Burden and outcome of prevalent ischemic brain disease in a national acute stroke registry.

Background And Purpose: Previous overt stroke and subclinical stroke are frequent in patients with stroke; yet, their clinical significance and effects on stroke outcome are not clear. We studied the burden and outcome after acute ischemic stroke by prevalent ischemic brain disease in a national registry of hospitalized patients with acute stroke.

Methods: Patients with ischemic stroke in the National Acute Stroke Israeli prospective hospital-based registry (February to March 2004, March to April 2007, and April to May 2010) with information on previous overt stroke and subclinical stroke per computed tomography/MRI (n=3757) were included.

Asymmetric fluorogenic organophosphates for the development of active organophosphate hydrolases with reversed stereoselectivity.

In order to enhance the enzymatic detoxification rate of organophosphorus (OP) nerve agents we have searched for more active variants of recombinant mammalian paraoxonase (PON1). We have previously identified three key positions in PON1 that affect OP hydrolysis: Leu69, Val346 and His115, that significantly enhance the hydrolysis of cyclosarin (GF), soman, chlorpyrifos-oxon (ChPo), O-isopropyl-O-(p-nitrophenyl)methylphosphonate (IMP-pNP) and diisopropyl fluorophosphate (DFP). GC/FPD analysis compared to residual AChE inhibition assay displayed stereoselective hydrolysis of GF, soman and IMP-pNP, indicating that wild type PON1 and its variant V346A are more active toward the less toxic P(+) optical isomer.

Enhanced stereoselective hydrolysis of toxic organophosphates by directly evolved variants of mammalian serum paraoxonase.

We addressed the ability of various organophosphorus (OP) hydrolases to catalytically scavenge toxic OP nerve agents. Mammalian paraoxonase (PON1) was found to be more active than Pseudomonas diminuta OP hydrolase (OPH) and squid O,O-di-isopropyl fluorophosphatase (DFPase) in detoxifying cyclosarin (O-cyclohexyl methylphosphonofluoridate) and soman (O-pinacolyl methylphosphonofluoridate). Subsequently, nine directly evolved PON1 variants, selected for increased hydrolytic rates with a fluorogenic diethylphosphate ester, were tested for detoxification of cyclosarin, soman, O-isopropyl-O-(p-nitrophenyl) methyl phosphonate (IMP-pNP), DFP, and chlorpyrifos-oxon (ChPo).

General anesthetics attenuate gap junction coupling in P19 cell line.

Gap junction communication is widespread throughout the mammalian nervous system among neurons as well as glia. We addressed the hypothesis that general anesthetics attenuate gap junction mediated coupling in P19 cell line that can differentiate into neuronal-like cells and astrocytes and oligodendrocytes. We characterized the extent of dye coupling over time in the P19 cell line using colocalization of chlormethylbenzamido-1,1 dioctadecyl-3,3,3',3'-tetramethylindocarbocyamine (CM-DiI) and calcein-AM in donor and recipient cells in cocultures.

Characterization of early plasma concentrations of midazolam in pigs after administration by an autoinjector.

The treatment of organophosphate-induced poisoning is based mainly on atropine and an oxime. Prompt anticonvulsive intervention is usually also required to terminate the ensuing seizure activity and to prevent delayed permanent brain damage. Midazolam, a water-soluble benzodiazepine agonist, has the advantage of rapid absorption following intramuscular administration.

Ethanol inhibits gap-junctional coupling between P19 cells.

Background: Gap junctions are plaques of multiple intercellular channels that connect the cytoplasm of adjacent cells. They provide both electrical and metabolic coupling and are an essential element in normal growth, development, and physiology. Little research exists on the relationship between alcohol administration and gap-junctional function or expression.