Basiliximab in pediatric liver transplantation: A pharmacokinetic-derived dosing algorithm

The pharmacokinetics and immunodynamics of basiliximab were assessed in 37 pediatric de novo liver allograft recipients to rationally design a dose regimen for this age-group. In part one of the study, patients were given 12 mg/m 2 basiliximab by bolus intravenous injection after organ perfusion and on day 4 after transplant. An interim pharmacokinetic evaluation supported a fixed-dose approach for part two of the study in which infants and children received two 10-mg doses of basiliximab and adolescents received two 20-mg doses. Blood samples were collected over a 12-week period for screening for anti-idiotype antibodies and analysis of basiliximab and soluble interleukin-2 receptor (IL-2R) concentrations. Basiliximab clearance in infants and children  5 L of ascites fluid drainage tended to have lower systemic exposure to basiliximab. CD25-saturating basiliximab concentrations were maintained for 27 ± 9 days in part one of the study (mg/m 2 dosing) with infants exhibiting the lowest durations. CD25 saturation lasted 37 ± 11 days in part two of the study, based on the fixed-dose regimen (p = 0.004 vs. mg/mg 2 dosing), but did not show the age-related bias observed in part one of the study. Anti-idiotype antibodies were detected in four patients, but this did not influence the clearance of basiliximab or duration of CD25 saturation. All 40 enrolled patients were included in the intent-to-treat clinical analysis. Episodes of acute rejection occurred in 22 patients (55%) during the first 12 months post-transplant. Three patients experienced loss of their graft as a result of technical complications, and six patients died during the 12-month study. Basiliximab was well tolerated by intravenous bolus injection, with no cytokine-release syndrome or other infusion-related adverse events. Hence, basiliximab was safe and well tolerated in pediatric patients undergoing orthotopic liver transplantation. To achieve similar basiliximab exposure as is efficacious in adults, pediatric patients < 35 kg in weight should receive two 10-mg doses and those ≥ 35 kg should receive two 20-mg doses of basiliximab by intravenous infusion or bolus injection. The first dose should be given within 6 h after organ perfusion and the second on day 4 after transplantation. A supplemental dose may be considered for patients with a large volume of drained ascites fluid relative to body size.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72080/1/j.1399-3046.2002.01086.x.pd

A mathematical model for unsteady mixed flows in closed water pipes

We present the formal derivation of a new unidirectional model for unsteady mixed flows in non uniform closed water pipe. In the case of free surface incompressible flows, the \FS-model is formally obtained, using formal asymptotic analysis, which is an extension to more classical shallow water models. In the same way, when the pipe is full, we propose the \Pres-model, which describes the evolution of a compressible inviscid flow, close to gas dynamics equations in a nozzle. In order to cope the transition between a free surface state and a pressured (i.e. compressible) state, we propose a mixed model, the \PFS-model, taking into account changes of section and slope variation

Estímulo no crescimento e na hidrólise de ATP em raízes de alface tratadas com humatos de vermicomposto: i - efeito da concentração.

O vermicomposto contém uma concentração elevada de substâncias húmicas e já é bem conhecido o efeito do seu uso sobre as propriedades do solo. No entanto,a ação direta das substâncias húmicas sobre o metabolismo das plantas é menos conhecida. O objetivo deste trabalho foi avaliar o uso de humatos extraídos de vermicomposto de esterco de curral com KOH 0,1 mol L-1 sobre o desenvolvimento e metabolismo de ATP em plântulas de alface. Após a germinação, plântulas de alface foram tratadas com os humatos em concentrações que variaram de 0 a 100 mg L-1 de C, durante quinze dias. Foram avaliados o crescimento da raiz e a atividade das bombas de H+ isoladas da fração microssomal do sistema radicular. Foi observado aumento na matéria fresca e seca do sistema radicular, bem como no número de sítios de mitose, raízes emergidas do eixo principal, na área e no comprimento radiculares, com o uso do humato na concentração de 25 mg L-1 de C. Também foi observado, nessa concentração, aumento significativo na hidrólise de ATP pelas bombas de H+, responsáveis pela geração de energia necessária à absorção de íons e pelo crescimento celular

Gating of aquaporins by heavy metals in Allium cepa L. epidermal cells

Changes in the water permeability, aquaporin (AQP) activity, of leaf cells were investigated in response to different heavy metals (Zn2+, Pb2+, Cd2+, Hg2+). The cell pressure probe experiments were performed on onion epidermal cells as a model system. Heavy metal solutions at different concentrations (0.05 μM–2 mM) were used in our experiments. We showed that the investigated metal ions can be arranged in order of decreasing toxicity (expressed as a decrease in water permeability) as follows: Hg>Cd>Pb>Zn. Our results showed that β-mercaptoethanol treatment (10 mM solution) partially reverses the effect of AQP gating. The magnitude of this reverse differed depending on the metal and its concentration. The time course studies of the process showed that the gating of AQPs occurred within the first 10 min after the application of a metal. We also showed that after 20–40 min from the onset of metal treatment, the water flow through AQPs stabilized and remained constant. We observed that irrespective of the metal applied, the effect of AQP gating can be recorded within the first 10 min after the administration of metal ions. More generally, our results indicate that the toxic effects of investigated metal ions on the cellular level may involve AQP gating

Weak and strong solutions of equations of compressible magnetohydrodynamics

International audienceThis article proposes a review of the analysis of the system of magnetohydrodynamics (MHD). First, we give an account of the modelling asumptions. Then, the results of existence of weak solutions, using the notion of renormalized solutions. Then, existence of strong solutions in the neighbourhood of equilibrium states is reviewed, in particular with the method of Kawashima and Shizuta. Finally, the special case of dimension one is highlighted : the use of Lagrangian coordinates gives a simpler system, which is solved by standard techniques

The high diversity of aquaporins reveals novel facets of plant membrane functions

International audienc

Added-mass effect in the design of partitioned algorithms for fluid-structure problems

The aim of this work is to provide a mathematical contribution to explain the numerical instabilities encountered under certain combinations of physical parameters in the simulation of fluid-structure interaction (FSI) when using loosely coupled time advancing schemes. It is also shown how the same combinations of parameters lead, in the case of strongly coupled schemes, to problems that demand a greater computational effort to be solved, requiring for example a high number of subiterations. The application that we have in mind is FSI simulation for blood flow in large human arteries, but the discussion applies as well to several FSI problems in which an incompressible fluid interacts with a thin elastic structure. To carry out the mathematical analysis, we consider a simplified model representing the interaction between a potential fluid and a linear elastic thin tube. Despite its simplicity, this model reproduces propagation phenomena and takes into account the added-mass effect of the fluid on the structure, which is known to be source of numerical difficulties. This allows to draw conclusions that apply to more realistic problems, as well

Added-mass effect in the design of partitioned algorithms for fluid-structure problems

The aim of this work is to provide a mathematical contribution to explain the numerical instabilities encountered under certain combinations of physical parameters in the simulation of fluid-structure interaction (FSI) when using loosely coupled time advancing schemes. It is also shown how the same combinations of parameters lead, in the case of strongly coupled schemes, to problems that demand a greater computational effort to be solved, requiring for example a high number of subiterations. The application that we have in mind is FSI simulation for blood flow in large human arteries, but the discussion applies as well to several FSI problems in which an incompressible fluid interacts with a thin elastic structure. To carry out the mathematical analysis, we consider a simplified model representing the interaction between a potential fluid and a linear elastic thin tube. Despite its simplicity, this model reproduces propagation phenomena and takes into account the added-mass effect of the fluid on the structure, which is known to be source of numerical difficulties. This allows to draw conclusions that apply to more realistic problems, as well. (c) 2005 Elsevier B.V. All rights reserved