rhegf-Loaded -Alginate Microspheres Enhance The Healing Of Full-Thickness Excisional Wounds In Diabetised Wistar Rats

[EN] Diabetic foot ulcers (DFUs) represent a major clinical challenge in the ageing population. To address this problem, rhEGF-loaded Poly-Lactic-co-Glycolic- ()-Alginate microspheres (MS) were prepared by a modified w/o/w-doubleemulsion/ solvent evaporation method. Different formulations were evaluated with the aim of optimising MSs properties by adding NaCl to the surfactant solution and/or the solvent removal phase and adding alginate as a second polymer. The characterization of the developed MS showed that alginate incorporation increased the encapsulation efficiency (EE) and NaCl besides increasing the EE also became the particle surface smooth and regular. Once the MS were optimised, the target loading of rhEGF was increased to 1% (-Alginate MS), and particles were sterilised by gamma radiation to provide the correct dosage for in vivo studies. In vitro cell culture assays demonstrated that neither the microencapsulation nor the sterilisation process affected rhEGF bioactivity or rhEGF wound contraction. Finally, the MS were evaluated in vivo for treatment of the full-thickness wound model in diabetised Wistar rats. rhEGF MS treated animals showed a statistically significant decrease of the wound area by days 7 and 11, a complete re-epithelisation by day 11 and an earlier resolution of the inflammatory process. Overall, these findings demonstrate the promising potential of rhEGF-loaded MS (-Alginate MS) to promote faster and more effective wound healing, and suggest its possible application in DFU treatment.

Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson's disease

Current research efforts are focused on the application of growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), as neuroregenerative approaches that will prevent the neurodegenerative process in Parkinson's disease. Continuing a previous work published by our research group, and with the aim to overcome different limitations related to growth factor administration, VEGF and GDNF were encapsulated in poly(lactic-co-glycolic ) nanospheres (NS). This strategy facilitates the combined administration of the VEGF and GDNF into the brain of 6-hydroxydopamine (6-OHDA) partially lesioned rats, resulting in a continuous and simultaneous drug release. The NS particle size was about 200 nm and the simultaneous addition of VEGF NS and GDNF NS resulted in significant protection of the PC-12 cell line against 6-OHDA in vitro. Once the poly(lactic-co-glycolic ) NS were implanted into the striatum of 6-OHDA partially lesioned rats, the amphetamine rotation behavior test was carried out over 10 weeks, in order to check for in vivo efficacy. The results showed that VEGF NS and GDNF NS significantly decreased the number of amphetamine-induced rotations at the end of the study. In addition, tyrosine hydroxylase immunohistochemical analysis in the striatum and the external substantia nigra confirmed a significant enhancement of neurons in the VEGF NS and GDNF NS treatment group. The synergistic effect of VEGF NS and GDNF NS allows for a reduction of the dose by half, and may be a valuable neurogenerative/neuroreparative approach for treating Parkinson's disease.

Subcutaneous fat composition of youthful and mature Canadian beef: emphasis on individual conjugated linoleic and trans-18:1 isomers

[EN]A comprehensive evaluation of the fatty composition of subcutaneous adipose tissue from beef cattle produced in western Canada was undertaken to determine if the current Canadian grading system is able to distinguish classes of animals with value added potential due to their fatty composition. Grades included youthful Canadian Yield Grade 1 A/AA beef, under (YUTM) and over (YOTM) 30 mo of age and the four mature grades (D1, D2, D2 and D4). Subcutaneous fat between the 12th and 13th ribs over the longissimus muscle was obtained from 18_21 animals per grade. Fatty s were analyzed using a combination of silver-ion HPLC and GC with a highly polar 100 m column. There were no differences in total trans-18:1 content amongst grades, but adipose tissue from grade D1, D2 and D4 had more 11t-18:1 than YUTM (PB0.05), whereas adipose tissue from YUTM carcasses had more 10t-18:1 than all other grades (PB0.05). Adipose tissue from YUTM carcasses also had less total CLA (PB0.05) than the D grades, mainly due to a lower level of 9c,11t-CLA, but they had slightly more 7t,9c-CLA and 10t,12c-CLA (PB0.05). Adipose tissue from YOTM and D grades contained more n-3 fatty s relative to YUTM (0.56% vs. 0.29%; PB0.05) and lower n-6:n-3 ratios (PB0.05). Overall, older animals (YOTM and D grades) had adipose tissue compositions with higher levels of fatty s with reported health benefits. Taken together, these higher levels may provide opportunities for value added marketing if regulatory authorities allow claims for their enrichment based on demonstrated health benefits. Higher concentrations of beneficial fatty s, however, need to be considered within the context of the complete fatty profile and it would be important to demonstrate their advantages in the presence of relatively high levels of saturated fatty s.

Survey of the fatty composition of Canadian beef: Backfat and longissimus lumborum muscle

[EN]A survey of Canadian retail beef was undertaken with emphasis on the trans fatty (TFA) and conjugated linoleic (CLA) isomers, and compared with current health recommendations. Thirty striploin steaks were collected in the winter and summer from major grocery stores in Calgary (Alberta, Canada). Steak fatty compositions (backfat and longissimus lumborum muscle analysed separately) showed minor seasonal differences with lower total saturates (PB0.05) and higher total monounsaturates (PB 0.01) in winter, but no differences in total polyunsaturated fatty s. The ratio of n-6 and n-3 polyunsaturated fatty in longissimus lumborum averaged 5.8. The average TFA content in longissimus lumborum was 0.128 g 100 g_1 serving size, and 10t-18:1 was found to be the predominant isomer (32% of total trans), while vaccenic was second most abundant (15% of total trans). The CLA content in longissimus lumborum was similar to that of backfat, ranging from 0.43 to 0.60% of total fatty s and rumenic represented 60% of total isomers. Overall, there is still room for improvement in the saturated, mono- and polyunsaturated fatty composition of Canadian beef to meet general dietary guidelines for human consumption and additional targets should include reducing 10t-18:1 while increasing both rumenic and vaccenic s.

Phenotypic correlations of fatty composition among intramuscular, subcutaneous and intermuscular fat tissues in concentrate-fed beef cattle of differing genotypes

[EN]In an attempt to predict intramuscular fatty composition using easily accessible fat depots, between-tissue correlations were studied in 75 Asturiana de los Valles bulls with different levels of muscular hypertrophy, and 25 Asturiana de la Montan˜ a bulls. Trans-18:1 in intramuscular fat was highly and positively correlated with levels in subcutaneous and intermuscular fats, while levels of total n-3 were not correlated. Predicting intramuscular fatty composition using easily accessible depots is thus possible for some fatty s exhibiting high between-tissue correlations (e.g., trans-18:1) but breed and tissue specific deposition may limit this for others (e.g., n-3 fatty s).

Review: Trans-forming beef to provide healthier fatty profiles

[EN]Trans fatty s are found naturally in foods, particularly in those derived from ruminant animals, such as beef and dairy cattle. Over the past few decades, human consumption of trans fatty s has increased, but this has been mainly from products containing partially hydrogenated vegetable oils. The correlation of trans fatty consumption with diseases such as coronary heart disease has been cause for concern, and led to recommendations to reduce their consumption. Trans fatty s, however, have differing effects on human health. Therefore, in foods produced from ruminant animals, it is important to know their trans fatty composition, and how to enrich or deplete fatty s that have positive or negative health effects. This review will cover the analysis of trans fatty s in beef, their origin, how to manipulate their concentrations, and give a brief overview of their health effects.

Association analyses of DNA polymorphisms in bovine SREBP-1, LXRα,FADS1 genes with fatty composition in Canadian commercial crossbred beef steers

Two previously reported DNA polymorphisms of sterol regulatory element binding transcription factor 1 (SREBP1) and liver X receptor alpha (LXRα) and two DNA polymorphisms of fatty desaturase 1 (FADS1) were evaluated for associations with fatty s in brisket adipose tissue of Canadian cross-bred beef steers. The polymorphism of 84 bp insert/deletion in intron 5 of SREBP1 was significantly associated with the concentration of 9c C17:1 (P=0.013). The G>A single nucleotide polymorphism (SNP) in the exon 4 of LXRα gene was associated with the concentration of 9c, 11t C18:2 (P=0.04), sum of conjugated linoleic s (CLA) (P=0.025) and 11c C20:1(P=0.042). Two DNA polymorphisms in the promoter region of FADS1, deletion/insertion of ->GTG in rs133053720 and SNP A>G in rs42187276, were significantly associated with concentrations of C17:0 iso, C17:0 ai, total branched chain fatty s (BFA), 12t C18:1, 13t/14t C18:1, 15t C18:1, and 13c C18:1 (P<0.05). Further studies are needed to validate the associations and to delineate the roles of the gene polymorphisms in determining the fatty composition in beef tissues.

Length of concentrate finishing affects the fatty composition of grass-fed andgenetically lean beef: an emphasis on trans-18:1 and conjugated linoleic profiles

2.4. The author may post the VoR version of the article (in PDF or HTML form) in the Institutional Repository of the institution in which the author worked at the time the article was first submitted, or (for appropriate journals) in PubMed Central or UK PubMed Central or arXiv, no sooner than one year after first publication of the article in the Journal, subject to file availability and provided the posting includes a prominent statement of the full bibliographical details, a copyright notice in the name of the copyright holder (Cambridge University Press or the sponsoring Society, as appropriate), and a link to the online edition of the Journal at Cambridge Journals Online.

Phosphorus substituted hydroxylamine and hydroxamic derivatives: synthesis and reactivity

Dedicated to Prof. Julio Alvarez-Builla on the occasion of his 65th anniversary.

Estudio de la trabeculectomía experimental mediante implante de como dispositivo de liberación controlada de fármacos

225 p. : il.

Poly(lactic )-based bio-blends and nanocomposites

172 p.

Development of the heterogeneous catalysts for the production of levulinic from furfuryl alcohol

207 p.

Neuroprotective effects of resveratrol and docosahexaenoic antioxidants in perinatal hypoxic-ischemic brain injury in rats

295 p.

Development of nucleic vaccines: use of self-amplifying RNA in lipid nanoparticles

Self-amplifying RNA or RNA replicon is a form of nucleic -based vaccine derived from either positive-strand or negative-strand RNA viruses. The gene sequences encoding structural proteins in these RNA viruses are replaced by mRNA encoding antigens of interest as well as by RNA polymerase for replication and transcription. This kind of vaccine has been successfully assayed with many different antigens as vaccines candidates, and has been shown to be potent in several animal species, including mice, nonhuman primates, and humans. A key challenge to realizing the broad potential of self-amplifying vaccines is the need for safe and effective delivery methods. Ideally, an RNA nanocarrier should provide protection from blood nucleases and extended blood circulation, which ultimately would increase the possibility of reaching the target tissue. The delivery system must then be internalized by the target cell and, upon receptor-mediated endocytosis, must be able to escape from the endosomal compartment into the cell cytoplasm, where the RNA machinery is located, while avoiding degradation by lysosomal enzymes. Further, delivery systems for systemic administration ought to be well tolerated upon administration. They should be safe, enabling the multiadministration treatment modalities required for improved clinical outcomes and, from a developmental point of view, production of large batches with reproducible specifications is also desirable. In this review, the concept of self-amplifying RNA vaccines and the most promising lipid-based delivery systems are discussed.

Early response to nanoparticles in the Arabidopsis transcriptome compromises plant defence and root-hair development through salicylic signalling

Background: The impact of nano-scaled materials on photosynthetic organisms needs to be evaluated. Plants represent the largest interface between the environment and biosphere, so understanding how nanoparticles affect them is especially relevant for environmental assessments. Nanotoxicology studies in plants allude to quantum size effects and other properties specific of the nano-stage to explain increased toxicity respect to bulk compounds. However, gene expression profiles after exposure to nanoparticles and other sources of environmental stress have not been compared and the impact on plant defence has not been analysed. Results: Arabidopsis plants were exposed to TiO2-nanoparticles, Ag-nanoparticles, and multi-walled carbon nanotubes as well as different sources of biotic (microbial pathogens) or abiotic (saline, drought, or wounding) stresses. Changes in gene expression profiles and plant phenotypic responses were evaluated. Transcriptome analysis shows similarity of expression patterns for all plants exposed to nanoparticles and a low impact on gene expression compared to other stress inducers. Nanoparticle exposure repressed transcriptional responses to microbial pathogens, resulting in increased bacterial colonization during an experimental infection. Inhibition of root hair development and transcriptional patterns characteristic of phosphate starvation response were also observed. The exogenous addition of salicylic prevented some nano-specific transcriptional and phenotypic effects, including the reduction in root hair formation and the colonization of distal leaves by bacteria. Conclusions: This study integrates the effect of nanoparticles on gene expression with plant responses to major sources of environmental stress and paves the way to remediate the impact of these potentially damaging compounds through hormonal priming.