Search results for "Agoni"

Paradoxical effect of increased diastolic Ca(2+) release and decreased sinoatrial node activity in a mouse model of catecholaminergic polymorphic ven…

2012

Background— Catecholaminergic polymorphic ventricular tachycardia is characterized by stress-triggered syncope and sudden death. Patients with catecholaminergic polymorphic ventricular tachycardia manifest sinoatrial node (SAN) dysfunction, the mechanisms of which remain unexplored. Methods and Results— We investigated SAN [Ca 2+ ] i handling in mice carrying the catecholaminergic polymorphic ventricular tachycardia–linked mutation of ryanodine receptor (RyR2 R4496C ) and their wild-type (WT) littermates. In vivo telemetric recordings showed impaired SAN automaticity in RyR2 R4496C mice after isoproterenol injection, analogous to what was observed in catecholaminergic polymorphic ventricul…

Study on the histamine-like activity of guanfacine

1990

Abstract The effects of guanfacine have been studied on guinea-pig isolated atria and diethylstilboestrol-treated rat isolated uterus to determine whether it possesses histamine-like activity. Guanfacine produced a concentration-dependent negative chronotropic effect which was not modified by ranitidine (0.1 μM). In rat isolated uterus contracted by KCl, clonidine (5–5000 μM) produced concentration-dependent relaxation which was blocked by ranitidine (0.1 μM), but guanfacine only produced relaxation at high concentrations (100–1000 μM), and this was not affected by ranitidine (0.1 μM). It is concluded that guanfacine, unlike clonidine, does not produce effects due to activation of H2-recept…

Genotoxicity characteristics of reverse diol-epoxides of chrysene.

2017

Trans-3,4-dihydroxy-3,4-dihydrochrysene (chrysene-3,4-diol), a major metabolite of chrysene, is further metabolized by rat liver enzymes to products which effectively revert the his- Salmonella typhimurium strain TA98 to histidine prototrophy, but are only weakly mutagenic in strain TA100 and in Chinese hamster V79 cells (acquisition of resistance to 6-thioguanine). The liver enzyme mediated mutagenicity of chrysene-3,4-diol is substantially enhanced in the presence of 1,1,1-trichloropropene 2,3-oxide, an inhibitor of microsomal epoxide hydrolase. The predominant metabolites of chrysene-3,4-diol, namely the anti- and syn-isomers of its 1,2-oxide (termed reverse diol-epoxides), proved to be …

Diurnal variation of corticotropin-releasing factor binding sites in the rat brain and pituitary.

1996

1. Corticotropin-releasing factor (CRF) is thought to be involved in the regulation of the diurnal activity of the hypothalamus-pituitary-adrenal (HPA) axis and to act as a neurotransmitter in the brain. To date it is unknown whether the binding sites of the central CRF system are subject to diurnal variations. 2. We measured the number of CRF binding sites over the course of a complete 24-hr light-dark cycle in the pituitary, amygdala, bed nucleus of the stria terminalis (BNST), cingulate cortex, visceral cortex, paraventricular nucleus of the hypothalamus, hippocampus, and locus ceruleus of rats by in vitro receptor autoradiography with iodinated ovine CRF. A 24-hr time course was also es…

Hacia el Genoma de los Derechos Humanos

2000

Paleoenvironmental evolution of the Pliocene Villarroya Lake, northern Spain. A multidisciplinary approach

2002

The Pliocene Villarroya basin fill consists of lacustrine and alluvial deposits over 100 m thick. The lacustrine deposits, up to 30 m thick, comprise three sequences. The two lower sequences consist of profundal, laminated deposits formed by mostly terrigenous facies that are overlain by charophytic carbonates and varves. The uppermost, third sequence made up of massive bioturbated mudstones corresponds to a very shallow lacustrine-palustrine environment. Bulk mineralogy comprises carbonates, clay minerals, quartz and feldspars. The carbonates are: exogenic, biogenic calcite and biogenic aragonite. Biogenic calcite constitutes ostracod shells and charophyte stem encrustations, whereas arago…

In vitro P-glycoprotein efflux inhibition by atypical antipsychotics is in vivo nicely reflected by pharmacodynamic but less by pharmacokinetic chang…

2011

Abstract Background P-glycoprotein (P-gp), an efflux transporter of the blood–brain barrier, limits the access of multiple xenobiotics to the central nervous system (CNS). Thus drug-dependent inhibition, induction or genetic variation of P-gp impacts drug therapy. Methods We investigated atypical antipsychotics and their interaction with P-gp. Amisulpride, clozapine, N-desmethylclozapine, olanzapine, and quetiapine were assessed in vitro on their inhibitory potential and in vivo on their disposition in mouse serum and brain, and behaviourally on the RotaRod test. In vivo wildtype (WT) and mdr1a/1b double knockout mice (mdr1a/1b (−/−, −/−); KO) were investigated. Results In rhodamine 123 eff…

Finding the right dose of fulvestrant in breast cancer

2012

Fulvestrant is a selective estrogen receptor downregulator, behaving as a complete antagonist. It was initially approved, at a dose of 250 mg, to treat hormone dependant breast cancer in second line setting. However, a series of pharmacological and pre-clinical studies have suggested that a higher dose of 500 mg may be more effective. The present work summarizes and discusses clinical trials that have aimed to test the benefits of administering fulvestrant at a higher dose. The data support the use of a higher, and more possibly, effective dose of the agent.

Almotriptan: meeting today’s needs in acute migraine treatment

2007

Migraine is a common disorder associated with considerable individual and economic burden. Triptans are recommended for the treatment of migraine of any severity in patients who have failed to gain adequate relief with nonspecific medication; early transition to triptans avoids prolonged morbidity in patients failing to respond to nonspecific medications. There is evidence that early intervention therapy with oral formulations in migraine, soon after the onset of an attack and when pain is still mild, improves efficacy. Seven different triptans are currently marketed, with differing pharmacologic, efficacy and tolerability profiles. Almotriptan has many positive features, which include rigo…

Calcification is not the Achilles' heel of cold-water corals in an acidifying ocean

2015

Ocean acidification is thought to be a major threat to coral reefs: laboratory evidence and CO2 seep research has shown adverse effects on many coral species, although a few are resilient. There are concerns that cold-water corals are even more vulnerable as they live in areas where aragonite saturation (?ara) is lower than in the tropics and is falling rapidly due to CO2 emissions. Here, we provide laboratory evidence that net (gross calcification minus dissolution) and gross calcification rates of three common cold-water corals, Caryophyllia smithii, Dendrophyllia cornigera, and Desmophyllum dianthus, are not affected by pCO2 levels expected for 2100 (pCO2 1058 ?atm, ?ara 1.29), and nor a…