Resistance arteries remain subject to pulsatility, a potent regulator of large elastic artery tone and structure, but the effect is incompletely understood. Extracorporeal circulation during cardiac surgery is often associated with absence of pulsatility, which may affect vascular tone. To define the role of the vascular wall in the inflammatory process that may occur with or without pulsatility, we studied resistance arteries functions ex vivo. We measured vascular reactivity, oxidative stress, and inflammation in the arterial wall.
Isolated rat mesenteric resistance arteries were mounted in an arteriograph and subjected to pulsatility or not in vitro. Arteries were perfused with a physiologic salt solution without circulating cells.
After 180 minutes, flow-mediated dilation was higher and pressure-induced myogenic tone lower in arteries subjected to pulsatility. Without pulsatility, reactive oxygen species and markers of inflammation (monocyte chemotactic protein 1 and tumor necrosis factor α) were higher than baseline. In perfused mesenteric beds under similar conditions, tumor necrosis factor α was higher in perfusate after 180 minutes of nonpulsatility (5.7 ± 1.6 pg/mL vs 1.1 ± 0.4 pg/mL; P < .01). In arteries treated with the antioxidant 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (tempol), flow-mediated dilation and myogenic tone were similar in nonpulsatile and pulsatile arteries; monocyte chemotactic protein 1 and nuclear factor κB expression levels were not increased in tempol-treated nonpulsatile arteries.
Absence of pulsatility in resistance arteries increased oxidative stress, which in turn induced inflammation and preferentially altered pressure and flow-dependent tone, which play a key role in control of local blood flow.
Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Mouse models of human cancers may provide a valuable resource for the discovery of cancer biomarkers. We have developed a practical strategy for profiling specific proteins in mouse plasma using low-volume sandwich-immunoassays. We used this method to profile the levels of 14 different cytokines, acute-phase reactants, and other cancer markers in plasma from a mouse models of intestinal tumors and their wild-type littermates, using as little as 1.5 microliters of diluted plasma per assay. Many of the proteins were significantly and consistently up-regulated in the mutant mice. The mutant mice could be distinguished nearly perfectly from the wild-type mice based on the combined levels of as few as three markers. Many of the proteins were up-regulated even in the mutant mice with few or no tumors, suggesting the presence of a systemic host response at an early stage of cancer development. These results have implications for the study of host responses in mouse models of cancers and demonstrate the value of a new low-volume, high-throughput sandwich-immunoassay method for sensitively profiling protein levels in cancer.

According to a previous report, the degree of the host immune response highly correlates with severity of the disease in the murine model for neurocysticercosis. In wild-type mice, Mesocestoides corti infection induced a rapid and extensive accumulation of gamma delta T cells and macrophages in the brain. NK cells, dendritic cells, alpha beta T cells, and B cells were also recruited to the brain but at lower levels. In contrast, gamma delta T-cell-deficient mice exhibited decreased cellular infiltration and reduced central nervous system (CNS) pathology. To understand the mechanisms of leukocyte recruitment into the CNS, chemokine expression was analyzed in infected brains in the present study. MCP-1 (CCL2), MIP-1 alpha (CCL3), and MIP-1 beta (CCL4) were up-regulated within 2 days after M. corti infection. Protein expression of RANTES (CCL5), eotaxin (CCL11), and MIP-2 was detected later, at 1 week postinfection. Correlating with the decreased cellular infiltration, delta chain T-cell receptor-deficient (TCR delta(-/-)) mice exhibited substantially reduced levels of most of the chemokines analyzed (with the exception of eotaxin). The results suggest that gamma delta T cells play an important role in the CNS immune response by producing chemokines such as MCP-1 and MIP-1 alpha, enhancing leukocyte trafficking into the brain during murine neurocysticercosis.