Cerebral ischaemia and matrix metalloproteinase-9 modulate the angiogenic function of early and late outgrowth endothelial progenitor cells

The enhancement of endogenous angiogenesis after stroke will be critical in neurorepair therapies where endothelial progenitor cells (EPCs) might be key players. Our aim was to determine the influence of cerebral ischaemia and the role of matrix metalloproteinase-9 (MMP-9) on the angiogenic function of EPCs. Permanent focal cerebral ischaemia was induced by middle cerebral artery (MCA) occlusion in MMP-9/knockout (MMP-9/KO) and wild-type (WT) mice. EPCs were obtained for cell counting after ischaemia (6 and 24 hrs) and in control animals. Matrigel™ assays and time-lapse imaging were conducted to monitor angiogenic function of WT and MMP9-deficient EPCs or after treatment with MMP-9 inhibitors. Focal cerebral ischaemia increased the number of early EPCs, while MMP-9 deficiency decreased their number in non-ischaemic mice and delayed their release after ischaemia. Late outgrowth endothelial cells (OECs) from ischaemic mice shaped more vessel structures than controls, while MMP-9 deficiency reduced the angiogenic abilities of OECs to form vascular networks, in vitro. Treatment with the MMP inhibitor GM6001 and the specific MMP-9 inhibitor I also decreased the number of vessel structures shaped by both human and mouse WT OECs, while exogenous MMP-9 could not revert the impaired angiogenic function in MMP-9/KO OECs. Finally, time-lapse imaging showed that the extension of vascular networks was influenced by cerebral ischaemia and MMP-9 deficiency early during the vascular network formation followed by a dynamic vessel remodelling. We conclude that focal cerebral ischaemia triggers the angiogenic responses of EPCs, while MMP-9 plays a key role in the formation of vascular networks by EPCs

Estudio estadístico en cirugía ungueal

Presentamos un estudio estadístico sobre los resultados de las técnicas de cirugía ungueal realizadas en el Servicio de Cirugía de la Clínica Podológica de la Universidad de Barcelona en los últimos años, describiendo el método empleado para su realización y las conclusiones obtenidas

Circulating cell-free DNA is a predictor of short-term neurological outcome in stroke patients treated with intravenous thrombolysis

Altres ajuts: This work has been funded by Instituto de Salud Carlos III, grant FIS PI15/354, co-financed by the European Regional Development Fund (FEDER). AB is supported by a Rio Hortega contract CM13/00265 from the Instituto de Salud Carlos III.Circulating cell-free DNA (cfDNA) has been described as a prognostic marker for several diseases. Its prognostic value for short-term outcome in stroke patients treated with intravenous thrombolysis remains unexplored. cfDNA was measured on admission in 54 tissue plasminogen activator (tPA)-treated patients and 15 healthy controls using a real-time quantitative polymerase chain reaction assay. Neurological outcome was assessed at 48 h. Predictors of neurological improvement were evaluated by logistic regression analysis, and the additional predictive value of cfDNA over clinical variables was determined by integrated discrimination improvement (IDI). Stroke patients presented higher baseline cfDNA than healthy controls (408.5 (179-700.5) vs. 153.5 (66.9-700.5) kilogenome-equivalents/L, p = 0.123). A trend towards lower cfDNA levels was found in patients who neurologically improved at 48 h (269.5 (143.3-680) vs. 504 (345.9-792.3) kilogenome-equivalents/L, p = 0.130). In logistic regression analysis, recanalization at 1 h and cfDNA < 302.75 kilogenome-equivalents/L was independently associated with neurological improvement after adjustment by age, gender and baseline National Institutes of Health Stroke Scale score. The addition of cfDNA to the clinical predictive model improved its discrimination (IDI = 21.2% (9.2-33.3%), p = 0.009). These data suggest that cfDNA could be a surrogate marker for monitoring tPA efficacy by the prediction of short-term neurological outcome

Global change at the Polar regions

CSIC SCIENTIFIC CHALLENGES: TOWARDS 2030, Vol. 7: GLOBAL CHANGE IMPACTS, CHALLENGE 4The Polar Regions are key Earth’s climate regulators and, hence, any perturbation in their baseline conditions can have global repercussions. Owing their intrinsic particularities such as the presence of huge amounts of sea and continental ice, their terrestrial and marine ecosystems are highly sensitive to temperature fluctuations. In fact, both the Arctic and the Antarctic Peninsula are the regions where temperature has raised most and faster than any other Earth’s place. Moreover, other environmental issues related to anthropogenic changes such as the occurrence of contaminants, invasive species, emerging diseases and exploitation of living marine resources are also affecting the Polar Regions. Therefore, sound, detailed and long-term knowledge of the polar systems functioning, interactions and feedbacks is of paramount importance to establish and characterize the main impacts and consequences in both polar and extra-polar latitudes. Only then, efficient and environmentally friendly measures would be established both to mitigate the negative effects of current anthropogenic impactsPeer reviewe

Protocol d'accés a les tècniques de reproducció assistida

Reproducció humana assistida; Tècniques de reproducció; Sistema sanitariReproducción humana asistida; Técnicas de reproducción; Sistema sanitarioAssisted human reproduction; Reproduction techniques; Sanitary systemAquest document defineix les diferents proves diagnòstiques i els criteris clínics per poder accedir a les diverses tècniques i les activitats que podran dur a terme els diferents proveïdors a Catalunya

Update on the Serum Biomarkers and Genetic Factors Associated with Safety and Efficacy of rt-PA Treatment in Acute Stroke Patients

An accurate understanding of the mechanisms underlying an individual's response to rt-PA treatment is critical to improve stroke patients' management. We thus reviewed the literature in order to identify biochemical and genetic factors that have been associated with safety and efficacy of rt-PA administration after stroke

Importance of Angiogenin and Endothelial Progenitor Cells After Rehabilitation Both in Ischemic Stroke Patients and in a Mouse Model of Cerebral Ischemia

Background: Rehabilitation therapy is the only available treatment for stroke survivors presenting neurological deficits; however, the underlying molecules and mechanisms associated with functional/motor improvement during rehabilitation are poorly understood.Objective: Our aim is to study the modulation of angiogenin and endothelial progenitor cells (EPCs) as repair-associated factors in a cohort of stroke patients and mouse models of rehabilitation after cerebral ischemia.Methods: The clinical study included 18 ischemic strokes admitted to an intensive rehabilitation therapy (IRT) unit, 18 non-ischemic controls and brain samples from three deceased patients. Angiogenin and EPCs were measured in blood obtained before and up to 6 months after IRT together with an extensive evaluation of the motor/functional status. In parallel, C57BL/6 mice underwent middle cerebral artery occlusion, and the pasta matrix reaching-task or treadmill exercises were used as rehabilitation models. Angiogenin RNA expression was measured after 2 or 12 days of treatment together with cell counts from EPCs cultures.Results: Brain angiogenin was identified in both human and mouse tissue, whereas serum levels increased after 1 month of IRT in association with motor/functional improvement. EPC populations were increased after stroke and remained elevated during follow-up after IRT. The mouse model of rehabilitation by the task-specific pasta matrix exercise increased the number of EPCs at 2 days and increased angiogenin expression after 12 days of rehabilitation.Conclusions: Angiogenin and EPCs are modulated by rehabilitation after cerebral ischemia, suggesting that both angiogenin and EPCs could serve as biomarkers of improvement during rehabilitation or future therapeutic targets

Factores genéticos de pacientes con ictus asociados al pronóstico

El objetivo de este trabajo es, utilizando una base de datos de pacientes que han padecido un ictus, encontrar tendencias entre pronóstico al alta y medicamentos que toman los pacientes previamente al ictus. Seguidamente, cruzar los factores genéticos asociados anteriormente con bases de datos del genoma humano para ver los genes asociados a las tendencias encontradas y ver la drogabilidad de los genes.L'objectiu d'aquest treball és, utilitzant una base de dades de pacients que han patit un ictus, trobar tendències entre pronòstic a l'alta i medicaments que prenen els pacients prèviament a l'ictus. Seguidament, creuar els factors genètics associats anteriorment amb bases de dades del genoma humà per veure els gens associats a les tendències trobades i veure la drogabilidad dels gens.The objective of this study is, using a stoke data base, find any trend between outcome at discharge and drugs that patients took before stroke. Then, cross the genetic factors found previously with genome database to find the associated genes of the trends were found previously and finally show the druggability of these genes

Factores genéticos de pacientes con ictus asociados al pronóstico

El objetivo de este trabajo es, utilizando una base de datos de pacientes que han padecido un ictus, encontrar tendencias entre pronóstico al alta y medicamentos que toman los pacientes previamente al ictus. Seguidamente, cruzar los factores genéticos asociados anteriormente con bases de datos del genoma humano para ver los genes asociados a las tendencias encontradas y ver la drogabilidad de los genes.L'objectiu d'aquest treball és, utilitzant una base de dades de pacients que han patit un ictus, trobar tendències entre pronòstic a l'alta i medicaments que prenen els pacients prèviament a l'ictus. Seguidament, creuar els factors genètics associats anteriorment amb bases de dades del genoma humà per veure els gens associats a les tendències trobades i veure la drogabilidad dels gens.The objective of this study is, using a stoke data base, find any trend between outcome at discharge and drugs that patients took before stroke. Then, cross the genetic factors found previously with genome database to find theassociated genes of the trends were found previously and finally show the druggability of these genes

The relevance of imidazole tautomerism for the hormonal activity of histidine-containing peptides

Substitution of 5-nitro-l-histidine for l-histidine is proposed as a useful tool to study the relationships among tautomerism, acid-base properties, and biological activity of peptide hormones. This approach is illustrated by an analog of the tripeptide thyroliberin, [5-nitro-l-histidine]2-thyroliberin, which has been prepared by solid-phase peptide synthesis. The acid-base properties of the hormone analog and the position of the imidazole ring tautomeric equilibrium have been investigated by spectroscopic methods. Correlation of these properties with the biological activity of the nitrated tripeptide strongly supports the idea that imidazole ring tautomerism is a key factor for hormonal activity and that the Nτ-H tautomer must be considered the biologically active form of thyroliberin.This work was partially supported by funds from the Comisión Asesora de Investigación Científica y Técnica (Grant 2899183).Peer reviewe