Seroprevalence of trypanosomosis and associated risk factors in cattle from coast and amazonian provinces of Ecuador.

Trypanosomosis is a tropical disease caused by various protozoan haemoparasites, which affects wild and domestic animals, the latter ones related to worldwide livestock production systems. Species such as Trypanosoma vivax and Trypanosoma evansi have been described using serological and molecular tools in several countries from South and Central America. However, Ecuador presents a relevant knowledge gap in the associated general epidemiology and risk factors of the disease. Therefore, the objective of this study was to determine the seroprevalence of trypanosomosis in cattle from different regions of Ecuador. 745 serum samples from 7 Coastal and 3 Amazon provinces were screened for IgG anti-Trypanosoma spp. antibodies, using an in-house indirect ELISA. The seropositivity was explored and associated with several variables such as sex, age, breed, region, management, and province, using statistical tools. The general seroprevalence of trypanosomosis was 19.1% (95% CI: 16.30-22.1%). The Amazonian provinces of Sucumbíos and Napo and the Coastal province of Esmeraldas presented the highest seroprevalence values of 36.7% (95% CI: 27.67-46.47%), 23.64% (95% CI: 16.06-32.68%) and 25% (95% CI: 15.99-35.94%), respectively. Statistical significance was found for the region, province, and management variables, indicating as relevant risk factors the extensive management and Amazon location of the cattle analyzed. Specific actions should be taken to identify the exact species on reservoirs and susceptible hosts, evaluate the implication of farm management and cattle movement as risk factors, and implement surveillance and treatment plans for affected herds.

Do adolescent trajectories of riding with an impaired driver and driving impaired predict similar behaviors in early adulthood?

BACKGROUND: A recent study shows four trajectories of riding with an impaired driver (RWI) and driving while impaired (DWI) from adolescence to emerging adulthood. We examined prospective associations of adolescent RWI/DWI trajectory class with early adulthood RWI/DWI behavior. METHODS: Data were from the NEXT Generation Health Study (NEXT), a nationally representative longitudinal study (N = 2783) beginning with a 10th-grade cohort completing 7 annual assessment waves (W1-W7) between 2010 and 2016 and a later follow-up mixed methods study. Four RWI and DWI trajectories derived from a recently published latent class analysis study (RWI (last 12 months); DWI (last 30 days) dichotomized as ≥ once vs. none) were used: Abstainer, Escalator, Decliner, and Persister. In the follow-up examination, a purposive subsample (N = 105, 26.3 ± 0.5 y/o, Female 50.5%) of NEXT participants were selected by trajectory (31 Abstainers, 33 Escalators, 14 Decliners, and 27 Persisters) for in-depth interviews 4 years after NEXT. In interviews, self-reported RWI events (number of times) related to alcohol (Alc-RWI) or marijuana (MJ-RWI) use in the last 12 months, and DWI events (number of times) related to alcohol (Alc-DWI) & marijuana (MJ-DWI) use in January 2020 (pre-COVID pandemic) were collected using structured surveys. General linear models were used to examine associations of adolescents' RWI/DWI trajectories with early adulthood RWI/DWI behavior, controlling for sex, health status, education attainment, and work hours. RESULTS: The mean number (SD) of Alc-RWI and MJ-RWI events reported by Escalators (3.83(2.48), 2.43(2.77)) and Persisters (3.83(2.43), 3.57(2.54)) were higher (p≤0.05) than Abstainers (0.82(1.42), 0.77(2.04)) and Decliners (1.81 (2.69), 1.38 (2.04)). Similarly, Escalators (1.61 (2.28), 1.88(2.69)) and Persisters (1.96(2.08), 1.93(2.48)) reported more Alc-DWI and MJ-DWI events than Abstainers (0.18 (0.53), 0.42(1.38)) and Decliners (0.00 (0.00), 0.08(0.28)). Linear regression models indicated membership in Escalator and Persister classes compared to Abstainer class was associated (p≤0.01) with higher engagement in RWI/DWI in early adulthood. CONCLUSION: Adolescents with escalating and persistent high RWI/DWI may continue these health risking behaviors into their mid-twenties. Decliners during the transition maintained low RWI/DWI into their mid-twenties. Taken together, these findings suggest that earlier reduction may have long-term effects. Our findings can be used to inform the precision tailoring of prevention efforts aimed at effectively reducing alcohol/drug impairment crash injuries and related deaths among those in early adulthood.

Molecular identification of Trypanosoma theileri in cattle from the Ecuadorian Amazon.

Trypanosoma theileri is a cosmopolitan opportunistic haemoparasite described in wild and domestic ruminants, and also in arthropod vectors. The presence of this parasite has been reported in several South American countries, including Amazonian regions. Despite the importance of livestock production, Ecuador possesses scarce studies about trypanosomosis and no T. theileri reports in its territory. Here, we showed molecular evidences of the presence of T. theileri in cattle from a province located in the Ecuadorian Amazon. Bovine blood samples were collected from 2014 to 2019, during campaigns to detect haemoparasites in the Ecuadorian provinces of Orellana and Sucumbíos. DNA was extracted from the buffy coat and used in PCR assays with three different molecular markers, ITS1, 18S and Cathepsin L-like. T. theileri was detected only in the Sucumbíos province, with a specific molecular prevalence of 8.6% (3/35) using the three primers and an additional animal detected as positive (11.4% prevalence) only by the ITS1 marker. DNA sequences derived from the generated amplicons were subjected to phylogenetics maximum parsimony and maximum likelihood analysis, which indicate the presence of TthI and TthII genotypes circulating in the evaluated animals. Molecular surveillance should be continually implemented in Ecuador in order to deepen the epidemiological and evolutionary knowledge about T. theileri as well other haemoparasites in the amazon parts of the country.

Chitosan/copper nanocomposites: Correlation between electrical and antibacterial properties.

Correlation between electrical and antibacterial properties of chitosan/copper nanocomposites (CS/CuNPs) is investigated. We aim at achieving the minimum CuNPs concentration in a CS-matrix while keeping high antibacterial activity. UV-vis, TEM and XRD measurements confirms the formation of polygonal metallic CuNPs (ca. 30-50 nm). Interactions between NH2/OH groups of CS and CuNPs were determined by FTIR and XPS suggesting Cu chelation-induced mechanism during the CuNPs formation. DC electrical conductivity measurements reveals a percolation threshold at CuNPs volumetric concentration of ca. 0.143%. Antibacterial assays against Gram-positive bacteria and DC measurements helps correlate the antibacterial potency to the electron transfer between the negatively charged bacteria and CuNPs. Our study suggests that nanocomposite's maximum antibacterial activity is obtained below the electrical percolation threshold at extremely low CuNPs concentrations; this fact may prove useful in the design of nontoxic nanocomposites for biomedical applications.

Combined antibacterial/tissue regeneration response in thermal burns promoted by functional chitosan/silver nanocomposites.

We report the combined antibacterial/tissue regeneration responses to thermal burns promoted by functional chitosan/silver nanocomposites (CS/nAg) with ultralow silver content (0.018wt.%, 7-30nm). Our approach allows one to produce CS/nAg nanocomposites without silver nanoparticles (nAg) agglomeration, with bactericide potency higher than 1wt.% of nAg (ca. 10nm) content and, promoting the healing process in controlled thermal burns. CS/nAg films exhibit high antibacterial activity against S. aureus and P. aeruginosa after 1.5h of incubation, demonstrating the bacterial penetration into hydrated films and their interaction with nAg. Additionally, exceptional healing of induced thermal burns was obtained by increasing myofibroblasts, collagen remodeling, and blood vessel neoformation. These factors are associated with epiderma regeneration after 7days of treatment with no nAg release. Our results corroborate the controlled synthesis of nAg embedded in CS matrix with combined antibacterial/biocompatibility properties aiming to produce functional nanocomposites with potential use in wound dressing and health care applications.

Preparación y Caracterización de Nanocompositos Quitosano-Cobre con Actividad Antibacteriana para aplicaciones en Ingeniería de Tejidos / Preparation and characterization of Copper Chitosan Nanocomposites with Antibacterial Activity for Applications in Tissue Engineering

RESUMEN: El presente trabajo describe la preparación de nanocompositos formulados a partir de quitosano (QS)/nanopartículas de cobre (nCu) con características antibacterianas y aplicación potencial en ingeniería de tejidos. Para ello, se prepararon nanocompositos mediante mezclado en solución asistido con ultrasonido con el objetivo de incrementar la dispersión de la carga nanométrica en el biopolímero. El análisis de FTIR demostró que la presencia de nCu en la matriz de QS favorece la interacción del nCu con los grupos amino/hidroxilo de la molécula del QS. Se determinó mediante UV-Vis que los nanocompositos QS/nCu presentan absorción asociada con la presencia de nanopartículas y la posible liberación de iones Cu2+ en medio líquido. Mediante AFM se determinó que el QS hidratado forma una malla con microporos, que puede favorecer la penetración de bacterias en el nanocomposito y su interacción con las nCu. Finalmente, se determinó el efecto antibacteriano del material al contacto con la bacteria Staphylococcus aureus, en donde se presenta una actividad antibacteriana superior al 90% entre los 90 y 180 min de interacción. Dichos resultados sugieren que es posible obtener nanomateriales antibacterianos biocompatibles para su posible aplicación en ingeniería tisular.

ABSTRACT: The Present work describes the preparation of nanocomposites based on chitosan (QS)/copper nanoparticles (nCu) with antibacterial properties and potential application in tissue engineering. For this purpose, nanocomposites were prepared by solution blending with ultrasound assisted, aiming to increase the nanoparticles dispersion in the biopolymer. FTIR analyses demonstrates that nCu supported in QS increase their interaction of nanoparticles with amine/hydroxyl groups of QS molecule. UV-Vis analyses demonstrates that QS/nCu nanocomposites have an absorption signal associated with the presence of nanoparticles and the possible Cu2+ ions release in liquid media. AFM analyses shown that hydrated QS form a mesh with micro pores, improving the bacterial penetration and the direct contact with nCu. This behavior was corroborated by antibacterial assays, where QS/nCu nanocomposites shown an antibacterial activity higher than 90% between 90-180 minutes of interaction. Our results suggest that is possible to obtain combined antibacterial/biocompatible nanomaterials with potential application in tissue engineering.

Modulation of autoimmune arthritis severity in mice by apolipoprotein E (ApoE) and cholesterol.

Apolipoprotein E (ApoE) deficiency promoted an exacerbation of autoimmune arthritis in mice by inducing proinflammatory immune responses. In this study we analysed the contribution of hypercholesterolaemia and/or the absence of ApoE anti-inflammatory properties, unrelated to its function in the control of cholesterol metabolism, towards the acceleration of arthritis in these mutant animals. The induction and severity of collagen type II-induced arthritis (CIA) were compared for B10.RIII wild-type (WT), B10.RIII.ApoE+/- , B10.RIII.ApoE-/- and B10.RIII.low-density lipoprotein receptor (LDLR-/- ) mice with different concentrations of circulating ApoE and cholesterol. A 50-70% reduction in serum levels of ApoE was observed in heterozygous B10.RIII.ApoE+/- mice in comparison to B10.RIII.WT, although both strains of mice exhibited similar circulating lipid profiles. This ApoE reduction was associated with an increased CIA severity that remained lower than in homozygous B10.RIII.ApoE-/- mice. An important rise in circulating ApoE concentration was observed in hypercholesterolaemic B10.RIII.LDLR-/- mice fed with a normal chow diet, and both parameters increased further with an atherogenic hypercholesterolaemic diet. However, the severity of CIA in B10.RIII.LDLR-/- mice was similar to that of B10.RIII.WT controls. In conclusion, by comparing the evolution of CIA between several strains of mutant mice with different levels of serum ApoE and cholesterol, our results demonstrate that both hypercholesterolaemia and ApoE regulate the intensity of in-vivo systemic autoimmune responses.

Spatial and temporal variation of surface ozone, NO and NO2 at urban, suburban, rural and industrial sites in the southwest of the Iberian Peninsula.

Surface ozone is one of the most important photochemical pollutants in the low atmosphere, causing damage to human health, vegetation, materials and climate. The weather (high temperatures and high solar radiation), orography (presence of the Guadalquivir valley) and anthropogenic (the cities of Cádiz, Córdoba, Huelva and Seville and two important industrial complexes) characteristics of the southwestern Iberian Peninsula make this region ideal for the formation and accumulation of ozone. To increase the knowledge of ozone behaviour in this area, the monthly, daily and weekly variations of ozone and its precursors, nitrogen oxides (NO(x) = NO + NO2), were analysed over a 4-year period (2003 to 2006). Using the k-means cluster technique, 12 representative stations of five different areas with different ozone behaviour were selected from a total of 29 monitoring sites. This is the first time that the analysis of these atmospheric pollutants has been carried out for the whole area, allowing therefore a complete understanding of the dynamics and the relationships of these compounds in this region. The results showed an opposite behaviour among ozone and NO and NO2 concentrations in urban and suburban zones, marked by maximums of ozone (minimums NO(x)) in spring and summer and minimums (maximums) in autumn and winter. A seasonal behaviour, with lower amplitude, was also observed in rural and industrial areas for ozone concentrations, with the NO and NO2 concentrations remaining at low and similar values during the year in rural zones due to the absence of emission sources in their surroundings. The daily cycles of ozone in urban, suburban and industrial sites registered a maximum value in the early afternoon (14:00-17:00 UTC) while for NOx two peaks were observed, at 7:00-10:00 UTC and 20:00-22:00. In the case of rural stations, no hourly peak of ozone or NO(x) was registered. The weekend effect was studied by using a statistical contrast tests (Student's t). The results indicated that only areas influenced by important traffic emissions presented a weekend effect for NO and NO2, whereas an ozone weekend effect was not detected in any case.

Geochemical behavior of metals and metalloids in an estuary affected by acid mine drainage (AMD).

The Tinto and Odiel rivers in southwest Spain drain the world's largest sulfide mineral formation: the Iberian Pyrite Belt which has been worked since 2,500 BC. The Tinto and Odiel estuarine zones include both an extensive area of salt marsh and an intensively industrialized urban area. As a consequence of pyrite oxidation, the Tinto and Odiel rivers are strongly acidic (pH < 3) with unusually high and quite variable metal concentrations. In this study, seasonally varying concentrations of dissolved major and trace elements were determined in the acid mine drainage affected estuary of the Ría de Huelva. During estuarine mixing, ore-derived metal concentrations exhibit excellent correlations with pH as the main controlling parameter. As pH increases, concentrations of dissolved ore-associated elements are attenuated, and this process is enhanced during the summer months. The decrease in Fe and Al concentrations ranged from 80 to 100 % as these elements are converted from dissolved to sediment-associated forms in the estuary. Coprecipitation/adsorption processes also removed between 60 and 90 % of the originally dissolved Co, Cu, Mn, Pb, Zn, and Th; however, Cd and Ni exhibited a greater propensity to remain in solution, with an average removal of approximately 60 %. On the other hand, As and U exhibited a different behavior; it is likely that these elements remain in dissolved forms because of the formation of U carbonates and soluble As species. Concentrations of As remain at elevated levels in the outer estuary (average = 48 µg L(-1)) which exceeds concentrations present in the Tinto River. Nevertheless, the estuary has recently witnessed improvements in water quality, as compared to results of several previous studies reported in the 1990s.

Uranium behaviour in an estuary polluted by mining and industrial effluents: the Ría of Huelva (SW of Spain).

This paper describes a comprehensive study of the behaviour of U in the Ría of Huelva estuary, formed by the Tinto and Odiel rivers. This ecosystem is conditioned by two hydrochemical facts: one connected with the acid mining drainage (AMD) generated in the first section of the river basins, and another one related to the fertilizer industry located at the estuary. AMD gives a singular character to these rivers; low pH and high redox potential that keep high amounts of toxic elements and radionuclides in dissolution. Most of the data for dissolved U in estuaries indicate conservative mixing, but there are examples of non-conservative behaviour attributed to oxidation/reduction processes or solubility variations. In the Ría of Huelva estuary the U shows a non-conservative behaviour due to solubility changes produced by variations in the pH. A complete removal of riverine dissolved U is observed in a pH range of 4-6. At higher pH values, U release from suspended matter, and probably also from sediments into the dissolved phase is found.

Radioactive characterization of the main materials involved in the titanium dioxide production process and their environmental radiological impact.

A study about the distribution of several radionuclides from the uranium and the thorium series radionuclides along the production process of a typical NORM industry devoted to the production of titanium dioxide has been performed. With this end the activity concentrations in raw materials, final product, co-products, and wastes of the production process have been determined by both gamma-ray and alpha-particle spectrometry. The main raw material used in the studied process (ilmenite) presents activity concentrations of around 300 Bq kg(-1) for Th-series radionuclides and 100 Bq kg(-1) for the U-series ones. These radionuclides in the industrial process are distributed in the different steps of the production process according mostly to the chemical behaviour of each radioelement, following different routes. As an example, most of the radium remains associated with the un-dissolved material waste, with activity concentrations around 3 kBq kg(-1) of (228)Ra and around 1 kBq kg(-1) of (226)Ra, while the final commercial products (TiO2 pigments and co-products) contain negligible amounts of radioactivity. The obtained results have allowed assessing the possible public radiological impact associated with the use of the products and co-products obtained in this type of industry, as well as the environmental radiological impact associated with the solid residues and liquid generated discharges.

Occupational exposures in two industrial plants devoted to the production of ammonium phosphate fertilisers.

In order to fill a gap in the open literature, occupational exposures and activity concentrations have been assessed in two NORM industrial plants, located in the south-west of Spain, devoted to the production of mono-ammonium phosphate (MAP) and di-ammonium phosphate (DAP) fertilisers. The annual effective doses received by the workers from these plants are clearly below 1 mSv yr(-1) and the contribution due to external radiation is similar to that due to inhalation. The contribution to the maximum effective doses due to inhalation of particulate matter has been estimated to be about 0.12 mSv yr(-1), while the (222)Rn concentrations inside the plants are of no concern. Consequently, no additional actions or radiological protection measures need to be taken to decrease the natural radiation received by the workers in these facilities.

Behavior of natural radionuclides in surficial sediments from an estuary impacted by acid mine discharge and industrial effluents in Southwest Spain.

The environmental degradation resulting from the acid mine drainage (AMD) and discharge from effluents of phosphogypsum (PG) piles in the watershed of Tinto and Odiel Rivers estuary over long periods of time has resulted in significant impact on the ecosystem of this estuary, resulting that the sediments are highly polluted by heavy metals and radionuclides from the discharge AMD and leachates from the PG. During resuspension of benthic sediments some of the radionuclides are desorbed making them bioavailable. In the present study, we investigate the spatial distribution of radionuclides U, Th and Ra and assess the factors and processes that caused the spatial distribution of these nuclides in this estuarine system. This study has global significance for other polluted environmental systems that are impacted by AMD and PG.

Physico-chemical and radioactive characterization of TiO2 undissolved mud for its valorization.

In order to find a potential valorization of a waste generated in the industrial process devoted to the production of TiO(2) pigments, and as an essential and basic step, this waste must firstly be physically and chemically characterized. Moreover, the content of radioactivity is taken in to account due to it comes from a NORM (Naturally Occurring Radioactive Material) industry. With this end, microscopic studies were performed by applying scanning electron microscopy with X-ray microanalysis (SEM-XRMA), while the mineralogical compositions were carried out by means of the X-ray diffraction (XRD) technique. The concentrations of its major elements were determined by X-ray fluorescence (XRF), while heavy metals and other trace elements were ascertained through Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The results obtained for this waste have revealed several lines of research into potential applications. Firstly, with the refractory properties of mineral phases observed leading to a possible use in the ceramics industry or in thermal isolators. And secondly, attending to the characteristic particle-size spectra can be used as an additive in the manufacture of cement and finally, its high concentration of titanium may be used as a bactericide in brick production.

Effect of atorvastatin on lipoprotein (a) and interleukin-10: a randomized placebo-controlled trial.

AIM: This study aimed to determine the effect of atorvastatin therapy on plasma lipoprotein (a) [Lp(a)] and biomarkers of inflammation in hypercholesterolaemic patients free of cardiovascular disease. METHODS: In this three-month randomized double-blind placebo-controlled trial, 63 hypercholesterolaemic patients were randomly treated with either placebo or atorvastatin (10 or 40 mg/day) for 12 weeks. Lp(a) and biomarkers of inflammation (C-reactive protein [CRP], interleukin [IL]-6 and -10, and tumour necrosis factor-alpha receptors [TNF-Rs]) were measured at study entry, and at four and 12 weeks of follow-up. RESULTS: At the end of the study, patients allocated to atorvastatin (10 or 40 mg/day) presented with significantly lower Lp(a) levels than those taking placebo (10 [1-41]mg/dL versus 6 [1-38]mg/dL [P = 0.02] and 21 [1-138]mg/dL versus 15 [1-103]mg/dL [P = 0.04], respectively]. In multivariate analyses, the relative changes in Lp(a) were independently related to baseline Lp(a) levels and CRP changes. No significant changes in CRP, IL-6 and TNF-Rs were observed. In contrast, IL-10 (pg/mL) increased significantly in patients taking atorvastatin (2.14 [0.49-43]pg/mL versus 4.54 [0.51-37.5]pg/mL; P = 0.01), and was even more increased with the 40-mg dose than with 10mg. CONCLUSION: Our results suggest that 12-week atorvastatin is effective in reducing Lp(a) in dyslipidaemic patients free of CVD. Furthermore, this is also the first evidence that the drug increases IL-10 in a dose-dependent manner.

Insights into Entamoeba histolytica virulence modulation.

Entamoeba histolytica is able to invade human tissues by means of several molecules and biological properties related to the virulence. Pathogenic amebas use three major virulence factors, Gal/GalNAc lectin, amebapore and proteases, for lyse, phagocytose, kill and destroy a variety of cells and tissues in the host. Responses of the parasite to host components such as mucins and bacterial flora influence the behavior of pathogenic amebas altering their expression of virulence factors. The relative virulence of different strains of E. histolytica has been shown to vary as a consequence of changes in conditions of in vitro cultivation which implies substantial changes in basic metabolic aspects and factors directly and indirectly related to amebic virulence. Comparison of E. histolytica strains with different virulence phenotypes and under different conditions of growth will help to identify new virulence factor candidates and define the interplay between virulence factors and invasive phenotype. Virulence attenuate mutants of E. histolytica are useful also to uncover novel virulence determinants. The comparison of biological properties and virulence factors between E. histolytica and E. dispar, a non-pathogenic species, has been a useful approach to investigate the key factors involved in the experimental presentation of amebiasis and its complex regulation. The molecular mechanisms that regulate these variations in virulence are not yet known. Their elucidation will help us to better understand the gene expression plasticity that enables the effective adaptation of the ameba to changes in growth culture conditions and host factors.

¿Son todas las partículas de lipoproteínas de alta densidad iguales? / Are all high-density lipoprotein particles equal?

El análisis de las modificaciones de genes que influencian el metabolismo y la función de las lipoproteínas de alta densidad (HDL) en modelos murinos, demuestra que los cambios (aumentos o disminución) de colesterol unido a HDL no son un predictor adecuado de la susceptibilidad a la arteriosclerosis de éstos. Por tanto, los diferentes tipos de partículas de HDL generados por intervención sobre distintas potenciales dianas terapéuticas no son iguales en cuanto a su potencial antiaterogénico. El análisis del transporte reverso de colesterol específico de macrófagos, y de la capacidad de las HDL de proteger frente a la modificación oxidativa de lipoproteínas de baja densidad, aporta una mejor predicción del efecto de la modificación genética efectuada sobre la susceptibilidad a la arteriosclerosis (AU)

Analysis of the genetic modifications that influence high-density lipoprotein (HDL) metabolism and function in murine models shows that changes (whether increases or decreases) in HDL-cholesterol do not accurately predict susceptibility to arteriosclerosis in these models. Therefore, the distinct types of HDL particles generated by interventions on the various potential therapeutic targets differ in their antiatherogenic potential. Analysis of macrophage-specific reverse cholesterol transport and the ability of HDL to protect LDL against oxidative modification is better able to predict the effect of genetic modification on susceptibility to arteriosclerosis (AU)

Tratamientos vitamínicos para disminuir la concentración de homocisteína: ¿reducen el riesgo de enfermedad cerebrovascular en prevención primaria? / Vitamin treatments that lower homocysteine concentration: can they decrease cerebrovascular disease in primary prevention?

Introducción. La concentración plasmática elevada de homocisteína (Hcy) o hiperhomocisteinemia se asocia a un aumento del riesgo de enfermedad vascular en estudios de casos y controles, y, en menor grado, en estudios prospectivos. Desarrollo. Han finalizado ya diversos grandes estudios aleatorios, doble ciego y controlados con placebo, que se realizaron con el objetivo de estudiar si había una reducción del riesgo vascular al disminuir la concentración plasmática de Hcy mediante tratamientos vitamínicos específicos (folatos y/o vitaminas B12 y B6). Su objetivo era analizar si esta estrategia reducía el riesgo de enfermedad cardiovascular (estudios HOPE, NORVIT, WAFACS y WENBIT) y cerebrovascular (estudio VISP) en un contexto de prevención secundaria. Los resultados obtenidos a partir de estos estudios y un metaanálisis, que incluye otros más pequeños hasta un total de 12, mostraron que el tratamiento disminuye la concentración plasmática de Hcy, pero no el riesgo vascular. Es, sin embargo, interesante señalar que un metaanálisis reciente que analizó los efectos de estos tratamientos vitamínicos detectó un efecto protector significativo en la prevención primaria del ictus. Estos datos son consistentes con el hecho de que la hiperhomocisteinemia se relaciona más con el riesgo cerebrovascular que con el cardiovascular. Y también con la observación reciente de que la suplementación con ácido fólico en las harinas está asociada con una disminución en la mortalidad por ictus en Estados Unidos y Canadá. Conclusiones. Obviamente, estos datos requerirán de posterior confirmación, pero parece que ahora existen razones que permiten esperar un desenlace positivo de los estudios de intervención para disminuir la Hcy (AU)

Introduction. High plasma homocysteine (Hcy) concentration or hyperhomocysteinemia is associated with an increased vascular risk of disease in case-control studies and, to a lesser extent, in prospective studies. Development. Several large randomized, double-blind, placebo-controlled trials have been already conducted using specific vitamin therapies with the aim of reducing secondary cardiovascular (HOPE, NORVIT, WAFACS and WENBIT studies) and cerebrovascular (VISP study) disease risk. The results from these major secondary prevention trials and one meta-analysis, that included other smaller studies up to 12 of them, showed that treatment decreased plasma Hcy concentration but failed to reduce cardiovascular risk. It is nevertheless noteworthy that a recent meta-analysis addressing the effects of these vitamin treatments on cerebrovascular risk found a positive effect on primary stroke prevention. These data would be consistent with the fact that increased Hcy is known to be associated more strongly with stroke risk than with cardiovascular risk. Moreover, folic acid supplementation in grain food has recently been shown to be associated with a decreased stroke incidence in USA and Canada. Conclusions. Obviously, these data on primary stroke prevention will require extensive confirmation. However, there now appear to be more reasons to expect a positive outcome of Hcy intervention studies (AU)

Disodium ascorbyl phytostanol phosphate (FM-VP4), a modified phytostanol, is a highly active hypocholesterolaemic agent that affects the enterohepatic circulation of both cholesterol and bile acids in mice.

Disodium ascorbyl phytostanol phosphate (FM-VP4) is a synthetic compound derived from sitostanol and campestanol that has proved to be efficient as a cholesterol-lowering therapy in mice and human subjects. However, the mechanism of action of FM-VP4 remains unknown. The present study tests the ability of FM-VP4 to alter intestinal and liver cholesterol homeostasis in mice. Female C57BL/6J mice were fed either a control chow or a 2 % FM-VP4-enriched diet for 4 weeks. FM-VP4 reduced the in vivo net intestinal cholesterol absorption and plasma and liver cholesterol concentrations by 2.2-, 1.5- and 1.6-fold, respectively, compared with control mice. Furthermore, FM-VP4 also showed an impact on bile acid homeostasis. In FM-VP4 mice, liver and intestinal bile acid content was increased by 1.3- and 2.3-fold, respectively, whereas faecal bile acid output was 3.3-fold lower. FM-VP4 also increased the intestinal absorption of orally administered [3H]taurocholic acid to small intestine in vivo. Inhibition of intestinal cholesterol absorption by FM-VP4 was not mediated via transcriptional increases in intestine liver X receptor (LXR)-alpha, adenosine triphosphate-binding cassette transporter (ABC)-A1, ABCG5/G8 nor to decreases in intestinal Niemann-Pick C1-like 1 (NPC1L1) expression. In contrast, FM-VP4 up-regulated liver LXRalpha, ABCA1, ABCG5, scavenger receptor class BI (SR-BI) and hydroxymethylglutaryl coenzyme A reductase (HMGCoA-R) gene expression, whereas it down-regulated several farnesoid X receptor (FXR)-target genes such as cytochrome P450 family 7 subfamily A polypeptide 1 (CYP7A1) and Na+/taurocholate co-transporter polypeptide (NTCP). In conclusion, FM-VP4 reduced intestinal cholesterol absorption, plasma and liver cholesterol and affected bile acid homeostasis by inducing bile acid intestinal reabsorption and changed the liver expression of genes that play an essential role in cholesterol homeostasis. This is the first phytosterol or stanol that affects bile acid metabolism and lowers plasma cholesterol levels in normocholesterolaemic mice.