PV-nephropathy is a rare but serious complication after renal transplantation. A small group of patients under intensive immunosuppression comprising tacrolimus in combination with mycophenolate mofetil has a significantly increased risk of acquiring this deleterious complication.

1. We used a non-invasive method to measure the breathing of conscious newborn rat pups continuously and studied the maturation of the respiratory response to reductions in inspired O2 fraction (FI,O2) from 0.21 to 0.15, 0.12 or 0.08 for 6 min. Newborn rats, like many other species, showed a "biphasic" respiratory response, ventilation (VE) increasing during the first 1-2 min of hypoxia (phase 1) and then falling towards control, or below it, over the next 4 min (phase 2). 2. The secondary fall in VE decreased with age up to 14 days. The presence of a significant fall in VE in phase 2 depended on the FI,O2 to which the pups were exposed acutely; the lower the FI,O2 the greater the age at which a biphasic VE response was observed. 3. Our results are discussed in terms of two opposing components which determine VE during acute hypoxia in the neonate: (a) a fast arterial chemoreceptor-mediated stimulation of VE and (b) a slower central nervous component which inhibits VE, possibly a persistence of a suprapontine mechanism which inhibits fetal breathing movements during hypoxia in utero. Both of these components undergo maturation after birth.

The urokinase receptor (uPAR) was originally identified as the membrane receptor of the serine protease urokinase (uPA), thereby implicated in the plasminogen activation cascade and regulation of pericellular proteolysis. Later on, vitronectin was showed to be another major ligand providing uPAR with a role in cell adhesion. Other unrelated ligands have been subsequently reported including for example factor XII and SRPX2 expanding the functions of uPAR to unexpected biological areas such as the initiation of the coagulation cascade or the regulation of language development. Due to its glycosylphosphatidylinositol (GPI) anchor, uPAR has no intracellular domain and thus exerts its signaling capacity through lateral interactions with other components of the plasma membrane that actually mediate uPAR-induced signals. As yet, a total 42 proteins interacting directly with uPAR can be numbered comprising 9 soluble ligands and 33 lateral partners. The fact that uPAR interacts with members of three major families of membrane receptors i.e. G protein-coupled receptors, receptor tyrosine kinases, and integrins implies that the actual number of components constituting the uPAR interacome is extremely high. For example, 156 factors belong to the integrin adhesome. Moreover, in the light of the wide diversity of the components of the uPAR interactome, uPAR appears to be an essential player of major biological systems including the blood coagulation, complement and plasma kallikrein-kinin cascades. This review describes the soluble ligands and lateral partners of the uPAR interactome, the mechanisms regulating uPAR interactions and their proved and/or potential biological functions.

BackgroundTherapeutic plasma exchange (TPE) is either performed using a highly permeable filter with standard multifunctional renal replacement equipment (mTPE) or a centrifugation device (cTPE). Although both techniques are well established in clinical practice, performance of these two modes of TPE was never compared in a prospective randomized fashion. Thus we aimed to compare two commercially available therapeutic apheresis systems: mTPE (Octonova with Plasmaflo filter) and cTPE (Spectra Optia apheresis system).MethodsTwenty-one patients (age 51.6 ± 13.5 years; 10 F/11 M; BMI 25.1 ± 5.0 kg/m2) were enrolled in this randomized, prospective, paired, crossover study performed in the Hannover Medical School, Germany. First treatment (either mTPE or cTPE) was chosen by an online randomization list. The primary endpoints were plasma removal efficiency with 1.2× of the total plasma volume exchanged. Secondary endpoints were total amount of plasma substances removed, such as IgG and fibrinogen. Further, the treatment effect on platelet count and complications were evaluated.ResultsDespite a comparable volume of the processed plasma, mTPE treatment time was 10.5 % longer than cTPE treatment time (p < 0.05), resulting in a 10 % lower plasma removal rate of the mTPE treatment. Both treatments were comparable in terms of decrease in median (IQR) IgG [pre-mTPE 5.34 (3.48–8.37), post-mTPE 1.96 (1.43–2.84) g/L; pre-cTPE 5.88 (3.42–8.84), post-cTPE 1.89 (1.21–3.52) g/L]. Also the median (IQR) amount of IgG removed in mTPE [13.14 (7.42–16.10) g] was not different from the cTPE treatment [9.30 (6.26–15.69) g]. This was also true for IgM removal. Platelet loss during mTPE was nearly twice as much as with cTPE (15 ± 9 versus 7 ± 9 %, p < 0.05).ConclusionAlthough the centrifugal procedures were conducted using flow rates that could easily be obtained using peripheral access, plasma removal efficiency was significantly higher and treatment time was significantly lower in cTPE as compared to mTPE. Despite this lower treatment time, the decline in markers of procedure efficacy was comparable. Especially in centers performing many procedures per year, cTPE in contrast to mTPE can reduce treatment time without compromising treatment efficacy.