Determinant factors of the decrease in aerobic performance in moderate acute hypoxia in women endurance athletes

The purpose of this study was to evaluate the limiting factors of maximal aerobic performance in endurance trained (TW) and sedentary (UW) women. Subjects performed four incremental tests on a cycle ergometer at sea level and in normobaric hypoxia corresponding to 1000, 2500 and 4500 m. Maximal oxygen uptake decrement (Delta VO2 max) was larger in TW at each altitude. Maximal heart rate and ventilation decreased at 4500 m in TW. Maximal cardiac output remained unchanged. In both groups, arterialized oxygen saturation (Sa'O2 max) decreased at and above 2500 m and maximal O2 transport (QaO2 max) decreased from 1000 m. At 4500 m, there was no more difference in QaO2 max between TW and UW. Mixed venous O2 pressure (PvO2 max) was lower and O2 extraction (O2ERmax) greater in TW at each altitude. The primary determinant factor of VO2 max decrement in moderate acute hypoxia in trained and untrained women is a reduced maximal O2 transport that cannot be compensate by tissue O2 extraction.     

Stability of muscle synergies for voluntary actions after cortical stroke in humans

Production of voluntary movements relies critically on the functional integration of several motor cortical areas, such as the primary motor cortex, and the spinal circuitries. Surprisingly, after almost 40 years of research, how the motor cortices specify descending neural signals destined for the downstream interneurons and motoneurons has remained elusive. In light of the many recent experimental demonstrations that the motor system may coordinate muscle activations through a linear combination of muscle synergies, we hypothesize that the motor cortices may function to select and activate fixed muscle synergies specified by the spinal or brainstem networks. To test this hypothesis, we recorded electromyograms (EMGs) from 12–16 upper arm and shoulder muscles from both the unaffected and the stroke-affected arms of stroke patients having moderate-to-severe unilateral ischemic lesions in the frontal motor cortical areas. Analyses of EMGs using a nonnegative matrix factorization algorithm revealed that in seven of eight patients the muscular compositions of the synergies for both the unaffected and the affected arms were strikingly similar to each other despite differences in motor performance between the arms, and differences in cerebral lesion sizes and locations between patients. This robustness of muscle synergies that we observed supports the notion that descending cortical signals represent neuronal drives that select, activate, and flexibly combine muscle synergies specified by networks in the spinal cord and/or brainstem. Our conclusion also suggests an approach to stroke rehabilitation by focusing on those synergies with altered activations after stroke.     

Similar protective effect of ischaemic and ozone oxidative preconditionings in liver ischaemia/reperfusion injury.

Many studies indicate that oxygen free-radical formation after reoxygenation of liver may initiate the cascade of hepatocellular injury. It has been demonstrated that controlled ozone administration may promote an oxidative preconditioning or adaptation to oxidative stress, preventing the damage induced by reactive oxygen species (ROS) and protecting against liver ischaemia-reperfusion (I/R) injury. On the basis of those results we postulated that ozone treatment in our experimental conditions has biochemical parameters similar to the ischaemic preconditioning (IscheP) mechanism. Four groups of rats were classified as follows: (1) sham-operated animals subjected to anaesthesia and laparotomy, plus surgical manipulation; (2) I/R animals were subjected to 90 min of right-lobe hepatic ischaemia, followed by 90 min of reperfusion; (3) IscheP, previous to the I/R period (as in group 2): animals were subjected to 10 min of ischaemia and 10 min of reperfusion; (4) ozone oxidative preconditioning (OzoneOP), previous to the I/R period (as in group 2): animals were treated with ozone by rectal insufflation 1 mg kg (-1). The rats received 15 ozone treatments, one per day, of 5-5.5 ml at the ozone concentration of 50 microg ml (-1). The following parameters were measured: serum transaminases (AST, ALT) and 5'-nucleotidase (5 '-NT), with morphological determinations, as indicators or hepatocellular injury; total sulfhydryl groups, calcium levels and calpain activity as mediators which take part in xanthine deshydrogenase (XDH) conversion to xanthine oxidase (XO) (reversible and irreversible forms, respectively); XO activities and malondialdehyde + 4-hydroyalkenals as indicators of increased oxidative stress. AST, ALT levels were attenuated in the IscheP (130 +/- 11.4 and 75 +/- 5.7 U l (-1)) with regard to the I/R group (200 +/- 22 and 117 +/- 21.7 U l (-1)) while the OzoneOP maintained both of the enzyme activities ( 89.5 +/- 12.6 and 43.7 +/- 10 U l (-1)) without statistical differences (P< 0.05) in comparison with the sham-operated ( 63.95 +/- 11 and 19.48 +/- 3.2 U l (-1)). Protective effects of both the preconditioning settings on the preservation of total sylfhydryl groups (IscheP: 6.28 +/- 0.07, OzoneOP: 6.34 +/- 0.07 micromol mg prot (-1)), calcium concentrations (IscheP: 0.18 +/- 0.09, OzoneOP: 0.20 +/- 0.06 micromol mg prot (-1)), and calpain activity (IscheP: 1.04 +/- 0.58, OzoneOP: 1.41 +/- 0.79 U mg prot (-1)) were observed. Both of the preconditionings attenuated the increase of total XO associated to I/R injury. Generation of malondialdehyde + 4 hydroxyalkenals was prevented by IscheP and OzoneOP without statistical differences between the two protective procedures. These results provide evidence that both of the preconditioning settings share similar biochemical mechanisms of protection in the parameters which were measured. Although there were no differences from a biochemical point of view between Ischaemic and OzoneOPs, the histological results showed a more effective protection of OzoneOP than IscheP in our experimental conditions.     

Serotonin triggers a transient epigenetic mechanism that reinstates adult visual cortex plasticity in rats

Cortical circuitries are highly sensitive to experience during early life but this phase of heightened plasticity decreases with development. We recently demonstrated that fluoxetine reinstates a juvenile-like form of plasticity in the adult visual system. Here we explored cellular and molecular mechanisms that underlie the occurrence of these plastic phenomena. Adult rats were intracortically treated with serotonin (5-HT) whereas long-term fluoxetine-treated rats were infused with the 5-HT(1A) -receptor antagonist WAY-100635, brain-derived neurotrophic factor (BDNF) scavenger trkB-IgG or the mitogen-activated protein kinase inhibitor U0126. Plasticity was assessed as variations of visual cortex responsiveness after unilateral eyelid suture and reverse occlusion by using an electrophysiological approach. Real-time PCR and chromatin immunoprecipitation analysis were then used to explore alterations in gene expression and modifications of chromatin structure associated with the plastic outcome caused by fluoxetine in the visual system. Local infusion of 5-HT into visual cortex restored susceptibility to monocular deprivation in adulthood whereas infusion of WAY-100635, trkB-IgG or U0126 prevented the process of plasticity reactivation in fluoxetine-treated animals. Long-term fluoxetine treatment promoted a transient increase of Bdnf expression in the visual cortex, which was paralleled by an increased histone acetylation status at Bdnf promoter regions and by decreased expression of Hdac5. Accordingly, enhancing histone acetylation levels by systemic treatment with Trichostatin-A reactivated plasticity in the adult while WAY-100635-infusion prevented epigenetic modifications in Bdnf promoter areas. The data suggest a key role for 5-HT(1A) receptor and BDNF-trkB signalling in driving a transitory epigenetic remodelling of chromatin structure that underlies the reactivation of plasticity in the visual system.     

Activation of Rho GTPases triggers structural remodeling and functional plasticity in the adult rat visual cortex

A classical example of age-dependent plasticity is ocular dominance (OD) plasticity, triggered by monocular deprivation (MD). Sensitivity of cortical circuits to a brief period of MD is maximal in juvenile animals and downregulated in adult age. It remains unclear whether a reduced potential for morphological remodeling underlies this downregulation of physiological plasticity in adulthood. Here we have tested whether stimulation of structural rearrangements is effective in promoting experience-dependent plasticity in adult age. We have exploited a bacterial protein toxin, cytotoxic necrotizing factor 1 (CNF1), that regulates actin dynamics and structure of neuronal processes via a persistent activation of Rho GTPases. Injection of CNF1 into the adult rat visual cortex triggered a long-lasting activation of the Rho GTPase Rac1, with a consequent increase in spine density and length in pyramidal neurons. Adult rats treated with CNF1, but not controls, showed an OD shift toward the open eye after MD. CNF1-mediated OD plasticity was selectively attributable to the enhancement of open-eye responses, whereas closed-eye inputs were unaffected. This effect correlated with an increased density of geniculocortical terminals in layer IV of monocularly deprived, CNF1-treated rats. Thus, Rho GTPase activation reinstates OD plasticity in the adult cortex via the potentiation of more active inputs from the open eye. These data establish a direct link between structural remodeling and functional plasticity and demonstrate a role for Rho GTPases in brain plasticity in vivo. The plasticizing effects of Rho GTPase activation may be exploited to promote brain repair.     

Epidemiology and clinical and pathologic characteristics of cutaneous malignant melanoma in Abruzzo (Italy)

Background  Malignant melanoma incidence has increased worldwide in recent decades. Cancer registry-derived epidemiologic data on malignant melanoma in Italy are available only in some northern regions of the country.
Aim  To report the number and characteristics of incident cases of cutaneous malignant melanoma in Abruzzo, a central-southern Italian region.
Methods  Screening of the archives of the pathology departments of regional hospitals from 2002 to 2005 was performed. For each patient, clinical and pathologic data were collected. Cases of metastatic, multiple, or relapsing melanoma were excluded.
Results  Six hundred and seventy-two cases of primary melanoma were recorded, with an incidence rate of 14.1 per 100,000 inhabitants per year. Differences related to gender (41.1% males and 58.9% females) and age (35% in the 50–70-year age group) were found. The trunk (30.7%) and lower limbs (25.94%) were the most frequent sites observed. The superficial spreading histiotype and thin melanoma (≤ 1.00 mm) were more often recorded (44.8% and 62%, respectively).
Conclusions  Despite the bias present in this study, linked to the nature and source of the data, we believe that the figures found in this report are comparable with those obtained in the international literature from other Mediterranean countries.