During sepsis endothelial dysfunction is an important pathogenetic mechanism in acute kidney injury (AKI). Lipopolysaccharide (LPS)-induced endotoxemia is associated with renal hemodynamic changes such as alterations of renal blood flow (RBF), vascular resistance, and glomerular filtration rate. We used adenoviral delivery of an engineered variant of native angiopoietin-1 (COMP-angiopoietin-1) containing anti-inflammatory and anti-permeability functions, to determine if regulation of renal endothelial cell dysfunction may have a beneficial role in preventing AKI during LPS-induced endotoxemia in mice. This treatment prevented the endotoxin-induced decrease of RBF and mean arterial pressure while improving glomerular filtration rate. Treatment also mitigated the effects of LPS on renal intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 protein expression, the number of ER-HR3-positive macrophages that infiltrated the kidney, serum nitrate/nitrite levels, renal inducible nitric oxide synthase protein expression, the induction of tubular epithelial reactive oxygen and nitrogen species, and renal microvascular permeability. Our findings show that COMP-angiopoietin-1, an endothelium-oriented therapeutic agent, protects against AKI caused by endotoxemia.

Acoustic backscatter using a single-frequency transducer can be used for field measurement of irregularly shaped, suspended sediment with a given size distribution. It is assumed that the size distribution of the suspended sediment does not change significantly along the sound path. A newly found explicit solution to acoustic backscatter equation is derived. This explicit solution reduces the computation time significantly during the inversion process. The near-field effect can be included in the inverted quantities by calculating the initial condition with the far-field acoustic backscatter equation and under the assumption of uniform near-field concentration. This method proved successful in the laboratory with initial concentrations of sand up to 3.5 g/L. The errors in estimation of concentration that result from errors in the attenuation coefficients or near-field concentration are significantly amplified with range in a uniform concentration field. However, with an exponential concentration profile, which is commonly found in sediment suspension phenomena, the inversion is only weakly sensitive to attenuation coefficients associated with sound absorption by water and sound scattering by suspended particles. Near-field concentration errors result in commensurate errors throughout the range in the exponential profile. 2649 2650 LEE AND HANES' A DIRECT INVERSION METHOD LEE AND HANES: A DIRECT INVERSION METHOD

Mast cells regulate both inflammatory responses and tissue repair in human diseases but there are conflicting reports on the role of these cells in the pathogenesis of various kidney diseases. Here we measured mast cell function in unilateral ureteral obstruction, a well-characterized model of renal fibrosis, using Kit(W)/Kit(W-v) mice genetically deficient in mast cells, wild-type mice, and deficient mice reconstituted by adoptive transfer with mast cells from the wild-type animals. Mast cell-deficient mice had higher levels of renal tubular damage, more stromal fibrosis, higher numbers of infiltrating ERHR3-positive macrophages and CD3-positive T cells, and higher tissue levels of profibrotic transforming growth factor-beta1 than wild-type mice or mice reconstituted by adoptive transfer of mast cells 3 weeks after ureteral obstruction. Similarly, while wild-type and adoptively transferred mice had increased alpha-smooth muscle actin and decreased E-cadherin expression, which are indicators of epithelial-mesenchymal transition, the obstructed kidneys of the mast cell-deficient mice had significant attenuation of those indicators. Thus, our study suggests that mast cells protect the kidney against fibrosis by modulation of inflammatory cell infiltration and by transforming growth factor-beta1-driven epithelial-to-mesenchymal transitions.

Background: A growing body of evidence shows that hypothalamic inflammation is an important factor in the initiation of obesity. In particular, reactive gliosis accompanied by inflammatory responses in the hypothalamus are pivotal cellular events that elicit metabolic abnormalities. In this study, we examined whether MyD88 signaling in hypothalamic astrocytes controls reactive gliosis and inflammatory responses, thereby contributing to the pathogenesis of obesity. Methods:To analyze the role of astrocyte MyD88 in obesity pathogenesis, we used astrocyte-specific Myd88 knockout (KO) mice fed a high-fat diet (HFD) for 16 weeks or injected with saturated free fatty acids. Astrocyte-specific gene expression in the hypothalamus was determined using real-time PCR with mRNA purified by the Ribo-Tag system. Immunohistochemistry was used to detect the expression of glial fibrillary acidic protein, ionized calcium-binding adaptor molecule 1, phosphorylated signal transducer and activator of transcription 3, and α-melanocyte-stimulating hormone in the hypothalamus. Animals' energy expenditure was measured using an indirect calorimetry system. Results:The astrocyte-specific Myd88 KO mice displayed ameliorated hypothalamic reactive gliosis and inflammation induced by injections of saturated free fatty acids and a long-term HFD. Accordingly, the KO mice were resistant to long-term HFD-induced obesity and showed an improvement in HFD-induced leptin resistance.Conclusions: These results suggest that MyD88 in hypothalamic astrocytes is a critical molecular unit for obesity pathogenesis that acts by mediating HFD signals for reactive gliosis and inflammation.

Epigallocatechin-3-O-gallate (EGCG), the main catechin in green tea, has anti-oxidant, anti-atherosclerotic and anti-inflammatory properties. Fractalkine, a chemokine involved in inflammation and early atherosclerotic processes, acts as a chemoattractant as well as an adhesion molecule in endothelial cells activated by proinflammatory cytokines. In the present study, we investigated the effect of EGCG on fractalkine expression in TNF-α-induced human umbilical vein endothelial cells (HUVECs). EGCG decreased TNF-α-induced fractalkine mRNA and protein expression in HUVECs in a time-dependent manner. EGCG suppressed the TNF-α-induced phosphorylation and degradation of IκB-α, thereby decreasing the phosphorylation and nuclear translocation of the NF-κB p65 subunit in HUVECs. The DNA binding activity of the NF-κB p65 subunit was lower in EGCG-pretreated HUVECs than in those treated with TNF-α alone. Furthermore, EGCG inhibited monocyte adhesion to HUVECs stimulated by TNF-α. The silencing of fractalkine with an siRNA or treatment with a blocking antibody against fractalkine suppressed the TNF-α-induced increase in monocyte adhesion. These results demonstrate that EGCG prevents TNF-α-induced vascular endothelial fractalkine expression.