Effects of Positive End-expiratory Pressure Titration and Recruitment Maneuver on Lung Inflammation and Hyperinflation in Experimental Acid Aspiration-induced Lung Injury

Background: In acute lung injury positive end-expiratory pressure (PEEP) and recruitment maneuver are proposed to optimize arterial oxygenation. The aim of the study was to evaluate the impact of such a strategy on lung histological inflammation and hyperinflation in pigs with acid aspiration-induced lung injury. Methods: Forty-seven pigs were randomly allocated in seven groups: (1) controls spontaneously breathing; (2) without lung injury, PEEP 5 cm H2O; (3) without lung injury, PEEP titration; (4) without lung injury, PEEP titration + recruitment maneuver; (5) with lung injury, PEEP 5 cm H2O; (6) with lung injury, PEEP titration; and (7) with lung injury, PEEP titration + recruitment maneuver. Acute lung injury was induced by intratracheal instillation of hydrochloric acid. PEEP titration was performed by incremental and decremental PEEP from 5 to 20 cm H2O for optimizing arterial oxygenation. Three recruitment maneuvers (pressure of 40 cm H2O maintained for 20 s) were applied to the assigned groups at each PEEP level. Proportion of lung inflammation, hemorrhage, edema, and alveolar wall disruption were recorded on each histological field. Mean alveolar area was measured in the aerated lung regions. Results: Acid aspiration increased mean alveolar area and produced alveolar wall disruption, lung edema, alveolar hemorrhage, and lung inflammation. PEEP titration significantly improved arterial oxygenation but simultaneously increased lung inflammation in juxta-diaphragmatic lung regions. Recruitment maneuver during PEEP titration did not induce additional increase in lung inflammation and alveolar hyperinflation. Conclusion: In a porcine model of acid aspiration-induced lung injury, PEEP titration aimed at optimizing arterial oxygenation, substantially increased lung inflammation. Recruitment maneuvers further improved arterial oxygenation without additional effects on inflammation and hyperinflation.

Severe lower respiratory tract infection in infants and toddlers from a non-affluent population: viral etiology and co-detection as risk factors

Abstract Background Lower respiratory tract infection (LRTI) is a major cause of pediatric morbidity and mortality, especially among non-affluent communities. In this study we determine the impact of respiratory viruses and how viral co-detections/infections can affect clinical LRTI severity in children in a hospital setting. Methods Patients younger than 3 years of age admitted to a tertiary hospital in Brazil during the months of high prevalence of respiratory viruses had samples collected from nasopharyngeal aspiration. These samples were tested for 13 different respiratory viruses through real-time PCR (rt-PCR). Patients were followed during hospitalization, and clinical data and population characteristics were collected during that period and at discharge to evaluate severity markers, especially length of hospital stay and oxygen use. Univariate regression analyses identified potential risk factors and multivariate logistic regressions were used to determine the impact of specific viral detections as well as viral co-detections in relation to clinical outcomes. Results We analyzed 260 episodes of LRTI with a viral detection rate of 85% (n = 222). Co-detection was observed in 65% of all virus-positive episodes. The most prevalent virus was Respiratory Syncytial Virus (RSV) (54%), followed by Human Metapneumovirus (hMPV) (32%) and Human Rhinovirus (HRV) (21%). In the multivariate models, infants with co-detection of HRV + RSV stayed 4.5 extra days (p = 0.004), when compared to infants without the co-detection. The same trends were observed for the outcome of days of supplemental oxygen use. Conclusions Although RSV remains as the main cause of LRTI in infants our study indicates an increase in the length of hospital stay and oxygen use in infants with HRV detected by RT-PCR compared to those without HRV. Moreover, one can speculate that when HRV is detected simultaneously with RSV there is an additive effect that may be reflected in more severe clinical outcome. Also, our study identified a significant number of children infected by recently identified viruses, such as hMPV and Human Bocavirus (HBov), and this is a novel finding for poor communities from developing countries.

Respiratory rhythms in stingless bee workers: circadian and ultradian components throughout adult development

The workers of the stingless bee, Melipona quadrifasciata, assume different tasks during their adult life. Newly emerged individuals remain inside the nest, without contact with the external environment. Maturing workers go to more peripheral regions and only the oldest, the foragers, leave the nest. As this diversity of activities implies different metabolic patterns, oxygen consumption has been measured in workers of three different ages: 24-48 h (nurses), 10-15 days (builders), and older than 25 days (foragers). Oxygen consumption of individually isolated workers was determined by intermittent respirometry, under constant darkness and temperature of 25 +/- 1 degrees C. Sets of 24-h measurements were obtained from individuals belonging to each of the three worker groups. Rhythmicity has been assessed in the daily (24 h) and ultradian (5-14 h) domains. This experimental design allowed detection of endogenous rhythms without the influence of the social group and without inflicting stress on the individuals, as would be caused by their longer isolation from the colony. Significant 24-h rhythms in oxygen consumption were present in nurses, builders and foragers; therefore, workers are rhythmic from the age of 24-48 h. However, the amplitude of the circadian rhythm changed according to age: nurses showed the lowest values, while foragers consistently presented the largest ones, about ten times larger than the amplitude of nurses` respiratory rhythm. Ultradian frequencies were detected for all worker groups, the power and frequencies of which varied little with age. This means that the ultradian strength was relatively larger in nurses and apparently maintains some relationship with the queen`s oviposition episodes.

Broncoscopia flexível como primeira opção para a remoção de corpo estranho das vias aéreas em adultos

OBJETIVO: Determinar a taxa de sucesso da broncoscopia flexível como primeira opção na remoção de corpos estranhos das vias aéreas em adultos. MÉTODOS: Estudo retrospectivo de todos os pacientes adultos (acima de 18 anos) com aspiração de corpo estranho submetidos a broncoscopia no Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, em São Paulo (SP). RESULTADOS: A amostra foi constituída por 40 pacientes adultos, com média de idade de 52 anos (variação: 18-88 anos). A mediana do tempo de permanência do corpo estranho na via aérea foi de 15 dias (variação: 12 h a 10 anos). Todos os pacientes foram submetidos primeiramente a broncoscopia flexível diagnóstica. A retirada do corpo estranho por meio de broncoscopia flexível foi bem-sucedida em 33 dos pacientes (82,5%). Em 1 paciente, um objeto metálico alojado na árvore brônquica distal requereu o uso de fluoroscopia. Seis pacientes (15%) foram submetidos a broncoscopia rígida devido a dispneia induzida por corpo estranho traqueal, em 2, e porque o corpo estranho era muito grande para as pinças flexíveis, em 4. A broncoscopia falhou em apenas 1 paciente, que portanto necessitou de broncotomia. CONCLUSÕES: Embora a broncoscopia rígida seja considerada o padrão ouro na remoção de corpos estranhos na via aérea, nossa experiência mostrou que a broncoscopia flexível pode ser utilizada segura e eficientemente no diagnóstico e tratamento de pacientes adultos estáveis.

Molecular epidemiology of the SH (small hydrophobic) gene of human respiratory syncytial virus (HRSV), over 2 consecutive years

Human respiratory syncytial virus (HRSV) strains were isolated from nasopharyngeal aspirates collected from 965 children between 2004 and 2005, yielding 424 positive samples. We sequenced the small hydrophobic protein (SH) gene of 117 strains and compared them with other viruses identified worldwide. Phylogenetic analysis showed a low genetic variability among the isolates but allowed us to classify the viruses into different genotypes for both groups, HRSVA and HRSVB. It is also shown that the novel BA-like genotype was well segregated from the others, indicating that the mutations are not limited to the G gene. (C) 2011 Elsevier B.V. All rights reserved.

Respiratory rehabilitation: a physiotherapy approach to the control of asthma symptoms and anxiety

OBJECTIVES: The objectives of this study were to verify the degree of anxiety, respiratory distress, and health-related quality of life in a group of asthmatic patients who have experienced previous panic attacks. Additionally, we evaluated if a respiratory physiotherapy program (breathing retraining) improved both asthma and panic disorder symptoms, resulting in an improvement in the health-related quality of life of asthmatics. METHODS: Asthmatic individuals were assigned to a chest physiotherapy group that included a breathing retraining program held once a week for three months or a paired control group that included a Subtle Touch program. All patients were assessed using the Diagnostic and Statistical Manual of Mental Disorders IV, the Sheehan Anxiety Scale, the Quality of Life Questionnaire, and spirometry parameter measurements. RESULTS: Both groups had high marks for panic disorder and agoraphobia, which limited their quality of life. The Breathing Retraining Group program improved the clinical control of asthma, reduced panic symptoms and agoraphobia, decreased patient scores on the Sheehan Anxiety Scale, and improved their quality of life. Spirometry parameters were unchanged. CONCLUSION: Breathing retraining improves the clinical control of asthma and anxiety symptoms and the health-related quality of life in asthmatic patients.

Diversity and Adaptation of Human Respiratory Syncytial Virus Genotypes Circulating in Two Distinct Communities: Public Hospital and Day Care Center

HRSV is one of the most important pathogens causing acute respiratory tract diseases as bronchiolitis and pneumonia among infants. HRSV was isolated from two distinct communities, a public day care center and a public hospital in Sao Jose do Rio Preto - SP, Brazil. We obtained partial sequences from G gene that were used on phylogenetic and selection pressure analysis. HRSV accounted for 29% of respiratory infections in hospitalized children and 7.7% in day care center children. On phylogenetic analysis of 60 HRSV strains, 48 (80%) clustered within or adjacent to the GA1 genotype; GA5, NA1, NA2, BA-IV and SAB1 were also observed. SJRP GA1 strains presented variations among deduced amino acids composition and lost the potential O-glycosilation site at amino acid position 295, nevertheless this resulted in an insertion of two potential O-glycosilation sites at positions 296 and 297. Furthermore, a potential O-glycosilation site insertion, at position 293, was only observed for hospital strains. Using SLAC and MEME methods, only amino acid 274 was identified to be under positive selection. This is the first report on HRSV circulation and genotypes classification derived from a day care center community in Brazil.

Distinct mechanisms underlie adaptation of proximal tubule Na+/H+ exchanger isoform 3 in response to chronic metabolic and respiratory acidosis

The Na+/H+ exchanger isoform 3 (NHE3) is essential for HCO3- reabsorption in renal proximal tubules. The expression and function of NHE3 must adapt to acid-base conditions. The goal of this study was to elucidate the mechanisms responsible for higher proton secretion in proximal tubules during acidosis and to evaluate whether there are differences between metabolic and respiratory acidosis with regard to NHE3 modulation and, if so, to identify the relevant parameters that may trigger these distinct adaptive responses. We achieved metabolic acidosis by lowering HCO3- concentration in the cell culture medium and respiratory acidosis by increasing CO2 tension in the incubator chamber. We found that cell-surface NHE3 expression was increased in response to both forms of acidosis. Mild (pH 7.21 +/- 0.02) and severe (6.95 +/- 0.07) metabolic acidosis increased mRNA levels, at least in part due to up-regulation of transcription, whilst mild (7.11 +/- 0.03) and severe (6.86 +/- 0.01) respiratory acidosis did not up-regulate NHE3 expression. Analyses of the Nhe3 promoter region suggested that the regulatory elements sensitive to metabolic acidosis are located between -466 and -153 bp, where two consensus binding sites for SP1, a transcription factor up-regulated in metabolic acidosis, were localised. We conclude that metabolic acidosis induces Nhe3 promoter activation, which results in higher mRNA and total protein level. At the plasma membrane surface, NHE3 expression was increased in metabolic and respiratory acidosis alike, suggesting that low pH is responsible for NHE3 displacement to the cell surface.

Luteal function and follicular growth following follicular aspiration during the peri-luteolysis period in bos indicus and crossbred cattle

Follicular estradiol triggers luteolysis in cattle. Therefore, the control of follicle growth and steroidogenesis is expected to modulate luteal function and might be used as an anti-luteolytic strategy to improve embryo survival. Objectives were to evaluate follicular dynamics, plasma concentrations of estradiol and luteal lifespan in Bos indicus and crossbred cows subjected to sequential follicular aspirations. From D13 to D25 of a synchronized cycle (ovulation = D1), Nelore or crossbred, non-pregnant and non-lactating cows were submitted to daily ultrasound-guided aspiration of follicles >6 mm (n = 10) or to sham aspirations (n = 8). Diameter of the largest follicle on the day of luteolysis (7.4 +/- 1.0 vs 9.7 +/- 1.0 mm; mean +/- SEM), number of days in which follicles >6 mm were present (2.3 +/- 0.4 vs 4.6 +/- 0.5 days) and daily mean diameter of the largest follicle between D15 and D19 (6.4 +/- 0.2 vs 8.5 +/- 0.3 mm) were smaller (p <0.01) in the aspirated group compared with the control group, respectively. Aspiration tended to reduce (p< 0.10) plasma estradiol concentrations between D18 and D20 (2.95 +/- 0.54 vs 4.30 +/- 0.55 pg/ml). The luteal lifespan was similar (p > 0.10) between the groups (19.6 +/- 0.4 days), whereas the oestrous cycle was longer (p <0.01) in the aspirated group (31.4 +/- 1.2 vs 21.2 +/- 1.3 days). Hyperechogenic structures were present at the sites of aspiration and were associated with increase in concentration of progesterone between luteolysis and oestrus. It is concluded that follicular aspiration extended the oestrous cycle and decreased the average follicular diameter on the peri-luteolysis period but failed to delay luteolysis.

Calorie restriction increases cerebral mitochondrial respiratory capacity in a NO center dot-mediated mechanism: Impact on neuronal survival

Calorie restriction (CR) enhances animal life span and prevents age-related diseases, including neurological decline. Recent evidence suggests that a mechanism involved in CR-induced life-span extension is NO-stimulated mitochondrial biogenesis. We examine here the effects of CR on brain mitochondrial content. CR increased eNOS and nNOS and the content of mitochondria] proteins (cytochrome c oxidase, citrate synthase, and mitofusin) in the brain. Furthermore, we established an in vitro system to study the neurological effects of CR using serum extracted from animals on this diet. In cultured neurons, CR serum enhanced nNOS expression and increased levels of nitrite (a NO product). CR serum also enhanced the levels of cytochrome c oxidase and increased citrate synthase activity and respiratory rates in neurons. CR serum effects were inhibited by L-NAME and mimicked by the NO donor SNAP. Furthermore, both CR sera and SNAP were capable of improving neuronal survival. Overall, our results indicate that CR increases mitochondrial biogenesis in a NO-mediated manner, resulting in enhanced reserve respiratory capacity and improved survival in neurons. (C) 2012 Elsevier Inc. All rights reserved.

KCNQ Channels Determine Serotonergic Modulation of Ventral Surface Chemoreceptors and Respiratory Drive

Chemosensitive neurons in the retrotrapezoid nucleus (RTN) regulate breathing in response to CO2/H+ changes. Their activity is also sensitive to neuromodulatory inputs from multiple respiratory centers, and thus they serve as a key nexus of respiratory control. However, molecular mechanisms that control their activity and susceptibility to neuromodulation are unknown. Here, we show in vitro and in vivo that KCNQ channels are critical determinants of RTN neural activity. In particular, we find that pharmacological block of KCNQ channels (XE991, 10 mu M) increased basal activity and CO2 responsiveness of RTN neurons in rat brain slices, whereas KCNQ channel activation (retigabine, 2-40 mu M) silenced these neurons. Interestingly, we also find that KCNQ and apamin-sensitive SK channels act synergistically to regulate firing rate of RTN chemoreceptors; simultaneous blockade of both channels led to a increase in CO2 responsiveness. Furthermore, we also show that KCNQ channels but not SK channels are downstream effectors of serotonin modulation of RTN activity in vitro. In contrast, inhibition of KCNQ channel did not prevent modulation of RTN activity by Substance P or thyrotropin-releasing hormone, previously identified neuromodulators of RTN chemoreception. Importantly, we also show that KCNQ channels are critical for RTN activity in vivo. Inhibition of KCNQ channels lowered the CO2 threshold for phrenic nerve discharge in anesthetized rats and decreased the ventilatory response to serotonin in awake and anesthetized animals. Given that serotonergic dysfunction may contribute to respiratory failure, our findings suggest KCNQ channels as a new therapeutic avenue for respiratory complications associated with multiple neurological disorders.

(+)alpha-Tocopheryl succinate inhibits the mitochondrial respiratory chain complex I and is as effective as arsenic trioxide or ATRA against acute promyelocytic leukemia in vivo

The vitamin E derivative (+)alpha-tocopheryl succinate (alpha-TOS) exerts pro-apoptotic effects in a wide range of tumors and is well tolerated by normal tissues. Previous studies point to a mitochondrial involvement in the action mechanism; however, the early steps have not been fully elucidated. In a model of acute promyelocytic leukemia (APL) derived from hCG-PML-RAR alpha transgenic mice, we demonstrated that alpha-TOS is as effective as arsenic trioxide or all-trans retinoic acid, the current gold standards of therapy. We also demonstrated that alpha-TOS induces an early dissipation of the mitochondrial membrane potential in APL cells and studies with isolated mitochondria revealed that this action may result from the inhibition of mitochondrial respiratory chain complex I. Moreover, alpha-TOS promoted accumulation of reactive oxygen species hours before mitochondrial cytochrome c release and caspases activation. Therefore, an in vivo antileukemic action and a novel mitochondrial target were revealed for alpha-TOS, as well as mitochondrial respiratory complex I was highlighted as potential target for anticancer therapy. Leukemia (2012) 26, 451-460; doi:10.1038/leu.2011.216; published online 26 August 2011

Resultados maternos e neonatais em centro de parto normal peri-hospitalar e hospital

OBJETIVO: Comparar os resultados maternos e neonatais em mulheres de baixo risco atendidas em centro de parto normal peri-hospitalar e hospital. MÉTODOS: Estudo transversal com amostra representativa de mulheres de baixo risco atendidas em São Paulo, SP, de 2003 a 2006. Foram incluídas 991 mulheres que tiveram o parto no centro de parto normal e 325 que deram à luz no hospital. Os dados foram obtidos dos prontuários. A análise comparativa foi realizada para o total de mulheres e estratifi cada segundo a paridade. Foram aplicados os testes qui-quadrado e exato de Fisher. RESULTADOS: Houve distribuição homogênea das mulheres segundo a paridade (45,4% nulíparas e 54,6% mulheres com um ou mais partos anteriores). Foram encontradas diferenças estatisticamente signifi cantes em relação às seguintes intervenções: amniotomia (mais freqüente entre nulíparas do hospital); utilização de ocitocina no trabalho de parto e utilização de analgésico no pós-parto (mais freqüentes no hospital entre as mulheres de todas as paridades). A taxa de episiotomia foi maior entre as nulíparas, tanto no centro de parto como no hospital. Houve maior freqüência de intervenções com o neonato no hospital: aspiração das vias aéreas superiores, aspiração gástrica, lavagem gástrica, oxigênio por máscara aberta. Também ocorreram com mais freqüência no hospital bossa serossanguínea, desconforto respiratório e internação na unidade neonatal. Não houve diferença nos valores de Apgar no quinto minuto nem casos de morte materna ou perinatal. CONCLUSÕES: A assistência no centro de parto normal foi realizada com menos intervenções e com resultados maternos e neonatais semelhantes aos do hospital.

EFFECT OF COMPETITION ON SALIVARY CORTISOL, IMMUNOGLOBULIN A, AND UPPER RESPIRATORY TRACT INFECTIONS IN ELITE YOUNG SOCCER PLAYERS

Mortatti, AL, Moreira, A, Aoki, MS, Crewther, BT, Castagna, C, de Arruda, AFS, and Filho, JM. Effect of competition on salivary cortisol, immunoglobulin A, and upper respiratory tract infections in elite young soccer players. J Strength Cond Res 26(5): 1396-1401, 2012-The present study examined the effect of a 20-day period of competition on salivary cortisol, mucosal immunity, and upper respiratory tract infections (URTI) in young male soccer players (n = 14). The players were monitored during the main under-19 Brazilian soccer championship, in which 7 matches were played in 20 days. Saliva samples were collected in the morning of each match and analyzed for cortisol and immunoglobulin A (IgA). Signs and symptoms of URTI were assessed across the study and a rating of perceived exertion (RPE) was obtained for each match. Compared with match 1, a significant increase in player RPE was observed in matches 4-7 (p < 0.05). Significant (p < 0.05) increases in the reporting of URTI occurred between matches 2 and 3, and 6 and 7, and this was accompanied by significant decreases in salivary IgA levels. Significant (p < 0.05) correlations were also seen between the individual reports of URTI and the decrease in IgA levels in match 2 (r = -0.60) and match 6 (r = -0.65). These results suggest that decrements in mucosal immunity, as measured by salivary IgA concentrations, may lead to a greater incidence of URTI in elite young soccer players. It may be speculated that the physiological and psychological stressors imposed by training and competition in a short timeframe are major contributing factors to these responses. Thus, the monitoring of salivary IgA could provide a useful and noninvasive approach for predicting URTI occurrences in young athletes during short-term competitions, especially if frequent sampling and rapid measurements are made.

The therapeutic journey of families of children with respiratory diseases in the public health service

This study's purpose was to identify the therapeutic journey of families seeking health care for their children with respiratory diseases. This qualitative study had the participation of parents of children younger than five years old who were hospitalized with respiratory diseases. Path mapping was used as an instrument to collect data, which was analyzed through thematic analysis. The finding indicate that families sought the health services as soon as they perceived symptoms and had access to medical care, however such care was not decisive in resolving their health issues. Even though the families returned to the service at least another three times, the children had to be hospitalized. The attributes of primary health care were not observed in the public health services, while therapeutic encounters had no practical success.