Photocytotoxic activity of a nitrosyl phthalocyanine ruthenium complex - A system capable of producing nitric oxide and singlet oxygen

The synthesis, structural aspects, pharmacological assays, and in vitro photoinduced cytotoxic properties of [Ru(NO)(ONO)(pc)] (pc = phthalocyanine) are described. Its biological effect on the B16F10 cell line was studied in the presence and absence of visible light irradiation. At comparable irradiation levels, [Ru(NO) (ONO)(pc)] was more effective than [Ru(pc)] at inhibiting cell growth, suggesting that occurrence of nitric oxide release following singlet oxygen production upon light irradiation may be an important mechanism by which the nitrosyl ruthenium complex exhibits enhanced biological activity in cells. Following visible light activation, the [Ru(NO)(ONO)(pc)] complex displayed increased potency in B16F10 cells upon modifications to the photoinduced dose; indeed, enhanced potency was detected when the nitrosyl ruthenium complex was encapsulated in a drug delivery system. The liposome containing the [Ru(NO)(ONO)(pc)] complex was over 25% more active than the corresponding ruthenium complex in phosphate buffer solution. The activity of the complex was directly proportional to the ruthenium amount present inside the cell, as determined by inductively coupled plasma mass spectroscopy. Flow cytometry analysis revealed that the photocytotoxic activity was mainly due to apoptosis. Furthermore, the vasorelaxation induced by [Ru(NO)(ONO)(pc)], proposed as NO carrier, was studied in rat isolated aorta. The observed vasodilation was concentration-dependent. Taken together, the present findings demonstrate that the [Ru(NO)(ONO)(pc)] complex induces vascular relaxation and could be a potent anti-tumor agent. Nitric oxide release following singlet oxygen production upon visible light irradiation on a nitrosyl ruthenium complex produces two radicals and may elicit phototoxic responses that may find useful applications in photodynamic therapy. Crown Copyright (C) 2011 Published by Elsevier Inc. All rights reserved.

Chitosan as a Bioadhesive Agent Between Porphyrins and Phospholipids in a Biomembrane Model

Porphyrins are currently used in photodynamic therapy as photosensitizers. In this paper we studied the interaction of two charged porphyrins, 5, 10, 15, 20-mesotetrakis(N-metyl-4-pyridyl) porphyrin, (TMPyP/chloride salt) cationic, and 5, 10, 15, 20-meso-tetrakis(sulfonatophenyl) porphyrin, (TPPS(4)/sodium salt) anionic, nanoassembled in phospholipid Langmuir monolayers and Langmuir-Blodgett films. Furthermore, we used chitosan to mediate the interaction between the porphyrins and the model membrane, aiming to understand the role of the polysaccharide in a molecular level. The effect of the interaction of the photosensitizers on the fluidity of the lipid monolayer was investigated by using dilatational surface elasticity. We also used photoluminescence (PL) spectroscopy to identify the porphyrins adsorbed in the phospholipid films. We observed an expansion of the monolayer promoted by the adsorption of the porphyrins into the lipid-air interface which was more pronounced in the case of TMPyP, as a consequence of a strong electrostatic interaction with the anionic monolayer. The chitosan promoted a higher adsorption of the porphyrins on the phospholipid monolayers and enabled the porphyrin to stay in its monomeric form (as confirmed by PL spectroscopy), thus demonstrating that chitosan can be pointed out as a potential photosensitizer delivery system in photodynamic therapy.

Approximate controllability of second-order distributed implicit functional systems

In this paper we study the approximate controllability of control systems with states and controls in Hilbert spaces, and described by a second-order semilinear abstract functional differential equation with infinite delay. Initially we establish a characterization for the approximate controllability of a second-order abstract linear system and, in the last section, we compare the approximate controllability of a semilinear abstract functional system with the approximate controllability of the associated linear system. (C) 2008 Elsevier Ltd. All rights reserved.

Characterization of the Biocompatible Magnetic Colloid on the Basis of Fe(3)O(4) Nanoparticles Coated with Dextran, Used as Contrast Agent in Magnetic Resonance Imaging

The magnetic resonance imaging contrast agent, the so-called Endorem (TM) colloidal suspension on the basis of superparamagnetic iron oxide nanoparticles (mean diameter of 5.5 nm) coated with dextran, were characterized on the basis of several measurement techniques to determine the parameters of their most important physical and chemical properties. It is assumed that each nanoparticle is consisted of Fe(3)O(4) monodomain and it was observed that its oxidation to gamma-Fe(2)O(3) occurs at 253.1 degrees C. The Mossbauer spectroscopy have shown a superparamagnetic behavior of the magnetic nanoparticles. The Magnetic Resonance results show an increase of the relaxation times T(1), T(2), and T(2)* with decreasing concentration of iron oxide nanoparticles. The relaxation effects of SPIONs contrast agents are influenced by their local concentration as well as the applied field strength and the environment in which these agents interact with surrounding protons. The proton relaxation rates presented a linear behavior with concentration. The measured values of thermooptic coefficient partial derivative n/partial derivative T, thermal conductivity K, optical birefringence Delta n(0), nonlinear refractive index n(2), nonlinear absorption beta` and third-order nonlinear susceptibility vertical bar chi((3))vertical bar are also reported.

Centella asiatica water extract inhibits iPLA(2) and cPLA(2) activities in rat cerebellum

Centella asiatica (L.) Urb an is distributed widely in South America and Asia and is known as a therapeutic agent in folk medicine, capable of improving memory and treating several neurological disorders. Asiaticoside is one of the compounds found in C asiatica leaves that is suggested to be responsible for its pharmacological potential. Phospholipase A(2) (PLA(2)) is a group of enzymes that has abnormal activity in the central nervous system in some neuropsychiatric diseases. In this work, the asiaticoside present in C asiatica water extract was quantified by HPLC analysis. We also evaluated the activity of subtypes of PLA(2) in cerebellar samples from rats after C asiatica water extract treatment using a radioenzymatic assay. Asiaticoside was the major compound (84%) found in Centella water extract. We found a dose-dependent inhibitory effect of C asiatica water extract on the activity of Ca(2+)-independent PLA(2) (iPLA(2)) and cytosolic PLA(2) (cPLA(2)). The inhibition of these enzymes in the brain suggests that C asiatica may be useful to treat conditions associated with increased PLA(2) activity in the brain, such as epilepsy, stroke, multiple sclerosis and other neuropsychiatric disorders. (C) 2008 Elsevier GmbH. All rights reserved.

Treatment for low-risk gestational trophoblastic disease: Comparison of single-agent methotrexate, dactinomycin and combination regimens

Objectives. To compare the efficacy of three different standard chemotherapy regimens for low-risk gestational trophoblastic disease according to the FIGO staging system in a single-institute setting. Methods. From 1980 until 2002, we retrospectively reviewed 108 cases with low-risk persistent gestational trophoblastic disease who were treated with first-line chemotherapy. Patients were divided in three groups according to chemotherapy regimen: patients treated with methotrexate (MTX group; n=42), patients treated with dactinomycin (ACT group; n=42) and patients treated with methotrexate and dactinomycin in combination (MACT group; n=24). We compared the number of chemotherapy courses for achieving remission, the duration of treatment, the adverse side effects, the efficacy of the treatment and the need for performing a hysterectomy among the groups Results. The complete remission rates were 69%, 61.4% and 79.1% for methotrexate (MTX), dactinomycin (ACT) and the combination regimen (MACT) treated groups, respectively (p=0.7). The duration of the treatment and the number of chemotherapy courses were similar among the groups (p = 0.2 and p = 0.4, respectively). Adverse side effects rate was reported to be 62.5% in the MACT group, 28.6% in the MTX group and 19.1% in the ACT group (p=0.0003). Second-line chemotherapy was indicated for 30 patients. Hysterectomy was performed in 21 patients overall, and there was no difference among the groups (P=0.6). Conclusion. Our analysis indicates that single-agent chemotherapy regimens are as effective as combination chemotherapy for low-risk gestational trophoblastic disease. Dactinomycin is a less toxic drug and might offer the best cost-effective treatment option. Methotrexate must be considered as the regimen of choice for low resource areas because of the feasibility of its administration. (c) 2007 Elsevier Inc. All rights reserved.

Organophosphate-related ototoxicity: Description of the vestibulocochlear system ultrastructural aspects of guinea pigs

Organophosphate toxic agents are used in agriculture and are currently part of the group of toxic agents which can lead to hearing loss, in which we have solvents, metals and asphyxiation agents. Aim: to analyze the acute ototoxic action of a group of organophosphate agents in the vestibulocochlear system. This is a prospective experimental study. Materials and Methods: we used male albino guinea pigs, broken down into three groups, to which we provided distilled water (group 1 - control), agrotoxic agent - 0.3mg/Kg/day (group 2), agrotoxic - 3 mg/Kg/day (group 3), during 7 seven consecutive days. The most used agrotoxic agent was Tamaron BR (metamidophos). The anatomical evaluation of the cochlea, saccule and utricle was carried out by means of electronic scanning microscopy after the use of the agrotoxic agent. Results: the guinea pigs submitted to the organophosphate presented cochlear morphological alterations with lesions on the three turns analyzed, as well as cilia alterations in the saccule and utricle, intensified according to the agent dosage. Conclusion: the morphological alterations seen in the hair cells exposed to daily doses of organophosphate promote evidences of an acute deleterious effect of agrotoxic agents on the vestibulocochlear system.

Development of disabled, replication-defective gene transfer vectors from the Jembrana disease virus, a new infectious agent of cattle

Jembrana disease virus (JDV) is a newly isolated and characterised bovine lentivirus. It causes an acute disease in Ball cattle (Bos javanicus). which can be readily transmitted to susceptible cattle with 17% mortality. There is as yet no treatment or preventive vaccine. We have developed a gene transfer vector system based on JDV that has three components. The first of the components is a bicistronic transfer vector plasmid that was constructed to contain cis-sequences from the JDV genome, including 5 '- and 3 ' -long terminal repeats (LTRs), 0.4 kb of truncated gag and 1.1 kb of 3 ' -env, a multiple cloning site to accommodate the gene(s) of interest for transfer, and an internal ribosome entry site plus the neomycin phosphotransferase (Neo) gene cassette for antibiotic selection. The second element is a packaging plasmid that contains trans-sequences. including gag, pol. vif, tar and rev: but without the env and packaging signals. The third is a plasmid encoding the G glycoprotein of vesicular stomatitis virus (VSV-G) to supply the vector an envelope for pseudotyping. Cotransfection of 293T cells with these three plasmid components produced VSV-G pseudotyped. disabled, replication defective, bicistronic JDV vectors encoding the green fluorescent protein (EGFP) and the Neo resistance selection maker simultaneously with a titre range of (0.4-1.2) x 10(6) CFU/ml. Transduction of several replicating primary and transformed cells from cattle, primate and human sources and importantly growth-arrested cells with the JDV vectors showed high efficiency of EGFP gene transfer at 35-75%, which was stable and the expression of EGFP was long term. Furthermore, these JDV vectors were designed to suit the inclusion and expression of genes corresponding to JDV specific proteins, such as gag or env, for the development of vaccines for Jembrana disease. This strategy should also be applicable to other bovine diseases as wall. The design and construction of the JDV vector system should facilitate the study of the lentivirology and pathogenesis of the diseases associated with JDV or other bovine virus infections. To our knowledge, this is the first such vector system developed from a cattle virus. (C) 2001 Elsevier Science B.V. All rights reserved.

Vascular dysfunction and heart failure: Epiphenomenon or etiologic agent?

Endothelial function plays a key role in the local regulation of vascular tone. Alterations in endothelial function may result in impaired release of endothelium-derived relaxing factors or increased release of endothelium-derived contracting factors. Heart failure may impair endothelial function by means of reduced synthesis and release of nitric oxide (NO) or by increased degradation of NO and increased production of endothelin-1. Endothelial dysfunction may worsen heart function by means of peripheral effects, causing increased afterload and central effects such as myocardial ischemia and inducible nitric oxide synthase (iNOS)-induced detrimental effects. Evidence from clinical studies has suggested that there is a correlation between decreased endothelial function and increasing severity of congestive heart failure (CHF). Treatments that improve heart function may also improve endothelial dysfunction. The relationship between endothelial dysfunction and heart failure may be masked by the stage of endothelial dysfunction, the location of vessels being tested, and the state of endothelial-dependent vasodilatation response.

Binder treatment and lubricant system for aluminium P/M

Organic binders are used in premixes for powder metallurgy applications to prevent dusting and segregation. This is a particular problem for aluminium powder metallurgy because the dust is a potential safety hazard. The binder must also burn out completely at low temperatures in an inert environment and not react with the metal powders. It is demonstrated that cellulose acetate, polyvinyl acetate and polyvinyl alcohol are effective dedusting agents but they react with the metal powders during sintering and decrease the sintered density. Paraffin wan is an effect dedusting agent that provided die wall lubricity, does not interfere with sintering and increases tensile strength and ductility.

In vitro growth and leaf anatomy of Cattleya walkeriana (Gardner, 1839) grown in natural ventilation system

Natural ventilation system facilitates gaseous exchanges in in vitro plants promoting changes in the leaf tissue, which can be evaluated through the leaf anatomy, and it allows a cultivation closer to the photoautrophic micropropagation. The objective of this work was to evaluate the effects on in vitro growth and on the leaf anatomy of Cattleya walkeriana grown in natural and conventional ventilation system with different concentrations of sucrose (0; 15; 30 and 45 L-1) combined with different cultivation systems (conventional micropropagation and natural ventilation system). The culture medium was composed of MS salts, solidified with 7 g L-1 of agar and pH adjusted to 5.8. Forty milliliters of culture medium were distributed in 250 mL flasks, autoclaved at 120 ºC for 20 minutes. The greater plant growth, as well as the greater thickness of the mesophyll was observed with the use of 20 g L-1 sucrose in natural ventilation system. Plants grown in natural ventilation system showed a thicker leaf mesophyll, which is directly related to photoautotrophic crops. The natural ventilation system induced more elliptical stomata and probably more functional formats.

Gradual correction of phosphorus availability in the no-tillage system

ABSTRACT In areas cultivated under no-tillage system, the availability of phosphorus (P) can be raised by means of the gradual corrective fertilization, applying phosphorus into sowing furrows at doses higher than those required by the crops. The objective of this work was to establish the amount of P to be applied in soybean crop to increase content of P to pre-established values at the depth of 0.0 to 0.10 m. An experiment was carried out on a clayey Haplorthox soil with a randomized block experimental design distributed in split-split plot, with four replications. Two soybean crop systems (single or intercropped with Panicum maximum Jaca cv. Aruana) were evaluated in the plots. In addition, it was evaluated four P levels (0, 60, 120 and 180 kg ha-1 P2O5) applied in the first year in the split plots; and four P levels (0, 30, 60 and 90 kg ha-1 P2O5) applied in the two subsequent crops in the split-split plot. Contents of P were extracted by Mehlich-1 and Anion Exchange Resin methods from soil samples collected in the split-split plot. It was found that it is necessary to apply 19.4 or 11.1 kg ha-1 of P2O5, via triple superphosphate as source, to increase 1 mg dm-3 of P extracted by Mehlich-1 or Resin, respectively, in the 0.0 to 0.10 m layer of depth. The soil drain P character decreases as the amount of this nutrient supplied in the previous crops is increased.

MASCEM improvement for agent based coalitions

This paper presents MASCEM - Multi-Agent Simulator for Electricity Markets improvement towards an enlarged model for Seller Agents coalitions. The simulator has been improved, both regarding its user interface and internal structure. The OOA, used as development platform, version was updated and the multi-agent model was adjusted for implementing and testing several negotiations regarding Seller agents’ coalitions. Seller coalitions are a very important subject regarding the increased relevance of Distributed Generation under liberalised electricity markets.

Residential energy resources management by a SCADA system in case of excess wind generation

The end consumers in a smart grid context are seen as active players. The distributed generation resources applied in smart home system as a micro and small-scale systems can be wind generation, photovoltaic and combine heat and power facility. The paper addresses the management of domestic consumer resources, i.e. wind generation, solar photovoltaic, combined heat and power, electric vehicle with gridable capability and loads, in a SCADA system with intelligent methodology to support the user decision in real time. The main goal is to obtain the better management of excess wind generation that may arise in consumer’s distributed generation resources. The optimization methodology is performed in a SCADA House Intelligent Management context and the results are analyzed to validate the SCADA system.

Cooperative scheduling system with emergent swarm based behavior

This paper presents a Swarm based Cooperation Mechanism for scheduling optimization. We intend to conceptualize real manufacturing systems as interacting autonomous entities in order to support decision making in agile manufacturing environments. Agents coordinate their actions automatically without human supervision considering a common objective – global scheduling solution taking advantages from collective behavior of species through implicit and explicit cooperation. The performance of the cooperation mechanism will be evaluated consider implicit cooperation at first stage through ACS, PSO and ABC algorithms and explicit through cooperation mechanism application.