Synthesis of 2-(5-((5-(4-chlorophenyl)furan 2-yl)methylene)-4-oxo-2-thioxo-thiazolidi n-3-yl)acetic acid derivatives and evaluation of their cytotoxicity and induction of apoptosis in human leukemia cells

In order to explore the anticancer effect associated with the thiazolidinone framework, several 2-(5-((5-(4-chlorophenyl)furan-2-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)acetic acid derivatives 5(a-1) were synthesized. Variation in the functional group at C-terminal of the thiazolidinone led to set of compounds bearing amide moiety. Their chemical structures were confirmed by H-1 NMR, IR and Mass Spectra analysis. These thiazolidinone compounds containing furan moiety exhibits moderate to strong antiproliferative activity in a cell cycle stage-dependent and dose dependent manner in two different human leukemia cell lines. The importance of the electron donating groups on thiazolidinone moiety was confirmed by MTT and Trypan blue assays and it was concluded that the 4th position of the substituted aryl ring plays a dominant role for its anticancer property. Among the synthesized compounds, 5e and 5f have shown potent anticancer activity on both the cell lines tested. To rationalize the role of electron donating group in the induction of cytotoxicity we have chosen two molecules (5e and 5k) having different electron donating group at different positions. LDH assay, Flow cytometric analysis and DNA fragmentation suggest that 5e is more cytotoxic and able to induce the apoptosis. (C) 2009 Elsevier Ltd. All rights reserved.

Synthesis of Unnatural C-2 Amino Acid Nucleosides Using NIS-Mediated Ring Opening of 1,2-Cyclopropane Carboxylated Sugar Derivatives

We have developed a general and efficient method for the stereoselective construction of pyrimidine-based pyranosyl C-2 amino acid nucleosides using NIS-mediated ring opening of 1,2-cyclopropanated sugar derivatives. This methodology has been successfully extended to the synthesis of furanosyl nucleosides, Which have potential applications in the development of novel, nontoxic antifungal therapeutics.

Haemodialysis work environment contributors to job satisfaction and stress: A sequential mixed methods study

Background: Haemodialysis nurses form long term relationships with patients in a technologically complex work environment. Previous studies have highlighted that haemodialysis nurses face stressors related to the nature of their work and also their work environments leading to reported high levels of burnout. Using Kanters (1997) Structural Empowerment Theory as a guiding framework, the aim of this study was to explore the factors contributing to satisfaction with the work environment, job satisfaction, job stress and burnout in haemodialysis nurses. Methods: Using a sequential mixed-methods design, the first phase involved an on-line survey comprising demographic and work characteristics, Brisbane Practice Environment Measure (B-PEM), Index of Work Satisfaction(IWS), Nursing Stress Scale (NSS) and the Maslach Burnout Inventory (MBI). The second phase involved conducting eight semi-structured interviews with data thematically analyzed. Results: From the 417 nurses surveyed the majority were female (90.9 %), aged over 41 years of age (74.3 %), and 47.4 % had worked in haemodialysis for more than 10 years. Overall the work environment was perceived positively and there was a moderate level of job satisfaction. However levels of stress and emotional exhaustion (burnout) were high. Two themes, ability to care and feeling successful as a nurse, provided clarity to the level of job satisfaction found in phase 1. While two further themes, patients as quasi-family and intense working teams, explained why working as a haemodialysis nurse was both satisfying and stressful. Conclusions: Nurse managers can use these results to identify issues being experienced by haemodialysis nurses working in the unit they are supervising.

Nutritional support in children with end-stage liver disease : a randomized crossover trial of a branched-chain amino acid supplement

Malnutrition is common in children with end-stage liver disease (ESLD) awaiting orthotopic liver transplantation (OLT), and nutritional support is assuming an important role in preoperative management. To evaluate preoperative nutritional therapy, 19 children (median age 1.25 y) with ESLD awaiting OLT were prospectively studied. Two high-energy, isoenergetic and isonitrogenous nutritional formulations delivered nasogastrically were compared: a branched-chain amino acid (BCAA)-enriched semielemental formulation and a matched standard semielemental formulation. Twelve of 19 patients completed a randomized controlled study before OLT and 10 of 19 completed a full crossover study. Improvements in weight and height occurred during the BCAA supplements, with no statistical change on the standard formulation. Significant increases in total body potassium, midupper arm circumference, and subscapular skinfold thickness occurred during the BCAA supplements, whereas no significant changes occurred during the standard formulation period. Significantly fewer albumin infusions were required during the BCAA supplement. These findings suggest that BCAA-enriched formulas have advantages over standard semielemental formulas in improving nutritional status in children with ESLD. and are deserving of wider application and study.

State of Charge of Lead Acid Battery

Lead acid batteries are used in hybrid vehicles and telecommunications power supply. For reliable operation of these systems, an indication of state of charge of battery is essential. To determine the state of charge of battery, current integration method combined with open circuit voltage, is being implemented. To reduce the error in the current integration method the dependence of available capacity as a function of discharge current is determined. The current integration method is modified to incorporate this factor. The experimental setup built to obtain the discharge characterstics of the battery is presented.

Families of asymptotic tensile crack tip stress fields in elastic-perfectly plastic single crystals

In this work, two families of asymptotic near-tip stress fields are constructed in an elastic-ideally plastic FCC single crystal under mode I plane strain conditions. A crack is taken to lie on the (010) plane and its front is aligned along the [(1) over bar 01] direction. Finite element analysis is first used to systematically examine the stress distributions corresponding to different constraint levels. The general framework developed by Rice (Mech Mater 6:317-335, 1987) and Drugan (J Mech Phys Solids 49:2155-2176, 2001) is then adopted to generate low triaxiality solutions by introducing an elastic sector near the crack tip. The two families of stress fields are parameterized by the normalized opening stress (tau(A)(22)/tau(o)) prevailing in the plastic sector in front of the tip and by the coordinates of a point where elastic unloading commences in stress space. It is found that the angular stress variations obtained from the analytical solutions show good agreement with finite element analysis.

Early life stress, nicotinic acetylcholine receptors and alcohol use disorders

Stress is a major driving force in alcohol use disorders (AUDs). It influences how much one consumes, craving intensity and whether an abstinent individual will return to harmful alcohol consumption. We are most vulnerable to the effects of stress during early development, and exposure to multiple traumatic early life events dramatically increases the risk for AUDs. However, not everyone exposed to early life stress will develop an AUD. The mechanisms determining whether an individual’s brain adapts and becomes resilient to the effects of stress or succumbs and is unable to cope with stress remain elusive. Emerging evidence suggests that neuroplastic changes in the nucleus accumbens (NAc) following early life stress underlie the development of AUDs. This review discusses the impact of early life stress on NAc structure and function, how these changes affect cholinergic signaling within the mesolimbic reward pathway and the role nicotinic acetylcholine receptors (nAChRs) play in this process. Understanding the neural pathways and mechanism determining stress resilience or susceptibility will improve our ability to identify individuals susceptible to developing AUDs, formulate cognitive interventions to prevent AUDs in susceptible individuals and to elucidate and enhance potential therapeutic targets, such as the nAChRs, for those struggling to overcome an AUD.

Influence of surface stress on elastic constants of nanohoneycombs

Surface effect on the four independent elastic constants of nanohoneycombs is investigated in this paper. The axial deformation of the horizontal cell wall is included, comparing to the Gibson's method, and the contributions of the two components of surface stress (i.e. surface residual stress and surface elasticity) are discussed. The result shows that the regular hexagonal honeycomb is not isotropic but orthotropic. An increase in the cell-wall thickness t leads to an increase in the discrepancy of the Young's moduli in both directions. Furthermore, the surface residual stress dominates the surface effect on the elastic constants when t < 15 nm (or the relative density <0.17), which is in contrast to that the surface elasticity does when t > 15 nm (or the relative density > 0.17) for metal Al. The present structure and theory may be useful in the design of future nanodevices.

Utility of magnetic resonance imaging-based finite element analysis for the biomechanical stress analysis of hemorrhagic and non-hemorrhagic carotid plaques

Background: Biomechanical stress analysis has been used for plaque vulnerability assessment. The presence of plaque hemorrhage (PH) is a feature of plaque vulnerability and is associated with thromboembolic ischemic events. The purpose of the present study was to use finite element analysis (FEA) to compare the stress profiles of hemorrhagic and non-hemorrhagic profiles. Methods and Results: Forty-five consecutive patients who had suffered a cerebrovascular ischemic event with an underlying carotid artery disease underwent high-resolution magnetic resonance imaging (MRI) of their symptomatic carotid artery in a 1.5-T MRI system. Axial images were manually segmented for various plaque components and used for FEA. Maximum critical stress (M-CstressSL) for each slice was determined. Within a plaque, the maximum M-CstressSL for each slice of a plaque was selected to represent the maximum critical stress of that plaque (M-CstressPL) and used to compare hemorrhagic and non-hemorrhagic plaques. A total of 62% of plaques had hemorrhage. It was observed that plaques with hemorrhage had significantly higher stress (M-CstressPL) than plaques without PH (median [interquartile range]: 315 kPa [247-434] vs. 200 kPa [171-282], P=0.003). Conclusions: Hemorrhagic plaques have higher biomechanical stresses than non-hemorrhagic plaques. MRI-based FEA seems to have the potential to assess plaque vulnerability.

Study of carotid arterial plaque stress for symptomatic and asymptomatic patients

Stroke is one of the leading causes of death in the world, resulting mostly from the sudden ruptures of atherosclerosis carotid plaques. Until now, the exact plaque rupture mechanism has not been fully understood, and also the plaque rupture risk stratification. The advanced multi-spectral magnetic resonance imaging (MRI) has allowed the plaque components to be visualized in-vivo and reconstructed by computational modeling. In the study, plaque stress analysis using fully coupled fluid structure interaction was applied to 20 patients (12 symptomatic and 8 asymptomatic) reconstructed from in-vivo MRI, followed by a detailed biomechanics analysis, and morphological feature study. The locally extreme stress conditions can be found in the fibrous cap region, 85% at the plaque shoulder based on the present study cases. Local maximum stress values predicted in the plaque region were found to be significantly higher in symptomatic patients than that in asymptomatic patients (200±43. kPa vs. 127±37. kPa, p=0.001). Plaque stress level, defined by excluding 5% highest stress nodes in the fibrous cap region based on the accumulative histogram of stress experienced on the computational nodes in the fibrous cap, was also significantly higher in symptomatic patients than that in asymptomatic patients (154±32. kPa vs. 111±23. kPa, p<0.05). Although there was no significant difference in lipid core size between the two patient groups, symptomatic group normally had a larger lipid core and a significantly thinner fibrous cap based on the reconstructed plaques using 3D interpolation from stacks of 2D contours. Plaques with a higher stenosis were more likely to have extreme stress conditions upstream of plaque throat. The combined analyses of plaque MR image and plaque stress will advance our understanding of plaque rupture, and provide a useful tool on assessing plaque rupture risk.

Stress analysis of carotid atheroma in transient ischemic attack patients: Evidence for extreme stress-induced plaque rupture

Plaque rupture has been considered to be the result of its structural failure. The aim of this study is to suggest a possible link between higher stresses and rupture sites observed from in vivo magnetic resonance imaging (MRI) of transient ischemic attack (TIA) patients, by using stress analysis methods. Three patients, who had recently suffered a TIA, underwent in vivo multi-spectral MR imaging. Based on plaque geometries reconstructed from the post-rupture status, six pre-rupture plaque models were generated for each patient dataset with different reconstructions of rupture sites to bridge the gap of fibrous cap from original MRI images. Stress analysis by fluid structure interaction simulation was performed on the models, followed by analysis of local stress concentration distribution and plaque rupture sites. Furthermore, the sensitivity of stress analysis to the pre-rupture plaque geometry reconstruction was examined. Local stress concentrations were found to be located at the plaque rupture sites for the three subjects studied. In the total of 18 models created, the locations of the stress concentration regions were similar in 17 models in which rupture sites were always associated with high stresses. The local stress concentration region moved from circumferential center to the shoulder region (slightly away from the rupture site) for a case with a thick fibrous cap. Plaque wall stress level in the rupture locations was found to be much higher than the value in non-rupture locations. The good correlation between local stress concentrations and plaque rupture sites, and generally higher plaque wall stress level in rupture locations in the subjects studied could provide indirect evidence for the extreme stress-induced plaque rupture hypothesis. Local stress concentration in the plaque region could be one of the factors contributing to plaque rupture.

Normalized wall index specific and MRI-based stress analysis of atherosclerotic carotid plaques: A study comparing acutely symptomatic and asymptomatic patients

Background: Biomechanical stresses play an important role in determining plaque stability. Quantification of these simulated stresses can be potentially used to assess plaque vulnerability and differentiate different patient groups. Methods and Results: 54 asymptomatic and 45 acutely symptomatic patients underwent in vivo multicontrast magnetic resonance imaging (MRI) of the carotid arteries. Plaque geometry used for finite element analysis was derived from in vivo MRI at the sites of maximum and minimum plaque burden. In total, 198 slices were used for the computational simulations. A pre-shrink technique was used to refine the simulation. Maximum principle stress at the vulnerable plaque sites (ie, critical stress) was extracted for the selected slices and a comparison was performed between the 2 groups. Critical stress in the slice with maximum plaque burden is significantly higher in acutely symptomatic patients as compared to asymptomatic patients (median, inter quartile range: 198.0 kPa (119.8-359.0 kPa) vs 138.4 kPa (83.8-242.6 kPa), P=0.04). No significant difference was found in the slice with minimum plaque burden between the 2 groups (196.7 kPa (133.3-282.7 kPa) vs 182.4 kPa (117.2-310.6 kPa), P=0.82). Conclusions: Acutely symptomatic carotid plaques have significantly high biomechanical stresses than asymptomatic plaques. This might be potentially useful for establishing a biomechanical risk stratification criteria based on plaque burden in future studies.

Arterial luminal curvature and fibrous-cap thickness affect critical stress conditions within atherosclerotic plaque: An in vivo MRI-based 2D finite-element study

High mechanical stress in atherosclerotic plaques at vulnerable sites, called critical stress, contributes to plaque rupture. The site of minimum fibrous cap (FC) thickness (FCMIN) and plaque shoulder are well-documented vulnerable sites. The inherent weakness of the FC material at the thinnest point increases the stress, making it vulnerable, and it is the big curvature of the lumen contour over FC which may result in increased plaque stress. We aimed to assess critical stresses at FCMIN and the maximum lumen curvature over FC (LCMAX) and quantify the difference to see which vulnerable site had the highest critical stress and was, therefore, at highest risk of rupture. One hundred patients underwent high resolution carotid magnetic resonance (MR) imaging. We used 352 MR slices with delineated atherosclerotic components for the simulation study. Stresses at all the integral nodes along the lumen surface were calculated using the finite-element method. FCMIN and LCMAX were identified, and critical stresses at these sites were assessed and compared. Critical stress at FC MIN was significantly lower than that at LCMAX (median: 121.55 kPa; inter quartile range (IQR) = [60.70-180.32] kPa vs. 150.80 kPa; IQR = [91.39-235.75] kPa, p < 0.0001). If critical stress at FCMIN was only used, then the stress condition of 238 of 352 MR slices would be underestimated, while if the critical stress at LCMAX only was used, then 112 out of 352 would be underestimated. Stress analysis at FCMIN and LCMAX should be used for a refined mechanical risk assessment of atherosclerotic plaques, since material failure at either site may result in rupture.