Fundamental and distinct roles of P-selectin and LFA-1 in ischemia/reperfusion-induced leukocyte-endothelium interactions in the mouse colon.

Objective: To study the adhesive mechanisms underlying ischemia/reperfusion (I/R)-induced leukocyte-endothelium interactions in the colon.

Summary Background Data: Leukocyte recruitment is a key feature in I/R-induced tissue injury, but the mechanisms regulating leukocyte rolling and adhesion in the colon are not known. The authors recently developed a new model to study the molecular mechanisms of I/R-provoked leukocyte-endothelium interactions in the colon microcirculation using inverted intravital fluorescence microscopy.

Age-associated loss of immunomodulatory protection by granulocyte-colony stimulating factor in endotoxic rats.

Elderly patients have a higher incidence of morbidity and mortality due to infectious diseases. Because most immune functions in the elderly differ compared with those in younger subjects, we studied the effect of the immunomodulating agent G-CSF on endotoxic liver injury and cytokine release in an aging animal model of acute sepsis. Young (3-month-old), mature (12-month-old), and senescent (24-month-old) male Sprague-Dawley rats (n = 6 each) were treated with bacterial endotoxin for 6 h.

In vivo quantification of ageing changes in the rat liver from early juvenile to senescent life.

Aims/method: Using high resolution multifluorescence in vivo microscopy, the present study was undertaken to determine the changes in rat hepatic tissue architecture and microvasculature during the growth associated with juvenile maturation and adult senescence, i.e. the age of 1, 3, 12 and 24 months.

Adverse effect of heparin on antithrombin action during endotoxemia: microhemodynamic and cellular mechanisms.

A recent clinical sepsis trial reported a significant reduction in 90-day mortality by antithrombin (AT) exclusively in the subgroup of patients without simultaneous heparin prophylaxis. Patients additionally receiving heparin did not benefit from AT treatment. Herein, we studied the microhemodynamic and cellular mechanisms of this adverse effect of heparin on AT actions by the use of intravital microscopy and granulocyte culturing.

Hydroxyethyl starch (130 kD), but not crystalloid volume support, improves microcirculation during normotensive endotoxemia.

Background: Increased leukocyte-endothelial cell interaction (LE) and deterioration of capillary perfusion represent key mechanisms of septic organ dysfunction. The type of volume support, however, which may be used during septic disorders, remains controversial. Using intravital microscopy, the authors studied the effect of different regimens of clinically relevant volume support on endotoxin-induced microcirculatory disorders, including the synthetic colloid hydroxyethyl starch (HES, 130 kD) and a crystalloid regimen with isotonic saline solution (NaCl).

High, but not low, dietary retinoids aggravate manifestation of rat liver fibrosis.

Background: Although there is strong implication that retinoids regulate Ito cell proliferation and collagen synthesis, results from in vivo studies on the relationship between vitamin A and liver fibrosis are conflicting. The present study focuses on the role of vitamin A in carbon tetrachloride (CCl4)-induced fibrosis by chronic feeding of rats with either a vitamin A-supplemented or -depleted diet.

Methods And Results: In animals with high dietary hepatic retinoid levels, liver fibrosis was more pronounced and was associated with an increased CCl4-toxicity resulting in high mortality (73%).

n-3 Polyunsaturated fatty acid-enriched diet does not protect from liver injury but attenuates mortality rate in a rat model of systemic endotoxemia.

Objective: We investigated the potential of dietary fish oil containing n-3 polyunsaturated fatty acids to attenuate hepatic injury and mortality rate of rats in response to systemic endotoxemia.

Design: Prospective, randomized, controlled animal study.

Setting: University laboratory.

Leukocyte rolling is exclusively mediated by P-selectinin colonic venules.

1. The objective of the present study was to examine the role of the endothelial selectins (i.e.

Antithrombin effects on endotoxin-induced microcirculatory disorders are mediated mainly by its interaction with microvascular endothelium.

Objective: To investigate whether the protective effect of antithrombin III, which has been shown to exert beneficial effects during septic disorders, including reduction of endotoxin-associated leukocyte/endothelial cell interaction and capillary perfusion failure, is mainly based on its anticoagulant capacity or direct effects on the microvascular endothelium.

Design: Animal study with three treatment groups.

Setting: Animal research facility.

Microtumor growth initiates angiogenic sprouting with simultaneous expression of VEGF, VEGF receptor-2, and angiopoietin-2.

Tumors have been thought to initiate as avascular aggregates of malignant cells that only later induce vascularization. Recently, this classic concept of tumor angiogenesis has been challenged by the suggestion that tumor cells grow by co-opting preexisting host vessels and thus initiate as well-vascularized tumors without triggering angiogenesis. To discriminate between these two mechanisms, we have used intravital epifluorescence microscopy and multi-photon laser scanning confocal microscopy to visualize C6 microglioma vascularization and tumor cell behavior.

Viewing the microcirculation through the window: some twenty years experience with the hamster dorsal skinfold chamber.

Intravital microscopy represents a sophisticated technique to study the microcirculation in health and disease. While most preparations used for those studies are acute in nature, the use of chamber preparations in the skinfold bear the advantage to allow for chronic studies with repeated analysis of the microcirculation over a prolonged period of time. The skinfold chamber model for microcirculatory analysis has been adapted to mice, rats and hamsters.

Leukocyte recruitment in hepatic injury: selectin-mediated leukocyte rolling is a prerequisite for CD18-dependent firm adhesion.

Background/aims: This study was designed to examine the role of selectins and CD18 in leukocyte recruitment in hepatic injury induced by tumor necrosis factor-alpha (TNF-alpha) and galactosamine (Gal) in vivo.

Methods: Intravital fluorescence microscopy of the hepatic microcirculation was used to quantify leukocyte-endothelium interactions provoked by 24 h of systemic TNF-alpha/Gal challenge in rats. Hepatic injury was evaluated with liver enzymes.