The tris formulation of Fluorouracil is more cardiotoxic than the sodium-salt formulations

The cardiotoxicity of 5-fluorouracil (FU) was attributed to degradation compounds present in the injected vials, fluoroacetaldehyde (Facet) and fluoromalonaldehydic acid (FMald). FU-NaOH vials were much less cardiotoxic than FU-Tris vials on the isolated perfused rabbit heart model since Facet and FMald are stored in stable depot forms in FU-Tris vials whereas, in FU-NaOH vials, they are extensively transformed. Cardiotoxic fluoroacetate (FAG), coming from Facet metabolization, was found in urine of patients, with a ratio FAC /FU catabolites 10-30 fold lower in patients treated with FU-NaOH than in those treated with FU-Tris

Transcript expression of vesicular glutamate transporters in lumbar dorsal root ganglia and the spinal cord of mice – Effects of peripheral axotomy or hindpaw inflammation

Using specific riboprobes, we characterized the expression of vesicular glutamate transporter (VGLUT)1–VGLUT3 transcripts in lumbar 4–5 (L4–5) dorsal root ganglions (DRGs) and the thoracolumbar to lumbosacral spinal cord in male BALB/c mice after a 1- or 3-day hindpaw inflammation, or a 7-day sciatic nerve axotomy. Sham animals were also included. In sham and contralateral L4–5 DRGs of injured mice, VGLUT1-, VGLUT2- and VGLUT3 mRNAs were expressed in ∼45%, ∼69% or ∼17% of neuron profiles (NPs), respectively. VGLUT1 was expressed in large and medium-sized NPs, VGLUT2 in NPs of all sizes, and VGLUT3 in small and medium-sized NPs. In the spinal cord, VGLUT1 was restricted to a number of NPs at thoracolumbar and lumbar segments, in what appears to be the dorsal nucleus of Clarke, and in mid laminae III–IV. In contrast, VGLUT2 was present in numerous NPs at all analyzed spinal segments, except the lateral aspects of the ventral horns, especially at the lumbar enlargement, where it was virtually absent. VGLUT3 was detected in a discrete number of NPs in laminae III–IV of the dorsal horn. Axotomy resulted in a moderate decrease in the number of DRG NPs expressing VGLUT3, whereas VGLUT1 and VGLUT2 were unaffected. Likewise, the percentage of NPs expressing VGLUT transcripts remained unaltered after hindpaw inflammation, both in DRGs and the spinal cord. Altogether, these results confirm previous descriptions on VGLUTs expression in adult mice DRGs, with the exception of VGLUT1, whose protein expression was detected in a lower percentage of mouse DRG NPs. A detailed account on the location of neurons expressing VGLUTs transcripts in the adult mouse spinal cord is also presented. Finally, the lack of change in the number of neurons expressing VGLUT1 and VGLUT2 transcripts after axotomy, as compared to data on protein expression, suggests translational rather than transcriptional regulation of VGLUTs after injury.Fil: Malet, Mariana. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vieytes, C. A.. Universidad Austral. Facultad de Ciencias Biomédicas; ArgentinaFil: Lundgren, K. H.. University of Cincinnati; Estados UnidosFil: Seal, R. P.. University of Pittsburgh; Estados UnidosFil: Tomasella, María Eugenia. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Seroogy, K. B.. University of Cincinnati; Estados UnidosFil: Hökfelt, T.. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Gebhart, G. F.. University of Pittsburgh; Estados UnidosFil: Brumovsky, Pablo Rodolfo. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Pittsburgh; Estados Unido

Forecasting the behaviour of complex landslides with a spatially distributed hydrological model

International audienceThe relationships between rainfall, hydrology and landslide movement are often difficult to establish. In this context, ground-water flow analyses and dynamic modelling can help to clarify these complex relations, simulate the landslide hydrological behaviour in real or hypothetical situations, and help to forecast future scenarios based on environmental change. The primary objective of this study is to investigate the possibility of including more temporal and spatial information in landslide hydrology forecasting, by using a physically based spatially distributed model. Results of the hydrological and geomorphological investigation of the Super-Sauze earthflow, one of the persistently active landslide occurring in clay-rich material of the French Alps, are presented. Field surveys, continuous monitoring and interpretation of the data have shown that, in such material, the groundwater level fluctuates on a seasonal time scale, with a strong influence of the unsaturated zone. Therefore a coupled unsaturated/saturated model, incorporating Darcian saturated flow, fissure flow and meltwater flow is needed to adequately represent the landslide hydrology. The conceptual model is implemented in a 2.5-D spatially distributed hydrological model. The model is calibrated and validated on a multi-parameters database acquired on the site since 1997. The complex time-dependent and three-dimensional groundwater regime is well described, in both the short- and long-term. The hydrological model is used to forecast the future hydrological behaviour of the earthflow in response to potential environmental changes

Cardiotoxicity of commercial 5-fluorouracil vials stems from the alkaline hydrolysis of this drug.

The cardiotoxicity of 5-fluorouracil (FU) was attributed to impurities present in the injected vials. One of these impurities was identified as fluoroacetaldehyde which is metabolised by isolated perfused rabbit hearts into fluoroacetate (FAC), a highly cardiotoxic compound. FAC was also detected in the urine of patients treated with FU. These impurities were found to be degradation products of FU that are formed in the basic medium employed to dissolve this compound. To avoid chemical degradation of this antineoplastic drug, the solution of FU that will be injected should be prepared immediately before use

Vertically coupled double quantum rings at zero magnetic field

Within local-spin-density functional theory, we have investigated the `dissociation' of few-electron circular vertical semiconductor double quantum ring artificial molecules at zero magnetic field as a function of inter-ring distance. In a first step, the molecules are constituted by two identical quantum rings. When the rings are quantum mechanically strongly coupled, the electronic states are substantially delocalized, and the addition energy spectra of the artificial molecule resemble those of a single quantum ring in the few-electron limit. When the rings are quantum mechanically weakly coupled, the electronic states in the molecule are substantially localized in one ring or the other, although the rings can be electrostatically coupled. The effect of a slight mismatch introduced in the molecules from nominally identical quantum wells, or from changes in the inner radius of the constituent rings, induces localization by offsetting the energy levels in the quantum rings. This plays a crucial role in the appearance of the addition spectra as a function of coupling strength particularly in the weak coupling limit.Comment: 18 pages, 8 figures, submitted to Physical Review

Understanding how alcohol environment influences youth drinking: A concept mapping study among university students

The aim of the study was to identify the environmental factors that influence alcohol consumption, according to university students, and assess the relative importance and the frequency attributed to each factor. A study using Concept Mapping methodology was performed with a sample of nursing students, who participated in two face-to-face data collection sessions. In session 1, a consensus about the environmental aspects that influence their alcohol consumption was obtained. In session 2, the statements obtained were rated according to their relative importance and frequency in alcohol use (1 = minimum; 5 = maximum). Subsequently, all data were analyzed with the RCMAP of the statistical package R 3.6.1. Approximately 60 students participated in each session. Most were women aged 20 to 24. In session 1, a total of 55 statements were obtained and classified into 7 different clusters: Advertising (9 statements); Family environment (4 statements); Social pressure (12 statements); Responsibilities/ norms (4 statements); Holidays and leisure time (7 statements); Emotional situations (8 statements); Accessibility (11 statements). Factors related to social pressure, holidays and leisure time, and alcohol accessibility were considered the most important and frequent in alcohol consumption. In contrast, alcohol advertising was considered the least important (mean 2.6 out of 5) and frequent (mean 2.1 out 5) factor. In conclusion, the factors considered most relevant among nursing students match those having more resources allocated for prevention and health promotion, except for alcohol advertising, which was perceived as less important and frequent compared with the other factors

Acrylonitrile butadiene styrene-based composites with permalloy with tailored magnetic response

This work reports on tailoring the magnetic properties of acrylonitrile butadiene styrene (ABS)-based composites for their application in magnetoactive systems, such as magnetic sensors and actuators. The magnetic properties of the composites are provided by the inclusion of varying permalloy (Py—Ni75Fe20Mo5) nanoparticle content within the ABS matrix. Composites with Py nanoparticle content up to 80 wt% were prepared and their morphological, mechanical, thermal, dielectric and magnetic properties were evaluated. It was found that ABS shows the capability to include high loads of the filler without negatively influencing its thermal and mechanical properties. In fact, the thermal properties of the ABS matrix are basically unaltered with the inclusion of the Py nanoparticles, with the glass transition temperatures of pristine ABS and its composites remaining around 105 °C. The mechanical properties of the composites depend on filler content, with the Young’s modulus ranging from 1.16 GPa for the pristine ABS up to 1.98 GPa for the sample with 60 wt% filler content. Regarding the magnetic properties, the saturation magnetization of the composites increased linearly with increasing Py content up to a value of 50.9 emu/g for the samples with 80 wt% of Py content. A numerical model has been developed to support the findings about the magnetic behavior of the NP within the ABS. Overall, the slight improvement in the mechanical properties and the magnetic properties provides the ABS composites new possibilities for applications in magnetoactive systems, including magnetic sensors, actuators and magnetic field shielding.This project was supported by the PID program CDTI (EXP-00131900/IDI-20210369). Funding is from the Basque Government Industry Department under the ELKARTEK program. Support was received from the Portuguese Fundação para a Ciência e Tecnologia, grant SFRH/BPD/110914/2015