Prolactin

During an oral glucose tolerance test (OGTT) glucose and insulin levels were measured in 26 patients with prolactin-producing pituitary tumours without growth hormone excess. Basal glucose and insulin levels did not differ from the values of an age-matched control group. After glucose load the hyperprolactinaemic patients showed a decrease in glucose tolerance and a hyperinsulinaemia. Bromocriptine (CB 154), which suppressed PRL, improved glucose tolerance and decreased insulin towards normal in a second OGTT. — Human PRL or CB 154 had no significant influence on insulin release due to glucose in the perfused rat pancreas. — These findings suggest a diabetogenic effect of PRL. CB 154 might be a useful drug in improving glucose utilization in hormone-active pituitary tumours

MHD simulations of jet acceleration from Keplerian accretion disks: the effects of disk resistivity

Accretion disks and astrophysical jets are used to model many active astrophysical objects, viz., young stars, relativistic stars, and active galactic nuclei. In this paper we present self-consistent time-dependent simulations of supersonic jets launched from magnetized accretion disks, using high resolution numerical techniques. In particular we study the effects of the disk magnetic resistivity, parametrized through an alpha-prescription, in determining the properties of the inflow-outflow system. Moreover we analyze under which conditions steady state solutions of the type proposed in the self similar models of Blandford and Payne can be reached and maintained in a self consistent nonlinear stage. We use the resistive MHD FLASH code with adaptive mesh refinement, allowing us to follow the evolution of the structure for a time scale long enough to reach steady state. A detailed analysis of the initial configuration state is given. We obtain the expected solutions in the axisymmetric (2.5D) limit. Assuming a magnetic field around equipartition with the thermal pressure of the disk, we show how the characteristics of the disk jet system, as the ejection efficiency and the energetics, are affected by the anomalous resistivity acting inside the disk.Comment: 20 pages, 18 figures, accepted for publication in Astronomy and Astrophysic

Sphingosine-1-phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin

Sphingosine-1-phosphate (S1P) participates in inflammation;however, its role in leukocyte rolling is still unclear. Here we use intravital microscopy in inflamed mouse cremaster muscle venules and human endothelial cells to show that S1P contributes to P-selectin-dependent leukocyte rolling through endothelial S1P receptor 3 (S1P(3)) and G alpha(q), PLC beta and Ca2+. Intraarterial S1P administration increases leukocyte rolling, while S1P(3) deficiency or inhibition dramatically reduces it. Mast cells involved in triggering rolling also release S1P that mobilizes P-selectin through S1P(3). Histamine and epinephrine require S1P(3) for full-scale effect accomplishing it by stimulating sphingosine kinase 1 (Sphk1). In a counter-regulatory manner, S1P1 inhibits cAMP-stimulated Sphk1 and blocks rolling as observed in endothelial-specific S1P(1)(-/-) mice. In agreement with a dominant pro-rolling effect of S1P(3),FTY720 inhibits rolling in control and S1P(1)(-/-) but not in S1P(3)(-/-) mice. Our findings identify S1P as a direct and indirect contributor to leukocyte rolling and characterize the receptors mediating its action

Gravitating discs around black holes

Fluid discs and tori around black holes are discussed within different approaches and with the emphasis on the role of disc gravity. First reviewed are the prospects of investigating the gravitational field of a black hole--disc system by analytical solutions of stationary, axially symmetric Einstein's equations. Then, more detailed considerations are focused to middle and outer parts of extended disc-like configurations where relativistic effects are small and the Newtonian description is adequate. Within general relativity, only a static case has been analysed in detail. Results are often very inspiring, however, simplifying assumptions must be imposed: ad hoc profiles of the disc density are commonly assumed and the effects of frame-dragging and completely lacking. Astrophysical discs (e.g. accretion discs in active galactic nuclei) typically extend far beyond the relativistic domain and are fairly diluted. However, self-gravity is still essential for their structure and evolution, as well as for their radiation emission and the impact on the environment around. For example, a nuclear star cluster in a galactic centre may bear various imprints of mutual star--disc interactions, which can be recognised in observational properties, such as the relation between the central mass and stellar velocity dispersion.Comment: Accepted for publication in CQG; high-resolution figures will be available from http://www.iop.org/EJ/journal/CQ

Isolation, characterization and microincapsulation of neonatal porcine Sertoli cells obtained from a specific pathogen free (SPF) herd

Porcine Sertoli cells (pSC) have been successfully employed as cell therapy in pre-clinical studies of several immune-based and chronic degenerative diseases. In order to prevent any transmission of infectious adventitious agents to the cells graft recipients, we have set up, according to our previously described method (Luca et al., 2007) pSC monolayers obtained from specific pathogen free (SPF) certified neonatal pigs, born in the unique SPF colony in Italy. pSC were assessed and characterized as far as viability, by ethidium bromide and fluorescein diacetate (EB/FD), Müllerian inhibiting substance (AMH), and insulin-like 3 (INSL3), alpha-smooth muscle actin (ASMI) both by immunofluorescence (IF) and cytofluorimetric analysis (CA) were concerned. pSC were encapsulated in alginate microcapsules (MCpSC), with MCp- SC functional competence and biocompatibility being determined both in vitro, by AMH, inhibin B, TGF-beta, IGF-I secretion and in vivo in experimental animal models, respectively. Results demonstrated the high purity of our pSC monolayers (95% of AMH+cells), with negligible contamination by Leydig (2%) and peritubular cells (3%). Microencapsulation did not alter pSC viability and even after 4 months postimplantation, all the retrieved microcapsules retained morphology and function. In conclusion, we have uniquely obtained, from a SPF herd, highly purified, viable and functional pSC that might poten-tially apply to humans

The Mice at play in the CALIFA survey: A case study of a gas-rich major merger between first passage and coalescence

We present optical integral field spectroscopy (IFS) observations of the Mice, a major merger between two massive (>10^11Msol) gas-rich spirals NGC4676A and B, observed between first passage and final coalescence. The spectra provide stellar and gas kinematics, ionised gas properties and stellar population diagnostics, over the full optical extent of both galaxies. The Mice provide a perfect case study highlighting the importance of IFS data for improving our understanding of local galaxies. The impact of first passage on the kinematics of the stars and gas has been significant, with strong bars likely induced in both galaxies. The barred spiral NGC4676B exhibits a strong twist in both its stellar and ionised gas disk. On the other hand, the impact of the merger on the stellar populations has been minimal thus far: star formation induced by the recent close passage has not contributed significantly to the global star formation rate or stellar mass of the galaxies. Both galaxies show bicones of high ionisation gas extending along their minor axes. In NGC4676A the high gas velocity dispersion and Seyfert-like line ratios at large scaleheight indicate a powerful outflow. Fast shocks extend to ~6.6kpc above the disk plane. The measured ram pressure and mass outflow rate (~8-20Msol/yr) are similar to superwinds from local ULIRGs, although NGC4676A has only a moderate infrared luminosity of 3x10^10Lsol. Energy beyond that provided by the mechanical energy of the starburst appears to be required to drive the outflow. We compare the observations to mock kinematic and stellar population maps from a merger simulation. The models show little enhancement in star formation during and following first passage, in agreement with the observations. We highlight areas where IFS data could help further constrain the models.Comment: 23 pages, 13 figures, accepted to A&A. A version with a complete set of high resolution figures is available here: http://www-star.st-and.ac.uk/~vw8/resources/mice_v8_astroph.pd

Systemic therapy of Cushing’s syndrome

Cushing’s disease (CD) in a stricter sense derives from pathologic adrenocorticotropic hormone (ACTH) secretion usually triggered by micro- or macroadenoma of the pituitary gland. It is, thus, a form of secondary hypercortisolism. In contrast, Cushing’s syndrome (CS) describes the complexity of clinical consequences triggered by excessive cortisol blood levels over extended periods of time irrespective of their origin. CS is a rare disease according to the European orphan regulation affecting not more than 5/10,000 persons in Europe. CD most commonly affects adults aged 20–50 years with a marked female preponderance (1:5 ratio of male vs. female). Patient presentation and clinical symptoms substantially vary depending on duration and plasma levels of cortisol. In 80% of cases CS is ACTH-dependent and in 20% of cases it is ACTH-independent, respectively. Endogenous CS usually is a result of a pituitary tumor. Clinical manifestation of CS, apart from corticotropin-releasing hormone (CRH-), ACTH-, and cortisol-producing (malign and benign) tumors may also be by exogenous glucocorticoid intake. Diagnosis of hypercortisolism (irrespective of its origin) comprises the following: Complete blood count including serum electrolytes, blood sugar etc., urinary free cortisol (UFC) from 24 h-urine sampling and circadian profile of plasma cortisol, plasma ACTH, dehydroepiandrosterone, testosterone itself, and urine steroid profile, Low-Dose-Dexamethasone-Test, High-Dose-Dexamethasone-Test, after endocrine diagnostic tests: magnetic resonance imaging (MRI), ultra-sound, computer tomography (CT) and other localization diagnostics. First-line therapy is trans-sphenoidal surgery (TSS) of the pituitary adenoma (in case of ACTH-producing tumors). In patients not amenable for surgery radiotherapy remains an option. Pharmacological therapy applies when these two options are not amenable or refused. In cases when pharmacological therapy becomes necessary, Pasireotide should be used in first-line in CD. CS patients are at an overall 4-fold higher mortality rate than age- and gender-matched subjects in the general population. The following article describes the most prominent substances used for clinical management of CS and gives a systematic overview of safety profiles, pharmacokinetic (PK)-parameters, and regulatory framework

Male-like sexual behavior of female mouse lacking fucose mutarotase

<p>Abstract</p> <p>Background</p> <p>Mutarotases are recently characterized family of enzymes that are involved in the anomeric conversions of monosaccharides. The mammalian fucose mutarotase (FucM) was reported in cultured cells to facilitate fucose utilization and incorporation into protein by glycosylation. However, the role of this enzyme in animal has not been elucidated.</p> <p>Results</p> <p>We generated a mutant mouse specifically lacking the fucose mutarotase (FucM) gene. The <it>FucM </it>knockout mice displayed an abnormal sexual receptivity with a drastic reduction in lordosis score, although the animals were fertile due to a rare and forced intromission by a typical male. We examined the anteroventral periventricular nucleus (AVPv) of the preoptic region in brain and found that the mutant females showed a reduction in tyrosine hydoxylase positive neurons compared to that of a normal female. Furthermore, the mutant females exhibited a masculine behavior, such as mounting to a normal female partner as well as showing a preference to female urine. We found a reduction of fucosylated serum alpha-fetoprotein (AFP) in a mutant embryo relative to that of a wild-type embryo.</p> <p>Conclusions</p> <p>The observation that <it>FucM</it>^-/-female mouse exhibits a phenotypic similarity to a wild-type male in terms of its sexual behavior appears to be due to the neurodevelopmental changes in preoptic area of mutant brain resembling a wild-type male. Since the previous studies indicate that AFP plays a role in titrating estradiol that are required to consolidate sexual preference of female mice, we speculate that the reduced level of AFP in <it>FucM</it>^-/-mouse, presumably resulting from the reduced fucosylation, is responsible for the male-like sexual behavior observed in the FucM knock-out mouse.</p

Delineating the GRIN1 phenotypic spectrum: a distinct genetic NMDA receptor encephalopathy

Objective:To determine the phenotypic spectrum caused by mutations in GRIN1 encoding the NMDA receptor subunit GluN1 and to investigate their underlying functional pathophysiology.Methods:We collected molecular and clinical data from several diagnostic and research cohorts. Functional consequences of GRIN1 mutations were investigated in Xenopus laevis oocytes.Results:We identified heterozygous de novo GRIN1 mutations in 14 individuals and reviewed the phenotypes of all 9 previously reported patients. These 23 individuals presented with a distinct phenotype of profound developmental delay, severe intellectual disability with absent speech, muscular hypotonia, hyperkinetic movement disorder, oculogyric crises, cortical blindness, generalized cerebral atrophy, and epilepsy. Mutations cluster within transmembrane segments and result in loss of channel function of varying severity with a dominant-negative effect. In addition, we describe 2 homozygous GRIN1 mutations (1 missense, 1 truncation), each segregating with severe neurodevelopmental phenotypes in consanguineous families.Conclusions:De novo GRIN1 mutations are associated with severe intellectual disability with cortical visual impairment as well as oculomotor and movement disorders being discriminating phenotypic features. Loss of NMDA receptor function appears to be the underlying disease mechanism. The identification of both heterozygous and homozygous mutations blurs the borders of dominant and recessive inheritance of GRIN1-associated disorders.Johannes R. Lemke (32EP30_136042/1) and Peter De Jonghe (G.A.136.11.N and FWO/ESF-ECRP) received financial support within the EuroEPINOMICS-RES network (www.euroepinomics.org) within the Eurocores framework of the European Science Foundation (ESF). Saskia Biskup and Henrike Heyne received financial support from the German Federal Ministry for Education and Research (BMBF IonNeurONet: 01 GM1105A and FKZ: 01EO1501). Katia Hardies is a PhD fellow of the Institute for Science and Technology (IWT) Flanders. Ingo Helbig was supported by intramural funds of the University of Kiel, by a grant from the German Research Foundation (HE5415/3-1) within the EuroEPINOMICS framework of the European Science Foundation, and additional grants of the German Research Foundation (DFG, HE5415/5-1, HE 5415/6-1), German Ministry for Education and Research (01DH12033, MAR 10/012), and grant by the German chapter of the International League against Epilepsy (DGfE). The project also received infrastructural support through the Institute of Clinical Molecular Biology in Kiel, supported in part by DFG Cluster of Excellence "Inflammation at Interfaces" and "Future Ocean." The project was also supported by the popgen 2.0 network (P2N) through a grant from the German Ministry for Education and Research (01EY1103) and by the International Coordination Action (ICA) grant G0E8614N. Christel Depienne, Caroline Nava, and Delphine Heron received financial support for exome analyses by the Centre National de Genotypage (CNG, Evry, France)