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Ventilator-induced lung injury plays a crucial role in the outcome of patients with acute lung injury. Previous studies have shown a role for the cytokine tumor necrosis factor-[alpha](TNF) in stretch-induced alveolar neutrophil recruitment, but the involvement of TNF in stretch-induced pulmonary edema is unclear. We investigated the effects of TNF through its individual p55 and p75 receptors on early pulmonary edema formation during high stretch ventilation, before neutrophil infiltration. Anesthetized wild-type or TNF receptor single/double knockout mice were ventilated with high tidal volume (~38 ml/kg) for 2 h or until they developed arterial hypotension. Pulmonary edema was assessed by physiological parameters including respiratory mechanics and blood gases, and by lavage fluid protein, lung wet:dry weight ratio, and lung permeability measurements using fluorescence-labeled albumin. High stretch ventilation in wild-type and TNF receptor double knockout animals induced similar pulmonary edema, and only 25-30% of mice completed the protocol. In contrast, the p55 receptor knockout mice were strongly protected from edema formation, with all animals completing the protocol. Myeloperoxidase assay indicated that this protective effect was not associated with decreased pulmonary neutrophil sequestration. The p75 receptor knockout mice, however, displayed increased susceptibility to edema formation, and no animals survived the full 2 h. These results demonstrate a novel role for TNF signaling (independent from its effects on neutrophil recruitment) specifically through the p55 receptor, in promoting high stretch-induced pulmonary edema, whereas p75 signaling may play an opposing role. acute lung injury; cytokines; inflammation; ventilator-induced lung injury doi:10.1152/ajplung.00284.2006

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of morbidity and mortality in the intensive care unit, but despite continuing research few effective therapies have been identified. In recent years, inhaled carbon monoxide (CO) has been reported to have cytoprotective effects in several animal models of tissue injury. We therefore evaluated the effects of inhaled CO in three different in vivo mouse models of ALI. Anesthetized C57BL/6 mice were ventilated with oxygen in the presence or absence of CO (500 parts per million) for 1 h before lung injury was induced by lipopolysaccharide (LPS) or oleic acid (OA) administration. Ventilation was then continued with the same gases for a further 2-3 h, with hemodynamic and respiratory parameters monitored throughout. Intratracheal LPS administration induced lung injury with alveolar inflammation (increased lavage fluid neutrophils, total protein, and cytokines). In contrast, intravenous LPS induced a predominantly vascular lung injury, with increased plasma TNF and increased neutrophil activation (surface Mac-1 upregulation and L-selectin shedding) and sequestration within the pulmonary vasculature. Intravenous OA produced deteriorations in lung function, reflected by changes in respiratory mechanics and blood gases and lavage fluid neutrophil accumulation. However, addition of CO to the inspired gas did not produce significant changes in the measured physiological or immunological parameters in the mouse models used in this study. Thus the results do not support the hypothesis that use of inhaled CO is beneficial in the treatment of ALI and ARDS. cytokines; lipopolysaccharide; oleic acid; neutrophil recruitment; pulmonary inflammation

Although high-stretch mechanical ventilation has been demonstrated to induce lung inflammation, the roles of soluble mediators, in particular TNF, remain controversial. We have previously shown in mice that high-stretch ventilation, in the absence of preceding lung injury, induces expression of bioactive TNF in lung lavage fluid early in the course of injury, but the biological significance of this, if any, has yet to be determined. We therefore investigated the pulmonary inflammatory response to a transient period of high-stretch ventilation in anesthetized mice lacking TNF receptors and mice treated with anti-TNF antibodies. A standardized stretch-induced lung injury (assessed by lung mechanics, blood gases, and lavage protein content), followed by noninjurious low-stretch ventilation for 3 h, produced significant alveolar neutrophil infiltration in wild-type mice. However, neutrophil recruitment was substantially attenuated in TNF receptor double knockout mice and in wild-type mice treated with intratracheal anti-TNF antibody. This attenuation was not associated with decreased concentrations of neutrophil attractant CXC chemokines (macrophage inflammatory protein-2 and keratinocyte-derived chemokine) in lavage fluid. In contrast to intratracheal antibody, intravenous anti-TNF antibody did not reduce neutrophil infiltration, suggesting that the role of TNF signaling is localized within the alveolar space and does not require decompartmentalization of TNF into the circulation. These findings provide the first direct evidence that pulmonary inflammation induced by high-stretch ventilation without underlying lung injury possesses a significant TNF-dependent component. The results suggest a potential for regional anti-TNF treatment in attenuating stretch-induced pulmonary inflammation. tumor necrosis factor receptor knockout mice; anti-tumor necrosis factor antibody; chemokine; ventilator-induced lung injury

Mechanisms of early pulmonary neutrophil sequestration in ventilator-induced lung injury in mice. Am J Physiol Lung Cell Mol Physiol 287:L902-L910, 2004. First published July 16, 2004; doi:10.1152/ajplung.00187.2004.--Polymorphonuclear leukocytes (PMN) play an important role in ventilator-induced lung injury (VILI), but the mechanisms of pulmonary PMN recruitment, particularly early intravascular PMN sequestration during VILI, have not been elucidated. We investigated the physiological and molecular mechanisms of pulmonary PMN sequestration in an in vivo mouse model of VILI. Anesthetized C57/BL6 mice were ventilated for 1 h with high tidal volume (injurious ventilation), low tidal volume and high positive end-expiratory pressure (protective ventilation), or normal tidal volume (control ventilation). Pulmonary PMN sequestration analyzed by flow cytometry of lung cell suspensions was substantially enhanced in injurious ventilation compared with protective and control ventilation, preceding development of physiological signs of lung injury. Anesthetized, spontaneously breathing mice with continuous positive airway pressure demonstrated that raised alveolar pressure alone does not induce PMN entrapment. In vitro leukocyte deformability assay indicated stiffening of circulating leukocytes in injurious ventilation compared with control ventilation. PMN sequestration in injurious ventilation was markedly inhibited by administration of anti-L-selectin antibody, but not by anti-CD18 antibody. These results suggest that mechanical ventilatory stress initiates pulmonary PMN sequestration early in the course of VILI, and this phenomenon is associated with stretch-induced inflammatory events leading to PMN stiffening and mediated by L-selectin-dependent but CD18-independent mechanisms. leukocytes; lung inflammation; mechanical ventilation

This article analyzes Social Security benefits as a retirement resource for selected subgroups of recent cohorts of near-retirees. The analysis therein examines the distribution of benefits among subgroups by (1) [...]

The causes behind the divorce in monogamous birds are yet to be comprehended in spite of the study on avian mating system. Many hypotheses are put forth to understand why and when individuals may divorce but they are yet to be properly organized theoretically and empirically. There are confusions about the assumptions and predictions of the individual models due to the absence of substantial theoretical framework. Further progress in the area needs sound mathematical modelling of the hypotheses.

Analysis of the breeding behavior of wild barnacle geese, Branta leucopsis, suggests that the geese pair randomly with individuals from their own breeding sites, despite occurrence of pairing in different breeding regions. Pairing with familiar individuals from the same breeding region improves mate complementarity in adjustment to the same habitat. The geese either select partners from past associates or individuals with phenotypic traits similar to their breeding region.

Mate selection strategies in the monogamous barnacle goose, Branta leucopsis, were investigated. Geese were found to make 'trial liaisons' with from one to six possible mates, with heavier and more vigilant females having a greater number of trial mates. Two strategies appear to be used; 'one-step decisions' in which the bird moves to a new partner after rejecting an earlier, and 'partner-held' where a mate is retained while a new one is sampled. Females appear to prefer the first strategy, males the second. The 'partner-held' and early pairing would appear to offer advantages.

Summary White households in the United States are far wealthier than black or Hispanic households, a disparity that remains unexplained even after taking into account income and demographic factors. This [...]

This article focuses on the relationship between women's economic status earlier in their lives and their poverty status in old age. Previous research on the determinants of poverty among aged [...]

Presents a study which examined racial and ethnic differences in housing equity in the U.S. Examination of total wealth by household income; Percentage of financial wealth of households; Analysis of risky assets by educational level.

Large-sized Barnacle Geese Branta leucopsis of both sexes had a higher probability of breeding successfully in any particular year and produced more goslings than did smaller birds. Large females paired at an earlier age, suggesting that they were preferred as mates and were likely to have entered the breeding population earlier. The relative sizes of the pair bond members also affected fitness. Most birds were able to maximize their breeding performance by mating with relatively similar sized partners; the greater the size disparity of mates, the lower the breeding performance. This supports the idea that compatibility of mates may be important in determining fitness of the pair. The success of different pair types was also affected by environmental conditions, with certain size combinations doing better in some years and poorly in other years. [ABSTRACT FROM AUTHOR]