Modulation of the oscillatory mechanics of lung tissue and the oxidative stress response induced by arginase inhibition in a chronic allergic inflammation model

Abstract Background The importance of the lung parenchyma in the pathophysiology of asthma has previously been demonstrated. Considering that nitric oxide synthases (NOS) and arginases compete for the same substrate, it is worthwhile to elucidate the effects of complex NOS-arginase dysfunction in the pathophysiology of asthma, particularly, related to distal lung tissue. We evaluated the effects of arginase and iNOS inhibition on distal lung mechanics and oxidative stress pathway activation in a model of chronic pulmonary allergic inflammation in guinea pigs. Methods Guinea pigs were exposed to repeated ovalbumin inhalations (twice a week for 4 weeks). The animals received 1400 W (an iNOS-specific inhibitor) for 4 days beginning at the last inhalation. Afterwards, the animals were anesthetized and exsanguinated; then, a slice of the distal lung was evaluated by oscillatory mechanics, and an arginase inhibitor (nor-NOHA) or vehicle was infused in a Krebs solution bath. Tissue resistance (Rt) and elastance (Et) were assessed before and after ovalbumin challenge (0.1%), and lung strips were submitted to histopathological studies. Results Ovalbumin-exposed animals presented an increase in the maximal Rt and Et responses after antigen challenge (p<0.001), in the number of iNOS positive cells (p<0.001) and in the expression of arginase 2, 8-isoprostane and NF-kB (p<0.001) in distal lung tissue. The 1400 W administration reduced all these responses (p<0.001) in alveolar septa. Ovalbumin-exposed animals that received nor-NOHA had a reduction of Rt, Et after antigen challenge, iNOS positive cells and 8-isoprostane and NF-kB (p<0.001) in lung tissue. The activity of arginase 2 was reduced only in the groups treated with nor-NOHA (p <0.05). There was a reduction of 8-isoprostane expression in OVA-NOR-W compared to OVA-NOR (p<0.001). Conclusions In this experimental model, increased arginase content and iNOS-positive cells were associated with the constriction of distal lung parenchyma. This functional alteration may be due to a high expression of 8-isoprostane, which had a procontractile effect. The mechanism involved in this response is likely related to the modulation of NF-kB expression, which contributed to the activation of the arginase and iNOS pathways. The association of both inhibitors potentiated the reduction of 8-isoprostane expression in this animal model.

P2Y1 receptors expressed by C1 neurons determine peripheral chemoreceptor modulation of breathing, sympathetic activity, and blood pressure

Catecholaminergic C1 cells of the rostral ventrolateral medulla (RVLM) are key determinants of the sympathoexcitatory response to peripheral chemoreceptor activation. Overactivation of this reflex is thought to contribute to increased sympathetic activity and hypertension; however, molecular mechanisms linking peripheral chemoreceptor drive to hypertension remain poorly understood. We have recently determined that activation of P2Y1 receptors in the RVLM mimicked effects of peripheral chemoreceptor activation. Therefore, we hypothesize that P2Y1 receptors regulate peripheral chemoreceptor drive in this region. Here, we determine whether P2Y1 receptors are expressed by C1 neurons in the RVLM and contribute to peripheral chemoreceptor control of breathing, sympathetic activity, and blood pressure. We found that injection of a specific P2Y1 receptor agonist (MRS2365) into the RVLM of anesthetized adult rats increased phrenic nerve activity (≈55%), sympathetic nerve activity (38±6%), and blood pressure (23±1 mm Hg), whereas application of a specific P2Y1 receptor antagonist (MRS2179) decreased peripheral chemoreceptor–mediated activation of phrenic nerve activity, sympathetic nerve activity, and blood pressure. To establish that P2Y1 receptors are expressed by C1 cells, we determine in the brain slice preparation using cell-attached recording techniques that cells responsive to MRS2365 are immunoreactive for tyrosine hydroxylase (a marker of C1 cells), and we determine in vivo that C1-lesioned animals do not respond to RVLM injection of MRS2365. These data identify P2Y1 receptors as key determinants of peripheral chemoreceptor regulation of breathing, sympathetic nerve activity, and blood pressure.

Periaqueductal gray matter modulates the hypercapnic ventilatory response

The periaqueductal gray (PAG) is a midbrain structure directly involved in the modulation of defensive behaviors. It has direct projections to several central nuclei that are involved in cardiorespiratory control. Although PAG stimulation is known to elicit respiratory responses, the role of the PAG in the CO2-drive to breathe is still unknown. The present study assessed the effect of chemical lesion of the dorsolateral and dorsomedial and ventrolateral/lateral PAG (dlPAG, dmPAG, and vPAG, respectively) on cardiorespiratory and thermal responses to hypercapnia. Ibotenic acid (IBO) or vehicle (PBS, Sham group) was injected into the dlPAG, dmPAG, or vPAG of male Wistar rats. Rats with lesions outside the dlPAG, dmPAG, or vPAG were considered as negative controls (NC). Pulmonary ventilation (Ve), mean arterial pressure (MAP), heart rate (HR), and body temperature (Tb) were measured in unanesthetized rats during normocapnia and hypercapnic exposure (5, 15, 30 min, 7 % CO2). IBO lesioning of the dlPAG/dmPAG caused 31 % and 26.5 % reductions of the respiratory response to CO2 (1,094.3 +/- 115 mL/kg/min) compared with Sham (1,589.5 +/- 88.1 mL/kg/min) and NC groups (1,488.2 +/- 47.7 mL/kg/min), respectively. IBO lesioning of the vPAG caused 26.6 % and 21 % reductions of CO2 hyperpnea (1,215.3 +/- 108.6 mL/kg/min) compared with Sham (1,657.3 +/- 173.9 mL/kg/min) and NC groups (1,537.6 +/- 59.3). Basal Ve, MAP, HR, and Tb were not affected by dlPAG, dmPAG, or vPAG lesioning. The results suggest that dlPAG, dmPAG, and vPAG modulate hypercapnic ventilatory responses in rats but do not affect MAP, HR, or Tb regulation in resting conditions or during hypercapnia.

Describing fatigue crack growth and load ratio effects in Al 2524 T3 alloy with an enhanced exponential model

The fatigue crack behavior in metals and alloys under constant amplitude test conditions is usually described by relationships between the crack growth rate da/dN and the stress intensity factor range Delta K. In the present work, an enhanced two-parameter exponential equation of fatigue crack growth was introduced in order to describe sub-critical crack propagation behavior of Al 2524-T3 alloy, commonly used in aircraft engineering applications. It was demonstrated that besides adequately correlating the load ratio effects, the exponential model also accounts for the slight deviations from linearity shown by the experimental curves. A comparison with Elber, Kujawski and "Unified Approach" models allowed for verifying the better performance, when confronted to the other tested models, presented by the exponential model. (C) 2012 Elsevier Ltd. All rights reserved.

Opioid mu-receptors in the rostral medullary raphe modulate hypoxia-induced hyperpnea in unanesthetized rats

Aim: It has been suggested that the medullary raphe (MR) plays a key role in the physiological responses to hypoxia. As opioid mu-receptors have been found in the MR, we studied the putative role of opioid mu-receptors in the rostral MR (rMR) region on ventilation in normal and 7% hypoxic conditions. Methods: We measured pulmonary ventilation ((V) over dotE) and the body temperatures (Tb) of male Wistar rats before and after the selective opioid l-receptor antagonist CTAP ( d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2, cyclic, 0.1 mu g per 0.1 mu L) was microinjected into the rMR during normoxia or after 60 min of hypoxia. Results: The animals treated with intra-rMR CTAP exhibited an attenuation of the ventilatory response to hypoxia ( 430 +/- 86 mL kg) 1 min) 1) compared with the control group ( 790 +/- 82 mL kg) 1 min) 1) ( P < 0.05). No differences in the Tb were observed between groups during hypoxia. Conclusion: These data suggest that opioids acting on l-receptors in the rMR exert an excitatory modulation of hyperventilation induced by hypoxia.

Orthodontic measurements and nasal respiratory function after surgically assisted rapid maxillary expansion: an acoustic rhinometry and rhinomanometry study

The present study sought to assess nasal respiratory function in adult patients with maxillary constriction who underwent surgically assisted rapid maxillary expansion (SARME) and to determine correlations between orthodontic measurements and changes in nasal area, volume, resistance, and airflow. Twenty-seven patients were assessed by acoustic rhinometry, rhinomanometry, orthodontic measurements, and use of a visual analogue scale at three time points: before surgery; after activation of a preoperatively applied palatal expander; and 4 months post-SARME. Results showed a statistically significant increase (p < 0.001) in all orthodontic measurements. The overall area of the nasal cavity increased after surgery (p < 0.036). The mean volume increased between assessments, but not significantly. Expiratory and inspiratory flow increased over time (p < 0.001). Airway resistance decreased between assessments (p < 0.004). Subjective analysis of the feeling of breathing exclusively through the nose increased significantly from one point in time to the next (p < 0.05). There was a statistical correlation between increased arch perimeter and decreased airway resistance. Respiratory flow was the only variable to behave differently between sides. The authors conclude that the SARME procedure produces major changes in the oral and nasal cavity; when combined, these changes improve patients' quality of breathing.

Estudo do Padrão Respiratório e Movimento Toracoabdominal em Valvopatia Mitral

FUNDAMENTO: pacientes com valvopatia mitral podem evoluir com congestão pulmonar, que aumenta o trabalho dos músculos respiratórios; essa sobrecarga pode alterar o padrão respiratório com predomínio do deslocamento torácico ou presença de movimentos paradoxais. OBJETIVO: a) estudar o padrão respiratório e movimento toracoabdominal (MTA) em pacientes com doença mitral b) estudar o efeito do posicionamento nos parâmetros respiratórios c) correlacionar hipertensão pulmonar com presença de incoordenação do MTA. MÉTODOS: o padrão respiratório e o MTA de pacientes com doença mitral foram avaliados por pletismografia respiratória por indutância, nas posições dorsal e sentada, durante dois minutos de respiração tranquila. Analisou-se volume corrente (Vc) e tempos respiratórios e as variáveis do MTA. RESULTADOS: de 65 pacientes incluídos, 10 foram retirados, 29 participaram do grupo estenose mitral e 26 do grupo insuficiência mitral. O Vc, a ventilação pulmonar e o fluxo inspiratório médio aumentaram significantemente na posição sentada, sem diferenças entre os grupos. O MTA manteve-se coordenado entre os grupos e as posições; no entanto, cinco pacientes na posição dorsal apresentaram incoordenação (três no grupo estenose mitral; dois no grupo insuficiência mitral) com correlação significante com valores de pressão de artéria pulmonar (r = 0,992, p = 0,007). CONCLUSÃO: o padrão respiratório e o MTA não apresentam diferenças entre pacientes com estenose ou insuficiência mitral. A posição sentada aumenta o Vc sem alterar os tempos respiratórios. A presença de incoordenação toracoabdominal na posição dorsal esteve associação à hipertensão pulmonar.

Estudo do padrão respiratório e movimento toracoabdominal em valvopatia mitral

FUNDAMENTO: pacientes com valvopatia mitral podem evoluir com congestão pulmonar, que aumenta o trabalho dos músculos respiratórios; essa sobrecarga pode alterar o padrão respiratório com predomínio do deslocamento torácico ou presença de movimentos paradoxais. OBJETIVO: a) estudar o padrão respiratório e movimento toracoabdominal (MTA) em pacientes com doença mitral b) estudar o efeito do posicionamento nos parâmetros respiratórios c) correlacionar hipertensão pulmonar com presença de incoordenação do MTA. MÉTODOS: o padrão respiratório e o MTA de pacientes com doença mitral foram avaliados por pletismografia respiratória por indutância, nas posições dorsal e sentada, durante dois minutos de respiração tranquila. Analisou-se volume corrente (Vc) e tempos respiratórios e as variáveis do MTA. RESULTADOS: de 65 pacientes incluídos, 10 foram retirados, 29 participaram do grupo estenose mitral e 26 do grupo insuficiência mitral. O Vc, a ventilação pulmonar e o fluxo inspiratório médio aumentaram significantemente na posição sentada, sem diferenças entre os grupos. O MTA manteve-se coordenado entre os grupos e as posições; no entanto, cinco pacientes na posição dorsal apresentaram incoordenação (três no grupo estenose mitral; dois no grupo insuficiência mitral) com correlação significante com valores de pressão de artéria pulmonar (r = 0,992, p = 0,007). CONCLUSÃO: o padrão respiratório e o MTA não apresentam diferenças entre pacientes com estenose ou insuficiência mitral. A posição sentada aumenta o Vc sem alterar os tempos respiratórios. A presença de incoordenação toracoabdominal na posição dorsal esteve associação à hipertensão pulmonar.

THE ANALYSIS OF ACTIVITIES NOT PERFORMED BY THE NURSING TEAM REGARDING THE DIAGNOSIS OF INEFFECTIVE BREATHING PATTERN IN THE ELDERLY

The objective of this cross-sectional, descriptive study was to identify the activities of the Nursing Intervention Classification considered as priorities for an Ineffective Breathing Pattern and not performed for elderly inpatients of a teaching hospital in the state of Goias. The study participants were 43 nursing professionals, and data collection was performed in the period spanning October to December 2008, after receiving approval from the Ethics Committee. It was observed that among the 67 activities considered to be priorities for the referred diagnosis, only seven were performed by all of the participants; the other activities, with a varied frequency, were not performed, with the main reason cited being that a professional from a different area completed the activity. It is understood that the fact that the nursing staff does not perform these activities can cause lack of complete coverage in nursing care; therefore there is a need for a legal apparatus to describe the activities that comprise professional practice exclusive to nursing personnel and those activities that have an interdisciplinary nature.

The Effect of Adenoidectomy or Adenotonsillectomy on Occlusal Features in Mouth-breathing Preschoolers

Purpose: The purpose of this study was to evaluate mouth-breathing and nasal-breathing children prior to surgical intervention and 28 months postoperatively, comparing the occlusal features obtained pre- and postoperatively through orthodontic study costs. Methods: The mouth-breathing (MB) group consists of 33 MB children who underwent surgery and presented a nasal-breathing (NB) pattern after surgery The control group comprised 22 NB children. The orthodontic examinations were accomplished prior to surgery (77) and an average of 28 months postoperatively (T2). Results: At T1, the MB and NB children presented no statistically significant difference in any analyzed occlusal features and measurements. At T2, the MB presented larger overjet comparing to NB children (P<.05). MB and NB groups presented statistically similar results (P>.05) concerning intercanine and intermolor distances, second primary molar terminal plane and canine relationship, overbite, crossbite, and open bite. From T1 to T2, the MB and NB groups showed a statistically significant difference in the molar terminal plane. Conclusion: Neither the breathing pattern nor the surgery had any effect on occlusal features in 3- to 6-year-olds. (Pediatr Dent 2012;34:10842) Received May 14, 2010 vertical bar Last Revision April 11, 2010 vertical bar Accepted April 12, 2010

Quantum Mechanics Insight into the Microwave Nucleation of SrTiO3 Nanospheres

An extensive investigation of strontium titanate, SrTiO3 (STO), nanospheres synthesized via a microwave-assisted hydrothermal (MAH) method has been conducted to gain a better insight into thermodynamic, kinetic, and reaction phenomena involved in STO nucleation and crystal growth processes. To this end, quantum chemical modeling based on the density functional theory and periodic super cell models were done. Several experimental techniques were employed to get a deep characterization of structural and optical features of STO nanospheres. A possible formation mechanism was proposed, based on dehydration of titanium and strontium clusters followed by mesoscale transformation and a self-assembly process along an oriented attachment mechanism resulting in spherical like shape. Raman and XANES analysis renders a noncentrosymmetric environment for the octahedral titanium, while infrared and first order Raman modes reveal OH groups which are unsystematically incorporated into uncoordinated superficial sites. These results seem to indicate that the key component is the presence of distorted TiO6 clusters to engender a luminescence property. Analysis of band structure, density Of states, and charge map shows that there is a close relationship among local broken symmetry, polarization, and energy split of the 3d orbitals of titanium. The interplay among these electronic and structural features provides necessary conditions to evaluate its luminescent properties under two energy excitation.

A new simple class of superpotentials in SUSY quantum mechanics

In this work, we introduce the class of quantum mechanics superpotentials W(x) = g epsilon(x)x(2n) and study in detail the cases n = 0 and 1. The n = 0 superpotential is shown to lead to the known problem of two supersymmetrically related Dirac delta potentials (well and barrier). The n = 1 case results in the potentials V+/-(x) = g(2)x(4) +/- 2g|x|. For V-, we present the exact ground-state solution and study the excited states by a variational technique. Starting from the ground state of V- and using logarithmic perturbation theory, we study the ground states of V+ and also of V(x) = g(2)x(4) and compare the result obtained in this new way with other results for this last potential in the literature.

Structure and electronic properties of hydrated mesityl oxide: a sequential quantum mechanics/molecular mechanics approach

The hydration of mesityl oxide (MOx) was investigated through a sequential quantum mechanics/molecular mechanics approach. Emphasis was placed on the analysis of the role played by water in the MOx syn-anti equilibrium and the electronic absorption spectrum. Results for the structure of the MOx-water solution, free energy of solvation and polarization effects are also reported. Our main conclusion was that in gas-phase and in low-polarity solvents, the MOx exists dominantly in syn-form and in aqueous solution in anti-form. This conclusion was supported by Gibbs free energy calculations in gas phase and in-water by quantum mechanical calculations with polarizable continuum model and thermodynamic perturbation theory in Monte Carlo simulations using a polarized MOx model. The consideration of the in-water polarization of the MOx is very important to correctly describe the solute-solvent electrostatic interaction. Our best estimate for the shift of the pi-pi* transition energy of MOx, when it changes from gas-phase to water solvent, shows a red-shift of -2,520 +/- 90 cm(-1), which is only 110 cm(-1) (0.014 eV) below the experimental extrapolation of -2,410 +/- 90 cm(-1). This red-shift of around -2,500 cm(-1) can be divided in two distinct and opposite contributions. One contribution is related to the syn -> anti conformational change leading to a blue-shift of similar to 1,700 cm(-1). Other contribution is the solvent effect on the electronic structure of the MOx leading to a red-shift of around -4,200 cm(-1). Additionally, this red-shift caused by the solvent effect on the electronic structure can by composed by approximately 60 % due to the electrostatic bulk effect, 10 % due to the explicit inclusion of the hydrogen-bonded water molecules and 30 % due to the explicit inclusion of the nearest water molecules.

Sleep in patients with large pleural effusion: impact of thoracentesis

This study aimed to evaluate the sleep quality and impact of thoracentesis on sleep in patients with a large pleural effusion. Patients with large unilateral pleural effusion were evaluated by the Pittsburgh Sleep Quality Index (PSQI) questionnaire and dyspnea Borg scale. Full polysomnography (PSG) was performed on the night before and 36 h after thoracentesis. We studied 19 patients, 11 males and 8 females, age 55 +/- 18 years and body mass index of 26 +/- 5 kg/m(2). The baseline sleep quality was poor (PSQI = 9.1 +/- 3.5). Thoracentesis removed 1.624 +/- 796 mL of pleural fluid and resulted in a significant decrease in dyspnea Borg scale (2.3 +/- 2.1 vs. 0.8 +/- 0.9, p < 0.001). The PSG before and after thoracentesis showed no significant change in apnea-hypopnea index and sleep time with oxygen saturation < 90%. There was a significant improvement in sleep efficiency (76% vs. 81%, p = 0.006), decrease percent sleep stage 1 (16% vs. 14%, p = 0.002), and a trend improvement in total sleep time (344 +/- 92 vs. 380 +/- 69 min, p = 0.056) and percentage of rapid eye movement sleep (15% vs. 20%, p = 0.053). No significant changes occurred in six patients that performed two consecutive PSG before thoracentesis. The improvement in sleep quality was not associated with the volume of pleural fluid withdrawn or changes in dyspnea. Patients with large pleural effusion have poor subjective and objective sleep quality that improves after thoracentesis.

Effects of Repeated Stress on Distal Airway Inflammation, Remodeling and Mechanics in an Animal Model of Chronic Airway Inflammation

Background/Aims: Epidemiological studies suggest that stress has an impact on asthmatic exacerbations. We evaluated if repeated stress, induced by forced swimming, modulates lung mechanics, distal airway inflammation and extracellular matrix remodeling in guinea pigs with chronic allergic inflammation. Methods: Guinea pigs were submitted to 7 ovalbumin or saline aerosols (1-5 mg/ml during 4 weeks; OVA and SAL groups). Twenty-four hours after the 4th inhalation, guinea pigs were submitted to the stress protocol 5 times a week during 2 weeks (SAL-S and OVA-S groups). Seventy-two hours after the 7th inhalation, guinea pigs were anesthetized and mechanically ventilated. Resistance and elastance of the respiratory system were obtained at baseline and after ovalbumin challenge. Lungs were removed, and inflammatory and extracellular matrix remodeling of distal airways was assessed by morphometry. Adrenals were removed and weighed. Results: The relative adrenal weight was greater in stressed guinea pigs compared to non-stressed animals (p < 0.001). Repeated stress increased the percent elastance of the respiratory system after antigen challenge and eosinophils and lymphocytes in the OVA-S compared to the OVA group (p < 0.001, p = 0.003 and p < 0.001). Neither collagen nor elastic fiber contents were modified by stress in sensitized animals. Conclusions: In this animal model, repeated stress amplified bronchoconstriction and inflammatory response in distal airways without interfering with extracellular matrix remodeling. Copyright (C) 2011 S. Karger AG, Basel