Transport interactions of different organic cations during their excretion by the intact rat kidney

Transport interactions of different organic cations during their excretion by the intact rat kidney. Organic cations, in addition to being filtrated, are secreted or reabsorbed in the proximal renal tubule whereby they have to pass the contraluminal and the luminal cell membrane. Interactions with the transport of other organic cations can occur at either cell side, leading to inhibition or stimulation of net secretion or net reabsorption. A qualitative evaluation of such processes is possible by using the in vivo bolus injection of an organic cation as test substance. Measuring its urinary excretion profile in relation to that of inulin, under control conditions and after application of interfering organic cations, in combination with simultaneous registration of its tissue concentration, allows the demonstration of interaction and also the tentative identification of the cell side at which interference has taken place. As test substance the fluorescent organic cation 4-(4-dimethylaminostyryl)-N-methylpyridinium (4-Di-1-ASP⊕; ⊕ denotes permanent positively-charged organic cations was used, having a protein binding of 47% under the given experimental conditions. As interfering organic cations amiloride, benzylamiloride, choline⊕, cimetidine, and 2-methyl-4-(heptafluorobutoxy)-N-methylpyridinium⊕ were injected. It was found that: (1) 4-Di-1-ASP⊕ is filtered and net reabsorbed under control conditions (fractional excretion 0.54 ± 0.1). All net secreted interfering substances, except bidirectional transported choline⊕, injected simultaneously with 4-Di-1-ASP⊕, showed an interference with renal excretion of net reabsorbed 4-Di-1-ASP⊕, by (2) instantaneously increasing its reabsorption, resulting in a 28 to 33% decrease in urinary excretion, and (3) augmenting its tissue concentration by 19 to 58%. (4) A prolonged effect of the interfering substrates could be observed after a third injection of 4-Di-1-ASP⊕ (without inhibitor) showing an increased tissue concentration of 4-Di-1-ASP⊕ of 36 to 46%. The complex interfering pattern of the applied organic cations can be explained by a trans-stimulation of 4-Di-1-ASP⊕ net reabsorption at the luminal cell side, leading to an increased intracellular content of 4-Di-1-ASP⊕

Bone disease after renal transplantation

We propose a probabilistic key predistribution scheme for wireless sensor networks, where keying materials are distributed to sensor nodes for secure communication. We use a two-tier approach in which there are two types of nodes: regular nodes and agent nodes. Agent nodes are more capable than regular nodes. Our node deployment model is zone-based such that the nodes that may end up with closer positions on ground are grouped together. The keying material of nodes that belong to different zones is non-overlapping. However, it is still possible for nodes that belong to different zones to communicate with each other via agent nodes when needed. We give a comparative analysis of our scheme through simulations and show that our scheme provides good connectivity figures at reasonable communication cost by using minimal flooding in key distribution. Moreover, we show that our scheme is scalable such that no extra overhead in incurred in case of increased number of nodes and sensor field size. Most importantly, simulation results show that our scheme is highly resilient to node captures

Tacrolimus-Based, Steroid-Free Regimens in Renal Transplantation: 3-Year Follow-Up of the ATLAS Trial

BACKGROUND: Long-term use of corticosteroids is associated with considerable morbidity, including cardiovascular and metabolic adverse effects. METHODS: This study evaluated the long-term efficacy and safety of two steroid-free regimens compared with a triple immunosuppressive therapy in renal transplant recipients. This was a 3-year follow-up to a 6-month, open-label, randomized, multicenter study. RESULTS: Data from 3 years were available for 421 (93.3%) of 451 patients in the original intent-to-treat population (143 tacrolimus/basiliximab [Tac/Bas], 139 tacrolimus/mycophenolate mofetil [Tac/MMF], and 139 tacrolimus/MMF/steroids [triple therapy]). In the time interval from 6 months to 3 years after transplantation, the incidence of biopsy-proven acute rejection was low and similar (Tac/Bas, 2.1%; Tac/MMF, 2.2%; triple therapy, 2.2%); Most rejection episodes occurred during the first 6 months of the study. Graft survival was high (Kaplan-Meier estimates: 92.7%, 92.5%, and 92.5%), as was patient survival (93.1%, 96.4%, and 97.0%). There were 10 graft losses (n=2, 4, and 4) and 12 patient deaths (n=5, 2, and 5). Renal function was well preserved throughout the study and similar between groups. There was a trend toward improved cardiovascular risk factors in the Tac/Bas group, including reduced total and low-density lipoprotein cholesterol and lower new-onset insulin use. There were no between-group differences in the incidence or type of adverse events. CONCLUSION: Higher rates of acute rejection early in treatment were seen with the steroid-free regimens, but this did not translate into poorer long-term outcomes, such as graft and patient survival and renal function. A trend for a more favorable cardiovascular risk profile was observed for steroid-free immunosuppression with Tac/Bas