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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:

Characterisation of Population Pharmacokinetics and Endogenous Follicle-Stimulating Hormone (FSH) Levels After Multiple Dosing of a Recombinant Human FSH (FE 999049) in Healthy Women

OBJECTIVE: The aim of this study was to characterise the population pharmacokinetics of FE 999049, a novel recombinant human follicle-stimulating hormone (FSH), after multiple dosing in healthy women, taking into account endogenous FSH levels and the reproductive hormone dynamics.METHODS: Longitudinal measurements of FSH, luteinising hormone, progesterone, estradiol, and inhibin B levels were coll

Pharmacokinetics and bioavailability of a new testosterone gel formulation in comparison to Testogel® in healthy men

This randomized, open-label, multiple-dose three-way cross-over study compared the pharmacokinetics of a new testosterone gel formulation in two strengths, testosterone gel 1% and testosterone gel 2% (FE 999303), with Testogel® in 11 testosterone-suppressed healthy men. Subjects received one of six treatment sequences; 50 mg of testosterone was administered once daily for 7 consecutive days, with

Different pharmacokinetic and pharmacodynamic properties of recombinant follicle-stimulating hormone (rFSH) derived from a human cell line compared with rFSH from a non-human cell line

Pharmacokinetic and pharmacodynamic properties of a novel recombinant follicle-stimulating hormone (rFSH) preparation (FE 999049), expressed by a human cell line (PER.C6), was compared with an rFSH preparation (follitropin α) expressed by a Chinese hamster ovary (CHO) cell line in healthy pituitary-suppressed women. Following single intravenous administration of 225 IU (Steelman-Pohley assay), the

Human neuropeptide Y signal peptide gain-of-function polymorphism is associated with increased body mass index : possible mode of function

Neuropeptide Y (NPY) has been implicated in the control of food intake and energy balance based on many observations in animals. We have studied single nucleotide polymorphisms (SNPs) within the regulatory and coding sequences of the human NPY gene. One variant (1128 T>C), which causes an amino acid change from leucine to proline at codon 7 in the signal peptide of NPY, was associated with increas

The cloned guinea pig neuropeptide Y receptor Y1 conforms to other mammalian Y1 receptors

We have cloned the guinea pig neuropeptide Y (NPY) Y1 receptor and found it to be 92-93% identical to other cloned mammalian Y1 receptors. Porcine NPY and peptide YY (PYY) displayed affinities of 43 pM and 48 pM, respectively. NPY2-36 and NPY3-36 had 6- and 46-fold lower affinity, respectively, than intact NPY. Functional coupling was measured by using a microphysiometer. Human NPY and PYY were eq

Suppression of sensory C fiber-mediated contractions by neuropeptide Y Y1 receptors in the guinea pig bronchi

The aim of the study was to examine which neuropeptide Y (NPY) receptor types that are coupled to inhibition of sensory C fiber-mediated contractions of the guinea pig bronchi. NPY and PYY evoked a concentration-dependent inhibition of the electrically stimulated contractions. The Y1 receptor-selective antagonist BIBP3226 (1 microM) evoked a rightward shift of the NPY-induced response. Also the Y1

Pathogen suppression by microbial volatile organic compounds in soils

There is increasing evidence that microbial volatile organic compounds (mVOCs) play an important role in interactions between microbes in soils. In this minireview, we zoom in on the possible role of mVOCs in the suppression of plant-pathogenic soil fungi. In particular, we have screened the literature to see what the actual evidence is that mVOCs in soil atmospheres can contribute to pathogen sup

Deep mining of complex antibody phage pools generated by cell panning enables discovery of rare antibodies binding new targets and epitopes

Phage display technology is a common approach for discovery of therapeutic antibodies. Drug candidates are typically isolated in two steps: First, a pool of antibodies is enriched through consecutive rounds of selection on a target antigen, and then individual clones are characterized in a screening procedure. When whole cells are used as targets, as in phenotypic discovery, the output phage pool

Pulse-Picking by Resonant Excitation (PPRE) for Timing Users at the MAX IV 3 GeV Storage Ring

At synchrotron light storage rings there is demand for serving both high-brilliance and timing users simultaneously. At many rings this is commonly achieved by operating fill patterns with gaps of sufficient length, but this is not favorable for rings that operate with passive harmonic cavities to damp instabilities and increase Touschek lifetime by lengthening the bunches. For such rings, gaps in

Lack of Ability to Present Antigens on Major Histocompatibility Complex Class II Molecules Aggravates Atherosclerosis in ApoE-/- Mice

BACKGROUND: Hypercholesterolemic mice lacking factors required for activation of CD4+ T cells are characterized by reduced development of atherosclerosis. Consequently, it has been assumed that atherosclerosis involves loss of tolerance against modified self-antigens generated in response to hypercholesterolemia and that presentation of such antigens on major histocompatibility complex class II (M

Spirituality among Iranian nursing students during undergraduate study

Background Nursing students are expected to deliver holistic care in their upcoming career. Developing spirituality during nursing training is poorly understood. Objectives The current study aimed to explore the process of developing spirituality among Iranian nursing undergraduates. Patients and Methods The study employed Grounded theory approach and purposive sampling with maximum variation to s