introduction: spreading depression (sd) is a propagating wave of depolarization followed by depression of the neuroglial activities and can modulate extracellular dopamine concentrations in the neocortex. it has been shown that the dopaminergic system plays a role in migraine. sd has been suggested as a critical phenomenon in the pathophysiology of migraine. the aim of this study was to investi...

background: endometrial secretion analysis is a non-invasive and promising method in evaluation of endometrial receptivity. objective: the aim of the present study was to assess the relationship between the success rate of ivf procedures and some endometrial secretion cytokines, including interleukin-1β (il-1β), tumor necrosis factor (tnf-α), interferon gamma-induced protein 10 (ip-10), and mon...

BACKGROUND Understanding the complexities associated with the ischemic condition and identifying therapeutic targets in ischemia is a continued challenge in stroke biology. Emerging evidence reveals the potential involvement of epigenetic mechanisms in the incident and outcome of stroke, suggesting novel therapeutic options of targeting different molecules related to epigenetic regulation. OB...

The tremendous potential of biologic drugs is hampered by short half-lives in vivo, resulting in significantly lower potency than activity seen in vitro. These short-acting therapeutic agents require frequent dosing profiles that can reduce applicability to the clinic, particularly for chronic conditions. Therefore, half-life extension technologies are entering the clinic to enable improved or ...

In this study, we present efavirenz physiologically based pharmacokinetic (PBPK) model development as an example of our best practice approach that uses a stepwise approach to verify the different components of the model. First, a PBPK model for efavirenz incorporating in vitro and clinical pharmacokinetic (PK) data was developed to predict exposure following multiple dosing (600 mg q.d.). Alfe...

A series of pyrido[3,4-d]azepines that are potent and selective 5-HT2C receptor agonists is disclosed. Compound 7 (PF-04781340) is identified as a suitable lead owing to good 5-HT2C potency, selectivity over 5-HT2B agonism, and in vitro ADME properties commensurate with an orally available and CNS penetrant profile. The synthesis of a novel bicyclic tetrasubstituted pyridine core template is ou...

Background: Phthalates are a group of multifunctional chemicals. Diethyl phthalate (DEP) is one of the most frequently used phthalates in solvents and fixatives for numerous industrial products. Method: The present experiment was designed to assess oxidative stress, if any, caused by diethyl phthalate. For this the homogenates of liver and kidney were treated with different concentrations ( 1...

A preclinical drug candidate, MRK-1 (Merck candidate drug parent compound), was found to elicit tumor regression in a mouse xenograft model. Analysis of samples from these studies revealed significant levels of two circulating metabolites, whose identities were confirmed by comparison with authentic standards using liquid chromatography-tandem mass spectrometry. These metabolites were found to ...

Abstract Introduction: The aim of this study was to identify the antibacterial components in the ethanol extraction of Aloe vera against four clinically frequent pathogenic  bacteria. Materials and Methods: In this in-vitro study, Aloe vera extraction was prepared by dissolving 500 grams of the powder in 5L of 95% ethanol. The antibacterial activity of the extraction against Staphylococcus a...