Enantiospecific antitrypanosomal in vitro activity of eflornithine

The polyamine synthesis inhibitor eflornithine is a recommended treatment for the neglected tropical disease Gambian human African trypanosomiasis in late stage. This parasitic disease, transmitted by the tsetse fly, is lethal unless treated. Eflornithine is administered by repeated intravenous infusions as a racemic mixture of L-eflornithine and D-eflornithine. The study compared the in vitro antitrypanosomal activity of the two enantiomers with the racemic mixture against three Trypanosoma brucei gambiense strains. Antitrypanosomal in vitro activity at varying drug concentrations was analysed by non-linear mixed effects modelling. For all three strains, L-eflornithine was more potent than D-eflornithine. Estimated 50% inhibitory concentrations of the three strains combined were 9.1 muM (95% confidence interval [8.1; 10]), 5.5 muM [4.5; 6.6], and 50 muM [42; 57] for racemic eflornithine, L-eflornithine and D-eflornithine, respectively. The higher in vitro potency of L-eflornithine warrants further studies to assess its potential for improving the treatment of late-stage Gambian human African trypanosomiasis

Positron range estimations with PeneloPET

Technical advances towards high resolution PET imaging try to overcome the inherent physical limitations to spatial resolution. Positrons travel in tissue until they annihilate into the two gamma photons detected. This range is the main detector-independent contribution to PET imaging blurring. To a large extent, it can be remedied during image reconstruction if accurate estimates of positron range are available. However, the existing estimates differ, and the comparison with the scarce experimental data available is not conclusive. In this work we present positron annihilation distributions obtained from Monte Carlo simulations with the PeneloPET simulation toolkit, for several common PET isotopes (18F, 11C, 13N, 15O, 68Ga and 82Rb) in different biological media (cortical bone, soft bone, skin, muscle striated, brain, water, adipose tissue and lung). We compare PeneloPET simulations against experimental data and other simulation results available in the literature. To this end the different positron range representations employed in the literature are related to each other by means of a new parameterization for positron range profiles. Our results are generally consistent with experiments and with most simulations previously reported with differences of less than 20% in the mean and maximum range values. From these results, we conclude that better experimental measurements are needed, especially to disentangle the effect of positronium formation in positron range. Finally, with the aid of PeneloPET, we confirm that scaling approaches can be used to obtain universal, material and isotope independent, positron range profiles, which would considerably simplify range correction.We kindly acknowledge support from Comunidad de Madrid (ARTEMIS S2009/DPI-1802), Spanish Ministry of Science and Innovation (grants FPA2010-17142 and ENTEPRASE, PSE-300000-2009-5), by European Regional Funds, by CDTI under the CENIT Programme (AMITProject) and by CPAN, CSPD-2007-00042@Ingenio2010. Part of the calculations of this work were performed in the “Cluster de Cálculo de Alta Capacidad para Técnicas Físicas” funded in part by UCM and in part by UE under FEDER programme. This is a contribution to the Campus of International Excellence of MoncloaPublicad

Development of brown rot epidemics in Spanish peach orchards

A new approach to modelling epidemics of brown rot caused by Monilinia spp. in Ebro Valley peach orchards has been developed. This compartmental model was subdivided according to the phenological stages in which the disease can develop (blossom, immature fruit, and ripe fruit). Information host susceptibility, primary and secondary inoculum sources and latent infections in immature fruit was taken into account. The compartmental model is described by a system of differential equations, and is simple enough to allow an analytical study of the main epidemiological factors that determine the rate of disease progress during a single growing season. The proposed model fits well to the epidemic pattern of brown rot observed in north-eastern Spain. The transmission of the disease as a non-linear term implied that small changes in the infection rate had a large effect on the development of the disease. The model has confirmed the usefulness of removing mummies (infected fruit that remains in the crop during winter) from the field to reduce the final incidence of the disease. In addition, all control measures that reduce the rate of secondary infection in ripe fruit, either through the use of more resistant varieties or the use of fungicides, are effective in reducing brown rot incidence. The proposed epidemic model is flexible and allows to add complexities to the system and evaluate the effectiveness of different control strategies.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This study was supported by grant PID2020-115702RB-C21 and AGL2017-84389-C2-2-R from the Ministry of Science and Innovation (Spain)