Clinical pharmacokinetics of mycophenolic acid and its metabolites in solid organ transplant recipient

Mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), is widely used for maintenance immunosuppressive therapy and prevention of renal allograft rejection in renal transplant recipients.MPA inhibits inosine monophosphate dehydrogenase (IMPDH), an enzyme involved in the “de novo” synthesis of purine nucleotides, thus suppressing both T-cell and B-cell proliferation. MPA shows a complex pharmacokinetics with considerable interand intra- patient by between- and within patient variabilities associated to MPA exposure. Several factors may contribute to it. The pharmacokinetic modeling according to the population pharmacokinetic approach with the non-linear mixed effects models has shown to be a powerful tool to describe the relationships between MMF doses and the MPA exposures and also to identify potential predictive patients’ demographic and clinical characteristics for dose tailoring during the post-transplant immunosuppresive treatment.

Clinical pharmacokinetics of mycophenolic acid and its metabolites in solid organ transplant recipient

Mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), is widely used for maintenance immunosuppressive therapy and prevention of renal allograft rejection in renal transplant recipients.MPA inhibits inosine monophosphate dehydrogenase (IMPDH), an enzyme involved in the “de novo” synthesis of purine nucleotides, thus suppressing both T-cell and B-cell proliferation. MPA shows a complex pharmacokinetics with considerable interand intra- patient by between- and within patient variabilities associated to MPA exposure. Several factors may contribute to it. The pharmacokinetic modeling according to the population pharmacokinetic approach with the non-linear mixed effects models has shown to be a powerful tool to describe the relationships between MMF doses and the MPA exposures and also to identify potential predictive patients’ demographic and clinical characteristics for dose tailoring during the post-transplant immunosuppresive treatment.

Clinical pharmacokinetics of mycophenolic acid and its metabolites in solid organ transplant recipient

Mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), is widely used for maintenance immunosuppressive therapy and prevention of renal allograft rejection in renal transplant recipients.MPA inhibits inosine monophosphate dehydrogenase (IMPDH), an enzyme involved in the “de novo” synthesis of purine nucleotides, thus suppressing both T-cell and B-cell proliferation. MPA shows a complex pharmacokinetics with considerable interand intra- patient by between- and within patient variabilities associated to MPA exposure. Several factors may contribute to it. The pharmacokinetic modeling according to the population pharmacokinetic approach with the non-linear mixed effects models has shown to be a powerful tool to describe the relationships between MMF doses and the MPA exposures and also to identify potential predictive patients’ demographic and clinical characteristics for dose tailoring during the post-transplant immunosuppresive treatment.

Thermal and magnetic field-induced martensite-austenite transition in Ni50.3Mn35.3Sn14.4 ribbons

Thermal and field-induced martensite-austenite transition was studied in melt spun Ni50.3Mn35.3Sn14.4 ribbons. Its distinct highly ordered columnarlike microstructure normal to ribbon plane allows the direct observation of critical fields at which field-induced and highly hysteretic reverse transformation starts (H=17kOe at 240K), and easy magnetization direction for austenite and martensite phases with respect to the rolling direction. Single phase L21 bcc austenite with TC of 313K transforms into a 7M orthorhombic martensite with thermal hysteresis of 21K and transformation temperatures of MS=226K, Mf=218K, AS=237K, and Af=244K

Good practice for dialogue and communication as strategic principle for policing political manifestations in Europe (GODIAC):field study handbook

This handbook describes the peer review methodology that was applied at the GODIAC project fi eld studies1. The peer review evaluation method as initiated by Otto Adang in the Netherlands and further developed in a European football context (Adang & Brown, 2008) involves experienced police offi cers cooperating with researchers to perform observational fi eld studies to identify good practices and learning points for public order management. The handbook builds on the GODIAC seminars and workshops, for the fi eld study members, which took place in September 2010, January 2012 and January 2013. The handbook has been discussed in the project group and in the steering committee. It is primarily written for the GODIAC fi eld study members as background material for understanding the fi eld study process and for clarifying the different responsibilities that enable active participation in the fi eld study. The handbook has been developed during the project period and incorporates learning points and developments of the peer review method. The handbook aims at promoting the use of fi eld studies for evaluation of policing major events.

Constraints on effective field theory parameters for the Lambda N -> NN transition

The relation between the low-energy constants appearing in the effective field theory description of the Lambda N -> NN transition potential and the parameters of the one-meson-exchange model previously developed is obtained. We extract the relative importance of the different exchange mechanisms included in the meson picture by means of a comparison to the corresponding operational structures appearing in the effective approach. The ability of this procedure to obtain the weak baryon-baryon-meson couplings for a possible scalar exchange is also discussed.

Constraints on effective field theory parameters for the Lambda N -> NN transition

The relation between the low-energy constants appearing in the effective field theory description of the Lambda N -> NN transition potential and the parameters of the one-meson-exchange model previously developed is obtained. We extract the relative importance of the different exchange mechanisms included in the meson picture by means of a comparison to the corresponding operational structures appearing in the effective approach. The ability of this procedure to obtain the weak baryon-baryon-meson couplings for a possible scalar exchange is also discussed.

Controlling anomalous stresses in soft field-responsive systems

We report a phenomenon occurring in field-responsive suspensions: shear-induced anomalous stresses. Competition between a rotating field and a shear flow originates a multiplicity of anomalous stress behaviors in suspensions of bound dimers constituted by induced dipoles. The great variety of stress regimes includes nonmonotonic behaviors, multiresonances, negative viscosity effect, and blockades. The reversibility of the transitions between the different regimes and the self-similarity of the stresses make this phenomenon controllable and therefore applicable to modify macroscopic properties of soft condensed matter phases.

Effectiveness of substituting cyclosporin A with tacrolimus in reducing gingival overgrowth in renal transplant patients

Objectives: This study aims to evaluate the effectiveness of periodontal therapy combined with tacrolimus in the suppression of gingival overgrowth (GO) and the effect on GO of changing from cyclosporin A to tacrolimus. Patients and Methods: Sixteen renal transplant patients, averaging 52 years of age, whose kidney function was stable and were receiving treatment with cyclosporin A, were randomly assigned to one of two groups. In the experimental group, patients were instructed in oral hygiene and underwent periodontal treatment, whereas in the control group, only oral hygiene instructions were given. After the first visit and the change of medication from cyclosporine to tacrolimus in both groups, periodic clinical revisions were carried out for 3 months in order to assess the evolution of GO. Results: All patients showed a progressive decrease in GO. There were no statistically significant differences between the two groups (p>0.05). A greater decrease in GO occurred within the first month after changing the medication. Conclusions: No improved effectiveness in reducing GO was observed for periodontal therapy in combination with tacrolimus. Tacrolimus is an alternative to cyclosporine when attempting to avoid GO in patients with kidney transplants

Settlement evolution, field systems and sedimentary processes in a Mediterranean mid-mountain (Montseny Massif, Catalunya)

This paper presents the first results of a current research project about human – environmental interactions in the Montseny Massif. Our work sets out to integrate two research lines in the studied area: - Archaeological and archaeo-morphological surveys in a lower part of the mountains in order to characterize the evolution of the settlements and field systems. - The geological and geomorphological characterization of the slope and terrace deposits in relation with field systems and archaeological data. First results point out the intensive occupation of these inland areas during the Iberian and the Roman periods. Post-Roman sediments show different processes of erosion.

A germination study of herbicide-resistant field poppies in Spain

Field poppy, Papaver rhoeas L., is a very common weed in winter cereals in North-Eastern Spain. Its control is becoming difficult due to expanding herbicide resistance. To control field poppies there are alternative strategies such as non-chemical control that take into account the weed emergence period. However, there is a lack of knowledge of P. rhoeas emergence patterns in semi-arid conditions. Thus, here we conducted pot experiments on the emergence of P. rhoeas. We aimed to describe the emergence period and to quantify the emergence of a susceptible and of a herbicide-resistant P. rhoeas population at two locations in Catalonia, Spain, from 1998 to 2001 and until 2004 at one of them. Therefore, pots containing seeds of both populations were established at the two locations and emergence was recorded monthly. We studied the origin of the population, the sowing location, the effect of cultivation and the sowing year. First, we found that the main emergence peaks in our experiments occurred in autumn, accounting for between 65.7 and 98.5% of the annual emergence from October to December, and only little emergence was recorded in spring. This emergence pattern is different from those found in the literature corresponding to Northern European countries, where in some cases main flushes occur only in autumn, in spring and winter or only in spring. The emergence was mainly affected by cultivation, but the effect of light stimulus was observed several months later. As a consequence, cultivation should be done in early autumn, promoting emergence during the whole autumn and winter so that emerged seedlings can be controlled before sowing a spring crop. Second, most experiments showed that the emergence was significantly higher in the first autumn than in the following seasons, e.g. 4.1% emergence in the first year and only 2.1, 2.3, 0.5 and 0.6% new emergence at one of the locations for the second, third, fourth and fifth years. Thus, after having a severe P. rhoeas infestation causing a big seed rain, emergence should be stimulated by autumn cultivation in the following season and seedlings controlled by trying to deplete the soil seed bank as much as possible. Despite the fact that emergence will be staggered throughout several years and that there was a significant relationship between rainfall and emergence, so that dry years will cause a smaller emergence rate of the weed, these findings define a cultural management strategy to reduce P. rhoeas infestations and to contribute to integrated weed management strategies combining it with other tools.

Short communication. Mutual pheromone antagonism in two sympatric corn borers, Sesamia nonagrioides and Ostrinia nubilalis, under field conditions

In previous studies, we demonstrated cross-antagonism in pheromone perception between pheromone componentsof the two corn (Zea mays L.) borers Sesamia nonagrioides Lefèbvre (Lepidoptera: Noctuidae) and Ostrinia nubilalis (Hübner) (Lepidoptera: Crambidae) in the laboratory and in the field. The two pheromone components identified as responsible for this cross-antagonism were Z 11-16:Ald, a minor component of S. nonagrioides pheromone, and Z 11-14:Ac, the main component of the pheromone of the Z-strain of O. nubilalis, which inhibited the response of O. nubilalis and S. nonagrioides, respectively. Here, we study this antagonism phenomenon in the field by air permeation of maize plots with each of the two components separately and measurement of mating in caged couples of the two corn borers on treated and untreated plots during three years. A significant reduction in mating rates was observed on the permeated plots: 7% for S. nonagrioides and 12% for O. nubilalis. When dispenser charges (200 ng) were increased by 50% and 75% in the third year, no decrease in mating rates was recorded at either of the increased concentrations. On the other hand, the use of large cages resulted in an increase of 8% to 12% in the percentage of unmated females in each of the two corn borers suggesting that at more realistic field corn borer densities, 0,1 couples/plant instead of the 2 couples/plant used in this experiment, cross-antagonism in the two corn borers could be higher than that recorded in small cages.