Neuroprotection and regeneration of adult lesioned retinal ganglion cells by the modulation of fibroblast growth factor-2 and receptor tyrosine phosphatase-sigma

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Diatom isotope data from ODP Hole 178-1098A for the last deglaciation (12.2-12.8 ka BP)

Understanding the response of the Antarctic ice sheets during the rapid climatic change that accompanied the last deglaciation has implications for establishing the susceptibility of these regions to future 21st Century warming. A unique diatom d18O record derived from a high-resolution deglacial seasonally laminated core section off the west Antarctic Peninsula (WAP) is presented here. By extracting and analysing single species samples from individual laminae, season-specific isotope records were separately generated to show changes in glacial discharge to the coastal margin during spring and summer months. As well as documenting significant intra-annual seasonal variability during the deglaciation, with increased discharge occurring in summer relative to spring, further intra-seasonal variations are apparent between individual taxa linked to the environment that individual diatom species live in. Whilst deglacial d18O are typically lower than those for the Holocene, indicating glacial discharge to the core site peaked at this time, inter-annual and inter-seasonal alternations in excess of 3 per mil suggest significant variability in the magnitude of these inputs. These deglacial variations in glacial discharge are considerably greater than those seen in the modern day water column and would have altered both the supply of oceanic warmth to the WAP as well as regional marine/atmospheric interactions. In constraining changes in glacial discharge over the last deglaciation, the records provide a future framework for investigating links between annually resolved records of glacial dynamics and ocean/climate variability along the WAP.

Mixing of 0(+) and 0(-) observed in the hyperfine and Zeeman structure of ultracold Rb-2 molecules

We study the combination of the hyperfine and Zeeman structure in the spin-orbit coupled A(1)Sigma(+)(u) = b(3)Pi(u) complex of Rb-87(2). For this purpose, absorption spectroscopy at a magnetic field around B = 1000 G is carried out. We drive optical dipole transitions from the lowest rotational state of an ultracold Feshbach molecule to various vibrational levels with 0(+) symmetry of the A - b complex. In contrast to previous measurements with rotationally excited alkali-dimers, we do not observe equal spacings of the hyperfine levels. In addition, the spectra vary substantially for different vibrational quantum numbers, and exhibit large splittings of up to 160 MHz, unexpected for 0(+) states. The level structure is explained to be a result of the repulsion between the states 0(+) and 0(-) of b(3)Pi(u), coupled via hyperfine and Zeeman interactions. In general, 0(-) and 0(+) have a spin-orbit induced energy spacing Delta, that is different for the individual vibrational states. From each measured spectrum we are able to extract Delta, which otherwise is not easily accessible in conventional spectroscopy schemes. We obtain values of Delta in the range of +/- 100 GHz which can be described by coupled channel calculations if a spin-orbit coupling is introduced that is different for 0(-) and 0(+) of b(3)Pi(u).

Solid Lipid Nanoparticles For Hydrophilic Biotech Drugs: Optimization And Cell Viability Studies (caco-2 & Hepg-2 Cell Lines).

Insulin was used as model protein to developed innovative Solid Lipid Nanoparticles (SLNs) for the delivery of hydrophilic biotech drugs, with potential use in medicinal chemistry. SLNs were prepared by double emulsion with the purpose of promoting stability and enhancing the protein bioavailability. Softisan(®)100 was selected as solid lipid matrix. The surfactants (Tween(®)80, Span(®)80 and Lipoid(®)S75) and insulin were chosen applying a 2(2) factorial design with triplicate of central point, evaluating the influence of dependents variables as polydispersity index (PI), mean particle size (z-AVE), zeta potential (ZP) and encapsulation efficiency (EE) by factorial design using the ANOVA test. Therefore, thermodynamic stability, polymorphism and matrix crystallinity were checked by Differential Scanning Calorimetry (DSC) and Wide Angle X-ray Diffraction (WAXD), whereas the effect of toxicity of SLNs was check in HepG2 and Caco-2 cells. Results showed a mean particle size (z-AVE) width between 294.6 nm and 627.0 nm, a PI in the range of 0.425-0.750, ZP about -3 mV, and the EE between 38.39% and 81.20%. After tempering the bulk lipid (mimicking the end process of production), the lipid showed amorphous characteristics, with a melting point of ca. 30 °C. The toxicity of SLNs was evaluated in two distinct cell lines (HEPG-2 and Caco-2), showing to be dependent on the concentration of particles in HEPG-2 cells, while no toxicity in was reported in Caco-2 cells. SLNs were stable for 24 h in in vitro human serum albumin (HSA) solution. The resulting SLNs fabricated by double emulsion may provide a promising approach for administration of protein therapeutics and antigens.

Synthesis And Antitumor Activity Of Novel 1-substituted Phenyl 3-(2-oxo-1,3,4-oxadiazol-5-yl) β-carbolines And Their Mannich Bases.

A series of novel 1-(substituted phenyl)-3-(2-oxo-1,3,4-oxadiazol-5-yl) β-carbolines (4a-e) and the corresponding Mannich bases 5-9(a-c) were synthesized and evaluated for their in vitro antitumor activity against seven human cancer cell lines. Compounds of 4a-e series showed a broad spectrum of antitumor activity, with GI50 values lower than 15μM for five cell lines. The derivative 4b, having the N,N-dimethylaminophenyl group at C-1, displayed the highest activity with GI50 in the range of 0.67-3.20μM. A high selectivity and potent activity were observed for some Mannich bases, particularly towards resistant ovarian (NCI-ADR/RES) cell lines (5a, 5b, 6a, 6c and 9b), and ovarian (OVCAR-03) cell lines (5b, 6a, 6c, 9a, 9b and 9c). In addition, the interaction of compound 4b with DNA was investigated by using UV and fluorescence spectroscopic analysis. These studies indicated that 4b interact with ctDNA by intercalation binding.

Efficacy And Safety Of Intravitreal Bevacizumab In Eyes With Neovascular Glaucoma Undergoing Ahmed Glaucoma Valve Implantation: 2-year Follow-up.

To evaluate the efficacy and safety of intravitreal bevacizumab (IVB) in eyes with neovascular glaucoma (NVG) undergoing Ahmed glaucoma valve (AGV) implantation. This was a multicentre, prospective, randomized clinical trial that enrolled 40 patients with uncontrolled neovascular glaucoma that had undergone panretinal photocoagulation and required glaucoma drainage device implantation. Patients were randomized to receive IVB (1.25 mg) or not during Ahmed valve implant surgery. Injections were administered intra-operatively, and 4 and 8 weeks after surgery. After a mean follow-up of 2.25 ± 0.67 years (range 1.5-3 years), both groups showed a significant decrease in IOP (p < 0.05). There was no difference in IOP between groups except at the 18-month interval, when IOP in IVB group was significantly lower (14.57 ± 1.72 mmHg vs. 18.37 ± 1.06 mmHg - p = 0.0002). There was no difference in survival success rates between groups. At 24 months, there was a trend to patients treated with IVB using less antiglaucoma medications than the control group (p = 0.0648). Complete regression of rubeosis iridis was significantly more frequent in the IVB group (80%) than in the control group (25%) (p = 0.0015). Intravitreal bevacizumab may lead to regression of new vessels both in the iris and in the anterior chamber angle in patients with neovascular glaucoma undergoing Ahmed glaucoma valve implantation. There is a trend to slightly lower IOPs and number of medications with IVB use during AGV implantation for neovascular glaucoma.

A Rapid And Simple Capillary Electrophoresis Method For Indirect Determination Of The Biocide 2,2-dibromo-3-nitrilo-propionamide (dbnpa) In Cooling Waters.

A capillary zone electrophoresis (CE) method was developed for the determination of the biocide 2,2-dibromo-3-nitrilo-propionamide (DBNPA) in water used in cooling systems. The biocide is indirectly determined by CE measurement of the concentration of bromide ions produced by the reaction between the DBNPA and bisulfite. The relationship between the bromide peak areas and the DBNPA concentrations showed a good linearity and a coefficient of determination (R(2)) of 0.9997 in the evaluated concentration range of 0-75 μmol L(-1). The detection and quantification limits for DBNPA were 0.23 and 0.75 μmol L(-1), respectively. The proposed CE method was successfully applied for the analysis of samples of tap water and cooling water spiked with DBNPA. The intra-day and inter-day (intermediary) precisions were lower than 2.8 and 6.2%, respectively. The DBNPA concentrations measured by the CE method were compared to the values obtained by a spectrophotometric method and were found to agree well.

Epicardial And Pericardial Fat In Type 2 Diabetes: Favourable Effects Of Biliopancreatic Diversion.

Ectopic fat is often identified in obese subjects who are susceptible to the development of type 2 diabetes mellitus (T2DM). The ectopic fat favours the decrease in insulin sensitivity (IS) and adiponectin levels. We aimed to evaluate the effect of biliopancreatic diversion (BPD) on the accumulation of ectopic fat, adiponectin levels and IS in obese with T2DM. A nonrandomised controlled study was performed on sixty-eight women: 19 lean-control (23.0 ± 2.2 kg/m(2)) and 18 obese-control (35.0 ± 4.8 kg/m(2)) with normal glucose tolerance and 31 obese with T2DM (36.3 ± 3.7 kg/m(2)). Of the 31 diabetic women, 20 underwent BPD and were reassessed 1 month and 12 months after surgery. The subcutaneous adipose tissue, visceral adipose tissue, epicardial adipose tissue and pericardial adipose tissue were evaluated by ultrasonography. The IS was assessed by a hyperglycaemic clamp, applying the minimal model of glucose. One month after surgery, there was a reduction in visceral and subcutaneous adipose tissues, whereas epicardial and pericardial adipose tissues exhibited significant reduction at the 12-month assessment (p < 0.01). Adiponectin levels and IS were normalised 1 month after surgery, resembling lean-control values and elevated above the obese-control values (p < 0.01). After 12 months, the improvement in IS and adiponectin was maintained, and 17 of the 20 operated patients exhibited fasting glucose and glycated haemoglobin within the normal range. After BPD, positive physiological adaptations occurred in grade I and II obese patients with T2DM. These adaptations relate to the restoration of IS and decreased adiposopathy and explain the acute (1 month) and chronic (12 months) improvements in the glycaemic control.

Bp-13 Pla2: Purification And Neuromuscular Activity Of A New Asp49 Toxin Isolated From Bothrops Pauloensis Snake Venom.

A new PLA2 (Bp-13) was purified from Bothrops pauloensis snake venom after a single chromatographic step of RP-HPLC on μ-Bondapak C-18. Amino acid analysis showed a high content of hydrophobic and basic amino acids and 14 half-cysteine residues. The N-terminal sequence showed a high degree of homology with basic Asp49 PLA2 myotoxins from other Bothrops venoms. Bp-13 showed allosteric enzymatic behavior and maximal activity at pH 8.1, 36°-45°C. Full Bp-13 PLA2 activity required Ca(2+); its PLA2 activity was inhibited by Mg(2+), Mn(2+), Sr(2+), and Cd(2+) in the presence and absence of 1 mM Ca(2+). In the mouse phrenic nerve-diaphragm (PND) preparation, the time for 50% paralysis was concentration-dependent (P < 0.05). Both the replacement of Ca(2+) by Sr(2+) and temperature lowering (24°C) inhibited the Bp-13 PLA2-induced twitch-tension blockade. Bp-13 PLA2 inhibited the contractile response to direct electrical stimulation in curarized mouse PND preparation corroborating its contracture effect. In biventer cervicis preparations, Bp-13 induced irreversible twitch-tension blockade and the KCl evoked contracture was partially, but significantly, inhibited (P > 0.05). The main effect of this new Asp49 PLA2 of Bothrops pauloensis venom is on muscle fiber sarcolemma, with avian preparation being less responsive than rodent preparation. The study enhances biochemical and pharmacological characterization of B. pauloensis venom.

Propriedades elétricas e magnéticas de novos compostos com o ânion condutor [Ni(dmit)2]- e radicais magnéticos nitronil nitróxido

Three compounds have been synthesized with formulae [3-MeRad][Ni(dmit)2] (1), [4-MeRad][Ni(dmit)2] (2) and [4-PrRad][Ni(dmit)2] (3) where [Ni(dmit)2]- is an anionic pi-radical (dmit = 1,3-dithiol-2-thione-4,5-dithiolate) and [3-MeRad]+ is 3-N-methylpyridinium alpha-nitronyl nitroxide, [4-MeRad]+ is 4-N-methylpyridinium alpha-nitronyl nitroxide and [4-PrRad]+ is 4-N-propylpyridinium alpha-nitronyl nitroxide. The temperature-dependent magnetic susceptibility of 1 revealed that an antiferromagnetic interaction operates between the 3-MeRad+ radical cations with exchange coupling constants of J1 = - 1.72 cm-1 and antiferromagnetism assigned to the spin ladder chains of the Ni(dmit)2 radical anions. Compound 1 exhibits semiconducting behavior and 3 presents capacitor behavior in the temperature range studied (4 - 300 K).

Avaliações autonômicas e cardiovasculares em pessoas com lesão da medula espinhal nas situações de repouso, em um teste de estresse mental e durante exercício físico

Universidade Estadual de Campinas . Faculdade de Educação Física

Análise do desempenho muscular do quadríceps e dos isquiotibiais em função da série temporal e da amplitude de movimento de atletas amadoras de futsal feminino = : Analysis of muscle performance of the quadriceps and hamstrings as a function of the times series and range of motion of amateurfemale futsal athletes

Universidade Estadual de Campinas . Faculdade de Educação Física

EPR and magnetic studies of a carboxylate-bridged dinuclear copper(II) compound: [cu2(flu)4(dmf)2]

We report magnetic and EPR (electron paramagnetic resonance) spectroscopy studies of [Cu2(flu)4(dmf)2] (flu = flufenamate and dmf = dimethylformamide), which has CuII ions in tetracarboxylate "paddle wheel" dinuclear units. Susceptibility measurements at 10 < T < 275 K allowed the evaluation of an antiferromagnetic intradinuclear exchange coupling J0 = -294 ± 5 cm-1 between CuII ions (Hex = "J0 S1·S2). EPR experiments at 300 K in powder and single-crystals at 9.5 and 34.4 GHz indicated g// = 2.373, g⊥ = 2.073 and zero field splitting parameters D = (-0.334 ± 0.001) cm"1 and E ca. 0. EPR signal intensity measurements at X-band in the range 4 < T < 295 K indicated that J0 = "283 ± 5 cm"1. A higher limit |J´| < 5×10-3 cm-1 for the interdinuclear exchange coupling between neighbor units at ca.14.24 Å was estimated from the angular variation of the single crystal spectra around the magic angles. The results are discussed in terms of the structure of the dinuclear unit and the bridges connecting CuII ions and compared with values reported for similar compounds.

Time resolved emission spectroscopy of poly(2,5-dicyano-p-phenylene-vinylene) films

Films of poly (2,5-dicyano-p-phenylene vinylene), DCNPPV, were obtained by electrochemical synthesis over gold thin layer (20 nm) transparent electrode deposited on a glass plate. The DCNPPV films of 4 µm thickness were produced by electropolymerization process of α,α,α',α'-tetrabromo-2-5-dicyano-p-xilene at different applied potentials (-0.15, -0.25, -0.40, -0.60, -0.80, and -1.0 V) using 0.1 mol L-1 of tetraethylammonium bromide in acetonitrile as the supporting electrolyte. The emission decays have three exponential components: a fast component in the picosecond range (200-400 ps), and two other of about one and five nanoseconds at 293 K. The fluorescence quenching process seems to occur by exciton trapping in a low-energy site and quenching by residual bromine monomer attached at the end of the polymer chain. However, the electrochemical synthesis generates entrapped bromide or ion pairs during the growth step of the film which also contributes to the deactivation. The change of the electrolyte from bromide to perchlorate reduces significantly this additional quenching effect by allowing ion exchange of formed bromide with the nonquenching perchloride anion.

Solid-phase microextraction for determination of 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone in water

Solid-phase microextraction, using on-line bis(trimethylsilyl)trifluoroacetamide derivatisation, gas chromatography, and mass spectrometry, was evaluated in the quantification of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in water samples. Fibres encompassing a wide range of polarities were used with headspace and direct immersion sampling. For the immersion procedure, various parameters affecting MX extraction, including pH, salinity, temperature, and extraction time were evaluated. The optimised method (polyacrylate fibre; 20% Na2SO4; pH 2.0; 60 min; 20 °C) was applied for reservoir chlorinated water samples-either natural or spiked with MX (50 ng L-1 and 100 ng L-1). The recovery of MX ranged from 44 to 72%. Quantification of MX in water samples was done using external standard and the selected ion monitoring mode. Correlation coefficient (0.98%), relative standard deviation (5%), limit of detection (30 ng L-1) and limit of quantification (50 ng L-1) were obtained from calibration curve.