Current Pharmaceutical Design - Volume 19, Issue 38, 2013

Background: Bioavailability (F) and clearance (CL) are two pharmacokinetic parameters difficult to differentiate from simple plasma measurement when a drug is administered orally. Venous (V) / artery (A) concentration ratio of a drug could be a reliable index of its CL if measurements of plasma concentration were performed during a period of time where the absorption process was not longer operative, then during a pu Read More

Glutamic acid (Glu) is the major excitatory neurotransmitter in the central nervous system, and interacts with two classes of receptor: metabotropic and ionotropic receptors. Ionotropic receptors are divided according to the affinity of their specific agonists: Nmethyl- D-aspartate (NMDA), amino acid-3-hydroxy-5-methyl-4-isoxazole acid (AMPA) and kainic acid (KA). NMDA receptors (NMDA-R) are macromolecular structures that ar Read More

This review summarizes the effects of resveratrol in neurodegenerative diseases and speculates on the direction the field will take in the immediate future. In particular, we emphasize studies on the effects of resveratrol on new pathways related to neurodegenerative diseases such as inflammatory processes, mitochondrial biogenesis and its control through gamma coactivator 1-α (PGC1α), and the role of the tandem s Read More

P-glycoprotein (P-gp) has been associated with pharmacoresistance and mechanisms regulating the membrane potential. However, at present it is unknown if P-gp overexpression in brain is associated with changes in membrane depolarization in refractory epilepsy. Experiments were designed to evaluate the membrane depolarization and P-gp overexpression induced by repetitive pentilenetetrazole (PTZ)-induced-seizures. Wist Read More

The more common sporadic form of Alzheimer disease (SAD) and the metabolic syndrome are two highly prevalent pathological conditions of Western society due to incorrect diet, lifestyle, and vascular risk factors. Due to the increasing aging of populations, prevalence of AD in western industrialized countries will rise in the near future and, thus, new knowledge in the area of molecular biology and epigenetics will probab Read More

The majority of patients suffering from Alzheimer’s disease (AD) demonstrate cerebral vascular changes and impaired regulation of cerebral blood flow, which has been assumed to play an important role in AD pathogenesis (vascular hypothesis of AD). There is strong evidence that both β-amyloid (Aβ) oligomers and plaques contribute to vascular injuries and functional impairments of the neurovascular unit. Vice versa, Aβ l Read More

All common contributing factors to epilepsy such as trauma, malignancies and infections are accompanied by different levels of central nervous system inflammation that in turn have been associated with the occurrence of seizure. Emerging data from human brain tissue and experimental models of epilepsy support the proposed involvement of inflammation in epilepsy. Key mediators of this process include, among others: i Read More

Ghrelin is a gastric hormone that stimulates growth hormone (GH) secretion and food intake to regulate energy homeostasis and body weight by binding to its receptor, GH secretagogue receptor (GHSR1a), which is most highly expressed in the pituitary and hypothalamus. Nowadays there is considerable evidence showing that the GHSR1a is also expressed in numerous extra-hypothalamic neuronal populations and the physiol Read More

Neuronal damage secondary to brain injuries such as cerebral hypoxia, seizures as well as neurodegenerative process, may include pro-inflammatory changes. The activation of a common mechanism related to survival or cell death, mediated by the stabilization and trans-activation of Hypoxia-Inducible Factor 1 (HIF-1), has been observed in these conditions. HIF-1 may induce over expression of P-glycoprotein, the pr Read More

Antiepileptic drugs can cause some adverse effects ranging from mild to acute and serious ones. The inducing properties of some of them may result in vitamin D, vitamin K and estrogens catabolism and thus risk of fractures or efflux transport overexpression at the blood brain barrier and consequently lack of effect at the action site. Some are responsible for the formation of reactive metabolites, such as arene oxides or at Read More

Brain structural and functional integrity exquisitely relies on a regular supply of oxygen. In order to circumvent the potential deleterious consequences of deficient oxygen availability, brain triggers endogenous adaptive and pro-survival mechanisms - a phenomenon known as brain hypoxic tolerance. The highly conserved hypoxia-inducible family (HIF) of transcription factors is the “headquarter” of the homeostatic r Read More

Our understanding of the magnitude and physiological significance of proteome lysine acetylation remained incipient for five decades since it was first described. State-of-the-art methodologies, ranging from functional genomics to large-scale proteomics, have recently uncovered that this modification is more broadly represented in proteins than previously recognized, thus constituting the “acetylome.” At present, it is esti Read More