A systematic comparison of cockcroft-gault and modification of diet in renal disease equations for classification of kidney dysfunction and dosage adjustment.

Background: The dosing of drugs in patients with kidney dysfunction is often based on the estimates of kidney function.

Objective: To systematically compare the performance of the Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (CG) equations for dosage adjustment.

Methods: We assessed agreement (concordance, kappa statistics [κ,κ(ω)]) between CG and MDRD using a Food and Drug Administration database to evaluate the effect of renal function on the pharmacokinetics of 36 approved drugs.

Synergystic induction of HIF-1alpha transcriptional activity by hypoxia and lipopolysaccharide in macrophages.

Hypoxia Inducible Factor-1 (HIF-1) is activated by a variety of stimuli, including inflammatory mediators. In this report we investigated the role that bacterial lipopolysaccharide (LPS) and hypoxia play in the regulation of HIF-1-dependent gene expression in macrophages. We report that murine macrophages stimulated with low concentrations of LPS (1-10 ng/ml) expressed significantly higher levels of inducible nitric oxide synthase (iNOS) mRNA when cultured under hypoxic compared to normoxic conditions.

Signal transduction and biological functions of bone morphogenetic proteins.

Bone morphogenetic proteins (BMPs) are multi-functional growth factors and belong to the transforming growth factor beta (TGFbeta) superfamily. The roles of BMPs in embryonic development and cellular functions in postnatal animals have been extensively studied in recent years. Signal transduction studies have revealed that Smad1 and 5 are the immediate downstream molecules of BMP receptor and play a central role in BMP signal transduction.

Hypoxia selectively inhibits monocyte chemoattractant protein-1 production by macrophages.

Hypoxia, a local decrease in oxygen tension occurring in inflammatory and tumor lesions, modulates gene expression in macrophages. Because macrophages are important chemokine producers, we investigated the regulatory effects of hypoxia on macrophage-derived chemokines. We demonstrated that hypoxia inhibits the production of the macrophage and T lymphocyte chemotactic and activating factor, monocyte chemoattractant protein-1 (MCP-1).