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6 pags., 3 figs., 3 tabs., Background: The increase in the number of basal cell carcinoma (BCC) lesions has prompted use of minimally invasive therapies, including Photodynamic therapy (PDT). . The objective of the present work was to analyze the efficacy of methyl aminolevulinate-mediated photodynamic therapy (MAL-PDT) in patients suffering from superficial or nodular BCCs. Methods: A total of 220 BCC lesions (76 superficial and 144 nodular), clinically diagnosed and confirmed by histopathology analysis, were treated in 174 patients (mean age 72.5). Debulking using curettage was performed before two or three MAL-PDT sessions (λ = 630 nm; 90 J/cm; 23 min) at 4-week intervals. Analyses of clinical clearance and cosmetic outcome were carried out by direct examination, dermoscopy, photographs, as well as by fluorescence diagnosis using a Wood's lamp. Evaluations were carried out at the different PDT sessions and follow-ups over a 3-year period. Results: MAL-PDT was safe and highly tolerated. After an average of 2.6 MAL-PDT sessions, the overall clearance rate at 3-year follow-up was 96.1 % (95 % confidence interval [CI] 100 %–92 %) for superficial BCCs and 95.2 % (95 % [CI] 99 %-92 %) for nodular BCCs after an average of 2.7 sessions. Minimal side effects such as crushing, erythema and edema were reported. All BCC lesions showed excellent or good cosmetic results. Conclusion: The protocol followed in the present study has shown that MAL-PDT is a safe and effective treatment for superficial and nodular types of BCC., This research was supported by a grant from the Eugenio Rodríguez Pascual Foundation (Madrid, Spain) and by the Spanish Research Project MINECO (Ref.: MAT 2017-83856-C3).

We characterised the expression of semaphorin (sema)3A, sema7A and their receptors in the immune and the central nervous system (CNS) at different stages of experimental autoimmune encephalomyelitis (EAE). We also studied their expression in neonatal and adult oligodendrocyte progenitor cell (OPC) and in mature oligodendrocyte cultures. Our results show that sema3A is increased in the CNS and decreased in the immune system upon EAE induction. However, sema7A expression is increased in both the CNS and the immune system during EAE. We also detected sema3A, sema7A and their receptors in neonatal and adult OPCs and in mature oligodendrocytes. These data suggest that sema3A and sema7A are involved in the pathogenesis of EAE, in the modulation of the immune response and in the neurodegeneration that take place in the CNS. Sema7A may represent an intriguing potential therapeutic target for the treatment of both the neurodegenerative and immune-mediated disease processes in MS., This work has been financed with grants of the Spanish Ministry of Economy and Competitiveness by the Fondo de Investigación Sanitaria (FIS), the Instituto de Salud Carlos III (PS09/01180 granted to CE), and by MINECO (grants SAF2009-07842, SAF2012-40023, ADE10-0010, RD07-0060-2007, RD12-0032-12), the Fondation ARSEP (France, ARSEP-2012-tPA/NMDA-MS) and the Fundación Eugenio Rodríguez Pascual (Spain, FERP-2011-POHTCMS), all of them granted to FdC. We also thank the “Red Española de Esclerosis Múltiple (REEM)” (RD07/0060; RD12/0032), which is sponsored by FIS, the Instituto de Salud Carlos III, the Ministry of Economy and Competitiveness in Spain, and the “Ajuts per donar Suport als Grups de Recerca de Catalunya (2009 SGR 0793; 2014 SGR 1082)”, which is sponsored by the “Agència de Gestió d'Ajuts Universitaris i de Recerca” (AGAUR) of the Generalitat de Catalunya in Spain. AG-F was supported by the PFIS programme (FI10/00456) of the Ministry of Economy and Competitiveness. HE was supported by the “Sara Borrell” programme (CD09/00363) of the FIS of the Ministry of Economy and Competitiveness of Spain. CE was partially supported by the “Miguel Servet” programme (CP07/00146; CP13/00028) of the FIS of the Ministry of Economy and Competitiveness of Spain. AB was hired under the ADE10-0010 and EM.M-R was a recipient of a predoctoral fellowship (BES-2010-042593) from the MINECO FPI programme (associated to SAF2009-07842).

et al., Aging remains the main risk factor to suffer Alzheimer's disease (AD), though epidemiological studies also support that type 2 diabetes (T2D) is a major contributor. In order to explore the close relationship between both pathologies we have developed an animal model presenting both AD and T2D, by crossing APP/PS1 mice (AD model) with db/db mice (T2D model). We traced metabolic and cognitive evolution before T2D or AD pathology is present (4 weeks of age), when T2D has debuted but no senile plaques are present (14 weeks of age) and when both pathologies are well established (26 weeks of age). APP/PS1xdb/db mice showed an age-dependent synergistic effect between T2D and AD. Significant brain atrophy and tau pathology were detected in the cortex by 14 weeks, that spread to the hippocampus by 26 weeks of age. Severe cognitive impairment was also detected as soon as at 14 weeks of age. Interestingly, in APP/PS1xdb/db mice we observed a shift in Aβ soluble/insoluble levels, and whereas more toxic soluble species were favoured, senile plaques (SP) were reduced. An overall increase of microglia activation was observed in APP/PS1xdb/db mice. We also found exacerbated hemorrhagic burden in APP/PS1xdbd/db mice, suggesting that blood brain barrier alterations may be responsible for the early pathological features observed. Moreover, metabolic parameters can predict many of these alterations, supporting a role for T2D in AD pathology. This new model provides a relevant tool to further explore the relationship between T2D, AD and vascular implications, offering the possibility to assess therapeutic approaches, that by improving T2D metabolic control could delay or prevent AD pathology., Junta de Andalucia, Proyectos de Excelencia, Consejería de Economía, Innovación, Ciencia y Empleo (P11-CTS-7847), Fundación Eugenio Rodríguez Pascual 2015, ISCIII–Subdirección General de Evaluación y Fomento de la Investigación and cofinanced by the European Union (Fondo Europeo de Desarrollo Regional, FEDER) “Una manera de hacer Europa” PI12/00675 (Monica Garcia-Alloza).

Glioblastoma multiforme (GBM) is one of the deadliest forms of cancer, with an average survival time of approximately 1 year despite aggressive surgery, radiotherapy and chemotherapy. Here, we report a preclinical study by which the two main energy pathways of the tumor cells, oxidative phosphorylation and aerobic glycolysis, are simultaneously disrupted. The therapy is based on a plant gene encoding a β-glucosidase, linamarase (lis), which react with the substrate linamarin (lin) producing cyanide. We also use glucose oxidase (GO) to enhance oxidative stress and to induce cell death in the tumor. To test in vivo this suicide gene therapy system (lis/lin/GO), we used an orthotopic model of the human U87MG glioma cells, genetically modified to express the lis gene, and stereotactically implanted into the brains of nude rats (rnu/rnu). Despite its genetic condition, 6% of the animals immunorejected the xenotransplanted cells giving false curative results. We tried several delivery methods with limited success. The therapeutic cocktail, at dosages that perhaps eliminated the brain tumors, is too toxic for the animal causing its premature death., This work was supported by funds from: FINA Biotech; Fondo de Investigación Sanitaria, Ministerio de Sanidad y Consumo (PI06/0554) Spain; Ministerio de Ciencia e Innovación (SAF 2009-07259) Spain, and Fundación Eugenio Rodriguez Pascual (Madrid). The Centro de Biología Molecular S.O. is also the recipient of an institutional grant from the Ramón Areces Foundation. A.C. was the recipient of a grant MAEC-AECID, Spain.

The yolk granules of Artemia behave as unstable structures during isolation, especially after hatching. A stringent dechorionization of the cysts is required for an easy homogenization and good extraction of the yolk granules. The use of Ficoll and the avoidance of high dilutions in the homogenization process allows the isolation in an intact state of a pure yolk granules fraction without nuclear contamination. Previously described methods for the isolation of yolk granules lead to low recoveries of these structures in preparations with nuclear contamination. Lipovitellin, the major yolk protein, can be used as a biochemical marker to monitor the recovery of yolk granules and the possible yolk contamination of other subcellular fractions. The isolation of nuclei is also improved, their double membrane preserved in an enriched fraction with less yolk contamination than usually obtained with previously described methods. The other major storage structure, the lipoid bodies, can be isolated intact in these conditions, whereas they are also disrupted in common homogenization media., This work was supported by grants of the Rodriguez Pascual Foundation and the Fondo Nacional para la Investigación Científica. R.P. has a fellowship from Caja de Ahorros y M.P. de Madrid. R.G. was a fellow of the Consejo Superior de Investigaciones Científicas.

Collagenase digestion of minced lung tissue yielded isolated cells, functionally viable as judged by several metabolic and morphological criteria, representative of all the cell species normally present in the tissue. The efficiency of the isolation procedure was about 25 per cent. Aerobic metabolism was not affected by most of the substrates tested except by succinate which increased oxygen utilization, and glucose, fructose and octanoate which significantly decreased oxygen uptake. Since no significant changes have been observed in the cellular adenine nucleotide content during glucose depression of aerobic metabolism it is concluded that the glycolytic flux had to be sufficient as to account for the decrease in the mitochondrial energy production. The mechanism responsible for these effects as well as their physiological significance are discussed herewith., This work has been supported in part by grants from Fundación Rodríguez Pascual and Comisión Asesora para el Desarrollo de la Investigación. J. P. D. is recipient of a research fellowship from the Spanish Secretary of Education and Science.

Glucose decreases the oxygen utilization by isolated rat lung cells. Its effect displays saturation type kinetics with a “Ki” of 2.2. mM. The similarity of this value with the reported “Km” of 2.4 mM described for glucose uptake by these cells, suggests that both processes may be intimately related and both of them are under the control of the same rate limiting step. Several arguments point to glucose transport into these cells as the most important rate limiting step for its utilization: 1) Phloridzin prevented glucose inhibition of oxygen uptake while mannoheptulose did not; 2) The activity of hexokinase which is the least active glycolytic enzyme in these cells far exceeded the observed rates of glucose utilization and a decrease of 45 per cent in its activity in starved animals did not affect the rate of glucose uptake; 3) The “Km” of hexokinase for glucose is two orders of magnitude below the observed “Km” for glucose uptake and the “Ki” for glucose inhibition of respiration., This work was supported by grants from Fundación Rodríguez Pascual, Essex (Espana) S.A, and Comisión Asesora para el Desarrollo de la Investigación, J,P .D . and A,M.R . are recipients of research fellowships from the Spanish Secretary of Education and Science.