Search results for "Modulator"

Ulipristal acetate versus leuprolide acetate for uterine fibroids

2012

A b s t r ac t Background The efficacy and side-effect profile of ulipristal acetate as compared with those of leuprolide acetate for the treatment of symptomatic uterine fibroids before surgery are unclear. Methods In this double-blind noninferiority trial, we randomly assigned 307 patients with symptomatic fibroids and excessive uterine bleeding to receive 3 months of daily therapy with oral ulipristal acetate (at a dose of either 5 mg or 10 mg) or once-monthly intramuscular injections of leuprolide acetate (at a dose of 3.75 mg). The primary outcome was the proportion of patients with controlled bleeding at week 13, with a prespecified noninferiority margin of −20%. Results Uterine bleed…

Synthesis and Biological Evaluation of 1-Methyl-2-(3',4',5'-trimethoxybenzoyl)-3-aminoindoles as a New Class of Antimitotic Agents and Tubulin Inhibi…

2008

The 2-(3,4,5-trimethoxybenzoyl)-2-aminoindole nucleus was used as the fundamental structure for the synthesis of compounds modified with respect to positions C-4 to C-7 with different moieties (chloro, methyl, or methoxy). Additional structural variations concerned the indole nitrogen, which was alkylated with small alkyl groups such as methyl or ethyl. We have identified 1-methyl-2-(3,4,5-trimethoxybenzoyl)-3-amino-7-methoxyindole as a new highly potent antiproliferative agent that targets tubulin at the colchicine binding site and leads to apoptotic cell death.

Involvement of CB1 and CB2 receptors in the modulation of cholinergic neurotransmission in mouse gastric preparations.

2007

Abstract While most of the studies concerning the role of cannabinoids on gastric motility have focused the attention on the gastric emptying in in vivo animal models, there is little information about the cannabinoid peripheral influence in the stomach. In addition, the functional features of CB2 receptors in the gastrointestinal tract have been poorly characterized. The purpose of the present study was to investigate the effects of cannabinoid drugs on the excitatory cholinergic and inhibitory non-adrenergic non-cholinergic (NANC) neurotransmission in mouse isolated gastric preparations. Intraluminal pressure from isolated whole stomach was recorded and mechanical responses induced by ele…

The endocannabinoid system controls key epileptogenic circuits in the hippocampus.

2006

SummaryBalanced control of neuronal activity is central in maintaining function and viability of neuronal circuits. The endocannabinoid system tightly controls neuronal excitability. Here, we show that endocannabinoids directly target hippocampal glutamatergic neurons to provide protection against acute epileptiform seizures in mice. Functional CB1 cannabinoid receptors are present on glutamatergic terminals of the hippocampal formation, colocalizing with vesicular glutamate transporter 1 (VGluT1). Conditional deletion of the CB1 gene either in cortical glutamatergic neurons or in forebrain GABAergic neurons, as well as virally induced deletion of the CB1 gene in the hippocampus, demonstrat…

Neuronal populations mediating the effects of endocannabinoids on stress and emotionality

2011

An adequate emotional response to stress is essential for survival and requires the fine-tuned regulation of several distinct neuronal circuits. Therefore, a precise control of these circuits is necessary to prevent behavioral imbalances. During the last decade, numerous investigations have evidenced that the endocannabinoid (eCB) system is able to crucially control stress coping. Its central component, the cannabinoid type 1 receptor (CB1 receptor), is located at the presynapse, where it is able to attenuate neurotransmitter release after its activation by postsynaptically produced and released eCBs. To date, the eCB system has been found to control the neurotransmitter release from severa…

Relaxant Effects of the Selective Estrogen Receptor Modulator, Bazedoxifene, and Estrogen Receptor Agonists in Isolated Rabbit Basilar Artery

2016

We have previously shown that the selective estrogen receptor modulator, bazedoxifene, improves the consequences of ischemic stroke. Now we aimed to characterize the effects and mechanisms of action of bazedoxifene in cerebral arteries. Male rabbit isolated basilar arteries were used for isometric tension recording and quantitative polymerase chain reaction. Bazedoxifene relaxed cerebral arteries, as 17-β-estradiol, 4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol [estrogen receptor (ER) α agonist], and G1 [G protein-coupled ER (GPER) agonist] did it (4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol > bazedoxifene = G1 > 17-β-estradiol). 2,3-Bis(4-hydroxyphenyl)-propionitrile (E…

Long-term follow-up of hepatitis B e antigen-negative patients treated with peginterferon α-2a: progressive decrease in hepatitis B surface antigen i…

2012

Neuroprotective action of diazepam at very low and moderate doses in Alzheimer's disease model rats

2018

Abstract Early manifestations of Alzheimer's disease (AD) include neuroinflammation, disrupted neurotransmission and cognitive deficits. Impairment of the GABAergic system is essentially involved in the pathogenesis of AD. Traditionally, agonists of GABAA receptors at doses above 1 mg/kg are known to possess memory impairing effects. However, we have previously found that GABAA receptor GABA site ligand muscimol at very low doses acted contrary – enhanced spatial learning/memory, as well as prevented neuroinflammation and augmented neurotransmission in AD model rats. Therefore, in the present study we focused on the assessment of the effects of non-sedative – very low (0.05 mg/kg) and moder…

Integrated photonic routers driven by surface acoustic waves

2016

Durante la segunda mitad del siglo XX se produjo un desarrollo excepcional de la capacidad de transmitir y procesar información electrónicamente. Esto fue debido en parte a la capacidad de integrar en un único substrato una gran cantidad de transistores, que son las unidades fundamentales de procesamiento de datos. Este comportamiento quedó resumido en la ley de Moore, que predecía que el número de transistores integrados se duplicaría cada 24 meses. Esta tendencia, que se ha mantenido hasta la actualidad con transistores de tamaño nanométrico, no puede continuar indefinidamente. Uno de los problemas fundamentales reside en la capacidad limitada para disipar el calor que generan los disposi…

Taking the stock of granule cargo: Platelet releasate proteomics.

2016

Human platelets are key players in a multitude of physiological and pathological processes. Upon activation they release cargo from different types of granules as well as microparticles in an apparently well-regulated and orchestrated manner. The resulting specific platelet releasates create microenvironments of biologically active compounds and proteins during platelet aggregation and thrombus formation, allowing efficient delivery of growth factors and immune modulators to their sites of effect and enhancing the coagulative response in a positive feedback loop. Thus, platelet releasates play a central role in the regulation of platelet homeostasis and heterotypic cell interaction. Additio…