and basolaterally throughout the airway epithelium. One consequence of basolateral PAR2 activation is the rapid, Ca2+-dependent ion flux that favors secretion in the normally absorptive airway epithelium. However, roles for apically expressed PAR2 activation have not been demonstrated, in part due to the lack of specific, high-potency PAR2 ligands. In the present study, we used the newly developed PAR2 ligand 2at-LIGRLO(PEG3-Pam)-NH2 in combination with well-differentiated, primary cultured airway epithelial cells from wild-type and PAR2−/− mice to examine the physiological role of PAR2 in the conducting airway after apical activation. Using digital imaging microscopy of intracellular Ca2+ concentration changes, we verified ligand potency on PAR2 in primary cultured airway cells. Examination of airway epithelial tissue in an Ussing chamber showed that apical activation of PAR2 by 2at-LIGRLO(PEG3-Pam)-NH2 resulted in a transient decrease in transepithelial resistance that was due to increased apical ion efflux. We determined pharmacologically that this increase in ion conductance was through Ca2+-activated Cl− and large-conductance K+ channels that were blocked with a Ca2+-activated Cl− channel inhibitor and clotrimazole, respectively. Stimulation of Cl− efflux via PAR2 activation at the airway epithelial surface can increase airway surface liquid that would aid in clearing the airway of noxious inhaled agents. PMID:25143347

  16. Airway epithelial-derived factor relaxes pulmonary vascular smooth muscle.

    PubMed

    Farah, Omar R; Li, Dongge; McIntyre, Brendan A S; Pan, Jingyi; Belik, Jaques

    2009-01-01

    The factors controlling the pulmonary vascular resistance under physiological conditions are poorly understood. We have previously reported on an apparent cross talk between the airway and adjacent pulmonary arterial bed where a factor likely derived from the bronchial epithelial cells reduced the magnitude of agonist-stimulated force in the vascular smooth muscle. The main purpose of this investigation was to evaluate whether bronchial epithelial cells release a pulmonary arterial smooth muscle relaxant factor. Conditioned media from SPOC-1 or BEAS-2B, a rat- and a human-derived bronchial epithelial cell line, respectively, were utilized. This media significantly relaxed precontracted adult but not fetal pulmonary arterial muscle in an oxygen tension-dependent manner. This response was mediated via soluble guanylate cyclase, involving AKT/PI3-kinase and neuronal nitric oxide synthase. Airway epithelial cell-conditioned media increased AKT phosphorylation in pulmonary smooth muscle cells (SMC) and reduced intracellular calcium change following ATP stimulation to a significantly greater extent than observed for bronchial SMC. The present data strongly support the evidence for bronchial epithelial cells releasing a stable and soluble factor capable of inducing pulmonary arterial SMC relaxation. We speculate that under physiological conditions, the maintenance of a low pulmonary vascular resistance, postnatally, is in part modulated by the airway epithelium.

  17. Increase in Antibiotic-Resistant Gram-Negative Bacterial Infections in Febrile Neutropenic Children

    PubMed Central

    2016-01-01

    Background The incidence of bacteremia caused by Gram-negative bacteria has increased recently in febrile neutropenic patients with the increase of antibiotic-resistant Gram-negative bacterial infections. This study aimed to identify the distribution of causative bacteria and the proportion of antibiotic-resistant bacteria in bacteremia diagnosed in febrile neutropenic children. Materials and Methods The medical records of febrile neutropenic children diagnosed with bacteremia between 2010 and 2014 were retrospectively reviewed. The causative bacteria and proportion of antibiotic-resistant bacteria were investigated and compared yearly during the study period. The clinical impact of antibiotic-resistant bacterial infections was also determined. Results A total of 336 bacteremia episodes were identified. During the entire study period, 181 (53.9%) and 155 (46.1%) episodes were caused by Gram-negative and Gram-positive bacteria, respectively. Viridans streptococci (25.9%), Klebsiella spp. (16.7%), and Escherichia coli (16.4%) were the most frequent causative bacteria. The overall distribution of causative bacteria was not significantly different annually. Antibiotic-resistant bacteria were identified in 85 (25.3%) episodes, and the proportion of antibiotic-resistant bacteria was not significantly different annually. Extended-spectrum β-lactamase-producing E. coli and Klebsiella spp. were most common among antibiotic-resistant Gram-negative bacteria, and they accounted for 30.6% (n = 34) of the identified E. coli and K. pneumoniae. Methicillin-resistant coagulase-negative staphylococci were most common among antibiotic-resistant Gram-positive bacteria, and it accounted for 88.5% (n = 23) of the identified coagulase-negative staphylococci. Antibiotic-resistant bacterial infections, especially antibiotic-resistant Gram-negative bacterial infections, caused significantly higher mortality due to bacteremia compared with non-antibiotic-resistant bacterial infections (P <0

  18. Increased sensitivity to platinum drugs of cancer cells with acquired resistance to trabectedin

    PubMed Central

    Colmegna, B; Uboldi, S; Frapolli, R; Licandro, S A; Panini, N; Galmarini, C M; Badri, Nadia; Spanswick, V J; Bingham, J P; Kiakos, Konstantinos; Erba, E; Hartley, J A; D'Incalci, M

    2015-01-01

    Background: In order to investigate the mechanisms of acquired resistance to trabectedin, trabectedin-resistant human myxoid liposarcoma (402-91/T) and ovarian carcinoma (A2780/T) cell lines were derived and characterised in vitro and in vivo. Methods: Resistant cell lines were obtained by repeated exposures to trabectedin. Characterisation was performed by evaluating drug sensitivity, cell cycle perturbations, DNA damage and DNA repair protein expression. In vivo experiments were performed on A2780 and A2780/T xenografts. Results: 402-91/T and A2780/T cells were six-fold resistant to trabectedin compared with parental cells. Resistant cells were found to be hypersensitive to UV light and did not express specific proteins involved in the nucleotide excision repair (NER) pathway: XPF and ERCC1 in 402-91/T and XPG in A2780/T. NER deficiency in trabectedin-resistant cells was associated with the absence of a G2/M arrest induced by trabectedin and with enhanced sensitivity (two-fold) to platinum drugs. In A2780/T, this collateral sensitivity, confirmed in vivo, was associated with an increased formation of DNA interstrand crosslinks. Conclusions: Our finding that resistance to trabectedin is associated with the loss of NER function, with a consequent increased sensitivity to platinum drugs, provides the rational for sequential use of these drugs in patients who have acquired resistance to trabectedin. PMID:26633559

  19. Anti-inflammatory drug (BW755C) inhibits airway hyperresponsiveness induced by ozone in dogs

    SciTech Connect

    Fabbri, L.M.; Aizawa, H.; O'Byrne, P.M.; Bethel, R.A.; Walters, E.H.; Holtzman, M.J.; Nadel, J.A.

    1985-08-01

    To follow up a previous observation that airway hyperresponsiveness induced by ozone is linked to airway inflammation, the authors investigated the effect of BW755C, an anti-inflammatory drug, on ozone-induced hyperresponsiveness in dogs. Airway responsiveness was assessed with dose-response curves of acetylcholine aerosol versus pulmonary resistance in two sets of experiments. In one set (placebo treatment), five dogs were given only saline solution treatment and were studied before treatment or ozone exposure and then after treatment both before and after ozone (3.0 ppm, 2 hours); in another set (BW755C treatment), the same dogs were studied before BW755C treatment or ozone and then after treatment (10 mg/kg intravenously) both before and after ozone. When the dogs were given no BW755C treatment, ozone induced a marked increase in airway responsiveness to acetylcholine. When the dogs were given BW755C, responsiveness was no different during treatment than before treatment but, more importantly, responsiveness did not increase significantly after ozone. The authors conclude that BW755C markedly inhibits ozone-induced airway hyperresponsiveness in dogs, probably by inhibiting the formation of oxygenation products of arachidonic acid.

  20. Identification of genes differentially regulated by vitamin D deficiency that alter lung pathophysiology and inflammation in allergic airways disease.

    PubMed

    Foong, Rachel E; Bosco, Anthony; Troy, Niamh M; Gorman, Shelley; Hart, Prue H; Kicic, Anthony; Zosky, Graeme R

    2016-09-01

    Vitamin D deficiency is associated with asthma risk. Vitamin D deficiency may enhance the inflammatory response, and we have previously shown that airway remodeling and airway hyperresponsiveness is increased in vitamin D-deficient mice. In this study, we hypothesize that vitamin D deficiency would exacerbate house dust mite (HDM)-induced inflammation and alterations in lung structure and function. A BALB/c mouse model of vitamin D deficiency was established by dietary manipulation. Responsiveness to methacholine, airway smooth muscle (ASM) mass, mucus cell metaplasia, lung and airway inflammation, and cytokines in bronchoalveolar lavage (BAL) fluid were assessed. Gene expression patterns in mouse lung samples were profiled by RNA-Seq. HDM exposure increased inflammation and inflammatory cytokines in BAL, baseline airway resistance, tissue elastance, and ASM mass. Vitamin D deficiency enhanced the HDM-induced influx of lymphocytes into BAL, ameliorated the HDM-induced increase in ASM mass, and protected against the HDM-induced increase in baseline airway resistance. RNA-Seq identified nine genes that were differentially regulated by vitamin D deficiency in the lungs of HDM-treated mice. Immunohistochemical staining confirmed that protein expression of midline 1 (MID1) and adrenomedullin was differentially regulated such that they promoted inflammation, while hypoxia-inducible lipid droplet-associated, which is associated with ASM remodeling, was downregulated. Protein expression studies in human bronchial epithelial cells also showed that addition of vitamin D decreased MID1 expression. Differential regulation of these genes by vitamin D deficiency could determine lung inflammation and pathophysiology and suggest that the effect of vitamin D deficiency on HDM-induced allergic airways disease is complex.

  1. KyoT2 downregulates airway remodeling in asthma.

    PubMed

    Hu, Mei; Ou-Yang, Hai-Feng; Han, Xing-Peng; Ti, Xin-Yu; Wu, Chang-Gui

    2015-01-01

    The typical pathological features of asthma are airway remodeling and airway hyperresponsiveness (AHR). KyoT2, a negative modulator of Notch signaling, has been linked to asthma in several previous studies. However, whether KyoT2 is involved in the regulation of airway remodeling or the modulation of airway resistance in asthma is unclear. In this study, we aimed to evaluate the therapeutic potential of KyoT2 in preventing asthma-associated airway remodeling and AHR. BALB/c mice were used to generate a mouse model of asthma. Additionally, the expression of Hes1 and Notch1 in airway was analyzed using Immunofluorescence examination. The asthmatic mice were intranasally administered adenovirus expressing KyoT2 and were compared to control groups. Furthermore, subepithelial fibrosis and other airway remodeling features were analyzed using hematoxylin and eosin staining, Van Gieson's staining and Masson's trichrome staining. AHR was also evaluated. This study revealed that KyoT2 downregulated the expression of Hes1, repressed airway remodeling, and alleviated AHR in asthmatic mice. It is reasonable to assume that KyoT2 downregulates airway remodeling and resistance in asthmatic mice through a Hes1-dependent mechanism. Therefore, KyoT2 is a potential clinical treatment strategy for asthma.

  2. Impact of airway morphological changes on pulmonary flows in scoliosis

    NASA Astrophysics Data System (ADS)

    Farrell, James; Garrido, Enrique; Valluri, Prashant

    2016-11-01

    The relationship between thoracic deformity in scoliosis and lung function is poorly understood. In a pilot study, we reviewed computed tomography (CT) routine scans of patients undergoing scoliosis surgery. The CT scans were processed to segment the anatomy of the airways, lung and spine. A three-dimensional model was created to study the anatomical relationship. Preliminary analysis showed significant airway morphological differences depending on the anterior position of the spine. A computational fluid dynamics (CFD) study was also conducted on the airway geometry using the inspiratory scans. The CFD model assuming non-compliant airway walls was capable of showing pressure drops in areas of high airway resistance, but was unable to predict regional ventilation differences. Our results indicate a dependence between the dynamic deformation of the airway during breathing and lung function. Dynamic structural deformation must therefore be incorporated within any modelling approaches to guide clinicians on the decision to perform surgical correction of the scoliosis.

  3. Relationship Between Respiratory Dynamics and Body Mass Index in Patients Undergoing General Anesthesia with Laryngeal Mask Airway (LMA) and Comparison Between Lithotomy and Supine Positions.

    PubMed

    Zhao, Xiao; Huang, Shiwei; Wang, Zhaomin; Chen, Lianhua; Li, Shitong

    2016-08-01

    BACKGROUND This study aimed to compare respiratory dynamics in patients undergoing general anesthesia with a laryngeal mask airway (LMA) in lithotomy and supine positions and to validate the impact of operational position on effectiveness of LMA ventilation. MATERIAL AND METHODS A total of 90 patients (age range, 18-65 years) who underwent general anesthesia were selected and divided into supine position (SP group) and lithotomy position groups (LP group). Vital signs and respiratory dynamic parameters of the 2 groups were measured at different time points and after implantation of an LMA. The arterial blood gas was monitored at 15 min after induction. The intraoperative changes of hemodynamic indexes and postoperative adverse reactions of LMA were recorded. The possible correlation between body mass index (BMI) and respiratory dynamic indexes was analyzed. RESULTS With prolonged duration of the operation, the inspiratory plateau pressure (Pplat), inspiratory resistance (RI), and work of breathing (WOB) gradually increased, while chest-lung compliance (Compl) and partial pressure of carbon dioxide in end-expiratory gas (PetCO2) gradually decreased (all P value <0.05). The mean airway pressure (Pmean), Pplat, and expiratory resistance (Re) in the LP group were significantly higher than in the SP group (P<0.05), while the peak inspiratory flow (FImax), peak expiratory flow (FEmax), WOB, and Compl in the LP group were significantly lower than in the SP group (P<0.05). BMI was positively correlated with peak airway pressure (PIP/Ppeak), Pplat, and airway resistance (Raw) and was negatively correlated with Compl; the differences among patients in lithotomy position were more remarkable (P<0.05). CONCLUSIONS The inspiratory plateau pressure and airway resistance increased with prolonged duration of the operation, accompanied by decreased chest-lung compliance. Peak airway pressure and airway resistance were positively correlated with BMI, and chest-lung compliance was

  4. Comparison of analysis methods for airway quantification

    NASA Astrophysics Data System (ADS)

    Odry, Benjamin L.; Kiraly, Atilla P.; Novak, Carol L.; Naidich, David P.

    2012-03-01

    Diseased airways have been known for several years as a possible contributing factor to airflow limitation in Chronic Obstructive Pulmonary Diseases (COPD). Quantification of disease severity through the evaluation of airway dimensions - wall thickness and lumen diameter - has gained increased attention, thanks to the availability of multi-slice computed tomography (CT). Novel approaches have focused on automated methods of measurement as a faster and more objective means that the visual assessment routinely employed in the clinic. Since the Full-Width Half-Maximum (FWHM) method of airway measurement was introduced two decades ago [1], several new techniques for quantifying airways have been detailed in the literature, but no approach has truly become a standard for such analysis. Our own research group has presented two alternative approaches for determining airway dimensions, one involving a minimum path and the other active contours [2, 3]. With an increasing number of techniques dedicated to the same goal, we decided to take a step back and analyze the differences of these methods. We consequently put to the test our two methods of analysis and the FWHM approach. We first measured a set of 5 airways from a phantom of known dimensions. Then we compared measurements from the three methods to those of two independent readers, performed on 35 airways in 5 patients. We elaborate on the differences of each approach and suggest conclusions on which could be defined as the best one.

  5. ClC-3 expression enhances etoposide resistance by increasing acidification of the late endocytic compartment.

    PubMed

    Weylandt, Karsten H; Nebrig, Maxim; Jansen-Rosseck, Nils; Amey, Joanna S; Carmena, David; Wiedenmann, Bertram; Higgins, Christopher F; Sardini, Alessandro

    2007-03-01

    Resistance to anticancer drugs and consequent failure of chemotherapy is a complex problem severely limiting therapeutic options in metastatic cancer. Many studies have shown a role for drug efflux pumps of the ATP-binding cassette transporters family in the development of drug resistance. ClC-3, a member of the CLC family of chloride channels and transporters, is expressed in intracellular compartments of neuronal cells and involved in vesicular acidification. It has previously been suggested that acidification of intracellular organelles can promote drug resistance by increasing drug sequestration. Therefore, we hypothesized a role for ClC-3 in drug resistance. Here, we show that ClC-3 is expressed in neuroendocrine tumor cell lines, such as BON, LCC-18, and QGP-1, and localized in intracellular vesicles co-labeled with the late endosomal/lysosomal marker LAMP-1. ClC-3 overexpression increased the acidity of intracellular vesicles, as assessed by acridine orange staining, and enhanced resistance to the chemotherapeutic drug etoposide by almost doubling the IC(50) in either BON or HEK293 cell lines. Prevention of organellar acidification, by inhibition of the vacuolar H(+)-ATPase, reduced etoposide resistance. No expression of common multidrug resistance transporters, such as P-glycoprotein or multidrug-related protein-1, was detected in either the BON parental cell line or the derivative clone overexpressing ClC-3. The probable mechanism of enhanced etoposide resistance can be attributed to the increase of vesicular acidification as consequence of ClC-3 overexpression. This study therefore provides first evidence for a role of intracellular CLC proteins in the modulation of cancer drug resistance.

  6. Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

    SciTech Connect

    Xu, Yuan Cardell, Lars-Olaf

    2014-02-15

    Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B{sub 2} receptor agonist) and des-Arg{sup 9}-bradykinin- (selective B{sub 1} receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE{sub 2}. The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg{sup 9}-bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B{sub 2} receptors, but not those on B{sub 1}. Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance seen in

  7. GM trees with increased resistance to herbivores: trait efficiency and their potential to promote tree growth.

    PubMed

    Hjältén, Joakim; Axelsson, E Petter

    2015-01-01

    Climate change, as well as a more intensive forestry, is expected to increase the risk of damage by pests and pathogens on trees, which can already be a severe problem in tree plantations. Recent development of biotechnology theoretically allows for resistance enhancement that could help reduce these risks but we still lack a comprehensive understanding of benefits and tradeoffs with pest resistant GM (genetically modified) trees. We synthesized the current knowledge on the effectiveness of GM forest trees with increased resistance to herbivores. There is ample evidence that induction of exogenous Bacillus thuringiensis genes reduce performance of target pests whereas upregulation of endogenous resistance traits e.g., phenolics, generates variable results. Our review identified very few studies estimating the realized benefits in tree growth of GM trees in the field. This is concerning as the realized benefit with insect resistant GM plants seems to be context-dependent and likely manifested only if herbivore pressure is sufficiently high. Future studies of secondary pest species and resistance evolution in pest to GM trees should be prioritized. But most importantly we need more long-term field tests to evaluate the benefits and risks with pest resistant GM trees.

  8. GM trees with increased resistance to herbivores: trait efficiency and their potential to promote tree growth

    PubMed Central

    Hjältén, Joakim; Axelsson, E. Petter

    2015-01-01

    Climate change, as well as a more intensive forestry, is expected to increase the risk of damage by pests and pathogens on trees, which can already be a severe problem in tree plantations. Recent development of biotechnology theoretically allows for resistance enhancement that could help reduce these risks but we still lack a comprehensive understanding of benefits and tradeoffs with pest resistant GM (genetically modified) trees. We synthesized the current knowledge on the effectiveness of GM forest trees with increased resistance to herbivores. There is ample evidence that induction of exogenous Bacillus thuringiensis genes reduce performance of target pests whereas upregulation of endogenous resistance traits e.g., phenolics, generates variable results. Our review identified very few studies estimating the realized benefits in tree growth of GM trees in the field. This is concerning as the realized benefit with insect resistant GM plants seems to be context-dependent and likely manifested only if herbivore pressure is sufficiently high. Future studies of secondary pest species and resistance evolution in pest to GM trees should be prioritized. But most importantly we need more long-term field tests to evaluate the benefits and risks with pest resistant GM trees. PMID:25983736

  9. Effects of maxillary advancement and impaction on nasal airway function.

    PubMed

    Pourdanesh, F; Sharifi, R; Mohebbi, A; Jamilian, A

    2012-11-01

    The effects of Le Fort I osteotomy on the nasal airway are controversial. This study aimed to evaluate nasal airway changes after Le Fort I. 25 patients underwent conventional Le Fort I osteotomy and were separated into three groups depending on the type of surgery they underwent. 11 patients needed maxillary impaction, 9 underwent maxillary advancement, and 5 had both maxillary impaction and advancement. Rhinological examinations, anterior rhinomanometry and acoustic rhinometry were carried out 1 week before surgery and 3 months after that. Wilcoxon and χ(2) tests were used for data analysis. The samples included 19 females and 6 males with a mean age of 22.4 ± 3.32 years. Rhinomanometric assessment showed that total nasal airflow was increased from 406 ± 202 ml/s to 543 ± 268 ml/s in all three groups. Significant decrease in nasal airway resistance was seen in all three groups. Acoustic rhinometry revealed a significant decrease in total nasal volume but an increase in the cross-sectional areas of isthmus nasi (IN) and inferior concha. The rhinomanometric measurements showed improvements in the total nasal airflow after Le Fort I osteotomy with alar base cinch suture in cases where the impaction was not higher than 5.5mm.

  10. Peripheral airways obstruction in idiopathic pulmonary artery hypertension (primary).

    PubMed

    Fernandez-Bonetti, P; Lupi-Herrera, E; Martinez-Guerra, M L; Barrios, R; Seoane, M; Sandoval, J

    1983-05-01

    The mechanical properties of the lung were studied in ten nonsmokers with idiopathic pulmonary artery hypertension (IPAH) (mean pulmonary artery pressure 65.7 +/- 30 mm Hg). In the routine lung test, residual volume was found to be abnormal (greater than 120 percent of the predicted) in seven patients, and measured airway resistance was normal in eight out of the ten patients. A decreased FEF 75-85 percent, abnormal values for the helium-air flow ratios and increased closing capacities were documented in eight of ten patients in whom lung elastic recoil was normal (six of ten) or increased (four of ten). These features suggest peripheral airways obstruction (PAO) which was also supported by histopathologic findings in three cases (one biopsy and two necropsies). The observed changes in lung compliance could be related to the behavior of the coupling of the air-space and vascular compartments. The etiology of PAO in IPAH patients is not known, but our results indicate that both the peripheral airways and the pulmonary circulation are affected. The knowledge of PAO in IPAH patients could help to better understand the observed V/Q inequality in this entity.

  11. Increased Water Activity Reduces the Thermal Resistance of Salmonella enterica in Peanut Butter

    PubMed Central

    He, Yingshu; Li, Ye; Salazar, Joelle K.; Yang, Jingyun; Tortorello, Mary Lou

    2013-01-01

    Increased water activity in peanut butter significantly (P < 0.05) reduced the heat resistance of desiccation-stressed Salmonella enterica serotypes treated at 90°C. The difference in thermal resistance was less notable when strains were treated at 126°C. Using scanning electron microscopy, we observed minor morphological changes of S. enterica cells resulting from desiccation and rehydration processes in peanut oil. PMID:23728806

  12. Resistance training increases total energy expenditure and free-living physical activity in older adults.

    PubMed

    Hunter, G R; Wetzstein, C J; Fields, D A; Brown, A; Bamman, M M

    2000-09-01

    The purpose of this study was to determine what effects 26 wk of resistance training have on resting energy expenditure (REE), total free-living energy expenditure (TEE), activity-related energy expenditure (AEE), engagement in free-living physical activity as measured by the activity-related time equivalent (ARTE) index, and respiratory exchange ratio (RER) in 61- to 77-yr-old men (n = 8) and women (n = 7). Before and after training, body composition (four-compartment model), strength, REE, TEE (doubly labeled water), AEE (TEE - REE + thermic response to meals), and ARTE (AEE adjusted for energy cost of standard activities) were evaluated. Strength (36%) and fat-free mass (2 kg) significantly increased, but body weight did not change. REE increased 6.8%, whereas resting RER decreased from 0.86 to 0.83. TEE (12%) and ARTE (38%) increased significantly, and AEE (30%) approached significance (P = 0.06). The TEE increase remained significant even after adjustment for the energy expenditure of the resistance training. In response to resistance training, TEE increased and RER decreased. The increase in TEE occurred as a result of increases in both REE and physical activity. These results suggest that resistance training may have value in increasing energy expenditure and lipid oxidation rates in older adults, thereby improving their metabolic profiles.

  13. Fungal colonization with Pneumocystis correlates to increasing chloride channel accessory 1 (hCLCA1) suggesting a pathway for up-regulation of airway mucus responses, in infant lungs

    PubMed Central

    Pérez, Francisco J.; Ponce, Carolina A.; Rojas, Diego A.; Iturra, Pablo A.; Bustamante, Rebeca I.; Gallo, Myriam; Hananias, Karime; Vargas, Sergio L.

    2014-01-01

    Fungal colonization with Pneumocystis is associated with increased airway mucus in infants during their primary Pneumocystis infection, and to severity of COPD in adults. The pathogenic mechanisms are under investigation. Interestingly, increased levels of hCLCA1 – a member of the calcium-sensitive chloride conductance family of proteins that drives mucus hypersecretion – have been associated with increased mucus production in patients diagnosed with COPD and in immunocompetent rodents with Pneumocystis infection. Pneumocystis is highly prevalent in infants; therefore, the contribution of Pneumocystis to hCLCA1 expression was examined in autopsied infant lungs. Respiratory viruses that may potentially increase mucus, were also examined. hCLCA1 expression was measured using actin-normalized Western-blot, and the burden of Pneumocystis organisms was quantified by qPCR in 55 autopsied lungs from apparently healthy infants who died in the community. Respiratory viruses were diagnosed using RT-PCR for RSV, metapneumovirus, influenza, and parainfluenza viruses; and by PCR for adenovirus. hCLCA1 levels in virus positive samples were comparable to those in virus-negative samples. An association between Pneumocystis and increased hCLCA1 expression was documented (P=0.028). Additionally, increasing Pneumocystis burden correlated with increasing hCLCA1 protein expression levels (P=0.017). Results strengthen the evidence of Pneumocystis-associated up-regulation of mucus-related airway responses in infant lungs. Further characterization of this immunocompetent host-Pneumocystis-interaction, including assessment of potential clinical significance, is warranted. PMID:25379375

  14. Estimation of airway obstruction using oximeter plethysmograph waveform data

    PubMed Central

    Arnold, Donald H; Spiro, David M; Desmond, Renee' A; Hagood, James S

    2005-01-01

    Background Validated measures to assess the severity of airway obstruction in patients with obstructive airway disease are limited. Changes in the pulse oximeter plethysmograph waveform represent fluctuations in arterial flow. Analysis of these fluctuations might be useful clinically if they represent physiologic perturbations resulting from airway obstruction. We tested the hypothesis that the severity of airway obstruction could be estimated using plethysmograph waveform data. Methods Using a closed airway circuit with adjustable inspiratory and expiratory pressure relief valves, airway obstruction was induced in a prospective convenience sample of 31 healthy adult subjects. Maximal change in airway pressure at the mouthpiece was used as a surrogate measure of the degree of obstruction applied. Plethysmograph waveform data and mouthpiece airway pressure were acquired for 60 seconds at increasing levels of inspiratory and expiratory obstruction. At each level of applied obstruction, mean values for maximal change in waveform area under the curve and height as well as maximal change in mouth pressure were calculated for sequential 7.5 second intervals. Correlations of these waveform variables with mouth pressure values were then performed to determine if the magnitude of changes in these variables indicates the severity of airway obstruction. Results There were significant relationships between maximal change in area under the curve (P < .0001) or height (P < 0.0001) and mouth pressure. Conclusion The findings suggest that mathematic interpretation of plethysmograph waveform data may estimate the severity of airway obstruction and be of clinical utility in objective assessment of patients with obstructive airway diseases. PMID:15985171

  15. The effect of surface roughness on the resistivity increase in nanometric dimensions

    NASA Astrophysics Data System (ADS)

    Marom, H.; Eizenberg, M.

    2006-06-01

    Materials with nanometric dimensions exhibit higher electrical resistivity due to additional scattering centers for the conduction electrons, mainly from surfaces and grain boundaries. In this study we focus on the effect of surfaces by implementing an experimental technique in which the resistivity of thin films is measured during and after etching them inside a solution. This technique enables to analyze the contribution of surfaces to the resistivity and gives a unique insight as for the effect of surface roughness. It is shown that the scattering of electrons from annealed copper films with smooth enough surfaces is mostly specular and that the resistivity in this case is dominated by the effect of grain boundaries. However, when the roughness of the surface becomes larger than the de Broglie wavelength of the electrons, a substantial increase in resistivity occurs. This roughness-induced resistivity is analyzed and shown to be much larger in certain cases than the resistivity predicted for a flat surface, even when all electron scatterings are assumed to be completely diffused.

  16. Overexpression of a Chitinase Gene from Trichoderma asperellum Increases Disease Resistance in Transgenic Soybean.

    PubMed

    Zhang, Fuli; Ruan, Xianle; Wang, Xian; Liu, Zhihua; Hu, Lizong; Li, Chengwei

    2016-12-01

    In the present study, a chi gene from Trichoderma asperellum, designated Tachi, was cloned and functionally characterized in soybean. Firstly, the effects of sodium thiosulfate on soybean Agrobacterium-mediated genetic transformation with embryonic tip regeneration system were investigated. The transformation frequency was improved by adding sodium thiosulfate in co-culture medium for three soybean genotypes. Transgenic soybean plants with constitutive expression of Tachi showed increased resistance to Sclerotinia sclerotiorum compared to WT plants. Meanwhile, overexpression of Tachi in soybean exhibited increased reactive oxygen species (ROS) level as well as peroxidase (POD) and catalase (SOD) activities, decreased malondialdehyde (MDA) content, along with diminished electrolytic leakage rate after S. sclerotiorum inoculation. These results suggest that Tachi can improve disease resistance in plants by enhancing ROS accumulation and activities of ROS scavenging enzymes and then diminishing cell death. Therefore, Tachi represents a candidate gene with potential application for increasing disease resistance in plants.

  17. Gender related differences in airway tone in children.

    PubMed

    Landau, L I; Morgan, W; McCoy, K S; Taussig, L M

    1993-07-01

    The effects of gender, volume history, and inhaled atropine and isoproterenol on lung mechanics were assessed in 16 normal boys and 14 normal girls using lung volumes, flow-volume curves, and oscillatory resistances. Flows were measured from full and partial forced expiratory flow-volume curves. Six girls and 6 boys were studied before and after inhaled atropine, and 10 boys and 8 girls before and after inhaled isoproterenol. Girls demonstrated a significant increase in flows on full and partial curves with a deep inspiration [Vmax-partial 0.73 +/- 0.34 (SD) to Vmax-full 0.80 +/- 0.37 and 0.83 +/- 0.20 to 1.06 +/- 0.29 TLC/s in each group] and following inhalation of isoproterenol on the partial curves only (0.73 +/- 0.34 to 0.93 +/- 0.40 TLC/s). Boys showed a small but significant increase in Vmax with isoproterenol on full curves but not on partial curves. Following atropine, boys demonstrated a significant increase in Vmax on partial flow-volume curves (0.78 +/- 0.28 to 1.00 +/- 0.35 TLC/s) and a significant decrease in specific respiratory resistance (7.6 +/- 2.7 to 5.1 +/- 0.9 cmH2O/s), whereas girls had no such changes. These data suggest that boys have greater resting airway tone than girls and that this tone is less responsive to deep inspiration and isoproterenol independently, although a combination of isoproterenol and a deep inspiration will produce increased flows in boys. Atropine reduces airway tone predominantly in boys, suggesting that the increased resting airway tone in boys is partially mediated via the vagus nerve.

  18. New treatment options for infections caused by increasingly antimicrobial-resistant Neisseria gonorrhoeae.

    PubMed

    Lee, Hyukmin; Lee, Kyungwon; Chong, Yunsop

    2016-01-01

    The emergence of high-level resistance to ceftriaxone is giving rise to serious concern about absence of effective treatment options to cure gonococcal infections. Increasing the dosage regimen can be applied to ceftriaxone and azithromycin, but the emergence of high-level resistance has already been reported. Spectinomycin is another active drug but has low efficacy in the treatment of pharyngeal gonorrhoea. Conventional antibiotics could be introduced for gonococcal treatment, but they have some limitations, such as the absence of clinical trials and breakpoint. Combining antibiotics is another promising method to cure patients and to prevent the emergence of resistance. The most important strategy to maintain the efficacy of antibiotics is rapid detection and dissemination control of novel resistant isolate.

  19. Controversies in Pediatric Perioperative Airways

    PubMed Central

    Klučka, Jozef; Štourač, Petr; Štoudek, Roman; Ťoukálková, Michaela; Harazim, Hana; Kosinová, Martina

    2015-01-01

    Pediatric airway management is a challenge in routine anesthesia practice. Any airway-related complication due to improper procedure can have catastrophic consequences in pediatric patients. The authors reviewed the current relevant literature using the following data bases: Google Scholar, PubMed, Medline (OVID SP), and Dynamed, and the following keywords: Airway/s, Children, Pediatric, Difficult Airways, and Controversies. From a summary of the data, we identified several controversies: difficult airway prediction, difficult airway management, cuffed versus uncuffed endotracheal tubes for securing pediatric airways, rapid sequence induction (RSI), laryngeal mask versus endotracheal tube, and extubation timing. The data show that pediatric anesthesia practice in perioperative airway management is currently lacking the strong evidence-based medicine (EBM) data that is available for adult subpopulations. A number of procedural steps in airway management are derived only from adult populations. However, the objective is the same irrespective of patient age: proper securing of the airway and oxygenation of the patient. PMID:26759809

  20. Acid aspiration-induced airways hyperresponsiveness in mice

    PubMed Central

    Leclair, Timothy R.; von Reyn, Jessica; Larrabee, Yuna C.; Cloutier, Mary E.; Irvin, Charles G.; Bates, Jason H. T.

    2009-01-01

    The role of gastroesophageal reflux and micro-aspiration as a trigger of airways hyperresponsiveness (AHR) in patients with asthma is controversial. The role of acid reflux and aspiration as a direct cause of AHR in normal subjects is also unclear. We speculated that aspiration of a weak acid with a pH (1.8) equivalent to the upper range of typical gastric contents would lead to AHR in naive mice. We further speculated that modest reductions in aspirate acidity to a level expected during gastric acid suppression therapy (pH 4.0) would impede aspiration-induced AHR. BALB/c female mice were briefly anesthetized with isoflurane and allowed to aspirate 75 μl of saline with HCl (pH 1.8, 4.0, or 7.4) or underwent sham aspiration. Mice were re-anesthetized 2 or 24 h later, underwent tracheostomy, and were coupled to a mechanical ventilator. Forced oscillations were used to periodically measure respiratory impedance (Zrs) following aerosol delivery of saline and increasing doses of methacholine to measure for AHR. Values for elastance (H), airways resistance (RN), and tissue damping (G) were derived from Zrs. Aspirate pH of 1.8 led to a significant overall increase in peak RN, G, and H compared with pH 4.0 and 7.4 at 2 and 24 h. Differences between pH 7.4 and 4.0 were not significant. In mice aspirating pH 1.8 compared with controls, airway lavage fluid contained more neutrophils, higher protein, and demonstrated higher permeability. We conclude that acid aspiration triggers an acute AHR, driven principally by breakdown of epithelial barrier integrity within the airways. PMID:19797689

  1. Duplication and amplification of antibiotic resistance genes enable increased resistance in isolates of multidrug-resistant Salmonella Typhimurium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    During normal bacterial DNA replication, gene duplication and amplification (GDA) events occur randomly at a low frequency in the genome throughout a population. In the absence of selection, GDA events that increase the number of copies of a bacterial gene (or a set of genes) are lost. Antibiotic ...

  2. Metformin prevents the effects of Pseudomonas aeruginosa on airway epithelial tight junctions and restricts hyperglycaemia-induced bacterial growth.

    PubMed

    Patkee, Wishwanath R A; Carr, Georgina; Baker, Emma H; Baines, Deborah L; Garnett, James P

    2016-04-01

    Lung disease and elevation of blood glucose are associated with increased glucose concentration in the airway surface liquid (ASL). Raised ASL glucose is associated with increased susceptibility to infection by respiratory pathogens including Staphylococcus aureus and Pseudomonas aeruginosa. We have previously shown that the anti-diabetes drug, metformin, reduces glucose-induced S. aureus growth across in vitro airway epithelial cultures. The aim of this study was to investigate whether metformin has the potential to reduce glucose-induced P. aeruginosa infections across airway epithelial (Calu-3) cultures by limiting glucose permeability. We also explored the effect of P. aeruginosa and metformin on airway epithelial barrier function by investigating changes in tight junction protein abundance. Apical P. aeruginosa growth increased with basolateral glucose concentration, reduced transepithelial electrical resistance (TEER) and increased paracellular glucose flux. Metformin pre-treatment of the epithelium inhibited the glucose-induced growth of P. aeruginosa, increased TEER and decreased glucose flux. Similar effects on bacterial growth and TEER were observed with the AMP activated protein kinase agonist, 5-aminoimidazole-4-carboxamide ribonucleotide. Interestingly, metformin was able to prevent the P. aeruginosa-induced reduction in the abundance of tight junction proteins, claudin-1 and occludin. Our study highlights the potential of metformin to reduce hyperglycaemia-induced P. aeruginosa growth through airway epithelial tight junction modulation, and that claudin-1 and occludin could be important targets to regulate glucose permeability across airway epithelia and supress bacterial growth. Further investigation into the mechanisms regulating metformin and P. aeruginosa action on airway epithelial tight junctions could yield new therapeutic targets to prevent/suppress hyperglycaemia-induced respiratory infections, avoiding the use of antibiotics.

  3. Pressure-volume behaviour of the rat upper airway: effects of tongue muscle activation

    PubMed Central

    Bailey, E Fiona; Fregosi, Ralph F

    2003-01-01

    Our hypothesis was that the simultaneous activation of tongue protrudor and retractor muscles (co-activation) would constrict and stiffen the pharyngeal airway more than the independent activation of tongue protrudor muscles. Upper airway stiffness was determined by injecting known volumes of air into the sealed pharyngeal airway of the anaesthetized rat while measuring nasal pressure under control (no-stimulus) and stimulus conditions (volume paired with hypoglossal (XII) nerve stimulation). Stimulation of the whole XII nerves (co-activation) or the medial XII branches (protrudor activation) effected similar increases in total pharyngeal airway stiffness. Importantly, co-activation produced volume compression (airway narrowing) at large airway volumes (P < 0.05), but had no effect on airway dimension at low airway volumes. In comparison, protrudor activation resulted in significant volume expansion (airway dilatation) at low airway volumes and airway narrowing at high airway volumes (P < 0.05). In conclusion, both co-activation and independent protrudor muscle activation increase airway stiffness. However, their effects on airway size are complex and depend on the condition of the airway at the time of activation. PMID:12640023

  4. Experimental elimination of parasites in nature leads to the evolution of increased resistance in hosts

    PubMed Central

    Dargent, Felipe; Scott, Marilyn E.; Hendry, Andrew P.; Fussmann, Gregor F.

    2013-01-01

    A reduction in the strength of selection is expected to cause the evolution of reduced trait expression. Elimination of a parasite should thus cause the evolution of reduced resistance to that parasite. To test this prediction in nature, we studied the fourth- and eighth-generation descendants of guppies (Poecilia reticulata) introduced into four natural streams following experimental elimination of a common and deleterious parasite (Gyrodactylus spp.). After two generations of laboratory rearing to control for plasticity and maternal effects, we infected individual fish to assess their resistance to the parasite. Contrary to theoretical expectations, the introduced guppy populations had rapidly and repeatably evolved increased resistance to the now-absent parasite. This evolution was not owing to a resistance-tolerance trade-off, nor to differences in productivity among the sites. Instead, a leading candidate hypothesis is that the rapid life-history evolution typical in such introductions pleiotropically increases parasite resistance. Our study adds a new dimension to the growing evidence for contemporary evolution in the wild, and also points to the need for a re-consideration of simple expectations from host–parasite theory. In particular, our results highlight the need for increased consideration of multiple sources of selection and pleiotropy when studying evolution in natural contexts. PMID:24197417

  5. Increased insulin translation from an insulin splice-variant overexpressed in diabetes, obesity, and insulin resistance.

    PubMed

    Minn, Alexandra H; Lan, Hong; Rabaglia, Mary E; Harlan, David M; Peculis, Brenda A; Attie, Alan D; Shalev, Anath

    2005-03-01

    Type 2 diabetes occurs when pancreatic beta-cells become unable to compensate for the underlying insulin resistance. Insulin secretion requires beta-cell insulin stores to be replenished by insulin biosynthesis, which is mainly regulated at the translational level. Such translational regulation often involves the 5'-untranslated region. Recently, we identified a human insulin splice-variant (SPV) altering only the 5'-untranslated region and conferring increased translation efficiency. We now describe a mouse SPV (mSPV) that is found in the cytoplasm and exhibits increased translation efficiency resulting in more normal (prepro)insulin protein per RNA. The RNA stability of mSPV is not increased, but the predicted secondary RNA structure is altered, which may facilitate translation. To determine the role of mSPV in insulin resistance and diabetes, mSPV expression was measured by quantitative real-time RT-PCR in islets from three diabetic and/or insulin-resistant, obese and nonobese, mouse models (BTBRob/ob, C57BL/6ob/ob, and C57BL/6azip). Interestingly, mSPV expression was significantly higher in all diabetic/insulin-resistant mice compared with wild-type littermates and was dramatically induced in primary mouse islets incubated at high glucose. This raises the possibility that the mSPV may represent a compensatory beta-cell mechanism to enhance insulin biosynthesis when insulin requirements are elevated by hyperglycemia/insulin resistance.

  6. Wastewater treatment contributes to selective increase of antibiotic resistance among Acinetobacter spp.

    PubMed

    Zhang, Yongli; Marrs, Carl F; Simon, Carl; Xi, Chuanwu

    2009-06-01

    The occurrence and spread of multi-drug resistant bacteria is a pressing public health problem. The emergence of bacterial resistance to antibiotics is common in areas where antibiotics are heavily used, and antibiotic-resistant bacteria also increasingly occur in aquatic environments. The purpose of the present study was to evaluate the impact of the wastewater treatment process on the prevalence of antibiotic resistance in Acinetobacter spp. in the wastewater and its receiving water. During two different events (high-temperature, high-flow, 31 degrees C; and low-temperature, low-flow, 8 degrees C), 366 strains of Acinetobacter spp. were isolated from five different sites, three in a wastewater treatment plant (raw influent, second effluent, and final effluent) and two in the receiving body (upstream and downstream of the treated wastewater discharge point). The antibiotic susceptibility phenotypes were determined by the disc-diffusion method for 8 antibiotics, amoxicillin/clavulanic acid (AMC), chloramphenicol (CHL), ciprofloxacin (CIP), colistin (CL), gentamicin (GM), rifampin (RA), sulfisoxazole (SU), and trimethoprim (TMP). The prevalence of antibiotic resistance in Acinetobacter isolates to AMC, CHL, RA, and multi-drug (three antibiotics or more) significantly increased (p<0.01) from the raw influent samples (AMC, 8.7%; CHL, 25.2%; RA, 63.1%; multi-drug, 33.0%) to the final effluent samples (AMC, 37.9%; CHL, 69.0%; RA, 84.5%; multi-drug, 72.4%), and was significantly higher (p<0.05) in the downstream samples (AMC, 25.8%; CHL, 48.4%; RA, 85.5%; multi-drug, 56.5%) than in the upstream samples (AMC, 9.5%; CHL, 27.0%; RA, 65.1%; multi-drug, 28.6%). These results suggest that wastewater treatment process contributes to the selective increase of antibiotic resistant bacteria and the occurrence of multi-drug resistant bacteria in aquatic environments.

  7. Deletion of airway cilia results in noninflammatory bronchiectasis and hyperreactive airways

    PubMed Central

    Gilley, Sandra K.; Stenbit, Antine E.; Pasek, Raymond C.; Sas, Kelli M.; Steele, Stacy L.; Amria, May; Bunni, Marlene A.; Estell, Kimberly P.; Schwiebert, Lisa M.; Flume, Patrick; Gooz, Monika; Haycraft, Courtney J.; Yoder, Bradley K.; Miller, Caroline; Pavlik, Jacqueline A.; Turner, Grant A.; Sisson, Joseph H.

    2013-01-01

    The mechanisms for the development of bronchiectasis and airway hyperreactivity have not been fully elucidated. Although genetic, acquired diseases and environmental influences may play a role, it is also possible that motile cilia can influence this disease process. We hypothesized that deletion of a key intraflagellar transport molecule, IFT88, in mature mice causes loss of cilia, resulting in airway remodeling. Airway cilia were deleted by knockout of IFT88, and airway remodeling and pulmonary function were evaluated. In IFT88− mice there was a substantial loss of airway cilia on respiratory epithelium. Three months after the deletion of cilia, there was clear evidence for bronchial remodeling that was not associated with inflammation or apparent defects in mucus clearance. There was evidence for airway epithelial cell hypertrophy and hyperplasia. IFT88− mice exhibited increased airway reactivity to a methacholine challenge and decreased ciliary beat frequency in the few remaining cells that possessed cilia. With deletion of respiratory cilia there was a marked increase in the number of club cells as seen by scanning electron microscopy. We suggest that airway remodeling may be exacerbated by the presence of club cells, since these cells are involved in airway repair. Club cells may be prevented from differentiating into respiratory epithelial cells because of a lack of IFT88 protein that is necessary to form a single nonmotile cilium. This monocilium is a prerequisite for these progenitor cells to transition into respiratory epithelial cells. In conclusion, motile cilia may play an important role in controlling airway structure and function. PMID:24213915

  8. Cisplatin-resistant cells express increased levels of a factor that recognizes damaged DNA

    SciTech Connect

    Chu, G.; Chang, E. )

    1990-05-01

    Cancer treatment with the drug cisplatin is often thwarted by the emergence of drug-resistant cells. To study this phenomenon, the authors identified two independent cellular factors that recognize cisplatin-damaged DNA. One of the two factors, designated XPE binding factor, is deficient in complementation group E of xeroderma pigmentosum, an inherited disease characterized by defective repair of DNA damaged by ultraviolet radiation, cisplatin, and other agents. Human tumor cell lines selected for resistance to cisplatin showed more efficient DNA repair and increased expression of XPE binding factor. These results suggest that XPE binding factor may be responsible, at least in part, for the development of cisplatin resistance in human tumors and that the mechanism may be increased DNA repair.

  9. Inspiratory-resistive loading increases the ventilatory response to arousal but does not reduce genioglossus muscle activity on the return to sleep.

    PubMed

    Cori, Jennifer M; Nicholas, Christian L; Baptista, Shaira; Huynh, Ivan; Rochford, Peter D; O'Donoghue, Fergal J; Trinder, John A; Jordan, Amy S

    2012-09-01

    Arousals from sleep are thought to predispose to obstructive sleep apnea by causing hyperventilation and hypocapnia, which reduce airway dilator muscle activity on the return to sleep. However, prior studies of auditory arousals have not resulted in reduced genioglossus muscle activity [GG-electromyogram (EMG)], potentially because airway resistance prior to arousal was low, leading to a small ventilatory response to arousal and minimal hypocapnia. Thus we aimed to increase the ventilatory response to arousal by resistive loading prior to auditory arousal and determine whether reduced GG-EMG occurred on the return to sleep. Eighteen healthy young men and women were recruited. Subjects were instrumented with a nasal mask with a pneumotachograph, an epiglottic pressure catheter, and intramuscular GG-EMG electrodes. Mask CO(2) levels were monitored. Three- to 15-s arousals from sleep were induced with auditory tones after resting breathing (No-Load) or inspiratory-resistive loading (Load; average 8.4 cmH(2)O·l(-1)·s(-1)). Peak minute ventilation following arousal was greater after Load than No-Load (mean ± SE; 8.0 ± 0.6 vs. 7.4 ± 0.6 l/min, respectively). However, the nadir end tidal partial pressure of CO(2) did not differ between Load conditions (43.1 ± 0.6 and 42.8 ± 0.5 mmHg, respectively), and no period of reduced GG activity occurred following the return to sleep (GG-EMG baseline, minimum after Load and No-Load = 2.9 ± 1.2%, 3.1 ± 1.3%, and 3.0 ± 1.3% max, respectively). These findings indicate that the hyperventilation, which occurs following tone-induced arousal, is appropriate for the prevailing level of respiratory drive, because loading did not induce marked hypocapnia or lower GG muscle activity on the return to sleep. Whether similar findings occur following obstructive events in patients remains to be determined.

  10. Increased resistance to a generalist herbivore in a salinity-stressed non-halophytic plant

    PubMed Central

    Renault, Sylvie; Wolfe, Scott; Markham, John; Avila-Sakar, Germán

    2016-01-01

    Plants often grow under the combined stress of several factors. Salinity and herbivory, separately, can severely hinder plant growth and reproduction, but the combined effects of both factors are still not clearly understood. Salinity is known to reduce plant tissue nitrogen content and growth rates. Since herbivores prefer tissues with high N content, and biochemical pathways leading to resistance are commonly elicited by salt-stress, we hypothesized that plants growing in saline conditions would have enhanced resistance against herbivores. The non-halophyte, Brassica juncea, and the generalist herbivore Trichoplusia ni were used to test the prediction that plants subjected to salinity stress would be both more resistant and more tolerant to herbivory than those growing without salt stress. Plants were grown under different NaCl levels, and either exposed to herbivores and followed by removal of half of their leaves, or left intact. Plants were left to grow and reproduce until senescence. Tissue quality was assessed, seeds were counted and biomass of different organs measured. Plants exposed to salinity grew less, had reduced tissue nitrogen, protein and chlorophyll content, although proline levels increased. Specific leaf area, leaf water content, transpiration and root:shoot ratio remained unaffected. Plants growing under saline condition had greater constitutive resistance than unstressed plants. However, induced resistance and tolerance were not affected by salinity. These results support the hypothesis that plants growing under salt-stress are better defended against herbivores, although in B. juncea this may be mostly through resistance, and less through tolerance. PMID:27169610

  11. Increasing Incidence of Multidrug Resistance Among Cystic Fibrosis Respiratory Bacterial Isolates.

    PubMed

    Rutter, W Cliff; Burgess, Donna R; Burgess, David S

    2017-01-01

    Pseudomonas aeruginosa and Staphylococcus aureus are common pathogens in cystic fibrosis (CF) patients with increasing multidrug resistance (MDR). This study characterized antimicrobial susceptibility trends among organisms isolated from the respiratory tract of CF patients. Microbiological culture and sensitivity results for all CF patients were collected from January 2010 through December 2014. Minimum inhibitory concentrations were obtained using Phoenix(®) and Etest(®) methods. Clinical and Laboratory Standards Institute guidelines were used to remove duplicate isolates and develop antimicrobial susceptibility reports. MDR was defined as resistance to one agent in three or more antibiotic classes or oxacillin resistance in S. aureus. Overall, 542 bacterial isolates from 376 cultures were analyzed for trends. P. aeruginosa (41%), S. aureus (40%), and Stenotrophomonas maltophilia (8%) were the most commonly isolated organisms. Multidrug-resistant organism isolation increased from 39% to 49% (r = 0.76, p = 0.13), while representing 47.6% of all isolates. Multidrug-resistant P. aeruginosa incidence increased each year from 26% to 43% (r = 0.89, p = 0.046), while P. aeruginosa isolation decreased from 47% to 38% over the study period (r = -0.93, p = 0.02). MRSA accounted for 62.6% of all S. aureus isolated, while overall multidrug-resistant S. aureus incidence was 73.1% in all cultures. MDR among common pathogens in CF continues to increase. Empiric therapy for CF exacerbations should be targeted to previous antimicrobial susceptibility, and P. aeruginosa and S. aureus should be empirically covered.

  12. Streptomycin use in apple orchards did not increase abundance of mobile resistance genes.

    PubMed

    Duffy, Brion; Holliger, Eduard; Walsh, Fiona

    2014-01-01

    Streptomycin is used as a first-line defense and tetracycline as a second-line defense, in the fight against fire blight disease in apple and pear orchards. We have performed the first study to quantitatively analyze the influence of streptomycin use in agriculture on the abundance of streptomycin and tetracycline resistance genes in apple orchards. Flowers, leaves, and soil were collected from three orchard sites in 2010, 2011, and 2012. Gene abundance distribution was analyzed using two-way anova and principal component analysis to investigate relationships between gene abundance data over time and treatment. The mobile antibiotic resistance genes, strA, strB, tetB, tetM, tetW, and the insertion sequence IS1133, were detected prior to streptomycin treatment in almost all samples, indicating the natural presence of these resistance genes in nature. Statistically significant increases in the resistance gene abundances were occasional, inconsistent, and not reproducible from one year to the next. We conclude that the application of streptomycin in these orchards was not associated with sustained increases in streptomycin or tetracycline resistance gene abundances.

  13. Increased Risk for Multidrug-Resistant Tuberculosis in Migratory Workers, Armenia

    PubMed Central

    Crape, Byron; Grigoryan, Ruzanna; Martirosyan, Hripsime; Petrosyan, Varduhi

    2015-01-01

    To understand use of tuberculosis (TB) services for migrant workers, we conducted a cross-sectional census of 95 migrant workers with TB from Armenia by using medical record reviews and face-to-face interviews. Prolonged time between diagnosis and treatment, treatment interruption, and treatment defaults caused by migrant work might increase the risk for multidrug-resistant TB. PMID:25695488

  14. Bleomycin increases amikacin and streptomycin resistance in Escherichia coli harboring transposon Tn5.

    PubMed Central

    Blazquez, J; Martinez, J L; Baquero, F

    1993-01-01

    The antitumor antibiotic bleomycin acts as a transcriptional inducer of the neo-ble-str operon of the transposon Tn5, increasing the resistance level to streptomycin and amikacin in Tn5-containing Escherichia coli. The mechanism may involve a recA-independent induction mediated by DNA damage. Images PMID:7694544

  15. Overexpression of a citrus NDR1 ortholog increases disease resistance in Arabidopsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Emerging devastating diseases, such as Huanglongbing (HLB) and citrus canker, have caused tremendous losses to the citrus industry worldwide. Genetic engineering is a powerful approach that could allow us to increase citrus resistance against these diseases. The key to the success of this approach r...

  16. Preparation and characterization of sorghum flour with increased resistant starch content

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The primary objective of this research was to develop an effective process to increase the resistant starch content of sorghum flour. A secondary objective was to investigate the role of the sorghum proteins on starch digestibility. Samples of white sorghum flour (28.9% amylose content) with differe...

  17. Morphological and morphometric studies of the airways of sheep with acute airway hypersensitivity to inhaled Ascaris suum.

    PubMed

    Chen, W; Alley, M R; Manktelow, B W

    1991-10-01

    The airways of 12 sheep with naturally-occurring allergic airway hypersensitivity, six of which had changes in both airway resistance and dynamic lung compliance (Group A) and six of which had changes in only dynamic lung compliance (Group B), were compared quantitatively with six non-reacting sheep (Group C) in order to examine the relation between airway hypersensitivity and various morphological features thought to be related to airway hypersensitivity. Compared to the non-reacting sheep (Group C), the hypersensitive sheep (Groups A and B) had a thinner epithelium in medium bronchi and bronchioles, fewer goblet cells in bronchioles, and greater gland area at most airway levels. The differences of the gland dimensions and the types of mucosubstance between hypersensitive and non-reacting animals were more variable. No significant differences between the three groups were noted with regard to luminal occlusion or epithelial sloughing and squamous metaplasia. Although there was a positive association between epithelial thickness and goblet cell density in the small airways, the development of allergic airway hypersensitivity in sheep may occur in the absence of major morphological changes in the airway epithelium.

  18. Nitrogen Dioxide Exposure and Airway Responsiveness in ...

    EPA Pesticide Factsheets

    Controlled human exposure studies evaluating the effect of inhaled NO2 on the inherent responsiveness of the airways to challenge by bronchoconstricting agents have had mixed results. In general, existing meta-analyses show statistically significant effects of NO2 on the airway responsiveness of individuals with asthma. However, no meta-analysis has provided a comprehensive assessment of clinical relevance of changes in airway responsiveness, the potential for methodological biases in the original papers, and the distribution of responses. This paper provides analyses showing that a statistically significant fraction, 70% of individuals with asthma exposed to NO2 at rest, experience increases in airway responsiveness following 30-minute exposures to NO2 in the range of 200 to 300 ppb and following 60-minute exposures to 100 ppb. The distribution of changes in airway responsiveness is log-normally distributed with a median change of 0.75 (provocative dose following NO2 divided by provocative dose following filtered air exposure) and geometric standard deviation of 1.88. About a quarter of the exposed individuals experience a clinically relevant reduction in their provocative dose due to NO2 relative to air exposure. The fraction experiencing an increase in responsiveness was statistically significant and robust to exclusion of individual studies. Results showed minimal change in airway responsiveness for individuals exposed to NO2 during exercise. A variety of fa

  19. Innate Immune Signaling Activated by MDR Bacteria in the Airway.

    PubMed

    Parker, Dane; Ahn, Danielle; Cohen, Taylor; Prince, Alice

    2016-01-01

    Health care-associated bacterial pneumonias due to multiple-drug resistant (MDR) pathogens are an important public health problem and are major causes of morbidity and mortality worldwide. In addition to antimicrobial resistance, these organisms have adapted to the milieu of the human airway and have acquired resistance to the innate immune clearance mechanisms that normally prevent pneumonia. Given the limited efficacy of antibiotics, bacterial clearance from the airway requires an effective immune response. Understanding how specific airway pathogens initiate and regulate innate immune signaling, and whether this response is excessive, leading to host-induced pathology may guide future immunomodulatory therapy. We will focus on three of the most important causes of health care-associated pneumonia, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, and review the mechanisms through which an inappropriate or damaging innate immune response is stimulated, as well as describe how airway pathogens cause persistent infection by evading immune activation.

  20. Innate Immune Signaling Activated by MDR Bacteria in the Airway

    PubMed Central

    Parker, Dane; Ahn, Danielle; Cohen, Taylor; Prince, Alice

    2015-01-01

    Health care-associated bacterial pneumonias due to multiple-drug resistant (MDR) pathogens are an important public health problem and are major causes of morbidity and mortality worldwide. In addition to antimicrobial resistance, these organisms have adapted to the milieu of the human airway and have acquired resistance to the innate immune clearance mechanisms that normally prevent pneumonia. Given the limited efficacy of antibiotics, bacterial clearance from the airway requires an effective immune response. Understanding how specific airway pathogens initiate and regulate innate immune signaling, and whether this response is excessive, leading to host-induced pathology may guide future immunomodulatory therapy. We will focus on three of the most important causes of health care-associated pneumonia, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, and review the mechanisms through which an inappropriate or damaging innate immune response is stimulated, as well as describe how airway pathogens cause persistent infection by evading immune activation. PMID:26582515

  1. Overexpression of a citrus NDR1 ortholog increases disease resistance in Arabidopsis

    PubMed Central

    Lu, Hua; Zhang, Chong; Albrecht, Ute; Shimizu, Rena; Wang, Guanfeng; Bowman, Kim D.

    2013-01-01

    Emerging devastating diseases, such as Huanglongbing (HLB) and citrus canker, have caused tremendous losses to the citrus industry worldwide. Genetic engineering is a powerful approach that could allow us to increase citrus resistance against these diseases. The key to the success of this approach relies on a thorough understanding of defense mechanisms of citrus. Studies of Arabidopsis and other plants have provided a framework for us to better understand defense mechanisms of citrus. Salicylic acid (SA) is a key signaling molecule involved in basal defense and resistance (R) gene-mediated defense against broad-spectrum pathogens. The Arabidopsis gene NDR1 (NON-RACE-SPECIFIC DISEASE RESISTANCE 1) is a positive regulator of SA accumulation and is specifically required for signaling mediated by a subset of R genes upon recognition of their cognate pathogen effectors. Our bioinformatic analysis identified an ortholog of NDR1 from citrus, CsNDR1. Overexpression of CsNDR1 complemented susceptibility conferred by the Arabidopsis ndr1-1 mutant to Pseudomonas syringae strains and also led to enhanced resistance to an oomycete pathogen Hyaloperonospora arabidopsidis. Such heightened resistance is associated with increased SA production and expression of the defense marker gene PATHOGENESIS RELATED 1 (PR1). In addition, we found that expression of PR1 and accumulation of SA were induced to modest levels in citrus infected with Candidatus Liberibacter asiaticus, the bacterial pathogen associated with HLB disease. Thus, our data suggest that CsNDR1 is a functional ortholog of Arabidopsis NDR1. Since Ca. L. asiaticus infection only activates modest levels of defense responses in citrus, we propose that genetically increasing SA/NDR1-mediated pathways could potentially lead to enhanced resistance against HLB, citrus canker, and other destructive diseases challenging global citrus production. PMID:23761797

  2. Stability and Normal Zone Propagation Speed in YBCO Coated Conductors with Increased Interfacial Resistance (PREPRINT)

    DTIC Science & Technology

    2010-03-01

    AFRL-RZ-WP-TP-2010-2085 STABILITY AND NORMAL ZONE PROPAGATION SPEED IN YBCO COATED CONDUCTORS WITH INCREASED INTERFACIAL RESISTANCE...August 2006 – 25 August 2008 4. TITLE AND SUBTITLE STABILITY AND NORMAL ZONE PROPAGATION SPEED IN YBCO COATED CONDUCTORS WITH INCREASED INTERFACIAL...reproduce, release, perform, display, or disclose the work. 14. ABSTRACT We will discuss how stability and speed of normal zone propagation in YBCO

  3. Airway acidification initiates host defense abnormalities in cystic fibrosis mice

    PubMed Central

    Shah, Viral S.; Meyerholz, David K.; Tang, Xiao Xiao; Reznikov, Leah; Alaiwa, Mahmoud Abou; Ernst, Sarah E.; Karp, Philip H.; Wohlford-Lenane, Christine L.; Heilmann, Kristopher P.; Leidinger, Mariah R.; Allen, Patrick D.; Zabner, Joseph; McCray, Paul B.; Ostedgaard, Lynda S.; Stoltz, David A.; Randak, Christoph O.; Welsh, Michael J.

    2016-01-01

    Cystic fibrosis (CF) is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. In humans and pigs, the loss of CFTR impairs respiratory host defenses, causing airway infection. But CF mice are spared. We found that in all three species, CFTR secreted bicarbonate into airway surface liquid. In humans and pigs lacking CFTR, unchecked H+ secretion by the nongastric H+/K+ adenosine triphosphatase (ATP12A) acidified airway surface liquid, which impaired airway host defenses. In contrast, mouse airways expressed little ATP12A and secreted minimal H+; consequently, airway surface liquid in CF and non-CF mice had similar pH. Inhibiting ATP12A reversed host defense abnormalities in human and pig airways. Conversely, expressing ATP12A in CF mouse airways acidified airway surface liquid, impaired defenses, and increased airway bacteria. These findings help explain why CF mice are protected from infection and nominate ATP12A as a potential therapeutic target for CF. PMID:26823428

  4. Dynamics of Surfactant Liquid Plugs at Bifurcating Lung Airway Models

    NASA Astrophysics Data System (ADS)

    Tavana, Hossein

    2013-11-01

    A surfactant liquid plug forms in the trachea during surfactant replacement therapy (SRT) of premature babies. Under air pressure, the plug propagates downstream and continuously divides into smaller daughter plugs at continuously branching lung airways. Propagating plugs deposit a thin film on airway walls to reduce surface tension and facilitate breathing. The effectiveness of SRT greatly depends on the final distribution of instilled surfactant within airways. To understand this process, we investigate dynamics of splitting of surfactant plugs in engineered bifurcating airway models. A liquid plug is instilled in the parent tube to propagate and split at the bifurcation. A split ratio, R, is defined as the ratio of daughter plug lengths in the top and bottom daughter airway tubes and studied as a function of the 3D orientation of airways and different flow conditions. For a given Capillary number (Ca), orienting airways farther away from a horizontal position reduced R due to the flow of a larger volume into the gravitationally favored daughter airway. At each orientation, R increased with 0.0005 < Ca < 0.05. This effect diminished by decrease in airways diameter. This approach will help elucidate surfactant distribution in airways and develop effective SRT strategies.

  5. Airway Inflammation and Hypersensitivity Induced by Chronic Smoking

    PubMed Central

    Kou, Yu Ru; Kwong, Kevin; Lee, Lu-Yuan

    2011-01-01

    Airway hypersensitivity, characterized by enhanced excitability of airway sensory nerves, is a prominent pathophysiological feature in patients with airway inflammatory diseases. Although the underlying pathogenic mechanism is not fully understood, chronic airway inflammation is believed to be primarily responsible. Cigarette smoking is known to cause chronic airway inflammation, accompanied by airway hyperresponsiveness. Experimental evidence indicates that enhanced excitability of vagal bronchopulmonary sensory nerves and increased tachykinin synthesis in these nerves resulting from chronic inflammation are important contributing factors to the airway hyperresponsiveness. Multiple inflammatory mediators released from various types of structural and inflammatory cells are involved in the smoking-induced airway inflammation, which is mainly regulated by redox-sensitive signaling pathways and transcription factors. Furthermore, recent studies have reported potent sensitizing and stimulatory effects of these inflammatory mediators such as prostanoids and reactive oxygen species on these sensory nerves. In summary, these studies using cigarette smoking as an experimental approach have identified certain potentially important cell signaling pathways and underlying mechanisms of the airway hypersensitivity induced by chronic airway inflammation. PMID:21397052

  6. Increased corrosion resistance of the AZ80 magnesium alloy by rapid solidification.

    PubMed

    Aghion, E; Jan, L; Meshi, L; Goldman, J

    2015-11-01

    Magnesium (Mg) and Mg-alloys are being considered as implantable biometals. Despite their excellent biocompatibility and good mechanical properties, their rapid corrosion is a major impediment precluding their widespread acceptance as implantable biomaterials. Here, we investigate the potential for rapid solidification to increase the corrosion resistance of Mg alloys. To this end, the effect of rapid solidification on the environmental and stress corrosion behavior of the AZ80 Mg alloy vs. its conventionally cast counterpart was evaluated in simulated physiological electrolytes. The microstructural characteristics were examined by optical microscopy, SEM, TEM, and X-ray diffraction analysis. The corrosion behavior was evaluated by immersion, salt spraying, and potentiodynamic polarization. Stress corrosion resistance was assessed by Slow Strain Rate Testing. The results indicate that the corrosion resistance of rapidly solidified ribbons is significantly improved relative to the conventional cast alloy due to the increased Al content dissolved in the α-Mg matrix and the correspondingly reduced presence of the β-phase (Mg17 Al12 ). Unfortunately, extrusion consolidated solidified ribbons exhibited a substantial reduction in the environmental performance and stress corrosion resistance. This was mainly attributed to the detrimental effect of the extrusion process, which enriched the iron impurities and increased the internal stresses by imposing a higher dislocation density. In terms of immersion tests, the average corrosion rate of the rapidly solidified ribbons was <0.4 mm/year compared with ∼2 mm/year for the conventionally cast alloy and 26 mm/year for the rapidly solidified extruded ribbons.

  7. Increase in whole-body peripheral vascular resistance during three hours of air or oxygen prebreathing

    NASA Technical Reports Server (NTRS)

    Waligora, J. M.; Horrigan, D. J., Jr.; Conkin, J.; Dierlam, J. J.; Stanford, J., Jr.; Riddle, J. R.

    1984-01-01

    Male and female subjects prebreathed air or 100% oxygen through a mask for 3.0 hours while comfortably reclined. Blood pressures, heart rate, and cardiac output were collected before and after the prebreathe. Peripheral vascular resistance (PVR) was calculated from these parameters and increased by 29% during oxygen prebreathing and 15% during air prebreathing. The oxygen contributed substantially to the increase in PVR. Diastolic blood pressure increased by 18% during the oxygen prebreathe while stystolic blood pressure showed no change under either procedure. The increase in PVR during air prebreathing was attributed to procedural stress common to air and oxygen prebreathing.

  8. The Three A’s in Asthma – Airway Smooth Muscle, Airway Remodeling & Angiogenesis

    PubMed Central

    Keglowich, L.F; Borger, P

    2015-01-01

    Asthma affects more than 300 million people worldwide and its prevalence is still rising. Acute asthma attacks are characterized by severe symptoms such as breathlessness, wheezing, tightness of the chest, and coughing, which may lead to hospitalization or death. Besides the acute symptoms, asthma is characterized by persistent airway inflammation and airway wall remodeling. The term airway wall remodeling summarizes the structural changes in the airway wall: epithelial cell shedding, goblet cell hyperplasia, hyperplasia and hypertrophy of the airway smooth muscle (ASM) bundles, basement membrane thickening and increased vascular density. Airway wall remodeling starts early in the pathogenesis of asthma and today it is suggested that remodeling is a prerequisite for other asthma pathologies. The beneficial effect of bronchial thermoplasty in reducing asthma symptoms, together with the increased potential of ASM cells of asthmatics to produce inflammatory and angiogenic factors, indicate that the ASM cell is a major effector cell in the pathology of asthma. In the present review we discuss the ASM cell and its role in airway wall remodeling and angiogenesis. PMID:26106455

  9. Transpulmonary pressure gradient verifies pulmonary hypertension is initiated by increased arterial resistance in broilers.

    PubMed

    Lorenzoni, A G; Anthony, N B; Wideman, R F

    2008-01-01

    Previous hemodynamic evaluations demonstrated that pulmonary arterial pressure (PAP) is higher in broilers that are susceptible to pulmonary hypertension syndrome (PHS, ascites) than in broilers that are resistant to PHS. We compared key pulmonary hemodynamic parameters in broilers from PHS-susceptible and PHS-resistant lines (selected for 12 generations under hypobaric hypoxia) and in broilers from a relaxed (control) line. In experiment 1 the PAP was measured in male broilers in which a flow probe positioned on one pulmonary artery permitted the determination of cardiac output and pulmonary vascular resistance (PVR). The PAP and relative PVR were higher in susceptible broilers than in relaxed and resistant broilers, whereas absolute and relative cardiac output did not differ between lines. In experiment 2 male and female broilers from the 3 lines were catheterized to measure pressures in the wing vein, right atrium, right ventricle, pulmonary artery, and pulmonary veins (WP, wedge pressure). The transpulmonary pressure gradient (TPG) was calculated as (PAP-WP), with PAP quantifying precapillary pressure and WP approximating postcapillary pulmonary venous pressure. When compared with resistant and relaxed broilers, PAP values in susceptible broilers were > or =10 mmHg higher, TPG values were > or =8 mmHg higher, and WP values were < or =2 mmHg higher, regardless of sex. The combined hemodynamic criteria (elevated PAP and PVR combined with a proportionally elevated TPG) demonstrate that susceptibility to PHS can be attributed primarily to pulmonary arterial hypertension associated with increased precapillary (arteriole) resistance rather than to pulmonary venous hypertension caused by elevated postcapillary (venous and left atrial) resistance.

  10. Oxygen exposure increases resistance of Desulfovibrio vulgaris Hildenborough to killing by hydrogen peroxide.

    PubMed

    Wildschut, Janine D; Caffrey, Sean M; Voordouw, Johanna K; Voordouw, Gerrit

    2012-02-01

    Inactivation of PerR by oxidative stress and a corresponding increase in expression of the perR regulon genes is part of the oxidative stress defense in a variety of anaerobic bacteria. Diluted anaerobic, nearly sulfide-free cultures of mutant and wild-type Desulfovibrio vulgaris (10(5)-10(6) colony-forming units/ml) were treated with 0 to 2,500 μM H(2)O(2) for only 5 min to prevent readjustment of gene expression. Survivors were then scored by plating. The wild type and perR mutant had 50% survival at 58 and 269 μM H(2)O(2), respectively, indicating the latter to be 4.6-fold more resistant to killing by H(2)O(2) under these conditions. Significantly increased resistance of the wild type (38-fold; 50% killing at 2188 μM H(2)O(2)) was observed if cells were pretreated with full air for 30 min, conditions that did not affect cell viability. The resistance of the perR mutant increased less (4.6-fold; 50% killing at 1230 μM H(2)O(2)), when similarly pretreated. Interestingly, no increased resistance of either was achieved by exposure with 10.6 μM H(2)O(2) for 30 min, the highest concentration that could be used without killing the cells. Hence, in environments with low D. vulgaris biomass only the presence of external O(2) effectively activates the perR regulon. As a result, mutant strains lacking one of the perR regulon genes ahpC, dvu0772, rbr1 or rbr2 displayed decreased resistance to H(2)O(2) stress only following pretreatment with air.

  11. Cooperating JAK1 and JAK3 mutants increase resistance to JAK inhibitors.

    PubMed

    Springuel, Lorraine; Hornakova, Tekla; Losdyck, Elisabeth; Lambert, Fanny; Leroy, Emilie; Constantinescu, Stefan N; Flex, Elisabetta; Tartaglia, Marco; Knoops, Laurent; Renauld, Jean-Christophe

    2014-12-18

    The acquisition of growth signal self-sufficiency is 1 of the hallmarks of cancer. We previously reported that the murine interleukin-9-dependent TS1 cell line gives rise to growth factor-independent clones with constitutive activation of the Janus kinase (JAK)- signal transducer and activator of transcription (STAT) pathway. Here, we show that this transforming event results from activating mutations either in JAK1, JAK3, or in both kinases. Transient and stable expression of JAK1 and/or JAK3 mutants showed that each mutant induces STAT activation and that their coexpression further increases this activation. The proliferation of growth factor-independent TS1 clones can be efficiently blocked by JAK inhibitors such as ruxolitinib or CMP6 in short-term assays. However, resistant clones occur upon long-term culture in the presence of inhibitors. Surprisingly, resistance to CMP6 was not caused by the acquisition of secondary mutations in the adenosine triphosphate-binding pocket of the JAK mutant. Indeed, cells that originally showed a JAK1-activating mutation became resistant to inhibitors by acquiring another activating mutation in JAK3, whereas cells that originally showed a JAK3-activating mutation became resistant to inhibitors by acquiring another activating mutation in JAK1. These observations underline the cooperation between JAK1 and JAK3 mutants in T-cell transformation and represent a new mechanism of acquisition of resistance against JAK inhibitors.

  12. Antibiotic-Resistant Acinetobacter baumannii Increasing Success Remains a Challenge as a Nosocomial Pathogen.

    PubMed

    Gonzalez-Villoria, Ana Maria; Valverde-Garduno, Veronica

    2016-01-01

    Antibiotic-resistant infectious bacteria currently imply a high risk and therefore constitute a strong challenge when treating patients in hospital settings. Characterization of these species and of particular strains is a priority for the establishment of diagnostic tests and preventive procedures. The relevance of Acinetobacter baumannii as a problematic microorganism in inpatient facilities, particularly intensive care units, has increased over time. This review aims to draw attention to (i) the historical emergence of carbapenem-resistant Acinetobacter baumannii, (ii) the current status of surveillance needs in Latin America, and (iii) recent data suggesting that A. baumannii continues to spread and evolve in hospital settings. First, we present synopsis of the series of events leading to the discovery and precise identification of this microorganism in hospital settings. Then key events in the acquisition of antibiotic-resistant genes by this microorganism are summarized, highlighting the race between new antibiotic generation and emergence of A. baumannii resistant strains. Here we review the historical development of this species as an infectious threat, the current state of its distribution, and antibiotic resistance characteristics, and we discuss future prospects for its control.

  13. Antibiotic-Resistant Acinetobacter baumannii Increasing Success Remains a Challenge as a Nosocomial Pathogen

    PubMed Central

    Gonzalez-Villoria, Ana Maria; Valverde-Garduno, Veronica

    2016-01-01

    Antibiotic-resistant infectious bacteria currently imply a high risk and therefore constitute a strong challenge when treating patients in hospital settings. Characterization of these species and of particular strains is a priority for the establishment of diagnostic tests and preventive procedures. The relevance of Acinetobacter baumannii as a problematic microorganism in inpatient facilities, particularly intensive care units, has increased over time. This review aims to draw attention to (i) the historical emergence of carbapenem-resistant Acinetobacter baumannii, (ii) the current status of surveillance needs in Latin America, and (iii) recent data suggesting that A. baumannii continues to spread and evolve in hospital settings. First, we present synopsis of the series of events leading to the discovery and precise identification of this microorganism in hospital settings. Then key events in the acquisition of antibiotic-resistant genes by this microorganism are summarized, highlighting the race between new antibiotic generation and emergence of A. baumannii resistant strains. Here we review the historical development of this species as an infectious threat, the current state of its distribution, and antibiotic resistance characteristics, and we discuss future prospects for its control. PMID:26966582

  14. Chemical Changes Associated with Increased Acid Resistance of Er:YAG Laser Irradiated Enamel

    PubMed Central

    Olea-Mejía, Oscar Fernando; García-Fabila, María Magdalena; Rodríguez-Vilchis, Laura Emma; Sánchez-Flores, Ignacio; Centeno-Pedraza, Claudia

    2014-01-01

    Background. An increase in the acid resistance of dental enamel, as well as morphological and structural changes produced by Er:YAG laser irradiation, has been reported. Purpose. To evaluate the chemical changes associated with acid resistance of enamel treated with Er:YAG laser. Methods. Forty-eight enamel samples were divided into 4 groups (n = 12). Group I (control); Groups II, III, and IV were irradiated with Er:YAG at 100 mJ (12.7 J/cm2), 200 mJ (25.5 J/cm2), and 300 mJ (38.2 J/cm2), respectively. Results. There were significant differences in composition of irradiated groups (with the exception of chlorine) and in the amount of calcium released. Conclusions. Chemical changes associated with an increase in acid resistance of enamel treated with Er:YAG laser showed a clear postirradiation pattern characterized by a decrease in C at.% and an increase in O, P, and Ca at.% and no changes in Cl at.%. An increased Ca/P ratio after Er:YAG laser irradiation was associated with the use of higher laser energy densities. Chemical changes produced by acid dissolution showed a similar trend among experimental groups. Stable or increased Ca/P ratio after acid dissolution was observed in the irradiated groups, with reduction of Ca released into the acid solution. PMID:24600327

  15. Sensory nerves in lung and airways.

    PubMed

    Lee, Lu-Yuan; Yu, Jerry

    2014-01-01

    Sensory nerves innervating the lung and airways play an important role in regulating various cardiopulmonary functions and maintaining homeostasis under both healthy and disease conditions. Their activities conducted by both vagal and sympathetic afferents are also responsible for eliciting important defense reflexes that protect the lung and body from potential health-hazardous effects of airborne particulates and chemical irritants. This article reviews the morphology, transduction properties, reflex functions, and respiratory sensations of these receptors, focusing primarily on recent findings derived from using new technologies such as neural immunochemistry, isolated airway-nerve preparation, cultured airway neurons, patch-clamp electrophysiology, transgenic mice, and other cellular and molecular approaches. Studies of the signal transduction of mechanosensitive afferents have revealed a new concept of sensory unit and cellular mechanism of activation, and identified additional types of sensory receptors in the lung. Chemosensitive properties of these lung afferents are further characterized by the expression of specific ligand-gated ion channels on nerve terminals, ganglion origin, and responses to the action of various inflammatory cells, mediators, and cytokines during acute and chronic airway inflammation and injuries. Increasing interest and extensive investigations have been focused on uncovering the mechanisms underlying hypersensitivity of these airway afferents, and their role in the manifestation of various symptoms under pathophysiological conditions. Several important and challenging questions regarding these sensory nerves are discussed. Searching for these answers will be a critical step in developing the translational research and effective treatments of airway diseases.

  16. CCND1 mutations increase protein stability and promote ibrutinib resistance in mantle cell lymphoma.

    PubMed

    Mohanty, Atish; Sandoval, Natalie; Das, Manasi; Pillai, Raju; Chen, Lu; Chen, Robert W; Amin, Hesham M; Wang, Michael; Marcucci, Guido; Weisenburger, Dennis D; Rosen, Steven T; Pham, Lan V; Ngo, Vu N

    2016-11-08

    Mantle cell lymphoma (MCL) is characterized by the t(11;14) translocation, which leads to deregulated expression of the cell cycle regulatory protein cyclin D1 (CCND1). Genomic studies of MCL have also identified recurrent mutations in the coding region of CCND1. However, the functional consequence of these mutations is not known. Here, we showed that, compared to wild type (WT), single E36K, Y44D or C47S CCND1 mutations increased CCND1 protein levels in MCL cell lines. Mechanistically, these mutations stabilized CCND1 protein through attenuation of threonine-286 phosphorylation, which is important for proteolysis through the ubiquitin-proteasome pathway. In addition, the mutant proteins preferentially localized to the nucleus. Interestingly, forced expression of WT or mutant CCND1 increased resistance of MCL cell lines to ibrutinib, an FDA-approved Bruton tyrosine kinase inhibitor for MCL treatment. The Y44D mutant sustained the resistance to ibrutinib even at supraphysiologic concentrations (5-10 μM). Furthermore, primary MCL tumors with CCND1 mutations also expressed stable CCND1 protein and were resistant to ibrutinib. These findings uncover a new mechanism that is critical for the regulation of CCND1 protein levels, and is directly relevant to primary ibrutinib resistance in MCL.

  17. Increasing resistivity of electrically conductive ceramics by insulating grain boundary phase.

    PubMed

    Kusunose, Takafumi; Sekino, Tohru

    2014-02-26

    Increasing resistivity of electrically conductive nonoxide ceramics was investigated by insulating conductive pathways through conductive grains in a sintered body by addition of an insulating grain boundary phase, which was produced by the reaction of sintering additives in liquid phase sintering. When SiC was hot pressed with an additive of 10 vol % of Al2O3 and Y2O3, the resistivity decreased as sintering temperature increased owing to contact between SiC grains during densification. However, by hot pressing at 1750°C, a high resistivity of greater than 1 × 10(11) Ω cm was achieved because of the penetration of an insulating grain boundary phase between the SiC grains. It is possible to fabricate high-resistivity SiC ceramics without losing their excellent mechanical properties by introduction of an insulating grain boundary phase, the volume of which is approximately 1/7 that of the insulating phase incorporated in conventional ceramic composites.

  18. Growth on Alpha-Ketoglutarate Increases Oxidative Stress Resistance in the Yeast Saccharomyces cerevisiae

    PubMed Central

    Burdyliuk, Nadia; Lushchak, Volodymyr

    2017-01-01

    Alpha-ketoglutarate (AKG) is an important intermediate in cell metabolism, linking anabolic and catabolic processes. The effect of exogenous AKG on stress resistance in S. cerevisiae cells was studied. The growth on AKG increased resistance of yeast cells to stresses, but the effects depended on AKG concentration and type of stressor. Wild-type yeast cells grown on AKG were more resistant to hydrogen peroxide, menadione, and transition metal ions (Fe2+ and Cu2+) but not to ethanol and heat stress as compared with control ones. Deficiency in SODs or catalases abolished stress-protective effects of AKG. AKG-supplemented growth led to higher values of total metabolic activity, level of low-molecular mass thiols, and activities of catalase and glutathione reductase in wild-type cells compared with the control. The results suggest that exogenous AKG may enhance cell metabolism leading to induction of mild oxidative stress. It turn, it results in activation of antioxidant system that increases resistance of S. cerevisiae cells to H2O2 and other stresses. The presence of genes encoding SODs or catalases is required for the expression of protective effects of AKG. PMID:28154578

  19. Volatiles produced by soil-borne endophytic bacteria increase plant pathogen resistance and affect tritrophic interactions.

    PubMed

    D'Alessandro, Marco; Erb, Matthias; Ton, Jurriaan; Brandenburg, Anna; Karlen, Danielle; Zopfi, Jakob; Turlings, Ted C J

    2014-04-01

    Volatile organic compounds (VOCs) released by soil microorganisms influence plant growth and pathogen resistance. Yet, very little is known about their influence on herbivores and higher trophic levels. We studied the origin and role of a major bacterial VOC, 2,3-butanediol (2,3-BD), on plant growth, pathogen and herbivore resistance, and the attraction of natural enemies in maize. One of the major contributors to 2,3-BD in the headspace of soil-grown maize seedlings was identified as Enterobacter aerogenes, an endophytic bacterium that colonizes the plants. The production of 2,3-BD by E. aerogenes rendered maize plants more resistant against the Northern corn leaf blight fungus Setosphaeria turcica. On the contrary, E. aerogenes-inoculated plants were less resistant against the caterpillar Spodoptera littoralis. The effect of 2,3-BD on the attraction of the parasitoid Cotesia marginiventris was more variable: 2,3-BD application to the headspace of the plants had no effect on the parasitoids, but application to the soil increased parasitoid attraction. Furthermore, inoculation of seeds with E. aerogenes decreased plant attractiveness, whereas inoculation of soil with a total extract of soil microbes increased parasitoid attraction, suggesting that the effect of 2,3-BD on the parasitoid is indirect and depends on the composition of the microbial community.

  20. Evolution of a Heavy Metal Homeostasis/Resistance Island Reflects Increasing Copper Stress in Enterobacteria

    PubMed Central

    Staehlin, Benjamin M.; Gibbons, John G.; Rokas, Antonis; O’Halloran, Thomas V.; Slot, Jason C.

    2016-01-01

    Copper homeostasis in bacteria is challenged by periodic elevation of copper levels in the environment, arising from both natural sources and human inputs. Several mechanisms have evolved to efflux copper from bacterial cells, including the cus (copper sensing copper efflux system), and pco (plasmid-borne copper resistance system) systems. The genes belonging to these two systems can be physically clustered in a Copper Homeostasis and Silver Resistance Island (CHASRI) on both plasmids and chromosomes in Enterobacteria. Increasing use of copper in agricultural and industrial applications raises questions about the role of human activity in the evolution of novel copper resistance mechanisms. Here we present evidence that CHASRI emerged and diversified in response to copper deposition across aerobic and anaerobic environments. An analysis of diversification rates and a molecular clock model suggest that CHASRI experienced repeated episodes of elevated diversification that could correspond to peaks in human copper production. Phylogenetic analyses suggest that CHASRI originated in a relative of Enterobacter cloacae as the ultimate product of sequential assembly of several pre-existing two-gene modules. Once assembled, CHASRI dispersed via horizontal gene transfer within Enterobacteriaceae and also to certain members of Shewanellaceae, where the original pco module was replaced by a divergent pco homolog. Analyses of copper stress mitigation suggest that CHASRI confers increased resistance aerobically, anaerobically, and during shifts between aerobic and anaerobic environments, which could explain its persistence in facultative anaerobes and emergent enteric pathogens. PMID:26893455

  1. CCND1 mutations increase protein stability and promote ibrutinib resistance in mantle cell lymphoma

    PubMed Central

    Mohanty, Atish; Sandoval, Natalie; Das, Manasi; Pillai, Raju; Chen, Lu; Chen, Robert W.; Amin, Hesham M.; Wang, Michael; Marcucci, Guido; Weisenburger, Dennis D.; Rosen, Steven T.; Pham, Lan V.; Ngo, Vu N.

    2016-01-01

    Mantle cell lymphoma (MCL) is characterized by the t(11;14) translocation, which leads to deregulated expression of the cell cycle regulatory protein cyclin D1 (CCND1). Genomic studies of MCL have also identified recurrent mutations in the coding region of CCND1. However, the functional consequence of these mutations is not known. Here, we showed that, compared to wild type (WT), single E36K, Y44D or C47S CCND1 mutations increased CCND1 protein levels in MCL cell lines. Mechanistically, these mutations stabilized CCND1 protein through attenuation of threonine-286 phosphorylation, which is important for proteolysis through the ubiquitin-proteasome pathway. In addition, the mutant proteins preferentially localized to the nucleus. Interestingly, forced expression of WT or mutant CCND1 increased resistance of MCL cell lines to ibrutinib, an FDA-approved Bruton tyrosine kinase inhibitor for MCL treatment. The Y44D mutant sustained the resistance to ibrutinib even at supraphysiologic concentrations (5–10 μM). Furthermore, primary MCL tumors with CCND1 mutations also expressed stable CCND1 protein and were resistant to ibrutinib. These findings uncover a new mechanism that is critical for the regulation of CCND1 protein levels, and is directly relevant to primary ibrutinib resistance in MCL. PMID:27713153

  2. Evolution of a Heavy Metal Homeostasis/Resistance Island Reflects Increasing Copper Stress in Enterobacteria.

    PubMed

    Staehlin, Benjamin M; Gibbons, John G; Rokas, Antonis; O'Halloran, Thomas V; Slot, Jason C

    2016-02-17

    Copper homeostasis in bacteria is challenged by periodic elevation of copper levels in the environment, arising from both natural sources and human inputs. Several mechanisms have evolved to efflux copper from bacterial cells, including thecus(copper sensing copper efflux system), andpco(plasmid-borne copper resistance system) systems. The genes belonging to these two systems can be physically clustered in a Copper Homeostasis and Silver Resistance Island (CHASRI) on both plasmids and chromosomes in Enterobacteria. Increasing use of copper in agricultural and industrial applications raises questions about the role of human activity in the evolution of novel copper resistance mechanisms. Here we present evidence that CHASRI emerged and diversified in response to copper deposition across aerobic and anaerobic environments. An analysis of diversification rates and a molecular clock model suggest that CHASRI experienced repeated episodes of elevated diversification that could correspond to peaks in human copper production. Phylogenetic analyses suggest that CHASRI originated in a relative ofEnterobacter cloacaeas the ultimate product of sequential assembly of several pre-existing two-gene modules. Once assembled, CHASRI dispersed via horizontal gene transfer within Enterobacteriaceae and also to certain members of Shewanellaceae, where the originalpcomodule was replaced by a divergentpcohomolog. Analyses of copper stress mitigation suggest that CHASRI confers increased resistance aerobically, anaerobically, and during shifts between aerobic and anaerobic environments, which could explain its persistence in facultative anaerobes and emergent enteric pathogens.

  3. Growth on Alpha-Ketoglutarate Increases Oxidative Stress Resistance in the Yeast Saccharomyces cerevisiae.

    PubMed

    Bayliak, Maria; Burdyliuk, Nadia; Lushchak, Volodymyr

    2017-01-01

    Alpha-ketoglutarate (AKG) is an important intermediate in cell metabolism, linking anabolic and catabolic processes. The effect of exogenous AKG on stress resistance in S. cerevisiae cells was studied. The growth on AKG increased resistance of yeast cells to stresses, but the effects depended on AKG concentration and type of stressor. Wild-type yeast cells grown on AKG were more resistant to hydrogen peroxide, menadione, and transition metal ions (Fe(2+) and Cu(2+)) but not to ethanol and heat stress as compared with control ones. Deficiency in SODs or catalases abolished stress-protective effects of AKG. AKG-supplemented growth led to higher values of total metabolic activity, level of low-molecular mass thiols, and activities of catalase and glutathione reductase in wild-type cells compared with the control. The results suggest that exogenous AKG may enhance cell metabolism leading to induction of mild oxidative stress. It turn, it results in activation of antioxidant system that increases resistance of S. cerevisiae cells to H2O2 and other stresses. The presence of genes encoding SODs or catalases is required for the expression of protective effects of AKG.

  4. Role of IRE1α/XBP-1 in Cystic Fibrosis Airway Inflammation

    PubMed Central

    Ribeiro, Carla M. P.; Lubamba, Bob A.

    2017-01-01

    Cystic fibrosis (CF) pulmonary disease is characterized by chronic airway infection and inflammation. The infectious and inflamed CF airway environment impacts on the innate defense of airway epithelia and airway macrophages. The CF airway milieu induces an adaptation in these cells characterized by increased basal inflammation and a robust inflammatory response to inflammatory mediators. Recent studies have indicated that these responses depend on activation of the unfolded protein response (UPR). This review discusses the contribution of airway epithelia and airway macrophages to CF airway inflammatory responses and specifically highlights the functional importance of the UPR pathway mediated by IRE1/XBP-1 in these processes. These findings suggest that targeting the IRE1/XBP-1 UPR pathway may be a therapeutic strategy for CF airway disease. PMID:28075361

  5. Heterozygous caveolin-3 mice show increased susceptibility to palmitate-induced insulin resistance.

    PubMed

    Talukder, M A Hassan; Preda, Marilena; Ryzhova, Larisa; Prudovsky, Igor; Pinz, Ilka M

    2016-03-01

    Insulin resistance and diabetes are comorbidities of obesity and affect one in 10 adults in the United States. Despite the high prevalence, the mechanisms of cardiac insulin resistance in obesity are still unclear. We test the hypothesis that the insulin receptor localizes to caveolae and is regulated through binding to caveolin-3 (CAV3). We further test whether haploinsufficiency forCAV3 increases the susceptibility to high-fat-induced insulin resistance. We used in vivo and in vitro studies to determine the effect of palmitate exposure on global insulin resistance, contractile performance of the heart in vivo, glucose uptake in the heart, and on cellular signaling downstream of theIR We show that haploinsufficiency forCAV3 increases susceptibility to palmitate-induced global insulin resistance and causes cardiomyopathy. On the basis of fluorescence energy transfer (FRET) experiments, we show thatCAV3 andIRdirectly interact in cardiomyocytes. Palmitate impairs insulin signaling by a decrease in insulin-stimulated phosphorylation of Akt that corresponds to an 87% decrease in insulin-stimulated glucose uptake inHL-1 cardiomyocytes. Despite loss of Akt phosphorylation and lower glucose uptake, palmitate increased insulin-independent serine phosphorylation ofIRS-1 by 35%. In addition, we found lipid induced downregulation ofCD36, the fatty acid transporter associated with caveolae. This may explain the problem the diabetic heart is facing with the simultaneous impairment of glucose uptake and lipid transport. Thus, these findings suggest that loss ofCAV3 interferes with downstream insulin signaling and lipid uptake, implicatingCAV3 as a regulator of theIRand regulator of lipid uptake in the heart.

  6. Spirometric and plethysmographic assessment of upper airway obstruction in laryngeal hemiplegia.

    PubMed

    Cantarella, Giovanna; Fasano, Valter; Bucchioni, Enrica; Domenichini, Elena; Cesana, Bruno M

    2003-12-01

    Laryngeal hemiplegia (LH) is the most common disorder of laryngeal motility. It is deemed not to cause obstruction of the upper airway; in fact, the main symptoms are dysphonia and breathiness, and respiratory impairment is not commonly reported. The aim of this study was to objectively assess upper airway patency in 41 patients affected by LH (mean age, 54.4 +/- 15.2 years; 27 female) and 30 controls (mean age, 50.0 +/- 16.1 years; 19 female) by means of flow-volume loop spirometry and body plethysmography to measure specific airway resistance (sRaw) at increasing respiratory frequencies. The causes of LH were cervical surgery (28), tumor infiltration (5), and unexplained (8). None of the patients or controls was affected by lower airway disease. Spirometry showed that the patients had inspiratory flows (PIF, FIF50) significantly lower than those of the controls (p < .0001), whereas the expiratory flows (FEV1, FEF50) were normal, with the exception of peak expiratory flow (PEF), which was reduced, especially in female patients. The mean FEF50/FIF50 ratio (about unity in the normal subjects) was >1, as is typical of variable extrathoracic obstruction. Plethysmography showed that the values of sRaw of the LH group were not statistically different from those of the controls at 30 +/- 5 breaths per minute, but they progressively and significantly increased at 60 +/- 5 (p < .01) and 90 +/- 5 breaths per minute (p < .002), whereas no significant sRaw change was observed in the controls. These results show that LH causes obstruction of the upper airway that can be assessed and quantified by means of spirometry and body plethysmography. A dynamic narrowing due to inspiratory medialization of the paralytic vocal fold and flow turbulence during hyperventilation seem to be the causes of patency impairment. The flow-volume loop is an excellent, inexpensive, and easily available means of functionally evaluating upper airway obstruction, but some patients have difficulty in

  7. Effects of nitric acid on carbachol reactivity of the airways in normal and allergic sheep

    SciTech Connect

    Abraham, W.M.; Kim, C.S.; King, M.M.; Oliver, W. Jr.; Yerger, L.

    1982-01-01

    The airway effects of a 4-hr exposure (via a Plexiglas hood) to 1.6 ppm nitric acid vapor were evaluated in seven normal and seven allergic sheep, i.e., animals that have a history of reacting with bronchospasm to inhalation challenge with Ascaris suum antigen. The nitric acid vapor was generated by ultrasonic nebulization of a 2% nitric acid solution. Airway effects were assessed by measuring the change in specific pulmonary flow resistance before and after a standard inhalation challenge with 2.5% carbachol aerosol. Nitric acid exposure did not produce bronchoconstriction in either group. Pre-exposure increases in specific pulmonary flow resistance after carbachol inhalation were 68% (SD+/- 13%) and 82% (SD+/- 35%) for the normal and allergic sheep, respectively. Within 24 hr, the largest post-exposure increases in specific pulmonary flow resistance for the normal and allergic sheep were 108% (SD+/- 51%(P<.06)) and 175% (SD+/- 87% (p<.02)), respectively. We conclude that a short-term exposure to nitric acid vapor at levels below the industrial threshold limit (2 ppm), produces airway hyperreactivity to aerosolized carbachol in allergic sheep.

  8. Resistance training increases total daily energy expenditure in disabled older women with coronary heart disease.

    PubMed

    Ades, Philip A; Savage, Patrick D; Brochu, Martin; Tischler, Marc D; Lee, N Melinda; Poehlman, Eric T

    2005-04-01

    Physical activity energy expenditure (PAEE) is a determinant of prognosis and fitness in older patients with coronary heart disease (CHD). PAEE and total energy expenditure (TEE) are closely related to fatness, physical function, and metabolic risk in older individuals. The goal of this study was to assess effects of resistance training on PAEE, TEE, and fitness in older women with chronic CHD and physical activity limitations (N = 51, mean age: 72 + 5 yr). The study intervention consisted of a progressive, 6-mo program of resistance training vs. a control group condition of low-intensity yoga and deep breathing. The study interventions were completed by 42 of the 51 participants. The intervention group manifested a 177 +/- 213 kcal/day (+9%) increase in TEE, pre- to posttraining, measured by the doubly labeled water technique during a nonexercise 10-day period (P < 0.03 vs. controls). This was due to a 50 +/- 74 kcal/day (4%) increase in resting metabolic rate measured by indirect calorimetry (P < 0.01, P < 0.05 vs. controls) and a 123 +/- 214 kcal/day (9%) increase in PAEE (P < 0.03, P = 0.12 vs. controls). Resistance training was associated with significant increases in upper and lower body strength, but no change in fat-free mass, measured by dual X-ray absorptiometry, or left ventricular function, measured by echocardiography and Doppler. Women in the control group showed no alterations in TEE or its determinants. There were no changes between groups in body composition, aerobic capacity, or measures of mental depression. These results demonstrate that resistance training of 6-mo duration leads to an increase in TEE and PAEE in older women with chronic CHD.

  9. Improvement of daptomycin production via increased resistance to decanoic acid in Streptomyces roseosporus.

    PubMed

    Lee, Sung-Kwon; Kim, Hong Rip; Jin, Ying-Yu; Yang, Seung Hwan; Suh, Joo-Won

    2016-10-01

    Daptomycin, a cyclic anionic lipopeptide compound produced by Streptomyces roseosporus, is used to treat skin infections caused by multi-drug resistant gram-positive pathogens. The biosynthesis of daptomycin is initiated by the condensation of decanoic acid (DA, a 10-carbon unit fatty acid) and the N-terminal l-tryptophan. So, the addition of DA to the fermentation medium is essential for increasing daptomycin production. However, increasing of DA concentration in the fermentation medium was not possible due to the high toxicity of DA. The previous studies reported that the cell growth of S. roseosporus was halted from 1 mM DA. In order to improve daptomycin production with increasing DA concentration in the medium, the DA-resistant S. roseosporus was developed via a sequential-adaptation method. The DA-resistant strain (DAR) showed complete resistance to 1 mM DA, and the daptomycin production was increased 1.4-fold (40.5 ± 0.7 mg/L) compared with the wild-type (28.5 ± 0.8 mg/L) at 1 mM DA. Additionally, the initial step of the daptomycin biosynthesis was enhanced by the overexpression of dptE and dptF in DAR. The dptEF overexpression DAR showed 3.9-fold (156.3 ± 8.2 mg/L) increase in the daptomycin production compared with DAR (40.1 ± 2.6 mg/L) at 1 mM DA.

  10. Does Drought Increase the Risk of Insects Developing Behavioral Resistance to Systemic Insecticides?

    PubMed

    Khodaverdi, Haleh; Fowles, Trevor; Bick, Emily; Nansen, Christian

    2016-10-01

    Increases in severity and frequency of drought periods, average global temperatures, and more erratic fluctuations in rainfall patterns due to climate change are predicted to have a dramatic impact on agricultural production systems. Insect pest populations in agricultural and horticultural systems are also expected to be impacted, both in terms of their spatial and temporal distributions and in their status as pest species. In this opinion-based article, we discuss how indirect effects of drought may adversely affect the performance of systemic insecticides and also lead to increased risk of insect pests developing behavioral insecticide resistance. We hypothesize that more pronounced drought will decrease uptake and increase the magnitude of nonuniform translocation of systemic insecticides within treated crop plants, and that may have two concurrent consequences: 1) reduced pesticide performance, and 2) increased likelihood of insect pests evolving behavioral insecticide resistance. Under this scenario, pests that can sense and avoid acquisition of lethal dosages of systemic insecticides within crop plants will have a selective advantage. This may lead to selection for insect behavioral avoidance, so that insects predominantly feed and oviposit on portions of crop plants with low concentration of systemic insecticide. Limited research has been published on the effect of environmental variables, including drought, on pesticide performance, but we present and discuss studies that support the hypothesis described above. In addition, we wish to highlight the importance of studying the many ways environmental factors can affect, directly and indirectly, both the performance of insecticides and the risk of target insect pests developing resistance.

  11. Increase of resistance to stretch during the latent period in single muscle fibres of the frog.

    PubMed

    Haugen, P

    1982-02-01

    The time from stimulation to the first change of the extensibility in an isolated skeletal muscle fibre was measured by subjecting the fibre to a rapid, small stretch at various times during the latent period. The experiments were performed at constant temperatures in the range 1-16 degrees C. Irrespective of the temperature, the first increase of the resistance to stretch occurred after the onset of the latency relaxation. At a temperature or 10 degrees C and a sarcomere length of 3 microgram the resistance started to increase 5.5 ms after stimulation, i.e. 1.5-2 ms after the onset of the drop in tension, and then increased nearly linearly with time. Corresponding to the end of the latent period, i.e. when the tension recrosses the resting level, the amplitude of the response was about 1.5 times its resting value. There was an interval between the onset of increase f the resistance to stretch and the time when the rate of drop in tension had passed its maximum value. The results are compatible with the hypothesis that the latency relaxation arises from a minute lengthening of the thin filaments as proposed by Haugen & Sten-Knudsen, and that attachment and generation of force take place at separate steps of the cross-bridge cycle.

  12. Intermittent hypoxia selects for genotypes and phenotypes that increase survival, invasion, and therapy resistance.

    PubMed

    Verduzco, Daniel; Lloyd, Mark; Xu, Liping; Ibrahim-Hashim, Arig; Balagurunathan, Yoganand; Gatenby, Robert A; Gillies, Robert J

    2015-01-01

    Hypoxia in tumors correlates with greater risk of metastases, increased invasiveness, and resistance to systemic and radiation therapy. The evolutionary dynamics that links specific adaptations to hypoxia with these observed tumor properties have not been well investigated. While some tumor populations may experience fixed hypoxia, cyclical and stochastic transitions from normoxia to hypoxia are commonly observed in vivo. Although some phenotypic adaptations to this cyclic hypoxia are likely reversible, we hypothesize that some adaptations may become fixed through mutations promoted by hypoxia-induced genomic instability. Here we seek to identify genetic alterations and corresponding stable phenotypes that emerge following cyclic hypoxia. Although these changes may originate as adaptations to this specific environmental stress, their fixation in the tumor genome may result in their observation in tumors from regions of normoxia, a condition known as pseudohypoxia. We exposed several epithelial cell lines to 50 cycles of hypoxia-normoxia, followed by culture in normoxia over a period of several months. Molecular analyses demonstrated permanent changes in expression of several oncogenes and tumor-suppressors, including p53, E-cadherin, and Hif-1α. These changes were associated with increased resistance to multiple cytotoxins, increased survival in hypoxia and increased anchorage-independent growth. These results suggest cycles of hypoxia encountered in early cancers can select for specific and stable genotypic and phenotypic properties that persist even in normoxic conditions, which may promote tumor progression and resistance to therapy.

  13. Effects of Ginger and Its Constituents on Airway Smooth Muscle Relaxation and Calcium Regulation

    PubMed Central

    Siviski, Matthew E.; Zhang, Yi; Xu, Carrie; Hoonjan, Bhupinder; Emala, Charles W.

    2013-01-01

    The prevalence of asthma has increased in recent years, and is characterized by airway hyperresponsiveness and inflammation. Many patients report using alternative therapies to self-treat asthma symptoms as adjuncts to short-acting and long-acting β-agonists and inhaled corticosteroids (ICS). As many as 40% of patients with asthma use herbal therapies to manage asthma symptoms, often without proven efficacy or known mechanisms of action. Therefore, investigations of both the therapeutic and possible detrimental effects of isolated components of herbal treatments on the airway are important. We hypothesized that ginger and its active components induce bronchodilation by modulating intracellular calcium ([Ca2+]i) in airway smooth muscle (ASM). In isolated human ASM, ginger caused significant and rapid relaxation. Four purified constituents of ginger were subsequently tested for ASM relaxant properties in both guinea pig and human tracheas: [6]-gingerol, [8]-gingerol, and [6]-shogaol induced rapid relaxation of precontracted ASM (100–300 μM), whereas [10]-gingerol failed to induce relaxation. In human ASM cells, exposure to [6]-gingerol, [8]-gingerol, and [6]-shogaol, but not [10]-gingerol (100 μM), blunted subsequent Ca2+ responses to bradykinin (10 μM) and S-(−)-Bay K 8644 (10 μM). In A/J mice, the nebulization of [8]-gingerol (100 μM), 15 minutes before methacholine challenge, significantly attenuated airway resistance, compared with vehicle. Taken together, these novel data show that ginger and its isolated active components, [6]-gingerol, [8]-gingerol, and [6]-shogaol, relax ASM, and [8]-gingerol attenuates airway hyperresponsiveness, in part by altering [Ca2+]i regulation. These purified compounds may provide a therapeutic option alone or in combination with accepted therapeutics, including β2-agonists, in airway diseases such as asthma. PMID:23065130

  14. Increased Very Low Density Lipoprotein Secretion, Hepatic Steatosis, and Insulin Resistance

    PubMed Central

    Choi, Sung Hee; Ginsberg, Henry N

    2011-01-01

    Insulin resistance (IR) not only affects regulation of carbohydrate metabolism, but all aspects of lipid and lipoprotein metabolism. IR is associated with increased secretion of very low density lipoproteins (VLDL) and increased plasma triglycerides, as well as hepatic steatosis, despite the increased VLDL secretion. Here, we link IR with increased VLDL secretion and hepatic steatosis at both the physiologic and molecular levels. Increased VLDL secretion, together with the downstream effects on high density lipoprotein cholesterol and low density lipoprotein size is pro-atherogenic. Hepatic steatosis is a risk for steatohepatitis and cirrhosis. Understanding the complex inter-relationship between IR and these abnormalities of liver lipid homeostasis may provide insights relevant to new therapies for these increasing clinical problems. PMID:21616678

  15. Ectopic expression of catalase in Drosophila mitochondria increases stress resistance but not longevity.

    PubMed

    Mockett, Robin J; Bayne, Anne Cécile V; Kwong, Linda K; Orr, William C; Sohal, Rajindar S

    2003-01-15

    The goal of this study was to test the hypothesis that the rate of mitochondrial oxidant production governs the aging process of the fruit fly, Drosophila melanogaster. Catalase, an antioxidative enzyme expressed in the cytosol and peroxisomes of Drosophila, was targetted ectopically to the mitochondrial matrix by fusion of a leader peptide derived from ornithine aminotransferase with its N-terminus. The presence of the transgene encoding this fusion protein was associated with moderate (35 +/- 13%) increases in total catalase activity in most lines, and measurable levels of catalase activity in the mitochondria (30-140 U/mg protein). There was no impact on the life span of the flies at 25 degrees C, even in an exceptional line with a 149% increase in total catalase activity, and there was a small decrease in longevity at 29 degrees C. There were no compensatory changes in the rate of metabolism or physical activity, or in the levels of other major antioxidants, suggesting that the aging process was largely unaffected. Resistance to exogenous hydrogen peroxide, paraquat, and cold stress was enhanced, but there was no appreciable effect on resistance to hyperoxia. The results demonstrate the importance of mitochondrial antioxidant levels in the resistance to oxidative stress at the organismal level, and illustrate that different effects on aging and stress resistance may ensue from a single treatment. The main inferences drawn are that: (i) levels of stress resistance may neither be a cause nor a reliable indicator of the rate of aging, and (ii) bolstering antioxidant levels in Drosophila may not delay or slow down the aging process.

  16. Numerical analysis of respiratory flow patterns within human upper airway

    NASA Astrophysics Data System (ADS)

    Wang, Ying; Liu, Yingxi; Sun, Xiuzhen; Yu, Shen; Gao, Fei

    2009-12-01

    A computational fluid dynamics (CFD) approach is used to study the respiratory airflow dynamics within a human upper airway. The airway model which consists of the airway from nasal cavity, pharynx, larynx and trachea to triple bifurcation is built based on the CT images of a healthy volunteer and the Weibel model. The flow characteristics of the whole upper airway are quantitatively described at any time level of respiratory cycle. Simulation results of respiratory flow show good agreement with the clinical measures, experimental and computational results in the literature. The air mainly passes through the floor of the nasal cavity in the common, middle and inferior nasal meatus. The higher airway resistance and wall shear stresses are distributed on the posterior nasal valve. Although the airways of pharynx, larynx and bronchi experience low shear stresses, it is notable that relatively high shear stresses are distributed on the wall of epiglottis and bronchial bifurcations. Besides, two-dimensional fluid-structure interaction models of normal and abnormal airways are built to discuss the flow-induced deformation in various anatomy models. The result shows that the wall deformation in normal airway is relatively small.

  17. The effects of in utero vitamin D deficiency on airway smooth muscle mass and lung function.

    PubMed

    Foong, Rachel E; Bosco, Anthony; Jones, Anya C; Gout, Alex; Gorman, Shelley; Hart, Prue H; Zosky, Graeme R

    2015-11-01

    We have previously demonstrated increased airway smooth muscle (ASM) mass and airway hyperresponsiveness in whole-life vitamin D-deficient female mice. In this study, we aimed to uncover the molecular mechanisms contributing to altered lung structure and function. RNA was extracted from lung tissue of whole-life vitamin D-deficient and -replete female mice, and gene expression patterns were profiled by RNA sequencing. The data showed that genes involved in embryonic organ development, pattern formation, branching morphogenesis, Wingless/Int signaling, and inflammation were differentially expressed in vitamin D-deficient mice. Network analysis suggested that differentially expressed genes were connected by the hubs matrix metallopeptidase 9; NF-κ light polypeptide gene enhancer in B cells inhibitor, α; epidermal growth factor receptor; and E1A binding protein p300. Given our findings that developmental pathways may be altered, we investigated if the timing of vitamin D exposure (in utero vs. postnatal) had an impact on lung health outcomes. Gene expression was measured in in utero or postnatal vitamin D-deficient mice, as well as whole-life vitamin D-deficient and -replete mice at 8 weeks of age. Baseline lung function, airway hyperresponsiveness, and airway inflammation were measured and lungs fixed for lung structure assessment using stereological methods and quantification of ASM mass. In utero vitamin D deficiency was sufficient to increase ASM mass and baseline airway resistance and alter lung structure. There were increased neutrophils but decreased lymphocytes in bronchoalveolar lavage. Expression of inflammatory molecules S100A9 and S100A8 was mainly increased in postnatal vitamin D-deficient mice. These observations suggest that in utero vitamin D deficiency can alter lung structure and function and increase inflammation, contributing to symptoms in chronic diseases, such as asthma.

  18. Feeding of liquid silicon for high performance multicrystalline silicon with increased ingot height and homogenized resistivity

    NASA Astrophysics Data System (ADS)

    Krenckel, Patricia; Riepe, Stephan; Schindler, Florian; Strauch, Theresa

    2017-04-01

    Feeding of liquid silicon during the directional solidification process is a promising opportunity for cost reduction by increased throughput and improved material homogeneity due to constant resistivity over ingot height. In this work, a liquid feeding apparatus was developed for an industrial type directional solidification furnace. One n-type G2 sized High Performance multicrystalline ingot with liquid feeding of additional 14 kg of undoped silicon feedstock was crystallized. The resistivity was kept within a range of ±0.1 Ω cm of the target resistivity during the feeding sequence. A smaller mean grain area growth was observed during feeding, whereas the area fraction of recombination active dislocation structures was as low as in a reference ingot. Increased interstitial oxygen and substitutional carbon concentrations were measured for the ingot with liquid feeding. The measured mean bulk lifetime of 190 μs for passivated wafers in the feeding sequence can probably be increased by further pre-melting crucible improvements. For this laboratory experiment, energy reductions of 2% per wafer and time savings of 16% per wafer were realized.

  19. Increased gene dosage of Ink4a/Arf results in cancer resistance and normal aging

    PubMed Central

    Matheu, Ander; Pantoja, Cristina; Efeyan, Alejo; Criado, Luis M.; Martín-Caballero, Juan; Flores, Juana M.; Klatt, Peter; Serrano, Manuel

    2004-01-01

    Mammalian genes frequently present allelic variants that differ in their expression levels and that, in the case of tumor suppressor genes, can be of relevance for cancer susceptibility and aging. We report here the characterization of a novel mouse model with increased activity for the Ink4a and Arf tumor suppressors. We have generated a “super Ink4a/Arf” mouse strain carrying a transgenic copy of the entire Ink4a/Arf locus. Cells derived from super Ink4a/Arf mice have increased resistance to in vitro immortalization and oncogenic transformation. Importantly, super Ink4a/Arf mice manifest higher resistance to cancer compared to normal, nontransgenic, mice. Finally, super Ink4a/Arf mice have normal aging and lifespan. Together, these results indicate that modest increases in the activity of the Ink4a/Arf tumor suppressor result in a beneficial cancer-resistant phenotype without affecting normal viability or aging. PMID:15520276

  20. Increased virulence of neuraminidase inhibitor-resistant pandemic H1N1 virus in mice

    PubMed Central

    Song, Min-Suk; Hee Baek, Yun; Kim, Eun-Ha; Park, Su-Jin; Kim, Semi; Lim, Gyo-Jin; Kwon, Hyeok-il; Pascua, Philippe Noriel Q; Decano, Arun G; Lee, Byeong-Jae; Kim, Young-Il; Webby, Richard J; Choi, Young-Ki

    2013-01-01

    Pandemic H1N1 2009 (A[H1N1]pdm09) variants associated with oseltamivir resistance have emerged with a histidine-to-tyrosine substitution in the neuraminidase(NA) at position 274 (H274Y). To determine whether the H274Y variant has increased virulence potential, A(H1N1)pdm09 virus, with or without the H274Y mutation, was adapted by serial lung-to-lung passages in mice. The mouse-adapted H274Y (maCA04H274Y) variants showed increased growth properties and virulence in vitro and in vivo while maintaining high NA inhibitor resistance. Interestingly, most maCA04H274Y and maCA04 viruses acquired common mutations in HA (S183P and D222G) and NP (D101G), while only maCA04H274Y viruses had consensus additional K153E mutation in the HA gene, suggesting a potential association with the H274Y substitution. Collectively, our findings highlight the potential emergence of A(H1N1)pdm09 drug-resistant variants with increased virulence and the need for rapid development of novel antiviral drugs. PMID:23924955

  1. Antimicrobial susceptibilities of uropathogen Escherichia coli in renal transplant recipients: dramatic increase in ciprofloxacin resistance.

    PubMed

    Azap, Ö; Togan, T; Yesilkaya, A; Arslan, H; Haberal, M

    2013-04-01

    The urinary tract is the most common site of bacterial infections in renal transplant recipients. The management of urinary tract infections (UTI) in renal transplant recipients is becoming more difficult because of drug-resistant bacteria. The antimicrobial susceptibilities of uropathogen bacteria isolated from 398 patients who underwent renal transplantation between 2007 and 2011 were obtained from medical records. At least 1 UTI episode was diagnosed in 172 (43.2%) patients. Among the 703 bacteria isolated from these patients, Exherichia coli the most common pathogen, was isolated from 407/703 episodes (57.8%). Ciprofloxacin, co-trimoxazole, ceftriaxone, and gentamicin resistance rates were 59.4%, 85.7%, 40.7%, and 36.6%, respectively. Ninty six of 407 E. coli isolates (23.5%) were ESBL positive. Analysis of resistance rates in our center demonstrated ciprofloxacin resistance rate in uropathogenic E. coli to have increased gradually from 30.4% in 2003, 41.3% in 2007, and 59.4% in 2012. Instutional data regarding the etiologic agents and antimicrobial susceptibility results are important for proper management of patients with UTI.

  2. Acute hypervolaemia increases gastroduodenal resistance to the flow of liquid in the rat.

    PubMed Central

    Xavier-Neto, J; dos Santos, A A; Rola, F H

    1990-01-01

    The effect of volume expansion of extracellular fluid on gastroduodenal resistance to the flow of isotonic saline was assessed in three groups of rats using intravenous infusions of isotonic, isotonic-isoncotic, and isotonic-isoncotic-isohaemic solutions. The gastroduodenal segment of 29 male Wistar rats was barostatically perfused at a constant pressure gradient of 4 cm H2O and changes in flow (ml/minute) were taken as a reflection of changes in gastroduodenal resistance. Isotonic expansion led to a 33% drop in gastroduodenal flow compared with the normovolaemic period in the same animals (p less than 0.01). Extracellular fluid expansion with isotonic-isoncotic and isotonic-isoncotic-isohaemic solutions was associated with reductions in gastroduodenal flow of 29% (p less than 0.05) and 31% (p less than 0.01) respectively. The increase in gastroduodenal resistance is due to hypervolaemia per se and not to haemodilution, decreases in plasma oncotic pressure, or electrolyte imbalance. The effect of hypervolaemia on gastroduodenal resistance, which was reversed by small haemorrhages (0.5-1.0 ml per 100 g body weight), may be due to changes in tonus or phasic motor activity, or both, and may be part of the homeostatic processes that help the organism minimise liquid volume excess. PMID:2210444

  3. Serum betatrophin levels are increased and associated with insulin resistance in patients with polycystic ovary syndrome.

    PubMed

    Qu, Qinglan; Zhao, Dongmei; Zhang, Fengrong; Bao, Hongchu; Yang, Qiuhua

    2017-02-01

    Objective Betatrophin is a newly identified circulating protein that is significantly associated with type 2 diabetes mellitus (T2DM), adiposity, and metabolic syndrome. The aim of this study was to investigate whether betatrophin levels and polycystic ovary syndrome (PCOS) were associated. Methods Circulating betatrophin levels were measured in 162 patients with PCOS and 156 matched control females using specific enzyme-linked immunosorbent assay kits. Correlations between betatrophin levels and PCOS incidence as well as multiple key endocrine PCOS parameters were analyzed using multiple statistical methods. Results Betatrophin levels were significantly increased in patients with PCOS (685.3 ± 27.7 vs. 772.6 ± 42.5 pg/ml). When sub-grouping all investigated subjects according to the presence of insulin resistance, women with PCOS and insulin resistance exhibited markedly higher betatrophin concentrations. Furthermore, betatrophin levels were significantly correlated with fasting insulin levels and homeostatic model assessment of insulin resistance only in females with PCOS ( r = 0.531 and r = 0.628, respectively). Conclusion We provide the first report that betatrophin is strongly associated with PCOS. This study suggests that betatrophin may potentially serve as an independent predictor for the development of PCOS in at-risk women, especially those with insulin resistance.

  4. Potential Impact of Increased Use of Biocides in Consumer Products on Prevalence of Antibiotic Resistance

    PubMed Central

    Gilbert, Peter; McBain, Andrew J.

    2003-01-01

    There has recently been much controversy surrounding the increased use of antibacterial substances in a wide range of consumer products and the possibility that, as with antibiotics, indiscriminate use of biocides might contribute to the overall pattern of susceptibility in the general environment and in the clinic. Such speculation, based on the isolation of resistant mutants from in vitro monoculture experiments, is not reflected by an emergence of biocide-resistant strains in vivo. This review provides a broad coverage of the biocide and resistance literature and evaluates the potential risks, perceived from such laboratory monoculture experiments, against evidence gathered over 50 years of field studies. An explanation for the continued effectiveness of broad-spectrum biocidal agents against the decline in efficacy of therapeutic agents is provided based on the fitness costs of resistance and the ubiquity of naturally occurring substances that possess antibacterial effect. While we conclude from this review of the literature that the incorporation of antibacterial agents into a widening sphere of personal products has had little or no impact on the patterns of microbial susceptibility observed in the environment, the associated risks remain finite. The use of such products should therefore be associated with a clear demonstration of added value either to consumer health or to the product life. Hygienic products should therefore be targeted to applications for which the risks have been established. PMID:12692093

  5. Role of GLI1 and NDRG1 in Increased Resistance to Apoptosis Induction.

    PubMed

    Wu, Feng; Rom, William N; Koshiji, Minori; Mo, Yiqun; Hosomi, Yukio; Tchou-Wong, Kam-Meng

    2015-01-01

    We examined the effects of GLI1 expression in PW mouse embryo fibroblasts and H441 lung carcinoma cells. Ectopic expression of GLI1 in PW cells induced anchorage-independent growth and increased resistance to staurosporine-induced apoptosis, and overexpression of GLI1 in H441 cells caused resistance to apoptosis induced by staurosporine and etoposide. GLI1 expression in both H441 and PW cells was associated with increased expression of NDRG1, a gene known to be downregulated by the MYC family of proteins, indicating that upregulation of NDRG1 by GLI1 is not cell-type specific. Consistent with suppression of NDRG1 by c-MYC and N-MYC, increased NDRG1 expression correlated with decreased expression of c-MYC and N-MYC in GLI1-expressing H441 and GLI1-expressing PW cells, respectively. Downregulation of GLI1 expression in A549 cells by siRNA transfection increased sensitivity to etoposide-induced apoptosis, and downregulation of NDRG1 expression in H441 cells by siRNA transfection increased sensitivity to etoposide-induced apoptosis. Of clinical significance, inhibition of GLI1 and NDRG1 expression may increase sensitivity of cancer cells to chemotherapeutic drugs. Strategies that aim to inhibit GLI1 function and NDRG1 expression may be useful for targeted therapy of cancers induced by the SHH-GLI signaling pathway.

  6. Type IV resistant starch increases cecum short chain fatty acids level in rats.

    PubMed

    Le Thanh-Blicharz, Joanna; Anioła, Jacek; Kowalczewski, Przemysław; Przygoński, Krzysztof; Zaborowska, Zofia; Lewandowicz, Grażyna

    2014-01-01

    Resistant starches are type of dietary fibers. However, their physiological effects depend on the way they resist digestion in the gastrointestinal tract. The objective of this study was to examine the hypothesis that new type of RS4 preparations, of in vitro digestibility of about 50%, obtained by cross-linking and acetylation, acts as a prebiotic by increasing short chain fatty acids content in cecum digesta. The rats were fed with diet containing pregelatinized, cross-linked and acetylated starches as a main carbohydrate source. Pregelatinized, but not chemically modified, potato starch was used in the composition of the control diet. After two weeks of experiment the increase of short chain fatty acids contents in ceceum digesta was observed. The intake of starch A, cross-linked only with adipic acid, resulted in increase of about 40% of short chain fatty acids content, whereas starch PA cross-linked with sodium trimetaphosphate and adipic acid of about 50%. The utmost twofold increase was observed in the case of the production of propionic acid. In contrast, the content of butyric acid increased (12%) only as an effect of consumption of starch PA and even decreased (about 30%) in case of starch A. Both RS4 starches caused an increase of the production of acetic acid by more than 40%. No changes in serum biochemistry, liver cholesterol and organ weights of rats were stated.

  7. [Increasing trend of antimicrobial drug-resistance in organisms causing bacteremia at a tertiary-care hospital: 1995 to 2000].

    PubMed

    Kato-Maeda, Midori; Bautista-Alavez, Anabertha; Rolón-Montes-de-Oca, Ana Lilia; Ramos-Hinojosa, Ancelmo; Ponce-de-León, Alfredo; Bobadilla-del-Valle, Miriam; Ruiz-Palacios, Guillermo; Sifuentes-Osornio, José

    2003-01-01

    We described the trends of drug-resistant organisms isolated in blood cultures from patients detected in a teaching hospital from 1995 to 2000. We found an increase in the number of clinical isolates of Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter spp, Serratia spp, Staphylococcus aureus, S. epidermidis and Enterococcus spp, resistant to antibiotics commonly used to treat infections caused by these organisms. The frequency of gram-negative bacilli resistant to third-generation cephalosporins and quinolones increased during the period of study, and in 2000 more than 20% of the isolates were resistant. In contrast, the frequency of resistance to aminoglycosides and carbapenems was less than 20%. The frequency of resistant staphylococci increased exuberantly fifty fold to quinolones and five fold to oxacillin during the study period, therefore in 2000, 26.1% of S. aureus isolates and 61% of S. epidermidis were resistant to oxacillin. The frequency of resistant enterococci also increased, and in 2000, 50% were resistant to ampicillin, and 37.5% to gentamicin. The increase of drug resistant organisms isolated in blood had a direct impact in the empirical treatment of severely infected patients in our hospital. It is important to continuously supervise antibiotic use, and to adopt more strict control measures to decrease the frequency of infections caused by drug resistant organisms.

  8. Impact of endoscopic endonasal pituitary surgery on nasal airway patency

    PubMed Central

    Jalessi, Maryam; Farhadi, Mohammad; Asghari, Alimohamad; Hosseini, Maryam; Amini, Elahe; Pousti, Seyyed Behzad

    2016-01-01

    Background: Nose is used as a corridor in endoscopic endonasal transsphenoidal approach (EETSA) for pituitary adenoma. Thus, it may affect the nasal airway patency, function and sinonasal-related quality of life. The aim of this study is to objectively and subjectively evaluate these effects. Methods: In this prospective study, 43 patients with pituitary adenoma who were candidates for EETSA from March 2012 to October 2013 were enrolled. The patients were evaluated preoperatively using acoustic rhinometry and rhinomanometry (with/without the use of decongestant drops) and asked to complete the 22-Item Sinonasal Outcome Test (SNOT-22) questionnaire. The tests were repeated at one and three months postoperatively. The preoperative data were compared with the first and second postoperative ones using paired-sample t-test. Results: Without the use of decongestant drops, the total airway resistance increased significantly (p=0.016), and the nasal airflow decreased significantly (p=0.031) in the first postoperative evaluation. However, in the 3rd postoperative month, the difference was not significant. With the use of decongestant drops, the objective parameters showed no significant changes compared to preoperative data even at the first evaluation. The SNOT- 22 scores also did not differ significantly in 1st and 3rd postoperative months. The first postoperative SNOT-22 showed a strong correlation with the second minimal cross-sectional area on simultaneous evaluation, and with the preoperative total airway resistance. Conclusion: EETSA has a transient adverse effect on the nasal patency that quickly improves, making it a safe approach for the sinonasal system. Rhinomanometry is the most sensitive test for detecting these nasal functional changes objectively. PMID:27493923

  9. Optimization of Iron Cobalt-based Nanocomposite Alloys for High Induction and Increased Resistivity

    NASA Astrophysics Data System (ADS)

    Shen, Shen

    FeCo-based nanocrystalline soft magnetic materials are promising to provide high saturation induction, high Curie temperature and excellent soft magnetic properties for electric vehicle and high frequency power conversion applications. The increasing operation frequency of various inductive applications requires nanocomposite alloys with higher resistivity to suppress power losses. In this thesis, the method of measuring as-cast and annealed resistivity of melt-spun ribbon alloys by obtaining alloy densities was established. Archimedes method with deionized water as a medium was used to determine the density of crystalline alloys. A gas pycnometer using dry Helium gas as the medium exhibited improved accuracy in measuring the density of amorphous ribbon alloys compared to the conventional Archimedes method using a liquid medium. This method was applied to previously developed HITPERM (FeCoZrBCu) and HTX002 (FeCoBSiCu) type of alloys as well as carbon-containing (FeCoBCCu) alloys to guide composition adjustments pursuing for improved magnetic properties. In the HITPERM type of alloys, the composition dependence of as-cast resistivity was studied and simulated by Mott's two-current model with a rigid-band assumption which provided guidance for further adjusting alloy composition looking for higher resistivity. An alloy designed with the Fe:Co ratio for maximum as-cast resistivity and Hf as glass former exhibits low power loss values being approximately 1/4 of those measured on the alloy with the original HITPERM composition for a range of frequencies. The Al and Si additions were found effective to achieve a high resistivity of 151.9 muO·cm in the as-cast alloys but also lead to embrittlement of melt-spun ribbons. Composition adjustments on the HTX002 type of alloys which are castable in air and available for larger-scale production were also explored. Increasing the ferromagnetic late transition metal content by reducing glass formers was found effective to achieve

  10. Hyperinsulinaemia increases vascular resistance and endothelin-1 expression in the equine digit

    PubMed Central

    GAUFF, F.; PATAN-ZUGAJ, B.; LICKA, T. F.

    2014-01-01

    Summary Reasons for performing study Insulin leads to overexpression of endothelin-1 (ET-1) in the endothelium of insulin-resistant rodents. If this is also the case in equine laminar tissue, this could explain the predisposition of insulin-resistant horses to laminitis. Objectives To investigate the effect of hyperinsulinaemia on metabolism and vascular resistance of the isolated equine digit in a model of extracorporeal perfusion. Study design Randomised, controlled study with interventional group, with blinded evaluation of histology results. Method After exsanguination, equine digits (n = 11) and autologous blood were collected at an abattoir. One digit served as a hyperinsulinaemic pilot limb, 5 digits were assigned to the hyperinsulinaemic perfusion (IP) group and 5 to the control perfusion (CP) group. Digits were perfused for 10 h at a defined perfusion rate of 12 ml/min/kg. After the first hour of perfusion (equilibration period), insulin was added to the reservoir of the IP digits. Perfusion pressure, glucose consumption, lactate and lactate dehydrogenase were monitored. Vascular resistance was calculated as perfusion pressure (in millimetres of mercury) in relation to the flow rate (in millilitres per minute). After perfusion, histology samples of the dorsal hoof wall (haematoxylin & eosin or periodic acid-Schiff) were evaluated. Immunohistology with a polyclonal rabbit-derived anti-endothelin antibody was used for detection of ET-1. Results In the IP group, the mean insulin concentration in the plasma of the perfusate was 142 ± 81 μiu/ml, while insulin concentration was <3 μiu/ml in the CP group. Mean vascular resistance was significantly higher (P<0.01) in the IP group (2.04 ± 1.13 mmHg/ml/min) than in the CP group (1.31 ± 0.55 mmHg/ml/min). Histology of the IP group samples showed significantly more vessels with an open lumen, increased width of the secondary epidermal lamellae and formation of oedema. In the lamellar vessels (veins and arteries

  11. Suplatast tosilate ameliorates airway hyperreactivity and inflammation through inhibition of the GATA‑3/IL‑5 signaling pathway in asthmatic rats.

    PubMed

    Tan, Yupin; Li, Yun; Liu, Dan; Zhong, Lili

    2013-07-01

    Airway hyperreactivity and inflammation are important factors in the aggravation of lung function. Suplatast tosilate (IPD) is a novel and unique anti‑asthma clinical compound. However, the mechanisms of IPD action in the inhibition of asthma remain to be elucidated. The present study aimed to investigate the role of the GATA binding protein 3 (GATA‑3)/interleukin (IL)‑5 signaling pathway in IPD‑induced inhibition of asthma. Sprague‑Dawley rats were sensitized by intraperitoneal injection with ovalbumin (OVA) to establish an animal model of asthma. IPD was administered continuously (C‑IPD) or at a later stage (L‑IPD). Budesonide (BUD) was used as a positive control. Airway resistance and the expression of genes at the mRNA and protein levels were measured. Morphological changes in lung tissue and the percentage of eosinophils (EOS) in peripheral blood were observed and correlation analysis was performed. The results revealed that sensitization by OVA significantly increased airway resistance and the percentage of EOS in peripheral blood and induced significant inflammatory changes in lung tissue, as demonstrated by thick epithelium, goblet cell hyperplasia and submucosal cell infiltration. In addition, sensitization by OVA was found to markedly upregulate IL‑5 mRNA and protein expression. Airway resistance was found to positively correlate with the expression of IL‑5 in the rat lung tissues. Sensitization by OVA was also observed to markedly enhance GATA‑3 protein expression and GATA‑3 levels were found to positively correlate with airway resistance and IL‑5 levels. Similar to the effect of BUD, treatment with C‑IPD or L‑IPD was found to significantly attenuate OVA‑induced increases in airway resistance and the percentage of EOS in peripheral blood. Notably, treatment with C‑IPD or L‑IPD markedly reduced the OVA-induced expression of IL‑5 and GATA‑3. In the present study, IPD intervention was demonstrated to ameliorate airway

  12. MicroRNA in United Airway Diseases

    PubMed Central

    Liu, Zheng; Zhang, Xin-Hao; Callejas-Díaz, Borja; Mullol, Joaquim

    2016-01-01

    The concept of united airway diseases (UAD) has received increasing attention in recent years. Sustained and increased inflammation is a common feature of UAD, which is inevitably accompanied with marked gene modification and tight gene regulation. However, gene regulation in the common inflammatory processes in UAD remains unclear. MicroRNA (miRNA), a novel regulator of gene expression, has been considered to be involved in many inflammatory diseases. Although there are an increasing number of studies of miRNAs in inflammatory upper and lower airway diseases, few miRNAs have been identified that directly link the upper and lower airways. In this article, therefore, we reviewed the relevant studies available in order to improve the understanding of the roles of miRNAs in the interaction and pathogenesis of UAD. PMID:27187364

  13. Toll-like Receptor 7 Rapidly Relaxes Human Airways

    PubMed Central

    Scott, Gregory D.; Proskocil, Becky J.; Fryer, Allison D.; Jacoby, David B.; Kaufman, Elad H.

    2013-01-01

    Rationale: Toll-like receptors (TLRs) 7 and 8 detect respiratory virus single-stranded RNA and trigger an innate immune response. We recently described rapid TLR7-mediated bronchodilation in guinea pigs. Objectives: To characterize TLR7 expression and TLR7-induced airway relaxation in humans and in eosinophilic airway inflammation in guinea pigs. To evaluate the relaxant effects of other TLRs. Methods: Human airway smooth muscle strips were contracted with methacholine in vitro, and responses to TLR7 and TLR8 agonists were assessed. TLR7-mediated nitric oxide production was measured using a fluorescent indicator, and TLR7 expression was characterized using immunofluorescence. TLR7 signaling was also evaluated in ovalbumin-challenged guinea pigs. Measurements and Main Results: The TLR7 agonist imiquimod (R837) caused rapid dose-dependent relaxation of methacholine-contracted human airways in vitro. This was blocked by the TLR7 antagonist IRS661 and by inhibiting nitric oxide production but not by inhibiting prostaglandin production. TLR7 activation markedly increased fluorescence of a nitric oxide detector. TLR7 was expressed on airway nerves, but not airway smooth muscle, implicating airway nerves as the source of TLR7-induced nitric oxide production. TLR7-mediated relaxation persisted in inflamed guinea pigs airways in vivo. The TLR8 agonists polyuridylic acid and polyadenylic acid also relaxed human airways, and this was not blocked by the TLR7 antagonist or by blocking nitric oxide or prostaglandin production. No other TLRs relaxed the airways. Conclusions: TLR7 is expressed on airway nerves and mediates relaxation of human and animal airways through nitric oxide production. TLR7-mediated bronchodilation may be a new therapeutic strategy in asthma. PMID:23924358

  14. Production of Siderophores Increases Resistance to Fusaric Acid in Pseudomonas protegens Pf-5

    PubMed Central

    Ruiz, Jimena A.; Bernar, Evangelina M.; Jung, Kirsten

    2015-01-01

    Fusaric acid is produced by pathogenic fungi of the genus Fusarium, and is toxic to plants and rhizobacteria. Many fluorescent pseudomonads can prevent wilt diseases caused by these fungi. This study was undertaken to evaluate the effect of fusaric acid on P. protegens Pf-5 and elucidate the mechanisms that enable the bacterium to survive in the presence of the mycotoxin. The results confirm that fusaric acid negatively affects growth and motility of P. protegens. Moreover, a notable increase in secretion of the siderophore pyoverdine was observed when P. protegens was grown in the presence of fusaric acid. Concomitantly, levels of enzymes involved in the biosynthesis of pyoverdine and enantio-pyochelin, the second siderophore encoded by P. protegens, increased markedly. Moreover, while similar levels of resistance to fusaric acid were observed for P. protegens mutants unable to synthesize either pyoverdine or enanto-pyochelin and the wild type strain, a double mutant unable to synthesize both kinds of siderophores showed a dramatically reduced resistance to this compound. This reduced resistance was not observed when this mutant was grown under conditions of iron excess. Spectrophotometric titrations revealed that fusaric acid binds not only Fe2+ and Fe3+, but also Zn2+, Mn2+ and Cu2+, with high affinity. Our results demonstrate that iron sequestration accounts at least in part for the deleterious effect of the mycotoxin on P. protegens. PMID:25569682

  15. Sampling and Complementarity Effects of Plant Diversity on Resource Use Increases the Invasion Resistance of Communities

    PubMed Central

    Zhu, Dan H.; Wang, Ping; Zhang, Wei Z.; Yuan, Yue; Li, Bin; Wang, Jiang

    2015-01-01

    Background Although plant diversity is postulated to resist invasion, studies have not provided consistent results, most of which were ascribed to the influences of other covariate environmental factors. Methodology/Principal Findings To explore the mechanisms by which plant diversity influences community invasibility, an experiment was conducted involving grassland sites varying in their species richness (one, two, four, eight, and sixteen species). Light interception efficiency and soil resources (total N, total P, and water content) were measured. The number of species, biomass, and the number of seedlings of the invading species decreased significantly with species richness. The presence of Patrinia scabiosaefolia Fisch. ex Trev. and Mosla dianthera (Buch.-Ham. ex Roxburgh) Maxim. significantly increased the resistance of the communities to invasion. A structural equation model showed that the richness of planted species had no direct and significant effect on invasion. Light interception efficiency had a negative effect on the invasion whereas soil water content had a positive effect. In monocultures, Antenoron filiforme (Thunb.) Rob. et Vaut. showed the highest light interception efficiency and P. scabiosaefolia recorded the lowest soil water content. With increased planted-species richness, a greater percentage of pots showed light use efficiency higher than that of A. filiforme and a lower soil water content than that in P. scabiosaefolia. Conclusions/Significance The results of this study suggest that plant diversity confers resistance to invasion, which is mainly ascribed to the sampling effect of particular species and the complementarity effect among species on resources use. PMID:26556713

  16. Urban wastewater effluent increases antibiotic resistance gene concentrations in a receiving northern European river.

    PubMed

    Berglund, Björn; Fick, Jerker; Lindgren, Per-Eric

    2015-01-01

    Antibiotic-resistant bacteria are an emerging global problem that threatens to undermine important advances in modern medicine. The environment is likely to play an important role in the dissemination of antibiotic-resistance genes (ARGs) among both environmental and pathogenic bacteria. Wastewater treatment plants (WWTPs) accumulate both chemical and biological waste from the surrounding urban milieu and have therefore been viewed as potential hotspots for dissemination and development of antibiotic resistance. To assess the effect of wastewater effluent on a river that flows through a Swedish city, sediment and water samples were collected from Stångån River, both upstream and downstream of an adjacent WWTP over 3 mo. Seven ARGs and the integrase gene on class 1 integrons were quantified in the collected sediment using real-time polymerase chain reaction (PCR). Liquid chromatography-mass spectrometry was used to assess the abundance of 10 different antibiotics in the water phase of the samples. The results showed an increase in ARGs and integrons downstream of the WWTP. The measured concentrations of antibiotics were low in the water samples from the Stångån River, suggesting that selection for ARGs did not occur in the surface water. Instead, the downstream increase in ARGs is likely to be attributable to accumulation of genes present in the treated effluent discharged from the WWTP.

  17. Arginine Vasopressin Alters Both Spontaneous and Phase-Locked Synaptic Inputs to Airway Vagal Preganglionic Neuron via Activation of V1a Receptor: Insights into Stress-Related Airway Vagal Excitation

    PubMed Central

    Yan, Xianxia; Chen, Xingxin; Guo, Yuhong; He, Ding; Chen, Yonghua; Xia, Chunmei; Wang, Jijiang

    2017-01-01

    The airway vagal preganglionic neurons (AVPNs) in the external formation of the nucleus ambiguus (eNA) play a major role in the vagal control of tracheobronchial smooth muscle tone and maintenance of airway resistance. The eNA receives vasopressinergic projection from the hypothalamic paraventricular nucleus (PVN), the key node for the genesis of psychological stress. Since airway vagal excitation is reportedly to be associated with the psychological stress-induced/exacerbated airway hyperresponsiveness in asthmatics, arginine vasopressin (AVP) might be involved in stress-related airway vagal excitation. However, this possibility has not been validated. This study aimed to test whether and how AVP regulates AVPNs. In rhythmically active medullary slices of newborn rats, retrogradely labeled AVPNs were identified as inspiratory-activated and inspiratory-inhibited AVPNs (IA- and II-AVPNs) using patch-clamp techniques according to their inspiratory-related firing behavior and synaptic activities. The results show that under current clamp, AVP depolarized both IA- and II-AVPNs, and significantly increased their spontaneous firing rate. Under voltage clamp, AVP elicited a slow inward current, and significantly increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in both types of AVPNs. In addition, AVP significantly enhanced the phase-locked excitatory inspiratory inward current in inspiratory-activated airway vagal preganglionic neurons (IA-AVPNs), but significantly suppressed the phase-locked inhibitory inspiratory outward current in II-AVPNs. In both types AVPNs, AVP significantly increased the frequency and amplitude of pharmacologically isolated spontaneous GABAergic and glycinergic inhibitory postsynaptic currents (IPSCs). All of the AVP-induced effects were prevented by SR49059, an antagonist of V1a receptors, but unaffected by SSR149415, an antagonist of V1b receptors. AVP did not cause significant changes in the miniature excitatory

  18. INHIBITION OF PAN NEUROTROPHIN RECEPTOR P75 ATTENUATES DIESEL PARTICULATE-INDUCED ENHANCEMENT OF ALLERGIC AIRWAY RESPONSES IN C57/BL6J MICE

    EPA Science Inventory

    Recent investigations have linked neurotrophins including nerve growth factor (NGF), neurotrophin-3 (NT-3), and brain-derived neurotrophic factor (BDNF) to allergic airways diseases. Antibody blockade of NGF attenuates airway resistance in allergic mice. Diesel exhaust particle...

  19. Increased resistance to cucumber mosaic virus (CMV) in Lilium transformed with a defective CMV replicase gene.

    PubMed

    Azadi, Pejman; Otang, Ntui Valentaine; Supaporn, Hasthanasombut; Khan, Raham Sher; Chin, Dong Poh; Nakamura, Ikuo; Mii, Masahiro

    2011-06-01

    Lilium cv Acapulco was transformed with a defective cucumber mosaic virus (CMV) replicase gene (CMV2-GDD) construct using Agrobacterium tumefaciens. Four lines were analyzed for gene expression and resistance to CMV-O strain. Expression of the CMV2-GDD gene in the transgenic plants was confirmed by reverse transcription PCR (RT-PCR). When these four lines were mechanically inoculated with CMV-O, no signal of coat protein (CP) messages using RT-PCR was detected in newly produced leaves of two transgenic lines. Dot-immunobinding assay (DIBA) of CP was performed to examine the presence of the CMV in the newly produced leaves of challenged plants. Results, similar to those obtained with RT-PCR of the CP messages, were observed in DIBA. Therefore, our results imply that the two lines show increased levels of resistance to CMV, and CMV-GDD replicase gene is an effective construct that has protection against CMV in Lilium.

  20. Treatment Resistant Epilepsy in Autism Spectrum Disorder: Increased Risk for Females.

    PubMed

    Blackmon, Karen; Bluvstein, Judith; MacAllister, William S; Avallone, Jennifer; Misajon, Jade; Hedlund, Julie; Goldberg, Rina; Bojko, Aviva; Mitra, Nirmala; Giridharan, Radha; Sultan, Richard; Keller, Seth; Devinsky, Orrin

    2016-02-01

    The male:female ratio in autism spectrum disorder (ASD) averages greater than 4:1 while the male:female ratio of ASD with epilepsy averages less than 3:1. This indicates an elevated risk of epilepsy in females with ASD; yet, it is unknown whether phenotypic features of epilepsy and ASD differ between males and females with this comorbidity. The goal of this study is to investigate sex differences in phenotypic features of epilepsy and ASD in a prospective sample of 130 children and young adults with an initial ASD diagnosis and subsequent epilepsy diagnosis. All participants were characterized by standardized diagnostic inventories, parent/caregiver completed questionnaires, and medical/academic record review. Diagnostic classifications of epilepsy, ASD, and intellectual disability were performed by board certified neurologists and a pediatric neuropsychologist. Results demonstrated a lower male:female ratio (1.8:1) in individuals with ASD and treatment-resistant epilepsy relative to those with ASD and treatment-responsive epilepsy (4.9:1), indicating a higher risk of treatment-resistant epilepsy in females. Mild neuroimaging abnormalities were more common in females than males and this was associated with increased risk of treatment-resistance. In contrast, ASD symptom severity was lower in females compared with males. Findings distinguish females with ASD and epilepsy as a distinct subgroup at higher risk for a more severe epilepsy phenotype in the context of a less severe ASD phenotype. Increased risk of anti-epileptic treatment resistance in females with ASD and epilepsy suggests that comprehensive genetic, imaging, and neurologic screening and enhanced treatment monitoring may be indicated for this subgroup. Autism Res 2016, 9: 311-320. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

  1. A 'Good' muscle in a 'Bad' environment: the importance of airway smooth muscle force adaptation to airway hyperresponsiveness.

    PubMed

    Bossé, Ynuk; Chapman, David G; Paré, Peter D; King, Gregory G; Salome, Cheryl M

    2011-12-15

    Asthma is characterized by airway inflammation, with a consequent increase in spasmogens, and exaggerated airway narrowing in response to stimuli, termed airway hyperresponsiveness (AHR). The nature of any relationship between inflammation and AHR is less clear. Recent ex vivo data has suggested a novel mechanism by which inflammation may lead to AHR, in which increased basal ASM-tone, due to the presence of spasmogens in the airways, may "strengthen" the ASM and ultimately lead to exaggerated airway narrowing. This phenomenon was termed "force adaptation" [Bossé, Y., Chin, L.Y., Paré, P.D., Seow, C.Y., 2009. Adaptation of airway smooth muscle to basal tone: relevance to airway hyperresponsiveness. Am. J. Respir. Cell Mol. Biol. 40, 13-18]. However, it is unknown whether the magnitude of the effect of force adaptation ex vivo could contribute to exaggerated airway narrowing in vivo. Our aim was to utilize a computational model of ASM shortening in order to quantify the potential effect of force adaptation on airway narrowing when all other mechanical factors were kept constant. The shortening in the model is dictated by a balance between physiological loads and ASM force-generating capacity at different lengths. The results suggest that the magnitude of the effect of force adaptation on ASM shortening would lead to substantially more airway narrowing during bronchial challenge at any given airway generation. We speculate that the increased basal ASM-tone in asthma, due to the presence of inflammation-derived spasmogens, produces an increase in the force-generating capacity of ASM, predisposing to AHR during subsequent challenge.

  2. Muscle Volume Increases Following 16 Weeks of Resistive Exercise Training with the Advanced Resistive Exercise Device (ARED) and Free Weights

    NASA Technical Reports Server (NTRS)

    Nash, R. E.; Loehr, J. A.; Lee, S. M. C.; English, K. L.; Evans, H.; Smith, S. A.; Hagan, R. D.

    2009-01-01

    Space flight-induced muscle atrophy, particularly in the postural and locomotorymuscles, may impair task performance during long-duration space missions and planetary exploration. High intensity free weight (FW) resistive exercise training has been shown to prevent atrophy during bed rest, a space flight analog. NASA developed the Advanced Resistive Exercise Device (ARED) to simulate the characteristics of FW exercise (i.e. constant mass, inertial force) and to be used as a countermeasure during International Space Station (ISS) missions. PURPOSE: To compare the efficacy of ARED and FW training to induce hypertrophy in specific muscle groups in ambulatory subjects prior to deploying ARED on the ISS. METHODS: Twenty untrained subjects were assigned to either the ARED (8 males, 3 females) or FW (6 males, 3 females) group and participated in a periodizedtraining protocol consisting of squat (SQ), heel raise (HR), and deadlift(DL) exercises 3 d wk-1 for 16 wks. SQ, HR, and DL muscle strength (1RM) was measured before, after 8 wks, and after 16 wks of training to prescribe exercise and measure strength changes. Muscle volume of the vastigroup (V), hamstring group (H), hip adductor group (ADD), medial gastrocnemius(MG), lateral gastrocnemius(LG), and deep posterior muscles including soleus(DP) was measured using MRI pre-and post-training. Consecutive cross-sectional images (8 mm slices with a 2 mm gap) were analyzed and summed. Anatomical references insured that the same muscle sections were analyzed pre-and post-training. Two-way repeated measures ANOVAs (p<0.05) were used to test for differences in muscle strength and volume between training devices. RESULTS: SQ, HR, and DL 1RM increased in both FW (SQ: 49+/-6%, HR: 12+/-2%, DL: 23+/-4%) and ARED (SQ: 31+/-4%, HR: 18+/-2%, DL: 23+/-3%) groups. Both groups increased muscle volume in the V (FW: 13+/-2%, ARED: 10+/-2%), H (FW: 3+/-1%, ARED: 3+/-1 %), ADD (FW: 15=/-2%, ARED: 10+/-1%), LG (FW: 7+/-2%, ARED: 4+/-1%), MG (FW

  3. Has the airway microbiome been overlooked in respiratory disease?

    PubMed

    Salami, Olawale; Marsland, Benjamin J

    2015-01-01

    The respiratory disease field is changing because of recent advances in our understanding of the airway microbiome. Central to this is dysbiosis, an imbalance of microbial communities that can lead to and flag inflammation in the airways. The increasing momentum of research in this area holds promise for novel treatment strategies.

  4. Pulmonary Stress Induced by Hyperthermia: Role of Airway Sensory Nerves

    DTIC Science & Technology

    2012-10-01

    blind design was used to compare between the effects of pretreatments with ipratropium bromide and placebo aerosols on the airway responses to HA... ipratropium completely prevented the WA- induced bronchoconstriction in asthmatics. In conclusion, bronchoconstriction induced by increasing airway...patients was completely prevented by pretreatment with ipratropium aerosol, indicating an involvement of cholinergic reflex. Accompanying the

  5. Cigarette smoking reprograms apical junctional complex molecular architecture in the human airway epithelium in vivo.

    PubMed

    Shaykhiev, Renat; Otaki, Fouad; Bonsu, Prince; Dang, David T; Teater, Matthew; Strulovici-Barel, Yael; Salit, Jacqueline; Harvey, Ben-Gary; Crystal, Ronald G

    2011-03-01

    The apical junctional complex (AJC), composed of tight and adherens junctions, maintains epithelial barrier function. Since cigarette smoking and chronic obstructive pulmonary disease (COPD), the major smoking-induced disease, are associated with increased lung epithelial permeability, we hypothesized that smoking alters the transcriptional program regulating airway epithelial AJC integrity. Transcriptome analysis revealed global down-regulation of physiological AJC gene expression in the airway epithelium of healthy smokers (n = 59) compared to nonsmokers (n = 53) in association with changes in canonical epithelial differentiation pathways such as PTEN signaling accompanied by induction of cancer-related AJC components. The overall expression of AJC-related genes was further decreased in COPD smokers (n = 23). Exposure of airway epithelial cells to cigarette smoke extract in vitro resulted in down-regulation of several AJC genes paralleled by decreased transepithelial resistance. Thus, cigarette smoking induces transcriptional reprogramming of airway epithelial AJC architecture from its physiological pattern necessary for barrier function toward a disease-associated molecular phenotype.

  6. Synchronized imaging and acoustic analysis of the upper airway in patients with sleep-disordered breathing.

    PubMed

    Chang, Yi-Chung; Huon, Leh-Kiong; Pham, Van-Truong; Chen, Yunn-Jy; Jiang, Sun-Fen; Shih, Tiffany Ting-Fang; Tran, Thi-Thao; Wang, Yung-Hung; Lin, Chen; Tsao, Jenho; Lo, Men-Tzung; Wang, Pa-Chun

    2014-12-01

    Progressive narrowing of the upper airway increases airflow resistance and can produce snoring sounds and apnea/hypopnea events associated with sleep-disordered breathing due to airway collapse. Recent studies have shown that acoustic properties during snoring can be altered with anatomic changes at the site of obstruction. To evaluate the instantaneous association between acoustic features of snoring and the anatomic sites of obstruction, a novel method was developed and applied in nine patients to extract the snoring sounds during sleep while performing dynamic magnetic resonance imaging (MRI). The degree of airway narrowing during the snoring events was then quantified by the collapse index (ratio of airway diameter preceding and during the events) and correlated with the synchronized acoustic features. A total of 201 snoring events (102 pure retropalatal and 99 combined retropalatal and retroglossal events) were recorded, and the collapse index as well as the soft tissue vibration time were significantly different between pure retropalatal (collapse index, 2 ± 11%; vibration time, 0.2 ± 0.3 s) and combined (retropalatal and retroglossal) snores (collapse index, 13 ± 7% [P ≤ 0.0001]; vibration time, 1.2 ± 0.7 s [P ≤ 0.0001]). The synchronized dynamic MRI and acoustic recordings successfully characterized the sites of obstruction and established the dynamic relationship between the anatomic site of obstruction and snoring acoustics.

  7. Does Drought Increase the Risk of Insects Developing Behavioral Resistance to Systemic Insecticides?

    PubMed Central

    Fowles, Trevor; Bick, Emily; Nansen, Christian

    2016-01-01

    Increases in severity and frequency of drought periods, average global temperatures, and more erratic fluctuations in rainfall patterns due to climate change are predicted to have a dramatic impact on agricultural production systems. Insect pest populations in agricultural and horticultural systems are also expected to be impacted, both in terms of their spatial and temporal distributions and in their status as pest species. In this opinion-based article, we discuss how indirect effects of drought may adversely affect the performance of systemic insecticides and also lead to increased risk of insect pests developing behavioral insecticide resistance. We hypothesize that more pronounced drought will decrease uptake and increase the magnitude of nonuniform translocation of systemic insecticides within treated crop plants, and that may have two concurrent consequences: 1) reduced pesticide performance, and 2) increased likelihood of insect pests evolving behavioral insecticide resistance. Under this scenario, pests that can sense and avoid acquisition of lethal dosages of systemic insecticides within crop plants will have a selective advantage. This may lead to selection for insect behavioral avoidance, so that insects predominantly feed and oviposit on portions of crop plants with low concentration of systemic insecticide. Limited research has been published on the effect of environmental variables, including drought, on pesticide performance, but we present and discuss studies that support the hypothesis described above. In addition, we wish to highlight the importance of studying the many ways environmental factors can affect, directly and indirectly, both the performance of insecticides and the risk of target insect pests developing resistance. PMID:27551149

  8. Mechanisms of genioglossus responses to inspiratory resistive load in rabbits.

    PubMed

    Aleksandrova, N P; Goloubeva, E V; Isaev, G G

    2002-07-01

    The purpose of the present study has been to determine whether pharyngeal dilator muscles participate in inspiratory load compensatory responses and if so, to elucidate role of upper airway mechanoreceptors in these responses. The experiments were performed on anaesthetized rabbits. Each animal was tested in three ways by the imposition of inspiratory resistive load: (1) at upper airways via face mask, (2) at the tracheostomic cannula placed below larynx (all upper airway receptors were 'bypassed') and (3) at the mouth after the section of the hypoglossus nerves (motor denervation of genioglossus muscle). The inspiratory load applied to the upper airways evoked significant increases in integrated genioglossus activity (to 129 +/- 14.7% of control) and its inspiratory duration (to 113 +/- 5% of control) already within the first loaded breath (P < 0.05). The increases in the inspiratory activity of musculius genioglossus were relatively greater than the simultaneous increases in the activity of the diaphragm. Motor denervation of the pharynx dilator muscles (including m. genioglossus) increased airway resistance to 184 +/- 19% of control (P < 0.05) and induced obstructive alterations in the breathing pattern during unloaded breathing: decrease in maximal inspiratory flow (-13%) and increase in the level of negative oesophageal pressure (+14%) and the peak diaphragm activity (+6%). After nervi hypoglossus sections additional increases in motor and pressure outputs were required in order to maintain unaltered ventilation at the same degree of loading as before denervation. The results indicate that the pharyngeal dilator muscles have a role in compensation of added inspiratory load. Activation of these muscles facilitate the load compensating function of 'pump' muscles by decreasing airway resistance. Tracheostomy did not reduce the genioglossus response to inspiratory loading, ruling out any role for upper airways receptors in the genioglossus response to inspiratory

  9. Electrical stimulation of upper airway musculature.

    PubMed

    Smith, P L; Eisele, D W; Podszus, T; Penzel, T; Grote, L; Peter, J H; Schwartz, A R

    1996-12-01

    Investigators have postulated that pharyngeal collapse during sleep in patients with obstructive sleep apnea (OSA) may be alleviated by stimulating the genioglossus. The effect of electrical stimulation (ES) of the genioglossus on pharyngeal patency was examined in an isolated feline upper airway preparation and in apneic humans during sleep. We found that stimulation of the genioglossus (n = 8) and of the hypoglossal nerve (n = 1) increased maximum airflow through the isolated feline upper airway in humans during sleep. Additional findings in the isolated feline upper airway suggest that such increases in airflow were due to decreases in pharyngeal collapsibility. The evidence suggests that improvements in airflow dynamics with electrical stimulation are due to selective recruitment of the genioglossus, rather than due to nonspecific activation of the pharyngeal musculature or arousal from sleep. The implications of these results for future therapy with ES are discussed.

  10. Whole apple extracts increase lifespan, healthspan and resistance to stress in Caenorhabditis elegans.

    PubMed

    Vayndorf, Elena M; Lee, Siu Sylvia; Liu, Rui Hai

    2013-07-01

    Regular consumption of fruits and vegetables is associated with reduced risk of age-related functional decline and chronic diseases such as cancer and cardiovascular disease. These effects are primarily attributed to phytochemicals, plant compounds with a wide range of biological activities and health benefits. Apples, the top contributor of fruit phenolics in American diets, have high antioxidant, antiproliferative and chemopreventive activity in vitro and in vivo. However, little is known about their effects on aging. The objectives of this study were to determine the effects of whole apple phytochemical extracts on lifespan, healthspan and resistance to various stresses in vivo using C. elegans as a model. The mean and maximum lifespan of animals treated with 2.5, 5 and 10 mg/ml whole apple extracts increased significantly in a dose-dependent manner by up to 39 and 25%, respectively. Healthspan also significantly improved as indicated by improved motility and reduced lipofuscin accumulation. Animals pre-treated with whole apple extracts were more resistant to stresses such as heat, UV radiation, paraquat-induced oxidative stress, and pathogenic infection, suggesting that cellular defense and immune system functions also improved. Our findings indicate that, in C. elegans, whole apple extracts slow aging, extend lifespan, improve healthspan, and enhance resistance to stress.

  11. Athletic Training Students Demonstrate Airway Management Skill Decay, but Retain Knowledge over 6 Months

    ERIC Educational Resources Information Center

    Popp, Jennifer K.; Berry, David C.

    2016-01-01

    Context: Airway management (AM) knowledge and skills are taught in all athletic training programs; however, research suggests that skill decay occurs with acute care skills as length of nonpractice increases. Objective: Evaluate retention of AM knowledge and skills, specifically oropharyngeal airway (OPA) and nasopharyngeal airway (NPA) use, in…

  12. At-home resistance tubing strength training increases shoulder strength in the trained and untrained limb.

    PubMed

    Magnus, C R A; Boychuk, K; Kim, S Y; Farthing, J P

    2014-06-01

    The purpose was to determine if an at-home resistance tubing strength training program on one shoulder (that is commonly used in rehabilitation settings) would produce increases in strength in the trained and untrained shoulders via cross-education. Twenty-three participants were randomized to TRAIN (strength-trained one shoulder; n = 13) or CONTROL (no intervention; n = 10). Strength training was completed at home using resistance tubing and consisted of maximal shoulder external rotation, internal rotation, scaption, retraction, and flexion 3 days/week for 4 weeks. Strength was measured via handheld dynamometry and muscle size measured via ultrasound. For external rotation strength, the trained (10.9 ± 10.9%) and untrained (12.7 ± 9.6%) arm of TRAIN was significantly different than CONTROL (1.6 ± 13.2%; -2.7 ± 12.3%; pooled across arm; P < 0.05). For internal rotation strength, the trained (14.8 ± 11.3%) and untrained (14.6 ± 10.1%) arm of TRAIN was significantly different than CONTROL (6.4 ± 11.2%; 5.1 ± 8.8%; pooled across arm; P < 0.05). There were no significant differences for scaption strength (P = 0.056). TRAIN significantly increased muscle size in the training arm of the supraspinatus (1.90 ± 0.32 to 1.99 ± 0.31 cm), and the anterior deltoid (1.08 ± 0.37 to 1.21 ± 0.39 cm; P < 0.05). This study suggests that an at-home resistance tubing training program on one limb can produce increases in strength in both limbs, and has implications for rehabilitation after unilateral shoulder injuries.

  13. Increased endothelin-1 vasoconstriction in mesenteric resistance arteries after superior mesenteric ischaemia-reperfusion

    PubMed Central

    Martínez-Revelles, S; Caracuel, L; Márquez-Martín, A; Dantas, AP; Oliver, E; D'Ocon, P; Vila, E

    2012-01-01

    BACKGROUND AND PURPOSE Endothelin-1 (ET-1) plays an important role in the maintenance of vascular tone. We aimed to evaluate the influence of superior mesenteric artery (SMA) ischaemia-reperfusion (I/R) on mesenteric resistance artery vasomotor function and the mechanism involved in the changes in vascular responses to ET-1. EXPERIMENTAL APPROACH SMA from male Sprague-Dawley rats was occluded (90 min) and following reperfusion (24 h), mesenteric resistance arteries were dissected. Vascular reactivity was studied using wire myography. Protein and mRNA expression, superoxide anion (O2•−) production and ET-1 plasma concentration were evaluated by immunofluorescence, real-time quantitative PCR, ethidium fluorescence and elisa, respectively. KEY RESULTS I/R increased ET-1 plasma concentration, ET-1-mediated vasoconstriction and ETB mRNA expression, and down-regulated ETA mRNA expression. Immunofluorescence confirmed mRNA results and revealed an increase in ETB receptors in the mesenteric resistance artery media layer after I/R. Therefore, the ETB receptor agonist sarafotoxin-6 induced a contraction that was inhibited by the ETB receptor antagonist BQ788 only in vessels, with and without endothelium, from I/R rats. Furthermore, BQ788 potentiated ET-1 vasoconstriction only in sham rats. Endothelium removal in rings from I/R rats unmasked the inhibition of ET-1 vasoconstriction by BQ788. Endothelium removal, Nω-nitro-L-arginine methyl ester and superoxide dismutase abolished the differences in ET-1 vasoconstriction between sham and I/R rats. We also found that I/R down-regulates endothelial NOS mRNA expression and concomitantly enhanced O2•− production by increasing NADPH oxidase 1 (NOX-1) and p47phox mRNA. CONCLUSIONS AND IMPLICATIONS Mesenteric I/R potentiated the ET-1-mediated vasoconstriction by a mechanism that involves up-regulation of muscular ETB receptors and decrease in NO bioavailability. PMID:21806604

  14. Photochemical activation increases the porcine corneal stiffness and resistance to collagenase digestion.

    PubMed

    Wang, Ti; Peng, Yinbo; Shen, Nianci; Yu, Yan; Yao, Min; Zhu, Jingyin

    2014-06-01

    In this study, we explore the effect of photochemical activation induced corneal cross-linking, utilizing Rose Bengal (RB) and 532 nm green light irradiation (RB-PCL), on porcine corneal biomechanical rigidity and the biochemical resistance against collagenase digestion. A protocol with a wavelength of 532 nm and illumination intensity of 0.4W/cm(2) for 250 s to deliver a dose of 100 J/cm(2) was chosen. Using confocal microscopy, we demonstrated that the diffusion depth of RB into porcine cornea was approximately 150 μm and mostly localized in anterior stroma 25 min followed by RB application. After photochemical cross-linking, an increase in tensile strength (by average 200%) and Young's modulus (by average 200%) in porcine corneas was observed. The corneal buttons treated by RB-PCL showed doubling of collagenase digestion time from 10.8 ± 3.1 days in the blank group to 19.7 ± 6.2 days in the RB-PCL group, indicating increased resistance to enzymatic digestion. In conclusion, Collagen cross-linking by RB-PCL increased both the biomechanical stiffness and the biochemical resistance against collagenase digestion in porcine corneas, therefore to allow stabilizing and solidifier the cornea. The advantages and disadvantages of RB-PCL versus UVA/riboflavin cross-linking technique (UV-CXL) are fully explored. Due to the nature of minimal penetration of RB into corneal stroma, the RB-PCL method could potentially be used in patients with corneal thickness less than 400 μm where UV-CXL is limited.

  15. Insulin resistance, low cardiorespiratory fitness, and increased exercise blood pressure: contribution of abdominal obesity.

    PubMed

    Huot, Maxime; Arsenault, Benoit J; Gaudreault, Valérie; Poirier, Paul; Pérusse, Louis; Tremblay, Angelo; Bouchard, Claude; Després, Jean-Pierre; Rhéaume, Caroline

    2011-12-01

    Individuals with insulin resistance and low cardiorespiratory fitness are frequently found to have an increased waist circumference and high exercise blood pressure. We tested the hypothesis that the relationships among insulin resistance, low cardiorespiratory fitness, and increased exercise blood pressure may be mediated by an elevated waist circumference. This study included 317 apparently healthy men and women (mean age: 34.8±12.8 years; mean body mass index: 26.1±5.2 kg/m(2)). Exercise blood pressure values were measured using a submaximal ergometer test evaluating physical working capacity. Plasma insulin and glucose levels were measured during a 3-hour oral glucose tolerance test. Multivariate regression analyses showed that waist circumference accounted for 32.8% (P<0.0001) and 45.1% (P<0.0001) of the variance in exercise systolic blood pressure in men and women, respectively. Participants were classified into tertiles according to either insulin response, measured during the oral glucose tolerance test, or fitness levels and then further subdivided into 2 subgroups using sex-specific waist circumference thresholds. Individuals with an increased waist circumference (≥94 cm and ≥80 cm for men and women, respectively) had higher exercise systolic blood pressure compared with individuals with low waist circumference, irrespective of their level of insulin resistance (10.6 versus 6.8, 12.2 versus 7.7, and 13.2 versus 8.7 mm Hg/metabolic equivalent, respectively, for the low, intermediate, and high tertiles; P<0.05) or fitness levels (13.1 versus 8.2, 12.0 versus 7.9, and 10.6 versus 7.1 mm Hg/metabolic equivalent, respectively, for the low, intermediate, and high tertiles; P<0.05). Individuals with a higher waist circumference have elevated exercise systolic blood pressure, regardless of their insulin sensitivity or level of cardiorespiratory fitness.

  16. Proline metabolism increases katG expression and oxidative stress resistance in Escherichia coli.

    PubMed

    Zhang, Lu; Alfano, James R; Becker, Donald F

    2015-02-01

    The oxidation of l-proline to glutamate in Gram-negative bacteria is catalyzed by the proline utilization A (PutA) flavoenzyme, which contains proline dehydrogenase (PRODH) and Δ(1)-pyrroline-5-carboxylate (P5C) dehydrogenase domains in a single polypeptide. Previous studies have suggested that aside from providing energy, proline metabolism influences oxidative stress resistance in different organisms. To explore this potential role and the mechanism, we characterized the oxidative stress resistance of wild-type and putA mutant strains of Escherichia coli. Initial stress assays revealed that the putA mutant strain was significantly more sensitive to oxidative stress than the parental wild-type strain. Expression of PutA in the putA mutant strain restored oxidative stress resistance, confirming that depletion of PutA was responsible for the oxidative stress phenotype. Treatment of wild-type cells with proline significantly increased hydroperoxidase I (encoded by katG) expression and activity. Furthermore, the ΔkatG strain failed to respond to proline, indicating a critical role for hydroperoxidase I in the mechanism of proline protection. The global regulator OxyR activates the expression of katG along with several other genes involved in oxidative stress defense. In addition to katG, proline increased the expression of grxA (glutaredoxin 1) and trxC (thioredoxin 2) of the OxyR regulon, implicating OxyR in proline protection. Proline oxidative metabolism was shown to generate hydrogen peroxide, indicating that proline increases oxidative stress tolerance in E. coli via a preadaptive effect involving endogenous hydrogen peroxide production and enhanced catalase-peroxidase activity.

  17. Quantitative resistance affects the speed of frequency increase but not the diversity of the virulence alleles overcoming a major resistance gene to Leptosphaeria maculans in oilseed rape.

    PubMed

    Delourme, R; Bousset, L; Ermel, M; Duffé, P; Besnard, A L; Marquer, B; Fudal, I; Linglin, J; Chadœuf, J; Brun, H

    2014-10-01

    Quantitative resistance mediated by multiple genetic factors has been shown to increase the potential for durability of major resistance genes. This was demonstrated in the Leptosphaeria maculans/Brassica napus pathosystem in a 5year recurrent selection field experiment on lines harboring the qualitative resistance gene Rlm6 combined or not with quantitative resistance. The quantitative resistance limited the size of the virulent isolate population. In this study we continued this recurrent selection experiment in the same way to examine whether the pathogen population could adapt and render the major gene ineffective in the longer term. The cultivars Eurol, with a susceptible background, and Darmor, with quantitative resistance, were used. We confirmed that the combination of qualitative and quantitative resistance is an effective approach for controlling the pathogen epidemics over time. This combination did not prevent isolates virulent against the major gene from amplifying in the long term but the quantitative resistance significantly delayed for 5years the loss of effectiveness of the qualitative resistance and disease severity was maintained at a low level on the genotype with both types of resistance after the fungus population had adapted to the major gene. We also showed that diversity of AvrLm6 virulence alleles was comparable in isolates recovered after the recurrent selection on lines carrying either the major gene alone or in combination with quantitative resistance: a single repeat-induced point mutation and deletion events were observed in both situations. Breeding varieties which combine qualitative and quantitative resistance can effectively contribute to disease control by increasing the potential for durability of major resistance genes.

  18. Biodiversity increases functional and compositional resistance, but decreases resilience in phytoplankton communities.

    PubMed

    Baert, Jan M; De Laender, Frederik; Sabbe, Koen; Janssen, Colin R

    2016-12-01

    There is now ample evidence that biodiversity stabilizes aggregated ecosystem functions, such as primary production, in changing environments. In primary producer systems, this stabilizing effect is found to be driven by higher functional resistance (i.e., reduced changes in functions by environmental changes) rather than through higher functional resilience (i.e., rapid recovery following environmental changes) in more diverse systems. The stability of aggregated ecosystem functions directly depends on changes in species composition and by consequence their functional contributions to ecosystem functions. Still, it remains only theoretically explored how biodiversity can stabilize ecosystem functions by affecting compositional stability. Here, we demonstrate how biodiversity effects on compositional stability drive biodiversity effects on functional stability in diatom communities. In a microcosm experiment, we exposed 39 communities of five different levels of species richness (1, 2, 4, 6, and 8 species) to three concentrations of a chemical stressor (0, 25, and 250 μg/L atrazine) for four weeks, after which all communities were transferred to atrazine-free medium for three more weeks. Biodiversity simultaneously increased, increasing functional and compositional resistance, but decreased functional and compositional resilience. These results confirm the theoretically proposed link between biodiversity effects on functional and compositional stability in primary producer systems, and provide a mechanistic underpinning for observed biodiversity-stability relationships. Finally, we discuss how higher compositional stability can be expected to become increasingly important in stabilizing ecosystem functions under field conditions when multiple environmental stressors fluctuate simultaneously.

  19. Antibiotic surgical prophylaxis increases nasal carriage of antibiotic-resistant staphylococci.

    PubMed

    McMurray, Claire L; Hardy, Katherine J; Verlander, Neville Q; Hawkey, Peter M

    2015-12-01

    Staphylococci are a significant cause of hospital-acquired infection. Nasal carriage of Staphylococcus aureus is an important risk factor for infection in surgical patients and coagulase-negative staphylococci (CNS) are a major cause of prosthetic joint infections. The impact that antibiotic surgical prophylaxis has on the nasal carriage of staphylococci has not been studied. Daily nasal swabs were taken from 63 patients who received antibiotic surgical prophylaxis and 16 patients who received no antibiotics. Total aerobic bacterial count, S. aureus and CNS were enumerated by culture from nasal swabs. Representative isolates were typed by staphylococcal interspersed repeat units (SIRU) typing and PFGE, and MICs to nine antibiotics were determined. After antibiotic administration, there was a reduction in S. aureus counts (median - 2.3 log(10)c.f.u. ml(- 1)) in 64.0 % of S. aureus carriers, compared with only a 0.89 log(10)c.f.u. ml(- 1) reduction in 75.0 % of S. aureus carriers who did not receive antibiotics. A greater increase in the nasal carriage rate of meticillin-resistant CNS was observed after antibiotic surgical prophylaxis compared with hospitalization alone, with increases of 16.4 and 4.6 %, respectively. Antibiotic-resistant S. epidermidis carriage rate increased by 16.6 % after antibiotic administration compared with 7.5 % with hospitalization alone. Antibiotic surgical prophylaxis impacts the nasal carriage of both S. aureus and CNS.

  20. Development of the First Cisgenic Apple with Increased Resistance to Fire Blight.

    PubMed

    Kost, Thomas D; Gessler, Cesare; Jänsch, Melanie; Flachowsky, Henryk; Patocchi, Andrea; Broggini, Giovanni A L

    2015-01-01

    The generation and selection of novel fire blight resistant apple genotypes would greatly improve the management of this devastating disease, caused by Erwinia amylovora. Such resistant genotypes are currently developed by conventional breeding, but novel breeding technologies including cisgenesis could be an alternative approach. A cisgenic apple line C44.4.146 was regenerated using the cisgene FB_MR5 from wild apple Malus ×robusta 5 (Mr5), and the previously established method involving A. tumefaciens-mediated transformation of the fire blight susceptible cultivar 'Gala Galaxy' using the binary vector p9-Dao-FLPi. The line C44.4.146 was shown to carry only the cisgene FB_MR5, controlled by its native regulatory sequences and no transgenes were detected by PCR or Southern blot following heat induced recombinase-mediated elimination of the selectable markers. Although this line contains up to 452 bp of vector sequences, it still matches the original definition of cisgenesis. A single insertion of T-DNA into the genome of 'Gala Galaxy' in chromosome 16 was identified. Transcription of FB_MR5 in line C44.4.146 was similar to the transcription in classically bred descendants of Mr5. Three independent shoot inoculation experiments with a Mr5 avirulent strain of Erwinia amylovora were performed using scissors or syringe. Significantly lower disease symptoms were detected on shoots of the cisgenic line compared to those of untransformed 'Gala Galaxy'. Despite the fact that the pathogen can overcome this resistance by a single nucleotide mutation, this is, to our knowledge, the first prototype of a cisgenic apple with increased resistance to fire blight.

  1. Sphaeropsidin A shows promising activity against drug-resistant cancer cells by targeting regulatory volume increase

    PubMed Central

    Mathieu, Véronique; Chantôme, Aurélie; Lefranc, Florence; Cimmino, Alessio; Miklos, Walter; Paulitschke, Verena; Mohr, Thomas; Maddau, Lucia; Kornienko, Alexander; Berger, Walter; Vandier, Christophe; Evidente, Antonio; Delpire, Eric; Kiss, Robert

    2016-01-01

    Despite the recent advances in the treatment of tumors with intrinsic chemotherapy resistance, such as melanoma and renal cancers, their prognosis remains poor and new chemical agents with promising activity against these cancers are urgently needed. Sphaeropsidin A, a fungal metabolite whose anticancer potential had previously received little attention, was isolated from Diplodia cupressi and found to display specific anticancer activity in vitro against melanoma and kidney cancer subpanels in the National Cancer Institute (NCI) 60-cell line screen. The NCI data revealed a mean LC50 of ca. 10 μM and a cellular sensitivity profile that did not match that of any other agent in the 765,000 compound database. Subsequent mechanistic studies in melanoma and other multidrug-resistant in vitro cancer models showed that sphaeropsidin A can overcome apoptosis as well as multidrug resistance by inducing a marked and rapid cellular shrinkage related to the loss of intracellular Cl− and the decreased HCO3− concentration in the culture supernatant. These changes in ion homeostasis and the absence of effects on the plasma membrane potential were attributed to the sphaeropsidin A-induced impairment of regulatory volume increase (RVI). Preliminary results also indicate that depending on the type of cancer, the sphaeropsidin A effects on RVI could be related to Na–K–2Cl electroneutral cotransporter or Cl−/HCO3− anion exchanger(s) targeting. This study underscores the modulation of ion-transporter activity as a promising therapeutic strategy to combat drug-resistant cancers and identifies the fungal metabolite, sphaeropsidin A, as a lead to develop anticancer agents targeting RVI in cancer cells. PMID:25868554

  2. Multiwire conductor having greatly increased interwire resistance and method for making same

    DOEpatents

    Luhman, Thomas; Suenaga, Masaki

    1984-01-17

    An improved multiwire conductor of the type which is mechanically stabilized by a tin based solder filler. A solder filled conductor is heated to a temperature above its melting point for a period long enough to allow a substantial amount of copper to be dissolved from the wires comprising the conductor. The copper forms the brittle intermetallic compound Cu.sub.5 Sn.sub.6 with tin in the solder. After cooling the conductor is flexed causing a random cracking of the solder, and thereby increasing the interwire resistance of the conductor. The subject invention is particularly adapted for use with braided, ribbon-type solder filled superconductors.

  3. Multiwire conductor having increased interwire resistance and good mechanical stability and method for making same

    DOEpatents

    Luhman, Thomas; Klamut, Carl

    1984-02-14

    An improved multiwire conductor of the type which is mechanically stabilized by a solder filler. A solder filled conductor is heated to a temperature sufficient to make the solder brittle, but below the melting point of the solder. While still hot, the conductor is flexed, causing the solder to separate from the wires comprising the conductor, thereby increasing the interwire resistance. In one embodiment the conductor may be heated to a temperature above the eutectic temperature of the solder so that a controlled amount of solder is removed. The subject invention is particularly suited for use with braided, ribbon-type, solder filled superconductors.

  4. Multiwire conductor having increased interwire resistance and good mechanical stability and method for making same

    DOEpatents

    Luhman, T.; Klamut, C.

    1982-03-15

    An improved multiwire conductor of the type which is mechanically stabilized by a solder filler. A solder filled conductor is heated to a temperature sufficient to make the solder brittle, but below the melting point of the solder. While still hot, the conductor is flexed, causing the solder to separate from the wires comprising the conductor, thereby increasing the interwire resistance. In one embodiment the conductor may be heated to a temperature above the eutectic temperature of the solder so that a controlled amount of solder is removed. The subject invention is particularly suited for use with braided, ribbon-type, solder filled superconductors.

  5. Multiwire conductor having greatly increased interwire resistance and method for making same

    DOEpatents

    Luhman, T.; Suenaga, M.

    1982-03-15

    An improved multiwire conductor of the type which is mechanically stabilized by a tin based solder filler is described. A solder filled conductor is heated to a temperature above its melting point for a period long enough to allow a substantial amount of copper to be dissolved from the wires comprising the conductor. The copper forms the brittle intermetallic compound Cu/sub 5/Sn/sub 6/ with tin in the solder. After cooling the conductor is flexed causing a random cracking of the solder, and thereby increasing the interwire resistance of the conductor. The subject invention is particularly adapted for use with braided, ribbon-type solder filled superconductors.

  6. Light-load resistance exercise increases muscle protein synthesis and hypertrophy signaling in elderly men.

    PubMed

    Agergaard, Jakob; Bülow, Jacob; Jensen, Jacob K; Reitelseder, Søren; Drummond, Micah J; Schjerling, Peter; Scheike, Thomas; Serena, Anja; Holm, Lars

    2017-04-01

    The present study investigated whether well-tolerated light-load resistance exercise (LL-RE) affects skeletal muscle fractional synthetic rate (FSR) and anabolic intracellular signaling as a way to counteract age-related loss of muscle mass. Untrained healthy elderly (>65-yr-old) men were subjected to 13 h of supine rest. After 2.5 h of rest, unilateral LL-RE, consisting of leg extensions (10 sets, 36 repetitions) at 16% of 1 repetition maximum (RM), was conducted. Subsequently, the subjects were randomized to oral intake of 4 g of whey protein per hour (PULSE, n = 10), 28 g of whey protein at 0 h and 12 g of whey protein at 7 h postexercise (BOLUS, n = 10), or 4 g of maltodextrin per hour (placebo, n = 10). Quadriceps muscle biopsies were taken at 0, 3, 7, and 10 h postexercise from the resting and the exercised leg of each subject. Myofibrillar FSR and activity of select targets from the mechanistic target of rapamycin complex 1-signaling cascade were analyzed from the biopsies. LL-RE increased myofibrillar FSR compared with the resting leg throughout the 10-h postexercise period. Phosphorylated (T308) AKT expression increased in the exercised leg immediately after exercise. This increase persisted in the placebo group only. Levels of phosphorylated (T37/46) eukaryotic translation initiation factor 4E-binding protein 1 increased throughout the postexercise period in the exercised leg in the placebo and BOLUS groups and peaked at 7 h. In all three groups, phosphorylated (T56) eukaryotic elongation factor 2 decreased in response to LL-RE. We conclude that resistance exercise at only 16% of 1 RM increased myofibrillar FSR, irrespective of nutrient type and feeding pattern, which indicates an anabolic effect of LL-RE in elderly individuals. This finding was supported by increased signaling for translation initiation and translation elongation in response to LL-RE.

  7. Test of the Starling resistor model in the human upper airway during sleep

    PubMed Central

    Genta, Pedro R.; Owens, Robert L.; Edwards, Bradley A.; Sands, Scott A.; Loring, Stephen H.; White, David P.; Jackson, Andrew C.; Pedersen, Ole F.; Butler, James P.

    2014-01-01

    The human pharyngeal airway during sleep is conventionally modeled as a Starling resistor. However, inspiratory flow often decreases with increasing effort (negative effort dependence, NED) rather than remaining fixed as predicted by the Starling resistor model. In this study, we tested a major prediction of the Starling resistor model—that the resistance of the airway upstream from the site of collapse remains fixed during flow limitation. During flow limitation in 24 patients with sleep apnea, resistance at several points along the pharyngeal airway was measured using a pressure catheter with multiple sensors. Resistance between the nose and the site of collapse (the upstream segment) was measured before and after the onset of flow limitation to determine whether the upstream dimensions remained fixed (as predicted by the Starling resistor model) or narrowed (a violation of the Starling resistor model). The upstream resistance from early to mid inspiration increased considerably during flow limitation (by 35 ± 41 cmH2O·liter−1·s−1, P < 0.001). However, there was a wide range of variability between patients, and the increase in upstream resistance was strongly correlated with the amount of NED (r = 0.75, P < 0.001). Therefore, patients with little NED exhibited little upstream narrowing (consistent with the Starling model), and patients with large NED exhibited large upstream narrowing (inconsistent with the Starling model). These findings support the idea that there is not a single model of pharyngeal collapse, but rather that different mechanisms may dominate in different patients. These differences could potentially be exploited for treatment selection. PMID:25324514

  8. Acoustic simulation of a patient's obstructed airway.

    PubMed

    van der Velden, W C P; van Zuijlen, A H; de Jong, A T; Lynch, C T; Hoeve, L J; Bijl, H

    2016-01-01

    This research focuses on the numerical simulation of stridor; a high pitched, abnormal noise, resulting from turbulent airflow and vibrating tissue through a partially obstructed airway. Characteristics of stridor noise are used by medical doctors as indication for location and size of the obstruction. The relation between type of stridor and the various diseases associated with airway obstruction is unclear; therefore, simply listening to stridor is an unreliable diagnostic tool. The overall aim of the study is to better understand the relationship between characteristics of stridor noise and localization and size of the obstruction. Acoustic analysis of stridor may then in future simplify the diagnostic process, and reduce the need for more invasive procedures such as laryngoscopy under general anesthesia. In this paper, the feasibility of a coupled flow, acoustic and structural model is investigated to predict the noise generated by the obstruction as well as the propagation of the noise through the airways, taking into account a one-way coupled fluid, structure, and acoustic interaction components. The flow and acoustic solver are validated on a diaphragm and a simplified airway model. A realistic airway model of a patient suffering from a subglottic stenosis, derived from a real computed tomography scan, is further analyzed. Near the mouth, the broadband noise levels at higher frequencies increased with approximately 15-20 dB comparing the stridorous model with the healthy model, indicating stridorous sound.

  9. Brain-derived neurotrophic factor in cigarette smoke-induced airway hyperreactivity.

    PubMed

    Sathish, Venkatachalem; Vanoosten, Sarah Kay; Miller, Brent S; Aravamudan, Bharathi; Thompson, Michael A; Pabelick, Christina M; Vassallo, Robert; Prakash, Y S

    2013-04-01

    Enhanced airway smooth muscle (ASM) contractility contributes to increased resistance to airflow in diseases such as bronchitis and asthma that occur in passive smokers exposed to secondhand smoke. Little information exists on the cellular mechanisms underlying such airway hyperreactivity. Sputum samples of patients with chronic sinusitis, bronchitis, and asthma show increased concentrations of growth factors called neurotrophins, including brain-derived growth factor (BDNF), but their physiological significance remains unknown. In human ASM, we tested the hypothesis that BDNF contributes to increased contractility with cigarette smoke exposure. The exposure of ASM to 1% or 2% cigarette smoke extract (CSE) for 24 hours increased intracellular calcium ([Ca(2+)](i)) responses to histamine, and further potentiated the enhancing effects of a range of BDNF concentrations on such histamine responses. CSE exposure increased the expression of the both high-affinity and low-affinity neurotrophin receptors tropomyosin-related kinase (Trk)-B and p75 pan-neurotrophin receptor, respectively. Quantitative ELISA showed that CSE increased BDNF secretion by human ASM cells. BDNF small interfering (si)RNA and/or the chelation of extracellular BDNF, using TrkB-fragment crystallizable, blunted the effects of CSE on [Ca(2+)](i) responses as well as the CSE enhancement of cell proliferation, whereas TrkB siRNA blunted the effects of CSE on ASM contractility. These data suggest that cigarette smoke is a potent inducer of BDNF and TrkB expression and signaling in ASM, which then contribute to cigarette smoke-induced airway hyperresponsiveness.

  10. Upper airway radiographs in infants with upper airway insufficiency.

    PubMed Central

    Tonkin, S L; Davis, S L; Gunn, T R

    1994-01-01

    Upper airway measurements in nine infants considered to be at risk of upper airway insufficiency, six of whom presented after an apnoeic episode, were compared with measurements taken in two age groups of healthy infants. Paired, inspiratory and expiratory, lateral upper airway radiographs were obtained while the infants were awake and breathing quietly. The radiographs of all nine infants demonstrated narrowing in the oropharyngeal portion of the airway during inspiration and in six infants there was ballooning of the upper airway during expiration. Seven of the nine infants subsequently experienced recurrent apnoeic episodes which required vigorous stimulation to restore breathing. Experience suggests that respiratory phase timed radiographs are a useful adjunct to the evaluation of infants who are suspected of having upper airway dysfunction. They provide information regarding both the dimensions and compliance of the upper airway as well as the site of any restriction. Images PMID:8048825

  11. Airway epithelium stimulates smooth muscle proliferation.

    PubMed

    Malavia, Nikita K; Raub, Christopher B; Mahon, Sari B; Brenner, Matthew; Panettieri, Reynold A; George, Steven C

    2009-09-01

    Communication between the airway epithelium and stroma is evident during embryogenesis, and both epithelial shedding and increased smooth muscle proliferation are features of airway remodeling. Hence, we hypothesized that after injury the airway epithelium could modulate airway smooth muscle proliferation. Fully differentiated primary normal human bronchial epithelial (NHBE) cells at an air-liquid interface were co-cultured with serum-deprived normal primary human airway smooth muscle cells (HASM) using commercially available Transwells. In some co-cultures, the NHBE were repeatedly (x4) scrape-injured. An in vivo model of tracheal injury consisted of gently denuding the tracheal epithelium (x3) of a rabbit over 5 days and then examining the trachea by histology 3 days after the last injury. Our results show that HASM cell number increases 2.5-fold in the presence of NHBE, and 4.3-fold in the presence of injured NHBE compared with HASM alone after 8 days of in vitro co-culture. In addition, IL-6, IL-8, monocyte chemotactic protein (MCP)-1 and, more markedly, matrix metalloproteinase (MMP)-9 concentration increased in co-culture correlating with enhanced HASM growth. Inhibiting MMP-9 release significantly attenuated the NHBE-dependent HASM proliferation in co-culture. In vivo, the injured rabbit trachea demonstrated proliferation in the smooth muscle (trachealis) region and significant MMP-9 staining, which was absent in the uninjured control. The airway epithelium modulates smooth muscle cell proliferation via a mechanism that involves secretion of soluble mediators including potential smooth muscle mitogens such as IL-6, IL-8, and MCP-1, but also through a novel MMP-9-dependent mechanism.

  12. Synthesis and evaluation of airway targeted PLGA nanoparticles for drug delivery in obstructive lung diseases.

    PubMed

    Vij, Neeraj

    2012-01-01

    Chronic airway inflammation is a hallmark of chronic obstructive airway diseases, including asthma, COPD (chronic obstructive pulmonary disease), and CF (cystic fibrosis). It is also a major challenge in delivery and therapeutic efficacy of nano-based delivery systems in these chronic airway conditions as nanoparticle (NP) need to bypass airways defense mechanisms as we recently discussed. NPs which are capable of overcoming airways defense mechanisms should allow targeted drug delivery to disease cells. Over the last decade there has been increasing interest in development of targeted NPs for cancer but relatively little effort on designing novel systems for treating chronic inflammatory and obstructive airway conditions. Here we describe methods for preparing drug loaded multifunctional nanoparticles for targeted delivery to specific cell types in airways. The formulations and methods for selective drug delivery, discussed here are currently under preclinical development in our laboratory for treating chronic airway conditions such as COPD, CF, and asthma.

  13. Boulders increase resistance to clear-cut logging but not subsequent recolonization rates of boreal bryophytes.

    PubMed

    Schmalholz, Martin; Hylander, Kristoffer

    2011-12-01

    The extent to which a plant assemblage might recolonize a disturbed system is in general related to the availability of propagule sources and sites with appropriate conditions for establishment. Both these factors might be sensitive to aspects of spatial heterogeneity. Microtopographic variation may enhance initial resistance by reducing the impact of the disturbance and facilitating establishment of incoming propagules by providing shaded "safe-sites". This study explores the influence of microtopographic heterogeneity (caused by variation in surface boulder cover) on the recolonization of closed-canopy forest floor bryophytes using a chronosequence of 75 spruce-dominated forests in south-central Sweden (2-163 years after clear-cutting). We found that high boulder cover did increase survival and subsequent persistence in young forests at both investigated scales (i.e. 1,000 and 100 m(2)), although this pattern became less evident on the smaller spatial scale. Species accumulation in boulder-poor subplots was not different when surrounded by boulder-rich compared with boulder-poor subplots suggesting short-distance recolonization from boulder-created refugia to be of little importance during recolonization. To conclude, it seems that boulders increase initial resistance to clear-cutting for this bryophyte guild, but that the subsequent recolonization process is more likely to depend on external propagule sources and factors affecting establishment such as the microclimate in the developing stand.

  14. N-Myc overexpression increases cisplatin resistance in neuroblastoma via deregulation of mitochondrial dynamics

    PubMed Central

    Casinelli, Gabriella; LaRosa, Jeff; Sharma, Manika; Cherok, Edward; Banerjee, Swati; Branca, Maria; Edmunds, Lia; Wang, Yudong; Sims-Lucas, Sunder; Churley, Luke; Kelly, Samantha; Sun, Ming; Stolz, Donna; Graves, J Anthony

    2016-01-01

    N-Myc is a global transcription factor that regulates the expression of genes involved in a number of essential cellular processes including: ribosome biogenesis, cell cycle and apoptosis. Upon deregulation, N-Myc can drive pathologic expression of many of these genes, which ultimately defines its oncogenic potential. Overexpression of N-Myc has been demonstrated to contribute to tumorigenesis, most notably for the pediatric tumor, neuroblastoma. Herein, we provide evidence that deregulated N-Myc alters the expression of proteins involved in mitochondrial dynamics. We found that N-Myc overexpression leads to increased fusion of the mitochondrial reticulum secondary to changes in protein expression due to aberrant transcriptional and post-translational regulation. We believe the structural changes in the mitochondrial network in response to N-Myc amplification in neuroblastoma contributes to two important aspects of tumor development and maintenance—bioenergetic alterations and apoptotic resistance. Specifically, we found that N-Myc overexpressing cells are resistant to programmed cell death in response to exposure to low doses of cisplatin, and demonstrated that this was dependent on increased mitochondrial fusion. We speculate that these changes in mitochondrial structure and function may contribute significantly to the aggressive clinical ph9enotype of N-Myc amplified neuroblastoma. PMID:28028439

  15. Sequence-Specific Targeting of Bacterial Resistance Genes Increases Antibiotic Efficacy

    PubMed Central

    Wong, Michael; Daly, Seth M.; Greenberg, David E.; Toprak, Erdal

    2016-01-01

    The lack of effective and well-tolerated therapies against antibiotic-resistant bacteria is a global public health problem leading to prolonged treatment and increased mortality. To improve the efficacy of existing antibiotic compounds, we introduce a new method for strategically inducing antibiotic hypersensitivity in pathogenic bacteria. Following the systematic verification that the AcrAB-TolC efflux system is one of the major determinants of the intrinsic antibiotic resistance levels in Escherichia coli, we have developed a short antisense oligomer designed to inhibit the expression of acrA and increase antibiotic susceptibility in E. coli. By employing this strategy, we can inhibit E. coli growth using 2- to 40-fold lower antibiotic doses, depending on the antibiotic compound utilized. The sensitizing effect of the antisense oligomer is highly specific to the targeted gene’s sequence, which is conserved in several bacterial genera, and the oligomer does not have any detectable toxicity against human cells. Finally, we demonstrate that antisense oligomers improve the efficacy of antibiotic combinations, allowing the combined use of even antagonistic antibiotic pairs that are typically not favored due to their reduced activities. PMID:27631336

  16. Titanium dioxide nanoparticles increase plasma glucose via reactive oxygen species-induced insulin resistance in mice.

    PubMed

    Hu, Hailong; Guo, Qian; Wang, Changlin; Ma, Xiao; He, Hongjuan; Oh, Yuri; Feng, Yujie; Wu, Qiong; Gu, Ning

    2015-10-01

    There have been few reports about the possible toxic effects of titanium dioxide (TiO2 ) nanoparticles on the endocrine system. We explored the endocrine effects of oral administration to mice of anatase TiO2 nanoparticles (0, 64 and 320 mg kg(-1) body weight per day to control, low-dose and high-dose groups, respectively, 7 days per week for 14 weeks). TiO2 nanoparticles were characterized by scanning and transmission electron microscopy (TEM) and dynamic light scattering (DLS), and their physiological distribution was investigated by inductively coupled plasma. Biochemical analyzes included plasma glucose, insulin, heart blood triglycerides (TG), free fatty acid (FFA), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 and reactive oxygen species (ROS)-related markers (total SOD, GSH and MDA). Phosphorylation of IRS1, Akt, JNK1, and p38 MAPK were analyzed by western blotting. Increased titanium levels were found in the liver, spleen, small intestine, kidney and pancreas. Biochemical analyzes showed that plasma glucose significantly increased whereas there was no difference in plasma insulin secretion. Increased ROS levels were found in serum and the liver, as evidenced by reduced total SOD activity and GSH level and increased MDA content. Western blotting showed that oral administration of TiO2 nanoparticles induced insulin resistance (IR) in mouse liver, shown by increased phosphorylation of IRS1 (Ser307) and reduced phosphorylation of Akt (Ser473). The pathway by which TiO2 nanoparticles increase ROS-induced IR were included in the inflammatory response and phosphokinase, as shown by increased serum levels of TNF-α and IL-6 and increased phosphorylation of JNK1 and p38 MAPK in liver. These results show that oral administration of TiO2 nanoparticles increases ROS, resulting in IR and increasing plasma glucose in mice.

  17. Laser applications in pediatric airway surgery

    NASA Astrophysics Data System (ADS)

    Karamzadeh, Amir M.; Ahuja, Gurpreet S.; Nguyen, John D.; Crumley, Roger

    2003-06-01

    The smaller anatomy and limited access to instrumentation pose a challenge to the pediatric airway surgeon. The enhanced precision and ability to photocoagulate tissue while operating with the laser enhances the surgeon"s ability to successfully treat unique pediatric conditions such subglottic hemangiomas, congenital cysts, respiratory papillomatosis, and laryngeal or tracheal stenosis. Due to its shallow tissue penetration and thermal effect, the carbon dioxide (CO2) laser is generally considered the laser of choice for pediatric airway applications. The potential for increased scarring and damage to underlying tissue caused by the greater penetration depth and thermal effect of the Nd:YAG and KTP lasers preclude their use in this population. In this review, we will describe the specific advantages of using lasers in airway surgery, the current technology and where the current technology is deficient.

  18. Acute exercise improves endothelial function despite increasing vascular resistance during stress in smokers and nonsmokers.

    PubMed

    Rooks, Cherie R; McCully, Kevin K; Dishman, Rod K

    2011-09-01

    The present study examined the effect of acute exercise on flow mediated dilation (FMD) and reactivity to neurovascular challenges among female smokers and nonsmokers. FMD was determined by arterial diameter, velocity, and blood flow measured by Doppler ultrasonography after forearm occlusion. Those measures and blood pressure and heart rate were also assessed in response to forehead cold and the Stroop Color-Word Conflict Test (CWT) before and after 30 min of rest or an acute bout of cycling exercise (∼50% VO₂ peak). Baseline FMD and stress responses were not different between smokers and nonsmokers. Compared to passive rest, exercise increased FMD and decreased arterial velocity and blood flow responses during the Stroop CWT and forehead cold in both groups. Overall, acute exercise improved endothelial function among smokers and nonsmokers despite increasing vascular resistance and reducing limb blood flow during neurovascular stress.

  19. Noninvasive detection of airway constriction in awake guinea pigs

    SciTech Connect

    Silbaugh, S.A.; Mauderly, J.L.

    1984-01-01

    Tidal volume measured by the barometric method is very sensitive to increases in compression and expansion of alveolar gas, such as would be expected to occur during airway narrowing or closure. By comparing a barometric method tidal volume signal (VT') with a reference tidal volume (VT) obtained with a head-out pressure plethysmograph, a simple index related to gas compressibility effects was calculated (VT/VT'). Changes in this index were compared with decreases in dynamic compliance (Cdyn) during histamine aerosol challenge of 15 Charles River Hartley guinea pigs. Decreases in VT/VT' occurred during all aerosol challenges and were correlated with decreases in Cdyn. Decreases in VT/VT' were most marked at Cdyn values of less than 50% of base line. At Cdyn of less than 15% of base line, VT' was 3.1-4.8 times the VT reference signal. No increase in total pulmonary resistance was noted, and Cdyn and VT/VT' returned to base line after histamine exposure was stopped. The authors conclude that gas compressibility effects become substantial during histamine-induced airway constriction in the guinea pig and that the VT/VT' ratio appears to provide a simple noninvasive method of detecting these changes.

  20. Incorporation of adenovirus in calcium phosphate precipitates enhances gene transfer to airway epithelia in vitro and in vivo.

    PubMed Central

    Fasbender, A; Lee, J H; Walters, R W; Moninger, T O; Zabner, J; Welsh, M J

    1998-01-01

    Adenovirus (Ad)-mediated gene transfer to airway epithelia is inefficient because the apical membrane lacks the receptor activity to bind adenovirus fiber protein. Calcium phosphate (CaPi) precipitates have been used to deliver plasmid DNA to cultured cell lines. However, such precipitates are not effective in many primary cultures or in vivo. Here we show that incorporating recombinant adenovirus into a CaPi coprecipitate markedly enhances transgene expression in cells that are resistant to adenovirus infection. Enhancement requires that the virus be contained in the precipitate and viral proteins are required to increase expression. Ad: CaPi coprecipitates increase gene transfer by increasing fiber-independent binding of virus to cells. With differentiated cystic fibrosis (CF) airway epithelia in vitro, a 20-min application of Ad:CaPi coprecipitates that encode CF transmembrane conductance regulator produced as much CF transmembrane conductance regulator Cl- current as a 24-h application of adenovirus alone. We found that Ad:CaPi coprecipitates also increased transgene expression in mouse lung in vivo; importantly, expression was particularly prominent in airway epithelia. These results suggest a new mechanism for gene transfer that may be applicable to a number of different gene transfer applications and could be of value in gene transfer to CF airway epithelia in vivo. PMID:9649572

  1. Guinea pig lung resistance shows circadian rhythmicity not influenced by ozone.

    PubMed

    Sommer, B; Montaño, L M; Chávez, J; Gustin, P; Vargas, M H

    1998-09-01

    Increased circadian variability of airway caliber is a key feature of asthmatic patients, but it has not been addressed in animal models of asthma. Furthermore, animal studies on circadian rhythmicity of airway resistance are very scanty. We used a plethysmographic method for unrestrained guinea pigs to monitor a lung resistance index (iRL) during 24 h. We found circadian variability of iRL values, which were fitted by a sinusoidal curve. Acrophase and bathyphase, characterizing the timing of narrowest and widest airway caliber, respectively, were found at 02:03, and 15:34 h. iRL values at these time-points were statistically different (P < 10(-5)). Moreover, average resistance during the dark period was significantly higher (P < 0.0001) than during the light period. Immediately after an acute ozone exposure (3 ppm for 1 h) an increase in iRL was demonstrated (P < 0.01), which lasted for 2 h, and tended to remain high for the next hour. After guinea pigs recovered from this obstruction, the circadian rhythm and variability of airway caliber were unaffected. Our results show that a circadian rhythm of iRL takes place in guinea pigs, greatly resembling what occurs in humans, and that ozone exposure causes a transient airway obstruction, but fails to reproduce the increased variability of airway caliber observed in asthmatic patients.

  2. Supraglottic airway devices in children

    PubMed Central

    Ramesh, S; Jayanthi, R

    2011-01-01

    Modern anaesthesia practice in children was made possible by the invention of the endotracheal tube (ET), which made lengthy and complex surgical procedures feasible without the disastrous complications of airway obstruction, aspiration of gastric contents or asphyxia. For decades, endotracheal intubation or bag-and-mask ventilation were the mainstays of airway management. In 1983, this changed with the invention of the laryngeal mask airway (LMA), the first supraglottic airway device that blended features of the facemask with those of the ET, providing ease of placement and hands-free maintenance along with a relatively secure airway. The invention and development of the LMA by Dr. Archie Brain has had a significant impact on the practice of anaesthesia, management of the difficult airway and cardiopulmonary resuscitation in children and neonates. This review article will be a brief about the clinical applications of supraglottic airways in children. PMID:22174464

  3. Exposure to dairy manure leads to greater antibiotic resistance and increased mass-specific respiration in soil microbial communities.

    PubMed

    Wepking, Carl; Avera, Bethany; Badgley, Brian; Barrett, John E; Franklin, Josh; Knowlton, Katharine F; Ray, Partha P; Smitherman, Crystal; Strickland, Michael S

    2017-03-29

    Intensifying livestock production to meet the demands of a growing global population coincides with increases in both the administration of veterinary antibiotics and manure inputs to soils. These trends have the potential to increase antibiotic resistance in soil microbial communities. The effect of maintaining increased antibiotic resistance on soil microbial communities and the ecosystem processes they regulate is unknown. We compare soil microbial communities from paired reference and dairy manure-exposed sites across the USA. Given that manure exposure has been shown to elicit increased antibiotic resistance in soil microbial communities, we expect that manure-exposed sites will exhibit (i) compositionally different soil microbial communities, with shifts toward taxa known to exhibit resistance; (ii) greater abundance of antibiotic resistance genes; and (iii) corresponding maintenance of antibiotic resistance would lead to decreased microbial efficiency. We found that bacterial and fungal communities differed between reference and manure-exposed sites. Additionally, the β-lactam resistance gene ampC was 5.2-fold greater under manure exposure, potentially due to the use of cephalosporin antibiotics in dairy herds. Finally, ampC abundance was positively correlated with indicators of microbial stress, and microbial mass-specific respiration, which increased 2.1-fold under manure exposure. These findings demonstrate that the maintenance of antibiotic resistance associated with manure inputs alters soil microbial communities and ecosystem function.

  4. Treatment of Arabidopsis thaliana seeds with an HSP90 inhibitor increases plant resistance

    NASA Astrophysics Data System (ADS)

    Kozeko, Liudmyla

    2016-07-01

    Resistance of plants to unfavourable conditions is an important feature to use them as an autotrophic link of Life Support Systems in space exploration missions. It significantly depends on basic and stress-induced levels of heat shock proteins (HSP) in cells. It is known that HSP90 can bind and maintain heat shock transcription factors (HSF) as a monomer that lacks DNA binding activity and thereby regulate HSP expression. Modulation of activity of the HSP synthesis and resistance by HSP90 in plants is not well investigated. The objective of this study was to determine how treatment of seeds with an HSP90 inhibitor affects environmental responsiveness in Arabidopsis thaliana. Seed treatment with geldanamycin (GDA) was used to reduce HSP90 function. The affect of space flight stressors was simulated by gamma-irradiation and thermal upshift. Two series of experiments were carried out: 1) exposure of dry seeds to gamma-irradiation (1 kGy, ^{60}Co); 2) heat shock of seedlings. It was shown that GDA treatment of seeds stimulated the seedling growth after seed irradiation. It also increased both the basic thermotolerance (45°C for 45 min) and induced thermotolerance (45°C for 1,5-2,5 h after pretreatment at 37°C for 2 h) in seedlings. In addition, seed treatment with GDA had a prolonged effect on the HSP70 production in seedlings under normal and stressful conditions. It shows that the stimulatory effects of GDA may be caused by induction of HSP70 synthesis. The obtained data demonstrate that pre-treatment of seeds with GDA before planting allows inducing the stress resistance at least at early growth stages of plants.

  5. Eccentric resistance training increases and retains maximal strength, muscle endurance, and hypertrophy in trained men.

    PubMed

    Coratella, Giuseppe; Schena, Federico

    2016-11-01

    The aim of the present study was to evaluate the effects of different resistance training protocols on muscle strength, endurance, and hypertrophy after training and detraining. Thirty-four resistance-trained males were randomized in concentric-only (CONC), eccentric-only (ECC), traditional concentric-eccentric (TRAD) bench press resistance training or control group. The training volume was equalized among the intervention groups. Bench press of 1-repetition maximum (1RM)/body mass, maximum number of repetitions (MNR), and chest circumference were evaluated at the baseline, after 6 weeks of training, and after 6 weeks of detraining. All intervention groups reported significant 1RM/body mass increases after training (CONC baseline: 1.04 ± 0.06, post-training: 1.12 ± 0.08, p < 0.05; ECC baseline: 1.08 ± 0.04, post-training: 1.15 ± 0.05, p < 0.05; TRAD baseline: 1.06 ± 0.08, post-training: 1.11 ± 0.10, p < 0.05). After detraining, only ECC retained 1RM/body mass above the baseline (1.17 ± 0.07, p < 0.05), while CONC and TRAD returned to baseline values. Only ECC improved and retained MNR (baseline: 22 ± 3; post-training: 25 ± 3, and post-detraining: 25 ± 4, p < 0.05 compared with baseline) and chest circumference (baseline: 98.3 ± 2.4 cm, post-training: 101.7 ± 2.2 cm and post-detraining: 100.7 ± 2.3 cm. p < 0.05 compared with baseline), while no significant changes occurred in both CONC and TRAD. The incorporation of eccentric training can be recommended for counteracting the negative effects of detraining or forced physical inactivity.

  6. Increasing antimicrobial resistance in clinical isolates of Staphylococcus intermedius group bacteria and emergence of MRSP in the UK.

    PubMed

    Beever, L; Bond, R; Graham, P A; Jackson, B; Lloyd, D H; Loeffler, A

    2015-02-14

    Frequencies of antimicrobial resistance were determined amongst 14,555 clinical Staphylococcus intermedius group (SIG) isolates from UK dogs and cats to estimate resistance trends and quantify the occurrence of meticillin-resistant Staphylococcus pseudintermedius (MRSP). Reports from two diagnostic laboratories (13,313 general submissions, 1242 referral centre only submissions) were analysed retrospectively (2003/2006-2012). MRSP were defined by phenotypic resistance to meticillin and concurrent broad β-lactam resistance; a subset was confirmed genetically (SIG-specific nuc and mecA). Trends were analysed by Cochran-Armitage test. Resistance remained below 10 per cent for cefalexin, amoxicillin-clavulanic acid and the fluoroquinolones. Increasing resistance trends were seen in both laboratories for ampicillin/amoxicillin (both P<0.001), cefovecin (both P<0.046) and enrofloxacin (both P<0.02). Resistance to cefalexin increased over time in referral hospital isolates (P<0.001) to clindamycin (P=0.01) and trimethoprim-sulfamethoxazole (P=0.001) amongst general laboratory submissions. Overall, 106 MRSP were isolated (0.7 per cent of submissions) including 32 (2.6 per cent of submissions, all genetically confirmed) from the referral centre population (inter-laboratory difference P<0.001). Against a background of widely susceptible SIG isolates, a new trend of increasing resistance to important antimicrobials was identified overtime and the emergence of MRSP from UK clinical cases was confirmed. Attention to responsible use of antibacterial therapy in small animal practice is urgently needed.

  7. Enzymatic quorum quenching increases antibiotic susceptibility of multidrug resistant Pseudomonas aeruginosa

    PubMed Central

    Kiran, S; Sharma, P; Harjai, K; Capalash, N

    2011-01-01

    Background and Objectives There is increasing emergence of multidrug resistant Pseudomonas aeruginosa (MDRPA) strains and drug resistance is positively-correlated with biofilm-forming ability. Since about 10% of P. aeruginosa genome is controlled by quorum sensing (QS), alteration in its antibiotic susceptibility by targeting QS was the focus of the present study. Materials and Methods One day biofilms of PAO1 and three urinary tract infection MDRPA isolates (PA2, PA8 and PA18) were formed in 96-well microtiter plate. Biofilms were exposed to concentration gradient of ciprofloxacin and gentamicin to obtain Minimum Biofilm Eradication Concentration (MBEC) by direct enumeration method. Susceptibility of 24 h biofilms was evaluated by treatment with ciprofloxacin and gentamicin per se and in combination with lactonase. The effect was also examined on 72 h biofilms by Scanning Electron Microscopy. Results Lactonase treatment did not have any effect on growth of the selected strains but 73.42, 69.1, 77.34 and 72.5% reduction of biofilm was observed after lactonase (1 unit) treatment, respectively. Antibiotics in combination with lactonase (0.3 units) resulted in an increased susceptibility of the biofilm forms by>3.3, 4, 5 and 1.5 folds of MBEC, for ciprofloxacin and>6.67, 12.5, 6 and>2.5 folds, for gentamicin respectively, which could be due to the disruption of biofilm by lactonase treatment as shown by scanning electron microscopy. Also there was significant reduction (p<0.001) in virulence factor production by the strains. Conclusion Lactonase treatment increased antibiotic susceptibility of the biofilms of MDRPA isolates underscoring the potential of quorum quenching in antimicrobial therapeutics. PMID:22347576

  8. Spirulina elicits the activation of innate immunity and increases resistance against Vibrio alginolyticus in shrimp.

    PubMed

    Chen, Yu-Yuan; Chen, Jiann-Chu; Tayag, Carina Miranda; Li, Hui-Fang; Putra, Dedi Fazriansyah; Kuo, Yi-Hsuan; Bai, Jia-Chin; Chang, Yu-Hsuan

    2016-08-01

    The effect of Spirulina dried powder (SDP) on the immune response of white shrimp Litopenaeus vannamei was studied in vitro and in vivo. Incubating shrimp haemocytes in 0.5 mg ml(-1) SDP caused the degranulation of haemocytes and a reduction in the percentage of large cells within 30 min. Shrimp haemocytes incubated in 1 mg ml(-1) SDP significantly increased their phenoloxidase (PO) activity, serine proteinase activity, and respiratory burst activity (RB, release of superoxide anion). A recombinant protein of lipopolysaccharide and β-1,3-glucan binding protein (LGBP) of the white shrimp was produced, named rLvLGBP, and examined for its binding with SDP. An ELISA binding assay showed that rLvLGBP binds to SDP with a dissociation constant of 0.0507 μM. In another experiment, shrimp fed diets containing SDP at 0 (control), 30, and 60 g kg(-1) after four weeks were examined for LGBP transcript level and lysozyme activity, as well as phagocytic activity, clearance efficiency, and resistance to Vibrio alginolyticus. These parameters were significantly higher in shrimp receiving diets containing SDP at 60 g kg(-1) or 30 g kg(-1) than in controls. In conclusion, shrimp haemocytes receiving SDP provoked the activation of innate immunity as evidenced by the recognition and binding of LGBP, degranulation of haemocytes, reduction in the percentage of large cells, increases in PO activity, serine proteinase activity, superoxide anion levels, and up-regulated LGBP transcript levels. Shrimp receiving diets containing SDP had increased lysozyme activity and resistance against V. alginolyticus infection. This study showed the mechanism underlying the immunostimulatory action of Spirulina and its immune response in shrimp.

  9. Suppression in growth hormone during overeating ameliorates the increase in insulin resistance and cardiovascular disease risk

    PubMed Central

    Cornford, Andrea S.; Barkan, Ariel L.; Hinko, Alexander

    2012-01-01

    Previously, we reported that overeating for only a few days markedly suppressed the secretion of growth hormone (GH). The purpose of the present study was to determine the role of this reduction in GH concentration on key metabolic adaptations that occur during 2 wk of overeating. Nine nonobese, healthy adults were admitted to the hospital for 2 wk, during which time they ate ∼4,000 kcal/day (70 kcal·kg fat-free mass−1·day−1; 50% carbohydrate, 35% fat, and 15% protein), and their plasma GH concentration was allowed to decline naturally (control). An additional eight subjects underwent the same overeating intervention and received exogenous GH treatment (GHT) administered in four daily injections to mimic physiological GH secretion throughout the 2-wk overeating period. We measured plasma insulin and glucose concentrations in the fasting and postprandial state as well as fasting lipolytic rate, proteolytic rate, and fractional synthetic rate (FSR) using stable-isotope tracer methods. GHT prevented the fall in plasma GH concentration, maintaining plasma GH concentration at baseline levels (1.2 ± 0.2 ng/ml), which increased fasting and postprandial assessments of insulin resistance (P < 0.05) and increased fasting lipidemia (all P < 0.05 vs. control). In addition, preventing the suppression in GH with overeating also blunted the increase in systemic proteolysis (P < 0.05 GHT vs. control). However, GHT did not alter lipolysis or FSR in response to overeating. In conclusion, our main findings suggest that the suppression in GH secretion that naturally occurs during the early stages of overeating may help attenuate the insulin resistance and hyperlipidemia that typically accompany overeating. PMID:23011065

  10. Rhinovirus Disrupts the Barrier Function of Polarized Airway Epithelial Cells

    PubMed Central

    Sajjan, Umadevi; Wang, Qiong; Zhao, Ying; Gruenert, Dieter C.; Hershenson, Marc B.

    2008-01-01

    Rationale: Secondary bacterial infection following rhinovirus (RV) infection has been recognized in chronic obstructive pulmonary disease. Objectives: We sought to understand mechanisms by which RV infection facilitates secondary bacterial infection. Methods: Primary human airway epithelial cells grown at air–liquid interface and human bronchial epithelial (16HBE14o-) cells grown as polarized monolayers were infected apically with RV. Transmigration of bacteria (nontypeable Haemophilus influenzae and others) was assessed by colony counting and transmission electron microscopy. Transepithelial resistance (RT) was measured by using a voltmeter. The distribution of zona occludins (ZO)-1 was determined by immunohistochemistry and immunoblotting. Measurements and Main Results: Epithelial cells infected with RV showed 2-log more bound bacteria than sham-infected cultures, and bacteria were recovered from the basolateral media of RV- but not sham-infected cells. Infection of polarized airway epithelial cell cultures with RV for 24 hours caused a significant decrease in RT without causing cell death or apoptosis. Ultraviolet-treated RV did not decrease RT, suggesting a requirement for viral replication. Reduced RT was associated with increased paracellular permeability, as determined by flux of fluorescein isothiocyanate (FITC)-inulin. Neutralizing antibodies to tumor necrosis factor (TNF)-α, IFN-γ and IL-1β reversed corresponding cytokine-induced reductions in RT but not that induced by RV, indicating that the RV effect is independent of these proinflammatory cytokines. Confocal microscopy and immunoblotting revealed the loss of ZO-1 from tight junction complexes in RV-infected cells. Intranasal inoculation of mice with RV1B also caused the loss of ZO-1 from the bronchial epithelium tight junctions in vivo. Conclusions: RV facilitates binding, translocation, and persistence of bacteria by disrupting airway epithelial barrier function. PMID:18787220

  11. COLCHICINE DECREASES AIRWAY HYPERACTIVITY AFTER PHOSGENE EXPOSURE

    EPA Science Inventory

    Phosgene (COCl(2)) exposure affects an influx of inflammatory cells into the lung, which can be reduced in an animal model by pretreatment with colchicine. Inflammation in the respiratory tract can be associated with an increase in airway hyperreactivity. We tested the hypotheses...

  12. FSTL1 PROMOTES ASTHMATIC AIRWAY REMODELING BY INDUCING ONCOSTATIN M

    PubMed Central

    Miller, Marina; Beppu, Andrew; Rosenthal, Peter; Pham, Alexa; Das, Sudipta; Karta, Maya; Song, Dae Jin; Vuong, Christine; Doherty, Taylor; Croft, Michael; Zuraw, Bruce; Zhang, Xu; Gao, Xiang; Aceves, Seema; Chouiali, Fazila; Hamid, Qutayba; Broide, David H.

    2016-01-01

    Chronic asthma is associated with airway remodeling and decline in lung function. Here we show that follistatin like 1 (Fstl1), a mediator not previously associated with asthma is highly expressed by macrophages in the lungs of severe human asthmatics. Chronic allergen challenged Lys-Cretg/Fstl1Δ/Δ mice in whom Fstl1 is inactivated in macrophages/myeloid cells had significantly reduced airway remodeling and reduced levels of oncostatin M (OSM) a cytokine previously not known to be regulated by Fstl1. The importance of the Fstl1 induction of OSM to airway remodeling was demonstrated in murine studies in which administration of Fstl1 induced airway remodeling and increased OSM, while administration of an anti-OSM antibody blocked the effect of Fstl1 on inducing airway remodeling, eosinophilic airway inflammation, and airway hyperresponsiveness all cardinal features of asthma. Overall, these studies demonstrate that the Fstl1/oncostatin M pathway may be a novel pathway to inhibit airway remodeling in severe human asthma. PMID:26355153

  13. High-frequency gamblers show increased resistance to extinction following partial reinforcement.

    PubMed

    Horsley, Rachel R; Osborne, Matthew; Norman, Christine; Wells, Timothy

    2012-04-15

    Behaviours that have been rewarded intermittently persist for longer during periods of non-reward than behaviours that have been rewarded continuously. This classic phenomenon is known as the partial reinforcement extinction effect. For decades it has been generally understood that this phenomenon is fundamental to the persistence of gambling in the absence of winning. One obvious, yet untested hypothesis arising from this is that persistent (here, high-frequency) gamblers might be more sensitive to partial reinforcement contingencies. Therefore, our aim was to test the hypothesis that compared to low-frequency gamblers, high-frequency gamblers would show greater resistance to extinction following partial reinforcement in a computer based experiment. Participants were 19 high-frequency gamblers and 21 low-frequency gamblers, all healthy non-smokers aged between 18 and 52. Following partial or continuous reinforcement, persistence of responding in extinction was measured as the number of times a target response was made. After partial reinforcement, high-frequency gamblers made the target response a greater number of times in extinction (compared to low-frequency gamblers). Moreover, the partial reinforcement extinction effect was larger in high-frequency gamblers than in low-frequency gamblers. It remains to be seen whether increased sensitivity to partial reinforcement is a cause or effect of persistent gambling. Nevertheless, the present study represents an important first step in investigating the role of simple partial reinforcement contingencies in determining resistance to extinction in gamblers, the importance of which, whilst hitherto recognised, has never been demonstrated experimentally.

  14. The Metabolic Syndrome and Inflammation: 
Role of Insulin Resistance and Increased Adiposity

    PubMed Central

    Farooq, Wajiha; Farwa, Umme; Khan, Faisal Rashid

    2015-01-01

    Objectives We sought to determine the role of obesity and insulin resistance (IR) in the pathogenesis of inflammation in metabolic syndrome (MetS). Methods Our study included 100 patients with MetS and 100 age and gender matched control patients who attended a tertiary care laboratory in Rawalpindi, Pakistan. Anthropometric data was obtained including height and weight to calculate body mass index. A record of patient’s blood pressure (BP), waist circumference (WC) and hip circumference (HC) was made. Biochemical analysis included measurements of fasting glucose, triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), insulin, and high-sensitivity C reactive protein (hsCRP). IR was determined by the homeostasis mode assessment insulin resistance (HOMA-IR) method. Results The levels of hs-CRP were found to be elevated in all patients with MetS where it correlated significantly with all its components including measures of obesity, fasting insulin and glucose levels, IR, TG and HDL-c. However, on linear regression analysis only WC, fasting insulin, and HOMA-IR remained significantly correlated with hs-CRP. Conclusion MetS is a condition characterized by chronic low-grade inflammation, which arises because of increased abdominal adiposity and IR. Large multicenter studies are needed to gain insight into its pathogenesis and derive treatment strategies. PMID:25960834

  15. Insulin Resistance Increases the Risk of Contrast-Induced Nephropathy in Patients Undergoing Elective Coronary Intervention.

    PubMed

    Li, Yueping; Liu, Yuyang; Shi, Dongmei; Yang, Lixia; Liang, Jing; Zhou, Yujie

    2016-02-01

    We assessed the influence of insulin resistance (IR) on the development of contrast-induced nephropathy (CIN) in patients (n = 719) undergoing elective percutaneous coronary intervention (PCI). Patients were divided into diabetes mellitus (DM = 242), nondiabetic IR (IR = 120), and nondiabetic insulin sensitivity (IS = 357) groups according to medical history and homeostasis model assessment insulin resistance index. Serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) were measured before and 72 hours after PCI. There were no differences in SCr and eGFR among the groups before PCI; SCr increased and eGFR decreased significantly in the DM and IR groups post-PCI (P < .001). The incidence of CIN in the IR group was as high as in the DM group and were both significantly higher than in the IS group (6.7% vs 8.7% vs 2.2%, P < .05). Multivariate logistic regression analysis showed DM (odds ratio [OR] = 1.19, 95%CI = 1.08-1.510, P < .001), HOMA-IR (OR = 1.39, 95%CI = 1.23-1.58, P < 0.001), and eGFR (OR = 0.88, 95%CI = 0.84-0.92, P < .001) were independent risk factors in predicting CIN. Screening IR patients and taking appropriate prophylactic strategy before PCI may reduce the incidence of CIN.

  16. Large increase in fracture resistance of stishovite with crack extension less than one micrometer

    PubMed Central

    Yoshida, Kimiko; Wakai, Fumihiro; Nishiyama, Norimasa; Sekine, Risako; Shinoda, Yutaka; Akatsu, Takashi; Nagoshi, Takashi; Sone, Masato

    2015-01-01

    The development of strong, tough, and damage-tolerant ceramics requires nano/microstructure design to utilize toughening mechanisms operating at different length scales. The toughening mechanisms so far known are effective in micro-scale, then, they require the crack extension of more than a few micrometers to increase the fracture resistance. Here, we developed a micro-mechanical test method using micro-cantilever beam specimens to determine the very early part of resistance-curve of nanocrystalline SiO2 stishovite, which exhibited fracture-induced amorphization. We revealed that this novel toughening mechanism was effective even at length scale of nanometer due to narrow transformation zone width of a few tens of nanometers and large dilatational strain (from 60 to 95%) associated with the transition of crystal to amorphous state. This testing method will be a powerful tool to search for toughening mechanisms that may operate at nanoscale for attaining both reliability and strength of structural materials. PMID:26051871

  17. Nuclear hormone receptor DHR96 mediates the resistance to xenobiotics but not the increased lifespan of insulin-mutant Drosophila.

    PubMed

    Afschar, Sonita; Toivonen, Janne M; Hoffmann, Julia Marianne; Tain, Luke Stephen; Wieser, Daniela; Finlayson, Andrew John; Driege, Yasmine; Alic, Nazif; Emran, Sahar; Stinn, Julia; Froehlich, Jenny; Piper, Matthew D; Partridge, Linda

    2016-02-02

    Lifespan of laboratory animals can be increased by genetic, pharmacological, and dietary interventions. Increased expression of genes involved in xenobiotic metabolism, together with resistance to xenobiotics, are frequent correlates of lifespan extension in the nematode worm Caenorhabditis elegans, the fruit fly Drosophila, and mice. The Green Theory of Aging suggests that this association is causal, with the ability of cells to rid themselves of lipophilic toxins limiting normal lifespan. To test this idea, we experimentally increased resistance of Drosophila to the xenobiotic dichlordiphenyltrichlorethan (DDT), by artificial selection or by transgenic expression of a gene encoding a cytochrome P450. Although both interventions increased DDT resistance, neither increased lifespan. Furthermore, dietary restriction increased lifespan without increasing xenobiotic resistance, confirming that the two traits can be uncoupled. Reduced activity of the insulin/Igf signaling (IIS) pathway increases resistance to xenobiotics and extends lifespan in Drosophila, and can also increase longevity in C. elegans, mice, and possibly humans. We identified a nuclear hormone receptor, DHR96, as an essential mediator of the increased xenobiotic resistance of IIS mutant flies. However, the IIS mutants remained long-lived in the absence of DHR96 and the xenobiotic resistance that it conferred. Thus, in Drosophila IIS mutants, increased xenobiotic resistance and enhanced longevity are not causally connected. The frequent co-occurrence of the two traits may instead have evolved because, in nature, lowered IIS can signal the presence of pathogens. It will be important to determine whether enhanced xenobiotic metabolism is also a correlated, rather than a causal, trait in long-lived mice.

  18. Nuclear hormone receptor DHR96 mediates the resistance to xenobiotics but not the increased lifespan of insulin-mutant Drosophila

    PubMed Central

    Afschar, Sonita; Toivonen, Janne M.; Tain, Luke Stephen; Wieser, Daniela; Finlayson, Andrew John; Driege, Yasmine; Alic, Nazif; Emran, Sahar; Stinn, Julia; Froehlich, Jenny; Piper, Matthew D.; Partridge, Linda

    2016-01-01

    Lifespan of laboratory animals can be increased by genetic, pharmacological, and dietary interventions. Increased expression of genes involved in xenobiotic metabolism, together with resistance to xenobiotics, are frequent correlates of lifespan extension in the nematode worm Caenorhabditis elegans, the fruit fly Drosophila, and mice. The Green Theory of Aging suggests that this association is causal, with the ability of cells to rid themselves of lipophilic toxins limiting normal lifespan. To test this idea, we experimentally increased resistance of Drosophila to the xenobiotic dichlordiphenyltrichlorethan (DDT), by artificial selection or by transgenic expression of a gene encoding a cytochrome P450. Although both interventions increased DDT resistance, neither increased lifespan. Furthermore, dietary restriction increased lifespan without increasing xenobiotic resistance, confirming that the two traits can be uncoupled. Reduced activity of the insulin/Igf signaling (IIS) pathway increases resistance to xenobiotics and extends lifespan in Drosophila, and can also increase longevity in C. elegans, mice, and possibly humans. We identified a nuclear hormone receptor, DHR96, as an essential mediator of the increased xenobiotic resistance of IIS mutant flies. However, the IIS mutants remained long-lived in the absence of DHR96 and the xenobiotic resistance that it conferred. Thus, in Drosophila IIS mutants, increased xenobiotic resistance and enhanced longevity are not causally connected. The frequent co-occurrence of the two traits may instead have evolved because, in nature, lowered IIS can signal the presence of pathogens. It will be important to determine whether enhanced xenobiotic metabolism is also a correlated, rather than a causal, trait in long-lived mice. PMID:26787908

  19. When Parasites Are Good for Health: Cestode Parasitism Increases Resistance to Arsenic in Brine Shrimps

    PubMed Central

    Martínez-Haro, Mónica; Taggart, Mark A.; Lenormand, Thomas; Green, Andy J.

    2016-01-01

    Parasites and pollutants can both affect any living organism, and their interactions can be very important. To date, repeated studies have found that parasites and heavy metals or metalloids both have important negative effects on the health of animals, often in a synergistic manner. Here, we show for the first time that parasites can increase host resistance to metalloid arsenic, focusing on a clonal population of brine shrimp from the contaminated Odiel and Tinto estuary in SW Spain. We studied the effect of cestodes on the response of Artemia to arsenic (acute toxicity tests, 24h LC50) and found that infection consistently reduced mortality across a range of arsenic concentrations. An increase from 25°C to 29°C, simulating the change in mean temperature expected under climate change, increased arsenic toxicity, but the benefits of infection persisted. Infected individuals showed higher levels of catalase and glutathione reductase activity, antioxidant enzymes with a very important role in the protection against oxidative stress. Levels of TBARS were unaffected by parasites, suggesting that infection is not associated with oxidative damage. Moreover, infected Artemia had a higher number of carotenoid-rich lipid droplets which may also protect the host through the “survival of the fattest” principle and the antioxidant potential of carotenoids. This study illustrates the need to consider the multi-stress context (contaminants and temperature increase) in which host-parasite interactions occur. PMID:26938743

  20. Increased adipose tissue expression of Grb14 in several models of insulin resistance.

    PubMed

    Cariou, Bertrand; Capitaine, Nadège; Le Marcis, Véronique; Vega, Nathalie; Béréziat, Véronique; Kergoat, Micheline; Laville, Martine; Girard, Jean; Vidal, Hubert; Burnol, Anne-Françoise

    2004-06-01

    Grb14 is an effector of insulin signaling, which directly inhibits insulin receptor catalytic activity in vitro. Here, we investigated whether the expression of Grb14 and its binding partner ZIP (PKC zeta interacting protein) is regulated during insulin resistance in type 2 diabetic rodents and humans. Grb14 expression was increased in adipose tissue of both ob/ob mice and Goto-Kakizaki (GK) rats, whereas there was no difference in liver. An increase was also observed in subcutaneous adipose tissue of type 2 diabetic subjects when compared with controls. ZIP expression was increased in adipose tissue of ob/ob mice and type 2 diabetic patients, but it did not vary in GK rats. Hormonal regulation of Grb14 and ZIP expression was then investigated in 3T3-F442A adipocytes. In this model, insulin stimulated Grb14 expression, while TNF-alpha increased ZIP expression. Moreover, the insulin-sensitizing drugs thiazolidinediones (TZDs) decreased Grb14 expression in 3T3-F442A adipocytes. Finally, we investigated the dynamic regulation of Grb14 expression in ob/ob mice in several conditions improving their insulin sensitivity. Prolonged fasting and treatment with metformin significantly decreased Grb14 expression in peri-epidydimal adipose tissue, while there was only a trend to a diminution after TZD treatment. Taken together, these results suggest that the regulation of Grb14 expression in adipose tissue may play a physiological role in insulin sensitivity.

  1. Cold weather exercise and airway cytokine expression.

    PubMed

    Davis, Michael S; Malayer, Jerry R; Vandeventer, Lori; Royer, Christopher M; McKenzie, Erica C; Williamson, Katherine K

    2005-06-01

    Athletes who perform repeated exercise while breathing cold air have a high prevalence of asthmalike chronic airway disease, but the mechanism linking such activity to airway inflammation is unknown. We used a novel animal model (exercising horses) to test the hypothesis that exercise-induced chronic airway disease is caused by exposure of intrapulmonary airways to unconditioned air, resulting in the upregulation of cytokine expression. Bronchoalveolar lavage fluid (BALF) was obtained from eight horses 5 h after submaximal exercise while they breathed room temperature or subfreezing air in a random crossover design. BALF total and differential nucleated cell counts were determined, and relative cytokine mRNA expression in BALF nucleated cells was quantified by real-time RT-PCR using primer and probe sequences specific for equine targets. There were no significant changes in total or differential cell concentrations between BALF recovered after warm and cold air exercise, although there was a strong trend toward increased concentrations of airway epithelial cells after cold air exercise (P = 0.0625). T(H)2 cytokines IL-4, IL-5, and IL-10 were preferentially upregulated after cold air exercise 12-, 9-, and 10-fold, respectively, compared with warm air exercise. Other cytokines (IL-2 and IL-6) were upregulated to a lesser extent (6- and 3-fold, respectively) or not at all (IL-1, IL-8, IFN-gamma, and TNF-alpha). These results suggest that cold weather exercise can lead to asthmalike airway disease through the local induction of cytokines typical of the T(H)2 phenotype.

  2. Benign Nodular Goiter Causing Upper Airway Obstruction

    PubMed Central

    Başoğlu, Mahmut; Öztürk, Gürkan; Aydınlı, Bülent; Yıldırgan, M. İlhan; Atamanalp, S. Selçuk; Celebi, Fehmi

    2009-01-01

    Objective Benign nodular goiter (BNG) can cause narrowing of the upper airway. In some rare cases, obstruction of the upper airway also occurs. The following paper reports our experiences with regard to BNG patients who experienced obstruction of the upper airway. Materials and Methods. We retrospectively investigated the records of 13 patients with acute airway obstruction due to BNG who were admitted to the General Surgery Department of Ataturk University Medical School between January 2000 and December 2007. Results Thirteen patients with airway obstruction secondary to BNG were hospitalized during this period. There were two males and 11 females, and the mean age was 58.5 years (range 37–74 years). For all patients, the primary symptom upon admission was defined as respiratory distress; all patients had varying degrees of respiratory distress upon admission. Three of the patients underwent emergent endotracheal intubation in the emergency room. A preoperative radiological evaluation was performed with thyroid ultrasonography (US) and computed tomography (CT). There were retrosternal or substernal components of the BNG in nine patients. Twelve patients underwent operations, while one patient with mild respiratory distress elected not to be operated on. Ten patients underwent total thyroidectomies, while two patients underwent near-total thyroidectomies. One patient with retrosternal goiter also underwent a median sternotomy. Three patients received a tracheostomy after the operation. Suction drains were utilized in all operations. During the post-operative period, two patients suffered from voice impairment, and seven patients experienced hypocalcemia. Two patients died. Pathological examination of the thyroidectomy tissue revealed BNG in all cases. In addition, two patients had micropapillary carcinomas. Conclusion Although BNG causing upper airway obstruction is rare, it is an important clinical entity because of the need for emergent operation, the

  3. Inhibition of airway surface fluid absorption by cholinergic stimulation

    PubMed Central

    Joo, Nam Soo; Krouse, Mauri E.; Choi, Jae Young; Cho, Hyung-Ju; Wine, Jeffrey J.

    2016-01-01

    In upper airways airway surface liquid (ASL) depth and clearance rates are both increased by fluid secretion. Secretion is opposed by fluid absorption, mainly via the epithelial sodium channel, ENaC. In static systems, increased fluid depth activates ENaC and decreased depth inhibits it, suggesting that secretion indirectly activates ENaC to reduce ASL depth. We propose an alternate mechanism in which cholinergic input, which causes copious airway gland secretion, also inhibits ENaC-mediated absorption. The conjoint action accelerates clearance, and the increased transport of mucus out of the airways restores ASL depth while cleansing the airways. We were intrigued by early reports of cholinergic inhibition of absorption by airways in some species. To reinvestigate this phenomenon, we studied inward short-circuit currents (Isc) in tracheal mucosa from human, sheep, pig, ferret, and rabbit and in two types of cultured cells. Basal Isc was inhibited 20–70% by the ENaC inhibitor, benzamil. Long-lasting inhibition of ENaC-dependent Isc was also produced by basolateral carbachol in all preparations except rabbit and the H441 cell line. Atropine inhibition produced a slow recovery or prevented inhibition if added before carbachol. The mechanism for inhibition was not determined and is most likely multi-factorial. However, its physiological significance is expected to be increased mucus clearance rates in cholinergically stimulated airways. PMID:26846701

  4. CRISPR-Cas and restriction-modification systems are compatible and increase phage resistance.

    PubMed

    Dupuis, Marie-Ève; Villion, Manuela; Magadán, Alfonso H; Moineau, Sylvain

    2013-01-01

    Bacteria have developed a set of barriers to protect themselves against invaders such as phage and plasmid nucleic acids. Different prokaryotic defence systems exist and at least two of them directly target the incoming DNA: restriction-modification (R-M) and CRISPR-Cas systems. On their own, they are imperfect barriers to invasion by foreign DNA. Here, we show that R-M and CRISPR-Cas systems are compatible and act together to increase the overall phage resistance of a bacterial cell by cleaving their respective target sites. Furthermore, we show that the specific methylation of phage DNA does not impair CRISPR-Cas acquisition or interference activities. Taken altogether, both mechanisms can be leveraged to decrease phage contaminations in processes relying on bacterial growth and/or fermentation.

  5. Increased Amoxicillin–Clavulanic Acid Resistance in Escherichia coli Blood Isolates, Spain

    PubMed Central

    Oteo, Jesús; Lázaro, Edurne; Cuevas, Óscar; García-Cobos, Silvia; Pérez-Vázquez, María; de Abajo, F. J.

    2008-01-01

    To determine the evolution and trends of amoxicillin–clavulanic acid resistance among Escherichia coli isolates in Spain, we tested 9,090 blood isolates from 42 Spanish hospitals and compared resistance with trends in outpatient consumption. These isolates were collected by Spanish hospitals that participated in the European Antimicrobial Resistance Surveillance System network from April 2003 through December 2006. PMID:18680650

  6. Increased amoxicillin-clavulanic acid resistance in Escherichia coli blood isolates, Spain.

    PubMed

    Oteo, Jesús; Campos, José; Lázaro, Edurne; Cuevas, Oscar; García-Cobos, Silvia; Pérez-Vázquez, María; de Abajo, F J

    2008-08-01

    To determine the evolution and trends of amoxicillin-clavulanic acid resistance among Escherichia coli isolates in Spain, we tested 9,090 blood isolates from 42 Spanish hospitals and compared resistance with trends in outpatient consumption. These isolates were collected by Spanish hospitals that participated in the European Antimicrobial Resistance Surveillance System network from April 2003 through December 2006.

  7. Increased potassium conductance of brain mitochondria induces resistance to permeability transition by enhancing matrix volume.

    PubMed

    Hansson, Magnus J; Morota, Saori; Teilum, Maria; Mattiasson, Gustav; Uchino, Hiroyuki; Elmér, Eskil

    2010-01-01

    Modulation of K(+) conductance of the inner mitochondrial membrane has been proposed to mediate preconditioning in ischemia-reperfusion injury. The mechanism is not entirely understood, but it has been linked to a decreased activation of mitochondrial permeability transition (mPT). In the present study K(+) channel activity was mimicked by picomolar concentrations of valinomycin. Isolated brain mitochondria were exposed to continuous infusions of calcium. Monitoring of extramitochondrial Ca(2+) and mitochondrial respiration provided a quantitative assay for mPT sensitivity by determining calcium retention capacity (CRC). Valinomycin and cyclophilin D inhibition separately and additively increased CRC. Comparable degrees of respiratory uncoupling induced by increased K(+) or H(+) conductance had opposite effects on mPT sensitivity. Protonophores dose-dependently decreased CRC, demonstrating that so-called mild uncoupling was not beneficial per se. The putative mitoK(ATP) channel opener diazoxide did not mimic the effect of valinomycin. An alkaline matrix pH was required for mitochondria to retain calcium, but increased K(+) conductance did not result in augmented DeltapH. The beneficial effect of valinomycin on CRC was not mediated by H(2)O(2)-induced protein kinase Cepsilon activation. Rather, increased K(+) conductance reduced H(2)O(2) generation during calcium infusion. Lowering the osmolarity of the buffer induced an increase in mitochondrial volume and improved CRC similar to valinomycin without inducing uncoupling or otherwise affecting respiration. We propose that increased potassium conductance in brain mitochondria may cause a direct physiological effect on matrix volume inducing resistance to pathological calcium challenges.

  8. Plant Genetic Background Increasing the Efficiency and Durability of Major Resistance Genes to Root-knot Nematodes Can Be Resolved into a Few Resistance QTLs

    PubMed Central

    Barbary, Arnaud; Djian-Caporalino, Caroline; Marteu, Nathalie; Fazari, Ariane; Caromel, Bernard; Castagnone-Sereno, Philippe; Palloix, Alain

    2016-01-01

    With the banning of most chemical nematicides, the control of root-knot nematodes (RKNs) in vegetable crops is now based essentially on the deployment of single, major resistance genes (R-genes). However, these genes are rare and their efficacy is threatened by the capacity of RKNs to adapt. In pepper, several dominant R-genes are effective against RKNs, and their efficacy and durability have been shown to be greater in a partially resistant genetic background. However, the genetic determinants of this partial resistance were unknown. Here, a quantitative trait loci (QTL) analysis was performed on the F2:3 population from the cross between Yolo Wonder, an accession considered partially resistant or resistant, depending on the RKN species, and Doux Long des Landes, a susceptible cultivar. A genetic linkage map was constructed from 130 F2 individuals, and the 130 F3 families were tested for resistance to the three main RKN species, Meloidogyne incognita, M. arenaria, and M. javanica. For the first time in the pepper-RKN pathosystem, four major QTLs were identified and mapped to two clusters. The cluster on chromosome P1 includes three tightly linked QTLs with specific effects against individual RKN species. The fourth QTL, providing specific resistance to M. javanica, mapped to pepper chromosome P9, which is known to carry multiple NBS–LRR repeats, together with major R-genes for resistance to nematodes and other pathogens. The newly discovered cluster on chromosome P1 has a broad spectrum of action with major additive effects on resistance. These data highlight the role of host QTLs involved in plant-RKN interactions and provide innovative potential for the breeding of new pepper cultivars or rootstocks combining quantitative resistance and major R-genes, to increase both the efficacy and durability of RKN control by resistance genes. PMID:27242835

  9. Antimicrobial resistance of Neisseria gonorrhoeae isolates in south-west Germany, 2004 to 2015: increasing minimal inhibitory concentrations of tetracycline but no resistance to third-generation cephalosporins

    PubMed Central

    Regnath, Thomas; Mertes, Thomas; Ignatius, Ralf

    2016-01-01

    Increasing antimicrobial resistance of Neisseria gonorrhoeae, particularly to third-generation cephalosporins, has been reported in many countries. We examined the susceptibility (determined by Etest and evaluated using the breakpoints of the European Committee on Antimicrobial Susceptibility Testing) of 434 N. gonorrhoeae isolates collected from 107 female and 327 male patients in Stuttgart, south-west Germany, between 2004 and 2015. During the study period, high proportions of isolates were resistant to ciprofloxacin (70.3%), tetracycline (48.4%; increasing from 27.5% in 2004/2005 to 57.7% in 2014/2015; p = 0.0002) and penicillin (25.6%). The proportion of isolates resistant to azithromycin was low (5.5%) but tended to increase (p = 0.08). No resistance and stable minimum inhibitory concentrations were found for cefixime, ceftriaxone, and spectinomycin. High-level resistance was found for ciprofloxacin (39.6%) and tetracycline (20.0%) but not for azithromycin; 16.3% of the isolates produced betalactamase. Thus, cephalosporins can still be used for the treatment of gonorrhoea in the study area. To avoid further increasing resistance to azithromycin, its usage should be limited to patients allergic to cephalosporins, or (in combination with cephalosporins) to patients for whom no susceptibility testing could be performed or those co-infected with chlamydiae. PMID:27632642

  10. Platelet rich plasma improves the healing process after airway anastomosis.

    PubMed

    Gómez-Caro, Abel; Ausin, Pilar; Boada, Marc

    2011-12-01

    This study investigated whether platelet-rich plasma (PRP) promotes healing and reduces anastomotic complications following airway surgery in a pig model. PRP was obtained by spinning down the animal's own blood (60 ml) and collecting the buffy coat containing platelets and white blood cells. Fifteen adult pigs were randomized into three groups: (1) sham treatment (cervicotomy), (2) non-PRP group (50% tracheal resection and end-to-end anastomosis), and (3) PRP group (50% tracheal resection, end-to-end anastomosis and PRP application). Blood samples were taken at baseline and at one, six and 24. Animals were monitored for anastomotic complications, infection and local reactivity. Laser Doppler flowmetry was performed intraoperatively and at 30 days to assess differences in pre- and post-anastomotic blood flow. The tensile strength of the anastomosis was also tested. The platelet level was higher in PRP fluid than in the baseline blood sample (P<0.002). Vascular endothelial growth factor, transforming growth factor β-1 and epidermal growth factor immunoassay readings peaked at one and six hours in the animals that had received PRP (P<0.03); these also showed significantly increased transanastomotic flow and stress-strain resistance (P<0.04) at 30 days than the animals that had not received PRP. PRP therefore, accelerates the onset of healing in airway surgery by promoting an earlier release of platelet-derived growth factors that stimulate transanastomotic angiogenesis.

  11. Temephos resistance and esterase activity in the mosquito Aedes aegypti in Havana, Cuba increased dramatically between 2006 and 2008.

    PubMed

    Bisset, J A; Rodríguez, M M; Ricardo, Y; Ranson, H; Pérez, O; Moya, M; Vázquez, A

    2011-09-01

    Aedes aegypti (L.) (Diptera: Culicidae) control programmes in Cuba rely on the application of the organophosphate temephos for larval control. Hence, the monitoring of resistance to this insecticide is an essential component of such programmes. Here, 15 field populations from different municipalities of Havana City were assayed for resistance to temephos. High levels of resistance were detected in all strains and resistance ratios were highly correlated with esterase activity (P = 0.00001). Populations from three municipalities were tested in both 2006 and 2008; resistance and esterase activities both significantly increased during this 2-year period. Synergist studies demonstrated that neither glutathione transferases nor monooxygenases were associated with the increase in resistance to temephos in this period. The duration of the efficacy of commercial formulations of temephos in controlling Ae. aegypti populations in Havana City was reduced by the high level of temephos resistance observed; hence these data are of clear operational significance for the dengue control programme in Cuba. New integrated strategies to avoid further increases in temephos resistance in Cuba are necessary.

  12. Iron chelators increase the resistance of Ataxia telangeictasia cells to oxidative stress.

    PubMed

    Shackelford, Rodney E; Manuszak, Ryan P; Johnson, Cybele D; Hellrung, Daniel J; Link, Charles J; Wang, Suming

    2004-10-05

    Ataxia telangeictasia (A-T) is an autosomal recessive disorder characterized by immune dysfunction, genomic instability, chronic oxidative damage, and increased cancer incidence. Previously, desferal was found to increase the resistance of A-T, but not normal cells to exogenous oxidative stress in the colony forming-efficiency assay, suggesting that iron metabolism is dysregulated in A-T. Since desferal both chelates iron and modulates gene expression, we tested the effects of apoferritin and the iron chelating flavonoid quercetin on A-T cell colony-forming ability. We demonstrate that apoferritin and quercetin increase the ability of A-T cells to form colonies. We also show that labile iron levels are significantly elevated in Atm-deficient mouse sera compared to syngeniec wild type mice. Our findings support a role for labile iron acting as a Fenton catalyst in A-T, contributing to the chronic oxidative stress seen in this disease. Our findings further suggest that iron chelators might promote the survival of A-T cells and hence, individuals with A-T.

  13. Increased resistance to free radical damage induced by low-level sound conditioning.

    PubMed

    Harris, Kelly Carney; Bielefeld, Eric; Hu, Bo Hua; Henderson, Donald

    2006-03-01

    Conditioning is the phenomenon where exposure to moderate-level acoustic stimuli can increase the ear's resistance to subsequent more intense sound exposures. In recent years, research has shown that conditioning increases the availability of antioxidant enzymes which presumably protects the ear from oxidative stress induced by a traumatic noise exposure [Jacono, A.A., Hu, B., Kopke, R.D., Henderson, D., Van De Water, T.R., Steinman, H.M., 1998. Changes in cochlear antioxidant enzyme activity after sound conditioning and noise exposure in the chinchilla. Hear Res 117, 31-8]. The current study was designed to assess whether the increase in endogenous antioxidants seen following conditioning could provide protection from oxidative stress induced by Paraquat, a potent generator of superoxide. Chinchillas were exposed to a conditioning noise, 500 Hz OBN at 95 dB for 6 h/day for 10 days, followed 5 days later with Paraquat application to the round window. Controls underwent the Paraquat application surgery, without prior conditioning. Evoked potential thresholds were determined prior to conditioning, at day 1, 5 and 10 during conditioning, at day 15 (5 days after conditioning), and at day 17, 19, 23, and 35 (1, 3, 7, and 20 days post-Paraquat). The conditioned animals showed reductions in permanent threshold shift and reduced inner hair cell loss relative to controls. These results reinforce the hypothesis that antioxidants are primary mediators of the conditioning effect.

  14. Angiogenesis and airway reactivity in asthmatic Brown Norway rats.

    PubMed

    Wagner, Elizabeth M; Jenkins, John; Schmieder, Anne; Eldridge, Lindsey; Zhang, Qiong; Moldobaeva, Aigul; Zhang, Huiying; Allen, John S; Yang, Xiaoxia; Mitzner, Wayne; Keupp, Jochen; Caruthers, Shelton D; Wickline, Samuel A; Lanza, Gregory M

    2015-01-01

    Expanded and aberrant bronchial vascularity, a prominent feature of the chronic asthmatic airway, might explain persistent airway wall edema and sustained leukocyte recruitment. Since it is well established that there are causal relationships between exposure to house dust mite (HDM) and the development of asthma, determining the effects of HDM in rats, mammals with a bronchial vasculature similar to humans, provides an opportunity to study the effects of bronchial angiogenesis on airway function directly. We studied rats exposed bi-weekly to HDM (Der p 1; 50 μg/challenge by intranasal aspiration, 1, 2, 3 weeks) and measured the time course of appearance of increased blood vessels within the airway wall. Results demonstrated that within 3 weeks of HDM exposure, the number of vessels counted within airway walls of bronchial airways (0.5-3 mm perimeter) increased significantly. These vascular changes were accompanied by increased airway responsiveness to methacholine. A shorter exposure regimen (2 weeks of bi-weekly exposure) was insufficient to cause a significant increase in functional vessels or reactivity. Yet, 19F/1H MR imaging at 3T following αvβ3-targeted perfluorocarbon nanoparticle infusion revealed a significant increase in 19F signal in rat airways after 2 weeks of bi-weekly HDM, suggesting earlier activation of the process of neovascularization. Although many antigen-induced mouse models exist, mice lack a bronchial vasculature and consequently lack the requisite human parallels to study bronchial edema. Overall, our results provide an important new model to study the impact of bronchial angiogenesis on chronic inflammation and airways hyperreactivity.

  15. Does increased heat resistance result in higher susceptibility to predation? A test using Drosophila melanogaster selection and hardening.

    PubMed

    Hangartner, Sandra; Dworkin, Ian; DeNieu, Michael; Hoffmann, Ary A

    2017-04-07

    Heat resistance of ectotherms can be increased both by plasticity and evolution, but these effects may have trade-offs resulting from biotic interactions. Here we test for predation costs in Drosophila melanogaster populations with altered heat resistance produced by adult hardening and directional selection for increased heat resistance. In addition, we also tested for genetic trade-offs by testing heat resistance in lines that have evolved under increased predation risk. We show that while 35/37°C hardening increases heat resistance as expected, it does not increase predation risk from jumping spiders or mantids; in fact there was an indication that survival may have increased under predation following a triple 37°C compared to a single 35°C hardening treatment. Flies that survived a 39°C selection cycle showed lower survival under predation, suggesting a predation cost of exposure to a more severe heat stress. There was however no correlated response to selection because survival did not differ between control and selected lines after selection was relaxed for one or two generations. In addition, lines selected for increased predation risk did not differ in heat resistance. Our findings suggest independent evolutionary responses to predation and heat as measured in laboratory assays, and no costs of heat hardening on susceptibility to predation. This article is protected by copyright. All rights reserved.

  16. Protective Roles for RGS2 in a Mouse Model of House Dust Mite-Induced Airway Inflammation

    PubMed Central

    George, Tresa; Bell, Matthew; Chakraborty, Mainak; Siderovski, David P.; Giembycz, Mark A.

    2017-01-01

    The GTPase-accelerating protein, regulator of G-protein signalling 2 (RGS2) reduces signalling from G-protein-coupled receptors (GPCRs) that signal via Gαq. In humans, RGS2 expression is up-regulated by inhaled corticosteroids (ICSs) and long-acting β2-adrenoceptor agonists (LABAs) such that synergy is produced in combination. This may contribute to the superior clinical efficacy of ICS/LABA therapy in asthma relative to ICS alone. In a murine model of house dust mite (HDM)-induced airways inflammation, three weeks of intranasal HDM (25 μg, 3×/week) reduced lung function and induced granulocytic airways inflammation. Compared to wild type animals, Rgs2-/- mice showed airways hyperresponsiveness (increased airways resistance and reduced compliance). While HDM increased pulmonary inflammation observed on hematoxylin and eosin-stained sections, there was no difference between wild type and Rgs2-/- animals. HDM-induced mucus hypersecretion was also unaffected by RGS2 deficiency. However, inflammatory cell counts in the bronchoalveolar lavage fluid of Rgs2-/- animals were significantly increased (57%) compared to wild type animals and this correlated with increased granulocyte (neutrophil and eosinophil) numbers. Likewise, cytokine and chemokine (IL4, IL17, IL5, LIF, IL6, CSF3, CXCLl, CXCL10 and CXCL11) release was increased by HDM exposure. Compared to wild type, Rgs2-/- animals showed a trend towards increased expression for many cytokines/chemokines, with CCL3, CCL11, CXCL9 and CXCL10 being significantly enhanced. As RGS2 expression was unaffected by HDM exposure, these data indicate that RGS2 exerts tonic bronchoprotection in HDM-induced airways inflammation. Modest anti-inflammatory and anti-remodelling roles for RGS2 are also suggested. If translatable to humans, therapies that maximize RGS2 expression may prove advantageous. PMID:28107494

  17. Increasing activity and thermal resistance of Bacillus gibsonii alkaline protease (BgAP) by directed evolution.

    PubMed

    Martinez, Ronny; Jakob, Felix; Tu, Ran; Siegert, Petra; Maurer, Karl-Heinz; Schwaneberg, Ulrich

    2013-03-01

    Bacillus gibsonii Alkaline Protease (BgAP) is a recently reported subtilisin protease exhibiting activity and stability properties suitable for applications in laundry and dish washing detergents. However, BgAP suffers from a significant decrease of activity at low temperatures. In order to increase BgAP activity at 15°C, a directed evolution campaign based on the SeSaM random mutagenesis method was performed. An optimized microtiter plate expression system in B. subtilis was established and classical proteolytic detection methods were adapted for high throughput screening. In parallel, the libraries were screened for increased residual proteolytic activity after incubation at 58°C. Three iterative rounds of directed BgAP evolution yielded a set of BgAP variants with increased specific activity (K(cat)) at 15°C and increased thermal resistance. Recombination of both sets of amino acid substitutions resulted finally in variant MF1 with a 1.5-fold increased specific activity (15°C) and over 100 times prolonged half-life at 60°C (224 min compared to 2 min of the WT BgAP). None of the introduced amino acid substitutions were close to the active site of BgAP. Activity-altering amino acid substitutions were from non-charged to non-charged or from sterically demanding to less demanding. Thermal stability improvements were achieved by substitutions to negatively charged amino acids in loop areas of the BgAP surface which probably fostered ionic and hydrogen bonds interactions.

  18. Airway dynamics in COPD patients by within-breath impedance tracking: effects of continuous positive airway pressure.

    PubMed

    Lorx, András; Czövek, Dorottya; Gingl, Zoltán; Makan, Gergely; Radics, Bence; Bartusek, Dóra; Szigeti, Szabolcs; Gál, János; Losonczy, György; Sly, Peter D; Hantos, Zoltán

    2017-02-01

    Tracking of the within-breath changes of respiratory mechanics using the forced oscillation technique may provide outcomes that characterise the dynamic behaviour of the airways during normal breathing.We measured respiratory resistance (Rrs) and reactance (Xrs) at 8 Hz in 55 chronic obstructive pulmonary disease (COPD) patients and 20 healthy controls, and evaluated Rrs and Xrs as functions of gas flow (V') and volume (V) during normal breathing cycles. In 12 COPD patients, additional measurements were made at continuous positive airway pressure (CPAP) levels of 4, 8, 14 and 20 hPa.The Rrs and Xrsversus V' and V relationships displayed a variety of loop patterns, allowing characterisation of physiological and pathological processes. The main outcomes emerging from the within-breath analysis were the Xrsversus V loop area (AXV) quantifying expiratory flow limitation, and the tidal change in Xrs during inspiration (ΔXI) reflecting alteration in lung inhomogeneity in COPD. With increasing CPAP, AXV and ΔXI approached the normal ranges, although with a large variability between individuals, whereas mean Rrs remained unchanged.Within-breath tracking of Rrs and Xrs allows an improved assessment of expiratory flow limitation and functional inhomogeneity in COPD; thereby it may help identify the physiological phenotypes of COPD and determine the optimal level of respiratory support.

  19. Syk Regulates Neutrophilic Airway Hyper-Responsiveness in a Chronic Mouse Model of Allergic Airways Inflammation

    PubMed Central

    Juvet, Stephen; Scott, Jeremy A.; Chow, Chung-Wai

    2017-01-01

    Background Asthma is a chronic inflammatory disease characterized by airways hyper-responsiveness (AHR), reversible airway obstruction, and airway inflammation and remodeling. We previously showed that Syk modulates methacholine-induced airways contractility in naïve mice and in mice with allergic airways inflammation. We hypothesize that Syk plays a role in the pathogenesis of AHR; this was evaluated in a chronic 8-week mouse model of house dust mite (HDM)-induced allergic airways inflammation. Methods We used the Sykflox/flox//rosa26CreERT2 conditional Syk knock-out mice to assess the role of Syk prior to HDM exposure, and treated HDM-sensitized mice with the Syk inhibitor, GSK143, to evaluate its role in established allergic airways inflammation. Respiratory mechanics and methacholine (MCh)-responsiveness were assessed using the flexiVent® system. Lungs underwent bronchoalveolar lavage to isolate inflammatory cells or were frozen for determination of gene expression in tissues. Results MCh-induced AHR was observed following HDM sensitization in the Syk-intact (Sykflox/flox) and vehicle-treated BALB/c mice. MCh responsiveness was reduced to control levels in HDM-sensitized Sykdel/del mice and in BALB/c and Sykflox/flox mice treated with GSK143. Both Sykdel/del and GSK143-treated mice mounted appropriate immune responses to HDM, with HDM-specific IgE levels that were comparable to Sykflox/flox and vehicle-treated BALB/c mice. HDM-induced increases in bronchoalveolar lavage cell counts were attenuated in both Sykdel/del and GSK143-treated mice, due primarily to decreased neutrophil recruitment. Gene expression analysis of lung tissues revealed that HDM-induced expression of IL-17 and CXCL-1 was significantly attenuated in both Sykdel/del and GSK143-treated mice. Conclusion Syk inhibitors may play a role in the management of neutrophilic asthma. PMID:28107345

  20. Multiple Mechanisms Increase Levels of Resistance in Rapistrum rugosum to ALS Herbicides

    PubMed Central

    Hatami, Zahra M.; Gherekhloo, Javid; Rojano-Delgado, Antonia M.; Osuna, Maria D.; Alcántara, Ricardo; Fernández, Pablo; Sadeghipour, Hamid R.; De Prado, Rafael

    2016-01-01

    Rapistrum rugosum (turnip weed) is a common weed of wheat fields in Iran, which is most often controlled by tribenuron-methyl (TM), a sulfonylurea (SU) belonging to the acetolactate synthase (ALS) inhibiting herbicides group. Several cases of unexplained control failure of R. rugosum by TM have been seen, especially in Golestan province-Iran. Hence, there is lack of research in evaluation of the level of resistance of the R. rugosum populations to TM, using whole plant dose-response and enzyme assays, then investigating some potential resistance mechanisms Results revealed that the resistance factor (RF) for resistant (R) populations was 2.5–6.6 fold higher than susceptible (S) plant. Neither foliar retention, nor 14C-TM absorption and translocation were the mechanisms responsible for resistance in turnip weed. Metabolism of TM was the second resistant mechanism in two populations (Ag-R5 and G-1), in which three metabolites were found. The concentration of TM for 50% inhibition of ALS enzyme activity in vitro showed a high level of resistance to the herbicide (RFs were from 28 to 38) and cross-resistance to sulfonyl-aminocarbonyl-triazolinone (SCT), pyrimidinyl-thiobenzoate (PTB) and triazolopyrimidine (TP), with no cross-resistance to imidazolinone (IMI). Substitution Pro 197 to Ser 197 provided resistance to four of five ALS-inhibiting herbicides including SU, TP, PTB, and SCT with no resistance to IMI. These results documented the first case of R. rugosum resistant population worldwide and demonstrated that both RST and NRST mechanisms are involved to the resistance level to TM. PMID:26941749

  1. Acute resistance exercise reduces increased gene expression in muscle atrophy of ovariectomised arthritic rats

    PubMed Central

    Furlanetto, Roberto; de Paula Souza, Aletéia; de Oliveira, Anselmo Alves; Nunes, Paulo Ricardo Prado; Michelin, Márcia Antoniazi; Chica, Javier Emilio Lazo; Murta, Eddie Fernando Candido

    2017-01-01

    Objective We studied the effect of resistance exercise (RE) on mRNA levels of atrogin-1, MuRF-1, and myostatin in the gastrocnemius muscle of arthritic rats after loss of ovarian function (LOF). Material and methods Thirty female Wistar rats (nine weeks old, 195.3 ±17.4 grams) were randomly allocated into five groups: control group (CT-Sham; n = 6); group with rheumatoid arthritis (RA; n = 6); group with rheumatoid arthritis subjected to RE (RAEX; n = 6); ovariectomy group with rheumatoid arthritis (RAOV; n = 6); and an ovariectomy group with rheumatoid arthritis subjected to RE (RAOVEX; n = 6). After 15 days of intra-articular injections with Met-BSA the animals were subjected to RE and six hours after workout were euthanised. Results The rheumatoid arthritis provoked reduction in the cross-sectional area (CSA) of muscle fibres, but the CSA was lower in the RAOV when compared to the RA groups. Skeletal muscle atrogin-1 mRNA level was increased in arthritic rats (RA and RAOV), but the atrogin-1 level was higher in RAOV group when compared to other arthritic groups. The Muscle MuRF-1 mRNA level was also increased in the RAOV group. The increased atrogin-1 and MuRF-1 mRNA levels were lower in the RAOVEX group than in the RAOV group. The myostatin mRNA level was similar in all groups, except for the RAOVEX group, in which it was lower than the other groups. Conclusions LOF results in increased loss of skeletal muscle-related ubiquitin ligases (atrogin-1 and MuRF-1). However, the RE reduces the atrogin-1, MuRF-1, and myostatin mRNA levels in muscle of arthritic rats affected by LOF. PMID:28250722

  2. RESISTIN: A HORMONE WHICH INDUCES INSULIN RESISTANCE IS INCREASED IN NORMAL PREGNANCY

    PubMed Central

    Nien, Jyh Kae; Mazaki-Tovi, Shali; Romero, Roberto; Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Pineles, Beth L.; Friel, Lara A.; Espinoza, Jimmy; Goncalves, Luis; Santolaya, Joaquin; Gomez, Ricardo; Hong, Joon-Seok; Edwin, Samuel; Soto, Eleazar; Richani, Karina; Mazor, Moshe; Hassan, Sonia S.

    2008-01-01

    Aims Resistin, a newly discovered adipokine, is thought to play a key role in the regulation of insulin resistance. The objectives of this study were to develop a nomogram of maternal plasma concentrations of resistin from 11 weeks of gestation to term and to determine whether resistin concentrations differ between normal and overweight pregnant women. Methods In this cross-sectional study, plasma concentrations of resistin were determined in normal pregnant women of normal body mass index (BMI 18.5–24.9; n=261), overweight pregnant women (BMI ≥25; n=140), and non-pregnant women of normal weight (n=40). Blood samples were collected once from each woman between the first trimester and term. Percentiles for resistin concentration were determined for five pre-specified windows of gestational age. Plasma resistin concentration was determined by immunoassay. Non-parametric statistics were used for analysis. Results The median maternal plasma concentration of resistin between 11 to 14 weeks of gestation in women of normal weight was significantly higher than non-pregnant women; The plasma concentration of resistin increased with gestational age. Conclusions Normal pregnant women have a higher median plasma concentration of resistin than non-pregnant women and the concentration of this adipokine increases with advancing gestation. Alterations in the maternal plasma concentration of resistin during pregnancy may contribute to metabolic changes of pregnancy. PMID:17919114

  3. Increase in Mechanical Resistance to Force in a Shear-Activated Protein

    NASA Astrophysics Data System (ADS)

    Botello, Eric; Harris, Nolan; Choi, Huiwan; Zhou, Zhou; Bergeron, Angela; Dong, Jing-Fei; Kiang, Ching-Hwa

    2009-03-01

    von Willebrand factor (VWF) is the largest multimeric adhesion ligand found in human blood. Plasma VWF (pVWF) must be exposed to shear stress, like at sites of vascular injury, to be activated to bind platelets to induce blood clotting. In addition, adhesion activity of VWF is related to its polymer size, with the ultra-large form of VWF (ULVWF) being hyper-active, and forming fibers even without exposure to shear stress. We used the AFM to stretch pVWF, sheared VWF (sVWF) and ULVWF, and monitor the forces as a function of molecular extension. We showed a similar increase in force resistance to unfolding for sVWF and ULVWF when compared to pVWF. The increase in force is reduced when other molecules that are known to disrupt their fibril formation are present. Our results provide evidence that the common higher order structure of sVWF and ULVWF may affect the domain structure that causes difference in their adhesion activity compared to pVWF.

  4. Cell wall structure and formation of maturing fibres of moso bamboo (Phyllostachys pubescens) increase buckling resistance.

    PubMed

    Wang, Xiaoqing; Ren, Haiqing; Zhang, Bo; Fei, Benhua; Burgert, Ingo

    2012-05-07

    The mechanical stability of the culms of monocotyledonous bamboos is highly attributed to the proper embedding of the stiff fibre caps of the vascular bundles into the soft parenchymatous matrix. Owing to lack of a vascular cambium, bamboos show no secondary thickening growth that impedes geometrical adaptations to mechanical loads and increases the necessity of structural optimization at the material level. Here, we investigate the fine structure and mechanical properties of fibres within a maturing vascular bundle of moso bamboo, Phyllostachys pubescens, with a high spatial resolution. The fibre cell walls were found to show almost axially oriented cellulose fibrils, and the stiffness and hardness of the central part of the cell wall remained basically consistent for the fibres at different regions across the fibre cap. A stiffness gradient across the fibre cap is developed by differential cell wall thickening which affects tissue density and thereby axial tissue stiffness in the different regions of the cap. The almost axially oriented cellulose fibrils in the fibre walls maximize the longitudinal elastic modulus of the fibres and their lignification increases the transverse rigidity. This is interpreted as a structural and mechanical optimization that contributes to the high buckling resistance of the slender bamboo culms.

  5. Increased resistance to detachment of adherent microspheres and Bacillus spores subjected to a drying step.

    PubMed

    Faille, Christine; Bihi, Ilyesse; Ronse, Annette; Ronse, Gilles; Baudoin, Michael; Zoueshtiagh, Farzam

    2016-07-01

    In various environments, including that of food processing, adherent bacteria are often subjected to drying conditions. These conditions have been shown to result in changes in the ability of biofilms to cross-contaminate food in contact with them. In this study, we investigated the consequences of a drying step on the further ability of adherent bacterial spores to resist detachment. An initial series of experiment was set up with latex microspheres as a model. A microsphere suspension was deposited on a glass slide and incubated at 25, 35 and 50°C for times ranging from 1h to 48h. By subjecting the dried slides to increasing water flow rates, we showed that both time and temperature affected the ease of microsphere detachment. Similar observations were made for three Bacillus spores despite differences in their surface properties, especially regarding their surface physicochemistry. The differences in ease of adherent spore detachment could not be clearly linked to the minor changes in spore morphology, observed after drying in various environmental conditions. In order to explain the increased interaction between spheres or spores and glass slides, the authors made several assumptions regarding the possible underlying mechanisms: the shape of the liquid bridge between the sphere and the substratum, which is greatly influenced by the hydrophilic/hydrophobic characters of both surfaces; the accumulation of soil at the liquid/air interface; the presence of trapped nano-bubbles around and/or under the sphere.

  6. Increased beta -oxidation but no insulin resistance or glucose intolerance in mice lacking adiponectin.

    PubMed

    Ma, Ke; Cabrero, Agatha; Saha, Pradip K; Kojima, Hideto; Li, Lan; Chang, Benny Hung-Junn; Paul, Antoni; Chan, Lawrence

    2002-09-20

    Previous reports showed that recombinant fragments of adiponectin (adipo) displayed pharmacological effects when injected into rodents, but the relevance of these observations to the physiological function of adipo is unclear. We generated Adipo(-/-) mice by gene targeting. Adipo(-/-) mice are fertile with normal body and fat pad weights. Plasma glucose and insulin levels of Adipo(-/-) and Adipo(+/+) mice are similar under fasting conditions and during an intraperitoneal glucose tolerance test (GTT). Insulin tolerance test (ITT) also produces similar plasma glucose and insulin levels in the two groups of mice. Hyperinsulinemic-euglycemic clamp analysis showed that Adipo(-/-) and Adipo(+/+) mice have similar glucose infusion rates to maintain a similar serum glucose. High-fat diet feeding for 7 months led to similar weight gain and similar GTT and ITT responses. We next measured beta-oxidation and found it to be significantly increased in muscle and liver of Adipo(-/-) mice. In conclusion, our study indicates that absence of adipo causes increased beta-oxidation but does not cause glucose intolerance or insulin resistance in mice.

  7. Multidrug resistance 1 gene variants, pesticide exposure, and increased risk of DNA damage.

    PubMed

    Chen, Chun-Chieh; Huang, Chun-Huang; Wu, Man-Tzu Marcie; Chou, Chia-Hsuan; Huang, Chia-Chen; Tseng, Tzu-Yen; Chang, Fang-Yu; Li, Ying-Ti; Tsai, Chun-Cheng; Wang, Tsung-Shing; Wong, Ruey-Hong

    2014-01-01

    The P-glycoprotein, encoded by the multidrug resistance (MDR)1 gene, extrudes fat-soluble compounds to the extracellular environment. However, the DNA damage of pesticides in subjects with genetic variation in MDR1 has not been investigated. In this study, the comet assay was applied to examine the extent of DNA damage in the peripheral blood of 195 fruit growers who had been exposed to pesticides and 141 unexposed controls. The MDR1 polymorphisms were identified. Questionnaires were administered to obtain demographic data and occupational history. Results showed subjects experiencing high (2.14 μm/cell, P < 0.01) or low pesticide exposure (2.18 μm/cell, P < 0.01) had a significantly greater DNA tail moment than controls (1.28 μm/cell). Compared to the MDR1 T-129C (rs3213619) TC/CC carriers, the TT carriers had increased DNA tail moment in controls (1.30 versus 1.12 μm/cell, P < 0.01). Similar results were observed in the high and low pesticide-exposed groups. Combined analysis revealed that pesticide-exposed fruit growers with MDR1 -129 TT genotype had the greatest DNA damage in the subjects with the combinations of pesticide exposure and MDR1 -129 genotypes. In conclusion, pesticide exposed individuals with susceptible MDR1 -129 genotypes may experience increased risk of DNA damage.

  8. Laser Welded versus Resistance Spot Welded Bone Implants: Analysis of the Thermal Increase and Strength

    PubMed Central

    Fornaini, Carlo; Meleti, Marco; Bonanini, Mauro; Lagori, Giuseppe; Vescovi, Paolo; Merigo, Elisabetta; Nammour, Samir

    2014-01-01

    Introduction. The first aim of this “ex vivo split mouth” study was to compare the thermal elevation during the welding process of titanium bars to titanium implants inserted in pig jaws by a thermal camera and two thermocouples. The second aim was to compare the strength of the joints by a traction test with a dynamometer. Materials and Methods. Six pigs' jaws were used and three implants were placed on each side of them for a total of 36 fixtures. Twelve bars were connected to the abutments (each bar on three implants) by using, on one side, laser welding and, on the other, resistance spot welding. Temperature variations were recorded by thermocouples and by thermal camera while the strength of the welded joint was analyzed by a traction test. Results. For increasing temperature, means were 36.83 and 37.06, standard deviations 1.234 and 1.187, and P value 0.5763 (not significant). For traction test, means were 195.5 and 159.4, standard deviations 2.00 and 2.254, and P value 0.0001 (very significant). Conclusion. Laser welding was demonstrated to be able to connect titanium implant abutments without the risk of thermal increase into the bone and with good results in terms of mechanical strength. PMID:25110731

  9. Use of commercial organic fertilizer increases the abundance of antibiotic resistance genes and antibiotics in soil.

    PubMed

    Zhou, Xue; Qiao, Min; Wang, Feng-Hua; Zhu, Yong-Guan

    2017-01-01

    The application of manure-based commercial organic fertilizers (COFs) is becoming increasingly extensive because of the expanding market for organic food. The present study examined the effects of repeated applications of chicken or swine manure-based COFs on the fate of antibiotics and antibiotic resistance genes (ARGs) in soil by conducting a soil microcosm experiment. Application of COFs significantly increased antibiotics residues, as well as the relative abundance of ARGs and the integrase gene of class 1 integrons (intΙ1) in soil. Two months after each application, antibiotics and ARGs dissipated in amended soils, but they still remained at an elevated level, compared with the control. And, the accumulation of antibiotics was found due to repeated COF applications. However, the relative abundance of ARGs in most COF-amended soils did not differ significantly between the first application and the repeated application. The results imply that 2 months are not sufficient for ARGs to approach background levels, and that animal manure must be treated more effectively prior to using it in agriculture ecosystems.

  10. Altered detoxification status and increased resistance to oxidative stress by K-ras transformation.

    PubMed

    Recktenwald, Christian V; Kellner, Roland; Lichtenfels, Rudolf; Seliger, Barbara

    2008-12-15

    Mutated K-ras is frequently found in human malignancies and plays a key role in many signal transduction processes resulting in an altered gene and/or protein expression pattern. Proteins controlled by a constitutive activated mitogen-activated protein kinase pathway are primarily related to alterations in the mitochondrial and nuclear compartments. Therefore, different K-Ras mutants and respective control cells were subjected to two-dimensional gel electrophoresis using basic pH gradients. This approach led to the identification of differentially expressed proteins, such as members of the heterogeneous ribonucleoprotein family, and enzymes involved in cellular detoxification as well as in oxidative stress. Increased expression of these enzymes was paralleled by an elevated tolerance of K-ras mutants against the cytotoxic potential of hydrogen peroxide and formaldehyde as well as an altered redox status based on enhanced intracellular glutathione (GSH) levels indicating an improved detoxification potential of defined K-ras transfectants, whereas down-regulation by RNA interference of candidate proteins reversed the tolerance against these compounds. This hypothesis is supported by an up-regulated expression of a key enzyme of the pentose phosphate pathway resulting in an increased production of NADPH required for anabolic processes as well as the rebuilding of oxidized GSH. Both the enhanced resistance against xenobiotic compounds as well as an altered oxidative pathway might confer growth advantages for tumor cells carrying dominant-positive K-ras mutations such as in lung or pancreatic adenocarcinoma.

  11. Influence of air pollutants on allergic sensitization: the paradox of increased allergies and decreased resistance to infection.

    PubMed

    Gilmour, M Ian

    2012-01-01

    Air pollution has long been associated with health risks such as increased susceptibility to respiratory infections and potentiation of asthmatic-type responses. Experimental evidence in rodents indicates that air pollutants including diesel exhaust particles (DEPs), gases, and metals cause lung injury, inflammation, reduce aspects of host defense, and may potentiate allergic airway responses. Here we present evidence that diesel exhaust particles delivered by inhalation or aspiration can exacerbate allergic lung disease depending on the material's chemical properties. Genomic analysis of mouse lungs following instillation or inhalation of DEPs shows an alteration spectrum of pathways associated with immune signaling, cell metabolism, and oxidative stress. Diesel exposure also may worsen respiratory infections through depression of protective immune responses. Here we show that mice exposed to diesel and co-infected with influenza had increased influenza virus titers as well as higher levels of lung injury and inflammation in association with increased Th2 cytokines, and a concomitant decrease in Th1 polarization. A simplified model explains how the potentiation of the Th2 arm of immunity by diesel exhaust results in increased allergic sensitization, whereas cell-mediated (protective) immunity against viral infections is simultaneously reduced.

  12. The broader context of antibiotic resistance: zinc feed supplementation of piglets increases the proportion of multi-resistant Escherichia coli in vivo.

    PubMed

    Bednorz, Carmen; Oelgeschläger, Kathrin; Kinnemann, Bianca; Hartmann, Susanne; Neumann, Konrad; Pieper, Robert; Bethe, Astrid; Semmler, Torsten; Tedin, Karsten; Schierack, Peter; Wieler, Lothar H; Guenther, Sebastian

    2013-08-01

    Following the Europe-wide ban of antimicrobial growth promoters, feed supplementation with zinc has increased in livestock breeding. In addition to possible beneficial effects on animal health, feed supplementation with heavy metals is known to influence the gut microbiota and might promote the spread of antimicrobial resistance via co-selection or other mechanisms. As Escherichia coli is among the most important pathogens in pig production and often displays multi-resistant phenotypes, we set out to investigate the influence of zinc feed additives on the composition of the E. coli populations in vivo focusing on phylogenetic diversity and antimicrobial resistance. In a piglet feeding trial, E. coli were isolated from ileum and colon digesta of high dose zinc-supplemented (2500ppm) and background dose (50ppm) piglets (control group). The E. coli population was characterized via pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) for the determination of the phylogenetic background. Phenotypic resistance screening via agar disk diffusion and minimum inhibitory concentration testing was followed by detection of resistance genes for selected clones. We observed a higher diversity of E. coli clones in animals supplemented with zinc compared to the background control group. The proportion of multi-resistant E. coli was significantly increased in the zinc group compared to the control group (18.6% vs. 0%). For several subclones present both in the feeding and the control group we detected up to three additional phenotypic and genotypic resistances in the subclones from the zinc feeding group. Characterization of these subclones suggests an increase in antimicrobial resistance due to influences on plasmid uptake by zinc supplementation, questioning the reasonability of zinc feed additives as a result of the ban of antimicrobial growth promoters.

  13. Comparative effects of metal oxide nanoparticles on human airway epithelial cells and macrophages

    NASA Astrophysics Data System (ADS)

    Rotoli, Bianca Maria; Bussolati, Ovidio; Costa, Anna Luisa; Blosi, Magda; Di Cristo, Luisana; Zanello, Pier Paolo; Bianchi, Massimiliano G.; Visigalli, Rossana; Bergamaschi, Enrico

    2012-09-01

    Among nanomaterials of industrial relevance, metal-based nanoparticles (NPs) are widely used, but their effects on airway cells are relatively poorly characterized. To compare the effects of metal NPs on cells representative of the lung-blood barrier, Calu-3 epithelial cells and Raw264.7 macrophages were incubated with three industrially relevant preparations of TiO2 NPs (size range 4-33 nm), two preparations of CeO2 NPs (9-36 nm) and CuO NPs (25 nm). While Raw264.7 were grown on standard plasticware, Calu-3 cells were seeded on permeable filters, where they form a high-resistance monolayer, providing an in vitro model of the airway barrier. Metal NPs, obtained from industrial sources, were characterized under the conditions adopted for the biological tests. Cytotoxicity was assessed with resazurin method in both epithelial and macrophage cells, while epithelial barrier permeability was monitored measuring the trans-epithelial electrical resistance (TEER). In macrophages, titania and ceria had no significant effect on viability in the whole range of nominal doses tested (15-240 μg/cm2 of monolayer), while CuO NPs produced a marked viability loss. Moreover, only CuO NPs, but not the other NPs, lowered TEER of Calu-3 monolayers, pointing to the impairment of the epithelial barrier. TEER decreased by 30 % at the dose of 10 μg/cm2 of CuO NPs, compared to untreated control, and was abolished at doses ≥80 μg/cm2, in strict correlation with changes in cell viability. These results indicate that (1) CuO NPs increase airway epithelium permeability even at relatively low doses and are significantly toxic for macrophages and airway epithelial cells, likely through the release of Cu ions in the medium; (2) TiO2 and CeO2 NPs do not affect TEER and exhibit little acute toxicity for airway epithelial cells and macrophages; and (3) TEER measurement can provide a simple method to assess the impairment of in vitro airway epithelial barrier model by manufactured nanomaterials.

  14. Antimicrobial Peptide P60.4Ac-Containing Creams and Gel for Eradication of Methicillin-Resistant Staphylococcus aureus from Cultured Skin and Airway Epithelial Surfaces

    PubMed Central

    Haisma, Elisabeth M.; Göblyös, Anikó; Ravensbergen, Bep; Adriaans, Alwin E.; Cordfunke, Robert A.; Schrumpf, Jasmijn; Limpens, Ronald W. A. L.; Schimmel, Kirsten J. M.; den Hartigh, Jan; Hiemstra, Pieter S.; Drijfhout, Jan Wouter; El Ghalbzouri, Abdoelwaheb

    2016-01-01

    We previously found the LL-37-derived peptide P60.4Ac to be effective against methicillin-resistant Staphylococcus aureus (MRSA) on human epidermal models (EMs). The goal of this study was to identify the preferred carrier for this peptide for topical application on skin and mucosal surfaces. We prepared P60.4Ac in three formulations, i.e., a water-in-oil cream with lanolin (Softisan 649), an oil-in-water cream with polyethylene glycol hexadecyl ether (Cetomacrogol), and a hydroxypropyl methylcellulose (hypromellose) 4000 gel. We tested the antimicrobial efficacy of the peptide in these formulations against mupirocin-resistant and -sensitive MRSA strains on EMs and bronchial epithelial models (BEMs). The cytotoxic effects of formulated P60.4Ac on these models were determined using histology and WST-1 and lactate dehydrogenase assays. Moreover, we assessed the stability of the peptide in these formulations with storage for up to 3 months. Killing of MRSA by P60.4Ac in the two creams was less effective than that by P60.4Ac in the hypromellose gel. In agreement with those findings, P60.4Ac in the hypromellose gel was highly effective in eradicating the two MRSA strains from EMs. We found that even 0.1% (wt/wt) P60.4Ac in the hypromellose gel killed >99% of the viable planktonic bacteria and >85% of the biofilm-associated bacteria on EMs. Hypromellose gels containing 0.1% and 0.5% (wt/wt) P60.4Ac effectively reduced the numbers of viable MRSA cells from BEMs by >90%. No cytotoxic effects of P60.4Ac in the hypromellose gel with up to 2% (wt/wt) P60.4Ac on keratinocytes in EMs and in the hypromellose gel with up to 0.5% (wt/wt) P60.4Ac on epithelial cells in BEMs were observed. High-performance liquid chromatography analysis showed that P60.4Ac was stable in the Softisan cream and the hypromellose gel but not in the Cetomacrogol cream. We conclude that P60.4Ac formulated in hypromellose gel is both stable and highly effective in eradicating MRSA from colonized EMs and

  15. Strengthening of oxidation resistant materials for gas turbine applications. [treatment of silicon ceramics for increased flexural strength and impact resistance

    NASA Technical Reports Server (NTRS)

    Kirchner, H. P.

    1974-01-01

    Silicon nitride and silicon carbide ceramics were treated to form compressive surface layers. On the silicon carbide, quenching and thermal exposure treatments were used, and on the silicon nitride, quenching, carburizing, and a combination of quenching and carburizing were used. In some cases substantial improvements in impact resistance and/or flexural strength were observed. The presence of compressive surface stresses was demonstrated by slotted rod tests.

  16. Enhanced Locomotor Activity Is Required to Exert Dietary Restriction-Dependent Increase of Stress Resistance in Drosophila.

    PubMed

    Ghimire, Saurav; Kim, Man Su

    2015-01-01

    Dietary restriction (DR) is known to be one of the most effective interventions to increase stress resistance, yet the mechanisms remain elusive. One of the most obvious DR-induced changes in phenotype is an increase in locomotor activity. Although it is conceptually perceivable that nutritional scarcity should prompt enhanced foraging behavior to garner additional dietary resources, the significance of enhanced movement activity has not been associated with the DR-dependent increase of stress resistance. In this study, we confirmed that flies raised on DR exhibited enhanced locomotive activity and increased stress resistance. Excision of fly wings minimized the DR-induced increase in locomotive activity, which resulted in attenuation of the DR-dependent increase of stress resistance. The possibility that wing clipping counteracts the DR by coercing flies to have more intake was ruled out since it did not induce any weight gain. Rather it was found that elimination of reactive oxygen species (ROS) that is enhanced by DR-induced upregulation of expression of antioxidant genes was significantly reduced by wing clipping. Collectively, our data suggests that DR increased stress resistance by increasing the locomotor activity, which upregulated expression of protective genes including, but not limited to, ROS scavenger system.

  17. Expression of the mef(E) gene encoding the macrolide efflux pump protein increases in Streptococcus pneumoniae with increasing resistance to macrolides.

    PubMed

    Wierzbowski, Aleksandra K; Boyd, Dave; Mulvey, Michael; Hoban, Daryl J; Zhanel, George G

    2005-11-01

    Active macrolide efflux is a major mechanism of macrolide resistance in Streptococcus pneumoniae in many parts of the world, especially North America. In Canada, this active macrolide efflux in S. pneumoniae is predominantly due to acquisition of the mef(E) gene. In the present study, we assessed the mef(E) gene sequence as well as mef(E) expression in variety of low- and high-level macrolide-resistant, clindamycin-susceptible (M-phenotype) S. pneumoniae isolates (erythromycin MICs, 1 to 32 microg/ml; clindamycin MICs, < or = 0.25 microg/ml). Southern blot hybridization with mef(E) probe and EcoRI digestion and relative real-time reverse transcription-PCR were performed to study the mef(E) gene copy number and expression. Induction of mef(E) expression was analyzed by Etest susceptibility testing pre- and postincubation with subinhibitory concentrations of erythromycin, clarithromycin, azithromycin, telithromycin, and clindamycin. The macrolide efflux gene, mef(E), was shown to be a single-copy gene in all 23 clinical S. pneumoniae isolates tested, and expression post-macrolide induction increased 4-, 6-, 20-, and 200-fold in isolates with increasing macrolide resistance (erythromycin MICs 2, 4, 8, and 32 microg/ml, respectively). Sequencing analysis of the macrolide efflux genetic assembly (mega) revealed that mef(E) had a 16-bp deletion 153 bp upstream of the putative start codon in all 23 isolates. A 119-bp intergenic region between mef(E) and mel was sequenced, and a 99-bp deletion was found in 11 of the 23 M-phenotype S. pneumoniae isolates compared to the published mega sequence. However, the mef(E) gene was fully conserved among both high- and low-level macrolide-resistant isolates. In conclusion, increased expression of mef(E) is associated with higher levels of macrolide resistance in macrolide-resistant S. pneumoniae.

  18. Patterns of recruitment and injury in a heterogeneous airway network model

    PubMed Central

    Stewart, Peter S.; Jensen, Oliver E.

    2015-01-01

    In respiratory distress, lung airways become flooded with liquid and may collapse due to surface-tension forces acting on air–liquid interfaces, inhibiting gas exchange. This paper proposes a mathematical multiscale model for the mechanical ventilation of a network of occluded airways, where air is forced into the network at a fixed tidal volume, allowing investigation of optimal recruitment strategies. The temporal response is derived from mechanistic models of individual airway reopening, incorporating feedback on the airway pressure due to recruitment. The model accounts for stochastic variability in airway diameter and stiffness across and between generations. For weak heterogeneity, the network is completely ventilated via one or more avalanches of recruitment (with airways recruited in quick succession), each characterized by a transient decrease in the airway pressure; avalanches become more erratic for airways that are initially more flooded. However, the time taken for complete ventilation of the network increases significantly as the network becomes more heterogeneous, leading to increased stresses on airway walls. The model predicts that the most peripheral airways are most at risk of ventilation-induced damage. A positive-end-expiratory pressure reduces the total recruitment time but at the cost of larger stresses exerted on airway walls. PMID:26423440

  19. Selection for increased desiccation resistance in Drosophila melanogaster: Additive genetic control and correlated responses for other stresses

    SciTech Connect

    Hoffmann, A.A.; Parsons, P.A. )

    1989-08-01

    Previously we found that Drosophila melanogaster lines selected for increased desiccation resistance have lowered metabolic rate and behavioral activity levels, and show correlated responses for resistance to starvation and a toxic ethanol level. These results were consistent with a prediction that increased resistance to many environmental stresses may be genetically correlated because of a reduction in metabolic energy expenditure. Here we present experiments on the genetic basis of the selection response and extend the study of correlated responses to other stresses. The response to selection was not sex-specific and involved X-linked and autosomal genes acting additively. Activity differences contributed little to differences in desiccation resistance between selected and control lines. Selected lines had lower metabolic rates than controls in darkness when activity was inhibited. Adults from selected lines showed increased resistance to a heat shock, {sup 60}Co-gamma-radiation, and acute ethanol and acetic acid stress. The desiccation, ethanol and starvation resistance of isofemale lines set up from the F2s of a cross between one of the selected and one of the control lines were correlated. Selected and control lines did not differ in ether-extractable lipid content or in resistance to acetone, ether or a cold shock.

  20. Increased monooxygenase activity associated with resistance to permethrin in Pediculus humanus capitis (Anoplura: Pediculidae) from Argentina.

    PubMed

    González Audino, P; Barrios, S; Vassena, C; Mougabure Cueto, G; Zerba, E; Picollo, M I

    2005-05-01

    We studied the profile of permethrin resistance in populations of head lice infesting children 6-12 yr old in schools and their homes in and around Buenos Aires, Argentina. Five permethrin-resistant populations with different levels of resistance were collected: Hogar Loyola (HL), Republica de Turquia (RT), Hogar Mitre (HM), Guardia de Honor (GH), and Ricardo Guiraldes (RG). One susceptible population, Bandera Argentina (BA), also was collected. Their level of resistance was evaluated, and results showed resistance ratios of 13 for HL, 16 for RT, 22 for HM, 61 for GH, and 69 for RG. To elucidate the possible involvement of the cytochrome P450 monooxygenase system in conferring permethrin resistance, ethoxycoumarin-O-deethylase (ECOD) activity was measured in abdomens of individual third instars and adults by using a fluorometric assay. The ECOD activity was lower in the susceptible BA population (4.7 ng per louse) than in the resistant ones (13.7 ng per louse for RG, 12.3 ng per louse for GH, 8.6 ng per louse for RT, and 8.2 ng per louse for HL). ECOD activity was significantly correlated with the level of resistance in the field populations (r = 0.97, P = 0.0009), suggesting a role for cytochrome monooxygenase P450 system in permethrin resistance by head louse, Pediculus humanus capitis De Geer.

  1. Mutant IDH1-driven cellular transformation increases RAD51-mediated homologous recombination and temozolomide resistance.

    PubMed

    Ohba, Shigeo; Mukherjee, Joydeep; See, Wendy L; Pieper, Russell O

    2014-09-01

    Isocitrate dehydrogenase 1 (IDH1) mutations occur in most lower grade glioma and not only drive gliomagenesis but are also associated with longer patient survival and improved response to temozolomide. To investigate the possible causative relationship between these events, we introduced wild-type (WT) or mutant IDH1 into immortalized, untransformed human astrocytes, then monitored transformation status and temozolomide response. Temozolomide-sensitive parental cells exhibited DNA damage (γ-H2AX foci) and a prolonged G2 cell-cycle arrest beginning three days after temozolomide (100 μmol/L, 3 hours) exposure and persisting for more than four days. The same cells transformed by expression of mutant IDH1 exhibited a comparable degree of DNA damage and cell-cycle arrest, but both events resolved significantly faster in association with increased, rather than decreased, clonogenic survival. The increases in DNA damage processing, cell-cycle progression, and clonogenicity were unique to cells transformed by mutant IDH1, and were not noted in cells transformed by WT IDH1 or an oncogenic form (V12H) of Ras. Similarly, these effects were not noted following introduction of mutant IDH1 into Ras-transformed cells or established glioma cells. They were, however, associated with increased homologous recombination (HR) and could be reversed by the genetic or pharmacologic suppression of the HR DNA repair protein RAD51. These results show that mutant IDH1 drives a unique set of transformative events that indirectly enhance HR and facilitate repair of temozolomide-induced DNA damage and temozolomide resistance. The results also suggest that inhibitors of HR may be a viable means to enhance temozolomide response in IDH1-mutant glioma.

  2. Peripheral airway obstruction in primary pulmonary hypertension

    PubMed Central

    Meyer, F; Ewert, R; Hoeper, M; Olschewski, H; Behr, J; Winkler, J; Wilkens, H; Breuer, C; Kubler, W; Borst, M

    2002-01-01

    Background: As there is controversy about changes in lung function in primary pulmonary hypertension (PPH), lung mechanics were assessed with a focus on expiratory airflow in relation to pulmonary haemodynamics. Methods: A cross sectional study was performed in 64 controls and 171 patients with PPH (117 women) of mean (SD) age 45 (13) years, pulmonary artery pressure (PAPmean) 57 (15) mm Hg, and pulmonary vascular resistance 1371 (644) dyne.s/cm5. Results: Mean (SD) total lung capacity was similar in patients with PPH and controls (98 (12)% predicted v 102 (17)% predicted, mean difference –4 (95% confidence interval (CI) –7.89 to –0.11); residual volume (RV) was increased (118 (24)% predicted v 109 (27)% predicted, mean difference 9 (95% CI 1.86 to 16.14); and vital capacity (VC) was decreased (91 (16)% predicted v 102 (10)% predicted, mean difference –11 (95% CI 15.19 to –6.80). RV/TLC was increased (117 (27)% predicted v 97 (29)% predicted, mean difference 20 (95% CI 12.3 to 27.8)) and correlated with PAPmean (r=0.31, p<0.001). In patients with PAPmean above the median of 56 mm Hg, RV/TLC was further increased (125 (32)% predicted v 111 (22)% predicted, mean difference –14 (95% CI –22.2 to –5.8)). Expiratory flow-volume curves were reduced and curvilinear in patients with PPH. Conclusions: Peripheral airway obstruction is common in PPH and is more pronounced in severe disease. This may contribute to symptoms. Reversibility of bronchodilation and relation to exercise capacity need further evaluation. PMID:12037220

  3. The Diacetyl-exposed Human Airway Epithelial Secretome: New Insights Into Flavoring Induced Airways Disease.

    PubMed

    Brass, David M; Gwinn, William M; Valente, Ashlee M; Kelly, Francine L; Brinkley, Christie D; Nagler, Andrew E; Moseley, M Arthur; Morgan, Daniel L; Palmer, Scott M; Foster, Matthew W

    2017-03-01

    Bronchiolitis obliterans (BO) is an increasingly important lung disease characterized by fibroproliferative airway lesions and decrements in lung function. Occupational exposure to the artificial food flavoring ingredient diacetyl, commonly used to impart a buttery flavor to microwave popcorn, has been associated with BO development. In the occupational setting, diacetyl vapor is first encountered by the airway epithelium. To better understand the effects of diacetyl vapor on the airway epithelium we used an unbiased proteomic approach to characterize both the apical and basolateral secretomes of air liquid interface cultures of primary human airway epithelial cells from four unique donors after exposure to an occupationally relevant ~1100 ppm of diacetyl vapor or PBS as a control on alternating days. Basolateral and apical supernatants collected 48 hours after the third exposure were analyzed using one-dimensional liquid chromatography tandem mass spectrometry. Paired t-tests adjusted for multiple comparisons were used to assess differential expression between diacetyl and PBS exposure. Of the significantly differentially expressed proteins identified, 61 were unique to the apical secretome, 81 were unique to the basolateral secretome and there were an additional 11 present in both. Pathway enrichment analysis using publicly available databases reveals that proteins associated with matrix remodeling including degradation, assembly and new matrix organization were over-represented in the data sets. Similarly, protein modifiers of epidermal growth factor receptor signaling were significantly altered. The ordered changes in protein expression suggest that the airway epithelial response to diacetyl may contribute to BO pathogenesis.

  4. Protein tyrosine phosphatase SHP2 regulates TGF-β1 production in airway epithelia and asthmatic airway remodeling in mice

    PubMed Central

    Qin, X.-J.; Zhang, G.-S.; Zhang, X.; Qiu, Z.-W.; Wang, P.-L.; Li, Y.-W.; Li, W.; Xie, Q.-M.; Ke, Y.-H.; Lee, J. J.; Shen, H.-H.

    2014-01-01

    Background Transforming growth factor (TGF)-β1 produced in airway epithelia has been suggested as a contributor to the airway remodeling observed in asthma patients. The protein tyrosine phosphatase SHP2 is a demonstrable modulator of TGF-β1 production and thus a potential regulator of airway remodeling. Objectives To define the signal event by which SHP2 regulates asthmatic responses in airway epithelial cells by using a mouse model of experimental OVA-induced airway remodeling. Methods The airways of Shp2flox/flox mice were infected with recombinant adenovirus vectors expressing a Cre recombinase–green fluorescence protein (GFP) fusion protein as part of allergen provocation studies using mice sensitized with ovalbumin (OVA) and repeatedly challenged with OVA. Several endpoint pathologies were assessed, including airway hyper-responsiveness (AHR), lung inflammatory score, peribronchial collagen deposition, and α-smooth muscle actin (SMA) hyperplasia. In vitro studies using airway epithelial cells (BEAS-2B) were used to investigate the role of SHP2 in the regulation of pulmonary remodeling events, including the expression of collagen, α-SMA, and TGF-β1. Results Chronic OVA challenges in wild-type mice resulted in airway remodeling and lung dysfunction (e.g., increased inflammatory scores, collagen deposition (fibrosis), smooth muscle hyperplasia, and a significant increase in AHR). These endpoint pathology metrics were each significantly attenuated by conditional shp2 gene knockdown in airway epithelia. In vitro studies using BEAS-2B cells also demonstrated that the level of TGF-β1 production by these cells correlated with the extent of shp2 gene expression. Conclusions SHP2 activities in airway epithelial cells appear to modulate TGF-β1 production and, in turn, regulate allergic airway remodeling following allergen provocation. Clinical Implications Our findings identify SHP2 as a previously underappreciated contributor to the airway remodeling and lung

  5. Techniques of assessing small airways dysfunction

    PubMed Central

    McNulty, William; Usmani, Omar S.

    2014-01-01

    The small airways are defined as those less than 2 mm in diameter. They are a major site of pathology in many lung diseases, not least chronic obstructive pulmonary disease (COPD) and asthma. The small airways are frequently involved early in the course of these diseases, with significant pathology demonstrable often before the onset of symptoms or changes in spirometry and imaging. Despite their importance, they have proven relatively difficult to study. This is in part due to their relative inaccessibility to biopsy and their small size which makes their imaging difficult. Traditional lung function tests may only become abnormal once there is a significant burden of disease within them. This has led to the term ‘the quiet zone’ of the lung. In recent years, more specialised tests have been developed which may detect these changes earlier, perhaps offering the possibility of earlier diagnosis and intervention. These tests are now moving from the realms of clinical research laboratories into routine clinical practice and are increasingly useful in the diagnosis and monitoring of respiratory diseases. This article gives an overview of small airways physiology and some of the routine and more advanced tests of airway function. PMID:26557240

  6. Resistance exercise increase lean body mass and improves basal and hepatic insulin sensitivity in obese adolescents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Little is known about the metabolic effects of resistance exercise, for instance, weight lifting. We studied whether a resistance exercise program improves insulin sensitivity and glucose metabolism in sedentary obese adolescents. Elevn obese subjects (15.7 +/- 0.4 year; 35.4 +/- 0.8 kg/m2; 41.3 +/-...

  7. Antimicrobial susceptibility testing for Helicobacter pylori in times of increasing antibiotic resistance.

    PubMed

    Smith, Sinéad M; O'Morain, Colm; McNamara, Deirdre

    2014-08-07

    The gram-negative bacterium Helicobacter pylori (H. pylori) causes chronic gastritis, gastric and duodenal ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Treatment is recommended in all symptomatic patients. The current treatment options for H. pylori infection are outlined in this review in light of the recent challenges in eradication success, largely due to the rapid emergence of antibiotic resistant strains of H. pylori. Antibiotic resistance is a constantly evolving process and numerous studies have shown that the prevalence of H. pylori antibiotic resistance varies significantly from country to country, and even between regions within the same country. In addition, recent data has shown that previous antibiotic use is associated with harbouring antibiotic resistant H. pylori. Local surveillance of antibiotic resistance is warranted to guide clinicians in their choice of therapy. Antimicrobial resistance is assessed by H. pylori culture and antimicrobial susceptibility testing. Recently developed molecular tests offer an attractive alternative to culture and allow for the rapid molecular genetic identification of H. pylori and resistance-associated mutations directly from biopsy samples or bacterial culture material. Accumulating evidence indicates that surveillance of antimicrobial resistance by susceptibility testing is feasible and necessary to inform clinicians in their choice of therapy for management of H. pylori infection.

  8. Collateral damage: rapid exposure-induced evolution of pesticide resistance leads to increased susceptibility to parasites.

    PubMed

    Jansen, Mieke; Stoks, Robby; Coors, Anja; van Doorslaer, Wendy; de Meester, Luc

    2011-09-01

    Although natural populations may evolve resistance to anthropogenic stressors such as pollutants, this evolved resistance may carry costs. Using an experimental evolution approach, we exposed different Daphnia magna populations in outdoor containers to the carbamate pesticide carbaryl and control conditions, and assessed the resulting populations for both their resistance to carbaryl as well as their susceptibility to infection by the widespread bacterial microparasite Pasteuria ramosa. Our results show that carbaryl selection led to rapid evolution of carbaryl resistance with seemingly no cost when assessed in a benign environment. However, carbaryl-resistant populations were more susceptible to parasite infection than control populations. Exposure to both stressors reveals a synergistic effect on sterilization rate by P. ramosa, but this synergism did not evolve under pesticide selection. Assessing costs of rapid adaptive evolution to anthropogenic stress in a semi-natural context may be crucial to avoid too optimistic predictions for the fitness of the evolving populations.

  9. Expression of G-Ry derived from the potato (Solanum tuberosum L.) increases PVY(O) resistance.

    PubMed

    Lee, Changsu; Park, Jaeyoung; Hwang, Indeok; Park, Yoonkyung; Cheong, Hyeonsook

    2010-06-23

    In Solanaceae, potato virus Y(O) (PVY(O)) is a widespread virus leading to severe damages such as necrosis, molting, and yield reduction. The resistance Y gene (Ry gene) of potato specifically confers resistance to PVY infection. Previously, potatoes resistant to PVY(O) infection were screened among the 32 Korean cultivars. 'Golden Valley' displayed the most resistance to PVY(O) infection. 'Golden Valley''s Ry gene (G-Ry) was cloned from 'Golden Valley', and the function was investigated. G-Ry protein contains 1134 amino acid residues and is structurally similar to the Y-1, which confers resistance to PVY infection in Solanum tuberosum subsp. andigena. To generate a PVY(O)-resistant potato, the G-Ry gene has been introduced into 'Winter Valley', the cultivar most susceptible to PVY(O) infection among the 32 Korean cultivars. Transgenic 'Winter Valley' ('Winter Valley'-G) showed an increased resistance to PVY infection. This approach may ultimately lead to the development of a virus-resistant plant.

  10. Hypothalamic POMC Deficiency Improves Glucose Tolerance Despite Insulin Resistance by Increasing Glycosuria

    PubMed Central

    Adams, Jessica M.; Fagel, Brian; Lam, Daniel D.; Qi, Nathan; Rubinstein, Marcelo

    2016-01-01

    Hypothalamic proopiomelanocortin (POMC) is essential for the physiological regulation of energy balance; however, its role in glucose homeostasis remains less clear. We show that hypothalamic arcuate nucleus (Arc)POMC-deficient mice, which develop severe obesity and insulin resistance, unexpectedly exhibit improved glucose tolerance and remain protected from hyperglycemia. To explain these paradoxical phenotypes, we hypothesized that an insulin-independent pathway is responsible for the enhanced glucose tolerance. Indeed, the mutant mice demonstrated increased glucose effectiveness and exaggerated glycosuria relative to wild-type littermate controls at comparable blood glucose concentrations. Central administration of the melanocortin receptor agonist melanotan II in mutant mice reversed alterations in glucose tolerance and glycosuria, whereas, conversely, administration of the antagonist Agouti-related peptide (Agrp) to wild-type mice enhanced glucose tolerance. The glycosuria of ArcPOMC-deficient mice was due to decreased levels of renal GLUT 2 (rGLUT2) but not sodium–glucose cotransporter 2 and was associated with reduced renal catecholamine content. Epinephrine treatment abolished the genotype differences in glucose tolerance and rGLUT2 levels, suggesting that reduced renal sympathetic nervous system (SNS) activity is the underlying mechanism for the observed glycosuria and improved glucose tolerance in ArcPOMC-deficient mice. Therefore, the ArcPOMC-SNS-rGLUT2 axis is potentially an insulin-independent therapeutic target to control diabetes. PMID:26467632

  11. Hypothalamic POMC Deficiency Improves Glucose Tolerance Despite Insulin Resistance by Increasing Glycosuria.

    PubMed

    Chhabra, Kavaljit H; Adams, Jessica M; Fagel, Brian; Lam, Daniel D; Qi, Nathan; Rubinstein, Marcelo; Low, Malcolm J

    2016-03-01

    Hypothalamic proopiomelanocortin (POMC) is essential for the physiological regulation of energy balance; however, its role in glucose homeostasis remains less clear. We show that hypothalamic arcuate nucleus (Arc)POMC-deficient mice, which develop severe obesity and insulin resistance, unexpectedly exhibit improved glucose tolerance and remain protected from hyperglycemia. To explain these paradoxical phenotypes, we hypothesized that an insulin-independent pathway is responsible for the enhanced glucose tolerance. Indeed, the mutant mice demonstrated increased glucose effectiveness and exaggerated glycosuria relative to wild-type littermate controls at comparable blood glucose concentrations. Central administration of the melanocortin receptor agonist melanotan II in mutant mice reversed alterations in glucose tolerance and glycosuria, whereas, conversely, administration of the antagonist Agouti-related peptide (Agrp) to wild-type mice enhanced glucose tolerance. The glycosuria of ArcPOMC-deficient mice was due to decreased levels of renal GLUT 2 (rGLUT2) but not sodium-glucose cotransporter 2 and was associated with reduced renal catecholamine content. Epinephrine treatment abolished the genotype differences in glucose tolerance and rGLUT2 levels, suggesting that reduced renal sympathetic nervous system (SNS) activity is the underlying mechanism for the observed glycosuria and improved glucose tolerance in ArcPOMC-deficient mice. Therefore, the ArcPOMC-SNS-rGLUT2 axis is potentially an insulin-independent therapeutic target to control diabetes.

  12. Dragon enhances BMP signaling and increases transepithelial resistance in kidney epithelial cells.

    PubMed

    Xia, Yin; Babitt, Jodie L; Bouley, Richard; Zhang, Ying; Da Silva, Nicolas; Chen, Shanzhuo; Zhuang, Zhenjie; Samad, Tarek A; Brenner, Gary J; Anderson, Jennifer L; Hong, Charles C; Schneyer, Alan L; Brown, Dennis; Lin, Herbert Y

    2010-04-01

    The neuronal adhesion protein Dragon acts as a bone morphogenetic protein (BMP) coreceptor that enhances BMP signaling. Given the importance of BMP signaling in nephrogenesis and its putative role in the response to injury in the adult kidney, we studied the localization and function of Dragon in the kidney. We observed that Dragon localized predominantly to the apical surfaces of tubular epithelial cells in the thick ascending limbs, distal convoluted tubules, and collecting ducts of mice. Dragon expression was weak in the proximal tubules and glomeruli. In mouse inner medullary collecting duct (mIMCD3) cells, Dragon generated BMP signals in a ligand-dependent manner, and BMP4 is the predominant endogenous ligand for the Dragon coreceptor. In mIMCD3 cells, BMP4 normally signaled through BMPRII, but Dragon enhanced its signaling through the BMP type II receptor ActRIIA. Dragon and BMP4 increased transepithelial resistance (TER) through the Smad1/5/8 pathway. In epithelial cells isolated from the proximal tubule and intercalated cells of collecting ducts, we observed coexpression of ActRIIA, Dragon, and BMP4 but not BMPRII. Taken together, these results suggest that Dragon may enhance BMP signaling in renal tubular epithelial cells and maintain normal renal physiology.

  13. Altered Epithelial Gene Expression in Peripheral Airways of Severe Asthma

    PubMed Central

    Singhania, Akul; Rupani, Hitasha; Jayasekera, Nivenka; Lumb, Simon; Hales, Paul; Gozzard, Neil; Davies, Donna E.

    2017-01-01

    Management of severe asthma remains a challenge despite treatment with glucocorticosteroid therapy. The majority of studies investigating disease mechanisms in treatment-resistant severe asthma have previously focused on the large central airways, with very few utilizing transcriptomic approaches. The small peripheral airways, which comprise the majority of the airway surface area, remain an unexplored area in severe asthma and were targeted for global epithelial gene expression profiling in this study. Differences between central and peripheral airways were evaluated using transcriptomic analysis (Affymetrix HG U133 plus 2.0 GeneChips) of epithelial brushings obtained from severe asthma patients (N = 17) and healthy volunteers (N = 23). Results were validated in an independent cohort (N = 10) by real-time quantitative PCR. The IL-13 disease signature that is associated with an asthmatic phenotype was upregulated in severe asthmatics compared to healthy controls but was predominantly evident within the peripheral airways, as were genes related to mast cell presence. The gene expression response associated with glucocorticosteroid therapy (i.e. FKBP5) was also upregulated in severe asthmatics compared to healthy controls but, in contrast, was more pronounced in central airways. Moreover, an altered epithelial repair response (e.g. FGFBP1) was evident across both airway sites reflecting a significant aspect of disease in severe asthma unadressed by current therapies. A transcriptomic approach to understand epithelial activation in severe asthma has thus highlighted the need for better-targeted therapy to the peripheral airways in severe asthma, where the IL-13 disease signature persists despite treatment with currently available therapy. PMID:28045928

  14. Altered Epithelial Gene Expression in Peripheral Airways of Severe Asthma.

    PubMed

    Singhania, Akul; Rupani, Hitasha; Jayasekera, Nivenka; Lumb, Simon; Hales, Paul; Gozzard, Neil; Davies, Donna E; Woelk, Christopher H; Howarth, Peter H

    2017-01-01

    Management of severe asthma remains a challenge despite treatment with glucocorticosteroid therapy. The majority of studies investigating disease mechanisms in treatment-resistant severe asthma have previously focused on the large central airways, with very few utilizing transcriptomic approaches. The small peripheral airways, which comprise the majority of the airway surface area, remain an unexplored area in severe asthma and were targeted for global epithelial gene expression profiling in this study. Differences between central and peripheral airways were evaluated using transcriptomic analysis (Affymetrix HG U133 plus 2.0 GeneChips) of epithelial brushings obtained from severe asthma patients (N = 17) and healthy volunteers (N = 23). Results were validated in an independent cohort (N = 10) by real-time quantitative PCR. The IL-13 disease signature that is associated with an asthmatic phenotype was upregulated in severe asthmatics compared to healthy controls but was predominantly evident within the peripheral airways, as were genes related to mast cell presence. The gene expression response associated with glucocorticosteroid therapy (i.e. FKBP5) was also upregulated in severe asthmatics compared to healthy controls but, in contrast, was more pronounced in central airways. Moreover, an altered epithelial repair response (e.g. FGFBP1) was evident across both airway sites reflecting a significant aspect of disease in severe asthma unadressed by current therapies. A transcriptomic approach to understand epithelial activation in severe asthma has thus highlighted the need for better-targeted therapy to the peripheral airways in severe asthma, where the IL-13 disease signature persists despite treatment with currently available therapy.

  15. Identification of mechanisms involved in the acute airway toxicity induced by parathion.

    PubMed

    Segura, P; Chávez, J; Montaño, L M; Vargas, M H; Delaunois, A; Carbajal, V; Gustin, P

    1999-12-01

    Organophosphates are still widely used worldwide and cause thousands of intoxications every year. In this work we investigated the mechanisms of parathion (Pth) airway toxicity, using biochemical and functional approaches. A plethysmographic technique for unrestrained guinea pigs was used to analyze Pth-induced modifications of airway mechanics and responsiveness to acetylcholine (ACh: 0.1-3.2 mg/ml, 2-min inhalation each dose). The isolated perfused rabbit lung preparation was used to study the acute effects of Pth on airway responsiveness to ACh (10(-8)-10(-3) M), histamine (10(-8)-10(-3) M) and substance P (10(-10)-10(-6) M), pulmonary acetylcholinesterase inhibition and cytochrome P450 (P450) activity, and their modifications with previous administration of Pth (1 mg/kg s.c. daily, 7 days). We found that: (1) In guinea pigs Pth (3.2-17 mg/kg i.p.) produced a dose-dependent increase in a lung resistance index (iRL), which was greatly reverted (approximately 50%) by salbutamol (2 mg/ml, 2-min inhalation, or 10 microg/kg i.p.). This salbutamol effect was transient (5-10 min), suggesting that this bronchodilator triggered additional obstructive mechanisms. (2) Pth increased the water content in lung parenchyma samples, but not in trachea or bronchi, and augmented the respiratory secretions measured through monosaccharide content in bronchoalveolar lavage. (3) The increase in iRL was greater in female animals, probably due to a higher P450 basal activity, and completely blocked by pharmacological inhibition of P450 with piperonyl butoxide (500 mg/kg i.p.). (4) In male guinea pigs a subclinical dose of Pth (10 mg/kg i.p.) induced airway hyperresponsiveness to ACh. In isolated perfused rabbit lung Pth (10(-6) M) produced airway hyperresponsiveness to ACh and histamine, the latter prevented by atropine (10(-5) M). (5) Repetitive exposure to subclinical doses (1 mg/kg s.c.) of Pth during 1 week caused approximately 80% inhibition of P450 activity in rabbits, which was

  16. Vitamin E supplementation increases the resistance of both LDL and HDL to oxidation and increases cholesteryl ester transfer activity.

    PubMed

    Arrol, S; Mackness, M I; Durrington, P N

    2000-05-01

    There is increasing evidence that lipid peroxidation and oxidative modification of low density lipoprotein (LDL) is important in atherogenesis. Evidence that antioxidant therapy decreases mortality is, however, inconclusive. We have examined the effects of vitamin E on the susceptibility of LDL and high density lipoprotein (HDL) to oxidation, and on cholesteryl ester heteroexchange in an in vitro system using autologous serum lipoproteins. Vitamin E in doses of 200 and 400 mg/day were administered orally to 21 healthy volunteers (12 females and nine males) aged between 23 and 50 years, and to 16 healthy volunteers (eight females and eight males) aged between 22 and 51 years for 50 days, respectively. Fasting serum lipoproteins, susceptibility of lipoproteins to oxidation and cholesteryl ester transfer activity (CETA) were measured before and after vitamin E supplementation. Serum lipoprotein and lipid concentrations did not change significantly in either group. The LDL-conjugated diene (CD) lag phase during incubation with Cu(2+) was increased by 157% (110-232%) (median (interquartile range)) (P<0.05) on vitamin E (200 mg/day) and by 235% (185-259%) (P<0.0001) on 400 mg/day. The lag phases for LDL-lipid peroxide (LPO) generation were also significantly increased by 146% (122-192%) (P<0.005) and 177% (101-267%) (P<0.005), respectively. The HDL-CD lag phase also increased on both doses 140% (115-169%) (P<0.005) and 171% (122-192%) (P<0.005), as did the HDL-LPO lag phase by 123% (104-153%) (P<0.05) on 200 mg/day and 240% (97-360%) (P<0.005) on 400 mg daily. Cholesteryl ester transfer activity from HDL to very low and low density lipoproteins significantly increased from 12. 7+/-2.6 (mean+/-SEM) to 16+/-3.4 nmol/ml/h (P<0.05) on 200 mg/daily and 10.4+/-2.0 to 19.2+/-3.3 nmol/ml/h (P<0.005) on vitamin E, 400mg day. Thus, vitamin E (200 and 400mg daily) significantly decreased the susceptibility of LDL and HDL to oxidation in vitro. However, the increase in CETA

  17. Increased disease resistance and enzyme activity induced by ethylene and ethylene production of black rot infected sweet potato tissue.

    PubMed

    Stahmann, M A; Clare, B G; Woodbury, W

    1966-11-01

    Exposure of root tissue from a susceptible variety of sweet potato to low concentrations of ethylene induced a resistance to infection by Ceratocystis fimbriata and an increase in the activity of peroxidase and polyphenoloxidase in the tissue. Susceptible tissue that was inoculated with a pathogenic strain of C. fimbriata or a nonpathogenic strain that can induce resistance liberated more ethylene into closed chambers than tissue inoculated with strains that did not induce resistance. It is suggested that ethylene may be a stimulus that diffuses from infected areas into adjoining tissue to initiate metabolic changes which may lead to disease resistance. Polyphenol oxidase but not peroxidase activity was increased in slices of potato tubers and parsnip roots treated with ethylene. The activity of these enzymes in root tissue of carrot, radish or turnip was not altered by ethylene treatment.

  18. Increases in cytoplasmic dopamine compromise the normal resistance of the nucleus accumbens to methamphetamine neurotoxicity.

    PubMed

    Thomas, David M; Francescutti-Verbeem, Dina M; Kuhn, Donald M

    2009-06-01

    Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the caudate-putamen (CPu) where long-term DA depletion and microglial activation are most evident. Even damage within the CPu is remarkably heterogenous with lateral and ventral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared of the damage that accompanies binge METH intoxication. Increases in cytoplasmic DA produced by reserpine, L-DOPA or clorgyline prior to METH uncover damage in the NAc as evidenced by microglial activation and depletion of DA, tyrosine hydroxylase (TH), and the DA transporter. These effects do not occur in the NAc after treatment with METH alone. In contrast to the CPu where DA, TH, and DA transporter levels remain depleted chronically, DA nerve ending alterations in the NAc show a partial recovery over time. None of the treatments that enhance METH toxicity in the NAc and CPu lead to losses of TH protein or DA cell bodies in the substantia nigra or the ventral tegmentum. These data show that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of METH to include brain structures not normally targeted for damage by METH alone. The resistance of the NAc to METH-induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of METH neurotoxicity by alterations in DA homeostasis is significant in light of the important roles played by this brain structure.

  19. EGFR Activation Increases Parathyroid Hyperplasia and Calcitriol Resistance in Kidney Disease

    PubMed Central

    Arcidiacono, Maria Vittoria; Sato, Tetsuhiko; Alvarez-Hernandez, Daniel; Yang, Jing; Tokumoto, Masanori; Gonzalez-Suarez, Ignacio; Lu, Yan; Tominaga, Yoshihiro; Cannata-Andia, Jorge; Slatopolsky, Eduardo; Dusso, Adriana S.

    2008-01-01

    Calcitriol, acting through vitamin D receptors (VDR) in the parathyroid, suppresses parathyroid hormone synthesis and cell proliferation. In secondary hyperparathyroidism (SH), VDR content is reduced as hyperplasia becomes more severe, limiting the efficacy of calcitriol. In a rat model of SH, activation of the EGF receptor (EGFR) by TGF-α is required for the development of parathyroid hyperplasia, but the relationship between EGFR activation and reduced VDR content is unknown. With the use of the same rat model, it was found that pharmacologic inhibition of EGFR activation with erlotinib prevented the upregulation of parathyroid TGF-α, the progression of growth, and the reduction of VDR. Increased TGF-α/EGFR activation induced the synthesis of liver-enriched inhibitory protein, a potent mitogen and the dominant negative isoform of the transcription factor CCAAT enhancer binding protein-β, in human hyperplastic parathyroid glands and in the human epidermoid carcinoma cell line A431, which mimics hyperplastic parathyroid cells. Increases in liver-enriched inhibitory protein directly correlated with proliferating activity and, in A431 cells, reduced VDR expression by antagonizing CCAAT enhancer binding protein-β transactivation of the VDR gene. Similarly, in nodular hyperplasia, which is the most severe form of SH and the most resistant to calcitriol therapy, higher TGF-α activation of the EGFR was associated with an 80% reduction in VDR mRNA levels. Thus, in SH, EGFR activation is the cause of both hyperplastic growth and VDR reduction and therefore influences the efficacy of therapy with calcitriol. PMID:18216322

  20. Mitochondrial Transplantation Attenuates Airway Hyperresponsiveness by Inhibition of Cholinergic Hyperactivity

    PubMed Central

    Su, Yuan; Zhu, Liping; Yu, Xiangyuan; Cai, Lei; Lu, Yankai; Zhang, Jiwei; Li, Tongfei; Li, Jiansha; Xia, Jingyan; Xu, Feng; Hu, Qinghua

    2016-01-01

    Increased cholinergic activity has been highlighted in the pathogenesis of airway hyperresponsiveness, and alternations of mitochondrial structure and function appear to be involved in many lung diseases including airway hyperresponsiveness. It is crucial to clarify the cause-effect association between mitochondrial dysfunction and cholinergic hyperactivity in the pathogenesis of airway hyperresponsiveness. Male SD rats and cultured airway epithelial cells were exposed to cigarette smoke plus lipopolysaccharide administration; mitochondria isolated from airway epithelium were delivered into epithelial cells in vitro and in vivo. Both the cigarette smoke plus lipopolysaccharide-induced cholinergic hyperactivity in vitro and the airway hyperresponsiveness to acetylcholine in vivo were reversed by the transplantation of exogenous mitochondria. The rescue effects of exogenous mitochondria were imitated by the elimination of excessive reactive oxygen species or blockage of muscarinic M3 receptor, but inhibited by M receptor enhancer. Mitochondrial transplantation effectively attenuates cigarette smoke plus lipopolysaccharide-stimulated airway hyperresponsiveness through the inhibition of ROS-enhanced epithelial cholinergic hyperactivity. PMID:27279915

  1. Carinal and tubular airway particle concentrations in the large airways of non-smokers in the general population: evidence for high particle concentration at airway carinas.

    PubMed Central

    Churg, A; Vedal, S

    1996-01-01

    OBJECTIVE: To evaluate the extent to which human airway carinas accumulate ambient atmospheric particles, a newly developed technique was used to micro-dissect and analyse particle concentration in tubular segments and carinas of the large airways of 10 necropsy lungs from non-smokers from the general population of Vancouver. METHODS: Ratios of the particle concentrations on the carinas to the tubular segment immediately preceding it were measured with analytical electron microscopy for the mainstem bronchus, upper and lower lobe bronchi, and four different segmental or subsegmental bronchi--that is, Weibel generations 1 to about 5. A total of 119 carinal-tubular pairs was evaluated. RESULTS: Over all cases, both carinal and tubular particle concentrations increased with increasing airway generation; the median ratio of carinal to tubular particle concentration was 9:1 and did not show any trend with airway generation. The ratio was > 5 in 71% of carinal-tubular pairs, > 10 in 42% of pairs, > 20 in 31% of pairs, and > 100 in 9% of pairs. Some subjects showed a notable tendency to high ratios, with many ratios > 100, and other subjects had a tendency toward low ratios. The predominant mineral species in both carinas and tubular airway segments was crystalline silica and the relative proportion was similar in both sites; however, mean particle diameter was consistently less in the carinal tissues. CONCLUSIONS: These findings suggest that the ratio of carinal to tubular retained particles in the large airways in non-smokers is higher than might be supposed from data generated in airway casts, and that there is considerable variation in this ratio between subjects. This finding is of potential interest in models of carcinogen, toxin, and dose of fibrogenic agent to the large airways as it suggests high and sometimes extreme concentrations of toxic particles at carinas, and thus reinforces the notion that carinas may be sites of initiation of disease. PMID:8983467

  2. Tissue inhibitor of metalloproteinase-1 moderates airway re-epithelialization by regulating matrilysin activity.

    PubMed

    Chen, Peter; McGuire, John K; Hackman, Robert C; Kim, Kyoung-Hee; Black, Roy A; Poindexter, Kurt; Yan, Wei; Liu, Phillip; Chen, Ann J; Parks, William C; Madtes, David K

    2008-05-01

    Obliterative bronchiolitis (OB) is the histopathological finding in chronic lung allograft rejection. Mounting evidence suggests that epithelial damage drives the development of airway fibrosis in OB. Tissue inhibitor of metalloproteinase (TIMP)-1 expression increases in lung allografts and is associated with the onset of allograft rejection. Furthermore, in a mouse model of OB, airway obliteration is reduced in TIMP-1-deficient mice. Matrilysin (matrix metallproteinase-7) is essential for airway epithelial repair and is required for the re-epithelialization of airway wounds by facilitating cell migration; therefore, the goal of this study was to determine whether TIMP-1 inhibits re-epithelialization through matrilysin. We found that TIMP-1 and matrilysin co-localized in the epithelium of human lungs with OB and both co-localized and co-immunoprecipitated in wounded primary airway epithelial cultures. TIMP-1-deficient cultures migrated faster, and epithelial cells spread to a greater extent compared with wild-type cultures. TIMP-1 also inhibited matrilysin-mediated cell migration and spreading in vitro. In vivo, TIMP-1 deficiency enhanced airway re-epithelialization after naphthalene injury. Furthermore, TIMP-1 and matrilysin co-localized in airway epithelial cells adjacent to the wound edge. Our data demonstrate that TIMP-1 interacts with matrix metalloproteinases and regulates matrilysin activity during airway epithelial repair. Furthermore, we speculate that TIMP-1 overexpression restricts airway re-epithelialization by inhibiting matrilysin activity, contributing to a stereotypic injury response that promotes airway fibrosis via bronchiole airway epithelial damage and obliteration.

  3. Tissue Inhibitor of Metalloproteinase-1 Moderates Airway Re-Epithelialization by Regulating Matrilysin Activity

    PubMed Central

    Chen, Peter; McGuire, John K.; Hackman, Robert C.; Kim, Kyoung-Hee; Black, Roy A.; Poindexter, Kurt; Yan, Wei; Liu, Phillip; Chen, Ann J.; Parks, William C.; Madtes, David K.

    2008-01-01

    Obliterative bronchiolitis (OB) is the histopathological finding in chronic lung allograft rejection. Mounting evidence suggests that epithelial damage drives the development of airway fibrosis in OB. Tissue inhibitor of metalloproteinase (TIMP)-1 expression increases in lung allografts and is associated with the onset of allograft rejection. Furthermore, in a mouse model of OB, airway obliteration is reduced in TIMP-1-deficient mice. Matrilysin (matrix metallproteinase-7) is essential for airway epithelial repair and is required for the re-epithelialization of airway wounds by facilitating cell migration; therefore, the goal of this study was to determine whether TIMP-1 inhibits re-epithelialization through matrilysin. We found that TIMP-1 and matrilysin co-localized in the epithelium of human lungs with OB and both co-localized and co-immunoprecipitated in wounded primary airway epithelial cultures. TIMP-1-deficient cultures migrated faster, and epithelial cells spread to a greater extent compared with wild-type cultures. TIMP-1 also inhibited matrilysin-mediated cell migration and spreading in vitro. In vivo, TIMP-1 deficiency enhanced airway re-epithelialization after naphthalene injury. Furthermore, TIMP-1 and matrilysin co-localized in airway epithelial cells adjacent to the wound edge. Our data demonstrate that TIMP-1 interacts with matrix metalloproteinases and regulates matrilysin activity during airway epithelial repair. Furthermore, we speculate that TIMP-1 overexpression restricts airway re-epithelialization by inhibiting matrilysin activity, contributing to a stereotypic injury response that promotes airway fibrosis via bronchiole airway epithelial damage and obliteration. PMID:18385523

  4. Stacking of antimicrobial genes in potato transgenic plants confers increased resistance to bacterial and fungal pathogens.

    PubMed

    Rivero, Mercedes; Furman, Nicolás; Mencacci, Nicolás; Picca, Pablo; Toum, Laila; Lentz, Ezequiel; Bravo-Almonacid, Fernando; Mentaberry, Alejandro

    2012-01-20

    Solanum tuberosum plants were transformed with three genetic constructions expressing the Nicotiana tabacum AP24 osmotine, Phyllomedusa sauvagii dermaseptin and Gallus gallus lysozyme, and with a double-transgene construction expressing the AP24 and lysozyme sequences. Re-transformation of dermaseptin-transformed plants with the AP24/lysozyme construction allowed selection of plants simultaneously expressing the three transgenes. Potato lines expressing individual transgenes or double- and triple-transgene combinations were assayed for resistance to Erwinia carotovora using whole-plant and tuber infection assays. Resistance levels for both infection tests compared consistently for most potato lines and allowed selection of highly resistant phenotypes. Higher resistance levels were found in lines carrying the dermaseptin and lysozyme sequences, indicating that theses proteins are the major contributors to antibacterial activity. Similar results were obtained in tuber infection tests conducted with Streptomyces scabies. Plant lines showing the higher resistance to bacterial infections were challenged with Phytophthora infestans, Rhizoctonia solani and Fusarium solani. Considerable levels of resistance to each of these pathogens were evidenced employing semi-quantitative tests based in detached-leaf inoculation, fungal growth inhibition and in vitro plant inoculation. On the basis of these results, we propose that stacking of these transgenes is a promising approach to achieve resistance to both bacterial and fungal pathogens.

  5. Regional aerosol deposition in human upper airways. Final report

    SciTech Connect

    Swift, D.L.

    1997-11-01

    During the award period, a number of studies have been carried out related to the overall objective of the project which is to elucidate important factors which influence the upper airway deposition and dose of particles in the size range 0.5 nm - 10 {mu}m, such as particle size, breathing conditions, age, airway geometry, and mode of breathing. These studies are listed below. (1) A high voltage electrospray system was constructed to generate polydispersed 1-10 {mu}m diameter di-ethylhexyl sebacate aerosol for particle deposition studies in nasal casts and in human subjects. (2) The effect of nostril dimensions, nasal passage geometry, and nasal resistance on particle deposition efficiency in forty healthy, nonsmoking adults at a constant flowrate were studied. (3) The effect of nostril dimensions, nasal passage dimensions and nasal resistance on the percentage of particle deposition in the anterior 3 cm of the nasal passage of spontaneously breathing humans were studied. (4) The region of deposition of monodispersed aerosols were studied using replicate casts. (5) Ultrafine aerosol deposition using simulated breath holding path and natural path was compared. (6) An experimental technique was proposed and tested to measure the oral deposition of inhaled ultrafine particles. (7) We have calculated the total deposition fraction of ultrafine aerosols from 5 to 200 n in the extrathoracic airways and in the lung. (8) The deposition fraction of radon progeny in the head airways was studied using several head airway models.

  6. Rifampin resistance of Legionella pneumophila is not increased during therapy for experimental Legionnaires disease: study of rifampin resistance using a guinea pig model of Legionnaires disease.

    PubMed Central

    Edelstein, P H

    1991-01-01

    Isolates of Legionella pneumophila serogroup 1, obtained from guinea pigs with experimentally induced Legionnaires disease, were tested for rifampin resistance. Thirteen isolates were from animals treated with rifampin alone, four isolates were from animals treated with saline, and three isolates each were from animals treated with erythromycin or erythromycin plus rifampin; all of these isolates were derived from the same parent strain, F889. Most of the isolates were obtained from rifampin-treated animals that survived infection but had persistence of bacteria in their lungs at necropsy. No differences in rifampin agar dilution MICs were detected for the 23 isolates and parent strain that were tested. None of the 13 isolates from animals treated with rifampin alone had a high number of resistant organisms detected by using a rifampin gradient plate assay. Thirteen isolates plus the parent strain were tested by using a quantitative method of determining resistance frequency. Considerable heterogeneity among isolates was observed, but there was no evidence of increased resistance for any treatment group. The range of rifampin resistance frequencies was 10(-7) to 10(-8). No evidence for rifampin-induced resistance of L. pneumophila was found in this study. PMID:2014980

  7. Blunted angiogenesis and hypertrophy are associated with increased fatigue resistance and unchanged aerobic capacity in old overloaded mouse muscle.

    PubMed

    Ballak, Sam B; Busé-Pot, Tinelies; Harding, Peter J; Yap, Moi H; Deldicque, Louise; de Haan, Arnold; Jaspers, Richard T; Degens, Hans

    2016-04-01

    We hypothesize that the attenuated hypertrophic response in old mouse muscle is (1) partly due to a reduced capillarization and angiogenesis, which is (2) accompanied by a reduced oxidative capacity and fatigue resistance in old control and overloaded muscles, that (3) can be rescued by the antioxidant resveratrol. To investigate this, the hypertrophic response, capillarization, oxidative capacity, and fatigue resistance of m. plantaris were compared in 9- and 25-month-old non-treated and 25-month-old resveratrol-treated mice. Overload increased the local capillary-to-fiber ratio less in old (15 %) than in adult (59 %) muscle (P < 0.05). Although muscles of old mice had a higher succinate dehydrogenase (SDH) activity (P < 0.05) and a slower fiber type profile (P < 0.05), the isometric fatigue resistance was similar in 9- and 25-month-old mice. In both age groups, the fatigue resistance was increased to the same extent after overload (P < 0.01), without a significant change in SDH activity, but an increased capillary density (P < 0.05). Attenuated angiogenesis during overload may contribute to the attenuated hypertrophic response in old age. Neither was rescued by resveratrol supplementation. Changes in fatigue resistance with overload and aging were dissociated from changes in SDH activity, but paralleled those in capillarization. This suggests that capillarization plays a more important role in fatigue resistance than oxidative capacity.

  8. Effect of heparin on antigen-induced airway responses and pulmonary leukocyte accumulation in neonatally immunized rabbits

    PubMed Central

    Preuss, Janet M H; Page, Clive P

    2000-01-01

    The effect of single administrations of aerosolized heparin, low molecular weight heparin (LMWH) and the linear polyanionic molecule, polyglutamic acid (PGA) were examined on antigen-induced airway hyperresponsiveness and leukocyte accumulation in neonatally immunized rabbits.Adult litter-matched NZW rabbits immunized within 24 h of birth with Alternaria tenuis antigen were treated with heparin, LMWH or PGA prior to or following antigen challenge (Alternaria tenuis). For each drug-treated group, a parallel group of rabbits were treated with the appropriate vehicle. In all groups, airway responsiveness to inhaled histamine and bronchoalveolar lavage (BAL) was performed 24 h prior to and following antigen challenge.Basal lung function in terms of resistance (RL) and dynamic compliance (Cdyn) and acute bronchoconstriction was unaltered by pre-treatment with heparin, LMWH or PGA compared to their respective vehicles 24 h prior to or following antigen challenge.In vehicle-treated animals, airway hyperresponsiveness to inhaled histamine was indicated by an increase in the maximal responses of the cumulative concentration-effect curves to histamine and reductions in RLPC50 and CdynPC35 values 24 h following antigen challenge.Heparin and LMWH given prior to antigen challenge significantly inhibited the development of airway hyperresponsiveness, whereas PGA did not. When given following antigen challenge, all three drugs failed to inhibit the development of airway hyperresponsiveness.Eosinophil and neutrophil cell numbers in BAL fluid increased significantly 24 h following antigen challenge. Heparin, LMWH and PGA failed to inhibit the increase in cell numbers following antigen challenge whether given prior to or following antigen challenge. PMID:10780962

  9. Induced mutations in the starch branching enzyme II (SBEII) genes increase amylose and resistant starch content in durum wheat

    PubMed Central

    Hazard, Brittany; Zhang, Xiaoqin; Colasuonno, Pasqualina; Uauy, Cristobal; Beckles, Diane M.; Dubcovsky, Jorge

    2016-01-01

    Starch is the largest component of the wheat (Triticum aestivum L.) grain and consists of approximately 70-80% amylopectin and 20-30% amylose. Amylopectin is a highly-branched, readily digested polysaccharide, whereas amylose has few branches and forms complexes that resist digestion and mimic dietary fiber (resistant starch). Down-regulation of the starch branching enzyme II (SBEII) gene by RNA interference (RNAi) was previously shown to increase amylose content in both hexaploid and tetraploid wheat. We generated ethyl methane sulphonate (EMS) mutants for the SBEIIa-A and SBEIIa-B homoeologs in the tetraploid durum wheat variety Kronos (T. turgidum ssp. durum L.). Single-gene mutants showed non-significant increases in amylose and resistant starch content, but a double mutant combining a SBEIIa-A knock-out mutation with a SBEIIa-B splice-site mutation showed a 22% increase in amylose content (P<0.0001) and a 115% increase in resistant starch content (P<0.0001). In addition, we obtained mutants for the A and B genome copies of the paralogous SBEIIb gene, mapped them 1-2 cM from SBEIIa, and generated double SBEIIa-SBEIIb mutants to study the effect of the SBEIIb gene in the absence of SBEIIa. These mutants are available to those interested in increasing amylose content and resistant starch in durum wheat. PMID:26924849

  10. Differential Reinforcement of Alternative Behavior Increases Resistance to Extinction: Clinical Demonstration, Animal Modeling, and Clinical Test of One Solution

    ERIC Educational Resources Information Center

    Mace, F. Charles; McComas, Jennifer J.; Mauro, Benjamin C.; Progar, Patrick R.; Taylor, Bridget; Ervin, Ruth; Zangrillo, Amanda N.

    2010-01-01

    Basic research with pigeons on behavioral momentum suggests that differential reinforcement of alternative behavior (DRA) can increase the resistance of target behavior to change. This finding suggests that clinical applications of DRA may inadvertently increase the persistence of target behavior even as it decreases its frequency. We conducted…

  11. Increased prevalence of antibiotic-resistant E. coli in gulls sampled in Southcentral Alaska is associated with urban environments

    PubMed Central

    Atterby, Clara; Ramey, Andrew M.; Hall, Gabriel Gustafsson; Järhult, Josef; Börjesson, Stefan; Bonnedahl, Jonas

    2016-01-01

    Background Antibiotic-resistant bacteria pose challenges to healthcare delivery systems globally; however, limited information is available regarding the prevalence and spread of such bacteria in the environment. The aim of this study was to compare the prevalence of antibiotic-resistant bacteria in large-bodied gulls (Larus spp.) at urban and remote locations in Southcentral Alaska to gain inference into the association between antibiotic resistance in wildlife and anthropogenically influenced habitats. Methods Escherichia coli was cultured (n=115 isolates) from fecal samples of gulls (n=160) collected from a remote location, Middleton Island, and a more urban setting on the Kenai Peninsula. Results Screening of E. coli from fecal samples collected from glaucous-winged gulls (Larus glaucescens) at Middleton Island revealed 8% of isolates were resistant to one or more antibiotics and 2% of the isolates were resistant to three or more antibiotics. In contrast, 55% of E. coli isolates derived from fecal samples collected from large-bodied gulls (i.e. glaucous, herring [Larus argentatus], and potentially hybrid gulls) on the Kenai Peninsula were resistant to one or more antibiotics and 22% were resistant to three or more antibiotics. In addition, total of 16% of the gull samples from locations on the Kenai Peninsula harbored extended-spectrum cephalosporin-resistant E. coli isolates (extended-spectrum beta-lactamases [ESBL] and plasmid-encoded AmpC [pAmpC]), in contrast to Middleton Island where no ESBL- or pAmpC-producing isolates were detected. Conclusion Our findings indicate that increased prevalence of antibiotic resistance is associated with urban environments in Southcentral Alaska and presumably influenced by anthropogenic impacts. Further investigation is warranted to assess how migratory birds may maintain and spread antimicrobial-resistant bacteria of relevance to human and animal health. PMID:27649798

  12. Increased prevalence of antibiotic-resistant E. coli in gulls sampled in southcentral Alaska is associated with urban environments

    USGS Publications Warehouse

    Atterby, Clara; Ramey, Andrew M.; Gustafsson Hall, Gabriel; Jarhult, Josef; Borjesson, Stefan; Bonnedahl, Jonas

    2016-01-01

    BackgroundAntibiotic-resistant bacteria pose challenges to healthcare delivery systems globally; however, limited information is available regarding the prevalence and spread of such bacteria in the environment. The aim of this study was to compare the prevalence of antibiotic-resistant bacteria in large-bodied gulls (Larus spp.) at urban and remote locations in Southcentral Alaska to gain inference into the association between antibiotic resistance in wildlife and anthropogenically influenced habitats.MethodsEscherichia coli was cultured (n=115 isolates) from fecal samples of gulls (n=160) collected from a remote location, Middleton Island, and a more urban setting on the Kenai Peninsula.ResultsScreening of E. coli from fecal samples collected from glaucous-winged gulls (Larus glaucescens) at Middleton Island revealed 8% of isolates were resistant to one or more antibiotics and 2% of the isolates were resistant to three or more antibiotics. In contrast, 55% of E. coli isolates derived from fecal samples collected from large-bodied gulls (i.e. glaucous, herring [Larus argentatus], and potentially hybrid gulls) on the Kenai Peninsula were resistant to one or more antibiotics and 22% were resistant to three or more antibiotics. In addition, total of 16% of the gull samples from locations on the Kenai Peninsula harbored extended-spectrum cephalosporin-resistant E. coli isolates (extended-spectrum beta-lactamases [ESBL] and plasmid-encoded AmpC [pAmpC]), in contrast to Middleton Island where no ESBL- or pAmpC-producing isolates were detected.ConclusionOur findings indicate that increased prevalence of antibiotic resistance is associated with urban environments in Southcentral Alaska and presumably influenced by anthropogenic impacts. Further investigation is warranted to assess how migratory birds may maintain and spread antimicrobial-resistant bacteria of relevance to human and animal health.

  13. Glutathione redox regulates airway hyperresponsiveness and airway inflammation in mice.

    PubMed

    Koike, Yoko; Hisada, Takeshi; Utsugi, Mitsuyoshi; Ishizuka, Tamotsu; Shimizu, Yasuo; Ono, Akihiro; Murata, Yukie; Hamuro, Junji; Mori, Masatomo; Dobashi, Kunio

    2007-09-01

    Glutathione is the major intracellular redox buffer. We have shown that glutathione redox status, which is the balance between intracellular reduced (GSH) and oxidized (GSSG) glutathione, in antigen-presenting cells (APC) regulates the helper T cell type 1 (Th1)/Th2 balance due to the production of IL-12. Bronchial asthma is a typical Th2 disease. Th2 cells and Th2 cytokines are characteristic of asthma and trigger off an inflammation. Accordingly, we studied the effects of the intracellular glutathione redox status on airway hyperresponsiveness (AHR) and allergen-induced airway inflammation in a mouse model of asthma. We used gamma-Glutamylcysteinylethyl ester (gamma-GCE), which is a membrane-permeating GSH precursor, to elevate the intracellular GSH level and GSH/GSSG ratio of mice. In vitro, gamma-GCE pretreatment of human monocytic THP-1 cells elevated the GSH/GSSG ratio and enhanced IL-12(p70) production induced by LPS. In the mouse asthma model, intraperitoneal injection of gamma-GCE elevated the GSH/GSSG ratio of lung tissue and reduced AHR. gamma-GCE reduced levels of IL-4, IL-5, IL-10, and the chemokines eotaxin and RANTES (regulated on activation, normal T cell expressed and secreted) in bronchoalveolar lavage fluid, whereas it enhanced the production of IL-12 and IFN-gamma. Histologically, gamma-GCE suppressed eosinophils infiltration. Interestingly, we also found that gamma-GCE directly inhibited chemokine-induced eosinophil chemotaxis without affecting eotaxin receptor chemokine receptor 3 (CCR3) expressions. Taken together, these findings suggest that changing glutathione redox balance, increase in GSH level, and the GSH/GSSG ratio by gamma-GCE, ameliorate bronchial asthma by altering the Th1/Th2 imbalance through IL-12 production from APC and suppressing chemokine production and eosinophil migration itself.

  14. Airway evaluation in obstructive sleep apnea.

    PubMed

    Stuck, Boris A; Maurer, Joachim T

    2008-12-01

    As the interest in sleep-disordered breathing has increased, various attempts have been made to assess upper airway anatomy in patients with this relatively frequent disorder. The aim is not only to reveal potential differences in upper airway anatomy to better understand origin and pathophysiology of the disease but also to improve patient management and treatment success. The present review is based on a systematic literature search with regard to upper airway evaluation in sleep-disordered breathing; the articles were selected and discussed in light of our clinical experiences. Based on clinical assessment including endoscopy during wakefulness, the value of the Mueller Maneuver, static radiologic imaging techniques (X-ray cephalometry, computed tomography (CT) scanning and magnetic resonance imaging (MRI)), dynamic scanning protocols (e.g. ultrafast CT or cine MRI), upper airway endoscopy during sleep and sedated sleep, pressure measurements and the assessment of the critical closing pressure are discussed. Each technique itself and its history in the field of sleep medicine are briefly reviewed and problems of standardization and interpretation are discussed when appropriate. Insights into the pathophysiology of the disease gained with the help of the investigational techniques are presented and the impact of the techniques on patient management is reported. Although all these additional techniques for upper airway assessment have substantially improved our understanding of sleep-disordered breathing, their significance in daily practice is limited. In contrast to the widespread use of the Mueller maneuver and sedated endoscopy, convincing data supporting their use in terms of treatment outcome are lacking. So far, there is only very limited evidence that selected techniques improve treatment outcome for selected indications. In general, there is not enough evidence that these techniques are superior to the routine clinical assessment.

  15. Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability

    SciTech Connect

    Li, E.J.; Cook, J.A.; Spicer, K.M.; Wise, W.C.; Rokach, J.; Halushka, P.V. )

    1990-06-01

    Resistance to endotoxin in essential fatty acid-deficient (EFAD) rats is associated with reduced synthesis of certain arachidonic acid metabolites. It was hypothesized that EFAD rats would manifest decreased vascular permeability changes during endotoxemia as a consequence of reduced arachidonic acid metabolism. To test this hypothesis, changes in hematocrit (HCT) and mesenteric localization rate of technetium-labeled human serum albumin (99mTc-HSA) and red blood cells (99mTc-RBC) were assessed in EFAD and normal rats using gamma-camera imaging. Thirty minutes after Salmonella enteritidis endotoxin, EFAD rats exhibited less hemoconcentration as determined by % HCT than normal rats. Endotoxin caused a less severe change in permeability index in the splanchnic region in EFAD rats than in normal rats (1.2 +/- 0.6 x 10(-3)min-1 vs. 4.9 +/- 1.7 x 10(-3)min-1 respectively, P less than 0.05). In contrast to 99mTc-HSA, mesenteric localization of 99mTc-RBC was not changed by endotoxin in control or EFAD rats. Supplementation with ethyl-arachidonic acid did not enhance susceptibility of EFAD rats to endotoxin-induced splanchnic permeability to 99mTc-HSA. Leukotrienes have been implicated as mediators of increased vascular permeability in endotoxin shock. Since LTC3 formation has been reported to be increased in EFA deficiency, we hypothesized that LTC3 may be less potent than LTC4. Thus the effect of LTC3 on mean arterial pressure and permeability was compared to LTC4 in normal rats. LTC3-induced increases in peak mean arterial pressure were less than LTC4 at 10 micrograms/kg (39 +/- 5 mm Hg vs. 58 +/- 4 mm Hg respectively, P less than 0.05) and at 20 micrograms/kg (56 +/- 4 mm Hg vs. 75 +/- 2 mm Hg respectively, P less than 0.05). LY171883 (30 mg/kg), an LTD4/E4 receptor antagonist, attenuated the pressor effect of LTC4, LTD4, and LTC3.

  16. Classification of pulmonary airway disease based on mucosal color analysis

    NASA Astrophysics Data System (ADS)

    Suter, Melissa; Reinhardt, Joseph M.; Riker, David; Ferguson, John Scott; McLennan, Geoffrey

    2005-04-01

    Airway mucosal color changes occur in response to the development of bronchial diseases including lung cancer, cystic fibrosis, chronic bronchitis, emphysema and asthma. These associated changes are often visualized using standard macro-optical bronchoscopy techniques. A limitation to this form of assessment is that the subtle changes that indicate early stages in disease development may often be missed as a result of this highly subjective assessment, especially in inexperienced bronchoscopists. Tri-chromatic CCD chip bronchoscopes allow for digital color analysis of the pulmonary airway mucosa. This form of analysis may facilitate a greater understanding of airway disease response. A 2-step image classification approach is employed: the first step is to distinguish between healthy and diseased bronchoscope images and the second is to classify the detected abnormal images into 1 of 4 possible disease categories. A database of airway mucosal color constructed from healthy human volunteers is used as a standard against which statistical comparisons are made from mucosa with known apparent airway abnormalities. This approach demonstrates great promise as an effective detection and diagnosis tool to highlight potentially abnormal airway mucosa identifying a region possibly suited to further analysis via airway forceps biopsy, or newly developed micro-optical biopsy strategies. Following the identification of abnormal airway images a neural network is used to distinguish between the different disease classes. We have shown that classification of potentially diseased airway mucosa is possible through comparative color analysis of digital bronchoscope images. The combination of the two strategies appears to increase the classification accuracy in addition to greatly decreasing the computational time.

  17. Induction of transient airway hyperresponsiveness by exposure to 4 ppm nitrogen dioxide in guinea pigs

    SciTech Connect

    Kobayashi, T.; Shinozaki, Y. )

    1992-11-01

    In the present study, we investigated (1) whether airway responsiveness to inhaled histamine-aerosol could be induced during 7-d exposure of guinea pigs to 4 ppm NO[sub 2] and, if so, (2) whether thromboxane A2 may be involved in such increase. Female Hartley guinea pigs were divided into 6 groups (n = 15/group). Three groups were exposed to filtered air and the other 3 groups were exposed to NO[sub 2] for 1, 3, or 7 d (24 h/d). Baseline specific airway resistance (SRaw) did not change significantly after exposure to 4 ppm NO[sub 2] or air. Airway responsiveness was determined 1 wk before the beginning of exposure and on the day of termination of the exposure. Prior to exposure to NO[sub 2], the EC200His, the concentrations of inhaled histamine necessary to double SRawNaCl (SRaw after inhalation of 0.9% NaCl), were 1.07 [plus minus] 0.20, 1.30 [plus minus] 0.20, and 1.01 [plus minus] 0.18 mM for the 3 groups later given NO[sub 2] for 1, 3, and 7 d, respectively. Following exposure to NO[sub 2] for 1, 3, or 7 d, EC200His values were 1.42 [plus minus] 0.25, 0.66 [plus minus] 0.10 (p < .05), and 1.05 [plus minus] 0.22 mM, respectively. These results show that 7-d exposure to 4 ppm NO[sub 2] induced a significant increase in airway responsiveness on d 3. Exposure to air had no significant effect on the airway responsiveness. This transient hyperresponsiveness was inhibited by a specific inhibitor of thromboxane synthetase, OKY 046. These results indicated that (1) a lower concentration (4 ppm) of NO[sub 2] than that previously reported can induce transient hyperresponsiveness in guinea pigs during appropriate long-term exposure, and (2) thromboxane A2 may play an important role in this transient airway hyperresponsiveness.

  18. Increase in numbers of beta-lactam-resistant invasive Streptococcus pneumoniae in Brazil and the impact of conjugate vaccine coverage.

    PubMed

    Brandileone, Maria-Cristina C; Casagrande, Silvana Tadeu; Guerra, Maria-Luiza L S; Zanella, Rosemeire Cobo; Andrade, Ana-Lucia S S; Di Fabio, José-Luis

    2006-05-01

    A comprehensive investigation of invasive Streptococcus pneumoniae was carried out in Brazil as part of the programme of the national epidemiological surveillance system. The investigation provided data on the trends of resistance to antimicrobial agents. A total of 6470 isolates of S. pneumoniae collected in the country from 1993 to 2004 were tested. During this period of time, the number of penicillin-resistant strains rose from 10.2 to 27.9%. The proportions of intermediate and high-level resistant strains in 1993, which were 9.1 and 1.1%, respectively, rose to 22.0 and 5.9% in 2004. Geometric mean MICs for penicillin increased after the year 2000, to 0.19 microg ml(-1) in 2004; most of these isolates were from patients with pneumonia and from children under 5 years old, and belonged to serotype 14. There was a significant increase in the number of isolates belonging to serotypes included in the 7-valent conjugate vaccine from children under 5 years old: from 48.6% in 1993 to 69.6% in 2004, mainly related to an increase in the frequency of serotype 14 isolates. From 2000 to 2004, meningitis isolates showed higher resistance rates to cefotaxime (2.6%) compared to non-meningitis isolates (0.7%); percentages of isolates resistant to trimethoprim-sulfamethoxazole, tetracycline, erythromycin, chloramphenicol and rifampicin were 65, 14.6, 6.2, 1.3 and 0.7 %, respectively. No levoflaxin resistance was observed. Multidrug resistance was identified in 4.6% of isolates, of which 3.8% were resistant to three classes, 0.7% to four classes and 0.1% to five classes of antimicrobial agent. The study provides valuable information that may support empirical antimicrobial therapy for severe S. pneumoniae infections in Brazil, and emphasizes the need for conjugate pneumococcal vaccination.

  19. Operative endoscopy of the airway

    PubMed Central

    Walters, Dustin M.

    2016-01-01

    Airway endoscopy has long been an important and useful tool in the management of thoracic diseases. As thoracic specialists have gained experience with both flexible and rigid bronchoscopic techniques, the technology has continued to evolve so that bronchoscopy is currently the foundation for diagnosis and treatment of many thoracic ailments. Airway endoscopy plays a significant role in the biopsy of tumors within the airways, mediastinum, and lung parenchyma. Endoscopic methods have been developed to treat benign and malignant airway stenoses and tracheomalacia. And more recently, techniques have been conceived to treat end-stage emphysema and prolonged air leaks in select patients. This review describes the abundant uses of airway endoscopy, as well as technical considerations and limitations of the current technologies. PMID:26981263

  20. Global airway disease beyond allergy.

    PubMed

    Hellings, Peter W; Prokopakis, Emmanuel P

    2010-03-01

    Besides the anatomic continuity of the upper and lower airways, inflammation in one part of the airway influences the homeostasis of the other. The mechanisms underlying this interaction have been studied primarily in allergic disease, showing systemic immune activation, induction of inflammation at a distance, and a negative impact of nasal inflammation on bronchial homeostasis. In addition to allergy, other inflammatory conditions of the upper airways are associated with lower airway disease. Rhinosinusitis is frequently associated with asthma and chronic obstructive pulmonary disease. The impairment of purification, humidification, and warming up of the inspired air by the nose in rhinosinusitis may be responsible in part for bronchial pathology. The resolution of sinonasal inflammation via medical and/or surgical treatment is responsible for the beneficial effect of the treatment on bronchial disease. This article provides a comprehensive overview of the current knowledge of upper and lower airway communication beyond allergic disease.

  1. Recurrent airway obstruction: a review.

    PubMed

    Pirie, R S

    2014-05-01

    Recurrent airway obstruction is a widely recognised airway disorder, characterised by hypersensitivity-mediated neutrophilic airway inflammation and lower airway obstruction in a subpopulation of horses when exposed to suboptimal environments high in airborne organic dust. Over the past decade, numerous studies have further advanced our understanding of different aspects of the disease. These include clarification of the important inhaled airborne agents responsible for disease induction, improving our understanding of the underlying genetic basis of disease susceptibility and unveiling the fundamental immunological mechanisms leading to establishment of the classic disease phenotype. This review, as well as giving a clinical overview of recurrent airway obstruction, summarises much of the work in these areas that have culminated in a more thorough understanding of this debilitating disease.

  2. The airway microbiome and disease.

    PubMed

    Marsland, Benjamin J; Yadava, Koshika; Nicod, Laurent P

    2013-08-01

    Although traditionally thought to be sterile, accumulating evidence now supports the concept that our airways harbor a microbiome. Thus far, studies have focused upon characterizing the bacterial constituents of the airway microbiome in both healthy and diseased lungs, but what perhaps provides the greatest impetus for the exploration of the airway microbiome is that different bacterial phyla appear to dominate diseased as compared with healthy lungs. As yet, there is very limited evidence supporting a functional role for the airway microbiome, but continued research in this direction is likely to provide such evidence, particularly considering the progress that has been made in understanding host-microbe mutualism in the intestinal tract. In this review, we highlight the major advances that have been made discovering and describing the airway microbiome, discuss the experimental evidence that supports a functional role for the microbiome in health and disease, and propose how this emerging field is going to impact clinical practice.

  3. A seed mixture increases dominance of resistance to Bt cotton in Helicoverpa zea.

    PubMed

    Brévault, Thierry; Tabashnik, Bruce E; Carrière, Yves

    2015-05-07

    Widely grown transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt) can benefit agriculture, but adaptation by pests threatens their continued success. Refuges of host plants that do not make Bt toxins can promote survival of susceptible insects and delay evolution of resistance, particularly if resistance is inherited as a recessive trait. However, data have been lacking to compare the dominance of resistance when Bt and non-Bt seeds are planted in random mixtures versus separate blocks. Here we report results from greenhouse experiments with transgenic cotton producing Bt toxin Cry1Ac and the bollworm, Helicoverpa zea, showing that the dominance of resistance was significantly higher in a seed mixture relative to a block of Bt cotton. The proportion of larvae on non-Bt cotton plants in the seed mixture was also significantly higher than expected under the null hypothesis of random distribution. In simulations based on observed survival, resistance evolved 2- to 4.5-fold faster in the seed mixture relative to separate blocks of Bt and non-Bt cotton. These findings support previous modelling results indicating that block refuges may be more effective than seed mixtures for delaying resistance in pests with mobile larvae and inherently low susceptibility to the toxins in Bt crops.

  4. Increases of Antibiotic Resistance in Excessive Use of Antibiotics in Smallholder Dairy Farms in Northern Thailand

    PubMed Central

    Suriyasathaporn, W.; Chupia, V.; Sing-Lah, T.; Wongsawan, K.; Mektrirat, R.; Chaisri, W.

    2012-01-01

    Antibiotic resistance patterns of bacterial isolates from both quarter teat-tip swabs and their quarter milk samples were evaluated in smallholder dairy farms in northern Thailand with excessive use of antibiotics (HIGH) compared with normal use (NORM). Results from teat-tip swab samples showed that the percentage of Bacillus spp. resistance to overall antibiotics was significantly lower in the NORM group than that of the HIGH group, whereas, the resistance percentage of coagulase-negative staphylococci in the NORM group was higher than that of the HIGH one. The overall mastitis-causing bacteria isolated from milk samples were environmental streptococci (13.8%), coagulase-negative staphylococci (9.9%), Staphylococcus aureus (5.4%), and Corynebacterium bovis (4.5%). Both staphylococci and streptococci had significantly higher percentages of resistance to cloxacillin and oxacillin in the HIGH group when compared to the NORM one. An occurrence of vancomycin-resistant bacteria was also observed in the HIGH group. In conclusion, the smallholder dairy farms with excessive use of antibiotics had a higher probability of antibiotic-resistant pattern than the farms with normal use. PMID:25049697

  5. Undulatory physical resistance training program increases maximal strength in elderly type 2 diabetics

    PubMed Central

    dos Santos, Gilberto Monteiro; Montrezol, Fábio Tanil; Pauli, Luciana Santos Souza; Sartori-Cintra, Angélica Rossi; Colantonio, Emilson; Gomes, Ricardo José; Marinho, Rodolfo; de Moura, Leandro Pereira; Pauli, José Rodrigo

    2014-01-01

    Objective To investigate the effects of a specific protocol of undulatory physical resistance training on maximal strength gains in elderly type 2 diabetics. Methods The study included 48 subjects, aged between 60 and 85 years, of both genders. They were divided into two groups: Untrained Diabetic Elderly (n=19) with those who were not subjected to physical training and Trained Diabetic Elderly (n=29), with those who were subjected to undulatory physical resistance training. The participants were evaluated with several types of resistance training’s equipment before and after training protocol, by test of one maximal repetition. The subjects were trained on undulatory resistance three times per week for a period of 16 weeks. The overload used in undulatory resistance training was equivalent to 50% of one maximal repetition and 70% of one maximal repetition, alternating weekly. Statistical analysis revealed significant differences (p<0.05) between pre-test and post-test over a period of 16 weeks. Results The average gains in strength were 43.20% (knee extension), 65.00% (knee flexion), 27.80% (supine sitting machine), 31.00% (rowing sitting), 43.90% (biceps pulley), and 21.10% (triceps pulley). Conclusion Undulatory resistance training used with weekly different overloads was effective to provide significant gains in maximum strength in elderly type 2 diabetic individuals. PMID:25628192

  6. A seed mixture increases dominance of resistance to Bt cotton in Helicoverpa zea

    PubMed Central

    Brévault, Thierry; Tabashnik, Bruce E.; Carrière, Yves

    2015-01-01

    Widely grown transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt) can benefit agriculture, but adaptation by pests threatens their continued success. Refuges of host plants that do not make Bt toxins can promote survival of susceptible insects and delay evolution of resistance, particularly if resistance is inherited as a recessive trait. However, data have been lacking to compare the dominance of resistance when Bt and non-Bt seeds are planted in random mixtures versus separate blocks. Here we report results from greenhouse experiments with transgenic cotton producing Bt toxin Cry1Ac and the bollworm, Helicoverpa zea, showing that the dominance of resistance was significantly higher in a seed mixture relative to a block of Bt cotton. The proportion of larvae on non-Bt cotton plants in the seed mixture was also significantly higher than expected under the null hypothesis of random distribution. In simulations based on observed survival, resistance evolved 2- to 4.5-fold faster in the seed mixture relative to separate blocks of Bt and non-Bt cotton. These findings support previous modelling results indicating that block refuges may be more effective than seed mixtures for delaying resistance in pests with mobile larvae and inherently low susceptibility to the toxins in Bt crops. PMID:25950459

  7. Baculovirus p35 increases pancreatic {beta}-cell resistance to apoptosis

    SciTech Connect

    Hollander, Kenneth; Bar-Chen, Michal; Efrat, Shimon . E-mail: sefrat@post.tau.ac.il

    2005-07-01

    {beta}-cells die by apoptosis in type 1 diabetes as a result of autoimmune attack mediated by cytokines, and in type 2 diabetes by various perpetrators including human islet amyloid polypeptide (hIAPP). The cascade of apoptotic events induced by cytokines and hIAPP is mediated through caspases and reactive oxygen species. The baculovirus p35 protein is a potent anti-apoptotic agent shown to be effective in a variety of species and able to inhibit a number of apoptotic pathways. Here, we aimed at determining the protective potential of p35 in {beta}-cells exposed to cytokines and hIAPP, as well as the effects of p35 on {beta}-cell function. The p35 gene was introduced into {beta}TC-tet cells, a differentiated murine {beta}-cell line capable of undergoing inducible growth-arrest. Both proliferating and growth-arrested cells expressing p35 manifested increased resistance to cytokines and hIAPP, compared with control cells, as judged by cell viability, DNA fragmentation, and caspase-3 activity assays. p35 was significantly more protective in growth-arrested, compared with proliferating, cells. No significant differences were observed in proliferation and insulin content between cells expressing p35 and control cells. In contrast, p35 manifested a perturbing effect on glucose-induced insulin secretion. These findings suggest that p35 could be incorporated as part of a multi-pronged approach of immunoprotective strategies to provide protection from recurring autoimmunity for transplanted {beta}-cells, as well as in preventive gene therapy in type 1 diabetes. p35 may also be protective from {beta}-cell damage caused by hIAPP in type 2 diabetes.

  8. Changes in multifractal parameters from profiles of soil penetration resistance obtained with increasing soil dryness

    NASA Astrophysics Data System (ADS)

    Germán Wilson, Marcelo; Lado Liñares, Marcos; González, Antonio Paz

    2015-04-01

    Soil penetration resistance (PR) is linked to basic soil physical properties and correlated to root growth and plant production, so that it has been extensively used as a practical tool for assessing soil compaction and to evaluate the effects of soil management on soil physical quality. We analyzed multifractality of PR vertical profiles, measured from 0 to 80 cm depth at 1 cm intervals. Soil PR was recorded at 10 successive dates with decreasing soil water content in Entre Ríos Province, Argentina, and 10 replicate PR profiles were obtained in each date. The scaling property of each depth-dependent PR profile was typified by the singularity spectrum, αs versus f(α)s and the generalized dimension spectrum, estimated by the method of moments. Both, singularity and Rènyi spectra showed the vertical PR data sets exhibited a well-defined multifractal structure. The multifractality (scaling heterogeneity) in our data series decreased as the mean soil water content decreased. Overall, singularity spectra were asymmetrical and shifted to the right, which is compatible with a greater heterogeneity of the low values in the PR data sets studied. The entropy dimension, D1, increased with decreasing soil water content, and mean values ranged from 0.956 to 0.981; this means that the wetter the soil the more homogeneously is distributed the measure over a large range of scales. Multifractal analysis yielded information about changes with scale of the higher moments, which gives a deep insight into the inner structure of soil PR depth-dependent profiles.

  9. Increased Antifungal Drug Resistance in Clinical Isolates of Cryptococcus neoformans in Uganda.

    PubMed

    Smith, Kyle D; Achan, Beatrice; Hullsiek, Kathy Huppler; McDonald, Tami R; Okagaki, Laura H; Alhadab, Ali A; Akampurira, Andrew; Rhein, Joshua R; Meya, David B; Boulware, David R; Nielsen, Kirsten

    2015-12-01

    Cryptococcal antigen screening is recommended among people living with AIDS when entering HIV care with a CD4 count of <100 cells/μl, and preemptive fluconazole monotherapy treatment is recommended for those with subclinical cryptococcal antigenemia. Yet, knowledge is limited of current antimicrobial resistance in Africa. We examined antifungal drug susceptibility in 198 clinical isolates collected from Kampala, Uganda, between 2010 and 2014 using the CLSI broth microdilution assay. In comparison with two previous studies from 1998 to 1999 that reported an MIC50 of 4 μg/ml and an MIC90 of 8 μg/ml prior to widespread human fluconazole and agricultural azole fungicide usage, we report an upward shift in the fluconazole MIC50 to 8 μg/ml and an MIC90 value of 32 μg/ml, with 31% of isolates with a fluconazole MIC of ≥ 16 μg/ml. We observed an amphotericin B MIC50 of 0.5 μg/ml and an MIC90 of 1 μg/ml, of which 99.5% of isolates (197 of 198 isolates) were still susceptible. No correlation between MIC and clinical outcome was observed in the context of amphotericin B and fluconazole combination induction therapy. We also analyzed Cryptococcus susceptibility to sertraline, with an MIC50 of 4 μg/ml, suggesting that sertraline is a promising oral, low-cost, available, novel medication and a possible alternative to fluconazole. Although the CLSI broth microdilution assay is ideal to standardize results, limit human bias, and increase assay capacity, such assays are often inaccessible in low-income countries. Thus, we also developed and validated an assay that could easily be implemented in a resource-limited setting, with similar susceptibility results