001 g/100 mu L) injection into the 4(th) V Vehicle treatment did

001 g/100 mu L) injection into the 4(th) V. Vehicle treatment did not change

baroreflex responses. ATZ attenuated bradycardic peak and reduced HR range at 30 minutes. ATZ into the 4(th) V reduced bradycardic and tachycardic reflex responses to increase and decrease MAP, respectively (p < 0.05) 30 minutes after its microinjection without significantly changing the basal MAP and HR. In conclusion, central catalase inhibition influenced the highest parasympathetic response to MAP increase in conscious Wistar rats without change baroreflex gain.”
“Exudative age-related macular degeneration (ARMD) is one of the conditions which has been shown to be associated with a risk of massive subretinal hemorrhage. Patients with thick submacular hemorrhage complicating ARMD HIF inhibitor typically have a poor visual prognosis. Antiplatelet therapy with aspirin, clopidogrel or ticlopidine has significant benefits in the secondary prevention of fatal and non-fatal coronary and cerebrovascular events. Anticoagulation is frequently used in this elderly age group for a variety of other comorbidities including prosthetic heart valves, atrial Selleck MK-0518 fibrillation, ischemic heart disease, cerebrovascular disease and venous thromboembolism. However, it is a well established observation that the longer patients remain on anticoagulant therapy, the higher the cumulative risk of bleeding. Over the past years, there has been a rapidly growing body of literature concerning

the risk of hemorrhagic ocular complications with ophthalmic surgery in patients receiving anticoagulant therapy. By contrast, there are still little data on the relationship between anticoagulation or antiplatelet therapy and spontaneous ocular hemorrhages and only few reports have focused on patients with ARMD. Just recently, several authors reported a strong association of anticoagulants and antiplatelet agents with the development of large subretinal

hemorrhages in ARMD patients. Moreover, arterial hypertension is a high risk factor for large subretinal hemorrhages in ARMD patients receiving anticoagulants or antiplatelet agents. Physicians should be aware of an increased risk of extensive subretinal hemorrhage in ARMD patients when deciding on the initiation and duration of anticoagulant and antiplatelet therapy.”
“In this FG-4592 mw paper, we introduce a new approach for tensor field segmentation based on the definition of mixtures of Gaussians on tensors as a statistical model. Working over the well-known Geodesic Active Regions segmentation framework, this scheme presents several interesting advantages. First, it yields a more flexible model than the use of a single Gaussian distribution, which enables the method to better adapt to the complexity of the data. Second, it can work directly on tensor-valued images or, through a parallel scheme that processes independently the intensity and the local structure tensor, on scalar textured images.

As neurogenesis in adults is related to the hippocampus, the sign

As neurogenesis in adults is related to the hippocampus, the significance of the increase of membrane particle-associated CD133 especially in temporal lobe epilepsy needs further clinical correlation. (C) 2011 Elsevier B.V. All rights reserved.”
“Yersinia outer protein P (YopP) induces cell death in macrophages and dendritic THZ1 cells (DC). In DC this YopP-dependent cell death coincides with the inhibition of nuclear factor-kappa B (NF-kappa B) activation. However, as shown by measurement of propidium iodide uptake via disrupted cellular membranes, the preincubation of DC, with

several NF-kappa B inhibitors prior to infection with Yersinia did not restore the death-inducing capacity of a YopP-deficient Yersinia mutant. These results suggest that in contrast to macrophages, in DC the YopP-dependent inhibition of NF-kappa B activation is not causative for the induction of cell death. Instead, in DC, the inhibition of mitogen-activated protein kinases (MAPKs), in particular, p38 and c-Jun N-terminal kinase, prior to infection https://www.selleckchem.com/products/torin-2.html with a YopP-deficient Yersinia mutant substituted the death-inducing capacity of the Yersinia wild-type strain, indicating that the YopP-dependent inhibition of MAPKs mediates Yersinia-induced DC death. The differences

between DC and macrophages in the mechanisms of cell death induction by YopP presented herein might be crucial for the function of these antigen-presenting cells.”
“Brostallicin is a DNA minor groove binder in phase 11 clinical trials. Here, we show that brostallicin induces Y-H2AX nuclear foci that colocalize with 53BP1 and are dependent on glutathione, as shown by inhibition of those Y-H2AX foci by L-buthionine sulfoximine. To differentiate brostallicin from the clinically approved Stattic manufacturer minor groove binder trabectedin (ecteinascidin 743), we tested whether the brostallicin-induced Y-H2AX and anti proliferative responses were dependent on nucleotide excision repair and found that, unlike trabectedin, they are not. Additionally, brostallicin retained activity in the trabectedin-resistant HCT116-ER5

cell line. Induction of Y-H2AX foci by brostallicin was partially dependent on the repair nuclease Well. Pretreatment with aphidicolin partially reduced brostallicin-induced Y-H2AX foci, suggesting that brostallicin induces both replication-associated and replication-independent DNA damage. Replication-associated DNA damage was further shown by the colocalization of Y-H2AX foci with replication foci and by the rapid inhibition of DNA synthesis and accumulation of cells in S phase in response to brostallicin. In addition, brostallicin was able to induce lower intensity Y-H2AX foci in human circulating lymphocytes. Together, our results indicate that brostallicin induces DNA double-strand breaks and suggest Y-H2AX as a pharmacodynamic biomarker for brostallicin.

1%) had one, 62 patients (26 4%) two, and 34 patients (14 5%) thr

1%) had one, 62 patients (26.4%) two, and 34 patients (14.5%) three positive lymph nodes. Extracapsular spread (ECS) was described in 72 patients (30.6%). There were 67 patients (28.5%) who received additional radiotherapy to the ipsilateral periclavicular lymph nodes (PCLNI), while 168 patients did not (noPCLNI). Patients find more were re-examined or contacted by phone with regard to treatment-related late

effects.\n\nAfter a median follow-up of 78 months (range 7-107 months), 22 patients (9.4%) developed local, 9 (3.8%) axillary, 4 periclavicular (1.7%), and 41 distant failure (17.4%). The actuarial 8-year locoregional recurrence-free (LRRFS), disease-free (DFS), and overall survival rates (OS) were 83%, 67%, and 74%, respectively. Survival data for the PCLNI vs. noPCLNI group were 72% vs. 89% (p = 0.3), 56% vs. 73% (p = 0.4), and 86% vs. 70% (p = 0.3), respectively. No higher toxicity rates were reported in the PCLNI group compared to the noPCLNI group.\n\nWe could not demonstrate any difference in outcome in breast cancer patients with 1-3 positive axillary lymph node metastases with

or without periclavicular selleck products lymph node irradiation. In addition, patients with PCLNI did not complain about higher rates of late toxicities. However, patients with ECS, which may predict for locoregional failure, may benefit from adjuvant periclavicular irradiation.”
“Artificial cell scaffolds that support cell adhesion, growth, and organization need to be fabricated for various purposes. Recently, there have been increasing reports of cell patterning using electrical fields. We fabricated scaffolds consisting of silicone sheets coated with single-walled (SW) or multi-walled (MW) carbon nanotubes (CNTs) and evaluated their electrical properties and biocompatibility. We also performed cell alignment with dielectrophoresis using CNT-coated sheets as electrodes. Silicone coated with 10 mu g/cm(2) SWCNTs exhibited the least sheet resistance

(0.8 k Omega/sq); its conductivity was maintained even after 100 stretching cycles. CNT coating also improved cell adhesion and proliferation. When an electric field was applied to the cell suspension introduced on the CNT-coated selleck compound scaffold, the cells became aligned in a pearl-chain pattern. These results indicate that CNT coating not only provides electro-conductivity but also promotes cell adhesion to the silicone scaffold: cells seeded on the scaffold can be organized using electricity. These findings demonstrate that CNT-coated silicone can be useful as a biocompatible scaffold. (C) 2011 Elsevier B.V. All rights reserved.”
“A 15-year-old male orally consumed an unknown but fatal amount of sustained release hydromorphone. He was naive to opioid use. No other drugs or alcohol were involved.

While it remains unclear whether

management of diabetes w

While it remains unclear whether

management of diabetes will reduce the incidence of MCI and AD, emerging evidence suggests that diabetes therapies may improve cognitive function.”
“The tumor necrosis factor-alpha (TNF alpha) plays an important role in a number of chronic inflammatory disorders. Monoclonal camelidae variable heavy chain domain-only antibodies (V(H)H) have been developed to antagonize the action of human TNF alpha (anti-TNF-V(H)H). selleckchem Here we describe a strategy to obtain functional dimeric anti-TNF-V(H)H molecules, based on the C-terminal fusion of a kappa light chain domain to the anti-TNF-V(H)H. The resulting fusion protein was transiently expressed by use of viral vectors in Nicotiona benthandana((Nb)) leaves and purified. Competitive ELISA and cell cytotoxicity assays revealed that the dimerized anti-(Nb)TNF-V(H)H(C MAPK inhibitor kappa) proteins blocked TNF alpha-activity more effectively than either the

monomeric Escherichia coli((Ec)) produced anti-(Ec)TNF-V(H)H or the monomeric anti-(Nb)TNF-V(H)H(C kappa). We suggest that enhanced inhibition shown by dimeric anti-(Nb)TNF-V(H)H(C kappa), proteins is achieved by an increase in avidity. Biotechnol. Bioeng. 2010;106: 161-166. (C) 2009 Wiley Periodicals, Inc.”
“Drinking coffee has been associated with the development of several endocrine-related cancers. The interpretation of these data has often been limited to the role that caffeine plays. Trigonelline (Trig), a niacin-related compound, is a natural constituent of coffee accounting for similar to 1% dry matter in roasted beans. Studies exploring the effects of this bioactive compound on mammalian cells are limited. The initial purpose of our studies was to determine whether Trig alters the actions of estradiol (E(2)), using proliferation of estrogen-dependent human breast cancer (MCF-7) cells as a model system. find more When cells were cotreated with suboptimal doses of E(2) (10 pmol/L) and Trig (100 pmol/L), an additive enhancement of MCF-7 growth was observed.

In the absence of E(2), Trig stimulated MCF-7 cell proliferation in a dose-responsive manner and significantly enhanced cell growth at concentrations as low as 100 pmol/L. Cotreatment of MCF-7 cells with Trig and ICI 182,780, an estrogen receptor (ER) antagonist, inhibited Trig-induced cell proliferation. Trig treatment also induced activation of estrogen response element reporter assays in MCF-7 cells and increased expression of ER target genes (pS2, progesterone receptor, and cyclin D1) similar to E(2). While our data demonstrate that Trig activates the ER, competitive binding assays showed that Trig does not compete E(2) off of the ER at any concentration. This suggests that Trig is activating the ER through a separate mechanism.

Here, we identify that early growth response-1 (Egr-1) is a downs

Here, we identify that early growth response-1 (Egr-1) is a downstream target of RAGE in hepatic I/R injury.\n\nMethods: Hepatic I/R was induced in male mice. Liver remnants were analyzed for induction of Egr-1 and cytokines, as well as regulation of apoptotic pathways after reperfusion.\n\nResults: Egr-1 was upregulated in the liver remnants after hepatic I/R injury and was suppressed by administration of soluble RAGE or deletion of the RAGE gene. RAGE-mediated increased expression of Egr-1 upregulates a central downstream

EPZ5676 gene, M1P2. In contrast, RAGE-stimulated Egr(-/-)independent pathways regulate TNF-alpha production and apoptosis in response to I/R. Consistent with these findings, phospho-p44/42 and phospho-JNK MAPK and c-Jun were strikingly suppressed in RAGE(-/-) versus WT mice, but not in Egr-1(-/-) mice. RAGE ligand HMGB1 was upregulated after I/R in the liver remnants. In vitro, incubation of RAGE-expressing liver dendritic cells (DCs) with recombinant HMGB-1 resulted in increased Egr-1 transcripts, in a manner suppressed by RAGE gene deletion, soluble RAGE and inhibitors of p44/p42 or JNK

MAP kinase.\n\nConclusions: Suppression of Egr-1 may contribute to the protective mechanisms underlying the beneficial impact of RAGE blockade or deletion. (c) 2008 European Association for the Study of the Liver. Published CH5183284 mouse by Elsevier B.V. All rights reserved.”
“The common Grape L. (Vitaceae) is regarded

as an important medicinal plant. European healers have suggested the use of grapevine sap, juice, and whole grape in the treatment of pain, allergic reactions, inflammation, and to promote wound healing. We evaluated grape-skin powder for its wound-healing activity using an excision wound model in rats. Animals were randomly divided into three groups of six (n = 6) each. The test group animals were treated topically with the grape-skin powder (100 mg/kg/day). The controls and standard group animals were treated with petroleum jelly and mupirocin ointment respectively. Semaxanib nmr Healing was assessed by the rate of wound contraction, period of epithelialization, and hydroxyproline content. On day 13, treatment of the wounds with grape-skin powder enhanced significantly the rate of wound contraction (100 %). Treated animals showed significant decrease in the epithelialization period (p < 0.000) and increase in the hydroxyproline content (p < 0.05) when compared to control and the standard. Histological analysis was also consistent with the proposal that grape-skin powder exhibits significant wound-healing potential. Increased rate of wound contraction, hydroxyproline content, and decrease in epithelialization time in the treated animals support the use of grape-skin powder in the management of wound healing. Copyright (C) 2010 John Wiley & Sons, Lid. and Crown in the Right of Canada.

In conclusion, our data show that MAT II and SAMe are critical mo

In conclusion, our data show that MAT II and SAMe are critical molecular components essential for CD4(+) T-cell survival that are affected by ethanol, leading to enhanced AICD. Furthermore, these studies provide a clinical paradigm for the development of much needed therapy using SAMe supplementation in the treatment

of immune dysfunction induced by alcohol abuse. 2008 Elsevier Inc. All rights reserved.”
“A series of new 2-pyrazoline derivatives has been synthesized by reacting 3-(substituted-phenyl)-1-pyridin-2-yl-propenones using two routes one using thiosemicarbazide and the other by hydrazine hydrate. The chemical structures were MGCD0103 purchase established by IR, Mass, H-1-NMR, C-13-NMR spectroscopic data, and elemental analysis. The anticonvulsant activity of the synthesized compounds was evaluated by the “maximal electroshock seizure”

(MES) test and pentylenetetrazole (PTZ) test using male albino mice. Compounds 2e, 5-(naphthalene-1-yl)-3-(pyridine-2-yl)-4,5-dihydro-1H-pyrazole-1-carbothioic acid amide, and 3c, N-ethyl-5-(naphthalene-1-yl)-3-(pyridine-2-yl)-4,5-dihydro-1H-pyrazole-1-carbothioamide showed appreciable activity in the MES as well as PTZ test at learn more all the evaluated doses.”
“We newly developed lithium methyltriolborate as an air-stable white solid that is convenient to handle. The good performance of this triolborate for metal-catalyzed bond-forming reactions was demonstrated in palladium-catalyzed cross-coupling reactions with haloarenes. Cross-coupling reaction of [MeB(OCH2)(3)CCH3]Li with aryl halides occurred in the presence of Pd(OAc)(2)/RuPhos complex in refluxing MeOH/H2O and the absence of bases.”
“Background Caroli disease is a rare congenital disorder characterized by segmental, nonobstructive dilatation of intrahepatic bile ducts. The term Caroli syndrome is used for the association of Caroli disease with congenital hepatic fibrosis.\n\nStudy aims To provide an overview of the clinical presentation and imaging selleck products features of Caroli disease and syndrome, with an emphasis

on magnetic resonance imaging.\n\nPatients and methods Retrospective analysis of medical records on eight patients in whom a histologic diagnosis of Caroli disease or syndrome had been made.\n\nResults Presenting signs and symptoms were (hepato) splenomegaly, hematemesis and/or melena, cholangitis, jaundice, and recurrent fever. The central dot sign, defined in the literature as a dot or bundle of strong contrast enhancement within dilated intrahepatic ducts, was found in seven cases on various imaging modalities. A ‘dot-like structure’ was found in one case in which only unenhanced studies were available. There was a tendency toward a right hepatic-lobe predominance.\n\nConclusion There is an overlap between the imaging features of Caroli disease and Caroli syndrome.

Phylogenetic analyses of clone libraries exhibited that all of na

Phylogenetic analyses of clone libraries exhibited that all of nah sequences and most of C12O sequences were affiliated into Gammaproteobacteria and Betaproteobacteria. These results suggested that external stimuli produced by DOMs could enhance the microbial degradation of PAHs in soils through not only solubilizing PAHs but also altering abundance and composition of indigenous microbial degraders. Our results reinforce the understanding of role of DOMs in mediating degradation of PAHs by microorganims in soils.”
“An increasing number PS-095760 of patients with kidney transplants are found to develop abdominal aortic aneurysm (AAA) in the post-transplant period. Aortic surgery in these

patients places the pelvic allograft at risk for ischaemic damage. We report successful repair of two PARP inhibitor AAA in renal transplant recipients using cold graft perfusion and local hypothermia to protect the renal allograft during aortic cross-clamping. Conventional AAA surgery in patients with a kidney transplant is feasible without impairing renal function. In situ cold perfusion represents a safe method of

renal protection with low risk of atheromatous embolization. Likewise, endovascular techniques may be an option in selected cases.”
“Methods: Thirty patients (nine men and 21 women; mean age, 41.5 +/- 15 years) in sinus rhythm with mitral valve prolapse who had VT in 24-hour Holter analysis and 30 patients with MVP without VT (eight men and 22 women; mean age, 43 +/- 16 years) were included in this study. Transthoracic echocardiography, QT analyses from 12-lead electrocardiography, and 24-hour Holter electrocardiogram recordings were performed.\n\nResults: Mitral posterior leaflet thickness (0.48 +/- 0.03 cm vs 0.43 +/- 0,08 cm, P = 0.025), mitral anterior leaflet length

Vorinostat molecular weight (3.2 +/- 0.24 cm vs 2.9 +/- 0.36, P < 0.001), mitral posterior leaflet length (2.2 +/- 0.3 cm vs 1.9 +/- 0.35 cm, P = 0.01), left atrium anteroposterior diameter (4.2 +/- 0.8 cm vs 3.5 +/- 0.5 cm, P = 0.001), and mitral annulus circumference (15.7 +/- 1.3 cm vs 14.6 +/- 1.6 cm, P = 0.004) were increased significantly in MVP cases with VT. No significant difference was found between the cases with and without VT in terms of frequency- and time-domain analysis. QT dispersion (72 +/- 18 ms vs 55 +/- 15 ms, P = 0.0002) and corrected QT dispersion (QTcD) (76 +/- 18 ms vs 55 +/- 15 ms, P = 0.0002) were significantly increased in cases with VT compared with those without VT. Based on logistic regression analysis for MVP cases, in the case of VT, an enhancement in QTcD (P = 0.01) and the mitral anterior leaflet length (P = 0.003) were the independent predictors of VT.\n\nConclusion: Mitral anterior leaflet length and enhanced QTcD are closely related with VT in patients with classical MVP. (PACE 2010; 33:1224-1230).”
“Purpose of review\n\nIn the last 2 years, several reports have dealt with recruitment/positive end-expiratory pressure (PEEP) selection.

Towards that end, a variational multiscale approach to predict mi

Towards that end, a variational multiscale approach to predict mixed mode in-plane cohesive crack propagation is presented here. To demonstrate applicability and to provide validation of the finite element based predictive methodology, a comparative study of the numerical results with the corresponding experimental observations

of crack propagation in laminated fiber reinforced composite panels is presented. (C) 2012 Elsevier Ltd. All rights reserved.”
“Food drying kinetics is usually studied by 4SC-202 measuring the product average moisture content as a function of time, known as the drying curve, for constant air conditions. The slope of this curve is the drying rate. Most food drying studies consider that the drying rate decreases from the start, and propose the use of diffusion models. However, some authors have observed that in high-moisture foods there is an

initial period with a constant drying rate and a linear drying curve which is assumed to be externally controlled. A model similar to that used for pure water evaporation is usually proposed but this does not consider internal Smoothened Agonist solubility dmso moisture gradients. Here, drying curves were recorded for fruit pectic gels and an initial linear variation of the drying curve was observed. By applying an analytical solution of diffusion for mass transfer Biot number = 2, (the internal resistance is twice the external) in plane sheets, the linear behaviour was predicted for the average moisture content at early stages in the drying curve. However, a variant of this solution, which predicts moisture content as a function of time for the surface and several positions within the plane sheet, was utilised. Under the same conditions, it was found that all curves differed one to the other (internal gradients) and none was linear. Linear drying behaviour therefore appears to be restricted to the average moisture content only and

ACY-738 for a limited period, and thus the constant rate period of drying in high-moisture foods does not follow convective, purely external controls. (c) 2008 IAgrE. Published by Elsevier Ltd. All rights reserved.”
“In France, international adoption includes around to 90,000 children since 1980 and near 300,000 immigrant children were counted in 2008. This population is heterogeneous, according to age and country of origin, and its large number. It is not easy to completely and surely assess the vaccine status of the child. Due to a great variability of individual situations, it is not possible to have systematic and unchangeable rules. This article aims to give an update of catch-up vaccination of internationally adopted or refugee or migrant children in France. The vaccination status of a child who recently arrived in France is complex and has to be adapted to his country of origin. Some of them were never vaccinated whereas the vaccine status of others is uncertain or unknown.

Pups postnatally M

Pups postnatally learn more exposed to only water showed later in adult life behavioral responses when exposed to TMT that were statistically different from mice that were exposed as neonates to TMT. In addition, mice exposed as neonates to TMT showed a decrease of fear-related behaviors while no differences occurred in the corticosterone levels between both groups. (C) 2010 Elsevier B.V. All rights reserved.”
“Background: Zollinger-Ellison syndrome (ZES) is a rare disorder caused by tumor secretion of the hormone

gastrin, which results in gastric acid hypersecretion and secondarily complicated peptic ulcer and diarrhea. Until the development of H-2-receptor antagonists and later proton pump inhibitors

(PPIs), the disease was virulent, often associated with ulcer-related mortality, and the mainstay of treatment was total gastrectomy. Objective: To evaluate current approaches to diagnosis and therapy, focusing on the role of PPIs. Methods: An extensive literature search through PubMed using the search term ‘Zollinger-Ellison syndrome’ from 1964 to the present was performed. Primary articles were identified, and pertinent articles obtained from the reference lists were also examined. Results/conclusions: The clinical manifestations of ZES are well described, but overlaps with other more common disorders delay diagnosis. The use of abdominal imaging with somatostatin receptor

scintigraphy and endoscopic ultrasound has improved tumor staging. PPI therapy is remarkably effective in controlling gastric acid hypersecretion, Trichostatin A thereby reducing morbidity and potential mortality of this syndrome. The dose of drug necessary to control symptoms is highly variable but, even when used in high doses for prolonged periods of time, the disease remained controlled BI 2536 with very few drug-related side effects.”
“The freshwater littoral comprises a mosaic of habitats structured at several scales by a combination of hydrophyte architecture and physiology. Within this complex environment littoral invertebrates should distribute themselves to maximize fitness: that is, for sessile animals selection of permanent substrata is critical, while distribution of motile (periphytic) animals should follow predictions of Ideal Free Distribution theory. Here we explore the relationships between littoral rotifers and hydrophytes by conducting nestedness analyses on 10 published datasets (7 sessile; 3 periphytic); one dataset each of microcrustaceans and insects were included for comparison. We used four metrics to assess nestedness: mean matrix temperature (T); counts of discrepancy shifts and species segregation; and percent singletons. Six sessile rotifer datasets exhibited nestedness (T = 9.25-30.2 degrees, supported by bigger than = 2 null models; the other metrics varied widely).

Methods Eighty-four social drinkers took part in two studies that

Methods Eighty-four social drinkers took part in two studies that followed a counterbalanced repeated measure design. Fifteen men and 33 women were tested the morning (09:00, 11:00 or 13:00?h) following normal/usual alcohol consumption and the morning after no alcohol consumption; the order of testing was counterbalanced. In a second study, 36 participants (18 men and 18 women) were

tested after receiving alcohol to attain a blood alcohol concentration of 0.08%, and after no alcohol administration, the order of testing was counterbalanced. In both studies, participants completed Selleck R406 a task battery of memory, reaction time and attention tasks. Results Alcohol had no effect on the free recall task and the spatial attention task. Alcohol consumption, either acute or the next day, significantly affected reaction time, divided attention, selective attention and Stroop interference. The impairments during intoxication and hangover were of comparable magnitude. Performance on tasks of delayed recognition and irregular interstimulus reaction time was worse during hangover when compared with intoxication. Conclusion It is evident that awareness JNK-IN-8 needs to be raised

that performance the morning after alcohol consumption is at the same level if not worse than when participants are at the legal limit for driving (0.08% blood alcohol concentration). Copyright (c) 2012 John Galardin in vitro Wiley & Sons, Ltd.”
“Traditionally, medical therapy for epilepsy has aimed to suppress seizure activity, but has been unable to alter the progression of the underlying disease. Recent advances in our understanding of mechanisms of epileptogenesis open the door for the development of new therapies which prevent the pathogenic changes in the brain that predispose to spontaneous seizures. In particular, the mammalian target of rapamycin (mTOR) signaling pathway has recently

garnered interest as an important regulator of cellular changes involved in epileptogenesis, and mTOR inhibitors have generated excitement as potential antiepileptogenic agents. mTOR hyperactivation occurs in tuberous sclerosis complex (TSC), a common genetic cause of epilepsy, as a result of genetic mutations in upstream regulatory molecules. mTOR inhibition prevents epilepsy and brain pathology in animal models of TSC. mTOR dysregulation has also been demonstrated in a variety of other genetic and acquired epilepsies, including brain tumors, focal cortical dysplasias, and animal models of brain injury due to status epilepticus or trauma. Indeed, mTOR inhibitors appear to possess antiepileptogenic properties in animal models of acquired epilepsy as well. Thus, mTOR dysregulation may represent a final common pathway in epilepsies of various causes.