Tamoxifen Is Effective in the Treatment of Leishmania amazonensis Infections in Mice

Background: Chemotherapy is still a critical issue in the management of leishmaniasis. Until recently, pentavalent antimonials, amphotericin B or pentamidine compounded the classical arsenal of treatment. All these drugs are toxic and have to be administered by the parenteral route. Tamoxifen has been used as an antiestrogen in the treatment and prevention of breast cancer for many years. Its safety and pharmacological profiles are well established in humans. We have shown that tamoxifen is active as an antileishmanial compound in vitro, and in this paper we analyzed the efficacy of tamoxifen for the treatment of mice infected with Leishmania amazonensis, an etiological agent of localized cutaneous leishmaniasis and the main cause of diffuse cutaneous leishmaniasis in South America. Methodology/Principal Findings: BALB/c mice were infected with L. amazonensis promastigotes. Five weeks post-infection, treatment with 15 daily intraperitoneal injections of 20 mg/kg tamoxifen was administered. Lesion and ulcer sizes were recorded and parasite burden quantified by limiting dilution. A significant decrease in lesion size and ulcer development was noted in mice treated with tamoxifen as compared to control untreated animals. Parasite burden in the inoculation site at the end of treatment was reduced from 10(8.5 +/- 0.7) in control untreated animals to 10(5.0 +/- 0.0) in tamoxifen-treated mice. Parasite load was also reduced in the draining lymph nodes. The reduction in parasite number was sustained: 6 weeks after the end of treatment, 10(15.5 +/- 0.5) parasites were quantified from untreated animals, as opposed to 10(5.1 +/- 0.1) parasites detected in treated mice. Conclusions/Significance: Treatment of BALB/c mice infected with L. amazonensis for 15 days with tamoxifen resulted in significant decrease in lesion size and parasite burden. BALB/c mice infected with L. amazonensis represents a model of extreme susceptibility, and the striking and sustained reduction in the number of parasites in treated animals supports the proposal of further testing of this drug in other models of leishmaniasis.

Synchrotron X-ray powder diffraction study of the tetragonal-cubic phase transition in nanostructured ZrO2-Sc2O3 solid solutions

The transition between tetragonal and cubic phases in nanostructured ZrO2-Sc2O3 solid solutions by high-temperature X-ray powder diffraction using synchrotron radiation is presented. ZrO2-8 and 11 mol% Sc2O3 nanopowders that exhibit the t'- and t ''-forms of the tetragonal phase, respectively, were synthesized by a stoichiometric nitrate-lysine gel-combustion route. The average crystallite size treated at 900 degrees C was about 25 nm for both compositions. Our results showed that t'-t '' and t ''-cubic transitions take place for the 8 and 11 mol% Sc2O3 samples, respectively. (C) 2008 International Centre for Diffraction Data.

Absence of ferromagnetic order in high quality bulk Co-doped ZnO samples

Bulk Zn(1-x)Co(x)O samples were synthesized via standard solid-state reaction route with different Co molar concentrations up to 21%. A detailed microstructural analysis was carried out to investigate alternative sources of ferromagnetism, such as secondary phases and nanocrystals embedded in the bulk material. Conjugating different techniques we confirmed the Zn replacement by Co ions in the wurtzite ZnO structure, which retains, however, a high crystalline quality. No segregated secondary phases neither Co-rich nanocrystals were detected. Superconducting quantum interference device magnetometry demonstrates a paramagnetic Curie-Weiss behavior with antiferromagnetic interactions. We discuss the observed room temperature paramagnetism of our samples considering the current models for the magnetic properties of diluted magnetic semiconductors. (C) 2010 American Institute of Physics. [doi: 10.1063/1.3459885]

Interference with Hemozoin Formation Represents an Important Mechanism of Schistosomicidal Action of Antimalarial Quinoline Methanols

Background: The parasitic trematode Schistosoma mansoni is one of the major causative agents of human schistosomiasis, which afflicts 200 million people worldwide. Praziquantel remains the main drug used for schistosomiasis treatment, and reliance on the single therapy has been prompting the search for new therapeutic compounds against this disease. Our group has demonstrated that heme crystallization into hemozoin (Hz) within the S. mansoni gut is a major heme detoxification route with lipid droplets involved in this process and acting as a potential chemotherapeutical target. In the present work, we investigated the effects of three antimalarial compounds, quinine (QN), quinidine (QND) and quinacrine (QCR) in a murine schistosomiasis model by using a combination of biochemical, cell biology and molecular biology approaches. Methodology/Principal Findings: Treatment of S. mansoni-infected female Swiss mice with daily intraperitoneal injections of QN, and QND (75 mg/kg/day) from the 11(th) to 17(th) day after infection caused significant decreases in worm burden (39%-61%) and egg production (42%-98%). Hz formation was significantly inhibited (40%-65%) in female worms recovered from QN- and QND-treated mice and correlated with reduction in the female worm burden. We also observed that QN treatment promoted remarkable ultrastructural changes in male and female worms, particularly in the gut epithelium and reduced the granulomatous reaction to parasite eggs trapped in the liver. Microarray gene expression analysis indicated that QN treatment increased the expression of transcripts related to musculature, protein synthesis and repair mechanisms. Conclusions: The overall significant reduction in several disease burden parameters by the antimalarial quinoline methanols indicates that interference with Hz formation in S. mansoni represents an important mechanism of schistosomicidal action of these compounds and points out the heme crystallization process as a valid chemotherapeutic target to treat schistosomiasis.

Optimisation of environmental gas cleaning routes for solid wastes cogeneration systems. Part II - Analysis of waste incineration combined gas/steam cycle

In the first paper of this paper (Part I), conditions were presented for the gas cleaning technological route for environomic optimisation of a cogeneration system based in a thermal cycle with municipal solid waste incineration. In this second part, an environomic analysis is presented of a cogeneration system comprising a combined cycle composed of a gas cycle burning natural gas with a heat recovery steam generator with no supplementary burning and a steam cycle burning municipal solid wastes (MSW) to which will be added a pure back pressure steam turbine (another one) of pure condensation. This analysis aims to select, concerning some scenarios, the best atmospheric pollutant emission control routes (rc) according to the investment cost minimisation, operation and social damage criteria. In this study, a comparison is also performed with the results obtained in the Case Study presented in Part I. (c) 2007 Elsevier Ltd. All rights reserved.

Chemoenzymatic synthesis: a strategy to obtain xylitol monoesters

BACKGROUND: Fatty acid sugar esters are used as non-ionic surfactants in cosmetics, foodstuffs and pharmaceuticals. In particular, monoesters of xylitol have attracted industrial interest due to their outstanding biological activities. In this work, xylitol monoesters were obtained by chemoenzymatic synthesis, in which, first, xylitol was made soluble in organic solvent by chemo-protecting reaction, followed by enzymatic esterification reaction using different acyl donors. A commercial immobilized Candida antartica lipase was used as catalyst, and reactions with pure xylitol were carried out to generate data for comparison. RESULTS: t-BuOH was found to be the most suitable solvent to carry out esterification reactions with both pure and protected xylitol. The highest yields were obtained for reactions carried out with pure xylitol, but in this case by-products, such as di- and tri-esters isomers were formed, which required a multi-step purification process. For the systems with protected xylitol, conversions of 86%, 58% and 24% were achieved using oleic, lauric and butyric acids, respectively. The structures of the monoesters were confirmed by (13)C- and (1)H-NMR and microanalysis. CONCLUSION: The chemoenzymatic synthesis of xylitol monoesters avoided laborious downstream processing when compared with reactions performed with pure xylitol. Monoesters production from protected xylitol was shown to be a practical, economical, and clean route for this process, allowing a simple separation, because there are no other products formed besides xylitol monoesters and residual xylitol. (C) 2009 Society of Chemical Industry

Antimicrobial drug administration errors identified in Brazilian multicentric study

Medication administration errors (MAE) are the most frequent kind of medication errors. Errors with antimicrobial drugs (AD) are relevant because they may interfere inpatient safety and in the development of microbial resistance. The aim of this study is to analyze the AD errors detected in a Brazilian multicentric study of MAE. It was a devcriptive and explorotory study carried out in clinical units in five Brazilian teaching hospitals. The hospitals were investigated during 30 days. MAE were detected by observation technique. MAE were classified in categories: wrong route(WR), wrong patient(WP), wrong dose(WD) wrong time (WT) and unordered drug (UD). AD with MA E were classified by Anatomical-Therapeutical-Chemical Classification System. AD with narrow therapeutic index (NTI) wet-e identified A descriptive statistical analysis was performed using SPSS version 11.5 software. A total of 1500 errors were observed, 277 (18.5%) of them were error with AD. The hopes of AD error were: WT87.7%, QD 6.9%, WR 1.5%, UD 3.2% and WP 0.7%. The number of AD found was 36. The mostly ATC class were fluoroquinolones 13.9%, combinations of penicillin 13.9%, macrolides 8.3% and third-generation cephalosporines 5.6%. The parenteral drug dosage form was associated with 55.6% of AD. 16.7% of AD were NTI. 47.4% of WD and 21.8% WT were with NTI drugs. This study shows that these errors should be considered potential areas for improvement in the medication process and patient safety plus there is requirement to develop rational drug use of AD.

Degradation of formaldehyde in anaerobic sequencing batch biofilm reactor (ASBBR)

The present study evaluated the degradation of formaldehyde in a bench-scale anaerobic sequencing batch reactor, which contained biomass immobilized in polyurethane foam matrices. The reactor was operated for 212 days at 35 C with 8 h sequential cycles, under different affluent formaldehyde concentrations ranging from 31.6 to 1104.4 mg/L (formaldehyde loading rates from 0.08 to 2.78 kg/m(3) day). The results indicate excellent reactor stability and over 99% efficiency in formaldehyde removal, with average effluent formaldehyde concentration of 3.6 + 1.7 mg/L. Formaldehyde degradation rates increased from 204.9 to 698.3 mg/L h as the initial concentration of formaldehyde was increased from around 100 to around 1100 mg/L. However, accumulation of organic matter was observed in the effluent (chemical oxygen demand (COD) values above 500 mg/L) due to the presence of non-degraded organic acids, especially acetic and propionic acids, This observation poses an important question regarding the anaerobic route of formaldehyde degradation, which might differ Substantially from that reported in the literature. The anaerobic degradation pathway can be associated with the formation of long-chain oligomers from formaldehyde. Such long- or short-chain polymers are probably the precursors of organic acid formation by means of acidogenic anaerobic microorganisms. (C) 2008 Elsevier B.V. All rights reserved.

Effects of interactions between algal densities and cadmium concentrations on Ceriodaphnia dubia fecundity and survival

The influence of different densities of the algae Pseudokirchneriella subcapitata on the chronic toxicity of cadmium to Ceriodaphnia dubia was investigated. The importance of algal cells as a source of metal to zooplankton was studied by exposing P. subcapitata cells to free cadmium ions and supplying the algae as food to C. dubia. The results of a bifactorial analysis (metal versus food levels) showed that metal toxicity to zooplankton was dependent on food level. Significant toxic effects on the fecundity and survival of C. dubia were observed at low metal concentrations with high algal density. Algae contaminated with Cd2+ were less toxic to cladoceran than was the Cd2+ in solution. Green algae retained cadmium and released low metal concentration in the test medium. We concluded that algal cells are an important route of exposure to metal and a factor that has an appreciable influence on the expression of metal toxicity to daphnids. (C) 2007 Elsevier Inc. All rights reserved.

FWM Constraints Management for Lightpath Establishment in GMPLS Networks

In all-optical networks, management of physical layer restrictions should collaborate in lightpath establishment. Label-Switched Path validation in Generalized MultiProtocol Label Switching on Dense Wavelength Division Multiplexing network requires the treatment of the physical impairment-related parameters along the provisioned route. In this paper we propose, for the first time in our view, the generation of an optical layer database by simulation that specifically characterizes the dynamic FWM impairments for the lightpaths provisioned in a GMPLS/DWDM network.

Influence of the rubbery phase on the crystallinity and thermomechanical properties of poly(3-hydroxybutyrate)/elastomer blends

Poly(3-hydroxybutyrate) (PHB) is a very promising biopolymer. In order to improve its processability and decrease its brittleness, PHB/elastomer blends can be prepared. In the work reported, the effect of the addition of a rubbery phase, i.e. ethylene - propylene-diene terpolymer (EPDM) or poly(vinyl butyral) (PVB), on the properties of PHB was studied. The effects of rubber type and of changing the PHB/elastomer blend processing method on the crystallinity and physical properties of the blends were also investigated. For blends based on PHB, the main role of EPDM is its nucleating effect evidenced by a decrease of crystallization temperature and an increase of crystallinity with increasing EPDM content regardless of the processing route. While EPDM has a weak effect on PHB glass transition temperature, PVB induces a marked decrease of this temperature thank to its plasticizer that swells the PHB amorphous phase. A promising solution to improve the mechanical properties of PHB seems to be the melt-processing of PHB with both plasticizer and EPDM. In fact, the plasticizer is more efficient than the elastomer in decreasing the PHB glass transition temperature and, because of the nucleating effect of EPDM, the decrease of the PHB modulus due to the plasticizer can be counterbalanced. (C) 2010 Society of Chemical Industry

Thermomechanical processing for recovery of desired < 001 > fiber texture in electric motor steels

A processing route has been developed for recovering the desired lambda fiber in iron-silicon electrical steel needed for superior magnetic properties in electric motor application. The lambda fiber texture is available in directionally solidified iron-silicon steel with the < 001 > columnar grains but was lost after heavy rolling and recrystallization required for motor laminations. Two steps of light rolling each followed by recrystallization were found to largely restore the desired fiber texture. This strengthening of the < 001 > fiber texture had been predicted on the basis of the strain-induced boundary migration (SIBM) mechanism during recrystallization of lightly rolled steel from existing grains of near the ideal orientation, due to postulated low stored energies. Taylor and finite element models supported the idea of the low stored energy of the lambda fiber grains. The models also showed that the lambda fiber grains, though unstable during rolling, only rotated away from their initial orientations quite slowly.

Metal separation from mixed types of batteries using selective precipitation and liquid-liquid extraction techniques

The purpose of this paper is to study metal separation from a sample composed of a mixture of the main types of spent household batteries, using a hydrometallurgical route, comparing selective precipitation and liquid-liquid extraction separation techniques. The preparation of the solution consisted of: grinding the waste of mixed batteries, reduction and volatile metals elimination using electric furnace and acid leaching. From this solution two different routes were studied: selective precipitation with sodium hydroxide and liquid-liquid extraction using Cyanex 272 [bis(2,4,4-trimethylpentyl) phosphoric acid] as extracting agent. The best results were obtained from liquid-liquid extraction in which Zn had a 99% extraction rate at pH 2.5. More than 95% Fe was extracted at pH 7.0, the same pH at which more than 90% Ce was extracted. About 88% Mn, Cr and Co was extracted at this pH. At pH 3.0, more than 85% Ni was extracted, and at pH 3.5 more than 80% of Cd and La was extracted. (C) 2010 Elsevier Ltd. All rights reserved.

Quantification of the environmental impacts of road conditions in Brazil

This study evaluates the impacts of Brazilian highway conditions on fuel consumption and, consequently, on carbon dioxide (COO emissions. For the purpose of this study, highway conditions refer to the level of highway maintenance: the incidence of large potholes, large surface cracks, uneven sections, and debris. Primary computer collected data related to the fuel consumption of three types of trucks were analyzed. The data were derived from 88 trips taken over six routes, each route representative of one of two highway conditions: better or worse. Study results are initially presented for each type of truck being monitored. The results are then aggregated to approximate the entire Brazilian highway network. In all cases, results confirmed environmental benefits resulting from travel over the better routes. There was found to be an increase in energy efficiency from traveling better roads, which resulted in lower fuel consumption and lower CO(2) emissions. Statistical analysis of the results suggests that, in general, fuel consumption data were significant at *P < 0.05, rejecting the null hypothesis that average fuel consumption from traveling the better routes is statistically equal to average fuel consumption from traveling the worse routes. Improved Brazilian road conditions would generate economic benefits, reduce dependency on and consumption of fossil fuels (due to the increase in energy efficiency), and reduce CO(2) emissions. These findings may have additional relevancy if Brazil needs to reduce carbon dioxide emissions to reach future Kyoto Protocol`s emissions targets, which should take effect in January 2013. (c) 2008 Elsevier B.V. All rights reserved.

Synthesis of Cyclic Guanidine Intermediates of Anatoxin-a(s) in Both Racemic and Enantiomerically Pure Forms

The alkyl chain of anatoxin-a(s) (cyclic guanidines), which can be used as an intermediate in the total synthesis of anatoxin-a(s), was synthesized in both racemic and enantiomerically pure forms. These enantiomerically pure cyclic compounds can be used as chiral inductors in some reactions. The two racemic routes disclosed herein have the advantages of high overall yield and mild reaction conditions. Both routes proceed through an intermediate 2,3-diaminoacid - an important synthetic scaffold - with good yields. Furthermore, the N,N-dimethyl-2(tosylimino)imidazolidine-4-carboxamide might be obtained from 2-(tosylimino)imidazolidine-4-carboxylic acid followed by selective reduction of the carbonyl functionality. All synthesized compounds were analyzed by mass spectrometry and (1)H NMR and (13)C NMR spectroscopy.