Docosahexaenoic Acid and Melatonin Prevent Impaired Oligodendrogenesis Induced by Intrauterine Growth Restriction (IUGR).

In this study, our aims were to characterize oligodendrogenesis alterations in fetuses with intrauterine growth restriction (IUGR) and to find therapeutic strategies to prevent/treat them using a novel rabbit in vitro neurosphere culture. IUGR was surgically induced in one uterine horn of pregnant rabbits, while the contralateral horn served as a control. Neural progenitor cells (NPCs) were obtained from pup's whole brain and cultured as neurospheres mimicking the basic processes of brain development including migration and cell differentiation.

Developmental exposure to MDMA (ecstasy) in zebrafish embryos reproduces the neurotoxicity adverse outcome 'lower motor activity' described in humans.

The recreational use of MDMA (ecstasy) by pregnant women is associated with impaired neuromotor function in infants, but the Adverse Outcome Pathway behind this effect is not clear yet. We present for the first time the evaluation of developmental neurotoxic (DNT) effects of MDMA in zebrafish embryos. The aim of the study was to determine whether the zebrafish model reproduces the adverse outcome occurring in humans.

From virtual screening hits targeting a cryptic pocket in BACE-1 to a nontoxic brain permeable multitarget anti-Alzheimer lead with disease-modifying and cognition-enhancing effects.

Starting from six potential hits identified in a virtual screening campaign directed to a cryptic pocket of BACE-1, at the edge of the catalytic cleft, we have synthesized and evaluated six hybrid compounds, designed to simultaneously reach BACE-1 secondary and catalytic sites and to exert additional activities of interest for Alzheimer's disease (AD). We have identified a lead compound with potent in vitro activity towards human BACE-1 and cholinesterases, moderate Aβ42 and tau antiaggregating activity, and brain permeability, which is nontoxic in neuronal cells and zebrafish embryos at concentrations above those required for the in vitro activities. This compound completely restored short- and long-term memory in a mouse model of AD (SAMP8) relative to healthy control strain SAMR1, shifted APP processing towards the non-amyloidogenic pathway, reduced tau phosphorylation, and increased the levels of synaptic proteins PSD95 and synaptophysin, thereby emerging as a promising disease-modifying, cognition-enhancing anti-AD lead.

Rabbit neurospheres as a novel in vitro tool for studying neurodevelopmental effects induced by intrauterine growth restriction.

The aim of this study was to develop a rabbit neurosphere culture to characterize differences in basic processes of neurogenesis induced by intrauterine growth restriction (IUGR). A novel in vitro neurosphere culture has been established using fresh or frozen neural progenitor cells from newborn (PND0) rabbit brains. After surgical IUGR induction in pregnant rabbits and cesarean section 5 days later, neural progenitor cells from both control and IUGR groups were isolated and directly cultured or frozen at -80°C.

Modulation and Protection Effects of Antioxidant Compounds against Oxidant Induced Developmental Toxicity in Zebrafish.

The antioxidant effect of compounds is regularly evaluated by in vitro assays that do not have the capability to predict in vivo protective activity or to determine their underlying mechanisms of action. The aim of this study was to develop an experimental system to evaluate the in vivo protective effects of different antioxidant compounds, based on the zebrafish embryo test. Zebrafish embryos were exposed to tert-butyl hydroperoxide (tBOOH), tetrachlorohydroquinone (TCHQ) and lipopolysaccharides from (LPS), chemicals that are known inducers of oxidative stress in zebrafish.

Developmental neurotoxicity of MDMA. A systematic literature review summarized in a putative adverse outcome pathway.

The increasing use of illegal drugs by pregnant women causes a public health concern because it is associated with health risks for mothers and their developing children. One of such drugs is MDMA (3,4-methylenedioxymethamphetamine) or ecstasy due to its high consumption in relevant age and sex groups and its adverse effects on human and rodent developing brains. To thoroughly review the current knowledge on the developmentally neurotoxic potential of MDMA we systematically collected and summarized articles investigating developmental neurotoxicity (DNT) of MDMA in humans and animals in vivo and in vitro.

Implementation of a functional endpoint to the zebrafish embryotoxicity test to evaluate craniofacial abnormalities.

The inclusion of a read-out to detect functional consequences of craniofacial alterations in the zebrafish embryotoxicity test will allow to evaluate these alterations which are difficult to assess morphologically, and to detect alterations in cranial nerves functions leading to impairment of jaw movements. In this study we have established an ingestion test in zebrafish larvae younger than 120 hpf. To overcome the challenge of evaluating larvae which still do not present independent feeding behaviour, we have tested the ability of 72, 96 or 102 hpf larvae to ingest food mixed with fluorescent microspheres under several conditions (dark/light, with/without shaking) to find the best experimental set-up for the test.

Cardiovascular Effects of PCB 126 (3,3',4,4',5-Pentachlorobiphenyl) in Zebrafish Embryos and Impact of Co-Exposure to Redox Modulating Chemicals.

The developing cardiovascular system of zebrafish is a sensitive target for many environmental pollutants, including dioxin-like compounds and pesticides. Some polychlorinated biphenyls (PCBs) can compromise the cardiovascular endothelial function by activating oxidative stress-sensitive signaling pathways. Therefore, we exposed zebrafish embryos to PCB126 or to several redox-modulating chemicals to study their ability to modulate the dysmorphogenesis produced by PCB126.

Comparison of migration disturbance potency of epigallocatechin gallate (EGCG) synthetic analogs and EGCG PEGylated PLGA nanoparticles in rat neurospheres.

Epigallocatechin gallate (EGCG), the main catechin of green tea, is described to have potential health benefits in several fields like oncology, neurology or cardiology. Currently, it is also under pre-clinical investigation as a potential therapeutic or preventive treatment during pregnancy against developmental adverse effects induced by toxic substances. However, the safety of EGCG during pregnancy is unclear due to its proven adverse effects on neural progenitor cells' (NPCs) migration.

Identification of phenolic compounds in red wine extract samples and zebrafish embryos by HPLC-ESI-LTQ-Orbitrap-MS.

The zebrafish embryo is a highly interesting biological model with applications in different scientific fields, such as biomedicine, pharmacology and toxicology. In this study, we used liquid chromatography/electrospray ionisation-linear ion trap quadrupole-Orbitrap-mass spectrometry (HPLC/ESI-LTQ-Orbitrap-MS) to identify the polyphenol compounds in a red wine extract and zebrafish embryos. Phenolic compounds and anthocyanin metabolites were determined in zebrafish embryos previously exposed to the red wine extract.

Developmental effects and genotoxicity of 10 water disinfection by-products in zebrafish.

Disinfection by-products are contaminants produced during drinking water disinfection. Several DBPs have been implicated in a variety of toxic effects, mainly carcinogenic and genotoxic effects. Moreover, DBPs exposure has also been associated with an increased risk of developmental effects.

Human health risks derived from dietary exposure to toxic metals in Catalonia, Spain: temporal trend.

The present study was aimed at estimating the current (2012) dietary intake of arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) by the population of Catalonia, Spain. The temporal trends with respect to previous surveys, performed in 2000, 2005, and 2008, were also determined. For that purpose, metal concentrations were analyzed in a number of widely consumed foodstuffs.

Heavy metal and metalloids intake risk assessment in the diet of a rural population living near a gold mine in the Peruvian Andes (Cajamarca).

This study evaluates the diet composition of a rural population near a gold mine in the Cajamarca district of Peru. The main consumed items by this population were tubers and cereals, and the mean energy intake (1990 kcal) was shown not to cover the recommended intake values for the male population. The concentrations of As, Cd, Hg, Pb, Zn, Al, Cr and, Cu in drinking water and food samples of items contributing to 91% of this diet (145 samples, 24 different items) were determined and used to calculate their daily intakes for risk assessment.

Occurrence of patulin in organic and conventional apple-based food marketed in Catalonia and exposure assessment.

In the last years, consumption of organic foods has become increasingly popular. Nevertheless, safety of organic foods is still unclear, and needs to be thoroughly evaluated. Patulin is a mycotoxin mainly present in rotten apples and apple-based products.

Assessment of the temporal trend of the dietary exposure to PCDD/Fs and PCBs in Catalonia, over Spain: health risks.

The concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), as well as those of 18 polychlorinated biphenyls (PCBs), including 12-dioxin like (DL)-PCBs, were measured in foodstuffs randomly acquired in Catalonia (Spain) in November-December 2008. A total of 65 composite samples, belonging to various food groups were analyzed by HRGC/HRMS. The dietary intakes of PCDD/Fs and PCBs were subsequently estimated for four age groups of the population of Catalonia: children, teenagers, adults, and seniors, which were in turn divided according to sex.

Environmental versus dietary exposure to POPs and metals: a probabilistic assessment of human health risks.

The human health risks derived from the multipathway/multipollutant exposure to various chemicals were assessed in an area with significant petrochemical activity (Tarragona, Catalonia, Spain). Environmental exposure to several Persistent Organic Pollutants (POPs) (PCDD/Fs, PCBs, PCNs, and PAHs) and metals (As, Cd, Cr, Hg, Mn, Pb, and V) was determined and compared with the dietary intake of these pollutants. The mean environmental exposure to organic pollutants ranged from 6.

Chronic exposure to MDMA (ecstasy) increases DNA damage in sperm and alters testes histopathology in male rats.

3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is consumed mainly by young population. For this reason, it is especially relevant to take into consideration the effects on the reproductive system. The influence of MDMA on the fertility and reproduction of the male rat was assessed in this study.

Determination of aflatoxins in medicinal herbs by HPLC. An efficient method for routine analysis.

A fast and easy to perform method for the routine determination of aflatoxins in medicinal herbs was developed. The described method involves a single-step extraction with a non-chlorinated solvent, an immunoaffinity clean-up and HPLC with fluorescence detection. Whilst assays with naturally contaminated and with spiked samples of several herbs showed that the recoveries were somewhat low and dependent on the kind of sample and the degree of grinding, the intra-batch reproducibility was good, allowing a reliable quantitation by the standard-addition method.

Computational study of the conformational preferences of the (R)-8-amino-pentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecane-8-carboxylic acid monopeptide.

alpha-Amino acids are important building blocks for the synthesis of a large number of bioactive compounds and pharmaceutical drugs. However, a literature survey revealed that no theoretical conformational study of alpha-amino acids with cage carbon frameworks has been performed to date. This paper reports the results of a conformational study on the (R)-8-amino-pentacyclo[5.

Microsomal epoxide hydrolase and glutathione S-transferase polymorphisms in relation to laryngeal carcinoma risk.

Two polymorphic sites of the microsomal epoxide hydrolase gene (EPHX1, 113Tyr-->113His, 139His-->139Arg) and four glutathione S-transferase genes (GSTM1, GSTM3, GSTP1, GSTT1) were genotyped in a group of patients with larynx cancer (N=204) and in a group of healthy controls (N=203), all Spanish caucasians. After adjusting for gender, age, and tobacco smoking, none of the polymorphisms alone were found to be associated with larynx cancer risk. The analysis of EPHX1/GST combinations, however, showed a significant over-representation of patients with a combination of 113Tyr/113Tyr EPHX1 and 105Ile/105Ile GSTP1 (adjusted odds ratio (OR): 1.

Study of the conformational profile of the norbornane analogues of phenylalanine.

The conformational profile of the eight stereoisomeric 2-amino-3-phenylnorbornane-2-carboxylic acids (2-amino-3-phenylbicyclo[2.2.1]heptane-2-carboxylic acids) has been assessed by computational methods.