LC-MS-MS Identification and Determination of the Flavone-C-Glucoside Vicenin-2 in Rat Plasma Samples Following Intraperitoneal Administration of Lychnophora Extract

The flavone C-glucoside, vicenin-2, in semi-purified extracts of the leaves of Lychnophora ericoides was quantified in rat plasma samples using a method based on reversed-phase high performance liquid chromatography coupled to tandem mass spectrometry. Vicenin-2 was analyzed on a LiChrospher (R) RP18 column using an isocratic mobile phase consisting of a mixture of methanol: water (30:70, v/v) plus 2.0% glacial acetic acid at a flow rate of 0.8 mL min(-1). Genistein was used as internal standard. The mass spectrometer was operated in positive ionization mode and analytes were quantified by multiple reaction monitoring at m/z 595 > 457 for vicenin-2 and m/z 271 > 153 for internal standard. Prior to the analysis, each rat plasma sample was acidified with 200 mu L of 50 mmol L(-1) acetic acid solution and extracted by solid-phase extraction using a C18 cartridge. The absolute recoveries were reproducible and the coefficients of variation values were lower than 5.2%. The method was linear over the 12.5 - 1500 ng mL(-1) concentration range and the quantification limit was 12.5 ng mL(-1). Within-day and between-day assay precision and accuracy were studied at three concentration levels (40, 400 and 800 ng mL(-1)) and were lower than 15%. The developed and validated method seems to be suitable for analysis of vicenin-2 in plasma samples obtained from rats that receive a single i.p. dose of 200 mg kg(-1) vicenin-2 extract.

Effects of Caffeoylquinic Acid Derivatives and C-Flavonoid from Lychnophora ericoides on in vitro Inflammatory Mediator Production

In this study we aimed at evaluating the effect of the major polar constituents of the medicinal plant Lychnophora ericoides on the production of inflammatory mediators produced by LPS-stimulated U-937 cells. The 6,8-di-C-beta-glucosylapigenin (vicenin-2) presented no effect on tumor necrosis factor (TNF)-alpha production, but inhibited, in a dose-dependent manner, the production of prostaglandin (PG) E(2) without altering the expression of cyclooxygenase (COX) -2 protein. 3,5-Dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid, at lower concentrations, had small but significant effects on reducing PG E, levels; at higher doses these compounds stimulated PGE(2) and also TNF-alpha production by the cells. All the caffeoylquinic acid derivatives, in a dose-dependent fashion, were able to inhibit monocyte chemoattractant protein-3 synthesis/release, with 4,5-DCQ being the most potent at the highest tested concentration. These results add important information on the effects of plant natural polyphenols, namely vicenin-2 and caffeoylquinic acid derivatives, on the production of inflammatory mediators by cultured cells.

Evaluation of anti-Mycobacterium tuberculosis activity of Campomanesia adamantium (Myrtaceae)

The anti-Mycobacterium tuberculosis activity of Campomanesia adamantium fruits extracts were evaluated. Six compounds, identified as flavanones and chalcones were quantified by HPLC-DAD-UV. Promising antitubercular activity was observed with ethyl acetate extract (MIC 62.5 µg/mL) and their fractions (MIC values ranging from 39 to above 250 µg/mL). The better MIC result of 39 µg/mL was associated with two fractions that contain bigger amounts of 5,7-dihydroxy-6, 8-di-C-methylflavanone and 2',4'-dihydroxy-3',5'-dimethyl-6'-methoxychalcone. These compounds exhibited MICs >250 and 62.5 µg/mL, respectively, while their mixtures showed values ranging from 62.5 to 7.8 µg/mL, demonstrating a synergism between them.

Evaluation of anti-Mycobacterium tuberculosis activity of Campomanesia adamantium (Myrtaceae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Recueil de pièces originales, copies et gravures, formé par GAIGNIÈRES sur les duels et les combats. I Gravures allemandes représentant des duels (fol. 6), tournois et combats, signées « L. C. 1506 » [Lucas de Cranach] (fol. 8), « L. C. 1509 » (fol. 44 et suiv.) en triple exemplaire, et 71). [Cf. Bartsch, Le peintre-graveur, nos 124, 125, 126.] — Gravure de [Jacques Androuet-Ducerceau], avec légende, représentant Le chien de Montargis ou « Le combat d'un chien contre un gentilhomme qui avoit tué son maistre » (fol. 10).

Cartel, en italien, de Cagnino di Gonzaga à Cesare Fregoso. Bozolo,31 juillet 1539 (fol. 112), orig. imprimé, avec le sceau de Gonzaga. — Extraits des Mémoires de Sully (fol. 14). — Duels de Jean de Harcourt et Guillaume III de Tancarville, 1286 (fol. 20), — Raymond du Marcadil de Penne en Agenois et Étienne Donnadieu, 1330 (fol. 24), — M. de Sauvebeuf et Peyrot de Rastinhac, 1587 (fol. 26), — baron de Conros et Carbonat (fol. 29), — Louis de Loudierche, de Grizol et de Cheyladet, 1612 (fol 31, 59), — MM. de Candale et de Schomberg (fol. 36), — combat de la Barrière, 1605 (fol. 37). — Édit de Henri IV défendant les duels (fol. 39). — Accords faits par le connétable, les maréchaux de France et les lieutenants généraux des provinces entre MM. de Clermont et de S. Gery d'Avignon (fol. 50), — de Reilhac et de Drageac (fol. 53), — le duc de Nevers et M. de Montpensier, 1580 (fol. 55), — de Brezolles et de Carluz de Calvimond, 1610 (fol. 57), — de Naves et de Montaignac, 1613 (fol. 61), — le comte de Sault et M. de Brissac, 1638 (fol. 62). — Extraits du « stylus antiquus Parlamenti Parisiensis Caroli Molinoei », éd. 1558 (fol. 66, 72, 74, 156), — du « Coustumier de Normendie », éd. 1539 (fol. 76). — Duels de Jacques Le Gris et Jean de Carouges, 1387 (fol. 84) et autres duels extraits de Froissart (fol. 99 et suiv.). — Lettre orig. de Gaucher de Dinteville à Mgr le Dauphin [Henri II], Venise, 20 décembre 1538 (fol. 142). — « Les Cartelz, reponces et procès-verbaux du different d'entre le sieur de Vassé et le comte Guillaume de Furstenberg, 1540 (fol. 144).

UPTAKE, METABOLISM, AND METABOLIC EFFECTS OF THE ANTITUMOR TRICYCLIC NUCLEOSIDE, 3-AMINO-1, 5-DIHYDRO-5-METHYL-1-BETA-D-RIBOFURANOSYL-1, 4, 5, 6, 8 PENTAAZAACENAPHTHYLENE

The uptake, metabolism, and metabolic effects of the antitumor tricyclic nucleoside (TCN, NSC-154020) were studied in vitro. Uptake of TCN by human erythrocytes was concentrative, resulting mainly from the rapid intracellular phosphorylation of TCN. At high TCN doses, however, unchanged TCN was also concentrated within the erythrocytes. The initial linear rate of TCN uptake was saturable and obeyed Michaelis-Menten kinetics. TCN was metabolized chiefly to its 5'-monophosphate not only by human erythrocytes but also by wild-type Chinese hamster ovary (CHO) cells. In addition, three other metabolites were detected by means of high-performance liquid chromatography. The structures of these metabolites were elucidated by ultraviolet spectroscopy, infrared spectroscopy, mass spectrometry, and further confirmed by incubations with catabolic enzymes and intact wild-type or variant CHO cells. All were novel types of oxidative degradation products of TCN. Two are proposed to be (alpha) and (beta) anomers of a D-ribofuranosyl nucleoside with a pyrimido{4,5-c}pyridazine-4-one base structure. The third metabolite is most likely the 5'-monophosphate of the (beta) anomer. A CHO cell line deficient in adenosine kinase activity failed to phosphorylate either TCN or the (beta) anomer. No further phosphorylation of the 5'-monophosphates by normal cells occurred. Although the pathways leading to the formation of these TCN metabolites have not been proven, a mechanism is proposed to account for the above observations. The same adenosine kinase-deficient CHO cells were resistant to 500 (mu)M TCN, while wild-type cells could not clone in the presence of 20 (mu)M TCN. Simultaneous addition of purines, pyrimidines, and purine precursors failed to reverse this toxicity. TCN-treatment strongly inhibited formate or glycine incorporation into ATP and GTP of wild-type CHO cells. Hypoxanthine incorporation inhibited to a lesser degree, with the inhibition of incorporation into GTP being more pronounced. Although precursor incorporation into GTP was inhibited, GTP concentrations were elevated rather than reduced after 4-hr incubations with 20 (mu)M or 50 (mu)M TCN. These results suggested an impairment of GTP utilization. TCN (50 (mu)M) inhibited leucine and thymidine incorporation into HClO(,4)-insoluble material to 30-35% of control throughout 5-hr incubations. Incorporation of five other amino acids was inhibited to the same extent as leucine. Pulse-labeling assays (45 min) with uridine, leucine, and thymidine failed to reveal selective inhibition of DNA or protein synthesis by 0.05-50 (mu)M TCN; however, the patterns of inhibition were similar to those of known protein synthesis inhibitors. TCN 5'-monophosphate inhibited leucine incorporation by rabbit reticulocyte lysates; the inhibition was 2000 times less potent than that of cycloheximide. The 5'-monophosphate failed to inhibit a crude nuclear DNA-synthesizing system. Although TCN 5'-monophosphate apparently inhibits purine synthesis de novo, its cytotoxicity is not reversed by exogenous purines. Consequently, another mechanism such as direct inhibition of protein synthesis is probably a primary mechanism of toxicity. ^

Elastic scattering and total reaction cross sections for the (8)B, (7)Be, and (6)Li+(12)C systems

Angular distributions for the elastic scattering of (8)B, (7)Be, and (6)Li on a (12)C target have been measured at E(lab) = 25.8, 18.8, and 12.3 MeV, respectively. The analyses of these angular distributions have been performed in terms of the optical model using Woods-Saxon and double-folding type potentials. The effect of breakup in the elastic scattering of (8)B + (12)C is investigated by performing coupled-channels calculations with the continuum discretized coupled-channel method and cluster-model folding potentials. Total reaction cross sections were deduced from the elastic-scattering analysis and compared with published data on elastic scattering of other weakly and tightly bound projectiles on (12)C, as a function of energy. With the exception of (4)He and (16)O, the data can be described using a universal function for the reduced cross sections.

2,6,,9-trioxabicyclo[3.3.1]nona-3,7-dienes and 2,4,6,8-tetraoxaadamantanes: Novel chiral spacer units in macrocyclic polyethers

The unusual chiral heterocyclic systems, trioxabicyclo[3.3.1]nona-3,7-dienes (bridged bisdioxines), are incorporated as novel spacer molecules into macrocyclic polyether ring systems of various sizes (8, 9 as well as 11-15) by cyclocondensation reaction of the! bisacid chloride 4b or bisesters 6,7 and 10, with several ethylene glycols. The 2:2 macrocycles 12-14 are obtained in approximately 50:50 mixtures of diastereomers. These conclusions are mainly based on HPLC data presented in Table I as well as X-ray analyses of (1R,5R)-8c (space group Pbca, a = 10.163(3) Angstrom, b = 18.999(4) Angstrom, c = 36.187(10) Angstrom, V = 6987(3) Angstrom(3), Z = 8, d(calc) = 1.218 g cm(-3), 6974 reflections, R = 0.0553.), mesolrac-11 (space group P (1) over bar, a = 10.472(5) Angstrom, b = 16.390(5) Angstrom, c = 17.211(5) Angstrom, alpha = 98.69(2)degrees, beta = 93.04(2)degrees, gamma = 98.52(2)degrees, V = 2879.3(18) Angstrom(3), Z = 2, d(calc) = 1.173 g cm(-3), 11,162 reflections, R = 0.0945) and meso-12 (space group P2(1)/c, a = 9.927(2), b = 18.166(3), c = 17.820(3) Angstrom, beta = 96.590(10)degrees, V = 3192.3(10)Angstrom(3), Z = 4, D-c = 1.109 g cm(-3), 3490 reflections, R = 0.0646). The 1:1 macrocycles 8b,c are also formed by intramolecular transesterification of the open-chain bisesters 7b,c and their formation is favored by the use of metal ions as templates. The bridged bisdioxine moieties in 8b and 12 are converted into the corresponding chiral tetra-oxaadamantane spacers to afford macrocycles 16 and 17. Preliminary metal ion complexation studies with selected species (8c, 11-14) were also performed.

Razonamiento : lógico, matemático, temporal, espacial : c. inicial 6-8 años.

Material práctico de apoyo psicopedagógico para el desarrollo, afianzamiento o recuperación de la capacidad de pensar y razonar. Se aportan ejercicios que ofrecen diversas posibilidades de aplicación de los aspectos de razonamiento lógico, matemático, temporal y espacial. Se incluyen series lógicas, semejanzas y diferencias entre dibujos, búsqueda de relaciones entre conceptos representados a través del dibujo, etc. Al final aparecen las respuestas correctas de los diversos ejercicios.

Riabilitazione del mascellare posteriore atrofico mediante impianti corti (6-8 mm) o rialzo di seno con contestuale inserimento di impianti di lunghezza standard: studio retrospettivo con follow up a 3 anni

Background: sebbene la letteratura recente abbia suggerito che l’utilizzo degli impianti corti possa rappresentare una alternative preferibile alle procedure di rigenerazione ossea nelle aree posteriori atrofiche, perché è un trattamento più semplice e con meno complicazioni, esistono solo pochi studi a medio e lungo termine che abbiano comparato queste tecniche. Scopo: lo scopo di questo studio retrospettivo è quello di valutare se gli impianti corti (6-8 mm) (gruppo impianti corti) possano presentare percentuali di sopravvivenza e valori di riassorbimento osseo marginali simili a impianti di dimensioni standard (≥11 mm) inseriti contemporaneamente ad una grande rialzo di seno mascellare. Materiali e Metodi: in totale, 101 pazienti sono stati inclusi: 48 nel gruppo impianti corti e 53 nel gruppo seno. In ciascun paziente da 1 a 3 impianti sono stati inseriti e tenuti sommersi per 4-6 mesi. I parametri clinici e radiografici valutati sono: i fallimenti implantari, le complicazioni, lo stato dei tessuti molli, e il riassorbimento osseo marginale. Tutti i pazienti sono stati seguiti per almeno 3 anni dal posizionamento implantare. Risultati: il periodo di osservazione medio è stato di 43.47 ± 6.1 mesi per il gruppo impianti corti e 47.03 ± 7.46 mesi per il gruppo seno. Due su 101 impianti corti e 6 su 108 impianti standard sono falliti. Al follow-up finale, si è riscontrato un riassorbimento osseo medio di 0.47 ± 0.48 mm nel gruppo impianti corti versus 0.64 ± 0.58 mm nel gruppo seno. Non sono presenti differenze statisticamente significative fra i gruppi in termini di fallimenti implantari, complicazioni protesiche, tessuti molli, e riassorbimento osseo. Il gruppo seno ha presentato, invece, un maggior numero di complicazioni chirurgiche. Conclusioni: entrambe le tecniche hanno dimostrato un simile tasso di successo clinico e radiografico, ma gli impianti corti hanno ridotto il numero di complicazioni chirurgiche.

Call to action : better nutrition for mothers, children, and families : December 6-8, 1990, Washington, D.C. /

"This publication has been produced by the National Center for Education in Maternal and Child Health under its cooperative agreement (MCU-117007) with the Maternal and Child Health Bureau, Health Resources and Services Administration, Public Health Service, U.S. Department of Health and Human Services"--Verso of t.p.

Research in nonlinear structural and solid mechanics : keynote address and panel discussion presented at a symposium sponsored by NASA Langley Research Center, Hampton, Virginia, and the George Washington University, Washington, D.C., in cooperation with the National Science Foundation, the American Society of Civil Engineers, and the American Society of Mechanical Engineers, and held at Washington, D.C., October 6-8, 1980 /

Includes bibliographical references.

Synthesis and anticancer activity of N3-substituted-6,8-diaminopurines

[Excerpt] Cancer is the second most common cause of death in developed countries appearing just after cardiovascular diseases. The treatment of cancer remains a major medical challenge and the development of new anticancer drugs is an emerging topic for the scientific community. During the past three decades several chemical classes of anticancer drugs have been identified. In particular, 2,6-diamino purines proved to be important candidates as new anti-cancer agents.