Determinants of heart rate variability in obstructive sleep apnea syndrome during wakefulness and sleep

Heart rate variability (HRV) is mediated by at least three primary mechanisms: 1) vagal feedback from pulmonary stretch receptors (PSR), 2) central medullary coupling between respiratory and cardiovagal neurons (RCC), and 3) arterial baroreflex (ABR)-induced fluctuations. We employed a noninvasive experimental protocol in conjunction with a minimal model to determine how these sources of HRV are altered in obstructive sleep apnea syndrome (OSAS). Respiration, heart rate, and blood pressure were monitored in eight normal subjects and nine untreated OSAS patients in relaxed wakefulness and stage 2 and rapid eye movement sleep. A computer-controlled ventilator delivered inspiratory pressures that varied randomly from breath to breath. Application of the model to the corresponding subject responses allowed the delineation of the three components of HRV. In all states, RCC gain was lower in OSAS patients than in normal subjects (P < 0.04). ABR gain was also reduced in OSAS patients (P < 0.03). RCC and ABR gains increased from wakefulness to sleep (P < 0.04). However, there was no difference in PSR gain between subject groups or across states. The findings of this study suggest that the adverse autonomic effects of OSAS include impairment of baroreflex gain and central respiratory-cardiovascular coupling, but the component of respiratory sinus arrhythmia that is mediated by lung vagal feedback remains intact.     

Alpha-1B adrenergic receptor knockout mice are protected against methamphetamine toxicity

The psychostimulant methamphetamine (MA) is toxic to nigro-striatal dopaminergic terminals in both experimental animals and humans. In mice, three consecutive injections of MA (5 mg/kg, i.p. with 2 h of interval) induced a massive degeneration of the nigro-striatal pathway, as reflected by a 50% reduction in the striatal levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC), by a substantial reduction in striatal tyrosine hydroxylase and high-affinity DA transporter immunostaining, and by the development of reactive gliosis. MA-induced nigro-striatal degeneration was largely attenuated in mice lacking alpha1b-adrenergic receptors (ARs). MA-stimulated striatal DA release (measured by microdialysis in freely moving animals) and locomotor activity were also reduced in alpha1b-AR knockout mice. Pharmacological blockade of alpha-adrenergic receptors with prazosin also protected wild-type mice against MA toxicity. These results suggests that alpha1b-ARs may play a role in the toxicity of MA on nigro-striatal DA neurons.     

Unilamellar vesicles as potential capreomycin sulfate carriers: Preparation and physicochemical characterization

The aim of this work was to evaluate unilamellar liposomes as new potential capreomycin sulfate (CS) delivery systems for future pulmonary targeting by aerosol administration. Dipalmitoylphosphatidylcholine, hydrogenated phosphatidylcholine, and distearoylphosphatidylcholine were used for liposome preparation. Peptide-membrane interaction was investigated by differential scanning calorimetry (DSC) and attenuated total internal reflection Fourier-transform infrared spectroscopy (ATIR-FTIR). Peptide entrapment, size, and morphology were evaluated by UV spectrophotometry, photocorrelation spectroscopy, and transmission electron microscopy, respectively. Interaction between CS and the outer region of the bilayer was revealed by DSC and ATIR-FTIR. DSPC liposomes showed enhanced interdigitation when the CS molar fraction was increased. Formation of a second phase on the bilayer surface was observed. From kinetic and permeability studies, CS loaded DSPC liposomes resulted more stable if compared to DPPC and HPC over the period of time investigated. The amount of entrapped peptide oscillated between 10% and 13%. Vesicles showed a narrow size distribution, from 138 to 166 nm, and a good morphology. These systems, in particular DSPC liposomes, could represent promising carriers for this peptide.     

Hypergravity impairs angiogenic response of in vitro cultured human primary endothelial cells

A variety of evidence suggest that cardiovascular system functions are impaired in altered gravity conditions. In this study we investigated the influence of hypergravity environment (3g) on endothelial cell proliferation, endothelial vasoactive compound production and on in vitro angiogenesis. We found that cultured primary human endothelial cells were very sensitive to mild hypergravity conditions. Even if we did not record changes in cell viability and apoptosis, we found significant differences in cell proliferation, prostacyclin (PGI2) synthesis, nitric oxide (NO) synthesis, and in angiogenic responses. Using western blotting technique we detected an increased expression of cycloxygenase-2 (COX-2) in primary endothelial cells exposed for 48 hours to hypergravity, in comparison to those exposed to normal gravity.     

Involvement of G protein-coupled receptor kinases and arrestins in desensitization to follicle-stimulating hormone action.

FSH rapidly desensitizes the FSH-receptor (FSH-R) upon binding. Very little information is available concerning the regulatory proteins involved in this process. In the present study, we investigated whether G protein-coupled receptor kinases (GRKs) and arrestins have a role in FSH-R desensitization, using a mouse Ltk 7/12 cell line stably overexpressing the rat FSH-R as a model. We found that these cells, which express GRK2, GRK3, GRK5, and GRK6 as well as beta-arrestins 1 and 2 as detected by RT-PCR and by Western blotting, were rapidly desensitized in the presence of FSH. Overexpression of GRKs and/or beta-arrestins in Ltk 7/12 cells allowed us to demonstrate 1) that GRK2, -3, -5, -6a, and -6b inhibit the FSH-R-mediated signaling (from 71% to 96% of maximal inhibition depending on the kinase, P < 0.001); 2) that beta-arrestins 1 or 2 also decrease the FSH action when overexpressed (80% of maximal inhibition, P < 0.01) whereas dominant negative beta-arrestin 2 [319-418] potentiates it 8-fold (P < 0.001); 3) that beta-arrestins and GRKs (except GRK6a) exert additive inhibition on FSH-induced response; and 4) that FSH-R desensitization depends upon the endogenous expression of GRKs, since there is potentiation of the FSH response (2- to 3-fold, P < 0.05) with antisenses cDNAs for GRK2, -5, and -6, but not GRK3. Our results show that the desensitization of the FSH-induced response involves the GRK/arrestin system.     

The vegetation of alpine belt karst-tectonic basins in the central Apennines (Italy)

Abstract

The vegetation communities of the karst-tectonic basins of the Majella massif alpine belt were studied using the phytosociological methods, and analysed from coenological, synchorological and syntaxonomical viewpoints. During the field-work, 115 relevés were performed using the phytosociological approach of Braun-Blanquet, and these relevés were further subjected to multivariate analyses. Eight clusters of relevés resulted from the numerical classification. The plant communities identified in the study area were ascribed to the following five associations, two sub-associations and one community type: Leontopodio – Seslerietum juncifoliae (ass. nova); Helianthemo – Festucetum italicae (ass. nova); Gnaphalio – Plantaginetum atratae; Taraxaco – Trifolietum thalii gnaphalietosum magellensis (subass. nova); Luzulo italicae – Nardetum, Carici – Salicetum retusae; Saxifrago – Papaveretum julici, Saxifrago – Papaveretum androsacetosum (subass. nova), Plantago atrata and Leontodon montanus community. The distribution of these communities within the karst basins was found to be related to variations in topographic and geomorphological parameters, such as altitude, slope, soil availability and stoniness. All the new associations proposed in this paper belong to the suballiance Leontopodio – Elynenion and to the alliance Seslerion apenninae, both of which are endemic to the central Apennines. In order to compare the plant community types identified within the Majella massif to similar associations found in the rest of the Apennine chain, synoptic tables were constructed. Finally, a comparative phytogeographical analysis of the alpine belt vegetation of the Apennines, Dinarides, southern Balkans and eastern Alps is presented.     

Classification and mapping of the ecoregions of Italy

Ecological regions or ecoregions derive from ecological classification of land and represent broad and discrete ecologically homogeneous areas within which natural communities and species interact with the physical elements of the environment. The aim of this paper is to define the ecoregions of Italy, southern Europe, based on a robust methodological process for classification and mapping. The ecoregions of Italy comprise 2 Divisions, 7 Provinces, 11 Sections and 33 Subsections and constitute the first comprehensive ecological classification of the country that integrates accurate and updated cartographies and knowledges on climate, vegetation, land units and biogeography. This classification has the strength to be adopted as a proper framework for ecological modelling, biodiversity conservation policies and sustainable territorial planning at the national and subnational level.