Cobalt complexes bearing scorpionate ligands: Synthesis, characterization, cytotoxicity and DNA cleavage

A number of novel, water-stable redox-active cobalt complexes of the C-functionalized tripodal ligands tris(pyrazolyl)methane XC(pz)(3) (X = HOCH2, CH2OCH2Py or CH2OSO2Me) are reported along with their effects on DNA. The compounds were isolated as air-stable solids and fully characterized by IR and FIR spectroscopies, ESI-MS(+/-), cyclic voltammetry, controlled potential electrolysis, elemental analysis and, in a number of cases, also by single-crystal X-ray diffraction. They showed moderate cytotoxicity in vitro towards HCT116 colorectal carcinoma and HepG2 hepatocellular carcinoma human cancer cell lines. This viability loss is correlated with an increase of tumour cell lines apoptosis. Reactivity studies with biomolecules, such as reducing agents, H2O2, plasmid DNA and UV-visible titrations were also performed to provide tentative insights into the mode of action of the complexes. Incubation of Co(II) complexes with pDNA induced double strand breaks, without requiring the presence of any activator. This pDNA cleavage appears to be mediated by O-centred radical species.

Charting developmental EEG gamma changes in the auditory modality /

The oscillation of neuronal circuits reflected in the EEG gamma frequency may be fundamental to the perceptual process referred to as binding (the integration of various thoughts and perceptions into a coherent picture). The aim of our study was to expand our knowledge of the developmental course ofEEG gamma in the auditory modality. 2 We investigated EEG 40 Hz gamma band responses (35.2 to 43.0 Hz) using an auditory novelty oddball paradigm alone and with a visual-number-series distracter task in 208 participants as a function of age (7 years to adult) at 9 sites across the sagital and lateral axes (F3, Fz, F4, C3, Cz, C4, P3, Pz, P4). Gamma responses were operationally defined as change in power or a change in phase synchrony level from baseline within two time windows. The evoked gamma response was defined as a significant change from baseline occurring between 0 to 150 ms after stimulus onset; the induced gamma response was measured from 250 to 750 ms after stimulus onset. A significant evoked gamma band response was found when measuring changes in both power and phase synchrony. The increase in both measures was maximal at frontal regions. Decreases in both measures were found when participants were distracted by a secondary task. For neither measure were developmental effects noted. However, evoked gamma power was significantly enhanced with the presentation of a novel stimulus, especially at the right frontal site (F4); frontal evoked gamma phase synchrony also showed enhancement for novel stimuli but only for our two oldest age groups (16-18 year olds and adults). Induced gamma band responses also varied with task-dependent cognitive stimulus properties. In the induced gamma power response in all age groups, target stimuli generated the highest power values at the parietal region, while the novel stimuli were always below baseline. Target stimuli increased induced synchrony in all regions for all participants, but the novel stimulus selectively affected participants dependent on their age and gender. Adult participants, for example, exhibited a reduction in gamma power, but an increase in synchrony to the novel stimulus within the same region. Induced gamma synchrony was more sensitive to the gender of the participant than was induced gamma power. While induced gamma power produced little effects of age, gamma synchrony did have age effects. These results confirm that the perceptual process which regulates gamma power is distinct from that which governs the synchronization for neuronal firing, and both gamma power and synchrony are important factors to be considered for the "binding" hypothesis. However, there is surprisingly little effect of age on the absolute levels of or distribution of EEG gamma in the age range investigated.

ESI-MS[n] of anticancer pt[iv] organoamido complexes and their interactions with DNA-model compounds /

The general solution behaviour and" the major fragmentation pathways of the anticanceractive PtIV coordination complexes, trans, trans, cis, cis-[PtCIOH{N(pFC6F4) CH2h(pY)2] (1), trans, cis, cis-[Pt(OH)2{N(p-FC6F4)CH2h(Py)2] (2), trans, cis, cis-[Pt(OH)2{N(p-HC6F4)CH2h(Py)2] (3), trans, trans, cis, cis-[PtCIOH{N(pHC6F4) CH2h(Py)2] (4), and trans, trans, cis, cis-[PtOH(OCH3){N(p-HC6F4)CH2h(PY)2] (5) (Py = pyridine) have been deduced by positive-ion tandem-in-time ESI-MS. Overall, the acquired full-scan, positive-ion ESI-MS spectra of 2, 3, and 5 were characterized by the presence of relatively low-intensity [M+Nar and [M+Kt mass spectral peaks, whereas those of 1 and 4 were dominated by extremely intense [M+Hr peaks. Complexes 2 and 3 were also noted to form [2M+Ht and [2M+Nat dilneric cations. The source of Na + and K+ ions is believed to be the sample, the solvent systems used or the transport line carrying the sample solutions into the ES ion source. Further, the fragmentation pathway of all complexes studied was found to be almost identical with concurrent loss of py and H20 molecules, loss of a {N(p-YC6F4)CH2} (Y = F, H) group and/or concomitant release of the latter group and a py ligand being the most conunon. The photochemical degradation behaviour of 1 and 2 was also investigated using either fluorescent or ultraviolet light and some products of that degradation were positively identified. Altogether, light irradiation of solutions of both complexes resulted in cation cationisation, reductive-elimination, ligand-release, ligand-exchange and ligand-addition reactions. Finally, positive- and negative-ion ESI-MSn spectra of 5' -GMP, guanosine, inosine and products of their reactions with 1, 2,3, and 4 were also recorded. On the whole, full-scan ESI-MS spectra of the pure nucleobases revealed the presence of cationic and anionic species that are highly reflective of both their solution ionic composition and their propensity t9 form polymeric clusters. Analyses of mass spectra acquired from their reaction solutions with the aforementioned platinum complexes indicated very slow kinetics. However, all complexes investigated formed, to various degrees, Pt-nucleobase adducts with guanosine and inosine, but not with 5'-GMP. The products included species having coordination numbers of III, IV, V, and VI, among which the first-time· observed, coordinatively saturated, jive-coordinate PtlI-nucleobase complexes were of most interest. The latter complexes are presumably stabilized by 7tback- donation involving the filled d orbitals of the PtII centre and the empty pz· orbital of MeCN. All products, whose peaks appeared inlull-scan ESI-MS spectra, are believed to represent solution species rather than artifacts of gas-phase processes. Finally, negativeion ESI-MSn spectra recorded in reaction solutions of 1 and 4 with guanosine and of the latter complex with inosine revealed the negative-ion-ESI-MS first-time observed, noncovalent, nucleoside-chloride adducts, with the source of chloride anion being complexes 1 and 4 theillselves. In contrast, no such adducts were observed to form with Na25'-GMP or its protonated fonn. Few suggestions are offered for the possible cause(s) behind the absence of such adduct ions.

Caractérisation du co-transporteur Na+/myo-inositol SMIT2 dans les membranes en bordure en brosse de rein de lapin et d’intestin de rat

Le myo-inositol (MI) est un soluté organique impliqué dans diverses fonctions physiologiques de la cellule dont la signalisation cellulaire. Il est également un osmolyte compatible reconnu. Trois co-transporteurs de type actif secondaire responsables de son absorption ont été identifiés. Deux d’entre eux sont couplés au transport du sodium (SMIT1 et SMIT2) et le troisième est couplé au transport de protons (HMIT). L’objectif de cette étude a été la caractérisation du transport du MI par SMIT2 dans des membranes en bordure en brosse (BBMv) issues du rein de lapin et de l’intestin de rat ainsi qu’après expression dans les ovocytes de Xenopus laevis. La quantification de l’ARNm de SMIT1 et de SMIT2 dans le rein nous a appris que SMIT1 est majoritairement présent dans la médullaire alors que SMIT2 est principalement localisé dans le cortex. Ces résultats ont été confirmés par immunobuvardage en utilisant un anticorps dirigé contre SMIT2. Grâce à l’inhibition sélective de SMIT1 par le L-Fucose et de SMIT2 par le D-chiro-inositol (DCI), nous avons démontré que SMIT2 semble le seul responsable du transport luminal de MI dans le tubule contourné proximal avec un Km de 57 ± 14 µM. Pour ce qui est de l’intestin, des études de transport de MI radioactif ont démontré une absence de transport de MI chez le lapin alors que l’intestin de rat présente un transport de MI très actif. Une quantification par qRT-PCR nous a permis de constater que l’intestin de lapin ne semble pas posséder les transporteurs de MI nécessaires. Comme pour le rein, SMIT2 semble le seul transporteur de MI présent au niveau du pôle apical des entérocytes intestinaux chez le rat. Il est chargé du prélèvement du MI de l'alimentation avec un Km de 150 ± 40 µM. Les analyses fonctionnelles exécutées sur SMIT2 de rat en électrophysiologie après expression dans les ovocytes de Xenopus laevis donnent sensiblement les mêmes résultats que pour les BBMv de rein de lapin et d’intestin de rat. Dans les ovocytes, SMIT2 présente une grande affinité pour le MI (270 ± 19 µM) et le DCI (310 ± 60 µM) et aucune affinité pour le L-fucose. Il est ii également très sensible à la phlorizine (16 ± 7 µM). Une seule exception persiste : la constante d’affinité pour le glucose dans les BBMv d’intestin de rat est 40 fois plus petite que celle observée sur les ovocytes de Xenopus laevis. Nous avons également testé la capacité de certains transporteurs de sucre présents à la surface des membranes apicales des entérocytes à prélever le MI. Vu que l'inhibition de ces transporteurs (SGLT1 et GLUT5) ne changeait rien au taux de MI radioactif transporté, nous en avons conclu qu'ils ne sont pas impliqués dans son transport. Finalement, l’efflux de MI à partir du pôle basolatéral des entérocytes n’est pas effectué par GLUT2 puisque ce dernier lorsqu'il est exprimé dans des ovocytes, est incapable de transporter le MI.

Medición del potencial evocado cognitivo, P300, en un grupo de individuos colombianos sanos

Los potenciales evocados cognitivos son mediciones electrofisiológicas relacionadas con procesosque tienen que ver con ciertas funciones cognitivas. El potencial cognitivo P300 está específicamenterelacionado con procesos de atención. Objetivo: identificar valores para la latencia y amplitud deonda P300 en una muestra de individuos colombianos y describir su comportamiento con respectoa edad, género y escolaridad de los sujetos. Método: se estudiaron 122 sujetos sanos entre los 6 y80 años, se practicó medición del potencial según la metodología odd-ball, en las derivaciones Czy Pz. Resultados: se identificaron valores medianos, mínimos y máximos para diferentes gruposetarios y se estableció que la latencia de la onda P300 aumenta con la edad de los individuos yque, por el contrario, la amplitud de la misma tiende a disminuir. De igual forma, al correlacionarlatencia y amplitud, se evidenció una relación inversa. Conclusiones: no se encontraron diferenciaspara latencia y amplitud de onda relacionadas con el género ni la escolaridad de los sujetos, asícomo tampoco se halló diferencia al realizar la medición en la derivación Pz comparada con laonda obtenida en la derivación Cz.

Niveles de actividad física, condición física y tiempo en pantallas en escolares de Bogotá, Colombia: Estudio FUPRECOL

Examina la relación entre los niveles de actividad física (AF) de forma objetiva, la condición física (CF) y el tiempo de exposición a pantallas en niños y adolescentes de Bogotá, Colombia.

Índice de adiposidad corporal como predictor de obesidad y de síndrome metabólico en adultos de Bogotá, Colombia

Recientemente, Bergman et al. desarrollaron el índice de adiposidad corporal (IAC), como un marcador de obesidad por exceso de grasa corporal en la práctica clínica. En este estudio se evaluó la validez del IAC como marcador de obesidad por exceso de adiposidad, además de examinar la capacidad predictiva del IAC con componentes e índices metabólicos asociados al SM en adultos de Bogotá, Colombia.

La historia de mi pueblo.

El trabajo no ha sido publicado

A system for studying epithelial-stromal interactions reveals distinct inductive abilities of stromal cells from benign prostatic hyperplasia and prostate cancer

The development of normal and abnormal glandular structures in the prostate is controlled at the endocrine and paracrine levels by reciprocal interactions between epithelium and stroma. To study these processes it is useful to have an efficient method of tissue acquisition for reproducible isolation of cells from defined histologies. Here we assessed the utility of a standardized system for acquisition and growth of prostatic cells from different regions of the prostate with different pathologies, and we compared the abilities of stromal cells from normal peripheral zone (PZ-S), benign prostatic hyperplasia (BPH-S), and cancer (CA-S) to induce the growth of a human prostatic epithelial cell line (BPH-1) in vivo. Using the tissue recombination method, we showed that grafting stromal cells (from any histology) alone, or BPH-1 epithelial cells alone produced no visible grafts. Recombining PZ-S with BPH-1 cells also produced no visible grafts (n = 15). Recombining BPH-S with BPH-1 cells generated small, well-organized and sharply demarcated grafts approximately 3-4 mm in diameter (n = 9), demonstrating a moderate inductive ability of BPH-S. Recombining CA-S with BPH-1 cells generated highly disorganized grafts that completely surrounded the host kidney and invaded into adjacent renal tissue, demonstrating induction of an aggressive phenotype. We conclude that acquisition of tissue from toluidine blue dye stained specimens is an efficient method to generate high quality epithelial and/or stromal cultures. Stromal cells derived by this method from areas of BPH and cancer induce epithelial cell growth in vivo which mimics the natural history of these diseases.

On the variations of the Betti numbers of regular levels of Morse flows

We generalize results in Cruz and de Rezende (1999) [7] by completely describing how the Beth numbers of the boundary of an orientable manifold vary after attaching a handle, when the homology coefficients are in Z, Q, R or Z/pZ with p prime. First we apply this result to the Conley index theory of Lyapunov graphs. Next we consider the Ogasa invariant associated with handle decompositions of manifolds. We make use of the above results in order to obtain upper bounds for the Ogasa invariant of product manifolds. (C) 2011 Elsevier B.V. All rights reserved.