Dietary bioactive ingredients to modulate the gut microbiota-derived metabolite TMAO. New opportunities for functional food development.

There is a growing body of clinical evidence that supports a strong association between elevated circulating trimethylamine N-oxide (TMAO) levels with increased risk of developing adverse cardiovascular outcomes such as atherosclerosis and thrombosis. TMAO is synthesized through a meta-organismal stepwise process that involves (i) the microbial production of TMA in the gut from dietary precursors and (ii) its subsequent oxidation to TMAO by flavin-containing monooxygenases in the liver. Choline, l-carnitine, betaine, and other TMA-containing compounds are the major dietary precursors of TMA. TMAO can also be absorbed directly from the gastrointestinal tract after the intake of TMAO-rich foods such as fish and shellfish. Thus, diet is an important factor as it provides the nutritional precursors to eventually produce TMAO. A number of studies have attempted to associate circulating TMAO levels with the consumption of diets rich in these foods. On the other hand, there is growing interest for the development of novel food ingredients that reduce either the TMAO-induced damage or the endogenous TMAO levels through the interference with microbiota and host metabolic processes involved in TMAO pathway. Such novel functional food ingredients would offer great opportunities to control circulating TMAO levels or its effects, and potentially contribute to decrease cardiovascular risk. In this review we summarize and discuss current data regarding the effects of TMA precursors-enriched foods or diets on circulating TMAO levels, and recent findings regarding the circulating TMAO-lowering effects of specific foods, food constituents and phytochemicals found in herbs, individually or in extracts, and their potential beneficial effect for cardiovascular health.

Non-invasive metabolomics for improved determination of embryonic sex markers in chemically defined culture medium.

Metabolic differences between early male and female embryos can be reflected in culture medium (CM). We used a single bovine embryo culture step (24h) supporting improved birth rates under chemically defined conditions (CDC) to investigate biomarker detection of embryonic sex in contrast to classical BSA-containing medium. In vitro matured slaughterhouse oocytes were fertilized in vitro with a single bull. Embryos were initially cultured in synthetic oviduct fluid with BSA. On day-6, morulae were cultured individually in droplets with (BSA) or without protein (CDC). On day-7, expanded blastocysts were sexed (amelogenin gene amplification) and CM was stored at -145°C until metabolomic analysis by UHPLC-TOF MS. N=10 embryos per group (i.e. male-protein; female-protein; male-non-protein; female-non-protein) were produced. Statistical analysis revealed N=6 metabolites with different concentrations in CM, N=5 in male embryos (methionine, tryptophan, N-stearoyl-valine, biotin and pipecolic acid), N=1 in female embryos (threonine) (P<0.05 in BSA; P<10-7 in CDC). Only the clear threshold between males and females in CDC allowed correct classification of 100% males and 91% females within 5 out of 6 biomarkers (one female outlier showing the male biomarker profile). The use of CDC represents a critical aspect in the efficient detection of embryonic sex biomarkers by metabolomics.

Effects of migration on population aging (the case of the Valencian Community).

For Spain as a whole and the Valencian Community (VC) in particular both aging and migration have numerous important effects on their demographic development, e.g. in this century Spain has the greatest net migration in Europe, and inside Spain in the VC the proportion of the population of foreign citizenship is high. The paper aims at studying the interplay between aging and migration in the Valencian Community since the beginning of the 1990s. A number of aging characteristics have been computed for the VC and its regions for Spanish citizens and the population of foreign citizenship. Age structure of migration flows will be examined. The paper is based on censuses and micro-data on vital events. Results of the study revealing interrelations between migration and age structure may contribute to the management, administration and planning of social and health services.

Planar radial weakly dissipative diffeomorphisms.

We study the effect of a small dissipative radial perturbation acting on a one parameter family of area preserving diffeomorphisms. This is a specific type of dissipative perturbation. The interest is on the global effect of the dissipation on a fixed domain around an elliptic fixed/periodic point of the family, rather than on the effects around a single resonance. We describe the local/global bifurcations observed in the transition from the conservative to a weakly dissipative case: the location of the resonant islands, the changes in the domains of attraction of the foci inside these islands, how the resonances disappear, etc. The possible ω-limits are determined in each case. This topological description gives rise to three different dynamical regimes according to the size of dissipative perturbation. Moreover, we determine the conservative limit of the probability of capture in a generic resonance from the interpolating flow approximation, hence assuming no homoclinics in the resonance. As a paradigm of weakly dissipative radial maps, we use a dissipative version of the Hénon map.

Advances in Nutrigenomics research: novel and future analytical approaches to investigate the biological activity of natural compounds and food functions.

In recent years, nutrition research has moved from classical epidemiology and physiology to molecular biology and genetics. Following this trend, Nutrigenomics has emerged as a novel and multidisciplinary research field in nutritional science that aims to elucidate how diet can influence human health. It is already well known that bioactive food compounds can interact with genes affecting transcription factors, protein expression and metabolite production. The study of these complex interactions requires the development of advanced analytical approaches combined with bioinformatics. Thus, to carry out these studies Transcriptomics, Proteomics and Metabolomics approaches are employed together with an adequate integration of the information that they provide. In this article, an overview of the current methodologies and a thorough revision of the advances in analytical technologies and their possibilities for future developments and applications in the field of Nutrigenomics is provided.

Antimicrobial activity of the crude extracts and compounds from Ficus chlamydocarpa and Ficus cordata (Moraceae).

The aim of this study was to evaluate the antimicrobial activity of the methanol extracts from Ficus chlamydocarpa (FCR), Ficus cordata (FCB), mixture of the two plants (FCM), as well as that of the isolated flavonoids Alpinumisoflavone (2), Genistein (3), Laburnetin (4), Luteolin (5) (isolated from FCR), Catechin (7) and Epiafzelechin (8) (isolated from FCB). Mycobacteria, fungi, Gram-positive and Gram-negative bacterial species were tested for their susceptibility to the above samples. The microplate dilution and radiometric respiratory methods were used to determine the susceptibility testing of the samples against Mycobacterium smegmatis and Mycobacterium tuberculosis, respectively. The disc diffusion assay was used to determine the sensitivity of the samples, whilst the micro-dilution method was used for the determination of the minimal inhibition concentration (MIC) and the minimal microbicidal concentration (MMC) against fungi, Gram-positive and Gram-negative bacterial species. All the samples except compound 7 were found to be active to Mycobacterium smegmatis and the MIC ranged from 0.61 to 312.50microg/ml. Compound 4 showed the best activity against Mycobacterium tuberculosis exhibiting an MIC of 4.88microg/ml. The results of the diffusion test indicated that the crude extract from FCB, FCM as well as compounds 5 and 8 were able to prevent the growth of all tested (fungi, Gram-positive and Gram-negative bacteria) organisms. The inhibition effect of the crude extract from Ficus chlamydocarpa was observed on 10 (62.5%) of the 16 tested microorganisms (excluding mycobacteria) whereas that of compounds 4, 2 and 3 was respectively noted on 14 (87.5%), 8 (50.0%) and 7 (39.9%) of the tested microbial species. FCB was found to be more active than FCR on most of the tested organisms. The results provided evidence that the studied plants extract, as well as some of the isolated compounds might be potential sources of new antimicrobial drug.

Bifurcation analysis of multiple steady flow patterns for Rayleigh-Bénard convection in a cubical cavity at Pr = 130.

The bifurcation diagram of steady convective flow patterns inside a cubical cavity with adiabatic lateral walls heated from below and filled with silicone oil (Pr = 130) was determined for values of the Rayleigh number (Ra) up to 1.5 x 10(5). A continuation procedure based on the Galerkin spectral method was used to determine the steady convective solutions as a function of Ra. Bifurcations leading to either new steady or time-dependent solutions were identified and new steady solution branches were also continued. A total of fifteen steady solutions were tracked and the stability analysis predicted that six flow patterns were stable and that two, three, or even four of these patterns coexisted over certain ranges of Ra in the studied domain. Predicted flow patterns and transitions are in agreement with flow visualizations previously reported in the literature. The variation of the Nusselt number (Nu) as a function of Pr was investigated for three of the stable flow patterns identified: a x or y roll, a diagonal oriented roll and a pattern formed by four connected half rolls. It was found that whereas the Nusselt changes within the region 0.71 < or = Pr < or = 10 it tends to an asymptotic value with increasing Pr.

Monitoring ibuprofen enantiomers released from polymeric systems.

Two methacrylic derivatives of ibuprofen (N-[4-[2-(4-isobutylphenyl)propionyloxy]phenyl] methacrylamide (MAI) and 2-[(4-isobutylphenyl)propionyloxy]ethyl methacrylate (MEI)) were used together with 2-hydroxyethyl methacrylate (HEMA) to synthesize four polymeric materials: two hydrophobic homopolymers, PMAI and PMEI, and two hydrophilic copolymers containing 70% (w/w) HEMA, MAI-HEMA 30 and MEI-HEMA 30. The enantiomeric determination of R- and S-IBU released from these four systems has been carried out by capillary electrophoresis. Release of R- and S-IBU was monitored during in vitro assays done at 37 degrees C at pH 7.4 and 10 in buffered solutions and rat plasma. There is a hydrolytical activation in plasma and at pH 10 compared to pH 7.4; moreover, the release rate from the copolymers is much higher than from the homopolymers as a consequence of the greater hydrophilic character. A slight excess of the S-enantiomer of IBU is observed in all the experiments, being more relevant at higher release rates, i.e. copolymers at pH 10.

Fast and sensitive capillary electrophoresis method to quantitatively monitor ibuprofen enantiomers released from polymeric drug delivery systems.

In this work, the capability of two polymeric drug delivery systems (DDS) containing racemic ibuprofen (IBU) for controlled release of IBU in different media was studied carrying out assays in-vitro. To quantitatively monitor the release of R(-)- and S(+)-IBU, a fast, sensitive and inexpensive capillary electrophoresis (CE) method was developed. To do this, different chiral selectors, temperatures, buffer compositions and pHs were tested. This new CE method uses bare silica columns together with a buffer containing 6% Dextrin in a 150 mM sodium tetraborate buffer at pH 9. Baseline separations of R(-)- and S(+)-IBU were achieved in less than 5 min at 20 degrees C. By using this method, both enantiomers can be determined at concentrations as low as 1 microg/ml, allowing the detection of enantiomeric percentages of 0.5% of R(-)-IBU in the presence of 99.5% of the optical antipode. Moreover, the method shows a high reproducibility for the same day and different days. The usefulness of this method to quantitatively monitor the release of R(-)- and S(+)-IBU from two different polymeric DDS is demonstrated. It is shown that the release rate of IBU depends on the spacer of the side residue used in the polymeric device. Also, it is demonstrated that the release of both enantiomers is enzymatically activated in rat plasma.

Looking into the demography of an iron age population in the western Mediterranean. I. Mortality.

In this paper, we attempt to reconstruct the mortality pattern of the population buried in S'Illot des Porros (Majorca), an Iron Age necropolis in the western Mediterranean, by means of paleodemographic analysis. The skeletal sample consists of 285 individuals, 93 subadults (under 20 years old) and 192 adults. The aim of this study is twofold: first, to identify and to evaluate the structural anomalies of the skeletal sample, and second, to obtain a possible and realistic description of the biological dynamics of this population, with special reference to its mortality pattern. The study uses current demographic methodology and several demographic models (for comparison). An abridged life table was built to estimate the mortality parameters. To evaluate the likelihood of the estimated data, an indirect analysis, which consisted of a comparison of our results with different population models (Weiss [1973] American Antiquity 38; Coale and Demeny [1996] Regional Model Life Tables and Stable Populations. Princeton: Princeton University Press; Ledermann [1969] Nouvelles tables-types de mortalité. Paris: Presses Universitaires de France), was carried out. An important bias was identified in the case of children, mostly affecting infants but also children between the ages of 1 and 5. This was interpreted as a census error due to taphonomic reasons and to an excluding differential funeral rite. A life expectancy at birth of approximately 28 years was estimated from the observed data. When this bias was removed, the estimated life expectancy at birth dropped to 23 years. The use of the Brass logit system allowed us to sketch a possible mortality profile for this population: low life expectancy, high infant mortality and hard life conditions, which were the cause of the low levels of survivorship in old ages. Am J Phys Anthropol 110:285-301, 1999.

[Spinal cord ischemia as a consequence of dissection of an abdominal aortic aneurysm]. / Isquemia medular como consecuencia de un aneurisma de aorta abdominal.

INTRODUCTION: Ischemic spinal cord infarct is the most frequent vascular lesion, but although aortic aneurysms are a possible cause, it is unusual for such cases to be seen. Clinical case. We present a case of spinal ischemia as the first sign of the dissection of an aneurysm of the abdominal aorta. A 58 year old man was seen in the hospital Emergency Department complaining of lumbar pain and the sudden onset of paraplegia of the legs, associated with pain in the middle of his back but with no history of previous trauma or effort. The only relevant personal history was of smoking. Whilst he was in the Neurology Department, the anomaly was diagnosed after dorsal, and lumbar gadolinium magnetic resonance (MR), when a zone of ischaemia at T9-T10 was seen and, as a casual observation, an image compatible with an aneurysm of the abdominal aorta. The relationship between the dissection of the aorta and the neurological complications may be explained by a clear understanding of the vascular supply to the spinal cord. In this case, both the clinical findings and the MR were clearly indicative of an anterior spinal artery syndrome. CONCLUSIONS: In spite of its rarity, aortic aneurysm should be included in the differential diagnosis of a clinical picture of ischemic myelopathy, especially when there is lumbar and/or abdominal pain before the appearance of neurological symptoms. Spinal MR is important for this diagnosis.

Adjuvant chemotherapy and immunotherapy in high risk patients with melanoma.

Thirty-one patients with Stage II cutaneous melanoma received adjuvant chemotherapy or immunotherapy after radical excision of the primary and regional lymph nodes. Vaccinations with bacille Calmette Guérin produced minimal systemic reactions and was better tolerated by the patients than was chemotherapy. A higher survival rate and disease-free interval were noted in patients treated with bacille Calmette Guérin than those receving dimethyl Triazeno-imidazole carboximide. These results suggest that adjuvant chemotherapy with dimethyl Triazenoimidazole carboximide alone is not beneficial in the treatment of high risk patients with melanoma. In this study, adjuvant bacille Calmette Guérin therapy appears to be more advantageous than does chemotherapy.