Accumulation of advanced glycation end products (AGEs) induces alterations in the intracellular redox balance, leading cells to functional injury. Current literature reports that intracellular ...signaling triggered by the interaction of AGEs with their specific receptors RAGEs depends on the cell type and the state of activation/stress. In this work, NT2 human neurons were exposed for 48 h to glycated fetal serum containing 750–3000 pmol/ml pentosidine; the treatment induced an increase in apoptosis rate linear with AGE concentration up to 1500 pmol/ml, but necrotic death was elicited with the highest AGE amount employed (3000 pmol/ml pentosidine). Pentosidine at 1500 pmol/ml, which was the concentration responsible for the highest apoptotic effect (40% of apoptotic neurons), was able to determine early generation of intracellular reactive oxygen species and increase in RAGE levels. Under these conditions, protein kinase C (PKC) δ activity was increased approximately 2-fold, and DNA binding activity of redox-sensitive transcription factor activator protein-1 (AP-1) was enhanced 2.5-fold. A relationship among oxidative stress, PKCδ activity, AP-1 activation, and apoptosis was demonstrated by pretreating neurons with 500 μM vitamin E, with 20 μg/ml
Ginkgo biloba extract, or with 3 μM Rottlerin, inhibitor of PKCδ; these pretreatments were able to protect neurons from the glycoxidation-dependent effects.
Die Kluft zwischen Wirkstoffentwicklung und der erfolgreichen Umsetzung in die klinische Praxis (Translation) ist gewaltig. Wirksame Lösungen erfordern die Zusammenarbeit multidisziplinärer Teams von ...unterschiedlicher Expertise (Konvergenz). Dieser Essay stellt zwei Fallbeispiele für die Entwicklung dauerhafter Wirkstoffverabreichungssysteme für Antimalaria‐ und antiretrovirale Medikamente im Magen‐Darm‐Trakt vor.
chronic kidney disease (CKD) is a public health problem. Low-protein diets supplemented with ketoacids and essential aminoacids have proved effective at different CKD stages.
to assess the ...progression of renal failure in adult patients with CKD stages 3b and 4 receiving a protein-controlled diet supplemented with aminoacids and ketoanalogues.
retrospective, descriptive intervention study. The nutritional intervention consisted of a protein/calorie intake of 0.4-0.6 g/kg/day and 30-35 kcal/kg/day plus a tablet of ketoanalogues (Ketosteril®)/5 kg weight. We assessed nutritional condition, glomerular filtration (GF) and creatinine, urea and albumin levels at 0, 3, 6, 9 and 12 months. SPSS version 18 was used for data statistical analysis.
thirty-three patients were studied (67% male; mean age 59.7 years, r: 24-87). Protein/calorie intake was 0.55 ± 0.20 g/kg/day and 34 ± 4.51 kcal/kg/day. Ketosteril® intake was 11.87 tablets/day (r: 9-14). Initial GF was 24.97 ± 6.64 ml/min/1.73 m2, showing a significant increase between three and 12 months (25.51 ± 8.57 and 29.26 ± 10.33 ml/min/1.73 m2; p = 0.006). Urea nitrogen decreased significantly at six months compared with the initial level (p < 0.005). Body mass index did not change significantly (initial, 26. 63 ± 4.08 kg/m2; after a year, 26.78 ± 3.98 kg/m2). Initial and final albumin levels were 3.53 ± 0.64 g/l and 4.00 ± 0.53 g/l, respectively (p = 0.79).
a low-protein diet supplemented with ketoanalogues administered to patients with CKD stages 3b and 4 preserved nutritional condition and mineral balance, improved GF significantly and decreased urea levels.
Dans cette contribution, la définition est envisagée comme une activité interactionnelle qui se réalise dans des situations naturelles à travers la mise en place de ressources linguistiques, ...prosodiques, gestuelles et spatiales. Nous en étudions les réalisations dans la visite guidée de jardins, situation où définir les objets est une activité récurrente et attendue de l'interaction. Nous nous intéressons aux procédés utilisés par les participants pour introduire un objet, construire sa visibilité, le dénommer et le caractériser pour l’interlocuteur. L’objectif est d’examiner les formats définitoires, parmi lesquels notamment la dénomination, produits en relation avec la temporalité de l’interaction et la nature du jardin concerné, afin de montrer le caractère situé de l'activité définitoire.
This paper reports on the effect of on- and off-axis heating power deposition on the impurity confinement in purely electron cyclotron resonance heated He plasmas on the stellarator Wendelstein 7-X. ...Therefore, impurity transport times τI have been determined after Fe impurity injections by laser ablations and monitoring the temporal impurity emissivities by the x-ray imaging spectrometer HR-XIS. A significant increase of τI has been observed when changing the power deposition from on- to off-axis heating with energy confinement times τE being mainly unaffected. In addition, the scaling of impurity transport properties with respect to a variation of heating power PECRH and electron density ne has been investigated by keeping the heating power deposition on-axis. The observed τI scaling compares well to known τI scaling laws observed in other machines. A comparison of τI and τE yields an averaged ratio of τE/τI = 1.3 and transport times in the range of τI = 40-130 ms and τE = 40-190 ms. Comparing those absolute values to neoclassical predictions supports the recently observed nature of anomalous transport in Wendelstein 7-X, given within the up to now investigated operational parameters.
Cet article propose une réflexion sur l’analyse des « longues séquences » dans l’interaction et présente une méthodologie relevant de l’analyse conversationnelle pour étudier la façon dont les ...participants les organisent. Cette méthodologie est mise en œuvre sur un extrait de réunion. L’analyse prend en compte plusieurs dimensions rarement intégrées dans la description de ce niveau de l’interaction : le nombre de participants et la construction de cadres participatifs en perpétuelle reconfiguration et la multimodalité des ressources mises en œuvre, faisant intervenir, outre les regards et les orientations gestuelles et posturales, la prise de notes effectuée de ce qui se passe.
A Eucalyptus dunnii Maiden breeding population of 46 accessions originated in Australia and selected for fitness to subtropical and cold environments was screened by Amplified Fragment Length ...Polymorphism (AFLP) and microsatellite markers to obtain quantitative estimates of genetic diversity. A randomly chosen group of AFLP primers generated 205 AFLP bands that were used to fingerprint the genotypes and to evaluate genetic relationships among accessions. Sixty-eight percent (140) of the bands were polymorphic markers. The mean diversity index (DI) was 0.33 and about 52% of the loci had values greater than 0.4. Cluster analysis derived from similarity indices (SI) revealed no particular grouping among accessions suggesting the absence of closely related genotypes, except for five pairs of genotypes. Bootstrap analysis results confirmed the suitability of AFLP to describe genetic relationships in this breeding population. In addition, four highly informative microsatellites were used to construct an identification matrix that discriminated nearly all of the genotypes. Mean values for the number of alleles per locus, DI and SI among accessions were 13, 0.78 and 0.19, respectively, indicating that the breeding population has high genetic diversity. However, several genotypes showed the presence of single microsatellite bands suggesting a putatively important degree of homozygosity. Molecular data were used to design a clonal seed orchard. To achieve this aim, the nine most divergent pairs of genotypes were chosen, thereby retaining 95.2% of the total number of alleles from the 140 polymorphic AFLP loci and the four microsatellite loci analyzed. Mean DI and SI for AFLP and microsatellites showed no significant differences between the original breeding population and the selected seed orchard, confirming that a seed orchard can be designed with a limited number of individuals, which allows similar accessions to be discarded and avoids inbreeding.
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