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Effect of Degarelix, a Gonadotropin-Releasing Hormone Receptor Antagonist for the Treatment of Prostate Cancer, on Cardiac Repolarisation in a Randomised, Placebo and Active Comparator Controlled Thorough QT/QTc Trial in Healthy Men

BACKGROUND AND OBJECTIVES: Degarelix is a gonadotropin-releasing hormone antagonist registered for the treatment of advanced hormone-dependent prostate cancer. Treatment causing androgen deprivation is associated with QT prolongation and this study investigated whether degarelix at supratherapeutic concentrations has an intrinsic effect per se on cardiac repolarisation and the QT interval.METHODS:

Characterization of the receptor response for the neuropeptide Y-evoked suppression of parasympathetically-mediated contractions in the guinea pig trachea

Neuropeptide Y (NPY) acts via several distinct receptor types. The aim of the present study was to examine which NPY receptors are coupled to inhibition of parasympathetically-mediated contractions of the isolated guinea pig trachea. Electrical field stimulation of tracheal rings evoked a rapid twitch, which was abolished by atropine (1 microM). NPY, the structurally related hormone peptide YY (PY

Electroconvulsive treatment evokes release of preprotachykinin-A mRNA into the cerebrospinal fluid and ocular aqueous humor of rabbits

Following electroconvulsive treatment (ECT) of rabbits, preprotachykinin-A (PPT-A) mRNA was detected by Southern blot analysis of polymerase chain reaction (PCR)-amplified products in the cerebrospinal fluid (CSF) and aqueous humor of the eye. In contrast, no PPT-A mRNA could be detected in samples from untreated animals. In addition, several neuropeptides (substance P, neuropeptide Y, cholecystok

Multiple neuropeptide Y receptors are involved in cardiovascular regulation. Peripheral and central mechanisms

1. Neuropeptide Y (NPY) occurs in both the central and peripheral nervous system. In the periphery, NPY coexists with noradrenaline (NA) in perivascular sympathetic fibers. 2. NPY has a vasopressor effect, reflecting direct vasoconstriction of blood vessels and potentiation of the NA-evoked response. NPY also suppresses the release of NA from sympathetic fibers. 3. The post- and pre-junctional NPY

Swedish national guideline for prevention and treatment of neonatal hypoglycaemia in newborn infants with gestational age ≥35 weeks

Aim: Postnatal hypoglycaemia in newborn infants remains an important clinical problem where prolonged periods of hypoglycaemia are associated with poor neurodevelopmental outcome. The aim was to develop an evidence-based national guideline with the purpose to optimise prevention, diagnosis and treatment of hypoglycaemia in newborn infants with a gestational age ≥35 + 0 weeks. Methods: A PubMed sea

Reinterpretation of fossil reproductive structures Zlivifructus microtriasseris (Normapolles complex, Fagales) from the Czech and Polish Late Cretaceous

Flowers and fruits of Zlivifructus microtriasseris, originally described as Caryanthus microtriasseris from the late Turonian to Santonian of the South Bohemian Basins and the late Coniacian to early Santonian of the North Sudetic Basin, are reinterpreted here. Zlivifructus microtriasseris is represented by small, flat fruits, round in outline with persistent perianths, which are fused basally, fo

Effect of hypothermia on haemostasis and bleeding risk : a narrative review

It must be remembered that clinically important haemostasis occurs in vivo and not in a tube, and that variables such as the number of bleeding events and bleeding volume are more robust measures of bleeding risk than the results of analyses. In this narrative review, we highlight trauma, surgery, and mild induced hypothermia as three clinically important situations in which the effects of hypothe

Towards clinical grating-interferometry mammography

Objectives: Grating-interferometry-based mammography (GIM) might facilitate breast cancer detection, as several research works have demonstrated in a pre-clinical setting, since it is able to provide attenuation, differential phase contrast, and scattering images simultaneously. In order to translate this technique to the clinics, it has to be adapted to cover a large field-of-view within a clinic

Fast kicker systems for ALS-U

Fast kicker systems are required for the proposed upgrade of ALS to a diffraction-limited light source (ALS-U). The main approach is to have multiple stripline kicker magnets driven by inductive adders. The design details of the kicker structures and the inductive adder options will be discussed.

Lattice studies for a potential soft X-ray diffraction limited upgrade of the ALS

The Advanced Light Source (ALS) at Berkeley Lab has seen many upgrades over the years, keeping it one of the brightest sources for soft x-rays worldwide. Recent developments in magnet and vacuum technology, as well as lattice design (multi bend achromat lattices) appear to open the door for very large further increases in brightness [1]. This could be achieved by reducing the horizontal emittance,

Seizures induce widespread upregulation of cystatin B, the gene mutated in progressive myoclonus epilepsy, in rat forebrain neurons

Loss of function mutations in the gene encoding the cysteine protease inhibitor, cystatin B (CSTB), are responsible for the primary defect in human progressive myoclonus epilepsy (EPM1). CSTB inhibits the cathepsins B, H, L and S by tight reversible binding, but little is known regarding its localization and physiological function in the brain and the relation between the depletion of the CSTB pro

Influence of low-frequency electromagnetic field generated by transformation of endogenous Morris hepatoma field on its growth and metastatic ability (I)

As it has been shown in a number of reports, extremely-low- frequency (ELF) electromagnetic field (EMF) can induce different changes in various biological systems, even if its intensity is comparable to the level of thermal noise. According to the parameters of generated field variable results have been obtained, including these regarding cell proliferation. Simultaneously it has also been demonst

Rapid alterations of BDNF protein levels in the rat brain after focal ischemia : Evidence for increased synthesis and anterograde axonal transport

Cellular localization and tissue levels of BDNF protein were studied using immunocytochemistry and enzyme immunoassay, respectively, in the cortex and striatum at different reperfusion times (0-24 h) after 2 h of unilateral middle cerebral artery occlusion (MCAO) in rats. The distribution of neuronal injury was analyzed in NeuN-, cresyl violet-, and Fluoro-Jade-stained sections. At 2 h postischemi

Seeding of protein aggregation causes cognitive impairment in rat model of cortical synucleinopathy

Background: Cortical α-synuclein pathology plays a role in the development of cognitive dysfunction in both Parkinson's disease and dementia with Lewy bodies, although the causative cellular lesions have remained unclear. We aimed to address causal links between α-synuclein-driven pathology in the cerebral cortex and the development of cognitive impairments using new experimental models. Methods: