Argatroban pharmacokinetics and pharmacodynamics in critically ill cardiac surgical patients with suspected heparin-induced thrombocytopenia.

Only limited data are available on the pharmacokinetic and pharmacodynamic properties of argatroban in critically ill patients under clinical conditions. We determined plasma concentrations of argatroban, and its main metabolite M1, within a time period of 48 hours in 25 critically ill cardiac surgical patients, who were suspected of heparin-induced thrombocytopenia and had the clinical need for anticoagulation. Argatroban infusion was started at 0.

Methemoglobinemia in critically ill patients during extended hemodialysis and simultaneous disinfection of the hospital water supply.

Introduction: To evaluate the cause of methemoglobinemia in patients undergoing extended daily hemodialysis/hemodiafiltration we analyzed the relationship between methemoglobinemia and the water disinfection schedule of the hospital.

Methods: We reviewed all arterial blood gas analyses, obtained over a one-year period, in patients undergoing extended hemodialysis/hemodiafiltration, and compared the methemoglobin concentrations obtained on the days when the water supply was disinfected, using a hydrogen peroxide/silver ion preparation, with data measured on disinfection-free days.

Results: The evaluation of 706 measurements revealed a maximum methemoglobin fraction of 1.

Hypertension in mice lacking the CXCR3 chemokine receptor.

The CXC chemokine receptor 3 (CXCR3) has been linked to autoimmune and inflammatory disease, allograft rejection, and ischemic nephropathy. CXCR3 is expressed on endothelial and smooth muscle cells. Although a recent study posited that antagonizing of CXCR3 function may reduce atherosclerosis, the role of CXCR3 in controlling physiological vascular functions remains unclear.

Alpha/beta hydrolase 1 is upregulated in D5 dopamine receptor knockout mice and reduces O2- production of NADPH oxidase.

Renal dopamine receptors have been shown to play a critical role in ROS-dependent hypertension. D5 dopamine receptor deficient (D5-/-) mice are hypertensive and have increased systemic oxidative stress which is manifested in the kidney and the brain. To further investigate the underlying mechanisms of hypertension in D5-/- mice, we used RNA arrays to compare mRNA levels of kidneys from wildtype and D5-/- mice.

Upregulation of Id-1 via BMP-2 receptors induces reactive oxygen species in podocytes.

Bone morphogenetic proteins (BMPs) are secreted signaling molecules, which play a major role in kidney development and disease. Here, we show the existence of mRNA for BMP-2 and for the BMP receptors BMPR1A, BMPR1B, BMPRII, ACVR1A, ACVR2, and ACVR2B in differentiated mouse podocytes and the protein expression of BMPR1A in human glomerular podocytes. BMP-2 dose dependently increases the free cytosolic Ca(2+) concentration in podocytes proving the existence of a functional receptor in these cells.