Dietary Sodium Nitrate Activates Antioxidant and Mitochondrial Dynamics Genes after Moderate Intensity Acute Exercise in Metabolic Syndrome Patients.

Exercise can induce a pro-inflammatory response in aged subjects with metabolic disorders and nitrate supplementation has shown anti-inflammatory effects. We evaluated the influence of dietary nitrate on the response of the antioxidant and mitochondrial dynamics genes to acute exercise in peripheral blood mononuclear cells (PBMCs), as well as the antioxidant and the inflammatory response of PBMCs against immune stimulation. Metabolic syndrome patients participated in a crossover study in which they consumed a beverage containing 16 mM sodium nitrate or a placebo with the same composition without nitrate before performing a submaximal test at 60%-70% of their maximal heart rate for 30 min. The intake of nitrate increased the nitrate plus nitrite plasma levels about 8-fold and induced the upregulation of catalase, superoxide dismutase, glutathione peroxidase, mitofusin 2 and PGC1α in PBMCs after exercise. The gene expression of catalase and TNFα was enhanced by phorbol myristate acetate (PMA) only in the placebo group, while the glutathione peroxidase expression was enhanced by PMA only after nitrate intake. The intake of nitrate by metabolic syndrome patients induces an antioxidant and mitochondrial response to exercise at the same time that it attenuates the pro-inflammatory response to immune stimulation.

Oral Administration of Sodium Nitrate to Metabolic Syndrome Patients Attenuates Mild Inflammatory and Oxidative Responses to Acute Exercise.

The beneficial effects of exercise for the treatment and prevention of metabolic syndrome pathologies have been related to its anti-inflammatory and antioxidant effects. Dietary nitrate supplementation is an emerging treatment strategy to alleviate the symptoms of metabolic syndrome affections and to improve vascular function. In this double-blind crossover trial, metabolic syndrome patients performed two exercise tests for 30 min at 60-70% maximal heart rate after the intake of a placebo or a nitrate-enriched beverage. Acute exercise increased the plasma concentration of TNFα, intercellular adhesion molecule ICAM1, PGE1, PGE2 and the newly detected 16-hydroxypalmitic acid (16-HPAL) in metabolic syndrome patients. The cytokine and oxylipin production by peripheral blood mononuclear cells (PBMCs) and neutrophils could be responsible for the plasma concentrations of TNFα and IL6, but not for the plasma concentration of oxylipins nor its post-exercise increase. The intake of sodium nitrate 30 min before exercise increased the concentration of nitrate and nitrite in the oral cavity and plasma and reduced the oxygen cost of exercise. Additionally, nitrate intake prevented the enhancing effects of acute exercise on the plasma concentration of TNFα, ICAM1, PGE1, PGE2 and 16-HPAL, while reducing the capabilities of PBMCs and neutrophils to produce oxylipins.

Enhanced functionality for donor-acceptor oligothiophenes by means of inclusion of BODIPY: synthesis, electrochemistry, photophysics, and model chemistry.

We have synthesized several new push-pull oligothiophenes based on the boron dipyrromethene (BODIPY) moiety as the electron acceptor and the more well-known oligothiophenes substituted with N,N-dialkylamino functions to enhance their electron-donor ability. A complete characterization of the electronic properties has been carried out; it consists of their photophysical, electrochemical, and vibrational properties. The compounds have been studied after chemical treatment with acids and after oxidation. In this regard, they can be termed as NIR dyes and amphoteric redox electroactive molecules. We have described the presence of dual fluorescence in these molecules and fluorescence quenching either by energy transfer or, in the push-pull molecules, by electron exchange. The combination of electrochemical and proton reversibility along with the interesting optical properties of the new species offer an interesting platform for sensor and material applications.

Theoretical and experimental studies on the mechanism of norbornadiene Pauson-Khand cycloadducts photorearrangement. Is there a pathway on the excited singlet potential energy surface?

The intermolecular Pauson-Khand reaction (PKR), a carbonylative cycloaddition between an alkyne and an alkene, is a convenient method to prepare cyclopentenones. Using norbornadiene as alkene, a myriad of tricyclo[5.2.1.0(2,6)]deca-4,8-dien-3-ones 1 can be easily prepared. The mechanism of the photochemical rearrangement of these adducts 1 into tricyclo[5.2.1.0(2,6)]deca-3,8-dien-10-ones 2 has been studied. The ground state (S(0)) and the three lowest excited states ((3)(pi pi*), (1)(n pi*), and (3)(n pi*)) potential energy surfaces (PESs) concerning the prototypical rearrangement of 1a (the cycloadduct of the PK carbonylative cycloaddition of norbornadiene and ethyne) to 2a have been thoroughly explored by means of CASSCF and CASPT2 calculations. From this study, two possible nonadiabatic pathways for the photochemical rearrangement arise: one starting on the (3)(pi pi*) PES and the other on the (1)(n pi*) PES. Both involve initial C-C gamma-bond cleavage of the enone, which leads to the formation of a bis-allyl or an allyl-butadienyloxyl diradical, respectively, that then decays to the S(0) PES through a (3)(pi pi*)/S(0) surface crossing or a (1)(n pi*)/S(0) conical intersection, each one lying in the vicinity of the corresponding diradical minimum. Once on the S(0) PES, the ring-closure to 2a occurs with virtually no energy barrier. The viability of both pathways was experimentally studied by means of triplet sensitization and quenching studies on the photorearrangement of the substituted Pauson-Khand cycloadduct 1b (R = TMS, R' = H) to 2b. Using high concentrations of either piperylene as a triplet quencher, or benzophenone as a triplet sensitizer, the reaction rate significantly slowed down. A Stern-Volmer type plot of product 2b concentration vs triplet quencher concentration showed an excellent linear correlation, thus indicating that only one excited state is involved in the photorearrangement. We conclude that, though there is a nonadiabatic pathway starting on the (1)(n pi*) PES, the reaction product is formed through the (3)(pi pi*) state because the energy barrier involved in the initial C-C gamma-bond cleavage of the enone is much lower in the (3)(pi pi*) PES than in the (1)(n pi*) PES.

Dendrimerized cellulose as a scaffold for artificial antigens with applications in drug allergy diagnosis.

Cellulose-based dendrimerized material was prepared and its quality was assessed by determining the number of amine functional groups incorporated. Based on the results for a series of preparations, the material was obtained in a highly reproducible manner thanks to the particular chemical construction method used. The number of amine groups incorporated and the amount of dendrimer attached are directly related to the dendrimer generation. The combination of the properties of the cellulose polymer and those of the dendrimeric state provides biocompatible materials amenable to easy chemical characterization. The proposed method provides an effective tool for developing clinically testable materials with a view to studying adverse immunological responses to drugs in humans.

A molecular 1 : 2 demultiplexer.

A dual-channel fluorescent compound runs as a 1 : 2 digital demultiplexer (DEMUX) which can drive a single signal (proton) to two different destinations as a fluorescent photonic response; each fluorescent channel can be activated independently by careful selection of the excitation wavelength.

Partial demethylation of oligogalacturonides by pectin methyl esterase 1 is required for eliciting defence responses in wild strawberry (Fragaria vesca).

In addition to the role of the cell wall as a physical barrier against pathogens, some of its constituents, such as pectin-derived oligogalacturonides (OGA), are essential components for elicitation of defence responses. To investigate how modifications of pectin alter defence responses, we expressed the fruit-specific Fragaria x ananassa pectin methyl esterase FaPE1 in the wild strawberry Fragaria vesca. Pectin from transgenic ripe fruits differed from the wild-type with regard to the degree and pattern of methyl esterification, as well as the average size of pectin polymers. Purified oligogalacturonides from the transgenic fruits showed a reduced degree of esterification compared to oligogalacturonides from wild-type fruits. This reduced esterification is necessary to elicit defence responses in strawberry. The transgenic F. vesca lines had constitutively activated pathogen defence responses, resulting in higher resistance to the necrotropic fungus Botrytis cinerea. Further studies in F. vesca and Nicotiana benthamiana leaves showed that the elicitation capacity of the oligogalacturonides is more specific than previously envisaged.

Una experiencia única: 24 horas a nado. A propósito de un caso / An unic experience: 24 hours swimming. A case

Se presenta la experiencia de un nadador paralímpico de élite que nadó durante 24 horas seguidas una distancia de 58,5 km en una piscina climatizada de 50 metros. En los últimos tres meses se realizó un control nutricional y médico, incluidas analíticas. Inmediatamente antes de la pruebas se controlaron parámetros fisiológicos. Asimismo se realizó antes y después de la prueba una valoración del estado de ánimo del nadador. Durante la prueba se cuantificaron la cantidad de nutrientes y líquidos que el nadador iba ingiriendo. Se dispusieron paradas de 5 minutos cada hora, momentos utilizado para ingestión de alimentos,toma de frecuencias cardíacas, valoracióndel grado de cansancio, aplicación de vaselina y evaluar y solucionar cualquier problema que se presentase. Se disminuyó la cloración del agua de la piscina, y se aumentó a 30 grados su temperatura. Observamos un paralelismo entre la frecuencia cardiaca y la sensación subjetiva de fatiga, con valores altos al principio (145 lpm y 9 de fatiga) y una estabilización en valores inferiores (105 lpm y 6 de fatiga) a partir de las 6 h. de la prueba. Hubo un incremento de la actividad CPK (166U/L) y una leucocitosis (16400/mcl) con neutrofilia (82,7%). El deportista ingirió 3621 Kcal (93% CH, 6% Prot. 1% Lip.) y 6524 ml de agua. Las puntuaciones obtenidas en la escala de vigor antes (p=70) y después de la prueba (p=67) están por encima de las consideradas óptimas, en cambio las de fatiga están dentro de los valores óptimos

We expose the experience of a elit paralimpic swimmer who swan for 24 hours a distance of 58,8 km at a 50 m. acclimated swimming-pool. Three months before the event it was made a medical and nutritional control, blodd test included. Physiologic parameters were controlled just before the event. A psicological control was also made to asses the mood of the swimmer before and after the event. During the event we quantified the nutrients and liquid the swimmer was having. We program breaks of 5 minutes per hour to ear and take heart rate, assess the grade of fatigue, put some vaseline on the skin of the swimmer and assist and solve any problem. The chlorination of the water of the swimming-pool was reduced and the temperature was increased up to 30 grades C. We observed parallelism between the heart rate and the subjective feeling of fatigue, with high values at the beguinning (145 bpm and 9 of fatigue) and a stabilization at low values (105 bpm and 6 of fatigue) from the sith hour of the event. There was a increase of the CK activity (1661 U/L) and a leukocytosis (16400/mcl) with neutrophilia (82,7%). The swimmer ingested 3621 Kcal (93% Carbohydrates, 6% Proteins., 1% Lipids.) and 6524 ml. of water. the scoring obtained in the vigor scale before (p=70) and after the event (p=67) were higher up than the values believed optimun, however, the scoring in fatigue were just optimun

Photoinduced addition of phthalimide to unactivated alkynes.

Photoexcited phthalimide in equilibrium with its conjugated base produces the regioselective hydrophthalimidation of conjugated alkynes. The vinylphthalimide thus obtained is hydrolyzed to the corresponding carbonyl compound. With unconjugated alkynes, the outcome is a double addition of phthalimide to the triple bond. The reaction is assumed to take place via single electron transfer from either the alkyne or the phthalimide anion to the excited phthalimide as the primary photoprocess.

Cephalosporin chemical reactivity and its immunological implications.

PURPOSE OF REVIEW: The aim of this article is to analyze the chemical reactivity of cephalosporins resulting in the epitope responsible for recognition by IgE antibodies and to establish the basis of the allergenicity. RECENT FINDINGS: Increasing evidence supports the role of cephalosporins in IgE hypersensitivity reactions. Third and fourth generation cephalosporins appear to be more involved in specific IgE reactions and often no cross-reactivity with traditional benzyl penicillin determinants exists. In some instances selective responses to unique cephalosporins occur and in others common side-chain similarities exist. SUMMARY: Lack of knowledge of the exact chemical structure of cephalosporin antigenic determinants has hindered clinical interpretation of allergic reactions to these drugs and hampered understanding of the specific recognition by IgE molecules of these determinants. Data indicate that R2 is not present in the final conjugate and that recognition by IgE antibodies is mainly directed to the R1 acyl side chain and to the beta-lactam fragment that remains linked to the carrier protein in the cephalosporin conjugation process.

Photochemistry of phytoalexins containing phenalenone-like chromophores: photophysics and singlet oxygen photosensitizing properties of the plant oxoaporphine alkaloid oxoglaucine.

Oxoglaucine (OG) is an oxoaporphine alkaloid, which has been linked to plant defense mechanisms. It contains a phenalenone (PN)-like chromophore, which suggests a role as singlet oxygen ((1)O(2)) photosensitizer. Indeed, OG is able to photosensitize (1)O(2) with 100% efficiency in nonpolar environments, similar to PN. However, this efficiency decreases in polar and protic media, although (1)O(2) is formed in all environments ranging from benzene to water. OG is a rather inefficient (1)O(2) quencher (k(q) = 8 x 10(5) M(-1) s(-1)) unlike the related alkaloids boldine and glaucine, for which an antioxidant role has been suggested. The results of this study contribute to the view that plant defense mediated by PN-like secondary metabolites may have a photochemical component.

Synthesis and characterization of a new bisphosphonic acid and several metal hybrids derivatives.

Commercial bis-(4-bromophenyl)-ether, [BrC(6)H(4)](2)-O, has been used to prepare 4-[4'-(diethoxyphosphoryl)phenoxy]phenyl-phosphonic acid diethyl ester, [(CH(3)CH(2))(2)O(3)P-C(6)H(4)](2)-O, (I) following a slight modification of the Michaelis-Arbuzov reaction. The acid hydrolysis of I gave 4-(4'-phosphonophenoxy)phenyl phosphonic acid, [H(2)O(3)P-C(6)H(4)](2)-O (II), and both compounds have been characterized by (1)H NMR and (13)C NMR. The crystal structure of II has been determined by single-crystal X-ray diffraction. II crystallizes in an orthorhombic unit cell, space group Pbcn, with a = 7.822(3) A, b = 5.821(2) A, c = 28.982(9) A, and V = 1319.7(7) A(3). The final R factor was R1 = 0.0614. The structure is layered, being held together through a hydrogen bonding network. II has been used as precursor in the syntheses of new metal (Mn, Fe, Co, Ni, Cu, and Zn) bisphosphonates. The syntheses were carried out using a fixed metal/bisphosphonic acid molar ratio of 2.1:1 and the influence of the pH in the reactions has been studied. Nine new compounds have been isolated: Mn(2)(O(3)PC(6)H(4)OC(6)H(4)PO(3)).1.5H(2)O (III), Mn(5)(OH)(2)(O(3)PC(6)H(4)OC(6)H(4)PO(3))(2).2H(2)O (IV), Fe(HO(3)PC(6)H(4)OC(6)H(4)PO(3)).0.5H(2)O (V), Co(2)(O(3)PC(6)H(4)OC(6)H(4)PO(3)).2H(2)O (VI), Ni(2)(O(3)PC(6)H(4)OC(6)H(4)PO(3)).3H(2)O (VII), Ni(2)(O(3)PC(6)H(4)OC(6)H(4)PO(3)).2H(2)O (VIII), Cu(2)(O(3)PC(6)H(4)OC(6)H(4)PO(3)) (IX), Zn(2)(O(3)PC(6)H(4)OC(6)H(4)PO(3)) (X), and Zn(HO(3)PC(6)H(4)OC(6)H(4)PO(3)H) (XI). Compound IX crystallizes in an orthorhombic unit cell, space group Pbcn, and unit cell parameters a = 8.1012(5) A, b = 5.3109(3) A, c = 29.2595(5) A, and V = 1258.8(1) A(3). Its structure has been solved by ab initio powder diffraction and refined by the Rietveld method to R(F) = 0.042. IX has a pillared layer framework with highly distorted CuO(5) groups sharing edges to give isolated dimers. XI was indexed in a monoclinic unit cell, space group P112(1), with parameters a = 9.4991(9) A, b = 5.0445(5) A, c = 29.131(2) A, gamma = 91.945(7) degrees, and V = 1395.1(3) A(3). Its structure has been refined by the Rietveld method, R(F) = 0.054, since it is isostructural with the known compound, Zn[HO(3)P(C(6)H(4))(2)PO(3)H]. All solids were also characterized by thermal analysis and IR and UV-Vis spectroscopies.

Immediate allergic reactions to betalactams: facts and controversies.

PURPOSE OF REVIEW: To analyse the available data in the field of immediate allergic reactions to beta-lactams, with particular emphasis on more recent studies, and to comment on the future role of this group of antibiotics. RECENT FINDINGS: The world of beta-lactams has become more complex than initially thought, due to the increased number of chemical structures available, the wide variety of indications for their use in treating different infectious diseases, and possibly also due to the interaction of other as yet undetermined factors. Benzyl penicillin, the original inducer of allergic reactions, has now largely been replaced by amoxicillin and, to a lesser extent, by cephalosporins in inducing IgE-mediated allergic reactions. These structures often share extensive cross-reactivity, eliciting clinical reactions to many compounds, especially amongst penicillins. In other circumstances selective responses are observed which are restricted to one group or one single compound, as occurs in the group of cephalosporins. The application of new determinants for skin testing and the use of adapted in-vitro studies have enabled these findings to be confirmed in detail. SUMMARY: Results indicate that evaluation of immediate reactions to beta-lactams requires the use of several determinants for both in-vitro and in-vivo testing, and which must reflect the relevant drug involved in eliciting the response. This tendency will be strengthened in the future if use of benzyl penicillin continues to decrease as a drug to which populations are exposed.

A natural-product-inspired photonic logic gate based on photoinduced electron-transfer-generated dual-channel fluorescence.

[structure: see text] Modified 1-benzylisoquinoline N-oxides can operate as molecular logic gates. The combination of dual-channel fluorescence emissions and the preferred interaction for selected chemical inputs allows one to design multifunction and self-reprogrammable molecular logic gates.

Synthesis, characterization and immunochemical evaluation of cephalosporin antigenic determinants.

Lack of knowledge of the exact chemical structure of cephalosporin antigenic determinants has hindered clinical interpretation of adverse reactions to these drugs and delayed understanding of the mechanisms involved in the specific recognition and binding of IgE molecules to these antigenic determinants. We further resolve the relationship between structure and activity of proposed antigenic chemicals, including the rational design and synthesis of these haptenic structures. Comparative RAST inhibition studies of the synthesized molecules revealed that they were recognized by IgE antibodies induced by cephalosporin antibiotics. Thus, these data indicate that recognition is mainly directed to the acyl side chain and to the beta-lactam fragment that remains linked to the carrier protein in the cephalosporin conjugation course.

Covalently linked acceptor-donor systems based on isoquinoline N-oxide acceptor: photoinduced electron transfer produces dual-channel luminescent systems that evolve chemically to photohydroxylation of the aromatic donor.

Acceptor-donor compounds containing the isoquinoline N-oxide acceptor and (methoxy)(n)benzene (n = 0, 1, 2, 3) electron donors were studied. The two chromophores are connected by a CH(2) bridging unit. All acceptor-donor compounds exhibit photoinduced electron transfer in acid medium that results in the formation of a charge-transfer (CT) state. Measurements of the corresponding electronic emission spectra revealed that these bichromophoric systems exhibit a dual fluorescence that is strongly dependent on the protonation of the N-oxide function and the donor ability. The CT state responsible for the red-shifted luminescence in the studied compounds is directly connected with the initial excited state S(1). On the basis of the spectroscopic and photochemical evidence, N[bond]O scission is the dominant primary photochemical process involving the CT state, the subsequent radical coupling resulting in efficient aromatic hydroxylation. The outcome of both quenching and sensitization experiments confirms this assertion. The results strongly suggest that the ensuing photohydroxylation reaction is not a concerted process, but rather a two-step N[bond]O scission followed by C[bond]O formation, which is regioselectively guided by the electronic distribution of the resulting donor cation-radical.

Dendrimers as carrier protein mimetics for IgE antibody recognition. Synthesis and characterization of densely penicilloylated dendrimers.

The synthesis of benzylpenicilloyl-containing dendrimers has been achieved by a convenient procedure involving quantitative functionalization of the terminal amino groups of the three Starbust PAMAM generations used (G(n); n = 0, 1, 2). All these densely penicilloylated dendrimers (G(n)P) exhibit similar, simple NMR spectroscopic data suggesting highly symmetric structures and a monodisperse nature, and the results obtained from MALDI-TOF-MS demonstrate their exact chemical composition. The use of PAMAM dendrimers has allowed us to synthesize, for the first time, carrier benzylpenicilloyl conjugates (G(n)P) of precisely defined chemical structure. The attempts to synthesize G(2)P show that forced experimental conditions are not always useful for the functionalization of the dendrimer, especially in introducing bulky groups. The initial results with sera from patients with different RAST levels were positive and thus suggestive that inhibition occurs, so recognition exists; we can therefore conclude that the hapten-carrier (dendrimer) conjugates studied mimic recognition with natural hapten-carrier (protein) conjugates.

Bis(isoquinoline N-oxide) pincers as a new type of metal cation dual channel fluorosensor.

[structure: see text] A new type of donor-spacer-acceptor podand system has been synthesized and proved as an efficient dual channel fluorosensor for Li+, Mg2+, and Ca2+. The known ability for the N-oxide function to bind Lewis acids is the key step in the appearance of a new emitting charge-transfer (CT) excited state. The occurrence of this CT state for alkaline earth (Mg2+ and Ca2+) and not for alkaline metals (Li+) provided a new type of dual channel fluorosensors.