New Findings r What is the central question of this study?The assessment of Ca 2+ handling by isolated mitochondria can be biased by dysfunctions secondary to Ca 2+ -induced mitochondrial permeability transition (MPT). As a result of this uncertainty and the differing experimental conditions between studies, the tissue and sex diversities in mitochondrial Ca 2+ transport are still unsettled questions. r What is the main finding and its importance?If MPT is not prevented during Ca 2+ transport assays, some measured variables are biased. Accounting for the implied importance of preventing MPT, we observed substantial tissue specificities in the mitochondrial Ca 2+ handling, particularly in the Ca 2+ efflux pathways.The characteristics of mitochondria, including their Ca 2+ transport functions, may exhibit tissue specificity and sexual dimorphism. Given that measurements of Ca 2+ handling by isolated mitochondria may be biased by dysfunction secondary to Ca 2+ -induced mitochondrial permeability transition (MPT) pore opening, this study evaluated the extent to which MPT inhibition by ciclosporin affected the measurement of Ca 2+ transport in isolated rat liver mitochondria. The results indicate that the steady-state levels of external Ca 2+ and the rates of mitochondrial Ca 2+ efflux through the selective pathways can be overestimated by up to fourfold if MPT pore opening is not prevented. We analysed Ca 2+ transport in isolated mitochondria from the liver, skeletal muscle, heart and brain of male and female rats in incubation conditions containing MPT inhibitors, NAD-linked substrates and relevant levels of free Ca 2+ , Mg 2+ and Na + . The Ca 2+ influx rates were similar among the samples, except that the liver mitochondria displayed values fourfold higher. In contrast, the Ca 2+ efflux rates exhibited more tissue diversity, especially in the presence of Na + . Interestingly, the Na + -independent Ca 2+ efflux was highest in the heart mitochondria (ß4 nmol mg −1 min −1 ), thus challenging the view that cardiac mitochondrial Ca 2+ efflux relies almost exclusively on a Na + -dependent pathway. Sex specificity was observed in only two kinetic indexes of heart mitochondrial Ca 2+ homeostasis and in the ADP-stimulated respiration of liver mitochondria (ß20% higher in females). The present study

Although essential for inflammatory responses, leukocyte recruitment to blood vessel walls in response to inflammatory stimuli, such as TNF-, can contribute to vascular occlusion in inflammatory diseases, including atherosclerosis. We aimed to further characterize the mechanisms by which TNF stimulates adhesive and morphologic alterations in neutrophils.

Soluble guanylyl cyclase stimulation in sickle cell disease.