Several studies have found that RRF rather than overall adequacy ( as estimated

from total small solute removal rates) is an essential marker of patient and, to a lesser extent, technique survival during chronic peritoneal dialysis (PD) therapy. In addition, RRF is associated with a reduction in blood pressure and left ventricular hypertrophy, increased sodium removal and improved fluid status, lower serum beta(2)-microglobulin, phosphate and uric acid levels, higher serum hemoglobin and bicarbonate levels, better nutritional status, a more favorable lipid profile, decreased circulating inflammatory markers, and lower risk for peritonitis in PD. As compared with conventional hemodialysis, PD is associated with a slower QNZ solubility dmso decrease in RRF. This highlights the usefulness of

strategies oriented to preserve both RRF and the long-term viability of the peritoneal membrane. Several factors contributing to the loss of RRF have been identified and should be avoided. Renoprotective drugs and new glucose-sparing, more biocompatible PD regimes may prove useful tools to preserve RRF and peritoneal membrane function in the near future.”
“The selleck screening library role of nitric oxide (NO) in cardiac contractility is complex and controversial. Several NO donors have been reported to cause positive or negative inotropism. NO can bind to guanylate cyclase, increasing cGMP production and activating PKG. NO Inositol monophosphatase 1 may also directly S-nitrosylate cysteine residues of specific

proteins. We used the isolated rat heart preparation to test the hypothesis that the differential inotropic effects depend on the degree of NO production and the signaling recruited. SNAP (S-nitroso-N-acetylpenicillamine), a NO donor, increased contractility at 0.1, 1 and 10 M. This effect was independent of phospholamban phosphorylation, was not affected by PKA inhibition with H-89 (N-[2((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide), but it was abolished by the radical scavenger Tempol (4-hydroxy-[2,2,4,4]-tetramethyl-piperidine-1-oxyl). However, at 100 mu M SNAP reduced contractility, effect reversed to positive inotropism by guanylyl cyclase blockade with ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), and abolished by PKG inhibition with KT5823, but not affected by Tempol. SNAP increased tissue cGMP at 100 M, but not at lower concentrations. Consistently, a cGMP analog also reduced cardiac contractility. Finally, SNAP at 1 mu M increased the level of S-nitrosylation of various cardiac proteins, including the ryanodine receptor. This study demonstrates the biphasic role for NO in cardiac contractility in a given preparation; furthermore, the differential effect is clearly ascribed to the signaling pathways involved.