Does extracorporeal life support influence outcome after surgical management of post infarct ventricular septal rupture? A monocenter retrospective study.

Background: Ventricular septal rupture (VSR) is an uncommon but life-threatening complication of acute myocardial infarction. Extra corporeal life support (ECLS) use in the preoperative setting allows hemodynamic stabilization for a delayed surgery. We aimed to assess the role of ECLS in the preoperative period of post infarction VSR surgery.

Phostine PST3.1a Targets MGAT5 and Inhibits Glioblastoma-Initiating Cell Invasiveness and Proliferation.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor and accounts for a significant proportion of all primary brain tumors. Median survival after treatment is around 15 months. Remodeling of N-glycans by the N-acetylglucosamine glycosyltransferase (MGAT5) regulates tumoral development.

Development of NMDAR antagonists with reduced neurotoxic side effects: a study on GK11.

The NMDAR glutamate receptor subtype mediates various vital physiological neuronal functions. However, its excessive activation contributes to neuronal damage in a large variety of acute and chronic neurological disorders. NMDAR antagonists thus represent promising therapeutic tools that can counteract NMDARs' overactivation.

Expression of purinergic P2Y receptor subtypes by INS-1 insulinoma beta-cells: a molecular and binding characterization.

Purinergic P2Y-receptor agonists amplify glucose-induced insulin secretion from pancreatic beta-cells, thus offering new opportunities for the treatment of type 2 diabetes. However, little is known about which subtypes of purinergic P2Y receptors are expressed in these cells. The INS-1 beta-cell line is used as a model of pancreatic beta-cells, expressing most of their properties.

P2Y receptor mediated modulation of insulin release by a novel generation of 2-substituted-5'-O-(1-boranotriphosphate)-adenosine analogues.

Purpose: A series of C2-substituted ATP analogues was previously shown to have potent insulin-secreting properties, yet with poor tissue-selectivity for the pancreatic beta-cell. The present study was designed to evaluate the binding profile on beta-cell membranes and the effects on insulin release and pancreatic vascular resistance of a second generation of P2Y(1) receptor agonists, based on C2-substitution of the adenosine 5'-O-(1-boranotriphosphate) scaffold.

Materials And Methods: Functional experiments were performed in the rat isolated pancreas model; binding studies with ATP-alpha-[(35)S] were performed in membrane homogenates from the rat insulinoma INS-1 cell line.

Acute exposure to GSM 900-MHz electromagnetic fields induces glial reactivity and biochemical modifications in the rat brain.

The worldwide proliferation of mobile phones raises the question of the effects of 900-MHz electromagnetic fields (EMF) on the brain. Using a head-only exposure device in the rat, we showed that a 15-min exposure to 900-MHz pulsed microwaves at a high brain-averaged power of 6 W/kg induced a strong glial reaction in the brain. This effect, which suggests neuronal damage, was particularly pronounced in the striatum.

P2Y purinergic potentiation of glucose-induced insulin secretion and pancreatic beta-cell metabolism.

Purine nucleotides and their analogs increase insulin secretion through activation of pancreatic beta-cell P2Y receptors. The present study aimed at determining the role of glucose metabolism in the response to P2Y agonists and whether ATP-activated K+ channels (KATP channels) are involved in this response. The experiments were performed in the rat isolated pancreas, perfused with a Krebs-bicarbonate buffer supplemented with 2 g/l bovine serum albumin under dynamic glucose conditions from 5 mmol/l baseline to 11 mmol/l.

Re-evaluation of phencyclidine low-affinity or "non-NMDA" binding sites.

TCP and its derivative gacyclidine (+/- GK11) are high-affinity non-competitive antagonists of N-methyl-D-aspartate (NMDA) receptors (NMDARs) and as such exhibit significant neuroprotective properties. These compounds also bind with a low affinity to binding sites whose pharmacological profiles are different from that of NMDARs. With the intention to develop new strategies of neuroprotection, we found it mandatory to investigate whether 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP) and gacyclidine low-affinity sites are similar.

Gacyclidine: a new neuroprotective agent acting at the N-methyl-D-aspartate receptor.

Gacyclidine is a new phencyclidine derivative with neuroprotective properties. Tritiated gacyclidine and its enantiomers bind to NMDA receptors with binding parameters similar to those of other non-competitive NMDA receptor antagonists. The (-)enantiomer, (-)GK11, exhibits an affinity (2.

Characterization of 'non-N-methyl-D-Aspartate' binding sites for gacyclidine enantiomers in the rat cerebellar and telencephalic structures.

Gacyclidine is a non-competitive NMDA receptor antagonist with potent neuroprotective properties. However, we have previously demonstrated that gacyclidine enantiomers [(-) and (+)GK11] interact with other ('non-NMDA') binding sites which may play a role in the lower self-neurotoxicity of this compound relative to the other NMDA receptor antagonists. Evidence for these binding sites has been obtained from autoradiographic and membrane binding experiments.

Interaction of gacyclidine enantiomers with 'non-NMDA' binding sites in the rat central nervous system.

Gacyclidine, a channel blocker of N-methyl-D-aspartate receptors (NMDAR), exhibits potent neuroprotective properties and a low self-neurotoxicity. Preventing its interaction with NMDARs we demonstrate, through the use of its enantiomers, that gacyclidine also interacts with other ('non-NMDA') binding sites. The autoradiographic study showed that these sites displayed a uniform specific binding in the forebrain and a more discrete distribution in the molecular layer of the cerebellum.

Modulation of glutamate neurotoxicity on mesencephalic dopaminergic neurons in primary cultures by the presence of striatal target cells.

Glutamate toxicity was compared in substantia nigra (SN)/striatum (STR) and SN/cerebellum (CRB) co-cultures on both the entire neuronal population (neuron specific enolase (NSE) immunopositive cells) and dopaminergic neurons (tyrosine hydroxylase (TH) immunopositive cells). In SN/CRB co-cultures NSE- and TH-positive cells were more sensitive to glutamate-induced toxicity than in SN/STR co-cultures. Moreover, in SN/STR co-cultures as compared to SN/CRB and SN cultures, glutamate toxicity was prevented to a larger extent by TCP, a non-competitive NMDA antagonist.

The low affinity PCP sites in the rat cerebellum not only bind TCP-like but also BTCP-like structures.

Congeners of the potent dopamine (DA) re-uptake inhibitor 1-[1-(2-benzo[b]thiophenyl)cyclohexyl]piperidine (BTCP) are unexpectedly able to bind in the rat cerebellum, although this structure is devoid of dopaminergic nerve endings. In line with previous studies the hypothesis that they bind to low affinity PCP sites labelled with [3H]TCP in the rat cerebellum, even though they do not bind to the high affinity PCP sites in the forebrain, was considered. Analogues of 1-[1-(2-thiophenyl)cyclohexyl]piperidine (TCP) and BTCP with a modified aromatic moiety and with O or S atoms substituted in the cyclohexyl ring were prepared and tested in competition experiments both in rat forebrain and cerebellum membranes labelled with [3H]TCP, and in rat striatum membranes labelled with [3H]BTCP.

Binding properties of [3H]gacyclidine (cis(pip/me)-1-[1-(2-thienyl)-2-methylcyclohexyl]piperidine) enantiomers in the rat central nervous system.

Gacyclidine (cis(pip/me)-1-[1-(2-thienyl)-2-methylcyclohexyl]piperidine) is a TCP derivative, which exhibits potent neuroprotective properties against glutamate-induced neurotoxicity in vitro and in vivo. In order to better understand gacyclidine pharmacological properties, the binding parameters of its enantiomers ((-) and (+)[3H]GK11) were determined in the rat central nervous system (CNS). An autoradiographic study has shown that their binding distributions are correlated with those of N-methyl-D-aspartate (NMDA) receptors throughout the CNS.

Binding properties of [3H]gacyclidine in the rat central nervous system.

Gacyclidine (1-[1-(2-thienyl)-2-methylcyclohexyl]piperidine), the racemate of (+)-and (-)-GK11, exhibits potent neuroprotective properties due to its antagonism at the NMDA receptor. In its tritiated form, gacyclidine showed a binding distribution similar to that of NMDA receptors in the rat brain. With membrane preparations, the (-)-enantiomer of gacyclidine exhibited an affinity similar to that of MK-801 (dizocilpine, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a, d]cyclohepten-5,10-imine) in the low nanomolar range, while the (+)-enantiomer was about 10 times less potent.

1-[1-(2-Benzo[b]thiopheneyl)cyclohexyl]piperidine hydrochloride (BTCP) yields two active primary metabolites in vivo. Identification and quantification of BTCP primary metabolites in mice plasma, urine, and brain and their affinity for the neuronal dopamine transporter.

1-[1-(2-Benzo[b]thiopheneyl)cyclohexyl]piperidine hydrochloride (BTCP) and cocaine bind to the neuronal dopamine transporter (DAT) to strongly inhibit dopamine (DA) reuptake. Although similar to acute administration, cocaine and BTCP produce sensitization and tolerance, respectively, on chronic administration. We previously found that liver microsomes produced two primary metabolites from BTCP with a high affinity for DAT.

Pharmacological characterization of the discriminative stimulus properties of the phencyclidine analog, N-[1-(2-benzo(b)thiophenyl)-cyclohexyl]piperidine.

Rationale: Although both cocaine and the phencyclidine analog, BTCP, have dopamine (DA) re-uptake blocking properties, under some conditions their behavioral effects can be differentiated. Therefore, we examined whether the discriminative stimulus (DS) effects of BTCP are different from those of cocaine.

Objectives: To compare the effects of monoamine re-uptake blockers, varying in their in vitro potencies as inhibitors of DA, norepinephrine (NE), or serotonin re-uptake, in different groups of rats trained to discriminate either BTCP or cocaine from saline.

Does crossing over repeated treatment with the dopamine reuptake inhibitors cocaine and BTCP modify their effects on cocaine-induced locomotion?

Because the dopamine reuptake inhibitors cocaine and BTCP produce different behavioral effects after repeated administration, we studied whether they could alter each other's effects by examining the effects of crossing over repeated treatment with cocaine and BTCP on cocaine-induced locomotion. Male C57BL/6 mice were treated repeatedly with cocaine or BTCP during a first phase (days 1-3) and 3 days later, treated repeatedly with the same or the other compound during a second phase (days 7-9), after which they were administered one of several doses of cocaine on the next day. Locomotor activity was assessed after every daily treatment.

Comparison of glutamate and N-methyl-D-aspartate toxicities on rat mesencephalic primary cell cultures.

Excitotoxicities of glutamate and NMDA were studied on primary cultures of rat embryonic substantia nigra. The toxicity of the general neuronal population (identified with neuron specific enolase-NSE) was compared with that of dopaminergic neurons (identified with TH antibodies). We have shown that there exists a time-dependent toxicity to glutamate in 9 d old cultures in vitro and exposures as short as 5 min are significantly toxic.

1-[1-2-Benzo[b]thiopheneyl)cyclohexyl]piperidine hydrochloride (BTCP) yields two active primary metabolites in vitro: synthesis, identification from rat liver microsome extracts, and affinity for the neuronal dopamine transporter.

1-[1-(2-Benzo[b]thiopheneyl)cyclohexyl]piperidine hydrochloride (BTCP, 1) and cocaine bind to the neuronal dopamine transporter to inhibit dopamine (DA) reuptake. However, on chronic administration, cocaine produces sensitization, but 1 produces tolerance. Because metabolites of 1 might be responsible for some of its pharmacological properties, we have identified the primary metabolites of 1 produced by rat liver microsomes and determined their affinities for the DA transporter.

Synthesis and biodistribution of two potential PET radioligands for dopamine reuptake sites: no-carrier-added 4-(2-[18F]fluoroethyl) and 4-[11C]methyl BTCP-piperazine.

Radioligands that specifically target dopamine uptake sites can provide a means of determining dopamine fiber loss at intrastriatal mesencephalic grafts in Parkinsonian patients, using Positron Emission Tomography (PET). The BTCP derivative, 1-[1-(2-benzo(b)thiophenyl)cyclohexyl]-4-(2-hydroxyethyl)-piperazine, shows in vitro high affinity and selectivity for the dopamine transporter. To evaluate the potential of such a compound as a potential dopaminergic PET tracer the positron-emitting analogues, 1-[1-(2-benzo(b)thiophenyl)cyclohexyl]-4-(2-[18F]fluoroethyl)-piperazine and 1-[1-(2-benzo(b)thiophenyl)cyclohexyl]-4-[11C]methylpiperazine, were synthesized.

Long-term monitoring of extracellular dopamine concentration in the rat striatum by a repeated microdialysis procedure.

This study examined a protocol for repeated measurement of the extracellular dopamine (DA) concentration in the rat striatum by microdialysis. Rats were implanted with a guide cannula in the striatum and the probe was inserted on each dialysing day, i.e.

Binding of the antiretroviral drug, d-aspartate-β-hydroxamate on the NMDA receptor.

d-Aspartate-β-hydroxamate (d-A β H) exhibits antiretroviral properties in vitro and in vivo. It has glutamate agonist properties at the N-methyl-d-aspartate (NMDA) receptor in neuronal cell cultures. This study characterizes its binding properties to the NMDA receptor by measuring its stimulating effect on N-(1-(2-thienyl)[(3)H]cyclohexyl)piperidine ([(3)H]TCP) binding to the ionic channel in rat brain membranes.

N-[1-(2-Benzo(b)thiophenyl)cyclohexyl]piperidine (BTCP) and cocaine induce similar effects on striatal dopamine: a microdialysis study in freely moving rats.

N-[1-(2-Benzo(b)thiophenyl)cyclohexyl]piperidine (BTCP) and cocaine inhibit dopamine (DA) uptake but bind to different sites on the transporter. Their dose-dependent effects (i.p.

High affinity inositol 1,3,4,5-tetrakisphosphate receptor from rat liver nuclei: purification, characterization, and amino-terminal sequence.

Inositol 1,3,4,5-tetrakisphosphate (InsP4) mediates nuclear calcium signalling [Köppler P., Matter, N., Malviya A.