Ascorbyl-dipalmitate-stabilised nanoemulsions as a potential localised treatment of inflammatory bowel diseases.

Current efforts on inflammatory bowel diseases (IBD) treatment are focused on strategies for localised drug delivery at the intestinal mucosa. Despite the potential of curcumin (CC) for IBD treatment, its low solubility and stability limit its application. Thus, the design of nanocarriers that focus CC delivery at the intestinal epithelium is an area of interest. This work proposes α-tocopherol nanoemulsions (NE) stabilised by ascorbyl-2,6-dipalmitate (ADP) as intestinal CC-carriers. The antioxidant capacity of α-tocopherol and ADP could have a synergistic effect on IBD-affected tissues, characterised by an oxidative environment. We obtained nanoemulsions (NE-ADP) with size below 200 nm, negative surface charge, stable in gastrointestinal media and no toxic in the Caco-2 cell model. Intracellular retention of NE-ADP in Caco-2 cells was observed by confocal microscopy. The extremely low Papp values obtained for CC and α-tocopherol indicated the lack of transport across the Caco-2 monolayer. Control nanoemulsion stabilised by lecithin (NE-L) was greatly transported across the Caco-2 cells monolayer, confirming the relevance of ADP on the cellular retention of NE-ADP. The therapeutic potential of NE-ADP was shown by the significant decrease of intracellular ROS levels. Altogether, these results indicate the potential of NE-ADP as a novel approach for the treatment of IBD.

The role of the intestinal-protein corona on the mucodiffusion behaviour of new nanoemulsions stabilised by ascorbyl derivatives.

Nanoemulsions are vesicular systems with great potential for the delivery of drugs, which significantly depends on the appropriate selection of the components that constitute them. In this sense, the use of materials with adequate toxicity profiles for the oral route provides additional advantages in terms of safety concerns avoidance. This work describes the formulation of novel two-component nanoemulsions constituted by α-tocopherol and ascorbyl-palmitate derivatives. Among them, ascorbyl-dipalmitate allowed the formation of nanoemulsions with size values around 170 nm and negative charge; additionally, they showed strong antioxidant capacity. These nanoemulsions are proposed to the oral route, so their behaviour in intestinal conditions was evaluated by incubating the nanoemulsion in simulated intestinal fluid. This process led to the formation of an intestinal-protein corona (I-PC) at the colloidal surface that determined the interaction with the mucus barrier. The I-PC displaced the immobile-hindered particles towards a subdiffusive-diffusive population. These studies report for the first time the effect of the I-PC on the mucodiffusion behaviour of vesicular systems, a finding that may help to comprehend the performance of nanocarriers under intestinal conditions.

Vitamin transporters in mice brain with aging.

Its high metabolic rate and high polyunsaturated fatty acid content make the brain very sensitive to oxidative damage. In the brain, neuronal metabolism occurs at a very high rate and generates considerable amounts of reactive oxygen species and free radicals, which accumulate inside neurons, leading to altered cellular homeostasis and integrity and eventually irreversible damage and cell death. A misbalance in redox metabolism and the subsequent neurodegeneration increase throughout the course of normal aging, leading to several age-related changes in learning and memory as well as motor functions. The neuroprotective function of antioxidants is crucial to maintain good brain homeostasis and adequate neuronal functions. Vitamins E and C are two important antioxidants that are taken up by brain cells via the specific carriers αTTP and SVCT2, respectively. The aim of this study was to use immunohistochemistry to determine the distribution pattern of these vitamin transporters in the brain in a mouse model that shows fewer signs of brain aging and a higher resistance to oxidative damage. Both carriers were distributed widely throughout the entire brain in a pattern that remained similar in 4-, 12-, 18- and 24-month-old mice. In general, αTTP and SVCT2 were located in the same regions, but they seemed to have complementary distribution patterns. Double-labeled cell bodies were detected only in the inferior colliculus, entorhinal cortex, dorsal subiculum, and several cortical areas. In addition, the presence of αTTP and SVCT2 in neurons was analyzed using double immunohistochemistry for NeuN and the results showed that αTTP but not SVCT2 was present in Bergmann's glia. The presence of these transporters in brain regions implicated in learning, memory and motor control provides an anatomical basis that may explain the higher resistance of this animal model to brain oxidative stress, which is associated with better motor performance and learning abilities in old age.

Estudio comparativo de prácticas e intervenciones comunitarias destinadas al consumo de frutas y verduras en Misiones, Formosa, Salta y Río Negro / Comparative study of community practices and interventions aimed at the consumption of fruits and vegetables in Misiones, Formosa, Salta and Río Negro

INTRODUCCIÓN La salud alimentaria constituye un área prioritaria a nivel de política pública en Argentina. Existen diversos programas a nivel nacional, provincial y local que abordan la temática de salud alimentaria tanto desde la visión sanitaria como de producción y consumo de alimentos. Según las estadísticas nacionales y de acuerdo con las metas internacionales propuestas por la Organización Mundial de la Salud (OMS), la alimentación de la población argentina no alcanza el nivel adecuado de consumo de frutas y verduras, lo que provoca malnutrición y repercute en enfermedades y déficits de crecimiento y desarrollo. OBJETIVOS Evaluar los programas y las prácticas alimentarias (PA) respecto al consumo de frutas y verduras en niños/niñas y mujeres embarazadas de zonas rurales de las provincias de Misiones, Formosa, Salta y Río Negro. MÉTODOS Se realizó un estudio cuali-cuantitaivo, con comparación de estudios de casos. Se efectuaron observaciones y 75 entrevistas en total 32 a mujeres rurales, 29 a profesionales y agentes sanitarios (AS), 12 a técnicos extensionistas (TE) y 2 a otros actores. RESULTADOS Se analizaron los datos recogidos y se realizó una categorización con el software ATLAS.ti. A partir de esto, se hizo un análisis donde se observó que las intervenciones destinadas a la salud alimentaria y el consumo de frutas y verduras (CFV) se ven influidas por las pautas socio-culturales, que determinan las prácticas cotidianas de la población. DISCUSIÓN La relevancia de este proyecto radica en promover la recuperación crítica del saber y la discusión colectiva de las experiencias que viven los diferentes actores, contribuyendo de esta manera a la construcción de hábitos alimentarios saludables y duraderos. Como estrategia se considera necesario sumar en dichas intervenciones a los actores involucrados en las escuelas y comedores, articulando con AS, TE y profesionales de la salud.

PEGylated Nanoemulsions for Oral Delivery: Role of the Inner Core on the Final Fate of the Formulation.

Since the past decade, there has been growing interest to grant nanoparticles with diffusion properties across mucosae. In this sense, the nonionic block copolymer Pluronic F127 (PF127) has emerged as a promising coating agent to formulate mucus-penetrating particles. In the journey to find efficient coating agents, researchers have focused more on the effect of the coating agent architecture rather than on the role of the physicochemical properties of the nanoparticle used as the substrate. The current knowledge about mucodiffusive particles is in general based on model-like nanoparticles, such as polystyrene or poly(lactic-co-glycolic) acid nanoparticles, but there is a lack of information about the potential of PF127 on other colloidal systems. This work aims to shed some light on this issue by selecting three oils, palm (solid), coconut (semisolid), and wheat germ (liquid), with different physicochemical properties to formulate PF127-coated nanoemulsions. The obtained nanoemulsions were characterized, and their colloidal stability was tested. Their diffusion capacity was determined by particle tracking after challenging the nanoemulsions across an intestinal porcine mucus layer. In accordance with the evidence of model-like nanoparticles, our results state that PF127 allows mucodiffusion, but its effectiveness as a coating agent clearly depends on the physicochemical properties of the nanostructure core over which PF127 is placed. Among other physicochemical properties, the results certainly showed that the hydrophobic character of the nanostructure core emerges as a critical factor in the formulation of successful PF127 coatings.

Design of the interface of edible nanoemulsions to modulate the bioaccessibility of neuroprotective antioxidants.

Most frequently the use of bioactive molecules for the supplementation of food and beverages is hampered by stability limitations or inadequate intestinal absorption. This work evaluates in vitro the role that the interface of the nanoemulsion has on the physicochemical properties, the stability behavior and the enzymatic degradation after oral intake. For that purpose three soybean oil (SB) formulations were studied. These formulations were based on the emulsifier lecithin but modified with two non-ionic surfactants Pluronic(®) F68 (PF68) or Pluronic(®) F127 (PF127) yielding (i) SB-NE (only lecithin on the interface), (ii) SB-NE PF68 (lecithin plus PF68) and 9 (iii) SB-NE PF127 (lecithin plus PF127). All the formulations tested were low polydispersed and showed a size of about 200 nm and ζ-potential of -50 mV. The in vitro colloidal stability assay showed that lecithin itself was able to promote that formulations reach unaltered to the small intestine and facilitate the absorption of the antioxidant payload on a tunable fashion there (with in vitro bioaccessibility values from around 40% up to a 70%). PF68 was able to sterically stabilize the formulation against the aggregation induced by the pH and electrolytes of the simulated gastrointestinal track; however, this surfactant was easily displaced by the lipases of the simulated intestinal milieu being unable to modulate the digestion pattern of the oil droplets in the small intestine. Finally, PF127 displayed a strong steric potential that dramatically reduced the interaction of the oil droplets with lipases in vitro, which will compromise the capacity of the formulation to improve the bioaccessibility of the loaded antioxidant.

Evaluation of mathematical models to describe testicular growth in Blackbelly ram lambs.

The primary objective was to compare various mathematical models to describe scrotal circumference (SC) and paired testis volume development in Blackbelly ram lambs. The study was conducted in the state of Querétaro, México (20° 43' N, 100° 15' W). Spring-born Blackbelly ram lambs (n = 41) were housed outdoors and fed alfalfa hay and concentrate. Body weight, SC, and testis length, diameter, and volume were recorded every 2 wk from 24 to 172 d of age (June 18 to November 3). The following mathematical functions were used to model SC-age and testis volume-age relationship: Von Bertalanffy, Brody, Gompertz, Logistic, and Richards. The suitability of the models was evaluated based on parameter values and standard errors, residual mean square, the coefficient of determination (R(2)), and the average prediction error (APE). All models, except for Brody's, had good fit to SC (R(2) > 0.98) and testis volume (R(2) > 0.95), and produced similar growth curves in the range of ages studied. The logistic model predicted SC at maturity quite well, 33.6 ± 0.6 cm as compared with 33.9 ± 0.5 cm observed in adult animals; all models had APE's smaller than ± 7% between 56 and 168 d of age. The Bertalanffy model predicted testis volume at maturity quite well, 513 ± 22 cm(3) as compared with 488 ± 20 cm(3) calculated for adult animals. The logistic model had a good fit to testis volume during the period of study, but underestimated the volume at maturity by 28%. All models, except for Brody's, had APE's smaller than ± 14% between 98 and 168 d of age. The logistic and Bertalanffy models predicted the inflection point for SC at 83 and 59 d of age, and testis volume at 116 and 109 d of age, respectively. In conclusion, all models, except for Brody's, had good fit to actual SC and testis volume data in the range of age evaluated, whereas the logistic and Bertalanffy's models made the best predictions for adult SC and testis volume, respectively.

Differential effects of undernutrition during pregnancy on the behaviour of does and their kids at parturition and on the establishment of mutual recognition.

We investigated whether undernutrition during the second half of pregnancy impaired the behaviour of does and their kids at parturition and early mutual recognition. Twenty-two control and 22 underfed mixed-breed, multiparous dairy goats were used, together with their respective kids (control, n = 31: nine singles, 16 twins and six triplets; underfed, n = 32: 11 singles, 18 twins and three triplets). Undernutrition involved limiting protein and energy intake at 70% of the nutritional requirements for maintenance and foetal growth from day 70 of pregnancy until birth. The behaviour of mothers and their two first-born kids was observed for 90 min from the birth of each kid. Maternal olfactory recognition of the kid was assessed at 4 h post partum by testing selective nursing behaviour. Non-olfactory recognition was assessed at 8 h in a two-choice test excluding olfactory cues. In kids, preference for the mother was assessed in a two-choice test at either 12 or 24 h post partum. Bodyweight of does and kids were lower in the underfed group up to 2 weeks post partum. At parturition, licking, maternal bleating frequency and latency to nursing did not differ between nutritional groups. Control kids were faster than underfed kids to stand, search for and reach the udder, but underfed kids bleated more and tended to spend more time at the udder. Both control and underfed does accepted their own kid and rejected the alien in the selectivity test at 4 h. In contrast, at 8 h post partum, only control goats showed a significant preference for their own kid in the non-olfactory recognition test. Both control and underfed kids showed a preference for their own mother at 12 and 24 h and undernutrition during pregnancy had little influence on the performance of kids. However, 12 h-old underfed kids tended to be less active than control kids and visited their own mothers less than control kids. There were no significant correlations between the behaviour of the mother or of the kid at parturition and their performance in the discrimination tests. Overall, undernutrition in the second half of pregnancy appears to be more detrimental for the behaviour of the mother than for the kid. Furthermore, it has more impact on the establishment of maternal non-olfactory recognition than on maternal care at parturition or the establishment of maternal selectivity.

Optical coherence tomography characteristics of full-thickness traumatic macular holes.

PURPOSE: The objective of this paper is to describe the optical coherence tomography (OCT) characteristics of patients with full-thickness traumatic macular hole (TMH) and to correlate them with biomicroscopy findings. METHODS: Twelve eyes of ten consecutive patients with full-thickness TMH participated in this observational retrospective multicentre study. Patients underwent biomicroscopic fundus examination, colour fundus photography, and OCT. RESULTS: Traumatic macular hole was documented with OCT in five women and five men. Mean (range) time between trauma and macular hole (MH) diagnosis was 8.1 (1-24) months. The shape of TMHs was round in 11 (91.7%) eyes. The posterior vitreous was completely detached in six (50%) eyes, and with an operculum in one (8.3%) eye. The common findings seen on OCT were: (1) full-thickness loss of retinal tissue through the hole with sharp edges, perpendicular to the retinal pigment epithelium in five (41.7%) eyes; (2) TMH with an operculum totally detached from the hole's edge in two (16.7%) eyes; (3) presence of epiretinal membrane around of the hole in three (25%) eyes; and (4) presence of abnormalities of the surrounding retina in all (100%) eyes. The OCT characteristics correlated well with biomicroscopic findings, and these characteristics may be predictive for final visual acuity (VA) in TMHs. Only one of the TMHs closed spontaneously in our series. CONCLUSION: Optical coherence tomography complements biomicroscopy in the evaluation of full-thickness TMHs.

Screening of citalopram, fluoxetine and their metabolites in human urine samples by gas chromatography-mass spectrometry. A global robustness/ruggedness study.

Capillary gas chromatography with mass spectrometry detection in SIM mode (GC-MS-SIM) has been used for the analysis of citalopram (CIT), fluoxetine (FLX), and all of their metabolites in urine samples. The instrumental parameters affecting GC separation and MS-SIM detection were investigated. A validation procedure was performed on urine matrix and a simultaneous robustness/ruggedness evaluation is also presented in this paper. An optimized solid-phase extraction (SPE) has been applied, reaching in this way to limits of detection (LODs) between 0.7 ng L(-1) (CIT) and 33.6 microg L(-1) (CIT-PA). A pharmacokinetic screening in clinical urine samples has been also carried out.

Experimental observation of two-state on-off intermittency.

We observe a two-state on-off intermittency in a diode laser with an external cavity experimentally. The control parameter is the length of the external cavity that is periodically modulated. We demonstrate that the system exhibits an intermittent behavior between a two-mode chaotic regime and a single-mode state when the control parameter passes through the bifurcation point. Power-law scaling of the average laminar time with a critical exponent of -1 is found as a function of both the amplitude and frequency of the external modulation.

El caso de infecciosas. Entomoftoramicosis sistémica con compromiso mediastinal, pulmonar y pancreático. Informe de un caso y revisión del tema / The infectious case. Entomoftoramicosis systemic mediastinal involvement, lung and pancreatic cancer. Case report and literature review

Se presenta un caso fatal de entomoftoramicosis sistémica en una paciente joven, desnutrida, quien presentó compromiso de ambos pulmones, corazón, esófago y páncreas. El diagnóstico se estableció con base en el estudio histológico postmorten ya que esta entidad por ser tan poco frecuente, no fue sospechada clínicamente. En todas las vísceras comprometidas, se observó reacción granulomatosa crónica, la cual estaba centrada sobre las hifas del hongo; éstas eran aceptadas y aparecían rodeadas de un material eosinófilo amorfo (fenómeno de Hoeppli-Splendore). Se resumen brevemente los aspectos clínicos e histopatológicos del primer caso informado en el país de entomoftoramicosis sistémica.