911 research outputs found
Diagnosis of GH deficiency in the transition period: accuracy of insulin tolerance test and insulin-like growth factor-I measurement.
No full textEur J Endocrinol. 2005 Apr;152(4):589-96.
Diagnosis of GH deficiency in the transition period: accuracy of insulin tolerance test and insulin-like growth factor-I measurement.
Maghnie M, Aimaretti G, Bellone S, Bona G, Bellone J, Baldelli R, de Sanctis C, Gargantini L, Gastaldi R, Ghizzoni L, Secco A, Tinelli C, Ghigo E.
Source
Department of Pediatrics, University of Pavia, Italy. [email protected]
Abstract
OBJECTIVE:
A consensus exists that severe growth hormone deficiency (GHD) in adults is defined by a peak GH response to insulin-induced hypoglycemia (insulin tolerance test, ITT) of less than 3 microg/l based on a cohort of subjects with a mean age of 45 years.
DESIGN AND METHODS:
By considering one of the following two criteria for the diagnosis of probable permanent GHD, i.e. the severity of GHD (suggested by the presence of multiple pituitary hormone deficiencies (MPHD)) or the magnetic resonance (MR) imaging identification of structural hypothalamic-pituitary abnormalities, 26 patients (17 males, 9 females, mean age 20.8 +/- 2.3 years, range 17-25 years) were selected for re-evaluation of the GH response to ITT and their IGF-I concentration. Eight subjects had isolated GHD (IGHD) and 18 had MPHD. Normative data for peak GH were obtained after ITT in 39 healthy subjects (mean age 21.2 +/- 4.4 years, range 15.1-30.0 years) and the reference range for IGF-I was calculated using normative data from 117 healthy individuals.
RESULTS:
Mean peak GH response to ITT was significantly lower in the 26 patients (1.8+/-2.0 microg/l, range 0.1-6.1 microg/l) compared with the 39 controls (18.5 +/- 15.5 microg/l, range 6.1-84.0 microg/l; P < 0.0001). One subject with septo-optic dysplasia had a peak GH response of 6.1 microg/l that overlapped the lowest peak GH response obtained in normal subjects. There was an overlap for IGF-I SDS between subjects with IGHD and MPHD, as well as with normal controls. The diagnostic accuracy of a peak GH response of 6.1 microg/l showed a 96% sensitivity with 100% specificity. The maximum diagnostic accuracy with IGF-I SDS was obtained with a cut-off of -1.7 SDS (sensitivity 77%, specificity 100%) while an IGF-I < or = - 2.0 SDS showed a sensitivity of 62%.
CONCLUSION:
Our data show that the cut-off value of the peak GH response to ITT of less than 3 microg/l or 5 microg/l and of IGF-I of less than -2.0 SDS are too restrictive for the diagnosis of permanent GH deficiency in the transition period. We suggest that permanent GHD could be investigated more accurately by means of an integrated analysis of clinical history, the presence of MPHD, IGF-I concentration and the MR imaging findings of structural hypothalamic-pituitary abnormalities
Protein Kinase C Activation Modulates α-Calmodulin Kinase II Binding to NR2A Subunit of N-Methyl-D-Aspartate Receptor Complex
No full textThe N-methyl-D-aspartate (NMDA) receptor subunits NR2 possess extended intracellular C-terminal domains by which they can directly interact with a large number of postsynaptic density (PSD) proteins involved in synaptic clustering and signaling. We have previously shown that PSD-associated α-calmodulin kinase II (αCaMKII) binds with high affinity to the C-terminal domain of the NR2A subunit. Here, we show that residues 1412-1419 of the cytosolic tail of NR2A are critical for αCaMKII binding, and we identify, by site directed mutagenesis, PKC-dependent phosphorylation of NR2A-(Ser1416) as a key mechanism in inhibiting αCaMKII binding and promoting dissociation of αCaMKII·NR2A complex. In addition, we show that stimulation of PKC activity in hippocampal slices either with phorbol esters or with the mGluRs specific agonist trans-1-amino-1,3-cyclopentanedicarboxylic acid (t-ACPD) decreases αCa-MKII binding to NMDA receptor complex. Thus, our data provide clues on understanding the molecular basis of a direct cross-talk between αCaMKII and PKC pathways in the postsynaptic compartment
Esox bellone Linnaeus, 1758, spec. nov.
No full textEsox bellone [spec. nov.] E. rostro utraque maxilla subulato. Art gen. 10. syn. 27. Esox rostro cuspidato gracili subtereti spithamali. Fn. svec. 305. idem. @/D. 16. P. 13. V. 7. A. 20. C. - - Gron. mus. 1. n. 30. idem. @/B. 14. D. 16. P. 13. V. 7. A. 21. C. 23. Habitat in Oceano Europaeo. Ossa noctu lucent viridia.Published as part of Linnaeus, Carolus, 1758, Systema Naturae per regna tria naturae: secundum classes, ordines, genera, species, cum characteribus, differentiis, synonymis, locis, Stockholm :Laurentius Salvius on page 314, DOI: 10.5962/bhl.title.542, http://zenodo.org/record/392220
Sequential administration of arginine and arginine plus GHRH to test the somatotroph function in short children.
No full textA hypothalamic micro-circuit for social escape decision making
No full textAnimals display a wide range of behaviours that are in service to their survival, some of the most critical of which are defensive behaviours. These behavioural strategies help the animals cope with dangerous situations, and the exact behavioural choice depends upon the context and nature of threat. Some of the behavioural strategies such as active avoidance, passive defence and aggression are thought to be mediated by the centrally located hypothalamic nuclei constituting the medial hypothalamic defensive circuit. One of these is the Ventromedial Hypothalamus (VMH) which has been implicated in avoidance and attack directed towards threats. Even as the VMH has been implicated in modulating such behaviours, how it might threshold a transition to escape is unclear. In this thesis, I investigated the micro-circuit within the ventrolateral subdivision of the VMH (VMHvl) in mice that have a history of social defeat, as they faced a social threat and displayed avoidance. Using in vivo electrophysiology recordings in a novel behavioural test introduced here, I recorded from the VMHvl of male and female mice to find the neural correlates of avoidance. In combination to the extracellular recordings, I used optogenetic stimulation of targeted cell classes - namely the motor output cells and the inhibitory cells in the male VMHvl, to map out the connectivity within the micro-circuit and verify a proposed connectivity model for escape decision making. Using the activity dynamics of the correlates of avoidance, I propose a combinatorial encoding with which the cells within the male VMHvl might bring about assessment as well as avoidance behaviours, in the current context. Finally, I confirmed the presence of cells in female mice which modulated their activity with social avoidance in a manner similar to that seen in males. These results suggest a role of the VMHvl in setting an escape threshold in both the male and the female brain, under conditions of social fear
Modulation of the glutamatergic transmission by Dopamine: a focus on Parkinson, Huntington and Addiction Diseases.
No full textDopamine plays a major role in motor and cognitive functions as well as in reward processing by regulating glutamatergic inputs. In particular in the striatum the release of Dopamine rapidly influences synaptic transmission modulating both AMPA and NMDA receptors. Several neurodegenerative and neuropsychiatric disorders, including Parkinson, Huntington and addiction-related diseases, manifest a dysregulation of glutamate and Dopamine signaling. Here, we will focus our attention on the mechanisms underlying the modulation of the glutamatergic transmission by DA in striatal circuits
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