Endothelial Domes Encapsulate Adherent Neutrophils and Minimize Increases in Vascular Permeability in Paracellular and Transcellular Emigration

Local edema, a cardinal sign of inflammation associates closely with neutrophil emigration. Neutrophil emigration has been described to occur primarily through endothelial junctions (paracellular) and more rarely directly through endothelial cells (transcellular). Recently, we reported that unlike in wild-type (wt) mice, Mac-1-/- (CD11b) neutrophils predominantly emigrated transcellularly and was significantly delayed taking 20–30 min longer than the paracellular emigration (wt). In the present study we noted significant anatomical disruption of the endothelium and hypothesized that transcellular emigration would greatly increase vascular permeability. Surprisingly, despite profound disruption of the endothelial barrier as the neutrophils moved through the cells, the changes in vascular permeability during transcellular emigration (Mac-1-/-) were not increased more than in wt mice. Instead increased vascular permeability completely tracked the number of emigrated cells and as such, permeability changes were delayed in Mac-1-/- mice. However, by 60 min neutrophils from both sets of mice were emigrating in large numbers. Electron-microscopy and spinning disk multichannel fluorescence confocal microscopy revealed endothelial docking structures that progressed to dome-like structures completely covering wt and Mac-1-/- neutrophils. These domes completely enveloped the emigrating neutrophils in both wt and Mac-1-/- mice making the mode of emigration underneath these structures extraneous to barrier function. In conclusion, predominantly paracellular versus predominantly transcellular emigration does not affect vascular barrier integrity as endothelial dome-like structures retain barrier function

Metabolic control of diabetes is associated with an improved response of diabetic retinopathy to panretinal photocoagulation

OBJECTIVE - To study the influence of glycemic control and the presence of microalbuminutia on the initial response to partretinal photocoagulation (PRP) in patients with a high-risk proliferative diabetic retinopathy (PDR). RESEARCH DESIGN AND METHODS - This was a prospective cohort study with a two-by-two factorial design. We used full-scattered PRP to treat 115 eyes of type 2 diabetic patients who have high-risk PDR. HbA(1c) (AlC) and albumin levels in 24-h urine were constantly monitored during the preenrollment, treatment, and posttreatment periods. At a follow-up visit 12 weeks after the last PRP session, the fundus was examined for characteristics of regression from high-risk PDR and the response to PRP was determined to be successful or unsuccessful. The eyes were categorized into four groups based on average AlC levels and the presence or absence of microalbuminuria. The data were analyzed using a logistic regression model. Our statistical analysis determined the probability of achieving a satisfactory response to PRP in association with AIC levels and the presence or absence of microalbummuria. RESULTS - Of the 115 eyes examined, 65 (56.5%) had a successful initial response to PRP and 50 (43.5%) did not. The probability of a satisfactory response to PRP was related to AlC levels (P = 0.05). CONCLUSIONS - Low levels of hemoglobin glyco,sylation (AIC <8%) during the pretreatment, treatment, and posttreatment periods are associated with a regression of proliferative diabetic retinopathy after PRP