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Nucleus incertus (NI) neurons in the pontine tegmentum give rise to ascending forebrain projections and express the neuropeptide relaxin-3 (RLN3) which acts via the relaxin-family peptide 3 receptor (RXFP3). Activity in the hippocampus and entorhinal cortex can be driven from the medial septum (MS), and the NI projects to all these centers, where a prominent pattern of activity is theta rhythm, which is related to spatial memory processing. Therefore, we examined the degree of collateralization of NI projections to the MS and the medial temporal lobe (MTL), comprising medial and lateral entorhinal cortex (MEnt, LEnt) and dentate gyrus (DG), and the ability of the MS to drive entorhinal theta in the adult rat. We injected fluorogold and cholera toxin-B into the MS septum and either MEnt, LEnt or DG, to determine the percentage of retrogradely labeled neurons in the NI projecting to both or single targets, and the relative proportion of these neurons that were RLN3-positive (+). The projection to the MS was threefold stronger than that to the MTL. Moreover, a majority of NI neurons projected independently to either MS or the MTL. However, RLN3 + neurons collateralize significantly more than RLN3-negative (–) neurons. In in vivo studies, electrical stimulation of the NI induced theta activity in the MS and the entorhinal cortex, which was impaired by intraseptal infusion of an RXFP3 antagonist, R3(BΔ23-27)R/I5, particularly at ~ 20 min post-injection. These findings suggest that the MS plays an important relay function in the NI-induced generation of theta within the entorhinal cortex. [ABSTRACT FROM AUTHOR]

We present a polyad-preserving algebraic approach to molecular structure and, as an application, we fit the model parameters to reproduce an extensive experimental data set of vibrational energies of carbon dioxide in its ground electronic state. The data set includes levels with vibrational angular momentum ℓ = 1, ...,6 and some recently obtained term values that have not been previously considered. The obtained results are close to experimental uncertainty and we compare the results obtained making use of the three most common polyad schemes that can be found in the literature for this molecular species. Graphical abstract: [ABSTRACT FROM AUTHOR]

The role of microglial motility in the context of adult neurodegeneration is poorly understood. In the present work, we investigated the microanatomical details of microglia-neuron interactions in an experimental mouse model of Parkinson's disease following the intraperitoneal injection of MPTP. The specific intoxication of dopaminergic neurons induces the cellular polarization of microglia, leading to the formation of body-to-body neuron-glia contacts, called gliapses, which precede neuron elimination. Inhibiting ROCK/Cdc42-mediated microglial motility in vivo blocks the activating features of microglia, such as increased cell size and number of filopodia and diminishes their phagocyting/secreting domains, as the reduction of the Golgi apparatus and the number of microglia-neuron contacts has shown. High-resolution confocal images and three-dimensional rendering demonstrate that microglia engulf entire neurons at one-to-one ratio and the microglial cell body participates in the formation of the phagocytic cup, engulfing and eliminating neurons in areas of dopaminergic degeneration in adult mammals. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of hyaluronidase gel on the prevention of post-operative peritoneal adhesions to prosthetic materials used in laparosopic ventral hernia repair. Ten pigs were included in this study. The animals were anesthtetized using Na-penthotal for induction and isofluorane for maiteneance. The abdomen was opened and, using helical fasteners, four implantantions were perfomed (squares of 4 × 4 cm). Two of the implants, placed in an upper location, were in polypropylene mesh, and two of the implants, placed in a lower aera, were in polytetrafluoroethylene (PTFE-e, Dualmesh® Plus Corduroy). The implants located in the right side of animals were painted with hyaluronidase gel. Two helical fasteners, painted and unpainted, were implanted in a medial location. After a five-week period the pigs were operated on again, intraperitoneal adhesion ratios and grades were determined, and the pigs later sacrificed. Specimens having abdominal wall implants were taken for histological studies. Intraperitoneal adhesions decreased in implants painted with hyaluronidase gel in a comparative study with implants located in the left side of animals (not painted). On the other hand the polypropylene mesh, said typically to produce intraperitoneal adhesions, produced almost no adhesion in many animals. Hyaluronidase gel reduces post-operative peritoneal adhesions ratio and grades including in the presence of polypropylene mesh. [ABSTRACT FROM AUTHOR]

Objective: Interferon (IFN) α-2b is a protein with antiviral, antiproliferative and immunoregulatory properties that is approved for several clinical indications. A new liquid, albumin-free, IFNα-2b formulation has recently been developed. This study aimed to evaluate the equivalence of the pharmacokinetic, pharmacodynamic and safety properties of the new formulation with a reference one in healthy male volunteers. Methods: A randomised, crossover, double-blind study with a 3-week washout period was performed in which Heberon Alfa R® (formulation A) and Viraferon® (formulation B) were compared. A single 20 × 106 IU IFNα-2b dose was administered subcutaneously to 14 apparently healthy male subjects. Serum IFN level was measured over 48 hours by enzyme immunoassay (EIA) and by antiviral activity titration. Clinical and laboratory variables were determined, as were pharmacodynamic and safety criteria. Results: Groups were homogeneous with regard to all demographic and baseline variables. Pharmacokinetic comparison by EIA did not show differences between the formulations: area under the curve (AUC) 2572 versus 2561 ng · h/L, maximum plasma concentration (Cmax) 318 versus 354 ng/L, time to Cmax (tmax) 8.2 versus 8.5h, elimination half-life (t1/2) 5.87 versus 6.08h, terminal elimination rate (λ) 0.122 versus 0.118h-1, and mean residence time (MRT) 10.9 versus 12.0h for formulations A and B, respectively. The differences never reached 20%, which is the clinically significant threshold. The 90% confidence interval of the ratio between them was in all cases within the 0.8, 1.25 range. The two formulations were clinically equivalent with regard to serum IFN antiviral activity titration (0.8, 1.25 criterion) regarding their pharmacokinetic parameters. There were no significant differences with respect to the pharmacodynamic variables: serum β2-microglobulin and temperature increase. Heart rate and blood pressure changes did not differ either. Both products provoked similar haematological count decreases and had similar safety profiles. The most frequent adverse reactions were fever, tachycardia, headache and arthralgias. Conclusion: The overall analysis strongly suggests the bioequivalence of these two products. [ABSTRACT FROM AUTHOR]