Novel dihydrothieno[2,3-e]indazole derivatives as IκB kinase inhibitors.

Synthesis, and structure-activity relationship (SAR) studies of the novel IKK-β inhibitors 2 and 3 characterized by a dihydrothieno[2,3-e]indazole core are presented. Compound 2t was efficacious in a mouse model of LPS-stimulated TNF-α production.

Expression and localization of insulin-like growth factor binding proteins in normal and proteinuric kidney glomeruli.

Aim: Insulin-like growth factor I (IGF-I) acts on target cells in an endocrine and/or local manner through the IGF-I receptor (IGF-IR), and its actions are modulated by multiple IGF binding proteins (IGFBP). To elucidate the roles of local IGFBP in kidney glomeruli, the expression and localization of their genes were examined and compared with normal and proteinuric kidney glomeruli.

Methods: A cDNA microarray database (MAd-761) was constructed using human kidney glomeruli and cortices.

Expression of the chemokine fractalkine (FKN/CX3CL1) by podocytes in normal and proteinuric rat kidney glomerulus.

Background/aims: A chemokine fractalkine (FKN/CX3CL1) is induced primarily by endothelial cells and accumulates inflammatory cells via its receptor CX3CR1. Since glomerular preferential expression of FKN/CX3CL1 gene was reported in normal human kidney, we presumed FKN/CX3CL1 might play some roles in glomerular physiology. The purpose of this study is to examine the expression and localization of FKN/CX3CL1 in normal and proteinuric glomeruli.

Influenza vaccination for severely multiply handicapped persons/children in the 2005-2006 season.

In this study, we report the effectiveness of trivalent inactivated influenza vaccination (TIV) for severely multiply handicapped persons/children (SMHPs) in the 2005-2006 season. In 77 SMHPs, A/New York/55/2004 (H3N2) which was the changed vaccine-strain showed significant differences in the geometric mean titers (P<0.05) and seroprotection rates (P<0.

Blockade of nuclear factor-kappaB activation prevents hypodynamic shock and gastric hypoperfusion induced by endotoxin in anesthetized dogs.

Objective: To investigate whether pyrrolidinone derivative (N2733), an inhibitor of nuclear factor (NF)-kappaB activation, improves altered metabolic and hemodynamic changes and organ dysfunctions caused by endotoxic shock.

Design And Setting: Prospective, randomized, animal study in a laboratory at a university hospital.

Subjects: Twenty-three anesthetized male beagle dogs (10-14 kg).

Cytokine-activated Jak-2 is involved in inducible nitric oxide synthase expression independent from NF-kappaB activation in vascular smooth muscle cells.

Inflammatory cytokines, such as interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha, activate nuclear factor-kappa B (NF-kappaB) which transactivates inducible nitric oxide synthase (iNOS) gene in vascular smooth muscle cells (VSMCs). However, it remains obscure whether cytokine-mediated iNOS expression in VSMCs requires signaling pathway(s) other than NF-kappaB activation. The present study was designed to elucidate whether protein tyrosine kinases (PTKs) are involved in the cytokine-induced NF-kappaB activation and iNOS expression in cultured rat VSMCs.