Blood heat shock proteins evoked by some <Emphasis Type="Italic">Salmonella</Emphasis> strains infection in ducks

Bacterial heat-shock response is a global regulatory system required for effective adaptation to changes (stress) in the environment. An in vitro study was conducted to investigate the impact of a sublethal temperature (42°C) on heat shock protein (HSP) expression in 6 Salmonella strains (Salmonella Enteritidis, S. Typhimurium, S. Virchow, S. Shubra, S. Haifa and S. Eingedi). The 6 Salmonella strains were isolated from the tissues of ducklings that had died from avian salmonellosis. To determine the induction of HSP in the 6 Salmonella strains, they were exposed to the selected temperature level for 24 h and further kept for 48 h at culturing condition of 42°C. Growth under a sublethal temperature of 42°C increased the expression of several proteins of Salmonella, including a 63 kDa protein in addition to the generation and/or overexpression of 143 proteins which were specific to heat shock, concurrent to this acquired thermotolerance. The 6 Salmonella strains responded to 24 h of thermal stress at an elevated temperature 42°C by synthesizing different heat shock proteins (HSP) with molecular weights ranging between 13.62 and 96.61 kDa. At 48 h, the 6 Salmonella strains synthesized different HSPs with molecular weights ranging between 14.53 and 103.43 kDa. It follows that salmonellae would produce HSPs during the course of the infectious process. Salmonellosis produced several proteins after 24 and 48 h of infection. Seven of these proteins (100, 80, 60, 40, 30, 20 and 10 kDa) were recognized in the serum obtained from the ducklings infected with S. Enteritidis, S. Typhimurium, S. Virchow, S. Shubra, S. Haifa and S. Eingedi after 24 h of infection. After 48 h, the 1–7 kDa HSP became more evident and indicated their de novo generation.     

Widespread Myocardial Delivery of Heart-Derived Stem Cells by Nonocclusive Triple-Vessel Intracoronary Infusion in Porcine Ischemic Cardiomyopathy: Superior Attenuation of Adverse Remodeling Documented by Magnetic Resonance Imaging and Histology

Single-vessel, intracoronary infusion of stem cells under stop-flow conditions has proven safe but achieves only limited myocardial coverage. Continuous flow intracoronary delivery to one or more coronary vessels may achieve broader coverage for treating cardiomyopathy, but has not been investigated. Using nonocclusive coronary guiding catheters, we infused allogeneic cardiosphere-derived cells (CDCs) either in a single vessel or sequentially in all three coronary arteries in porcine ischemic cardiomyopathy and used magnetic resonance imaging (MRI) to assess structural and physiological outcomes. Vehicle-infused animals served as controls. Single-vessel stop-flow and continuous-flow intracoronary infusion revealed equivalent effects on scar size and function. Sequential infusion into each of the three major coronary vessels under stop-flow or continuous-flow conditions revealed equal efficacy, but less elevation of necrotic biomarkers with continuous-flow delivery. In addition, multi-vessel delivery resulted in enhanced global and regional tissue function compared to a triple-vessel placebo-treated group. The functional benefits after global cell infusion were accompanied histologically by minimal inflammatory cellular infiltration, attenuated regional fibrosis and enhanced vessel density in the heart. Sequential multi-vessel non-occlusive delivery of CDCs is safe and provides enhanced preservation of left ventricular function and structure. The current findings provide preclinical validation of the delivery method currently undergoing clinical testing in the Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC) trial of CDCs in heart failure patients.     

Glutathione/thioredoxin systems modulate mitochondrial H2O2 emission: an experimental-computational study

The net emission of hydrogen peroxide (H(2)O(2)) from mitochondria results from the balance between reactive oxygen species (ROS) continuously generated in the respiratory chain and ROS scavenging. The relative contribution of the two major antioxidant systems in the mitochondrial matrix, glutathione (GSH) and thioredoxin (Trx), has not been assessed. In this paper, we examine this key question via combined experimental and theoretical approaches, using isolated heart mitochondria from mouse, rat, and guinea pig. As compared with untreated control mitochondria, selective inhibition of Trx reductase with auranofin along with depletion of GSH with 2,4-dinitrochlorobenzene led to a species-dependent increase in H(2)O(2) emission flux of 17, 11, and 6 fold in state 4 and 15, 7, and 8 fold in state 3 for mouse, rat, and guinea pig mitochondria, respectively. The maximal H(2)O(2) emission as a percentage of the total O(2) consumption flux was 11%/2.3% for mouse in states 4 and 3 followed by 2%/0.25% and 0.74%/0.29% in the rat and guinea pig, respectively. A minimal computational model accounting for the kinetics of GSH/Trx systems was developed and was able to simulate increase in H(2)O(2) emission fluxes when both scavenging systems were inhibited separately or together. Model simulations suggest that GSH/Trx systems act in concert. When the scavenging capacity of either one of them saturates during H(2)O(2) overload, they relieve each other until complete saturation, when maximal ROS emission occurs. Quantitatively, these results converge on the idea that GSH/Trx scavenging systems in mitochondria are both essential for keeping minimal levels of H(2)O(2) emission, especially during state 3 respiration, when the energetic output is maximal. This suggests that the very low levels of H(2)O(2) emission observed during forward electron transport in the respiratory chain are a result of the well-orchestrated actions of the two antioxidant systems working continuously to offset ROS production.