387 research outputs found

    Anticonvulsant and procognitive properties of Novel Histamine H3 Receptor Antagonists in male adult rats

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    To determine the potential of histamine H3 receptor (H3R) ligands as new antiepileptic and procognitive drugs, aromatic ether derivatives (1-12) belonging to the nonimidazole class of ligands, with high in-vitro binding affinity at human H3R, were tested for their in-vivo anticonvulsive activity in maximal electroshock (MES)-, pentylenetetrazole (PTZ)-, and strychnine (STR)-induced seizure models in male adult rats having phenytoin (PHT) and valproic acid (VPA) as the reference antiepileptic drugs, pitolisant (PIT) as the standard H3R antagonist/inverse agonist, and donepezil (DOZ) as a reference procognitive drug. Among the H3R ligands (1-12) tested in the current project, H3R antagonist 4 showed significant and dose dependent reduction in the duration of tonic hind limb extension (THLE) subsequent to acute systemic administration (5, 10, and 15 mg/kg, i.p.). Importantly, the protective action observed for H3R antagonist 4 in MES-induced seizure was comparable to that of the reference antiepileptic drug phenytoin (PHT), and was also reversed when rats were pretreated with the CNS penetrant pyrilamine (PYR) (10 mg/kg, i.p.), or with the selective H3R agonist R-(α)-methylhistamine (RAMH) (10 mg/kg, i.p.). Furthermore, the procognitive studies indicate that acute pre-training systemic administration of H3R antagonist 4 (2.5 mg/kg, i.p.) facilitated acquisition, whereas pre-testing acute administration of 4 (5 and 10 mg/kg, i.p.) improved retrieval. Interestingly, the procognitive effect of 4 on retrieval was completely abrogated when rats were pretreated with the centrally-acting H2R antagonist zolantidine (ZOL) but not the centrally acting H1R antagonist PYR, indicating that histaminergic pathways through activation of H2Rs appear to be participating in neuronal circuits involved in the retrieval processes. Taken together, our results show that H3R antagonist 4 demonstrates anticonvulsant properties in the MES-induced seizure model and improves cognitive performance through actions on different memory stages. Therefore, H3Rs may have implications for the treatment of degenerative disorders associated with impaired memory function and may represent a novel therapeutic pharmacological target to tackle cognitive problems associated with the chronic use of antiepileptic drugs

    Detecting Fault Injection Attacks with Runtime Verification

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    International audienceFault injections are increasingly used to attack/test secure applications. In this paper, we define formal models of runtime monitors that can detect fault injections that result in test inversion attacks and arbitrary jumps in the control flow. Runtime verification monitors offer several advantages. The code implementing a monitor is small compared to the entire application code. Monitors have a formal semantics; and we prove that they effectively detect attacks. Each monitor is a module dedicated to detecting an attack and can be deployed as needed to secure the application. A monitor can run separately from the application or it can be weaved inside the application. Our monitors have been validated by detecting simulated attacks on a program that verifies a user PIN

    Formal Analysis of E-Cash Protocols

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    International audienceElectronic cash (e-cash) aims at achieving client privacy at payment, similar to real cash. Several security protocols have been proposed to ensure privacy in e-cash, as well as the necessary unforgery properties. In this paper, we propose a formal framework to define, analyze, and verify security properties of e-cash systems. To this end, we model e-cash systems in the applied π-calculus, and we define two client privacy properties and three properties to prevent forgery. Finally, we apply our definitions to an e-cash protocol from the literature proposed by Chaum et al., which has two variants and a real implementation based on it. Using ProVerif, we demonstrate that our framework is suitable for an automated analysis of this protocol

    Green House Gases: A Review of Losses and Benefits

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    This study provides a review of benefit and losses of greenhouse gases. For the last decades, the average global temperature is rising on the surface as well as on the oceans. There are a number of factors behind this rise, but the main cause of this rise is anthropogenic increase in greenhouse gases (GHG). The anthropogenic factors comprise of burning of fossil fuel, coal mining, industrialization etc. During the last century, the CO2 concentration increased by 391 PPM, CH4 and N2O have reached at warming levels. The rise in overall temperature is changing the living pattern of humans and it also damages the economy as well as ecosystem for other living species. The rising GHG concentration may also have some positive effects on the economy, but it has heavy costs as well. GHGs are responsible for the change in climate which include a rise in sea level, ice melting from ice sheets and ocean acidification and climate change is responsible for the other damages like low fresh water resources, damage to the coastal system, damage to human health and raise the issue of food security
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