Nanoparticle Platform to Modulate Reaction Mechanism of Phenothiazine Photosensitizers

Herein, we report on the synthesis of photosensitizing nanoparticles in which the generation of different oxidizing species, i.e., singlet oxygen ((1)O(2)) or radicals, was modulated. Sol gel and surface chemistry were used to obtain nanoparticles with specific ratios of dimer to monomer species of phenothiazine photosensitizers (PSs). Due to competition between the reactions involving electron transfer within dimer species and energy transfer from monomer triplets to oxygen, the efficiency of (1)O(2) generation could be controlled. Nanoparticles with an excess of dimer have an (1)O(2) generation efficiency (S(Delta)) of 0.01 while those without dimer have a S, value of 0.4. Furthermore, we demonstrate that the PS properties of the nanoparticles are not subjected to interference from the external medium as is commonly the case for free PSs, i.e., PS ground and triplet states are not reduced by NADH and ascorbate, respectively, and singlet excited states are less suppressed by bromide. The modulated (1)O(2) generation and the PS protection from external interferences make this nanoparticle platform a promising tool to aid in performing mechanistic studies in biological systems. Also, it offers potential application in technological areas in which photo-induced processes take place.

Mechanism of Trypanosoma cruzi death induced by Cratylia mollis seed lectin

Incubation of T. cruzi epimastigotes with the lectin Cramoll 1,4 in Ca(2+) containing medium led to agglutination and inhibition of cell proliferation. The lectin (50 A mu g/ml) induced plasma membrane permeabilization followed by Ca(2+) influx and mitochondrial Ca(2+) accumulation, a result that resembles the classical effect of digitonin. Cramoll 1,4 stimulated (five-fold) mitochondrial reactive oxygen species (ROS) production, significantly decreased the electrical mitochondrial membrane potential (Delta I(m)) and impaired ADP phosphorylation. The rate of uncoupled respiration in epimastigotes was not affected by Cramoll 1,4 plus Ca(2+) treatment, but oligomycin-induced resting respiration was 65% higher in treated cells than in controls. Experiments using T. cruzi mitochondrial fractions showed that, in contrast to digitonin, the lectin significantly decreased Delta I(m) by a mechanism sensitive to EGTA. In agreement with the results showing plasma membrane permeabilization and impairment of oxidative phosphorylation by the lectin, fluorescence microscopy experiments using propidium iodide revealed that Cramoll 1,4 induced epimastigotes death by necrosis.

Molecular modeling and UV-vis spectroscopic studies on the mechanism of action of reversed chloroquine (RCQ)

Reversed chloroquine (RCQ) is a multiple ligand compound active against chloroquine-sensitive and resistant falciparum malaria. It is composed by a 4-aminoquinoline moiety (like that present in chloroquine (CQ)) joined to imipramine (IMP), a modulating agent that also showed intrinsic antiplasmodial activity against Brazilian Plasmodium falciparum isolates resistant to CQ. Molecular modeling and ultraviolet-visible spectroscopy (UV-vis) studies strongly suggest that the interaction between RCQ and heme is predominant through the quinoline moiety in a mechanism of action similar to that observed for CQ. (C) 2010 Elsevier Ltd. All rights reserved.

In Situ Infrared (FTIR) Study of the Mechanism of the Borohydride Oxidation Reaction on Smooth Pt Electrode

Although Pt has been thoroughly studied regarding its activity for the borohydride oxidation reaction (BOR), the BOR mechanism at Pt remains unclear: Depending on the applied potential, spontaneous BH(4)(-) hydrolysis can compete with the direct BOR. The goal of the present work is to provide more insight into the behavior of smooth Pt electrodes toward the BOR, by coupling in situ infrared reflectance spectroscopy with electrochemistry. The measurements were performed on a Pt electrode in 1 M NaOH/1 M NaBH(4), so as to detect the reaction intermediate species generated as a function of the applied potential. Several bands were monitored in the B-H ((v) over bar approximate to 1180, 1080, and 972 cm(-1)) and B-O ((v) over bar = 1325 and similar to 1425 cm(-1)) bond regions upon increased electrode polarization. These absorption bands, which appear sequentially and were already detected for similar measurements on Au electrodes, are assigned to BH(3), BH(2), and BO(2)(-) species. In light of these experimental data and previous results obtained in our group for Pt- or Au-based electrodes, possible initial elementary steps of the BOR on platinum electrodes are proposed and discussed according to the relevant literature data.

Mechanism of Muscle Vibrations During Stimulated and Voluntary Isometric Contractions of Mammalian Skeletal Muscle

When a muscle contracts it produces vibrations. The origin of these vibrations is not known in detail. The purpose of this study was to determine the mechanism associated with muscle vibrations. Mechanisms which have been proposed in the literature were described as theories (cross-bridge cycling, vibrating string and unfused motor unit theories). Specific predictions were derived from each theory, and tested in three conceptually different studies. In the first study, the influence of recruitment strategies of motor units (MUs) on the vibromyographic (VMG) signal was studied in the in-situ cat soleus using electrical stimulation of the soleus nerve. VMG signals increased with increasing recruitment and decreased with increasing firing rates of MUs. Similar results were obtained for the human rectus femoris (RF) muscle using percutaneous electrical stimulation of the femoral nerve. The influence of MU activation on muscle vibrations was studied in RF by analyzing VMG signals at different percentages (0-100%) of the maximal voluntary contraction (MVC). In our second study, we tested the effects of changing the material properties of the in-situ cat soleus (through muscle length changes) on the VMG signal. The magnitude of the VMG signal was higher for intermediate muscle lengths compared to the longest and the shortest muscle lengths. The decreased magnitude of the VMG signal at the longest and at the shortest muscle lengths was associated with increased passive stiffness and with decreased force transients during unfused contractions, respectively. In the third study, the effect of fatigue on muscle vibrations was studied in human RF and vastus lateralis (VL) musc1es during isometric voluntary contractions at a leveI of 70% MVC. A decrease in the VMG signal magnitude was observed in RF (presumably due to derecruitment of MUs) and an increase in VL (probably related to the enhancement of physiological tremor, which may have occurred predorninantly in a mediolateral direction) with fatigue. The unfused MU theory, which is based on the idea that force transients produced by MUs during unfused tetanic contraction is the mechanism for muscle vibrations, was supported by the results obtained in the above three studies.

Mechanism of infection and colonization of Rhipicephalus sanguineus eggs by Mertarhizium anisopliae as revealed by scanning eletron microscopy and histopathology

O presente trabalho teve como objetivo verificar a forma de penetração do fungo Metarhizium anisopliae em ovos do carrapato Rhipicephalus sanguineus, assim como as lesões infringidas no interior do ovo. A aderência e penetração do fungo foram estudadas por meio da microscopia eletrônica de varredura e a ação do fungo nos tecidos internos avaliada em secções histológicas convencionais. Para observação destes eventos, realizaram-se infecções experimentais em 11 grupos de ovos do R. sanguineus contendo 25 mg cada. Os ovos foram banhados durante 3 minutos, sob agitação manual, em suspensão com concentração de 10(8) conídios/mL. Nos grupos controle o banho foi realizado apenas no veículo da suspensão. Os ovos foram processados para análise histopatológica e microscopia eletrônica de varredura nos seguintes tempos após a infecção: 1 e 18h, e um, dois, três, quatro, cinco, seis, sete, nove e onze dias. Observou-se grande germinação de conídios em 67% dos ovos 18h após a inoculação e o fungo penetrou em 92,6% dos ovos 5 dias após a infecção. A extrusão do patógeno ocorreu em 87% dos ovos 7 dias após a infecção, chegando a 100% no 9º dia. Nas análises histopatológicas não foram observadas lesões dignas de nota, porem deve-se ressaltar que houve significativa redução (53,9%) na eclosão a partir dos ovos infectados.

Mechanism of anticlastogenicity of Agaricus blazei Murill mushroom organic extracts in wild type CHO (K-1) and repair deficient (xrs5) cells by chromosome aberration and sister chromatid exchange assays

Agaricus blazei Murill is a medicinal mushroom native to Brazil. The present work assessed the clastogenic and anticlastogenic potential of organic extracts (ethanol and chloroform/methanol) from the lineage AB97/11 in chinese hamster CHO-K-1 (wild type) and CHO-xrs5 (repair deficient) cells using the chromosome aberration (CA) and sister chromatid exchange (SCE) assays. In these experimental conditions were observed: (a) anticlastogenic effect at concentrations of 0.06 and 0.09% of the EtOH extract and at the 0.03 and 0.06% concentrations of the C/MetOH extract in CHO-K-1; (b) absence of protector effect on CHO-xrs5 cells; and (c) absence of protector effect in the SCE assay. These results indicate that organic extracts of A. blazei lineage AB97/11 present bio-antimutagenic type protective activity. (C) 2003 Elsevier B.V. B.V. All rights reserved.

Interaction mechanism of poly (o-ethoxyaniline) and collagen blends

Blend films of poly (o-ethoxyaniline) (POEA) and collagen were fabricated by casting under optimized conditions and characterized by Raman scattering and UV-vis absorption spectroscopies. The UV-vis spectra showed that the addition of collagen in the aqueous solution of POEA promotes a dedoping of the POEA. This effect was also observed for the blend films as supported by Raman scattering and a mechanism for the chemical interaction between POEA-collagen is proposed. The influences of different percentage of collagen as well as the pH of stock solutions during the fabrication process of the blend films were also investigated. It was found that the preparation method plays an important role in the flexibility and freestanding properties of the films. Complementary, the surface morphology was studied by atomic force microscopy and the conductivity by dc measurements. (C) 2003 Elsevier Ltd. All rights reserved.

Understanding the Crystallization Mechanism of a Wollastonite Base Glass Using Isoconversional, IKP Methods and Master Plots

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

The reactivity of oytho-methoxy-substituted catechol radicals with sulfhydryl groups: Contribution for the comprehension of the mechanism of inhibition of NADPH oxidase by apocynin

Redox processes are involved in the mechanism of action of NADPH oxidase inhibitors such as diphenyleneiodonium and apocynin. Here, we studied the structure-activity relationship for apocynin and analogous ortho-methoxy-substituted catechols as inhibitors of the NADPH oxidase in neutrophils and their reactivity with peroxidase. Aiming to alter the reduction potential, the ortho-methoxy-catechol moiety was kept constant and the substituents at para position related to the hydroxyl group were varied. Two series of compounds were employed: methoxy-catechols bearing electron-withdrawing groups (MC-W) such as apocynin, vanillin, 4-nitroguaiacol, 4-cyanoguaiacol, and methoxy-catechol bearing electron-donating groups (MC-D) such as 4-methylguaiacol and 4-ethylguaiacol. We found that MC-D were weaker inhibitors compared to MD-W. Furthermore, the radicals generated by oxidation of MC-W via MPO/H(2)O(2), but not for MC-D, were able to oxidize glutathione (GSH) as verified by the formation of thiyl radicals, depletion of GSH, and recycling of the ortho-methoxy-catechols during their oxidations. The capacity of oxidizing sulfhydryl (SH) groups was also verified when ovalbumin was incubated with MC-W, but not for MC-D. Since the effect of apocynin has been correlated with inactivation of the cytosolic fractions of the NADPH oxidase complex and its oxidation during the inhibitory process develops a special role in this process, we suggest that the close relationship between the reactivity of the radicals of MC-W compounds with thiol groups and their efficacy as NADPH oxidase inhibitor could be the chemical pathway behind the mechanism of action of apocynin and should be taken into account in the design of new and specific NADPH oxidase inhibitors. (c) 2007 Elsevier B.V. All rights reserved.

Effect of PbS impurity on crystallization mechanism of phosphate glasses studied by differential scanning calorimetry

In this work, differential scanning calorimetry (DSC) was used to study effect of PbS impurity on crystallization mechanism of phosphate glasses. Bulk glasses presented one crystallization peak while powdered glasses presented two distinct crystallization peaks. For both undoped and doped glasses were determined the activation energies for the crystallization and the Avrami n parameters. The activation energies for undoped phosphate glass were 336 +/- 6 and 213 +/- 3 kJ mol(-1), respectively, associated with first and second crystallization peaks. For doped glass, the obtained energies were 373 +/- 9 and 286 +/- 7 kJ mol(-1). The calculated Avrami parameters, based on first crystallization peaks, for undoped and doped glasses were 2.25 +/- 0.01 and 1.75 +/- 0.02, respectively. These values suggest that the first DSC peak, in both glasses, may be associated with surface crystallization. (C) 2002 Elsevier B.V. B.V. All rights reserved.

Mechanism of charge transport in castor oil-based polyurethane/carbon black composite (PU/CB)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)