Microcirculation : the official journal of the Microcirculatory Society, Inc
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New strategies for cancer therapy include the combination of angiogenesis inhibitors with cytotoxins. However, angiogenesis inhibitors may alter tumor microvessel structure and transendothelial permeability thereby reducing tumoral delivery of cytotoxic agents. The aim of this study was to estimate quantitatively the apparent permeability-surface area product (K(PS)) in tumors to a macromolecular contrast medium (MMCM), to follow changes in K(PS) induced by antibodies to vascular endothelial growth factor (anti-VEGF), and to correlate the findings with tumor accumulation of cisplatin, a highly protein-bound cytotoxin, and 5-fluorouracil (5-FU), a small unbound cytotoxin. ⋯ MMCM-enhanced MRI can be used to detect and estimate changes in K(PS) to this contrast agent following a single dose of anti-VEGF antibody. The decline in K(PS) induced by this inhibitor of angiogenesis is associated with reduced tumor concentration of a protein-bound cytotoxin, similar in molecular weight to the contrast agent. MRI assays of microvascular status as performed here may be useful to clinically monitor responses to anti-angiogenesis drugs and to optimize the choice and timing of cytotoxic drug administration.
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Hypercholesterolemia promotes the adhesion of leukocytes to vascular endothelium in large and microscopic blood vessels. Lymphocytes that can modulate endothelial cell adhesion molecule expression have been implicated in the altered structure and function of large arterial vessels associated with chronic hypercholesterolemia. This study assesses the contribution of CD4(+) and CD8(+) T-cells to acute inflammatory responses observed in the microcirculation of hypercholesterolemic mice. ⋯ These findings indicate that both CD4(+) and CD8(+) T-cells contribute to granulocyte adhesion and emigration elicited in postcapillary venules by hypercholesterolemia.
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The overall objective of this study was to define the contribution of T-lymphocytes to the microvascular and inflammatory responses of the intestine to ischemia/reperfusion (I/R). ⋯ These findings indicate that intestinal I/R is associated with the recruitment of CD4+ and CD8+ T-cells, which is mediated by endothelial MAdCAM-1. T-cells seem to modulate the recruitment of neutrophils that occurs hours after reperfusion as well as the increased albumin extravasation that occurs within minutes after reperfusion.
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The microvascular dysfunction which occurs in sepsis involves all three elements of the microcirculation: arterioles, capillaries, and venules. In sepsis, the arterioles are hyporesponsive to vasoconstrictors and vasodilators. Sepsis also reduces the number of perfused capillaries, thereby impacting on oxygen diffusion to mitochondria. ⋯ In addition, PMN-endothelial adhesive interactions occur in precapillary microvessels and capillaries in organs, such as, the lung and heart. Thus, all these elements of the microcirculation are involved in the sepsis-induced inflammation. In this review we address emerging views on the mechanisms involved in the microvascular dysfunction induced by sepsis within the framework of these three basic elements of the microcirculatory unit.
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The elevated ambulatory pressure in the peripheral venous system of chronic venous insufficiency (CVI) patients manifests itself not only in the form of disturbed macrocirculation but also and particularly in microangiopathic changes. For this reason, it is closely correlated with trophic disorders of the skin and can ultimately lead to ulceration. Using microcirculation research techniques, we are able to provide clear evidence of a typical microangiopathy in chronic venous insufficiency. ⋯ These changes represent a plausible explanation for the development and to recurrency tendency of venous ulcers. The reduced expression of lymphocytic L-selectin in healthy controls during the orthostatic stress test may be an indication that the cells are activated by venous stasis. Clinically effective therapeutic measures improve the impaired microcirculation of the skin in the ankle area.