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.

Scale-free network of a dengue epidemic

In this work we show that the dengue epidemic in the city of Singapore organized itself into a scale-free network of transmission as the 2000-2005 outbreaks progressed. This scale-free network of cluster comprised geographical breeding places for the aedes mosquitoes, acting as super-spreaders nodes in a network of transmission. The geographical organization of the network was analysed by the corresponding distribution of weekly number of new cases. Therefore, our hypothesis is that the distribution of dengue cases reflects the geographical organization of a transmission network, which evolved towards a power law as the epidemic intensity progressed until 2005. (c) 2007 Elsevier Inc. All rights reserved.

Selective Decrease of Components of the Creatine Kinase System and ATP Synthase Complex in Chronic Chagas Disease Cardiomyopathy

Background: Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy with a worse prognosis than other cardiomyopathies. CCC occurs in 30 % of individuals infected with Trypanosoma cruzi, endemic in Latin America. Heart failure is associated with impaired energy metabolism, which may be correlated to contractile dysfunction. We thus analyzed the myocardial gene and protein expression, as well as activity, of key mitochondrial enzymes related to ATP production, in myocardial samples of end-stage CCC, idiopathic dilated (IDC) and ischemic (IC) cardiomyopathies. Methodology/Principal Findings: Myocardium homogenates from CCC (N = 5), IC (N = 5) and IDC (N = 5) patients, as well as from heart donors (N = 5) were analyzed for protein and mRNA expression of mitochondrial creatine kinase (CKMit) and muscular creatine kinase (CKM) and ATP synthase subunits aplha and beta by immunoblotting and by real-time RT-PCR. Total myocardial CK activity was also assessed. Protein levels of CKM and CK activity were reduced in all three cardiomyopathy groups. However, total CK activity, as well as ATP synthase alpha chain protein levels, were significantly lower in CCC samples than IC and IDC samples. CCC myocardium displayed selective reduction of protein levels and activity of enzymes crucial for maintaining cytoplasmic ATP levels. Conclusions/Significance: The selective impairment of the CK system may be associated to the loss of inotropic reserve observed in CCC. Reduction of ATP synthase alpha levels is consistent with a decrease in myocardial ATP generation through oxidative phosphorylation. Together, these results suggest that the energetic deficit is more intense in the myocardium of CCC patients than in the other tested dilated cardiomyopathies.

Exploiting Mn(III)/EDTA complex in a flow system with solenoid micro-pumps coupled to long pathlength spectrophotometry for fast manganese determination

The formation of the Mn(III)/EDTA complex in a flow system with solenoid micro-pumps was exploited for fast manganese determination in freshwater. Manganese(II) was oxidized in a solid-phase reactor containing lead dioxide immobilized on polyester. Long pathlength spectrophotometry was exploited to increase sensitivity, aiming to reach the threshold limit established by environmental legislation. A linear response was observed from 25 to 1500 mu g L(-1), with a detection limit of 6 mu g L(-1) (99.7% confidence level). Sample throughput and coefficient of variation were 36 samples/h and 2.6% (n = 10), respectively. EDTA consumption and waste generation were estimated as 500 mu g and 3 mL per determination, respectively. The amount of Pb in the residue corresponds to 250 mu g per determination and a solid-phase reactor could be used for up to 1600 determinations. Adsorption in active charcoal avoided interferences caused by organic matter and the developed procedure was successfully applied for determination of manganese in freshwater samples. Results were in agreement with those attained by GFAAS at the 95% confidence level. (C) 2010 Elsevier B.V. All rights reserved.

PERFORMANCE OF THE MODEL CALLED ACQUANETXL IN THE ALLOCATION OF WATER IN COMPLEX WATER RESOURCE SYSTEMS

This article presents a tool for the allocation analysis of complex systems of water resources, called AcquaNetXL, developed in the form of spreadsheet in which a model of linear optimization and another nonlinear were incorporated. The AcquaNetXL keeps the concepts and attributes of a decision support system. In other words, it straightens out the communication between the user and the computer, facilitates the understanding and the formulation of the problem, the interpretation of the results and it also gives a support in the process of decision making, turning it into a clear and organized process. The performance of the algorithms used for solving the problems of water allocation was satisfactory especially for the linear model.

A Dynamical Modeling to Study the Adaptive Immune System and the Influence of Antibodies in the Immune Memory

Immunological systems have been an abundant inspiration to contemporary computer scientists. Problem solving strategies, stemming from known immune system phenomena, have been successfully applied to chall enging problems of modem computing. Simulation systems and mathematical modeling are also beginning use to answer more complex immunological questions as immune memory process and duration of vaccines, where the regulation mechanisms are not still known sufficiently (Lundegaard, Lund, Kesmir, Brunak, Nielsen, 2007). In this article we studied in machina a approach to simulate the process of antigenic mutation and its implications for the process of memory. Our results have suggested that the durability of the immune memory is affected by the process of antigenic mutation.and by populations of soluble antibodies in the blood. The results also strongly suggest that the decrease of the production of antibodies favors the global maintenance of immune memory.

Modeling the Competition Between Viruses in a Complex Plant-Pathogen System

In this article, we propose a mathematical model that describes the competition between two plant virus strains (MAV and PAV) for both the host plant (oat) and their aphid vectors. We found that although PAV is transmitted by two aphids and MAV by only one, this fact, by itself, does not explain the complete replacement of MAV by PAV in New York State during the period from 1961 through 1976; an interpretation that is in agreement with the theories of A. G. Power. Also, although MAV wins the competition within aphids, we assumed that, in 1961, PAV mutated into a new variant such that this new variant was able to overcome MAV within the plants during a latent period. As shown below, this is sufficient to explain the swap of strains; that is, the dominant MAV was replaced by PAV, also in agreement with Power`s expectations.

The GABAergic system contributes to the anxiolytic-like effect of essential oil from Cymbopogon citratus (lemongrass)

Ethnopharmacological relevance: The essential oil (EO) from Cymbopogon citratus (DC) Stapf is reported to have a wide range of biological activities and is widely used in traditional medicine as an infusion or decoction. However, despite this widely use, there are few controlled studies confirming its biological activity in central nervous system. Materials and methods: The anxiolytic-like activity of the EO was investigated in light/dark box (LDB) and marble-burying test (MBT) and the antidepressant activity was investigated in forced-swimming test (FST) in mice. Flumazenil, a competitive antagonist of benzodiazepine binding and the selective 5-HT(1A) receptor antagonist WAY100635 was used in experimental procedures to determine the action mechanism of EO. To exclude any false positive results in experimental procedures, mice were submitted to the rota-rod test. We also quantified some neurotransmitters at specific brain regions after EO oral acute treatment. Results: The present work found anxiolytic-like activity of the EO at the dose of 10 mg/kg in a LDB. Flumazenil, but not WAY100635, was able to reverse the effect of the EO in the LOB, indicating that the EO activity occurs via the GABA(A) receptor-benzodiazepine complex. Only at higher doses did the EO potentiate diethyl-ether-induced sleeping time in mice. In the FST and MBT, EO showed no effect. Finally, the increase in time spent in the light chamber, demonstrated by concomitant treatment with ineffective doses of diazepam (DZP) and the EO, revealed a synergistic effect of the two compounds. The lack of activity after long-term treatment in the LDB test might be related to tolerance induction, even in the DZP-treated group. Furthermore, there were no significant differences between groups after either acute or repeated treatments with the EO in the rota-rod test. Neurochemical evaluation showed no amendments in neurotransmitter levels evaluated in cortex, striatum, pons, and hypothalamus. Conclusions: The results corroborate the use of Cymbopogon citratus in folk medicine and suggest that the anxiolytic-like effect of its EO is mediated by the GABA(A) receptor-benzodiazepine complex. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Sexual System, Sex Ratio, and Group Living in the Shrimp Thor amboinensis (De Man): Relevance to Resource-Monopolization and Sex-Allocation Theories

The sexual system of the symbiotic shrimp Thor amboinensis is described, along with observations on sex ratio and host-use pattern of different populations. We used a comprehensive approach to elucidate the previously unknown sexual system of this shrimp. Dissections, scanning electron microscopy, size-frequency distribution analysis, and laboratory observations demonstrated that T amboinensis is a protandric hermaphrodite: shrimp first mature as males and change into females later in life. Thor amboinensis inhabited the large and structurally heterogeneous sea anemone Stichoclactyla helianthus in large groups (up to 11 individuals) more frequently than expected by chance alone. Groups exhibited no particularly complex social structure and showed male-biased sex ratios more frequently than expected by chance alone. The adult sex ratio was male-biased in the four separate populations studied, one of them being thousands of kilometers apart from the others. This study supports predictions central to theories of resource monopolization and sex allocation. Dissections demonstrated that unusually large males were parasitized by an undescribed species of isopod (family Entoniscidae). Infestation rates were similarly low in both sexes (approximate to 11%-12%). The available information suggests that T. amboinensis uses pure search promiscuity as a mating system. This hypothesis needs to be formally tested with mating behavior observations and field measurements on the movement pattern of both sexes of the species. Further detailed studies on the lifestyle and sexual system of all the species within this genus and the development of a molecular phylogeny are necessary to elucidate the evolutionary history of gender expression in the genus Thor.

A new nitrosyl ruthenium complex: Synthesis, chemical characterization, in vitro and in vivo antitumor activities and probable mechanism of action

This study describes the synthesis of a new ruthenium nitrosyl complex with the formula [RuCl(2)NO(BPA)] [BPA = (2-hydroxybenzyl)(2-methylpyridyl)amine ion], which was synthesized and characterized by spectroscopy, cyclic voltammetry, X-ray crystallography, and theoretical calculation data. The biological studies of this complex included in vitro cytotoxic assays, which revealed its activity against two different tumor cell lines (HeLa and Tm5), with efficacy comparable to that of cisplatin, a metal-based drug that is administered in clinical treatment. The in vivo studies showed that [RuCl2NO(BPA)] is effective in reducing tumor mass. Also, our results suggest that the mechanism of action of [RuCl(2)NO(BPA)] includes binding to DNA, causing fragmentation of this biological molecule, which leads to apoptosis. (C) 2011 Elsevier Masson SAS. All rights reserved.

A multicommuted flow-system for spectrophotometric determination of tannin exploiting the Cu(I)/BCA complex formation

A flow system exploiting the multicommutation approach is proposed for spectrophotometric determination of tannin in beverages. The procedure is based on the reduction of Cu(II) in the presence of 4,4`-dicarboxy-2,2`-biquinoline, yielding a complex with maximum absorption at 558 nm. Calibration graph was linear (r=0.999) for tannic acid concentrations up to 5.00 mu mol L-1. The detection limit and coefficient of variation were estimated as 10 nmol L-1 (99.7% confidence level) and 1% (1.78 mu mol L-1 tannic acid, n=10), respectively. The sampling rate was 50 determinations per hour. The proposed procedure is more sensitive and selective than the official Folin-Denis method, also minimizing drastically waste generation. Recoveries within 91.8 and 115% were estimated for total tannin determination in tea and wine samples. (C) 2007 Elsevier B.V. All rights reserved.

Electrocatalytic oxidation of methanol by the [Ru3O(OAc)6(py)2(CH3OH)]3+cluster: improving the metal-ligand electron transfer by accessing the higher oxidation states of a multicentered system

The [Ru3O(Ac)6(py)2(CH3OH)]+ cluster provides an effective electrocatalytic species for the oxidation of methanol under mild conditions. This complex exhibits characteristic electrochemical waves at -1.02, 0.15 and 1.18 V, associated with the Ru3III,II,II/Ru3III,III,II/Ru 3III,III,III /Ru3IV,III,III successive redox couples, respectively. Above 1.7 V, formation of two RuIV centers enhances the 2-electron oxidation of the methanol ligand yielding formaldehyde, in agreement with the theoretical evolution of the HOMO levels as a function of the oxidation states. This work illustrates an important strategy to improve the efficiency of the oxidation catalysis, by using a multicentered redox catalyst and accessing its multiple higher oxidation states.

Anthropogenic influences in a lagoonal environment: a multiproxy approach at the valo grande mouth, Cananéia-Iguape system (SE Brazil)

The Cananéia-Iguape system, SE Brazil, consists of a complex of lagoonal channels, located in a United Nations Educational, Scientific and Cultural Organization (UNESCO) Biosphere Reserve. Nevertheless, important environmental changes have occurred in approximately the last 150 yrs due to the opening of an artificial channel, the Valo Grande, connecting the Ribeira de Iguape River to the lagoonal system. Our objective is to assess the historical record of the uppermost layers of the sedimentary column of the lagoonal system in order to determine the history of environmental changes caused by the opening of the artificial channel. In this sense, an integrated geochemical-faunal approach is used. The environmental changes led significant modifications in salinity, in changes of the depositional patterns of sediments and foraminiferal assemblages (including periods of defaunation), and, more drastically, in the input of heavy metals to the coastal environment. The concentrations Pb in the core analyzed here were up to two times higher than the values measured in contaminated sediments from the Santos estuary, the most industrialized coastal zone in Brazil.

Energy system contributions to the special judo fitness test

Purpose: This study investigated the energy system contributions of judo athletes to the Special Judo Fitness Test (SJFT). Methods: Fourteen male judo athletes performed the SJFT, which comprised three periods of judo activity (A = 15 s, B and C = 30 s) interspersed with 10 s rest intervals. During this test, one athlete threw two others positioned 6 m from each other using the ippon-seoi-nage technique. The fractions of the aerobic, anaerobic alactic and anaerobic lactic systems were calculated based on oxygen uptake, the fast component of excess postexercise oxygen uptake, and changes in net blood lactate, respectively. The contribution of the three energy systems was compared using a repeated measures analysis of variance and Bonferroni's multiple comparisons test. Compound symmetry, or sphericity, was determined by Mauchly's test. A level of significance of 5% (P < .05) was adopted in all analyses. Results: The alactic energy system presented a higher (F = 20.9; P < .001; power observed = 1.0) contribution (86.8 +/- 23.6 kJ; 42.3 +/- 5.9%) during the test when compared with both aerobic (57.1 +/- 11.3 kJ; 28.2 +/- 2.9%) and lactic (58.9 +/- 12.1 kJ; 29.5 +/- 6.2%) energy systems (P < .001 for both comparisons). Conclusions: The higher alactic contribution seems to be a consequence of the high-intensity efforts performed during the test, and its intermittent nature. Thus, when using the SJFT, coaches are evaluating mainly their athletes' anaerobic alactic system, which can be considered to be the most predominant system contributing to the actions (techniques) performed in the match.

DESCRIPTION OF THE MALE REPRODUCTIVE SYSTEM OF THE HERMIT CRAB CALCINUS TIBICEN (DECAPODA: ANOMURA: DIOGENIDAE)

We describe the male reproductive system of the intertidal hermit crab Calcinus tihicen, with emphasis on the sexual apparatus, spermatophore, and spermatozoa. The crabs were collected on the rocky shore of Praia Grande Beach, Ubatuba, southeastern Brazil. The morphological analysis, based on 30 specimens, was made with the use of a stereomicroscope, an optical microscope, and scanning and transmission electron microscopes. The male reproductive system is composed of a pair of juxtaposed testes, located dorsally in the pleon. From each testis emerges a vas deferens that links it to the exterior by the gonopores. located on the base of the fifth pair of pereiopods. The vas deferens has three macroscopically distinct regions that contain spermatophores in different stages of maturation. The spermatophore morphology is similar to that of other members of Paguroidea, having a distal, nearly spherical ampulla containing spermatozoa; an approximately cylindrical peduncle and a proximal foot connecting the spermatophores. We describe, for the first time, the variability in the spermatophore morphology and size in the three regions of the vas deferens using the type species of the genus Calcinus. The spermatozoa have three main regions (the acrosomal vesicle, the nucleus, and the cytoplasm). The morphological similarity of the male reproductive system of C. tihicen with previously studied species of Diogenidae is an indicative of complex phylogenetic relationships among the members of the genus.