Endothelin receptor antagonist improves donor lung function in an ex vivo perfusion system.

BACKGROUND: A lung transplant is the last resort treatment for many patients with advanced lung disease. The majority of donated lungs come from donors following brain death (BD). The endothelin axis is upregulated in the blood and lung of the donor after BD resulting in systemic inflammation, lung damage and poor lung graft outcomes in the recipient. Tezosentan (endothelin receptor blocker) improves the pulmonary haemodynamic profile; however, it induces adverse effects on other organs at high doses. Application of ex vivo lung perfusion (EVLP) allows the development of organ-specific hormone resuscitation, to maximise and optimise the donor pool. Therefore, we investigate whether the combination of EVLP and tezosentan administration could improve the quality of donor lungs in a clinically relevant 6-h ovine model of brain stem death (BSD). METHODS: After 6 h of BSD, lungs obtained from 12 sheep were divided into two groups, control and tezosentan-treated group, and cannulated for EVLP. The lungs were monitored for 6 h and lung perfusate and tissue samples were processed and analysed. Blood gas variables were measured in perfusate samples as well as total proteins and pro-inflammatory biomarkers, IL-6 and IL-8. Lung tissues were collected at the end of EVLP experiments for histology analysis and wet-dry weight ratio (a measure of oedema). RESULTS: Our results showed a significant improvement in gas exchange [elevated partial pressure of oxygen (P = 0.02) and reduced partial pressure of carbon dioxide (P = 0.03)] in tezosentan-treated lungs compared to controls. However, the lungs hematoxylin-eosin staining histology results showed minimum lung injuries and there was no difference between both control and tezosentan-treated lungs. Similarly, IL-6 and IL-8 levels in lung perfusate showed no difference between control and tezosentan-treated lungs throughout the EVLP. Histological and tissue analysis showed a non-significant reduction in wet/dry weight ratio in tezosentan-treated lung tissues (P = 0.09) when compared to control. CONCLUSIONS: These data indicate that administration of tezosentan could improve pulmonary gas exchange during EVLP.

Brain stem death induces pro-inflammatory cytokine production and cardiac dysfunction in sheep model.

INTRODUCTION: Organs procured following brain stem death (BSD) are the main source of organ grafts for transplantation. However, BSD is associated with inflammatory responses that may damage the organ and affect both the quantity and quality of organs available for transplant. Therefore, we aimed to investigate plasma and bronchoalveolar lavage (BAL) pro-inflammatory cytokine profiles and cardiovascular physiology in a clinically relevant 6-h ovine model of BSD. METHODS: Twelve healthy female sheep (37-42 Kg) were anaesthetized and mechanically ventilated prior to undergoing BSD induction and then monitored for 6 h. Plasma and BAL endothelin-1 and cytokines (IL-1ß, 6, 8 and tumour necrosis factor alpha (TNF-α)) were assessed by ELISA. Differential white blood cell counts were performed. Cardiac function during BSD was also examined using echocardiography, and cardiac biomarkers (A-type natriuretic peptide and troponin I were measured in plasma. RESULTS: Plasma concentrations big ET-1, IL-6, IL-8, TNF-α and BAL IL-8 were significantly (p < 0.01) increased over baseline at 6 h post-BSD. Increased numbers of neutrophils were observed in the whole blood (3.1 × 109 cells/L [95% confidence interval (CI) 2.06-4.14] vs. 6 × 109 cells/L [95%CI 3.92-7.97]; p < 0.01) and BAL (4.5 × 109 cells/L [95%CI 0.41-9.41] vs. 26 [95%CI 12.29-39.80]; p = 0.03) after 6 h of BSD induction vs baseline. A significant increase in ANP production (20.28 pM [95%CI 16.18-24.37] vs. 78.68 pM [95%CI 53.16-104.21]; p < 0.0001) and cTnI release (0.039 ng/mL vs. 4.26 [95%CI 2.69-5.83] ng/mL; p < 0.0001), associated with a significant reduction in heart contractile function, were observed between baseline and 6 h. CONCLUSIONS: BSD induced systemic pro-inflammatory responses, characterized by increased neutrophil infiltration and cytokine production in the circulation and BAL fluid, and associated with reduced heart contractile function in ovine model of BSD.

Chemotrophic growth of heliobacteria in darkness.

Conditions are described that support anaerobic dark chemotrophic growth of heliobacteria. Growth was pyruvate-dependent and was best in well-buffered pyruvate media supplemented with yeast extract. Heliobacterial cells grown in darkness synthesized bacteriochlorophyll g and carotenoids and fermented pyruvate to acidic products, CO2, and in some cases, H2. All recognized species of heliobacteria as well as several newly isolated strains were capable of dark anaerobic growth, suggesting that this growth mode may be ecologically important for survival of these organisms in their soil habitat.

Shape constancy from novel views.

Prior experiments on shape constancy from novel views are inconclusive: Some show that shapes of objects can be recognized reliably from novel views, whereas others show just the opposite. Our analysis of prior results suggests that shape constancy from novel views is reliable when the object has properties that constrain its shape: The object has volumetric primitives, it has surfaces, it is symmetrical, it is composed of geons, its contours are planar, and its images provide useful topological information about its three-dimensional structure. To test the role of some of these constraints, we performed a set of experiments. Solid shapes (polyhedra) were shown on a computer monitor by means of kinetic depth effect. Experiment 1 showed that shape constancy can be reliably achieved when a polyhedron is represented by its contours (most of the constraints are present), but not when it is represented by vertices or by a polygonal line connecting the vertices in a random order (all the constraints are absent). Experiments 2 and 3 tested the role of individual constraints. Results of these experiments show that shape constancy from novel views is reliable when the object has planar contours and when the shapes of the contours together with topological information about the relations among the contours constrain the possible interpretations of the shape. Symmetry of the object and the topological stability of its image also contribute to shape constancy.

Java experiments for introductory cognitive psychology courses.

Interactive on-line experiments provide a unique and useful method for communicating material to students that is otherwise cumbersome and often confusing. The Java programming language is particularly suited for Internet-based programming applications of this sort because it bypasses many technical issues, including resource availability, security, and cross-platform compatibility. In most cases, topics appropriate to this medium of presentation should (1) not be easily demonstrated by other means, (2) represent an important finding in the field, and (3) be robust with respect to variations in both participants and equipment. The present paper outlines the integration of interactive experiments into an introductory cognitive psychology classroom, describing several experiments currently available on the World-Wide Web (WWW). Evaluation of the technical aspects of the technology as well as expansion of the format to other courses is discussed.