Is autopsy tissue a valid control for epilepsy surgery tissue in microRNA studies?

MicroRNAs (miRNAs) are differentially expressed in the brain under pathologic conditions and may therefore represent both therapeutic targets and diagnostic or prognostic biomarkers for neurologic diseases, including epilepsy. In fact, miRNA expression profiles have been investigated in the hippocampi of patients with epilepsy in comparison with control, nonepileptic cases. Unfortunately, the interpretation of these data is difficult because surgically resected epileptic tissue is generally compared with control tissue obtained from autopsies. To challenge the validity of this approach, we performed an miRNA microarray on the laser microdissected granule cell layer of the human hippocampus obtained from surgical samples of patients with epilepsy, autoptic nonepileptic controls, and patients with autoptic epilepsy, using the latter as internal control. Unfortunately, it is extremely difficult to collect autopsy material from documented epilepsy individuals who died of non–epilepsy-related causes—we found only two such cases. However, hierarchical clustering of all samples showed that those obtained from autopsies of patients with epilepsy segregated with the other autoptic samples (controls) and not with the bioptic tissues from the surgery patients, suggesting that the origin of the tissue (surgery or autopsy) may be prevalent over the underlying pathology (epilepsy or not epilepsy). Even taking into account the limitations due to the small number of cases, this observation arises concerns on the use of autopsy tissue as control for this kind of studies

Video-game epilepsy: a European study.

Epilepsia. 1999;40 Suppl 4:70-4. Video-game epilepsy: a European study. Kasteleijn-Nolst Trenité DG, da Silva AM, Ricci S, Binnie CD, Rubboli G, Tassinari CA, Segers JP. Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands. [email protected] Abstract With the introduction of Nintendo video-games on a large scale, reports of children having seizures while playing suggested a possible specific, provocative factor. Although 50% of the photosensitive patients are also sensitive to a 50-Hz television, nonphotosensitive patients with a history of video-game seizures were described as well. The question arises whether this is a mere coincidence, provoked by fatigue and stress, is related to the reaction to the television screen itself, or depends on the movement and color of the pictures of this specific game. A European study was performed in four countries and five sites. All patients were selected because of a history of television, video- or computer-game seizures, with a history of sun-light-, discotheque-, or black and white pattern-evoked seizures, or were already known to be sensitive to intermittent photic stimulation. A total of 387 patients were investigated; 220 (75%) were female and 214 (55%) of those were < 18 years of age. After a routine examination, intermittent photic, pattern, and television stimulation were performed in a standardized way. The patients were investigated with Super Mario World and a standard relatively nonprovocative TV program, both on a 50- and 100-Hz television. Regardless of the distance, Super Mario World proved to be more provocative than the standard program (Wilcoxon, p < 0.05). Eighty-five percent showed epileptiform discharges evoked by intermittent photic stimulation. Forty-five percent of patients were 50-Hz television sensitive and 26% were 100-Hz television sensitive. Pattern sensitivity was found in 28% of patients. The patients, referred because of a television, video- or computer-game seizure, were significantly more sensitive to pattern and to the 50-Hz television (chi square, p < 0.001). More patients are sensitive when playing Super Mario, compared with the standard program (Wilcoxon, p = 0.001) and more sensitive with playing versus viewing (p = 0.016). Of the patients who were referred because of seizures in front of the television, or evoked by a video- or computer game, 14% proved not to be photosensitive. Although no difference in age or use of medication was found, twice as many men were found in this nonphotosensitive group. PMID: 10487177 [PubMed - indexed for MEDLINE

Disparate effects of adhesion and degranulation of platelets on myocardial and coronary function in postischaemic hearts

Beside the major effect of acute thrombus formation, little is known about the interaction of platelets with the coronary endothelium in an ischaemia–reperfusion situation. The present study was designed to investigate, separately, the consequences of platelet adhesion and degranulation during myocardial reperfusion. Methods: Isolated guinea pig hearts perfused with Krebs–Henseleit buffer and performing pressure–volume work were used. We infringed myocardial function by imposing ischaemia (20 min of low-flow perfusion with 1 ml/min and 10 min of global ischaemia) and reperfusion (15 min with 5 ml/min). During low-flow perfusion, the coronary endothelium was stimulated by thrombin before and during infusion of a bolus: 108 washed human platelets±the Arg–Gly–Asp (RGD) analogon lamifiban, the supernatant of 108 thrombin-stimulated platelets, fibrinogen (2 μM), lamifiban (2 μM) or Tyrode’s solution (control group). The parameter external heart work (EHW), determined pre- and postischaemically, served as criterion for recovery of myocardial function. Additionally, the formation of capillary transudate was measured during the reperfusion phase to assess coronary permeability. Coronary perfusion pressure was monitored continuously and myocardial production of lactate and consumption of pyruvate were measured. Electron microscopy of hearts was performed after platelet application to verify platelet adhesion in the coronary system. Results: Recovery of EHW by hearts without platelet application was 64±3% and was significantly reduced to 49±5% by platelet infusion (n=8 each). Infusion of supernatant of thrombin-stimulated platelets did not impair recovery of heart work. In the reperfusion phase (6th–10th min), hearts that either had received platelets or supernatant of platelets exhibited a significantly reduced production of capillary transudate (70 μl/min vs. 180 μl/min for the controls). Intracoronary bolus application of fibrinogen or lamifiban also reduced coronary leak. Coronary perfusion pressure and metabolic parameters were not statistically different between the groups at any time. Conclusions: Platelet adhesion to the coronary endothelium in a situation of myocardial ischaemia impairs cardiac recovery, whereas constituents released by platelets may have beneficial effects on the integrity of the coronary endothelium. In particular, fibrinogen seems to contribute to the permeability reducing effect, possibly by interaction with endothelial receptors recognising the RGD sequence

MicroRNA profiles in hippocampal granule cells and plasma of rats with pilocarpine-induced epilepsy - Comparison with human epileptic samples

The identification of biomarkers of the transformation of normal to epileptic tissue would help to stratify patients at risk of epilepsy following brain injury, and inform new treatment strategies. MicroRNAs (miRNAs) are an attractive option in this direction. In this study, miRNA microarrays were performed on laser-microdissected hippocampal granule cell layer (GCL) and on plasma, at different time points in the development of pilocarpine-induced epilepsy in the rat: latency, first spontaneous seizure and chronic epileptic phase. Sixty-three miRNAs were differentially expressed in the GCL when considering all time points. Three main clusters were identified that separated the control and chronic phase groups from the latency group and from the first spontaneous seizure group. MiRNAs from rats in the chronic phase were compared to those obtained from the laser-microdissected GCL of epileptic patients, identifying several miRNAs (miR-21-5p, miR-23a-5p, miR-146a-5p and miR- 181c-5p) that were up-regulated in both human and rat epileptic tissue. Analysis of plasma samples revealed different levels between control and pilocarpine-treated animals for 27 miRNAs. Two main clusters were identified that segregated controls from all other groups. Those miRNAs that are altered in plasma before the first spontaneous seizure, like miR-9a-3p, may be proposed as putative biomarkers of epileptogenesis

Video games are exciting: a European study of videogame‐induced seizures and epilepsy.

Epileptic Disord. 2002 Jun;4(2):121-8. Video games are exciting: a European study of video game-induced seizures and epilepsy. Kasteleijn-Nolst Trenité DG, Martins da Silva A, Ricci S, Rubboli G, Tassinari CA, Lopes J, Bettencourt M, Oosting J, Segers JP. Department of Neurology, Medical Centre Alkmaar, PO Box 501, 1800 AM, The Netherlands. [email protected] Abstract BACKGROUND: Video game seizures have been reported in photosensitive and non-photosensitive patients with epilepsy. The game Super Mario World, has led to many cases of first seizures. We examined whether this game was indeed more provocative than other programs and whether playing the game added to this effect. METHODS: We prospectively investigated 352 patients in four European cities, using a standard protocol including testing of a variety of visual stimuli. We correlated historical data on provocative factors in daily life with electroencephalographic laboratory findings. RESULTS: The video game, Super Mario World proved more epileptogenic than standard TV programs and as provocative as programs with flashing lights and patterns. Most striking was the fact that video game-viewing and-playing on the 50 and 100 Hz TV was significantly more provocative than viewing the standard program (P < 0.001, P < 0.05 respectively). Playing the video game Mario World on a 50 Hz TV, appeared to be significantly more provocative than playing this game on the 100 Hz TV (P < 0.001). Of 163 patients with a history of TV-, VG- or CG-seizures, 85% of them showed epileptiform discharges in response to photic stimulation, 44% to patterns, 59% to 50 Hz TV and 29% to 100 Hz TV. CONCLUSIONS: Children and adolescents with a history of video game seizures are, in the vast majority, photosensitive and should be investigated with standardised photic stimulation. Games and programs with bright background or flashing images are specifically provocative. Playing a video game on a 100 Hz TV is less provocative [published with videosequences]. PMID: 12105074 [PubMed - indexed for MEDLINE

Efficacy and Safety of Low-Molecular-Weight Heparins As An Adjunct to Thrombolysis in Acute ST-Elevation Myocardial Infarction

A 48-hour course of intravenous unfractionated heparin (UFH) is the standard of treatment in conjunction with fibrin-specific thrombolysis in ST-elevation myocardial infarction (STEMI). In recent trials, the efficacy and safety of in-hospital administration of subcutaneous low-molecular-weight heparins (LMWH), previously proven effective in non-ST-elevation acute coronary syndromes, have been investigated in the setting of STEMI. The aim of this review was to evaluate the available evidence supporting the use of LMWH in STEMI

Fundamental Limits on Correlated Catalytic State Transformations

Determining whether a given state can be transformed into a target state using free operations is one of the fundamental questions in the study of resources theories. Free operations in resource theories can be enhanced by allowing for a catalyst system that assists the transformation and is returned unchanged, but potentially correlated, with the target state. While this has been an active area of recent research, very little is known about the necessary properties of such catalysts. Here, we prove fundamental limits applicable to any correlated catalytic transformation by showing that a small residual correlation between catalyst and target state implies that the catalyst needs to be highly resourceful. In fact, the resources required diverge in the limit of vanishing residual correlation. We develop our results in a general resource theory framework and discuss its implications for the resource theory of athermality, the resource theory of coherence and entanglement theory

New additivity properties of the relative entropy of entanglement and its generalizations

We prove that the relative entropy of entanglement is additive when \emph{at least one of the two states} belongs to some specific class. We show that these classes include bipartite pure, maximally correlated, GHZ, Bell diagonal, isotropic, and generalized Dicke states. Previously, additivity was established only if \textit{both} states belong to the same class. Moreover, we extend these results to entanglement monotones based on the $\alpha$-$z$ R\'enyi relative entropy. Notably, this family of monotones includes also the generalized robustness of entanglement and the geometric measure of entanglement. In addition, we prove that any monotone based on a quantum relative entropy is not additive for general states. We also compute closed-form expressions of the monotones for bipartite pure, Bell diagonal, isotropic, generalized Werner, generalized Dicke, and maximally correlated Bell diagonal states. Our results rely on developing a method that allows us to recast the initial convex optimization problem into a simpler linear one. Even though we mostly focus on entanglement theory, we expect that some of our technical results could be useful in investigating more general convex optimization problems