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Background The body of knowledge regarding the different facets of frostbite injury continues to expand. However, beside the administration of physiological saline, local rewarming, local disinfection and symptomatic medications, today no causal therapy is known which would accelerate angiogenesis and wound healing. The aim of this study was to investigate the influences of dilative acting drugs on microcirculation, angiogenesis and leukocyte behavior. Materials and Methods Ears of male hairless mice (n = 40) were inflicted with full thickness frostbites using a cold air jet. Then the affects of four intraperitoneal injections of isosorbitdinitrate (ISDN, n = 10), l -nitroarginine-methyl-ester ( l -NAME, n = 10), selenium (n = 10) or sodium chloride (n = 10; each administered to one of four corresponding study groups), on microcirculation, leukocyte-endothelial interaction and angiogenesis were investigated over a 12-day period using intravital fluorescent microscopy. Results Angiogenesis was most improved by ISDN (36.8 vs. 54.5% non-perfused area on day 3, 3.9 vs. 17.0% on day 7 compared to selenium, p l -NAME showed significantly decreased diameter over the complete time of 12 days. ISDN had positive influences on edema formation, which was significantly reduced compared to control (27% lower values compared to control; p = 0.007 on day 3). The l -NAME-group showed the significant highest leukocyte-adhesion compared to control on days 7 and 12 (53% resp. 58% higher, p Conclusion Overall, out of all the drugs tested, ISDN improved angiogenesis, dilated venules and decreased edema formation and therefore seems to have the greatest positive impact on these crucial parameters after frostbite injury.

Background Chronic venous disease of the lower limbs is a common public health problem worldwide with negative impact on quality of life and results with drugs used to treat it are sparse, probably due to lack of good experimental models. Objective In this investigation we have tested the effects of two commonly used venotonic substances, Ruscus extract and micronized diosmine, on the microcirculation in vivo. Methods These substances were given orally, by gavage, during two weeks, twice daily and observations were made using the hamster cheek pouch preparation. Results The drugs elicited a dose-dependent inhibition of (1) macromolecular permeability increase induced by histamine or ischemia followed by reperfusion, being the Ruscus extract more active on both and (2) leukocyte-endothelium interaction, again being the Ruscus extract more effective in the inhibition of the number of adherent and rolling leukocytes. About the duration of the effect after the end of the treatment, both drugs had similar effects but Ruscus extract showed greater permanence of its effect on all observed parameters. Conclusions Our results suggest that both drugs have antioxidant and anti-inflammatory properties being Ruscus extract more active. It should be added that only Ruscus extract showed a significant venular constriction.

CG5601 is a novel immunomodulatory substance showing anti-inflammatory properties comparable to thalidomide. To investigate the anti-inflammatory effects of CG5601 in endotoxin-induced uveitis (EIU) and to evaluate its influence on leukocyte-endothelium interaction, the anterior chamber inflammatory reaction was assessed and intravital fluorescence microscopy was carried out at 2, 4, 8 and 24 h. Lewis rats received an intraperitoneal injection of CG5601 (200 mg/kg b.w.) at the time of lipopolysaccharide injection. At 8 and 24 h, CG5601 inhibited the cell migration and protein concentration in the aqueous humor compared to untreated EIU (p < 0.0001). There was no significant difference between nontreated animals and vehicle controls. The treatment of CG5601 reduced the number of rolling leukocytes. At early time points (2 and 4 h), inhibition of rolling leukocyte flux was significant (p < 0.005). The rise of serum TNF-α levels in EIU at 2 h was reduced. CG5601 exerts potent anti-inflammatory effects in EIU.

Leukocyte adhesion to vascular endothelium is an initial step of many inflammatory diseases. Although the atomic force microscopy (AFM) measurements of leukocyte–endothelial interaction have been recently introduced. with cell adhesion force unbinding curves (CAFUC). We obtained pico-Newton force in the initial interaction between a single living THP-1 cell and HUVEC monolayer using a custom-built laser tweezers (LT) system. The measured quantities included the non-linear force–distance relationship, and the effect of yielding in cell detachment. It is possible to introduce a time scale into the LT cell-detachment experiments for further exploration and more detailed information on the viscoelastic properties of living cells.

This paper describes a multi-agent strategy for blacklisting malicious nodes in a peer-to-peer network that is inspired by the innate immune system, including the recruitment of leukocytes to the site of an infection in the human body. Agents are based on macrophages, T-cells, and tumor necrosis factor, and exist on network nodes that have properties drawn from vascular endothelial tissue. Here I show that this strategy succeeds in blacklisting malicious nodes from the network using non-specific recruitment. This strategy is sensitive to parameters that affect the recruitment of leukocyte agents to malicious nodes. The strategy can eliminate even a large, uniform distribution of malicious nodes in the network.

Experimentelle Melanin-induzierte Uveitis (EMIU): Modulation der Leukozyten-Endothelzell-Interaktion durch Makrophagendepletion - intravitalmikroskopische Analysen. Einleitung: Die Experimentelle Melanininduzierte Uveitis (EMIU) dient als Modell für eine autoimmune Iridozyklitis und Choroiditis. Die frühe Entzündungsreaktion ist durch eine gesteigerte Leukozyten-Endothel-Interaktion gekennzeichnet. Um die Rolle von Makrophagen bei der Induktion der EMIU zu untersuchen, analysierten wir Veränderungen der Leukozyten-Endothel-Interaktionen in Irisvenolen anästhesierter Ratten nach Makrophagendepletion mit liposomalem Clodronat. Methoden: Die EMIU wurde durch intraperitoneale Injektion einer Emulsion aus 250 µg bovinen Melanosomen in komplettem Freund Adjuvant und Pertussistoxin bei Lewis Ratten induziert. Die Tiere wurden mit 2 ml Clodronat-Liposomen (Clodronat-lip) an den Tagen 2; 1; 4; 6 beziehungsweise 8 nach Immunisierung behandelt. Kontrolltiere erhielten anstelle von Clodronat-lip Leerliposomen (Kontrolle). Für die Intravitalfluoreszenzmikroskopie wurden Leukozyten intravasal mit Rhodamin 6G gefärbt. Anschließend wurden die postkapillären Irisvenolen am 4.; 6.; 8. und 10. Tag untersucht, um die Zahl der rollenden und fest am Endothel adhärenten Leukozyten zu quantifizieren. Weitere Parameter wie Zellzahl und Proteingehalt des Kammerwassers, TNF-alpha und IFN-gamma im Plasma und das Differentialblutbild wurden zur Charakterisierung der Entzündungsreaktion herangezogen. Ergebnisse: Bei makrophagendepletierten Tieren konnten spaltlampenmikroskopisch keine entzündlichen Veränderungen des Vorderabschnittes beobachtet werden. Der prozentuale Anteil rollender Leukozyten war am 8. Tag mit 2 +/- 1.1 vs. 15.2 +/- 1.6; 5.2 +/- 0.5% (Clodronat-lip vs. EMIU; Kontrolle, Mittelwert +/- MSF, ANOVA, p

Microvascular manifestation of postischemic reperfusion injury is hallmarked by two distinct events, i.e. perfusion failure of nutritive capillaries (“no-reflow”) (Majno et al., 1967; Menger et al., 1992a), and the sequelae of “reflow-paradox”-associated mechanisms, which include accumulation of leukocytes, leukocyte-endothelium interaction and loss of endothelial integrity (Menger et al., 1992b). Both reperfusion-dependent events contribute to the aggravation of ischemia-induced parenchymal tissue injury, either through prolongation of focal ischemia (“no-reflow”),or the action of leukocyte-derived cytotoxic mediators (“reflowparadox”),such as reactive oxygen metabolites and proteolytic enzymes (Granger, 1988; Lehr et al., 1991; Menger et al., 1993a).

Microcirculatory, leukocyte/endothelium interaction and 7-day survival time effects of human recombinant C-reactive protein (rCRP) associated or not with volume resuscitation were studied in the hamster window chamber model during resuscitation from nonhypotensive endotoxemia [1,2].

Leukocyte adhesion to the endothelium of postcapillary venules is increased in pathologic conditions such as inflammation and postischemic reperfusion injury. Enhanced adhesion results from leukocyte activation via membrane confined metabolic pathways, triggered by oxygen free radicals, complement factors, and lipid mediators [1].