Study of the first step of hydrogen release in ammonia borane using high-resolution Raman spectroscopy and different heating ramps.

Ammonia borane, as a source of hydrogen, has attracted much attention due to its high hydrogen content, low molecular weight, and high stability in solution. However, the process and enhancement of hydrogen release must be done practically under ambient conditions. For this work, Raman spectroscopy, principal component analysis (PCA), and molecular simulation were applied to study the hydrogen release process of ammonia borane. Three stages of release were observed from room temperature to 1300 °C. The shift, the appearance, and the disappearance of the Raman bands were evident in the whole process. In-situ monitoring of Raman and PCA, with four different heating rates between 70 and 130 °C, was done; ammonia borane showed visible variations in its first release step, in which a fast rate helped reduce distortion in the release process. Finally, molecular simulation of ammonia borane using the Density Functional Theory (DFT) in calculations showed that dihedral rotation and stretching of the hydrogen bonds can occur before the first release step.

Effect of bovine viral diarrhea virus on subsequent infectivity of bovine gammaherpesvirus 4 in endometrial cells in primary culture: An in vitro model of viral co-infection.

Bovine viral diarrhea virus (BVDV) and bovine gammaherpesvirus 4 (BoHV-4) infect the uterus of cattle, being responsible for huge economic losses. Most of the pathogenesis of BoHV-4 in the bovine reproductive tract has been elucidated by conducting tests on primary cultures. Thus, it is important to have optimal in vitro conditions, avoiding the presence of other pathogens that can alter the results. BVDV is one of the most frequent viral contaminants of cell cultures. Considering that non-cytopathic (NCP) BVDV biotype can generate persistently infected (PI) cattle, which are the major source for virus transmission in susceptible herds, it is important to check products derived from cattle that are intended to be used in research laboratories. The aim of this work was to evaluate how the natural infection of bovine endometrial cells (BEC) with a NCP BVDV strain (BEC + BVDV) affects BoHV-4 replication. We have demonstrated a delay in BoHV-4 gene expression and a decrease in viral load in the extracellular environment in BEC + BDVD cells compared to BEC (BVDV-free) cells. These results confirm that replication of BoHV-4 in BEC primary cultures is affected by previous infection with BVDV. This finding highlights the importance of ruling out BVDV infection in bovine primary cell cultures to avoid biological interference or misinterpretation of results at the time of performing in vitro studies with BoHV-4.

Gene expression and in vitro replication of bovine gammaherpesvirus type 4.

In vitro cell cultures are widely used models for dissecting cellular and molecular mechanisms that lead to certain physiological conditions and diseases. The pathogenesis of BoHV-4 in the bovine reproductive tract has been studied by conducting tests on primary cultures. However, many questions remain to be answered about the role of BoHV-4 in endometrial cells. The aim of this study was to compare the replication and gene expression of BoHV-4 in cell lines and bovine reproductive tract primary cells as an in vitro model for the study of this virus. We demonstrated that BoHV-4 strains differ in their in vitro growth kinetics and gene expression but have the same cell type preference. Our results demonstrate that BoHV-4 replicates preferentially in bovine endometrial cells (BEC). However, its replication capacity extends to various cell types, since all cells that were tested were permissive to BoHV-4 infection. The highest virus titers were obtained in BEC cells. Nevertheless, virus replication efficiency could not be fully predicted from the mRNA expression profiles. This implies that there are multiple cell-type-dependent factors and strain properties that determine the level of BoHV-4 replication. The results of this study provide relevant information about the in vitro behavior of two field isolates of BoHV-4 in different cell cultures. These findings may be useful for the design of future in vitro experiments to obtain reliable results not only about the pathogenic role of BoHV-4 in the bovine female reproductive tract but also in the development of efficient antiviral strategies.

Ammonia borane structural study by temperature through high-resolution Raman spectroscopy and principal component analysis.

The structural change by temperature of the ammonia borane has been studied through Raman spectroscopy and principal components analysis (PCA). Its phase transition, from tetragonal to orthorhombic, was observed at 212 K. In addition, between 99 and 83 K, a zone of structural stability was observed. These behaviors could be observed thanks to the application of the PCA technique to the Raman data. Here, we can find a characteristic Raman signal which can also be associated with the orthorhombic structure. Also using the PCA technique, we have observed two Raman bands in the low frequency region, below 100 cm-1, which could be associated with the lattice vibrational contribution.

Differences in clinical manifestations and increased severity of systemic lupus erythematosus between two groups of Hispanics: European Caucasians versus Latin American mestizos (data from the RELESSER registry).

BACKGROUND: Systemic lupus erythematosus (SLE) is regarded as a prototype autoimmune disease because it can serve as a means for studying differences between ethnic minorities and sex. Traditionally, all Hispanics have been bracketed within the same ethnic group, but there are differences between Hispanics from Spain and those from Latin America, not to mention other Spanish-speaking populations. OBJECTIVES: This study aimed to determine the demographic and clinical characteristics, severity, activity, damage, mortality and co-morbidity of SLE in Hispanics belonging to the two ethnic groups resident in Spain, and to identify any differences. METHODS: This was an observational, multi-centre, retrospective study. The demographic and clinical variables of patients with SLE from 45 rheumatology units were collected. The study was conducted in accordance with Good Clinical Practice guidelines. Hispanic patients from the registry were divided into two groups: Spaniards or European Caucasians (EC) and Latin American mestizos (LAM). Comparative univariate and multivariate statistical analyses were carried out. RESULTS: A total of 3490 SLE patients were included, 90% of whom were female; 3305 (92%) EC and 185 (5%) LAM. LAM patients experienced their first lupus symptoms four years earlier than EC patients and were diagnosed and included in the registry younger, and their SLE was of a shorter duration. The time in months from the first SLE symptoms to diagnosis was longer in EC patients, as were the follow-up periods. LAM patients exhibited higher prevalence rates of myositis, haemolytic anaemia and nephritis, but there were no differences in histological type or serositis. Anti-Sm, anti-Ro and anti-RNP antibodies were more frequently found in LAM patients. LAM patients also had higher levels of disease activity, severity and hospital admissions. However, there were no differences in damage index, mortality or co-morbidity index. In the multivariate analysis, after adjusting for confounders, in several models the odds ratio (95% confidence interval) for a Katz severity index >3 in LAM patients was 1.45 (1.038-2.026; p = 0.02). This difference did not extend to activity levels (i.e. SLEDAI >3; 0.98 (0.30-1.66)). CONCLUSION: SLE in Hispanic EC patients showed clinical differences compared to Hispanic LAM patients. The latter more frequently suffered nephritis and higher severity indices. This study shows that where lupus is concerned, not all Hispanics are equal.

Fine-tuning the neuroprotective and blood-brain barrier permeability profile of multi-target agents designed to prevent progressive mitochondrial dysfunction.

Alzheimer's disease is an irreversible, complex and progressive neurodegenerative disorder associated with oxidative stress and mitochondrial dysfunction. Exogenous antioxidants can be beneficial for decreasing oxidative stress, as they are able to reward the lack of efficacy of the endogenous defense systems and raise the overall antioxidant response in a pathological condition. Along our overarching project related with the design and development of potent and safe multi-target mitochondriotropic antioxidants, based on dietary antioxidants, novel derivatives were obtained. Overall, mitochondriotropic antioxidants showed remarkable antioxidant and chelating properties, presenting low cytotoxic effects on human differentiated neuronal (SH-SY5Y) and hepatocarcinoma (HepG2) cells and exhibited neuroprotective properties on SH-SY5Y cells against 6-hydroxydopamine (6-OHDA) or hydrogen peroxide (H2O2) oxidative insults. Moreover, compounds 58, 59, 62, 63, 66 and 67 were able to permeate a layer of hCMEC/D3 cells in a time-dependent manner. Mitochondriotropic antioxidant 67 stands out by its remarkable iron chelating and neuroprotective properties toward both H2O2 and 6-OHDA-induced oxidative damage, drug-like properties and BBB permeability.

In silico genotoxicity of coumarins: application of the Phenol-Explorer food database to functional food science.

Coumarins are a group of phytochemicals that may be beneficial or harmful to health depending on their type and dosage and the matrix that contains them. Some of these compounds have been proven to display pro-oxidant and clastogenic activities. Therefore, in the current work, we have studied the coumarins that are present in food sources extracted from the Phenol-Explorer database in order to predict their clastogenic activity and identify the structure-activity relationships and genotoxic structural alerts using alternative methods in the field of computational toxicology. It was necessary to compile information on the type and amount of coumarins in different food sources through the analysis of databases of food composition available online. A virtual screening using a clastogenic model and different software, such as MODESLAB, ChemDraw and STATISTIC, was performed. As a result, a table of food composition was prepared and qualitative information from this data was extracted. The virtual screening showed that the esterified substituents inactivate molecules, while the methoxyl and hydroxyl substituents contribute to their activity and constitute, together with the basic structures of the studied subclasses, clastogenic structural alerts. Chemical subclasses of simple coumarins and furocoumarins were classified as active (xanthotoxin, isopimpinellin, esculin, scopoletin, scopolin and bergapten). In silico genotoxicity was mainly predicted for coumarins found in beer, sherry, dried parsley, fresh parsley and raw celery stalks. The results obtained can be interesting for the future design of functional foods and dietary supplements. These studies constitute a reference for the genotoxic chemoinformatic analysis of bioactive compounds present in databases of food composition.

Randomized comparison of three transducer orientation approaches for ultrasound guided internal jugular venous cannulation.

BACKGROUND: Ultrasound-guided internal jugular venous access increases the rate of successful cannulation and reduces the incidence of complications, compared with the landmark technique. Three transducer orientation approaches have been proposed for this procedure: short-axis (SAX), long-axis (LAX) and oblique-axis (OAX). Our goal was to assess and compare the performance of these approaches. METHODS: A prospective randomized clinical trial was conducted in one teaching hospital. Patients aged 18 yr or above, who were undergoing ultrasound-guided internal jugular cannulation, were randomly assigned to one of three intervention groups: SAX, LAX and OAX group. The main outcome measure was successful cannulation on first needle pass. Incidence of mechanical complications was also registered. Restricted randomization was computer-generated. RESULTS: In total, 220 patients were analysed (SAX n=73, LAX n=75, OAX n=72). Cannulation was successful on first needle pass in 51 (69.9%) SAX patients, 39 (52%) LAX patients and 53 (73.6%) OAX patients. First needle pass failure was higher in the LAX group than in the OAX group (adjusted OR 3.7, 95% CI 1.71-8.0, P=0.002). A higher mechanical complication rate was observed in the SAX group (15.1%) than in the OAX (6.9%) and LAX (4%) groups (P=0.047). CONCLUSIONS: As OAX showed a higher first needle pass success rate than LAX and a lower mechanical complications rate than SAX, we recommend it as the standard approach when performing ultrasound-guided internal jugular venous access. Further clinical studies are needed to confirm this conclusion. CLINICAL TRIAL REGISTRATION: NCT 01966354.

Molecular and antigenic characterization of bovine Coronavirus circulating in Argentinean cattle during 1994-2010.

Bovine coronavirus (BCoV) is an important viral pathogen associated with neonatal calf diarrhea. Our aim was to investigate the incidence of BCoV in diarrhea outbreaks in beef and dairy herds from Argentina during 1994-2010. A total of 5.365 fecal samples from diarrheic calves were screened for BCoV diagnosis by ELISA. The virus was detected in 1.71% (92/5365) of the samples corresponding to 5.95% (63/1058) of the diarrhea cases in 239 beef and 324 dairy farms. The detection rate of BCoV was significantly higher in dairy than in beef herds: 12.13% (29/239) vs. 4.32% (14/324) respectively. Phylogenetic analysis of the hypervariable S1 region of seven representative samples (from different husbandry systems, farm locations and years of sampling) indicated that BCoV strains circulating in Argentinean beef and dairy herds formed a cluster distinct from other geographical regions. Interestingly, Argentinean strains are distantly related (at both the nucleotide and amino acid levels) with the Mebus historic reference BCoV strain included in the vaccines currently available in Argentina. However, Mebus-induced antibodies were capable of neutralizing the BCoV Arg95, a field strain adapted to grow in vitro, and vice versa, indicating that both strains belong to the same CoV serotype reported in cattle. This work represents the first large survey describing BCoV circulation in Argentinean cattle.

A magnonic gas sensor based on magnetic nanoparticles.

In this paper, we propose an innovative, simple and inexpensive gas sensor based on the variation in the magnetic properties of nanoparticles due to their interaction with gases. To measure the nanoparticle response a magnetostatic spin wave (MSW) tunable oscillator has been developed using an yttrium iron garnet (YIG) epitaxial thin film as a delay line (DL). The sensor has been prepared by coating a uniform layer of CuFe2O4 nanoparticles on the YIG film. The unperturbed frequency of the oscillator is determined by a bias magnetic field, which is applied parallel to the YIG film and perpendicularly to the wave propagation direction. In this device, the total bias magnetic field is the superposition of the field of a permanent magnet and the field associated with the layer of magnetic nanoparticles. The perturbation produced in the magnetic properties of the nanoparticle layer due to its interaction with gases induces a frequency shift in the oscillator, allowing the detection of low concentrations of gases. In order to demonstrate the ability of the sensor to detect gases, it has been tested with organic volatile compounds (VOCs) which have harmful effects on human health, such as dimethylformamide, isopropanol and ethanol, or the aromatic hydrocarbons like benzene, toluene and xylene more commonly known by its abbreviation (BTX). All of these were detected with high sensitivity, short response time, and good reproducibility.

Phylogenetic analyses of typical bovine rotavirus genotypes G6, G10, P[5] and P[11] circulating in Argentinean beef and dairy herds.

Group A rotavirus (RVA) is one of the main causes of neonatal calf diarrhea worldwide. RVA strains affecting Argentinean cattle mainly possess combinations of the G6, G10, P[5] and P[11] genotypes. To determine RVA diversity among Argentinean cattle, representative bovine RVA strains detected in diarrheic calves were selected from a survey conducted during 1997-2009. The survey covered the main livestock regions of the country from dairy and beef herds. Different phylogenetic approaches were used to investigate the genetic evolution of RVA strains belonging to the prevalent genotypes. The nucleotide phylogenetic tree showed that all genotypes studied could be divided into several lineages. Argentinean bovine RVA strains were distributed across multiple lineages and most of them were distinct from the lineage containing the vaccine strains. Only the aminoacid phylogenetic tree of G6 RVA strains maintained the same lineages as observed at the nucleotide level, whereas a different clustering pattern was observed for the aminoacid phylogenetic trees of G10, P[5] and P[11] suggesting that the strains are more closely related at the aminoacid level than G6 strains. Association between P[5] and G6(IV), prevalent in beef herd, and between P[11] and G6(III) or G10 (VI and V), prevalent in dairy herds, were found. In addition, Argentinean G6(III), G10, P[5] and P[11] bovine RVA strains grouped together with human strains, highlighting their potential for zoonotic transmission. Phylogenetic studies of RVA circulating in animals raised for consumption and in close contact with humans, such as cattle, contribute to a better understanding of the epidemiology of the RVA infection and evolution.

Bovine rotavirus strains circulating in beef and dairy herds in Argentina from 2004 to 2010.

Bovine Group A Rotavirus (RVA) is one of the main causes of neonatal calf diarrhea worldwide. The present study reports the genotyping of bovine RVA strains circulating in Argentinean cattle from 2004 to 2010. Additionally, a new set of typing primers was designed and tested to differentiate between G8 and G6 (lineage III and IV) RVA strains. Bovine RVA was detected in 30% (435/1462) of the tested samples, corresponding to 49% (207/423) of the studied outbreaks with a similar detection rates in beef (53%; 67/127) and dairy herds (52%; 65/126). The RVA strains circulating in Argentinean cattle belonged to the common bovine genotypes G6 (lineages III and IV), G8, G10, P[5] and P[11]. A different RVA G/P-genotype distribution was found between the exploitation types, with the combination G6(IV)P[5] being by fare the most prevalent RVA strain in beef herds (58%), whereas a more even distribution of G6(III)P[11] (15%), G10P[11] (17%), G6(IV)P[5] (14%), and G6(IV)P[11] (6%) RVA strains was detected in dairy herds. G8 RVA strains were found in two dairy farms in calves co-infected with G8+G6(III)P[11]. A high percentage of co-infections and co-circulation of RVA strains with different genotypes during the same outbreak were registered in both exploitation types (20% of the outbreaks from beef herds and 23% from dairy herds), indicating a potential environment for reassortment. This finding is significant because G10P[11] and G6(III)P[11] strains may possess zoonotic potential. Continuous surveillance of the RVA strains circulating in livestock provides valuable information for a better understanding of rotavirus ecology and epidemiology.

Spectroscopic and thermodynamic features of conical bubble luminescence.

The influence on luminescence from conical bubble collapse (CBL) with varying Ar gas content while perturbing the liquid 1,2-Propanediol (PD) has been investigated. The temporal, spatial, and spectral features were analysed with regards to the dynamics of collapse and liquid degradation. Sulphuric acid and sodium chloride were added to disturb the liquid. The following three cases were studied: PD/Ar, (I), (PD + H(2)SO(4))/Ar, (II), and (PD + H(2)SO(4) + NaCl)/Ar, (III). The intensities of those cases decrease as III > II > I. Temporally, single and multiple light emissions were found to occur. The pulse shape exhibited a large variety of profiles with a main maximum and up to two local maxima around the main maximum. These local maxima resembled those generated by laser cavitation. Spatially, no radial symmetry was detected in the light emissions. Spectrally, the Swan, CH and CN lines were observed at low volumes of gas and driving pressure. The ·OH radical and OH-Ar bands, as well as the Na and K lines, consistently appeared superimposed on an underlying continuum that almost disappeared in (III). The Na line was observed with two satellite diffuse bands representing Na-Ar complexes in (I) and (II), whereas in (III), only the line of sodium could be seen. Weak and diffuse emission lines from the Ar atom in the near-IR region were observed in (I) and (II). The proposed mechanism of bright CBL was based on the energy transfer from electron-excited homolytic cleavage products to the chromophore molecules generated during the collapse-rebound time line (~8200 K and ~1 ms of collapse time from model), which had accumulated inside the liquid and remained on the walls of cavity during the repetition of the collapse. A general mechanism for the bright CBL is broached.

3D entropy and moments prediction of enzyme classes and experimental-theoretic study of peptide fingerprints in Leishmania parasites.

The number of protein 3D structures without function annotation in Protein Data Bank (PDB) has been steadily increased. This fact has led in turn to an increment of demand for theoretical models to give a quick characterization of these proteins. In this work, we present a new and fast Markov chain model (MCM) to predict the enzyme classification (EC) number. We used both linear discriminant analysis (LDA) and/or artificial neural networks (ANN) in order to compare linear vs. non-linear classifiers. The LDA model found is very simple (three variables) and at the same time is able to predict the first EC number with an overall accuracy of 79% for a data set of 4755 proteins (859 enzymes and 3896 non-enzymes) divided into both training and external validation series. In addition, the best non-linear ANN model is notably more complex but has an overall accuracy of 98.85%. It is important to emphasize that this method may help us to predict not only new enzyme proteins but also to select peptide candidates found on the peptide mass fingerprints (PMFs) of new proteins that may improve enzyme activity. In order to illustrate the use of the model in this regard, we first report the 2D electrophoresis (2DE) and MADLI-TOF mass spectra characterization of the PMF of a new possible malate dehydrogenase sequence from Leishmania infantum. Next, we used the models to predict the contribution to a specific enzyme action of 30 peptides found in the PMF of the new protein. We implemented the present model in a server at portal Bio-AIMS (http://miaja.tic.udc.es/Bio-AIMS/EnzClassPred.php). This free on-line tool is based on PHP/HTML/Python and MARCH-INSIDE routines. This combined strategy may be used to identify and predict peptides of prokaryote and eukaryote parasites and their hosts as well as other superior organisms, which may be of interest in drug development or target identification.

The effect of Nd and Mg doping on the micro-Raman spectra of LiNbO(3) single-crystals.

The LiNbO(3) congruent crystals doped with small Nd concentrations, <1 mol% Nd, and co-doped with Mg ions, 0-9 mol% Mg, were systematically investigated by means of micro-Raman spectroscopy in the Y and Z crystal directions. Results obtained from an undoped congruent crystal, an Nd-doped crystal, a Mg-doped crystal and Nd, Mg-co-doped crystals are compared. From the analyses of the results obtained in the Y direction, the Nd and Mg content dependence of the two lowest-Raman A(1)(TO(1)) and A(1)(TO(2)) modes, the half-width composition and the area ratio of the A(1)(TO(4)) and E(TO(8)) bands, we reached several conclusions about the incorporation mechanism of the Nd and Mg ions into the LiNbO(3) lattice. Likewise the Raman shift and half-width of the E(TO(1)) and E(TO(7)) modes were investigated in the Z direction. Results indicate that Mg and Nd ions are located in the Li site for low doping concentrations and for larger concentrations there is a replacement in both Li and Nb ion sites.

Ligands and therapeutic perspectives of adenosine A(2A) receptors.

Adenosine A(2A) receptors are members of the G protein-coupled receptor family and mediate multiple physiological effects of adenosine, both at the central nervous system (CNS) and at peripheral tissues, by activating several pathways or interacting with other receptors or proteins. Increasing evidence relate A(2A) receptors with pharmacological stress testing, neurodegenerative disorders (such as Parkinson's disease) and inflammation, renewing the interest in these receptors, increasingly viewed as promising therapeutic targets. Series of agonists and antagonists have been developed by medicinal chemistry artwork either by structure activity relationship (SAR) or quantitative structure activity relationship (QSAR) studies. These studies have allowed identification of the structural and electrostatic requirements for high affinity A(2A) receptor binding and, therefore, contributing to the rational design of A(2A) receptor ligands. Additional rational chemical modifications of the existing A(2A) receptor ligands may further improve their affinity/selectivity. The purpose of this review is to analize and summarize aspects related to the medicinal chemistry of A(2A) receptor ligands, their present and potencial therapeutic applications by exploring the molecular structure and physiological and pathophysiological roles of A(2A) receptors.

A comparison of reactivity schemes for the prediction skin sensitization potential.

Skin sensitization is an important toxic end point for both regulatory frameworks and safety assessment. There are many hurdles for a chemical to overcome in terms of inducing skin sensitization, although the binding of chemicals to skin protein is thought to be the rate-determining step. Current strategies to predict the skin sensitization potential of chemicals in silico is through the identification of electrophilic characteristics. A number of predictive schemes have been developed in recent years, some based on broad structural rules and some with a reaction chemistry mechanistic basis. This work compares two schemes that are based on reaction chemistry. The first scheme comprises a set of rules that characterize reaction mechanistic domains as proposed by Aptula and Roberts [(2006) Chem. Res. Toxicol. 19, 1097-1105]. The second is a set of structure-toxicity and structure-metabolism pathways that are encoded and embedded into the TIssue MEtabolism Simulator skin sensitization model (TIMES-SS) [(2005) Int. J. Toxicol. 24, 189-204]. Here, a comparison of these schemes has been made using a recently published data set of 210 chemicals that have been tested in the local lymph node assay. The similarities and differences of the schemes are highlighted, together with modifications that could be made to TIMES-SS to harmonize the two approaches.

An evaluation of selected global (Q)SARs/expert systems for the prediction of skin sensitisation potential.

Skin sensitisation potential is an endpoint that needs to be assessed within the framework of existing and forthcoming legislation. At present, skin sensitisation hazard is normally identified using in vivo test methods, the favoured approach being the local lymph node assay (LLNA). This method can also provide a measure of relative skin sensitising potency which is essential for assessing and managing human health risks. One potential alternative approach to skin sensitisation hazard identification is the use of (Quantitative) structure activity relationships ((Q)SARs) coupled with appropriate documentation and performance characteristics. This represents a major challenge. Current thinking is that (Q)SARs might best be employed as part of a battery of approaches that collectively provide information on skin sensitisation hazard. A number of (Q)SARs and expert systems have been developed and are described in the literature. Here we focus on three models (TOPKAT, Derek for Windows and TOPS-MODE), and evaluate their performance against a recently published dataset of 211 chemicals. The current strengths and limitations of one of these models is highlighted, together with modifications that could be made to improve its performance. Of the models/expert systems evaluated, none performed sufficiently well to act as a standalone tool for hazard identification.

Application of principal component analysis and Raman spectroscopy in the analysis of polycrystalline BaTiO3 at high pressure.

The principal component analysis (PCA) was applied to Raman spectra of polycrystalline BaTiO(3) under pressure from atmospheric pressure to approximately 6.72 GPa. For the system utilized, PCA was able to distinguish spectral features and to determine the phase transition pressure: tetragonal to cubic at approximately 2.0 GPa. The present study demonstrates the potentialities of the application of PCA to the investigation on phase transitions at high pressure by Raman spectroscopy.

Simple coumarins and analogues in medicinal chemistry: occurrence, synthesis and biological activity.

Coumarins, also known as benzopyrones, are present in remarkable amounts in plants, although their presence has also been detected in microorganisms and animal sources. The structural diversity found in this family of compounds led to the division into different categories, from simple coumarins to many other kinds of policyclic coumarins, such as furocoumarins and pyranocoumarins. Simple coumarins and analogues are a large class of compounds that have attracted their interest for a long time due to their biological activities: they have shown to be useful as antitumoural, anti-HIV agents and as CNS-active compounds. Furthermore, they have been reported to have multiple biological activities (anticoagulant, anti-inflammatory), although all these properties have not been evaluated systematically. In addition, their enzyme inhibition properties, antimicrobial and antioxidant activities are other foremost topics of this field of research. The present work is to survey the information published or abstracted from 1990 till 2003, which is mainly related to the occurrence, synthesis and biological importance of simple coumarins and some analogues, such as biscoumarins and triscoumarins. Data are also highlighted, concerning the development of new synthetic strategies that could help in drug design and in the work on SAR or QSAR.