Juan Antonio Jiménez Sánchez

A flavonoid-rich diet increases nitric oxide production in rat aorta.

Red wine intake is associated with a low risk of cardiovascular disease. This effect has been partly attributed to the action of polyphenolic compounds, which decrease the oxidation of plasma low density lipoproteins. Moreover, nitric oxide (•NO) is a vasodilator and polyphenolic compounds induce endothelium‐dependent vasorelaxation in vitro. Here we studied whether a diet rich in dealcoholated red wine (DRW) increases acetylcholine‐induced vasorelaxation and whether ingestion of DRW‐, quercetin‐ or catechin‐rich diets modifies the •NO‐cyclic guanosine‐3′,5′‐monophosphate (cyclic GMP) pathway and superoxide anion (O2.−) release in aorta in a resting state in rats fed semi‐purified diets containing either 35% (v w−1) DRW, 0.3% (w w−1) quercetin or 0.3% (w w−1) catechin for 10 days. •NO‐mediated vasorelaxation induced by acetylcholine was greater in rats fed the DRW‐rich diet than in those that received the control diet. Expression of endothelial •NO synthase (eNOS) was similar in the four dietary groups. The aortic rings of rats fed either the DRW‐, quercetin‐, or catechin‐rich diets showed higher NOS activity, •NO production and cyclic GMP content than those of rats fed the control diet. No changes were observed in O2.− production. In summary, diets rich in either DRW, quercetin or catechin induced endothelium‐dependent vasorelaxation in rat aorta in a resting state through the enhancement of •NO production, without modifying O2.− generation, thus the bioavailability of •NO was increased. The increase in the •NO‐cyclic GMP pathway explains the beneficial effect of flavonoids at vascular level.

Loss of adaptation to oxidative stress as a mechanism for aortic damage in aging rats

Cells are armed with a vast repertoire of antioxidant defence mechanisms to prevent the accumulation of oxidative damage. The cellular adaptive response is an important antioxidant mechanism against physiological and pathophysiological oxidative alterations in a cell’s microenvironment. The aim of this paper was to study, in the rat aorta, whether this adaptive response and the inflammation associated with oxidative stress were expressed throughout the aging process. We examined the rat aorta, as it is a very sensitive tissue to oxidative stress. Male Wistar rats of 1.5, 3, 12, 18 and 24 months of age were used. Superoxide anion (O2−) generation; levels of two antioxidant enzymes, superoxide dismutase (SOD) and catalase; and the levels of prostaglandin E2 (PGE2), an inflammatory marker, were measured. The results for rats at different ages were compared with those for 3 months of age. A balance between production of O2− and SOD activity was found in the aorta of rats from 1.5 to 12 months old. Oxidative stress was present in the aorta of old animals (18–24) months), due to a failure in the mechanisms of adaptation to oxidative stress. The observed increase in PGE2 levels in these rats reflected an inflammatory response. All together suggest that vascular oxidative stress and the inflammatory process observed in the old groups of rats could be closely related to vascular aging. Our results also remark the importance of the adaptative response to oxidative stressResumenLas células están equipadas con una amplia gama de mecanismos de defensa antioxidante para prevenir la acumulación de lesiones oxidativas. La respuesta celular de adaptación constituye un importante mecanismo antioxidante para prevenir las alteraciones en el microentorno celular tanto a nivel fisiológico como patofisiológico. El propósito de este trabajo fue estudiar en aorta de rata si la respuesta de adaptación así como la inflamación, asociadas ambas con el estrés oxidativo, se expresan a lo largo del proceso de envejecimiento. Se ha empleado aorta de rata ya que constituye un tejido muy sensible al estrés oxidativo. Se utilizaron ratas macho Wistar de 1,5,3,12,18 y 24 meses de edad y se estudiaron la producción de anion superoxido (O2−), los niveles de dos enzimas antioxidantes, superoxido dismutasa (SOD) y catalasa, así como los niveles de prostaglandina E2 (PGE2), un indicador de la inflamación. Los resultados obtenidos a las diferentes edades se compararon con los obtenidos con las ratas de 3 meses de edad. Nuestros resultados demostraron un equilibrio entre producción de O2− y actividad de SOD en las ratas de entre 1,5 y 12 meses de edad. En la aorta de los animales viejos (18–24 meses) se detectó mayor estrés oxidativo debido a un fallo en los mecanismos de adaptación al mismo, mientras que el aumento observado en los niveles de PGE2 en estos animales refleja una respuesta inflamatoria. En conjunto, nuestros resultados sugieren que tanto el estrés oxidativo vascular, como el proceso inflamatorio observados en los grupos de ratas viejas podrían estar fuertemente relacionados con el envejecimiento vascular. Nuestros resultados remarcan también la importancia de la respuesta de adaptación al estrés oxidativo.

Oxidative stress markers in the neocortex of drug-resistant epilepsy patients submitted to epilepsy surgery

PURPOSE While there is solid experimental evidence of brain oxidative stress in animal models of epilepsy, it has not been thoroughly verified in epileptic human brain. Our purpose was to determine and to compare oxidative stress markers in the neocortex of epileptic and non-epileptic humans, with the final objective of confirming oxidative stress phenomena in human epileptic brain. METHODS Neocortical samples from drug-resistant epilepsy patients submitted to epilepsy surgery (n=20) and from control, non-epileptic cortex samples (n=11) obtained from brain bank donors without neurological disease, were studied for oxidative stress markers: levels of reactive oxygen species (ROS), such as superoxide anion (O2(-)); activity of antioxidant enzymes: superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione reductase (GR); and markers of damage to biomolecules (lipid peroxidation and DNA oxidation). RESULTS Compared with non-epileptic controls, the neocortex of epileptic patients displayed increased levels of superoxide anion (P≤0.001), catalase (P≤0.01), and DNA oxidation (P≤0.001); a decrease in GPx (P≤0.05), and no differences in SOD, GR and lipid peroxidation. CONCLUSIONS Our findings in humans are in agreement with those found in animal models, supporting oxidative stress as a relevant mechanism also in human epilepsy. The concurrent increase in catalase and decrease in GPx, together with unchanged SOD levels, suggests catalase as the main antioxidant enzyme in human epileptic neocortex. The substantial increase in the levels of O2(-) and 8-oxo-dG in epileptic patients supports a connection between chronic seizures and ROS-mediated neural damage.

Anti-oxidative effects produced by environmental enrichment in the hippocampus and cerebral cortex of male and female rats.

Both physical and intellectual activity may reduce the incidence of neurodegenerative disorders. There is evidence that environmental enrichment (EE) can induce profound behavioral, neurochemical and neuroanatomical changes, thus producing lasting improvements in memory and learning tasks. In this study we evaluated the anti-oxidative effects produced by EE in the hippocampus and the cerebral cortex of male and female rats. The animals had been reared in either EE or control conditions. The parameters studied were: thiobarbituric acid reactive substances (TBARS), protein oxidation, total radical antioxidant parameter, catalase, superoxide dismutase and superoxide anion activity. The results showed that our EE protocol reduced markers of oxidative stress in the hippocampus and in the cerebral cortex. Overall, the measures taken in the two cerebral regions revealed that EE rats showed higher values for antioxidant measures and lower values for oxidative stress parameters than control animals. More importantly, a consistent sex difference was found, indicating that in female rats the hippocampus and cerebral cortex are plastic brain regions receptive to external stimulation such as EE. Although EE males have higher levels for antioxidant capacity, catalase and SOD, it is likely that females do not need to activate all the antioxidant defenses since they have a greater capacity to assimilate external stimuli. This is suggested by the similarity of protein oxidation and TBARS levels in hippocampus in both sexes, and the even lower levels of protein oxidation and superoxide anion activity in the cerebral cortex in EE females.

Oxidative stress, nitric oxide and prostaglandin E2 levels in the gastrointestinal tract of aging rats

Objectives To evaluate the presence of oxidative stress and alterations in the levels of two cytoprotective agents, prostaglandin E2 and nitric oxide, in the gastrointestinal tract of aging rats.

Sex differences after environmental enrichment and physical exercise in rats when solving a navigation task

The effects of early environmental enrichment (EE) and voluntary wheel running on the preference for using a landmark or pool geometry when solving a simple spatial task in adult male and female rats were assessed. After weaning, rats were housed in same-sex pairs in enriched or standard cages (EE and control groups) for two and a half months. Then the rats were trained in a triangular-shaped pool to find a hidden platform whose location was defined in terms of these two sources of information, a landmark outside the pool and a particular corner of the pool. As expected, enriched rats reached the platform faster than control animals, and males and females did not differ. Enriched rats also performed better on subsequent test trials without the platform with the cues individually presented (either pool geometry or landmark). However, on a preference test without the platform, a clear sex difference was found: Females spent more time in an area of the pool that corresponded to the landmark, whereas males spent more time in the distinctive corner of the pool. The present EE protocol did not alter females’ preference for the landmark cue. The results agree with the claim that environmental enrichment is a consequence of a reduced anxiety response (measured by thigmotaxis) during cognitive testing. A possible implication of ancestral selection pressures is discussed.

Eicosanoid levels in the neocortex of drug-resistant epileptic patients submitted to epilepsy surgery

There is an increasing body of evidence implicating eicosanoids (arachidonic acid metabolites) in the experimental generation of epileptic seizures and the development of epilepsy. Our purpose was to measure the synthesis of eicosanoids from the cyclooxygenase and lipoxygenase pathways in human brain neocortex tissue samples obtained from epileptic patients, and to compare them with non-epileptic control subjects. Epileptic neocortex specimens demonstrated a significant increase (P<0.001) in the levels of three eicosanoids derived from the cyclooxygenase pathway: Prostaglandin E(2) (PGE(2)), Thromboxane A(2) (TXA(2)), and Prostacyclin (PGI(2)), compared to controls. In the epileptic samples the level of TXA(2) was twice as much the levels of PGI(2), while in the control samples the levels of PGI(2) were slightly higher than TXA(2). Conversely, there were no detectable levels of eicosanoids derived from the lipoxygenase pathway: Leukotriene B(4) (LTB(4)) and Leukotriene C(4) (LTC(4)). The lack of leukotrienes synthesis illustrates that COX pathway is dominant in neocortex of epileptic patients. Our human data are consistent with the results obtained in experimental animal models of epilepsy. The important increase in PGE(2) and TXA(2) suggests that selective inhibition of prostanoid synthesis or blockage of prostanoid receptors might provide novel antiepileptic strategies in human epilepsy.

Influence of aging on thromboxane A2 and prostacyclin levels in rat hippocampal brain slices

We have investigated the influence of age (3, 18, 24 months) on Thromboxane A2 (TXA2) and Prostacyclin (PGI2) levels in hippocampal slices from F344/NHSD rats. A significant increase in TXA2 and PGI2 levels was observed in 18 and 24 months old compared to 3 months old animals. A significant reduction in the ratio TXA2/PGI2 produced by a higher increase in PGI2 was observed in 24 month old animals. The reduction in the TXA2/PGI2 ratio has been related to vasodilatory and antiaggregating effects that may contribute to protect the brain against neuronal damage.

Environmental enrichment in the absence of wheel running produces beneficial behavioural and anti-oxidative effects in rats

The effects of early environmental enrichment (EE) when solving a simple spatial task in adult male rats were assessed. After weaning, rats were housed in pairs in enriched or standard cages (EE and control groups) for two and a half months. Then the rats were trained in a triangular-shaped pool to find a hidden platform whose location was defined in terms of two sources of information, a landmark outside the pool and a particular corner of the pool. As expected, enriched rats reached the platform faster than control animals. Enriched rats also performed better on a subsequent test trial without the platform with the geometry cue individually presented (in the absence of the landmark). Most importantly, the beneficial effects of the present protocol were obtained in the absence of wheel running. Additionally, the antioxidative effects in the hippocampus produced by the previous protocol are also shown.

La magia en la Galia merovingia = Magic in Merovingian Gaul

espanolEn el presente trabajo estudiamos los testimonios sobre magia documentados en la Galia entre finales del siglo V y mediados del siglo VIII, periodo en que este territorio estuvo parcial o totalmente bajo dominio merovingio. Para ello, recurriremos al analisis de la informacion proporcionada por una gran variedad documental: narraciones de tipo historico, hagiografias, fuentes legislativas y canonisticas, asi como tambien epigraficas. A partir de aqui, podemos colegir que la magia poseia una existencia innegable para los miembros de la sociedad franca, independientemente de su genero, edad o condicion social. Tambien resultaba un problema preocupante para las elites dirigentes: las autoridades laicas persiguieron la magia negra mientras que las jerarquias eclesiasticas la condenaron bajo todas sus formas, malefica y benefica. Todo esto manifiesta que los vestigios paganizantes tenian una presencia mucho mas real en la Galia merovingia de lo que admiten muchos autores actuales. EnglishIn the present work we study the testimonies about magic documented in Gaul between the end of the fifth century and the middle of the eighth century, period in which this territory was partially or totally under Merovingian rule. To do this, we will analyse the information provided by a large variety of documents: historical narratives, hagiographies, legislative and canonical sources, as well as epigraphic. From here, we may infer that magic possessed an undeniable existence for the members of the Frankish society, regardless of gender, age or social status. It was also a troubling problem for ruling elites: lay authorities pursued black magic while ecclesiastical hierarchies condemned it in all its forms, evil and beneficent. All this manifests that the pagan traces had a much more real presence in Merovingian Gaul than many current authors admit.