The curry spice curcumin selectively inhibits cancer cells growth in vitro and in preclinical model of glioblastoma.

Previous studies suggested that curcumin is a potential agent against glioblastomas (GBMs). However, the in vivo efficacy of curcumin in gliomas remains not established. In this work, we examined the mechanisms underlying apoptosis, selectivity, efficacy and safety of curcumin from in vitro (U138MG, U87, U373 and C6 cell lines) and in vivo (C6 implants) models of GBM.

Visualizing a homogeneous blend in bulk heterojunction polymer solar cells by analytical electron microscopy.

To increase efficiency of bulk heterojunctions for photovoltaic devices, the functional morphology of active layers has to be understood, requiring visualization and discrimination of materials with very similar characteristics. Here we combine high-resolution spectroscopic imaging using an analytical transmission electron microscope with nonlinear multivariate statistical analysis for classification of multispectral image data. We obtain a visual representation showing homogeneous phases of donor and acceptor, connected by a third composite phase, depending in its extent on the way the heterojunction is fabricated.

Predictors of outcome in World Federation of Neurologic Surgeons grade V aneurysmal subarachnoid hemorrhage patients.

Background: Only a small percentage of World Federation of Neurologic Surgeons grade V aneurysmal subarachnoid hemorrhage patients have a favorable outcome. The influence of clinical parameters on outcome was assessed.

Methods: Retrospective evaluation of consecutive patients admitted from 2000-2007 with grade V subarachnoid hemorrhage at two institutions by evaluating, over time, the motor value of the Glasgow Coma Scale, effects of external ventricular drainage and rebleeding on outcome.

A context-dependent combination of Wnt receptors controls axis elongation and leg development in a short germ insect.

Short germ embryos elongate their primary body axis by consecutively adding segments from a posteriorly located growth zone. Wnt signalling is required for axis elongation in short germ arthropods, including Tribolium castaneum, but the precise functions of the different Wnt receptors involved in this process are unclear. We analysed the individual and combinatorial functions of the three Wnt receptors, Frizzled-1 (Tc-Fz1), Frizzled-2 (Tc-Fz2) and Frizzled-4 (Tc-Fz4), and their co-receptor Arrow (Tc-Arr) in the beetle Tribolium.

Effects of catecholamines on hepatic and skeletal muscle mitochondrial respiration after prolonged exposure to faecal peritonitis in pigs.

Use of norepinephrine to increase blood pressure in septic animals has been associated with increased efficiency of hepatic mitochondrial respiration. The aim of this study was to evaluate whether the same effect could be reproduced in isolated hepatic mitochondria after prolonged in vivo exposure to faecal peritonitis. Eighteen pigs were randomized to 27 h of faecal peritonitis and to a control condition (n = 9 each group).

Dissecting the role of climacteric ethylene in kiwifruit (Actinidia chinensis) ripening using a 1-aminocyclopropane-1-carboxylic acid oxidase knockdown line.

During climacteric fruit ripening, autocatalytic (Type II) ethylene production initiates a transcriptional cascade that controls the production of many important fruit quality traits including flavour production and softening. The last step in ethylene biosynthesis is the conversion of 1-aminocyclopropane-1-carboxylic acid (ACC) to ethylene by the enzyme ACC oxidase (ACO). Ten independent kiwifruit (Actinidia chinensis) lines were generated targeting suppression of fruit ripening-related ACO genes and the fruit from one of these lines (TK2) did not produce detectable levels of climacteric ethylene.

GPR55 regulates cannabinoid 2 receptor-mediated responses in human neutrophils.

The directional migration of neutrophils towards inflammatory mediators, such as chemokines and cannabinoids, occurs via the activation of seven transmembrane G protein coupled receptors (7TM/GPCRs) and is a highly organized process. A crucial role for controlling neutrophil migration has been ascribed to the cannabinoid CB(2) receptor (CB(2)R), but additional modulatory sites distinct from CB(2)R have recently been suggested to impact CB(2)R-mediated effector functions in neutrophils. Here, we provide evidence that the recently de-orphanized 7TM/GPCR GPR55 potently modulates CB(2)R-mediated responses.

Arthroscopic soft tissue tenodesis versus bony fixation anchor tenodesis of the long head of the biceps tendon.

Background: Currently there are no prospective data available that compare the different tenodesis techniques of the long head of the biceps tendon with regard to their clinical and structural results.

Hypothesis: Soft tissue tenodesis provides clinical and structural results equivalent to those of bony fixation anchor tenodesis.

Study Design: Cohort study; Level of evidence, 3.

Object-wave reconstruction by carbon film-based Zernike- and Hilbert-phase plate microscopy: a theoretical study not restricted to weak-phase objects.

Transmission electron microscopy phase-contrast images taken by amorphous carbon film-based phase plates are affected by the scattering of electrons within the carbon film causing a modification of the image-wave function. Moreover, image artefacts are produced by non-centrosymmetric phase plate designs such as the Hilbert-phase plate. Various methods are presented to correct phase-contrast images with respect to the scattering of electrons and image artefacts induced by phase plates.

NFκB inhibitors induce cell death in glioblastomas.

Identification of novel target pathways in glioblastoma (GBM) remains critical due to poor prognosis, inefficient therapies and recurrence associated with these tumors. In this work, we evaluated the role of nuclear-factor-kappa-B (NFκB) in the growth of GBM cells, and the potential of NFκB inhibitors as antiglioma agents. NFκB pathway was found overstimulated in GBM cell lines and in tumor specimens compared to normal astrocytes and healthy brain tissues, respectively.

New electrostatic phase plate for phase-contrast transmission electron microscopy and its application for wave-function reconstruction.

A promising novel type of electrostatic phase plate for transmission electron microscopy (TEM) is presented. The phase plate consists of a single microcoaxial cable-like rod with its electrode exposed to the undiffracted electrons. The emerging field is used to shift the phase of the undiffracted electrons with respect to diffracted electrons.

[Ultrasound examination of the posterior ligament complex in thoracolumbar spinal fractures].

Background: thoracolumbar distraction injuries (AO classification type B) with damage to the posterior ligament complex (PLC) represent an indication for surgery but the use of X-ray and CT imaging often does not identify injuries of the PLC. The aim of this study was to evaluate the accuracy of ultrasound imaging in the assessment of the PLC status in thoracolumbar fractures of the spine.

Material And Methods: in a prospective study the findings of the preoperative ultrasound examination were compared to the intraoperative findings.

Strumpellin is a novel valosin-containing protein binding partner linking hereditary spastic paraplegia to protein aggregation diseases.

Mutations of the human valosin-containing protein gene cause autosomal-dominant inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia. We identified strumpellin as a novel valosin-containing protein binding partner. Strumpellin mutations have been shown to cause hereditary spastic paraplegia.

Deconvolution of complex G protein-coupled receptor signaling in live cells using dynamic mass redistribution measurements.

Label-free biosensor technology based on dynamic mass redistribution (DMR) of cellular constituents promises to translate GPCR signaling into complex optical 'fingerprints' in real time in living cells. Here we present a strategy to map cellular mechanisms that define label-free responses, and we compare DMR technology with traditional second-messenger assays that are currently the state of the art in GPCR drug discovery. The holistic nature of DMR measurements enabled us to (i) probe GPCR functionality along all four G-protein signaling pathways, something presently beyond reach of most other assay platforms; (ii) dissect complex GPCR signaling patterns even in primary human cells with unprecedented accuracy; (iii) define heterotrimeric G proteins as triggers for the complex optical fingerprints; and (iv) disclose previously undetected features of GPCR behavior.

Randomized comparison of eptifibatide versus abciximab in primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction: results of the EVA-AMI Trial.

Objectives: The aim of this study was to compare eptifibatide and abciximab as adjuncts to primary percutaneous coronary intervention (PCI).

Background: The glycoprotein (GP) IIb/IIIa receptor inhibitor abciximab as adjunct to primary PCI in patients with ST-segment elevation myocardial infarctions has been shown to reduce ischemic complications and improve clinical outcomes. So far, no trial has been performed to compare the efficacy of another GP IIb/IIIa receptor inhibitor, eptifibatide, and abciximab in primary PCI.

Pulse-pressure variation and hemodynamic response in patients with elevated pulmonary artery pressure: a clinical study.

Introduction: Pulse-pressure variation (PPV) due to increased right ventricular afterload and dysfunction may misleadingly suggest volume responsiveness. We aimed to assess prediction of volume responsiveness with PPV in patients with increased pulmonary artery pressure.

Methods: Fifteen cardiac surgery patients with a history of increased pulmonary artery pressure (mean pressure, 27 +/- 5 mm Hg (mean +/- SD) before fluid challenges) and seven septic shock patients (mean pulmonary artery pressure, 33 +/- 10 mm Hg) were challenged with 200 ml hydroxyethyl starch boli ordered on clinical indication.

Cardiac conduction disturbances and differential effects on atrial and ventricular electrophysiological properties in desmin deficient mice.

Purpose: Desmin mutations in humans cause desmin-related cardiomyopathy, resulting in heart failure, atrial and ventricular arrhythmias, and sudden cardiac death. The intermediate filament desmin is strongly expressed in striated muscle cells and in Purkinje fibers of the ventricular conduction system. The aim of the present study was to characterize electrophysiological cardiac properties in a desmin-deficient mouse model.

Health-related quality of life in ALS, myasthenia gravis and facioscapulohumeral muscular dystrophy.

Neuromuscular disorders are rare diseases with a chronic and debilitating course. Unfortunately, data on the health-related quality of life (HRQoL) in neuromuscular diseases are limited. The objective of this multicentre cross-sectional study was to compare the HRQoL in patients with amyotrophic lateral sclerosis (ALS), facioscapulohumeral muscular dystrophy (FSHD) and myasthenia gravis (MG) and to identify the determinants of the HRQoL in these diseases.

Comparison between proliferative and neuron-like SH-SY5Y cells as an in vitro model for Parkinson disease studies.

The molecular mechanisms underlying the cellular lost found in the nigrostriatal pathway during the progression of Parkinson's disease (PD) are not completely understood. Human neuroblastoma cell line SH-SY5Y challenged with 6-hydroxydopamine (6-OHDA) has been widely used as an in vitro model for PD. Although this cell line differentiates to dopaminergic neuron-like cells in response to low serum and retinoic acid (RA) treatment, there are few studies investigating the differences between proliferative and RA-differentiated SH-SY5Y cells.

[Myosin storage myopathy: a rare subtype of protein aggregate myopathies].

Myopathies with pathological protein aggregates comprise a numerically significant group of sporadic and hereditary muscle disorders. A rare disease entity within the group of protein aggregate myopathies is the myosin storage myopathy, which is caused by heterozygous mutations in the MYH7 gene which encodes the slow/beta-myosin heavy chain. We report the clinical, myopathological and MRI findings in the first German patient suffering from a myosin storage myopathy due to a heterozygous R 1845W missense mutation.

Addictive overeating: lessons learned from medical students' perceptions of Overeaters Anonymous.

Aim: To explore medical students' perceptions of Overeaters Anonymous (OA).

Method: 72 fifth-year medical students' reports of their experiences of attending OA meetings were analysed using thematic analysis. Students were required to submit these reports in order to complete a compulsory component of the Addiction Medicine run in their medical training at the University of Otago, Christchurch during 2002-2007.

Object wave reconstruction by phase-plate transmission electron microscopy.

A method is described for the reconstruction of the amplitude and phase of the object exit wave function by phase-plate transmission electron microscopy. The proposed method can be considered as in-line holography and requires three images, taken with different phase shifts between undiffracted and diffracted electrons induced by a suitable phase-shifting device. The proposed method is applicable for arbitrary object exit wave functions and non-linear image formation.

GPR55 ligands promote receptor coupling to multiple signalling pathways.

Background And Purpose: Although GPR55 is potently activated by the endogenous lysophospholipid, L-alpha-lysophosphatidylinositol (LPI), it is also thought to be sensitive to a number of cannabinoid ligands, including the prototypic CB1 receptor antagonists AM251 and SR141716A (Rimonabant). In this study we have used a range of functional assays to compare the pharmacological activity of selected cannabinoid ligands, AM251, AM281 and SR141716A with LPI in a HEK293 cell line engineered to stably express recombinant, human GPR55.

Experimental Approach: We evaluated Ca(2+) signalling, stimulation of extracellular signal regulated kinase (ERK1/2) mitogen activated kinase MAP-kinases, induction of transcriptional regulators that are downstream of GPR55, including nuclear factor of activated T cells (NFAT), nuclear factor-kappaB (NF-kappaB) and cAMP response element binding protein (CREB), as well as receptor endocytosis.