A Novel Interhemispheric Interaction: Modulation of Neuronal Cooperativity in the Visual Areas

Background: The cortical representation of the visual field is split along the vertical midline, with the left and the right hemi-fields projecting to separate hemispheres. Connections between the visual areas of the two hemispheres are abundant near the representation of the visual midline. It was suggested that they re-establish the functional continuity of the visual field by controlling the dynamics of the responses in the two hemispheres. Methods/Principal Findings: To understand if and how the interactions between the two hemispheres participate in processing visual stimuli, the synchronization of responses to identical or different moving gratings in the two hemi-fields were studied in anesthetized ferrets. The responses were recorded by multiple electrodes in the primary visual areas and the synchronization of local field potentials across the electrodes were analyzed with a recent method derived from dynamical system theory. Inactivating the visual areas of one hemisphere modulated the synchronization of the stimulus-driven activity in the other hemisphere. The modulation was stimulus-specific and was consistent with the fine morphology of callosal axons in particular with the spatio-temporal pattern of activity that axonal geometry can generate. Conclusions/Significance: These findings describe a new kind of interaction between the cerebral hemispheres and highlight the role of axonal geometry in modulating aspects of cortical dynamics responsible for stimulus detection and/or categorization

Growth hormone bioactivity and levels of growth hormone, growth hormone-binding protein, insulinlike growth factor I, and insulinlike growth factor-binding proteins in premature and full-term newborns during the first month of life

Objective: To assess the pattern of growth hormone bioactivity (GH-BIO) and the levels of GH-binding protein (GH-BP), insulin-like growth factor I (IGF-I), and insulin-like growth factor-binding proteins (IGFBPs) in the first month of life in premature and full-term (FT) newborns. Patients and Methods: Serum samples were collected from 9 premature newborns who were small for gestational age, 18 premature newborns who were of appropriate size for gestational age, and 20 FT newborns on the 4th and 30th days of life to evaluate the GH-BIO using the Nb2 cell bioassay, the GH levels using a radioimmunoassay (GH-RIA), and the levels of GH-BP, IGF-I, and IGFBPs. Results: On day 4, the GH-RIA and GH-BIO values were increased in all newborns (P lt .05) compared with values in the prepubertal control subjects. The GH-BP levels were low in all newborns, with the lowest values (P lt .05) found in the premature newborns and positively correlated with gestation age (P lt .001). The IGF-I levels were also low, with lower values (than those found in the FT newborns) (P lt .005) found in the premature group and positively correlated with the GH-BP levels (P lt .001) and gestational age (P lt .001). The levels of IGFBP-1 and IGFBP-2 were high, with higher values found in the premature newborns than in the FT newborns (P lt .05) and negatively correlated with gestational age (P lt .005). The IGFBP-3 level was lower in the premature (P lt .05) than in the FT newborns and positively correlated with gestational age (P lt .005). During the first month of life, the GH-RIA and GH-BIO values were significantly decreased in all newborns (P lt .001), while the IGF-I level was increased in the premature newborns (P lt .005). The GH-BP levels were increased only in the FT newborns (P lt .001). Conclusions: The elevated bioactive GH level seen in the first few days of life seemed to be attributable to a low IGF-I level secondary to a decreased number and/or function of the GH receptors. The decrease in the serum GH level observed thereafter seemed to be secondary to an increase in the IGF-I level in the premature newborns; however, other factors may have been involved in the FT newborns in whom no increase in the IGF-I level was observed

Postnatal variations of growth hormone bioactivity and of growth hormone-dependent factors

Objective: To evaluate whether the low insulinlike growth factor I (IGF- I) levels that are observed in the neonate depend on the biological inactivity of the molecular forms of growth hormone (GH) or on the immaturity of the hepatic GH receptors during the early postnatal period. Materials and Methods: Serum samples were collected from 60 normal full-term neonates on day 5 and at 1 and 4 months of age to evaluate the GH concentrations by using both an immunofluorometric assay and Nb2 cell bioassay, as well as the GH- binding protein, IGF-1, and IGF-binding protein 3 values by radioimmunoassay. Results: Five-day-old neonates showed significantly higher (P<.001) mean±SEM GH levels that were measured by using the immunofluorometric assay (27.22±1.62 μg/L) and Nb2 cell bioassay (3.56±0.14 U/mL) compared with those levels in 11 prepubertal children who were studied as control subjects (1.26±0.28 μg/L and 0.74±0.08 U/mL, respectively). At 1 and 4 months of age, GH values that were measured by using both the immunofluorometric assay (9.15±089 and 2.58±0.32 μg/L, respectively) and Nb2 cell bioassay (2.52±0.11 and 1.71±0.15 U/mL, respectively) were decreased significantly (P<.001). In 5 day-old neonates, we observed significantly lower (P<.001) serum GH-binding protein (9.73%±0.42%), IGF-I (67.63±5.20 ng/mL), and IGF- binding protein 3 (1.46±0.17 mg/L) concentrations compared with those in the prepubertal children (30.74%±2.01%, 210±25 ng/mL, and 3.08±0.22 mg/L, respectively). At 1 month of age, serum GHbinding protein (16.00%±0.70%) and IGF-binding protein 3 (2.96±0.30 mg/L) values were increased significantly (P<.001), while IGF-I levels (72.55±7.6 ng/mL, P=.09) were not increased. Serum IGF-I values were increased significantly (P<.005) at 4 months of age (97.94±9.68 ng/mL). Conclusion: The interaction of bioactive molecular forms of GH with the increased hepatic GH receptors induces the rise in postnatal IGF-I levels in early infancy

Efficacy and safety of Nevirapine plus raltegravir as dual regimen in the clinical setting

Dual therapy based on raltegravir and nevirapine has been recently proposed as a possible switching strategy in selected patients, due to attractive tolerability and safety profile. We recently reported the pharmacokinetic compatibility of these drugs when administered twice-daily, but data on efficacy and safety of this combination in the clinical setting are scarce