The SuperB-Factory accelerator project

An international collaboration on the design of a Super B-Factory aiming at a 1036 cm-2 s-1 luminosity is in progress. The design relies on a new collision scheme with large Piwinski’s angle and very small IP beam sizes, where possible harmful resonances will be cancelled by the newly proposed “crab waist” method. A Conceptual Design Report has been published in April this year. A review of the design principles and of the project status will be given

Parameters for a Super-Flavor-Factory

A Super Flavor Factory, an asymmetric energy e+e- collider with a luminosity of order 10^36 cm-2s-1, can provide a sensitive probe of new physics in the flavor sector of the Standard Model. The success of the PEP-II and KEKB asymmetric colliders in producing unprecedented luminosity above 10^34 cm-2s-1 has taught us about the accelerator physics of asymmetric e+e- colliders in a new parameter regime. Furthermore, the success of the SLAC Linear Collider and the subsequent work on the International Linear Collider allow a new Super-Flavor collider to also incorporate linear collider techniques. This note describes the parameters of an asymmetric Flavor-Factory collider at a luminosity of order 10^36 cm-2s-1 at the Upsilon(4S) resonance and about 10^35 cm-2s-1 at the Tau production threshold. Such a collider would produce an integrated luminosity of about 10,000 fb-1 (10 ab-1) in a running year (10^7 sec) at the Upsilon(4S) resonance.Comment: Flavor Physics & CP Violation Conference, Vancouver, 200

Antiepileptogenic effects of trilostane in the kainic acid model of temporal lobe epilepsy

Objective: Epileptogenesis after status epilepticus (SE) has a faster onset in rats treated to reduce brain levels of the anticonvulsant neurosteroid allopregnanolone with the 5α-reductase inhibitor finasteride; however, it still has to be evaluated whether treatments aimed at increasing allopregnanolone levels could result in the opposite effect of delaying epileptogenesis. This possibility could be tested using the peripherally active inhibitor of 3β-hydroxysteroid dehydrogenase/Δ5-4 isomerase trilostane, which has been shown repeatedly to increase allopregnanolone levels in the brain. Methods: Trilostane (50 mg/kg) was administered subcutaneously once daily for up to six consecutive days, starting 10 min after intraperitoneal administration of kainic acid (15 mg/kg). Seizures were evaluated by video-electrocorticographic recordings for 70 days maximum, and endogenous neurosteroid levels were assessed by liquid chromatography–electrospray tandem mass spectrometry. Immunohistochemical staining was performed to evaluate the presence of brain lesions. Results: Trilostane did not alter the latency of kainic acid-induced SE onset or its overall duration. When compared to the vehicle-treated group, rats receiving six daily trilostane injections presented a remarkable delay of the first spontaneous electrocorticographic seizure and subsequent tonic–clonic spontaneous recurrent seizures (SRSs). Conversely, rats treated with only the first trilostane injection during SE did not differ from vehicle-treated rats in developing the SRSs. Notably, trilostane did not modify neuronal cell densities or the overall damage in the hippocampus. In comparison to the vehicle group, repeated administration of trilostane significantly decreased the activated microglia morphology in the subiculum. As expected, allopregnanolone and other neurosteroid levels were remarkably increased in the hippocampus and neocortex of rats treated for 6 days with trilostane, but pregnanolone was barely detectable. Neurosteroids returned to basal levels after a week of trilostane washout.. Significance: Overall, these results suggest that trilostane led to a remarkable increase in allopregnanolone brain levels, which was associated with protracted effects on epileptogenesis

Lacosamide: a new approach to target voltage-gated sodium currents in epileptic disorders

The mechanism of action of several antiepileptic drugs (AEDs) rests on their ability tomodulate the activity of voltage-gated sodium currents that are responsible for fast action potentialgeneration. Recent data indicate that lacosamide - a compound with analgesic and anticonvulsanteffects in animal models - shares a similar mechanism. When compared with other AEDs, lacosamidehas the unique ability to interact with sodium channel slow inactivation without affecting fastinactivation. This article reviews these findings and discusses their relevance within the context ofneuronal activity seen during epileptiform discharges generated by limbic neuronal networks in thepresence of chemical convulsants. These seizure-like events are characterized by sustained dischargesof sodium-dependent action potentials supported by robust depolarizations thus providingsynchronization within neuronal networks. Generally, AEDs such as phenytoin, carbamazepine andlamotrigine block sodium channels when activated. By contrasts, lacosamide facilitates slowinactivation of sodium channels both in term of kinetics and voltage-dependency. This effect may berelatively selective for repeatedly depolarized neurons such as those participating in seizure activity inwhich the persistence of sodium currents is more pronounced and promotes neuronal excitation. Theclinical effectiveness of lacosamide has been demonstrated in randomized placebo-controlled doubleblindparallel-group, adjunctive-therapy trials in patients with refractory partial seizures. Furtherstudies should determine whether lacosamide effects in animal models and in clinical settings are fullyexplained by its selective action on sodium current slow inactivation or whether other effects (e.g.,interactions with the collapsin-response mediator protein 2) play a contributory role