The Electrophilicities of XCF3 and XCl (X=H, Cl, Br, I) and the Propensity of These Molecules To Form Hydrogen and Halogen Bonds with Lewis Bases: An Ab Initio Study.

Equilibrium dissociation energies, De , of four series of halogen- and hydrogen-bonded complexes B⋅⋅⋅XCF3 (X=H, Cl, Br and I) are calculated ab initio at the CCSD(T)(F12c)/cc-pVDZ-F12 level. The Lewis bases B involved are N2 , CO, PH3 , C2 H2 , C2 H4 , H2 S, HCN, H2 O and NH3 . Plots of De versus NB , where the NB are the nucleophilicities assigned to the Lewis bases previously, are good straight lines through the origin, as are those for the corresponding set of complexes B⋅⋅⋅XCl. The gradients of the De versus NB plots define the electrophilicities EXCF3 and EXCl of the various Lewis acids. The determined values are: EXCF3 =2.58(22), 1.40(9), 2.15(2) and 3.04(9) for X=H, Cl, Br and I, respectively, and EXCl =4.48(22), 2.31(9), 4.37(27) and 6.06(37) for the same order of X. Thus, it is found that, for a given X, the ratio EXCl / EXCF3 is 2 within the assessed errors, and therefore appears to be independent of the atom X and of the type of non-covalent interaction (hydrogen bond or different varieties of halogen bond) in which it is involved. Consideration of the molecular electrostatic surface potentials shows that De and the maximum positive electrostatic potential σmax (the most electrophilic region of XCF3 and XCl, which lies on the symmetry axes of these molecules, near to the atom X) are strongly correlated.

A Commensal Strain of Staphylococcus epidermidis Overexpresses Membrane Proteins Associated with Pathogenesis When Grown in Biofilms.

Staphylococcus epidermidis has emerged as one of the major nosocomial pathogens associated with infections of implanted medical devices. The most important factor in the pathogenesis of these infections is the formation of bacterial biofilms. Bacteria grown in biofilms are more resistant to antibiotics and to the immune defence system than planktonic bacteria. In these infections, the antimicrobial therapy usually fails and the removal of the biofilm-coated implanted device is the only effective solution. In this study, three proteomic approaches were performed to investigate membrane proteins associated to biofilm formation: (i) sample fractionation by gel electrophoresis, followed by isotopic labelling and LC-MS/MS analysis, (ii) in-solution sample preparation, followed by isotopic labelling and LC-MS/MS analysis and (iii) in-solution sample preparation and label-free LC-MS/MS analysis. We found that the commensal strain S. epidermidis CECT 231 grown in biofilms expressed higher levels of five membrane and membrane-associated proteins involved in pathogenesis: accumulation-associated protein, staphylococcal secretory antigen, signal transduction protein TRAP, ribonuclease Y and phenol soluble modulin beta 1 when compared with bacteria grown under planktonic conditions. These results indicate that a commensal strain can acquire a pathogenic phenotype depending on the mode of growth.

New antimicrobial contact catalyst killing antibiotic resistant clinical and waterborne pathogens.

Microbial growth on medical and technical devices is a big health issue, particularly when microorganisms aggregate to form biofilms. Moreover, the occurrence of antibiotic-resistant bacteria in the clinical environment is dramatically growing, making treatment of bacterial infections very challenging. In search of an alternative, we studied a novel antimicrobial surface coating based on micro galvanic elements formed by silver and ruthenium with surface catalytic properties. The antimicrobial coating efficiently inhibited the growth of the nosocomial pathogens Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis and Enterococcus faecium as demonstrated by the growth inhibition on agar surface and in biofilms of antibiotic resistant clinical E. faecalis, E. faecium, and S. aureus isolates. It also strongly reduced the growth of Legionella in a drinking water pipeline and of Escherichia coli in urine. We postulate a mode of action of the antimicrobial material, which is independent of the release of silver ions. Thus, the novel antimicrobial coating could represent an alternative to combat microbial growth avoiding the toxic side effects of high levels of silver ions on eukaryotic cells.

Self-assembly structures of 1H-indazoles in the solution and solid phases: a vibrational (IR, FIR, Raman, and VCD) spectroscopy and computational study.

1H-indazoles are good candidates for studying the phenomena of molecular association and spontaneous resolution of chiral compounds. Thus, because the 1H-indazoles can crystallize as dimers, trimers, or catemers, depending on their structure and the phase that they are in, the difficulty in the experimental analysis of the structure of the family of 1H-indazoles becomes clear. This difficulty leads us to contemplate several questions: How can we determine the presence of different structures of a given molecular species if they change according to the phase? Could these different structures be present in the same phase simultaneously? How can they be determined? To shed light on these questions, we outline a very complete strategy by using various vibrational spectroscopic techniques that are sensitive (VCD) and insensitive (IR, FIR, and Raman) towards the chirality, together with quantum chemical calculations.

Phytostabilization of metal contaminated soils.

The contamination of soils with heavy metals represents a worldwide environmental problem of great concern. Traditional methods for the remediation of metal contaminated soils are usually very expensive and frequently induce adverse effects on soil properties and biological activity. Consequently, biological methods of soil remediation like phytoremediation (the use of green plants to clean up contaminated sites) are currently receiving a great deal of attention. In particular, chemophytostabilization of metal contaminated soils (the use of metal tolerant plants together with different amendments like organic materials, liming agents, or phosphorus compounds and such) to reduce metal mobility and bioavailability in soils appears most promising for sites contaminated with high levels of several metals when phytoextraction is not a feasible option. During chemophytostabilization processes, one must at all times be cautious with a possible future reversal of soil metal immobilization, with concomitant adverse environmental consequences.

Dendroremediation of heavy metal polluted soils.

Heavy metals are among the most common and harmful pollutants reaching the soil ecosystem all over the world. Phytoextraction is an effective, non-intrusive, inexpensive, aesthetically pleasing, socially accepted, highly promising phytotechnology for the remediation of soils polluted with heavy metals. To overcome the so-called 'Achilles' heel' of phytoextraction, namely, the long time needed for effective remediation, this phytotechnology should be combined with other profit-making activities such as forestry or bioenergy production. Dendroremediation, or the use of trees to clean up polluted soil and water, appears of great potential for metal phytoextraction, especially when using fast-growing tree species, for example, willows (Salix sp. pl.) and poplars (Populus sp. pl.). Most important, the ecologic and environmental risks of dispersing heavy metals into the ecosystems by dendroremediation strategies should be minimized by selecting the right tree species, properly managing/disposing the polluted plant material, or a combination of both options.

Bioluminescent bacterial biosensors for the assessment of metal toxicity and bioavailability in soils.

A major factor governing the toxicity of heavy metals in soils is their bioavailability. Traditionally, sequential extraction procedures using different extractants followed by chemical analysis have been used for determining the biologically available fraction of metals in soils. Yet, the transfer of results obtained on non-biological systems to biological ones is certainly questionable. Therefore, bioluminescence-based bacterial biosensors have been developed using genetically engineered microorganisms, constructed by fusing transcriptionally active components of metal resistance mechanisms to lux genes from naturally bioluminescent bacteria like Vibrio fischeri for the assessment of metal toxicity and bioavailability in polluted soils. As compared to chemical methods, bacterial biosensors present certain advantages, such as selectivity, sensitivity, simplicity, and low cost. Despite certain inherent limitations, bacterial bioluminescent systems have proven their usefulness in soils under laboratory and field conditions. Finally, green fluorescent protein-based bacterial biosensors are also applicable for determining with high sensitivity the bioavailability of heavy metals in soil samples.

Guía de práctica clínica sobre asma (2ª parte) / Clinical practice guideline on asthma (part II)

No disponible

Guía de práctica clínica sobre asma (1ª parte) / Clinical practice guideline on asthma (part I)

No disponible

Phytoextraction and phytofiltration of arsenic.

Arsenic, a ubiquitous contaminant in groundwater and soils, is currently drawing much public attention. Arsenic-contaminated soils can be cleaned up via phytoextraction-the use of plants to extract the arsenic from soil and transport it into aboveground tissues. Arsenic removal from polluted soils can be carried out using hyperaccumulator ferns like the Chinese brake fern Pteris vittata, which accumulates very high concentrations of the element in aboveground tissues. The capacity of the plant to take up large concentrations of arsenic, even at low levels in soil, illustrates efficient bioaccumulation. The possibility of using Pteris ferns to remove arsenic from water by phytofiltration has been proposed.

Climbing a ladder: a step-by-step approach to understanding the concept of agroecosystem health.

Population and individual health is linked to agroecosystem health. To comprehend the concept of agroecosystem health, one should climb a ladder consisting of several successive steps, each rung presenting a certain degree of instability (conceptual difficulty and uncertainty) in an advisable but not inevitable order. Here we suggest a ladder consisting of the following concepts: ecosystem, agroecosystem, biodiversity, sustainability, ecosystem health, and agroecosystem health. Although these concepts are to a certain extent well understood and grasped by scientists, politicians, natural resource managers, and environmentalists, some steps are still highly debatable, unclear, and present a considerable degree of reluctance to be defined and understood. Consequently, much empirical and theoretical effort must be made to construct solid conceptual ladders made up of such steps. In this enterprise, a traditional reductionistic approach confining interpretations to narrow scientific disciplines is unadvisable. Holistic, transdisciplinary approaches are required to reach the desired goal.

[Induced prescription in primary health care in area Bilbao]. / Prescripción inducida en atención primaria de la Comarca Bilbao.

MAIN OBJECTIVES: to know the proportion of induced prescription (IP) in Area Bilbao and its source, the proportion of cost IP accounts for, the proportion of IP in the main therapeutic groups, the attitude of GP when requested for prescription and its influence on cost, the proportion of disagreement with requested prescription, the reasons for disagreement, and the proportion with letter from specialist. SECONDARY OBJECTIVES: to know the proportion of IP in the remaining therapeutic groups, in drugs of low clinical value, in generic drugs and in new drugs with low or no therapeutic improvement. DESIGN: A descriptive cross-sectional study.Setting. Primary health care. PARTICIPANTS: Drugs prescribable under National Health Service prescribed by and/or requested to GPs. Main results. 7.922 drugs were analysed. Type of prescription: IP, 48.3% (95% CI, 47.2-49.4); GP prescription (GPP), 50.6% (95% CI, 49.5-51.7); unknown source, 1,1% (95% CI, 0.9-1.3). Main source, public specialist (72.2%), private specialist (16.6%). IP accounted for 62.5% of cost. In the most prescribed therapeutic group, central nervous system (24.2%), IP, 39.8%; GPP, 58.9%; in cardiovascular system (19.1%), IP, 56.2%; GPP, 43.1%. 98.4% of requested prescription was actually prescribed, 1.2% was changed and 0.4%, suppressed. Proportion of disagreement, 11%; reasons for disagreement, no need for medical treatment (23.9%), therapeutic group (34.4%), active ingredient (13.2%), brand name (28.5%). There was a 62.4% with letter from specialist. CONCLUSIONS: Primary care is not accountable for a substantial proportion of prescription. GP prescribes a considerable proportion of drugs without agreement. It would be necessary a system that allows to separate the cost by care levels and also improve their communication.

Phytoremediation of organic contaminants in soils.

Soil pollution, a very important environmental problem, has been attracting considerable public attention over the last decades. Unfortunately, the enormous costs associated with the removal of pollutants from soils by means of traditional physicochemical methods have been encouraging companies to ignore the problem. Phytoremediation is an emerging technology that uses plants to clean up pollutants in the environment. As overwhelmingly positive results have become available regarding the ability of plants to degrade certain organic compounds, more and more people are getting involved in the phytoremediation of organic contaminants. Phytoremediation of organics appears a very promising technology for the removal of these contaminants from polluted sites.

A solid-state NMR, X-ray diffraction, and ab initio computational study of hydrogen-bond structure and dynamics of pyrazole-4-carboxylic acid chains.

Using high-resolution solid-state (15)N CMAS NMR, X-ray crystallography, and ab initio calculations, we have studied the structure of solid pyrazole-4-carboxylic acid (1). The crystal structure was determined at 295 and 150 K. Molecules of 1 are located on a two-fold axis, implying proton disorder of the NH and OH groups; no phase transition was observed between these two temperatures. The compound forms quasi-linear ribbons in which the molecules are linked by cyclic hydrogen bonds between pyrazole and carboxylic acid groups with disordered hydrogen-bonded protons. Crystallography is unable to decide whether the disorder is dynamic or static. NMR shows that this disorder is dynamic, that is, consisting of very fast degenerate double proton transfers between two rapidly interconverting O-H.N and O.H-N hydrogen bridges. However, at low temperature, NMR shows a proton disorder-order transition where the protons are preferentially localized on given nitrogen and oxygen atoms. An amorphous phase exhibiting proton order is observed when the compound is precipitated rapidly. In this case, the defects are annealed by moderate heating. Ab initio calculations performed on oligomers of 1 show that the O-H.N hydrogen bridge is about 0.064 A shorter and less bent ( approximately 171 degrees ) than the O.H-N hydrogen bridge ( approximately 150 degrees ). For an isolated ribbon, this result leads to structures with localized protons, either to a cycle with about 200 molecules, or to a quasi-linear ribbon involving an undulated structure, or to a combination of both motifs. Only the undulated structure is compatible with the linear ribbon observed by X-ray crystallography, where the fast proton transfer in the high-temperature phase is assisted by the motions of the undulated chain. A disordered structure is assigned to the amorphous phase, which exhibits the combination of the curved and the undulated motifs.

Phytoextraction: a cost-effective plant-based technology for the removal of metals from the environment.

Phytoremediation is an emerging technology that uses plants to clean up pollutants (metals and organics) from the environment. Within this field of phytoremediation, the utilization of plants to transport and concentrate metals from the soil into the harvestable parts of roots and above-ground shoots is usually called phytoextraction. Most traditional remediation methods do not provide acceptable solutions for the removal of metals from soils. By contrast, phytoextraction of metals is a cost-effective approach that uses metal-accumulating plants to clean up these soils. Subsequently, the harvestable parts, rich in accumulated metals, can be easily and safely processed by drying, ashing or composting. Some extracted metals can also be reclaimed from the ash, generating recycling revenues. Phytoextraction appears a very promising technology for the removal of metal pollutants from the environment and may be, at present, approaching commercialization.

Supramolecular structure of 1H-pyrazoles in the solid state: a crystallographic and ab initio study.

The secondary structure of 1H-unsubstituted pyrazole derivatives bearing only one hydrogen donor group and one or more acceptor groups has been analyzed in terms of some descriptors representing the substituents at C3 and C5. The substituent at C4 appears to affect mainly the tertiary or quaternary structure of these compounds. The proposed semi-quantitative model, which explains most hydrogen-bonded motifs as a combination of the effects of substituents at C3 and C5, has also been examined as a function of the steric and polarizability effects of these substituents represented by molar refractivity. The model also applies to other five-membered rings (1,2,4-triazoles, 1,2,4-diazaphospholes and 1,2, 4-diazaarsoles). Furthermore, ab initio calculations at RHF/6-31G* have been performed to discover the relative stability of three of the four hydrogen-bond patterns displayed by several symmetrical pyrazoles (dimers, trimers, tetramers). The fourth motif, catemers, has only been discussed geometrically.

Novel bronchodilators: synthesis, transamination reactions, and pharmacology of a series of pyrazino[2,3-c][1,2,6]thiadiazine 2, 2-dioxides.

The synthesis, pharmacological evaluation, and structure-activity relationships of a new class of bronchodilator agents, derivatives of pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxides are described. The compounds were prepared by reaction of 3,4,5-triamino-1,2, 6-thiadiazine 1,1-dioxide with suitable 1,2-dicarbonyl compounds or alpha-hydroxyiminoketones and subsequent N-alkylation. A transamination procedure for synthesizing derivatives with different substituents at the 4-amino group is reported for the first time. The pyrazino[2,3-c][1,2,6]thiadiazine derivatives were screened for tracheal relaxing activity in vitro, and the active compounds were evaluated in vivo in guinea pigs as bronchodilator agents in comparison to theophylline. Among the compounds studied, the most interesting properties were displayed by the 4-amino-1-ethyl-6-methyl derivative (21). The toxicological evaluation of this derivative is also reported.

Vibrational spectra of 3,5-dimethylpyrazole and deuterated derivatives.

The infrared (IR) and Raman spectra of 3,5-dimethylpyrazole have been recorded in the vapor, liquid (melt and solution) and solid states. Two deuterated derivatives, C5H7N-ND and C5D7N-NH, were also studied in solid state and in solutions. Instrumental resolution was relatively low, 2.0 cm(-1) in the IR and approximately 2.7 cm(-1) in the Raman spectra. The solids are made of cyclic hydrogen-bonded trimers. These trimers, present also in chloroform and acetone solutions, give rise to characteristic high absorption IR spectra in the 3200-2500 cm(-1) region, related to Fermi resonance involving nu(NH) vibrations. Bands from trimers are not present in water solutions but these solutions show spectral features similar in several ways to those of the trimer, attributable to solvent-bonded complexes. Evidence of H-bonding interactions with the other solvents is also visible in the high-frequency region. The two very intense bands in the Raman spectra of the solids appearing at 115 and 82 cm(-1) in the parent compound are also connected with a trimer formation. To interpret the experimental data, ab initio computations of the harmonic vibrational frequencies and IR and Raman intensities were carried out using the Gaussian 94 program package after full optimization at the RHF/6-31G* level for the three monomeric compounds as well as for three models of the trimer, with C3h, C3 and C1 symmetry. The combined use of experiments and computations allow a firm assignment of most of the observed bands for all the systems. In general, the agreement between theory and experiment is very good, with the exception of the IR and Raman intensities of some transitions. Particularly noticeable is the failure of the theoretical calculation in accounting for the high intensity of the Raman bands of the solid about 115 and 82 cm(-1).