19 research outputs found
Redetermination of trans-cyclohexane-1,4-diammonium dichloride
A redetermination of the crystal structure of the title compound, C6H16N2
2+·2Cl−, was undertaken. All atomic coordinates including those of the H atoms were refined freely. The cation is located on a centre of symmetry. Important for the crystal structure are wavy hydrogen-bonded layers that are formed by ammonium groups and chloride anions, giving hydrogen-bonded rings
The anticancer phytochemical rocaglamide inhibits Rho GTPase activity and cancer cell migration
Chemotherapy is one of the pillars of anti-cancer therapy. Although chemotherapeutics cause regression of the primary tumor, many chemotherapeutics are often shown to induce or accelerate metastasis formation. Moreover, metastatic tumors are largely resistant against chemotherapy. As more than 90% of cancer patients die due to metastases and not due to primary tumor formation, novel drugs are needed to overcome these shortcomings. In this study, we identified the anticancer phytochemical Rocaglamide (Roc-A) to be an inhibitor of cancer cell migration, a crucial event in metastasis formation. We show that Roc-A inhibits cellular migration and invasion independently of its anti-proliferative and cytotoxic effects in different types of human cancer cells. Mechanistically, Roc-A treatment induces F-actin-based morphological changes in membrane protrusions. Further investigation of the molecular mechanisms revealed that Roc-A inhibits the activities of the small GTPases RhoA, Rac1 and Cdc42, the master regulators of cellular migration. Taken together, our results provide evidence that Roc-A may be a lead candidate for a new class of anticancer drugs that inhibit metastasis formation
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A low mortality, high morbidity Reduced Intensity Status Epilepticus (RISE) model of epilepsy and epileptogenesis in the rat
Animal models of acquired epilepsies aim to provide researchers with tools for use in understanding the processes underlying the acquisition, development and establishment of the disorder. Typically, following a systemic or local insult, vulnerable brain regions undergo a process leading to the development, over time, of spontaneous recurrent seizures. Many such models make use of a period of intense seizure activity or status epilepticus, and this may be associated with high mortality and/or global damage to large areas of the brain. These undesirable elements have driven improvements in the design of chronic epilepsy models, for example the lithium-pilocarpine epileptogenesis model. Here, we present an optimised model of chronic epilepsy that reduces mortality to 1% whilst retaining features of high epileptogenicity and development of spontaneous seizures. Using local field potential recordings from hippocampus in vitro as a probe, we show that the model does not result in significant loss of neuronal network function in area CA3 and, instead, subtle alterations in network dynamics appear during a process of epileptogenesis, which eventually leads to a chronic seizure state. The model’s features of very low mortality and high morbidity in the absence of global neuronal damage offer the chance to explore the processes underlying epileptogenesis in detail, in a population of animals not defined by their resistance to seizures, whilst acknowledging and being driven by the 3Rs (Replacement, Refinement and Reduction of animal use in scientific procedures) principles
Early Post-ischemic Brain Glucose Metabolism Is Dependent on Function of TLR2: a Study Using [18F]F-FDG PET-CT in a Mouse Model of Cardiac Arrest and Cardiopulmonary Resuscitation
Purpose!#!The mammalian brain glucose metabolism is tightly and sensitively regulated. An ischemic brain injury caused by cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) affects cerebral function and presumably also glucose metabolism. The majority of patients who survive CA suffer from cognitive deficits and physical disabilities. Toll-like receptor 2 (TLR2) plays a crucial role in inflammatory response in ischemia and reperfusion (I/R). Since deficiency of TLR2 was associated with increased survival after CA-CPR, in this study, glucose metabolism was measured using non-invasive [!##!Procedures!#!Two PET-CT scans using 2-deoxy-2-[!##!Results!#!The absolute SUV!##!Conclusions!#!The altered mouse strains presented a different pattern in glucose uptake under normal and ischemic conditions, whereby the post-ischemic differences in glucose metabolism were associated with the function of key immune factor TLR2. There is evidence for using early FDG-PET-CT as an additional diagnostic tool after resuscitation. Further studies are needed to use PET-CT in predicting neurological outcomes
Reliability of Continuous Pulse Contour Cardiac Output Measurement during Hemodynamic Instability
Objective Arterial pulse contour analysis is gaining widespread acceptance as a monitor of continuous cardiac output (CO). While this type of CO measurement is thought to provide acceptable continuous measurements, only a few studies have tested its accuracy and repeatability under unstable hemodynamic conditions. We compared continuous CO measurement using the pulse contour method (PCCO) before and after calibration with intermittent transpulmonary thermodilution cardiac output (TpCO). Method We compared the two methods of CO measurements in 15 Landrace pigs weighing 20–25 kg in an experimental model of sepsis. Nine pigs were given an infusion of E. coli lipopolysacchride (LPS), and six pigs acted as controls. PCCO values before and after calibration (PCCO1 and PCCO2 respectively) were registered, and their errors relative to TpCO measurements were compared. Results The mean coefficient of variation for repeated PCCO measurements was 6.85% for the control group, and 13.99% for the endotoxin group. The range of TpCO was 1.01–3.15 L/min. In the control group the bias ±2SD was 0.11 ± 0.53 L/min (TpCO vs PCCO1) and −0.02 ± 0.38 L/min (TpCO vs PCCO2). In the endotoxin group, the agreement was poor between TpCO and PCCO1, 0.08 ± 1.02 L/min. This improved after calibration (TpCO vs PCCO2) to 0.01 ± 0.31 L/min. Conclusions In hemodynamically stable pigs, both pre- and post-calibration PCCO measurements agreed well with the intermittent transpulmonary thermodilution technique. However, during hemodynamic instability, and pre-calibration PCCO values had wide limits of agreement compared with TpCO. This was reflected by larger coefficients of variation for PCCO in hemodynamic instability. The error of PCCO measurement improved markedly after calibration, with bias and limits of agreement within clinically acceptable limits