Incidence of stroke and acute renal failure in patients of postoperative atrial fibrillation after myocardial revascularization

Introduction

Postoperative atrial fibrillation is the most common arrhythmia in cardiac surgery, its incidence range between 20% and 40%.

Objective

Quantify the occurrence of stroke and acute renal insufficiency after myocardial revascularization surgery in patients who had atrial fibrillation postoperatively.

Methods

Cohort longitudinal bidirectional study, performed at Portuguese Beneficent Hospital (SP), with medical chart survey of patients undergoing myocardial revascularization surgery between June 2009 to July 2010. From a total of 3010 patients were weaned 382 patients that presented atrial fibrillation preoperatively and/or associated surgeries. The study was conducted in accordance with national and international following resolutions: ICH Harmonized Tripartite Guidelines for Good Clinical Practice - 1996; CNS196/96 Resolution, and Declaration of Helsinki.

Results

The 2628 patients included in this study were divided into two groups: Group I, who didn''t show postoperative atrial fibrillation, with 2302 (87.6%) patients; and group II, with 326 (12.4%) who developed postoperative atrial fibrillation. The incidence of stroke in patients was 1.1% without postoperative atrial fibrillation vs. 4% with postoperative atrial fibrillation (P<0.001). Postoperative acute renal failure was observed in 12% of patients with postoperative atrial fibrillation and 2.4% in the group without postoperative atrial fibrillation (P<0.001), that is a relation 5 times greater.

Conclusion

In this study there was a high incidence of stroke and acute renal failure in patients with postoperative atrial fibrillation, with rates higher than those reported in the literature.     

Reinforcing a medical hypothesis with a new question: is there a subgroup of shrinking lungs syndrome that is induced by pleurisy in systemic lupus erythematosus and is this subgroup marked by anti-Ro/SSA?

Shrinking lungs syndrome (SLS) is a rare entity associated with autoimmune diseases and its underlying pathogenesis is still unclear. We describe a series of seven consecutive cases of SLS in systemic lupus erythematosus, all of them with serositis and six (85.7%) with anti-Ro/SSA antibodies. Our findings reinforce the hypothesis that SLS may be, in some cases, a consequence of diaphragmatic restriction due to pleuritic pain, and we suggest anti-Ro/SSA as a marker of this subgroup of SLS.     

Azaindole derivatives are inhibitors of microtubule dynamics,with anti-cancer and anti-angiogenic activities

Background and Purpose

Drugs targeting microtubules are commonly used for cancer treatment. However, the potency of microtubule inhibitors used clinically is limited by the emergence of resistance. We thus designed a strategy to find new cell-permeable microtubule-targeting agents.

Experimental Approach

Using a cell-based assay designed to probe for microtubule polymerization status, we screened a chemical library and identified two azaindole derivatives, CM01 and CM02, as cell-permeable microtubule-depolymerizing agents. The mechanism of the anti-tumour effects of these two compounds was further investigated both in vivo and in vitro.

Key Results

CM01 and CM02 induced G2/M cell cycle arrest and exerted potent cytostatic effects on several cancer cell lines including multidrug-resistant (MDR) cell lines. In vitro experiments revealed that the azaindole derivatives inhibited tubulin polymerization and competed with colchicines for this effect, strongly indicating that tubulin is the cellular target of these azaindole derivatives. In vivo experiments, using a chicken chorioallantoic xenograft tumour assay, established that these compounds exert a potent anti-tumour effect. Furthermore, an assay probing the growth of vessels out of endothelial cell spheroids showed that CM01 and CM02 exert anti-angiogenic activities.

Conclusions and Implications

CM01 and CM02 are reversible microtubule-depolymerizing agents that exert potent cytostatic effects on human cancer cells of diverse origins, including MDR cells. They were also shown to inhibit angiogenesis and tumour growth in chorioallantoic breast cancer xenografts. Hence, these azaindole derivatives are attractive candidates for further preclinical investigations.     

Substituted chromones as highly potent nontoxic inhibitors, specific for the breast cancer resistance protein

A series of 13 disubstituted chromones was synthesized. Two types of substituents, on each side of the scaffold, contributed to both the potency of ABCG2 inhibition and the cytotoxicity. The best compound, 5-(4-bromobenzyloxy)-2-(2-(5-methoxyindolyl)ethyl-1-carbonyl)-4H-chromen-4-one (6g), displayed high-affinity inhibition and low cytotoxicity, giving a markedly high therapeutic index. The chromone derivative specifically inhibited ABCG2 versus other multidrug ABC transporters and was not transported. It constitutes a highly promising candidate for in vivo chemosensitization of ABCG2-expressing tumors.     

Pharmacological Inhibition of LIM Kinase Stabilizes Microtubules and Inhibits Neoplastic Growth

The emergence of tumor resistance to conventional microtubule-targeting drugs restricts their clinical use. Using a cell-based assay that recognizes microtubule polymerization status to screen for chemicals that interact with regulators of microtubule dynamics, we identified Pyr1, a cell permeable inhibitor of LIM kinase, which is the enzyme that phosphorylates and inactivates the actin-depolymerizing factor cofilin. Pyr1 reversibly stabilized microtubules, blocked actin microfilament dynamics, inhibited cell motility in vitro and showed anticancer properties in vivo, in the absence of major side effects. Pyr1 inhibition of LIM kinase caused a microtubule-stabilizing effect, which was independent of any direct effects on the actin cytoskeleton. In addition, Pyr1 retained its activity in multidrug-resistant cancer cells that were resistant to conventional microtubule-targeting agents. Our findings suggest that LIM kinase functions as a signaling node that controls both actin and microtubule dynamics. LIM kinase may therefore represent a targetable enzyme for cancer treatment. Cancer Res; 72(17); 4429-39. ?2012 AACR.     

From the Cover: Origami tubes assembled into stiff,yet reconfigurable structures and metamaterials

Thin sheets have long been known to experience an increase in stiffness when they are bent, buckled, or assembled into smaller interlocking structures. We introduce a unique orientation for coupling rigidly foldable origami tubes in a “zipper” fashion that substantially increases the system stiffness and permits only one flexible deformation mode through which the structure can deploy. The flexible deployment of the tubular structures is permitted by localized bending of the origami along prescribed fold lines. All other deformation modes, such as global bending and twisting of the structural system, are substantially stiffer because the tubular assemblages are overconstrained and the thin sheets become engaged in tension and compression. The zipper-coupled tubes yield an unusually large eigenvalue bandgap that represents the unique difference in stiffness between deformation modes. Furthermore, we couple compatible origami tubes into a variety of cellular assemblages that can enhance mechanical characteristics and geometric versatility, leading to a potential design paradigm for structures and metamaterials that can be deployed, stiffened, and tuned. The enhanced mechanical properties, versatility, and adaptivity of these thin sheet systems can provide practical solutions of varying geometric scales in science and engineering.Introducing folds into a thin sheet can restrict its boundaries, cause self-interaction, and reduce the effective length for bending and buckling of the material (1–4). These phenomena make thin sheets practical for stiff and lightweight corrugated assemblies (5, 6); however, such systems tend to be static, i.e., functional in only one configuration. For creating dynamic structures, origami has emerged as a practical method in which continuous thin sheet panels (facets) are interconnected by prescribed fold lines (creases). Existing origami patterns and assemblages can easily be deployed; however, they tend to be flexible and need to be braced or locked into a fixed configuration for a high stiffness-to-weight ratio to be achieved (7–10). The zipper-coupled system is different because it is stiff throughout its deployment without having to be locked into a particular configuration.Origami principles have broad and varied applications, from solar arrays (11) and building façades (12) to robotics (13), mechanisms in stent grafts (14), and DNA-sized boxes (15). The materials and methods used for fabricating, actuating, and assembling these systems can vary greatly with length scale. On the microscale, metallic and polymer films or, more often, layered composites consisting of stiff and flexible materials can be folded by inducing current, heat, or a chemical reaction (16, 17). Large-scale origami structures can be constructed from thickened panels connected by hinges and can be actuated with mechanical forces (11, 18, 19). The kinematic motion, functionality, and mechanical properties of the origami are governed largely by the folding pattern geometry. For example, rigid origami systems are defined as those having a kinematic deformation mode in which movement is concentrated along the fold lines, whereas the panels remain flat (20, 21). Among various rigid folding patterns, the Miura-ori has attracted attention for its folding characteristics (22, 23), elastic stiffness properties beyond rigid folding (24, 25), geometric versatility (26, 27), and intrinsic material-like characteristics (28, 29).The zipper-coupled tubes introduced here are derived from the Miura-ori pattern and can undergo the same type of rigid kinematic deployment. All other deformations are restrained as they require stretching and shear of the thin sheets. Thus, the structure is light and retains a high stiffness throughout its deployment. It has only one flexible degree of freedom and can be actuated by applying a force at any point (Fig. 1 and Movie S1). To explore unique mechanical properties of the zipper tubes, we introduce concepts of eigenvalue bandgaps and cantilever analyses to the field of origami engineering. Zipper assemblages can be fabricated with a variety of materials and methods. We envision applications of these assemblages will range in size from microscale metamaterials that harness the novel mechanical properties to large-scale deployable systems in engineering and architecture (Movies S2–S4).Open in a separate windowFig. 1.Deployment and retraction sequence of a zipper-coupled tube system. This origami has only one flexible motion through which it can deform, and thus it is deployed by actuating only on the right end. See Movie S1 for complete simulation.This paper is organized as follows. First, the Miura-ori pattern is introduced, and the geometries of three fundamental coupling orientations are discussed. Next, we demonstrate how the system stiffness changes as we assemble two sheets into a tube and then two tubes into the unique zipper-coupled tubes. The fundamental coupling orientations are then studied as deployable cantilevers that can carry perpendicular loads. Next, we discuss cellular assemblages, geometric variations, and practical applications that can be created from coupled tubes, and we conclude with some final remarks.     

Effect of Different Tensoactives on the Morphology and Release Kinetics of PLA-b-PEG Microcapsules Loaded With the Natural Anticancer Compound Perillyl Alcohol

Perillyl alcohol is a natural compound that has attracted a significant interest due to its potent antitumor activity. However, clinical trials have exhibited poor tolerance by oral administration, mainly due to gastrointestinal side effects. We propose the entrapment of perillyl alcohol into poly(D,L-lactic acid)-block-poly(ethylene glycol) (PLA-b-PEG) as delivery platform (entrapment efficiency of 63%-68%). The influence of different concentrations of the tensoactives poly(vinyl alcohol) and sodium cholate (SC) on shear strength and morphology was evaluated by confocal laser scanning microscopy and interfacial tension studies. Only the microcapsules formulated with SC maintained their sphericity when submitted to shear stress. These results indicate that the interface is better organized with SC, conferring mutual stacked packing that is able to better stabilize the organic drop. The in vitro release profile of the drug from the microcapsules was correlated with pore formation and polymer degradation, best fitted to the Baker-Lonsdale model. The loaded microcapsules showed an IC₅₀ equivalent to that of the free drug (80 μg/mL) after 72 h of exposure. However, after 24 h of exposure, loaded microcapsules showed an IC₅₀ almost two-fold higher (220 μg/mL) suggesting gradual release.     

Titanium alloy mini-implants for orthodontic anchorage: immediate loading and metal ion release

Removable osseointegrated titanium mini-implants were successfully used as anchorage devices in orthodontics. The early load is necessary to simplify the mini-implant methodology, but can lead to failure during osseointegration. The Ti-6Al-4V alloy was used instead of commercially pure Ti due to its superior strength. However, the corrosion resistance is low, allowing for metal ion release. The purpose of this work was to analyze the immediately loaded mini-implant fixation and to gauge the vanadium ion release during the healing process. Titanium alloy mini-implants were inserted in the tibiae of rabbits. After 1, 4 and 12 weeks, they were submitted to removal torque testing. There was no increase in the removal torque value between 1 and 4 weeks of healing, regardless of the load. Nevertheless, after 12 weeks, a significant improvement was observed in both groups, with the highest removal torque value for the unloaded group. The kidney, liver and lung were also extracted and analyzed by atomic absorption spectrometry. In comparison with the control values, the content of vanadium increased slightly after 1week, significantly increased after 4 weeks and decreased slightly after 12 weeks, without reaching the 1 week values. A stress analysis was carried out which enables both the prediction of the torque at which commercially pure (CP) Ti and Ti-6Al-4V deform plastically and the shear strength of the interface. This analysis reveals that the removal torques for CP Ti dangerously approach the yield stress. The results of this rabbit model study indicate that titanium alloy mini-implants can be loaded immediately with no compromise in their stability. The detected concentration of vanadium did not reach toxic levels in the animal model.