Publication year: 2012
Source: Ecological Economics, Available online 4 February 2012

Anke Reichhuber, Till Requate

This paper presents a cost-benefit analysis of three different use systems for the remaining cloud forests in Ethiopia, which at present are being depleted at the rate of 8% per year. These use systems are a) traditional conversion to crop land, b) sustainable management of the forest (e.g. by growing high-quality, semi-forest coffee), and c) strict conservation. We find that under business as usual conversion to cropland yields the highest net present income value for the local population. Taking into account watershed services, sustainable forest use is in the best interests of the country for discount rates of 10% or lower. Taking into account theglobalbenefits of biodiversity conservation and carbon storage, sustainable forest management also yields the highest total economic value while strict conservation does not pass a cost-benefit test even at a discount rate of 3%.

Publication year: 2012
Source: Ecological Economics, Available online 3 February 2012

Ethan D. Schoolman, Chunbo Ma

Systematic research into social inequalities in the distribution of environmental hazards, though well-established in American sociology, has largely not been conducted using quantitative data from developing countries. In this study we consider whether theory and methods developed to test for and explain environmental inequality in the U.S. can be extended to a major developing country such as China. We argue that, due in part to the state'shukouregistry system, urban workers in China with an official rural residence may be subject to disproportionate exposure to environmental pollution. We also argue that environmental inequalities in China may be shaped in part by social processes analogous to those which have been held to explain racial differences in pollution exposure in the U.S. In an analysis of the locations and emissions of pollution-producing facilities in China's Jiangsu province, we find that townships with a higher percentage of rural migrants are more likely to be exposed to high levels of air and water pollution. This finding holds even after we control for income and for the presence of “dirty and hard” industries in which rural migrants are most likely to find work.

Highlights? We argue that rural migrants in China occupy a place analogous to that of racial minorities in the U.S. ? We examine a major Chinese province for evidence of environmental inequality. ? We consider both facility locations and emissions weighted by proximity to township centers. ? Rural migrants are exposed to disproportionately high levels of pollution. ? This relationship holds after controlling for employment in heavy industries.

Publication year: 2012
Source: Ecological Economics, Available online 3 February 2012

Constantin Chilarescu, Ioana Viasu

In this paper we give some comments onto the paper of Kozo Mayumi and Mario Giampietro, recently published in this journal and, finally we present some conclusions.

Publication year: 2012
Source: Urology, Available online 2 February 2012

Matthew S. Christman, Stephen A. Zderic, Thomas F. Kolon

Concordant and discordant presentations of posterior urethral valves (PUV) in twins have been described. Twin gestation may complicate the diagnosis of PUV based on prenatal evaluation. A case series of 2 sets of twin births is presented, each of which was discordant for the diagnosis of PUV. A delay in diagnosis occurred in both cases, despite prenatal ultrasound abnormalities. This delay could result from failed sensitivity of prenatal ultrasound or from postnatal evaluation of the incorrect twin. Caution must be exercised during follow-up of abnormalities identified on prenatal ultrasound in diseases in which there are no external distinguishing characteristics.

Publication year: 2012
Source: Urology, Available online 2 February 2012

Yun-Lin Ye, Xiang-Zhou Sun, Fu-Fu Zheng, Jun Bian, Yan-Ping Huang, ...

ObjectiveTo analyze our experiences of pediatric testicular tumors and investigate the management of pediatric testicular germ cell tumors. Pediatric testicular tumors are rare and the treatment of them has not been well defined.MethodsChildren treated for primary testicular tumors between January 1998 and July 2010 were retrospectively analyzed. For yolk sac tumor, the difference of survival rates between patients with and without retroperitoneal lymph node dissection (RPLND) was calculated.ResultsEighty-seven cases met our criteria and 78 were germ cell tumors, including 40 cases with yolk sac tumor. Patients were 3–128 months old (median 19), and 53 patients were diagnosed at younger than 2 years of age. For germ cell tumors, serum ?-fetoprotein and ?-human chorionic gonadotropin were elevated in 48 and 7 patients, respectively, including 38 and 2 in those with yolk sac tumor. RPLND and chemotherapy were performed in 13 and 19 patients, respectively, and surveillance was performed in 50 patients. With median follow-up of 50 months, 6 patients had recurrence, 4 patients died, and the others achieved complete remission. For stage I yolk sac tumor, the difference of survival rates between patients with and without RPLND was not significant (P= .808).ConclusionYolk sac tumor is the most common type of pediatric testicular tumor. For stage I yolk sac tumor, radical inguinal orchiectomy is effective, salvage chemotherapy is promising, and RPLND may not be necessary.

Publication year: 2012
Source: Urology, Available online 2 February 2012

Kevinjit Sandhu, Jonathan Masters, Yaron Ehrlich

ObjectiveTo evaluate the outcome of ureteropyelostomy using the native ureter for the management of ureteric obstruction or symptomatic reflux after renal transplantation.Materials and methodsThis is a single-center retrospective review of consecutive patients who underwent ureteropyelostomy after renal transplantation between the years 2000 and 2009. Ureteropyelostomy was performed using the ipsilateral native ureter. The native kidney was not removed. Patients' baseline characteristics, preceding interventions, and postprocedural outcomes were analyzed.ResultsTen patients underwent ureteropyelostomy after renal transplantation. All had initial Lich Gregoir ureterovesical anastomosis. Reasons for the reconstructive surgery were transplant ureteric stenosis in 8 patients or vesicoureteric reflux causing recurrent graft pyelonephritis in 2 patients. Median follow-up was 53 months (range 24-76). Postoperative complications included 3 patients who had transient anastomotic obstruction after removal of the double pigtail stent. They were managed with short-term ureteric restenting or nephrostomy tube insertion. In addition, 2 patients required delayed ipsilateral native nephrectomy because of infection. At last follow-up, all grafts remained unobstructed and free of infections.ConclusionUreteropyelostomy using the native ureter for the management of transplant ureteric obstruction or symptomatic reflux is safe and provides good long-term preservation of graft function in selected patients.

Publication year: 2012
Source: Urology, Available online 2 February 2012

Xu-sheng Chen, Zhen-ting Zhang, Jun Du, Xin-chun Bi, Guang Sun, ...

ObjectiveTo determine the optimal surgical margins in nephron-sparing surgery (NSS) for T1b renal cell carcinomas (RCC).Materials and methodsWe retrospectively assessed 87 T1b RCC specimens after radical nephrectomy through whole-kidney continuous sections, with 92 T1a RCCs included as controls. The completeness of pseudocapsule (PS) and extra-PS lesions and multifocality were microscopically examined, as was the greatest distance between extra-PS lesions and primary tumors.ResultsThe rates of incomplete PS (34% [30/87] vs 18% [17/92],P= .015) and positive cancer lesions beyond the PS (39% [34/87] vs 25% [23/92],P= .043) were significantly higher in the T1b than in the T1a group. All extra-PS lesions were located within 3.0 mm of the primary tumor. Multifocal tumors were found in 6% (5/87) of patients with T1b and 5% (5/92) of patients with T1a tumors (P= .928).ConclusionThese results indicate that 4 mm may be the optimal surgical margin for NSS for patients with T1b RCC because all extra-PS lesions were located within 3 mm of the primary tumors.

Publication year: 2012
Source: Ecological Economics, Available online 1 February 2012

F. Vieux, N. Darmon, D. Touazi, L.G. Soler

The aim was to estimate the greenhouse gas emissions (GHGE) associated with self-selected diets and to evaluate the impact of modifying dietary structures on diet-associated GHGE. Food consumption data from 1918 adults participating in the French national dietary survey and GHGE of 73 highly consumed foods (in g CO2e/100 g of edible food) were used to estimate the GHGE of each individual diet. The mean diet-associated GHGE was 4170 g CO2e/day and a high inter-individual variability was observed. When the total caloric intakes were reduced to meet the individual energy needs, the diet-associated GHGE decreased by either 10.7% or 2.4%, depending on the assumption made on the average physical activity level of the population. The meat and deli meat food group represented the strongest diet-associated GHGE contributor, but the impact of different meat reduction scenarios was modest. In particular, when fruit and vegetables were iso-calorically substituted for meat, either null or even positive diet-associated GHGE variations were observed because the needed amounts of fruit and vegetables to maintain the caloric content of the diet were high. Therefore, substituting fruit and vegetables for meat (especially deli meat) may be desirable for health but is not necessarily the best approach to decreasing diet-associated GHGE.

Highlights? Diet-associated greenhouse gas emissions (GHGE) were estimated using the French individual food consumption survey data. ? The mean diet-associated GHGE was estimated at 4170g CO2e/d and was higher for men than for women. ? Individual diet-associated GHGE showed a high variability due to the variability of both diet quantity and diet structure. ? Meat was the strongest contributor to diet-associated GHGE. ? When meat was iso-calorically replaced with fruit and vegetables, only small diet-associated GHGE variations were observed.

Publication year: 2012
Source: Journal of Inorganic Biochemistry, Available online 31 January 2012

Robert M. Breece, Leticia I. Llarrull, Mariana F. Tioni, Alejandro J. Vila, David L. Tierney

Cobalt and zinc binding by the subclass B1 metallo-?-lactamase BcII fromBacillus cereusis examined by X-ray absorption spectroscopy, at various levels of metal loading. The data show that a significant amount of the dinuclear enzyme is formed, even at substoichiometric levels of metal loading, whether the added metal is Zn(II) or Co(II). Increasing metal addition, from 0.5 to 1.0 to 2.0 eq per mole of enzyme, are shown to result in a more ordered active site. While Zn(II) appears to show no preference for the Zn1(3H) or Zn2(DCH) sites, the extended X-ray absorption fine structure (EXAFS) suggests that Co(II) shows a slight preference for the DCH site at low levels of added Co(II). The results are discussed in the context of similar metal binding studies of other B1 metallo-?-lactamases.

Cobalt and zinc binding by the subclass B1 metallo-?-lactamase BcII fromBacillus cereusis examined by X-ray absorption spectroscopy, at various levels of metal loading. While Zn(II) shows no preference for either site, Co(II) shows a slight preference for the DCH site at low levels of added Co(II); both show significant dinuclear enzyme at all metal loadings.

Publication year: 2012
Source: Journal of Inorganic Biochemistry, Available online 31 January 2012

Ljiljana E. Mihajlovi?, Aleksandar Savi?, Jelena Poljarevi?, Ivan Vu?kovi?, Marija Moji?, ...

This paper focuses on the synthesis, characterization and biological activity of newN,N?-methylene modified cyclohexyl ethylenediamine-N,N?-diacetate (edda)-type ligands and their Pt(IV) complexes. Both the ligands and complexes were characterized by infrared, UV–vis, ESI-MS, 1D (H, C,Pt) and 2D (COSY, HSQC, HMBC) NMR spectroscopy and elemental analysis. The possible correlation between the reduction potentials and the cytotoxicity of the complexes was examined. The potential antitumoral activity of all compounds was testedin vitroon human melanoma A375, human glioblastoma U251, human prostate cancer PC3, human colon cancer HCT116, mouse melanoma B16 and mouse colon cancer CT26CL25 cells, as well as primary fibroblasts and keratinocytes. The results obtained revealed strong antitumor potential of the newly synthesized drugs with preserved efficacy against cisplatin resistant lines and less toxicity towards nonmalignant counterparts. The mechanism found to be responsible for the observed tumoricidal action of each synthesized compound was induction of apoptosis generally accompanied with caspase activation. Taken together, the effective response to the treatment of a wide range of different cell lines, including cisplatin resistant subclones, as well as induction of apoptosis, as the mechanism suggested to be the most desirable way of eliminating malignant cells, represents a great advantage of this novel group of drugs in comparison to other members in this metallo-drug family.

This paper focuses on synthesis and biological activity of a newN,N?-methylene cyclohexyl ethylenediamine-N,N?-diacetate-type of ligands and Pt(IV) complexes. Antitumoral activity was testedin vitroin several tumor cells as well as primary fibroblasts and keratinocytes. Results showed that compounds induced apoptosis, which is mainly mediated by caspase activation.

Highlights? We synthesize modified cyclohexyl edda ligands and corresponding Pt(IV) complexes. ? Structure modifications lead to spectral changes and improved biological activity. ? Novel Pt(IV) complexes show higher cytotoxic activity than cisplatin. ? We confirmed that all compounds induce caspase-dependent apoptosis.

Publication year: 2012
Source: Journal of Inorganic Biochemistry, Available online 31 January 2012

Marta Ferraroni, Irene Matera, Alexey Chernykh, Marina Kolomytseva, Ludmila A. Golovleva, ...

The crystal structure of a blue laccase fromSteccherinum ochraceumhas been solved at 2.0 Å of resolution using a classic data acquisition from a single crystal. The overall structural features are typical of this class of enzymes, however, distances inside the trinuclear copper cluster are indicative of a reduction of the metal centers induced by free electrons produced during the X-ray data collection. UV-visible spectra collected during the X-ray exposure support the progressive reduction of the metal centers.In order to better detect the reduction progression steps in the trinuclear copper site, a multicrystal data collection strategy based on a systematic spread of the X-ray dose over many crystals has been employed. This approach is based on collecting multi-crystals data sets, then combining the slices of the individual data sets experiencing the same radiation dose to obtain composite complete data sets at progressively higher doses.Applying this technique, we have been able to capture sequential frames of the enzyme during the metal centers and molecular oxygen reduction mechanism obtaining a three-dimensional movie of the X-ray-driven catalytic conversion of the molecular oxygen in the active site of laccase: first, the copper ions reduction, then the molecular oxygen binding and its reductive splitting, thus allowing to reconstruct the entire catalytic cycle for multicopper oxidases.

A multicrystal composite data collection strategy allowed capturing sequential snapshots of laccase during metal centers and dioxygen X-ray induced reduction.

Highlights? Multicrystal composite data collection strategy performed on a blue copper laccase ? X-ray induced reduction of metal centers and dioxygen bound to laccase. ? Sequential frames of the catalytic cycle for multicopper oxidases observed upon progressive reduction

Publication year: 2012
Source: Ecological Economics, Available online 31 January 2012

Amit K. Biswas, Mohammad Reza Farzanegan, Marcel Thum

We study how the shadow economy affects pollution and how this effect depends on corruption levels in public administration. Production in the shadow economy allows firms to avoid environmental regulation policies; a large informal sector may be accompanied by higher pollution levels. Our theoretical model predicts that controlling the levels of corruption can limit the effect of the shadow economy on pollution. We use panel data covering the period from 1999 to 2005 in more than 100 countries to test this theoretical prediction. Our estimates confirm that the relationship between the shadow economy and the levels of pollution are dependent on the levels of corruption. Our results hold when we control for the effects of other determinants of pollution, time varying common shocks, country-fixed effects and various additional covariates.

Highlights? Our theoretical model shows the pollution effect of the shadow economy depends on the level of corruption. ? We use panel data covering the period from 1999–2005 from more than 100 countries to test our theoretical prediction. ? Our main result is that corruption reinforces the damaging effects of the shadow economy on environmental quality.

Publication year: 2012
Source: Ecological Economics, Available online 31 January 2012

Raffaele Vignola, Tim L. McDaniels, Roland W. Scholz

The nature and structure of institutional mechanisms is fundamental for commons management, and yet has received relatively little attention for ecosystem service provision. In this paper, we develop and employ a value-focused structured decision process for a negotiation analysis about mechanisms to maintain and enhance ecosystem service (ES) provision at the watershed scale. We use a case study in the Birris watershed of Costa Rica where upstream farmers and downstream hydropower might jointly benefit from the design of a mechanism to foster the provision of soil regulation services (SRS). We identify and use parties' fundamental objectives, and views on means to achieve these objectives, to structure a negotiation template representing the important components that a soil conservation program should include. A voting-based elicitation process was employed to identify sub-alternatives acceptable both parties, which in turn identifies the zone of bargaining, or negotiation space in which future negotiations should focus. We conclude with discussion of the potential for application of this approach to other ES contexts, and the importance of the overall policy framework to provide resources and incentives to achieve enhance ES provision.

Highlights? Little application of negotiation analysis to identify agreement among stakeholders on how to conserve ecosystem service. ? We apply value-based structured decision analysis to a negotiation for designing a mechanism to conserve ecosystem services. ? This approach opens opportunities to identify stakeholders’ convergences on procedures to achieve desired objectives. ? In this application to Soil Regulation Service we identified preferences of parties and their zone of agreement. ? Parties share consensus that the mechanism should focus on priority areas and provide technical assistance.

Publication year: 2012
Source: Ecological Economics, Available online 31 January 2012

L. Doyen, O. Thébaud, C. Béné, V. Martinet, S. Gourguet, ...

Academia and management agencies show a growing interest for ecosystem-based fishery management (EBFM). However, the way to operationalize this approach remains challenging. The present paper illustrates how the concepts of stochastic co-viability, which accounts for dynamic complexities, uncertainties, risk and sustainability constraints, can be useful for the implementation of EBFM. In the present case, this concept is used to identify fishing strategies that satisfy both ecological conservation and economic sustainability in a multi-species, multi-fleet context. Economic Viability Analysis (EVA) and the broader Co-Viability Analysis (CVA), are proposed to expand the usual Population Viability Analysis (PVA) and precautionary approach. An illustration is proposed, using data on the fisheries of Bay of Biscay (France) exploiting the stocks of nephrops and hake. Stochastic simulations show how CVA can guarantee both ecological (stock) and economic (profit) sustainability. Using 2008 as a baseline, the model is used to identify fishing efforts that ensure such co-viability.

Highlights? Stochastic viability is a useful approach for ecosystem based fisheries management. ? It is applied to the hake and nephrops fisheries of the Bay of Biscay. ? The status quo strategy (2006) is not viable. ? Co-viability strategy can guarantee both ecological and economic sustainability.

Publication year: 2012
Source: Urology, Available online 30 January 2012

Markéta Zelenková, Otakar Sohnel, Felix Grases

ObjectiveWe aimed to establish detailed morphology of the structureless amorphous hydroxyapatite (HAP) phase to improve our understanding of the formation mechanism of these concretions. Noninfectious phosphate renal calculi composed mainly of HAP consist of inorganic material in the form of spherules, in a seemingly structureless and amorphous phase and organic matter.MethodsSeveral cross-sections of a fraction of phosphate renal stone composed solely of the amorphous HAP phase were examined with atomic force microscope. Both 2- and 3-dimensional images of their structure and nanoscale elastic modulus maps were obtained.ResultsThe amorphous hap phase consists of 2 distinctly different morphologic forms of hydroxyapatite: separate and/or intergrown columnar crystals, and spherical agglomerates with diameters in the range 150-300 nm consisting of spherulites approximately 10 nm in diameter. The columnar crystals are irregularly disseminated in the stone interior, which is porous because of cavities with depths in excess of 100 nm. Organic matter is almost evenly distributed throughout the stone interior.ConclusionBased on the observed calculus structure, the following mechanism of formation of the noninfectious phosphate calculi is suggested: Spherulites formed via the perikinetic aggregation of Posner's clusters present in urine supersaturated with respect to hydroxyapatite aggregate into spherical agglomerates that, after reaching a certain size, are retained in cavities with poor urodynamics, gradually settle, and become incorporated into developing concretion. The columnar crystals are probably nucleated on the detritus of organic origin embedded in the hydroxyapatite structureless phase.

Publication year: 2012
Source: Urology, Available online 30 January 2012

Akinori Sato, Takako Asano, Keiichi Ito, Tomohiko Asano

ObjectiveTo investigate the combined effects of the HIV protease inhibitor ritonavir and proteasome inhibitor bortezomib on renal cancer cells. Ritonavir induces endoplasmic reticulum (ER) stress and we hypothesized that inhibiting proteasome activity under ER stress would further inhibit cancer cell growth by enhancing protein ubiquitination.MethodsThe effectiveness of the combination of ritonavir and bortezomib on renal cancer cells (Caki-1, ACHN, 786-O, 769-P) was assessed by MTS assay, colony formation assay, cell cycle analysis, and annexin-V assay. In vivo efficacy was evaluated using mice subcutaneous tumor models. Induction of ER stress, protein ubiquitination, histone acetylation, and changes in the expression of histone deacetylase (HDAC) were evaluated by Western blotting.ResultsRitonavir in combination with bortezomib induced apoptosis and inhibited renal cancer growth synergistically at clinically feasible concentrations. In subcutaneous tumor models using Caki-1 cells, 10-day treatment with the combination was well tolerated and inhibited tumor growth significantly. Ritonavir induced ER stress and the combination enhanced protein ubiquitination synergistically. The combination was also found to induce histone acetylation by suppressing the HDAC expression.ConclusionThe combination of ritonavir and bortezomib inhibits renal cancer growth synergistically. The effectiveness of the combination is caused by protein ubiquitination and histone acetylation. Our results provide a rationale for investigating the combination in patients with renal cancer.

Publication year: 2012
Source: Cardiovascular Revascularization Medicine, Available online 30 January 2012

Ronen Jaffe, Ariel Finkelstein, Basil S. Lewis, Victor Guetta, Nader Khader, ...

AimsHigh-risk patients with severe aortic stenosis (AS) who are candidates for transcatheter valve implantation (TAVI) or balloon aortic valvuloplasty (BAV) may additionally require revascularization of the unprotected left main coronary artery (UPLM). We aimed to assess the feasibility and procedural safety of UPLM stenting in such patients.Methods and ResultsTen cases of UPLM stenting prior to BAV or TAVI at three medical centers over a 2-year period were identified. Mean age was 84±4 years, aortic valve area was 0.70±0.12 cm, left ventricular ejection fraction was 58%±3%, and logistic EuroScore was 32±17. Intraaortic balloon counterpulsation was used in three patients. A single stent was used in seven patients, and two stents were used in three patients. One patient received a bare-metal stent, and the others received drug-eluting stents. No procedural complications occurred, and the patients were hemodynamically stable. Three patients subsequently underwent BAV, and seven underwent TAVI. During 6 months of follow-up, two patients died: one due to AS restenosis 6 months after BAV and one due to vascular complications 18 days after TAVI (34 days after UPLM stenting).ConclusionsStenting of the UPLM in patients with severe AS prior to percutaneous valve intervention seems feasible and safe. This approach may enable more patients to achieve comprehensive percutaneous therapy for severe coronary and valvular disease.

Publication year: 2012
Source: Cardiovascular Revascularization Medicine, Available online 30 January 2012

Madhu K. Natarajan, Bradley H. Strauss, Michael Rokoss, Christopher E. Buller, G.B. John Mancini, ...

BackgroundDiabetes status is an independent marker of restenosis after percutaneous coronary intervention (PCI). Previous studies suggest that metabolic abnormalities associated with diabetes increase stent restenosis by promoting intimal hyperplasia. Preclinical studies have indicated that insulin therapy reduces intimal hyperplasia. The objective of this study was to determine whether insulin-mediated glucose lowering reduces in-stent restenosis in patients with diabetes undergoing PCIs.MethodsWe conducted a prospective, randomized, multicenter, open-labeled study with blinded outcomes. Patients were randomized 1:1 to daily bedtime subcutaneous NPH insulin (Novo Nordisk) versus usual therapy with oral hypoglycemic agents. The main outcomes were change in volume of intimal hyperplasia within the stent measured by intravascular ultrasound and late lumen loss by quantitative coronary angiography at 6 months post-PCI.ResultsSeventy-eight patients (36 insulin, 42 usual care) were randomized. Eight patients in each group received drug-eluting stents. The insulin group achieved greater reductions in both glycosylated hemoglobin A1c (mean±S.D.) (insulin: 8.0%±1.2% to 6.7%±0.7% vs. control: 7.5%±1.2% to 7.1%±1.0 %,P=.0038) and fasting glucose (insulin: 9.3±3.8 to 5.8±1.7 vs. usual care: 8.4±2.4 to 7.7±2.0 mmol/l,P<.0001). There were no hypoglycemic events. At 6 months, there were no significant differences in either intravascular-ultrasound-determined neointimal volume (insulin: 41.2±38.9 vs. usual care: 48.4±40.2 mm,P=.33) or late lumen loss by angiography (insulin: 1.29±0.74 mm vs. usual care: 1.02±0.71 mm,P=.17).ConclusionsAddition of a single bedtime dose of insulin in patients with diabetes does not influence in-stent restenosis.

Publication year: 2012
Source: Journal of Inorganic Biochemistry, Available online 28 January 2012

Lorena Becco, Alejandra Rodríguez, María Elena Bravo, María José Prieto, Lena Ruiz-Azuara, ...

The mixed-chelate copper (II) complexes Casiopeínas® have been tested in several modelsin vitroandin vivo, showing promising antitumoral results. However, their mechanism of action remains to be defined. Trying to get a deeper insight into their molecular mode of action, further analyses, including gel electrophoresis, atomic force microscopy and circular dichroism were carried out to study their interaction with DNA and some cytoskeleton proteins. Our results revealed that the interaction of Casiopeínas triggers DNA cleavage by a free radical mechanism. The tested complexes showed a differential response to reducing and scavenger agents. Differences on target preference were also evident using double stranded oligonucleotides as sequence competitors. Surprisingly, distamycin A, a minor groove binder, enhanced the Casiopeínas action on DNA. On the other hand, the tested Casiopeínas produce strong changes in protein structure of tubulin, integrin and fibronectin. All together these results suggest a multiple mode of action for these metal-based drugs. In addition, since it has been proposed that antitumor drugs efficiently interacting with DNA could also show activity againstTrypanosoma cruzi, etiologic agent of Chagas disease, we evaluated the activity of these compounds on this protozoan parasite. The tested complexes showedin vitroanti-T. cruziactivity similar to the anti-trypanosomal reference drug Nifurtimox.

DNA and proteins interaction of copper(II) complexes Casiopeínas® was studied through gel electrophoresis, CD and AFM. Antitrypanosomal activity was evaluated.

Highlights? Mixed-chelate Cu(II) complexes Casiopeínas trigger DNA cleavage by a free radical mechanism. ? The DNA cleavage ability of the tested Casiopeínas follows an order that concurs with the efficiency of action of these compounds on tumoral eukaryotic cells. ? Competitions with double strand oligonucleotide revealed differences among the complex DNA target preferences. ? The interaction of the Casiopeína Cas III-Ea with tubulin, integrin and fibronectin was demonstrated by AFM imaging. ? The tested Casiopeínas showedin vitroanti-T. cruziactivities similar to that of the reference anti-trypanosomal drug Nifurtimox.

Publication year: 2012
Source: Journal of Inorganic Biochemistry, Available online 28 January 2012

Hani J. Alturkmani, Carlos Zgheib, Fouad A. Zouein, Nour Eddin F. Alshaaer, Mazen Kurdi, ...

Sodium selenate may have utility in treating Alzheimer's disease and diabetes; however, its impact on the associated proinflammatory cytokine signaling of endothelial cells has not been investigated. We report that treatment of human microvascular endothelial cells with sodium selenate at a pharmacological dose (100 ?M) enhanced tyrosine phosphorylation of nuclear STAT3 on Y705 in response to IL-6-type cytokine, leukemia inhibitory factor (LIF), indicative of enhanced STAT3 activity. Accordingly, STAT3 nuclear binding to DNA was increased, as well as LIF-induced gene expression of chemokine (C-C motif) ligand 2 (CCL2). CCL2 plays a key role in inflammatory processes associated with neuronal degenerative and vascular diseases. The enhancing action of selenate on LIF-induced STAT3 Y705 phosphorylation was replicated by vanadate and a specific inhibitor of protein tyrosine phosphatase, non-receptor type 1 (PTP1B). Moreover, we observed that selenite, the cellular reduction bioproduct of selenate but not selenate itself, inhibited enzymatic activity of human recombinant PTP1B. Our findings support the conclusion that in human microvascular endothelial cells selenate has a vanadate-like effect in inhibiting PTP1B and enhancing proinflammatory STAT3 activation. These findings raise the possibility that beneficial actions of supranutritional levels of selenate for treating Alzheimer's and diabetes may be offset by a proinflammatory action on endothelial cells.

Selenate enhanced LIF-induced STAT3 tyrosine phosphorylation, nuclear extract binding to a STAT3 consensus DNA site, and expression of inflammatory chemokine CCL2 in endothelial cells. These actions were replicated by vanadate and an inhibitor of protein tyrosine phosphatase PTP1B. The therapeutic benefits of selenate may be offset by pro-inflammatory actions.

Highlights? Selenate enhanced STAT3 activity of endothelial cells in response to LIF cytokine ? Tyrosine phosphorylation of nuclear STAT3 was increased ? Binding of nuclear proteins to a STAT3 consensus DNA site and CCL2 gene expression were increased ? The enhancing action of selenate was replicated by vanadate and an inhibitor of phosphatase PTP1B ? Beneficial action of selenate in Alzheimer's and diabetes may be offset by proinflammatory actions