Effects of selected food phytochemicals in reducing the toxic actions of TCDD and p,p′-DDT in U937 macrophages

To assess the effectiveness of selected food phytochemicals in reducing the toxic effects of the environmental toxicants, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and p,p′-DDT (DDT), we tested the potencies of auraptene, nobiletin, zerumbone, and (±)-13-hydroxy-10-oxo-trans-11-octadecenoic acid (13-HOA) in reversing the inflammatory action of these toxicants in U937 human macrophages. Using quantitative RT–PCR as the initial screening assay, we identified antagonistic actions of zerumbone and auraptene against the action of TCDD and DDT in up-regulating the mRNA expressions of COX-2 and VEGF. The functional significance of the inhibitory action of zerumbone on COX-2 expression was confirmed by demonstrating its suppression of TCDD-induced activation of COX-2 gene expression in mouse MMDD1 cells. We tested auraptene on DDT-induced reactive oxygen species (ROS) formation in U937 macrophages and found that auraptene is a powerful agent antagonizing this action of DDT. To confirm the significance of these actions of zerumbone and auraptene at the cellular level, we assessed their influence on TCDD-induced apoptosis resistance in intact U937 macrophages and found that they are capable of reversing this action of TCDD. In conclusion, zerumbone and auraptene were identified to be the most effective agents in protecting U937 macrophages from developing these cell toxic effects of TCDD and DDT

Membrane Sealant Poloxamer P188 Protects Against Isoproterenol Induced Cardiomyopathy in Dystrophin Deficient Mice

<p>Abstract</p> <p>Background</p> <p>Cardiomyopathy in Duchenne muscular dystrophy (DMD) is an increasing cause of death in patients. The absence of dystrophin leads to loss of membrane integrity, cell death and fibrosis in cardiac muscle. Treatment of cardiomyocyte membrane instability could help prevent cardiomyopathy.</p> <p>Methods</p> <p>Three month old female mdx mice were exposed to the β₁receptor agonist isoproterenol subcutaneously and treated with the non-ionic tri-block copolymer Poloxamer P188 (P188) (460 mg/kg/dose i.p. daily). Cardiac function was assessed using high frequency echocardiography. Tissue was evaluated with Evans Blue Dye (EBD) and picrosirius red staining.</p> <p>Results</p> <p>BL10 control mice tolerated 30 mg/kg/day of isoproterenol for 4 weeks while death occurred in mdx mice at 30, 15, 10, 5 and 1 mg/kg/day within 24 hours. Mdx mice tolerated a low dose of 0.5 mg/kg/day. Isoproterenol exposed mdx mice showed significantly increased heart rates (p < 0.02) and cardiac fibrosis (p < 0.01) over 4 weeks compared to unexposed controls. P188 treatment of mdx mice significantly increased heart rate (median 593 vs. 667 bpm; p < 0.001) after 2 weeks and prevented a decrease in cardiac function in isoproterenol exposed mice (Shortening Fraction = 46 ± 6% vs. 35 ± 6%; p = 0.007) after 4 weeks. P188 treated mdx mice did not show significant differences in cardiac fibrosis, but demonstrated significantly increased EBD positive fibers.</p> <p>Conclusions</p> <p>This model suggests that chronic intermittent intraperitoneal P188 treatment can prevent isoproterenol induced cardiomyopathy in dystrophin deficient mdx mice.</p

Detected troponin elevation is associated with high early mortality after lung resection for cancer

BACKGROUND: Myocardial infarction can be difficult to diagnose after lung surgery. As recent diagnostic criteria emphasize serum cardiac markers (in particular serum troponin) we set out to evaluate its clinical utility and to establish the long term prognostic impact of detected abnormal postoperative troponin levels after lung resection. METHODS: We studied a historic cohort of patients with primary lung cancer who underwent intended surgical resection. Patients were grouped according to known postoperative troponin status and survival calculated by Kaplan Meier method and compared using log rank. Parametric survival analysis was used to ascertain independent predictors of mortality. RESULTS: From 2001 to 2004, a total of 207 patients underwent lung resection for primary lung cancer of which 14 (7%) were identified with elevated serum troponin levels within 30 days of surgery, with 9 (64%) having classical features of myocardial infarction. The median time to follow up (interquartile range) was 22 (1 to 52) months, and the one and five year survival probabilities (95% CI) for patients without and with postoperative troponin elevation were 92% (85 to 96) versus 60% (31 to 80) and 61% (51 to 71) versus 18% (3 to 43) respectively (p < 0.001). T stage and postoperative troponin elevation remained independent predictors of mortality in the final multivariable model. The acceleration factor for death of elevated serum troponin after adjusting for tumour stage was 9.19 (95% CI 3.75 to 22.54). CONCLUSION: Patients with detected serum troponin elevation are at high risk of early mortality with or without symptoms of myocardial infarction after lung resection

ACL graft re-rupture after double-bundle reconstruction: factors that influence the intra-articular pattern of injury

To determine the most common rupture patterns of previously reconstructed DB-ACL cases, seen at the time of revision surgery, and to determine the influence of age, gender, time between the initial ACL reconstruction and re-injury, tunnel angle and etiology of failure. Forty patients who presented for revision surgery after previous double-bundle ACL reconstruction were enrolled. Three orthopedic surgeons independently reviewed the arthroscopic videos and determined the rupture pattern of both the anteromedial and posterolateral grafts. The graft rupture pattern was then correlated with the previously mentioned factors. The most common injury pattern seen at the time of revision ACL surgery was mid-substance AM and PL bundle rupture. Factors that influenced the rupture pattern (proximal vs. mid-substance and distal rupture vs. elongated, but in continuity) were months between ACL reconstruction and re-injury (P = 0.002), the etiology of failure (traumatic vs. atraumatic) (P = 0.025) and the measured graft tunnel angle (P = 0.048). The most common pattern of graft re-rupture was mid-substance AM and mid-substance PL. As the length of time from the initial DB-ACL reconstruction to revision surgery increased, the pattern of injury more closely resembled that of the native ACL. Evaluation of patients who have undergone double-bundle ACL reconstruction, with a particular focus on graft maturity, mechanism of injury and femoral tunnel angles, and graft rupture pattern assists in preoperative planning for revision surger

Balance-of-Powers Arguments and the Structural Constitution

Balance-of-powers arguments are ubiquitous in judicial opinions and academic articles that address separation-of-powers disputes over the president\u27s removal authority, power to disregard statutes, authority to conduct foreign wars, and much else. However, the concept of the balance of powers has never received a satisfactory theoretical treatment. This Essay examines possible theories of the balance of powers and rejects them all as unworkable and normatively questionable. Judges and scholars should abandon the balance-of-powers metaphor and instead address directly whether bureaucratic innovation is likely to improve policy outcomes

Spin dynamics of molecular nanomagnets fully unraveled by four-dimensional inelastic neutron scattering

Molecular nanomagnets are among the first examples of spin systems of finite size and have been test-beds for addressing a range of elusive but important phenomena in quantum dynamics. In fact, for short-enough timescales the spin wavefunctions evolve coherently according to the an appropriate cluster spin-Hamiltonian, whose structure can be tailored at the synthetic level to meet specific requirements. Unfortunately, to this point it has been impossible to determine the spin dynamics directly. If the molecule is sufficiently simple, the spin motion can be indirectly assessed by an approximate model Hamiltonian fitted to experimental measurements of various types. Here we show that recently-developed instrumentation yields the four-dimensional inelastic-neutron scattering function S(Q,E) in vast portions of reciprocal space and enables the spin dynamics to be determined with no need of any model Hamiltonian. We exploit the Cr8 antiferromagnetic ring as a benchmark to demonstrate the potential of this new approach. For the first time we extract a model-free picture of the quantum dynamics of a molecular nanomagnet. This allows us, for example, to examine how a quantum fluctuation propagates along the ring and to directly test the degree of validity of the N\'{e}el-vector-tunneling description of the spin dynamics

gViz, a novel tool for the visualization of co-expression networks

<p>Abstract</p> <p>Background</p> <p>The quantity of microarray data available on the Internet has grown dramatically over the past years and now represents millions of Euros worth of underused information. One way to use this data is through co-expression analysis. To avoid a certain amount of bias, such data must often be analyzed at the genome scale, for example by network representation. The identification of co-expression networks is an important means to unravel gene to gene interactions and the underlying functional relationship between them. However, it is very difficult to explore and analyze a network of such dimensions. Several programs (Cytoscape, yEd) have already been developed for network analysis; however, to our knowledge, there are no available GraphML compatible programs.</p> <p>Findings</p> <p>We designed and developed gViz, a GraphML network visualization and exploration tool. gViz is built on clustering coefficient-based algorithms and is a novel tool to visualize and manipulate networks of co-expression interactions among a selection of probesets (each representing a single gene or transcript), based on a set of microarray co-expression data stored as an adjacency matrix.</p> <p>Conclusions</p> <p>We present here gViz, a software tool designed to visualize and explore large GraphML networks, combining network theory, biological annotation data, microarray data analysis and advanced graphical features.</p

Chronic typhoid infection and the risk of biliary tract cancer and stones in Shanghai, China

Previous studies have shown a positive association between chronic typhoid carriage and biliary cancers. We compared serum Salmonella enterica serovar Typhi antibody titers between biliary tract cancer cases, biliary stone cases without evidence of cancer, and healthy subjects in a large population-based case-control study in Shanghai, China

Transparency in health economic modeling : options, issues and potential solutions

Economic models are increasingly being used by health economists to assess the value of health technologies and inform healthcare decision making. However, most published economic models represent a kind of black box, with known inputs and outputs but undisclosed internal calculations and assumptions. This lack of transparency makes the evaluation of the model results challenging, complicates comparisons between models, and limits the reproducibility of the models. Here, we aim to provide an overview of the possible steps that could be undertaken to make economic models more transparent and encourage model developers to share more detailed calculations and assumptions with their peers. Scenarios with different levels of transparency (i.e., how much information is disclosed) and reach of transparency (i.e., who has access to the disclosed information) are discussed, and five key concerns (copyrights, model misuse, confidential data, software, and time/resources) pertaining to model transparency are presented, along with possible solutions. While a shift toward open-source models is underway in health economics, as has happened before in other research fields, the challenges ahead should not be underestimated. Importantly, there is a pressing need to find an acceptable trade-off between the added value of model transparency and the time and resources needed to achieve such transparency. To this end, it will be crucial to set incentives at different stakeholder levels. Despite the many challenges, the many benefits of publicly sharing economic models make increased transparency a goal worth pursuing