Exercise training decreases oxidative stress in skeletal muscle of rats with pulmonary arterial hypertension.

The effects of exercise training on oxidative stress in gastrocnemius of rats with pulmonary hypertension were studied. Four groups were established: sedentary control (SC), sedentary monocrotaline (SM), trained control (TC), trained monocrotaline (TM). Exercise was applied for 4 weeks, 5 days/week, 50-60 min/session, at 60% of VO2 max. Right ventricular (RV) pressures were measured, heart and gastrocnemius were removed for morphometric/biochemical analysis. Lipid peroxidation (LPO), H2O2, GSH/GSSG, and activity/expression of antioxidant enzymes were evaluated. Increased RV hypertrophy, systolic and end-diastolic pressures (RVEDP) were observed in SM animals, and the RVEDP was decreased in TM vs. SM. H2O2, SOD-1, and LPO were higher in the SM group than in SC. In TM, H2O2 was further increased when compared to SM, with a rise in antioxidant defences and a decrease in LPO. GSH/GSSG was higher only in the TC group. Exercise induced an efficient antioxidant adaptation, preventing oxidative damage to lipids.

Role of inflammation, oxidative stress, and autonomic nervous system activation during the development of right and left cardiac remodeling in experimental pulmonary arterial hypertension.

This study investigated the impact of experimental pulmonary arterial hypertension (PAH) progression by evaluating morphometric and functional parameters, oxidative stress, autonomic nervous system (ANS) activation, and inflammation in the right (RV) and left (LV) ventricles. Male rats were first divided into two groups: monocrotaline (MCT) and control. The MCT group received a single MCT injection (60 mg/kg, intraperitoneal), while control received saline. The MCT and control groups were further divided into four cohorts based on how long they were observed: 1, 2, 3, and 4 weeks. Animals were submitted to echocardiographic and hemodynamic analysis. RV and LV were used for morphometric, biochemical, and histological measurements. Autonomic modulation was evaluated by cardiac spectral analysis, considering two components: low frequency (LF) and high frequency (HF). Lung and liver weight was used for morphometric analysis. MCT induced 100% mortality at 4 weeks. In the RV, disease progression led to mild inflammation and enhanced reactive oxygen species (ROS) in week 1, followed by moderate inflammation, ROS production, and hypertrophy in week 2. By week 3, there was moderate inflammation, oxidative stress, and ANS imbalance, with development of right heart dysfunction. LV biochemical changes and inflammation were observed at week 3. The initial changes appeared to be related to inflammation and ROS, and the later ones to inflammation, oxidative stress, and ANS imbalance in MCT animals. This study reinforces the severity of the disease in the RV, the late effects in the LV, and the role of ANS imbalance in the development of heart dysfunction.

Profile of pterostilbene-induced redox homeostasis modulation in cardiac myoblasts and heart tissue.

This study was designed to investigate the effect of pterostilbene (PTS) on cardiac oxidative stress in vitro, as this is a simple and promising methodology to study cardiac disease. Cardiac myoblasts (H9c2 cells) and homogenised cardiac tissue were incubated with the PTS and cyclodextrin (PTS + HPßCD) complex for 1 and 24 h, respectively, at concentrations of 50µM for the cells and 25 and 50µM for cardiac tissue. The PTS + HPßCD complex was used to increase the solubility of PTS in water. After the pretreatment period, cardiomyoblasts were challenged with hydrogen peroxide (6.67µM) for 10 min, while cardiac tissue was submitted to a hydroxyl radical generator system (30 min). Cellular viability, oxidative stress biomarkers (e.g. total reactive oxygen species (ROS), carbonyl assay and lipoperoxidation) and the antioxidant response (e.g. sulfhydryl and the antioxidant enzyme activities of superoxide dismutase, catalase and glutathione peroxidase) were evaluated. In cardiomyoblasts, the PTS + HPßCD complex (50µM) increased cellular viability. Moreover, the PTS + HPßCD complex also significantly increased sulfhydryl levels in the cells submitted to an oxidative challenge. In cardiac tissue, lipid peroxidation, carbonyls and ROS levels were significantly increased in the groups submitted to oxidative damage, while the PTS + HPßCD complex significantly reduced ROS levels in these groups. In addition, the PTS + HPßCD complex also provoked increased catalase activity in both experimental protocols. These data suggest that the PTS + HPßCD complex may play a cardioprotective role through a reduction of ROS levels associated with an improved antioxidant response.

Scalable Super-Resolution Synthesis of Core-Vest Composites Assisted by Surface Plasmons.

The behavior of composite nanostructures depends on both size and elemental composition. Accordingly, concurrent control of size, shape, and composition of nanoparticles is key to tuning their functionality. In typical core-shell nanoparticles, the high degree of symmetry during shell formation results in fully encapsulated cores with severed access to the surroundings. We commingle light parameters (wavelength, intensity, and pulse duration) with the physical properties of nanoparticles (size, shape, and composition) to form hitherto unrealized core-vest composite nanostructures (CVNs). Unlike typical core-shells, the plasmonic core of the resulting CVNs selectively maintains physical access to its surrounding. Tunable variations in local temperature profiles ≳50 °C are plasmonically induced over starburst-shaped nanoparticles as small as 50-100 nm. These temperature variations result in CVNs where the shell coverage mirrors the temperature variations. The precision thus offered individually tailors access pathways of the core and the shell.

A silicon carbide array for electrocorticography and peripheral nerve recording.

OBJECTIVE: Current neural probes have a limited device lifetime of a few years. Their common failure mode is the degradation of insulating films and/or the delamination of the conductor-insulator interfaces. We sought to develop a technology that does not suffer from such limitations and would be suitable for chronic applications with very long device lifetimes. APPROACH: We developed a fabrication method that integrates polycrystalline conductive silicon carbide with insulating silicon carbide. The technology employs amorphous silicon carbide as the insulator and conductive silicon carbide at the recording sites, resulting in a seamless transition between doped and amorphous regions of the same material, eliminating heterogeneous interfaces prone to delamination. Silicon carbide has outstanding chemical stability, is biocompatible, is an excellent molecular barrier and is compatible with standard microfabrication processes. MAIN RESULTS: We have fabricated silicon carbide electrode arrays using our novel fabrication method. We conducted in vivo experiments in which electrocorticography recordings from the primary visual cortex of a rat were obtained and were of similar quality to those of polymer based electrocorticography arrays. The silicon carbide electrode arrays were also used as a cuff electrode wrapped around the sciatic nerve of a rat to record the nerve response to electrical stimulation. Finally, we demonstrated the outstanding long term stability of our insulating silicon carbide films through accelerated aging tests. SIGNIFICANCE: Clinical translation in neural engineering has been slowed in part due to the poor long term performance of current probes. Silicon carbide devices are a promising technology that may accelerate this transition by enabling truly chronic applications.

Effects of aerobic exercise training on metabolism of nitric oxide and endothelin-1 in lung parenchyma of rats with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and proliferative obstruction of pulmonary vessels, which promotes a progressive increase in pulmonary vascular resistance (PVR). The effect of exercise training on oxidative stress, metabolism, and markers of nitric oxide (NO) and endothelin-1 (ET-1) was analyzed in the lung tissue of rats with PAH induced by monocrotaline (MCT).Twenty-four Wistar rats were divided into four groups (5-7 animals): sedentary control (SC), sedentary MCT (SM), trained control (TC), and trained MCT (TM). The TC and TM groups participated in a treadmill training protocol (60% VO2 max) for 5 weeks, 3 weeks of which were performed after the injection of MCT (60 mg/kg i.p.) or saline. MCT administration promoted an increase in PVR and right ventricle hypertrophy, and reduction of right ventricle systolic function assessed by echocardiography. These changes were not improved by exercise training. The activity of NO synthase was reduced in the animals of the TC, TM, and SM groups. No significant differences were found in total nitrite concentration and expression of endothelial NO synthase. Moreover, the TM group showed strong staining for iNOS and nitrotyrosine, suggesting an increase in oxidative stress in these animals. In parallel, reduced expression of type B ET-1 receptors was noticed in the SM and TM groups in comparison to controls. In conclusion, the aerobic training protocol was unable to mitigate changes in the metabolism of NO and ET-1, probably because of the disease severity in these animals, especially in the TM group.

Lifetimes of (214)Po and (212)Po measured with Counting Test Facility at Gran Sasso National Laboratory.

The decays of (214)Po into (210)Pb and of (212)Po into (208)Pb tagged by the previous decays from (214)Bi and (212)Bi have been studied inserting quartz vials inside the Counting Test Facility (CTF) at the underground laboratory in Gran Sasso (LNGS). We find that the mean lifetime of (214)Po is (236.00 ± 0.42(stat) ± 0.15(syst)) µs and that of (212)Po is (425.1 ± 0.9(stat) ± 1.2(syst)) ns. Our results are compatible with previous measurements, have a much better signal to background ratio, and reduce the overall uncertainties.

First evidence of pep solar neutrinos by direct detection in Borexino.

We observed, for the first time, solar neutrinos in the 1.0-1.5 MeV energy range. We determined the rate of pep solar neutrino interactions in Borexino to be 3.1±0.6{stat}±0.3{syst} counts/(day·100 ton). Assuming the pep neutrino flux predicted by the standard solar model, we obtained a constraint on the CNO solar neutrino interaction rate of <7.9 counts/(day·100 ton) (95% C.L.). The absence of the solar neutrino signal is disfavored at 99.97% C.L., while the absence of the pep signal is disfavored at 98% C.L. The necessary sensitivity was achieved by adopting data analysis techniques for the rejection of cosmogenic {11}C, the dominant background in the 1-2 MeV region. Assuming the Mikheyev-Smirnov-Wolfenstein large mixing angle solution to solar neutrino oscillations, these values correspond to solar neutrino fluxes of (1.6±0.3)×10{8} cm{-2} s^{-1} and <7.7×10{8} cm{-2} s{-1} (95% C.L.), respectively, in agreement with both the high and low metallicity standard solar models. These results represent the first direct evidence of the pep neutrino signal and the strongest constraint of the CNO solar neutrino flux to date.

Precision measurement of the (7)Be solar neutrino interaction rate in Borexino.

The rate of neutrino-electron elastic scattering interactions from 862 keV (7)Be solar neutrinos in Borexino is determined to be 46.0±1.5(stat)(-1.6)(+1.5)(syst) counts/(day·100 ton). This corresponds to a ν(e)-equivalent (7)Be solar neutrino flux of (3.10±0.15)×10(9) cm(-2) s(-1) and, under the assumption of ν(e) transition to other active neutrino flavours, yields an electron neutrino survival probability of 0.51±0.07 at 862 keV. The no flavor change hypothesis is ruled out at 5.0 σ. A global solar neutrino analysis with free fluxes determines Φ(pp)=6.06(-0.06)(+0.02)×10(10) cm(-2) s(-1) and Φ(CNO)<1.3×10(9) cm(-2) s(-1) (95% C.L.). These results significantly improve the precision with which the Mikheyev-Smirnov-Wolfenstein large mixing angle neutrino oscillation model is experimentally tested at low energy.

[Effectiveness of the treatment with beta-glucan in the HPV-CIN 1 lesions]. / Efficacia del carbossimetilbetaglucano nella regressione delle alterazioni citologiche cervicali di basso grado HPV correlate.

AIM: The aim of the study was to evaluate the effectiveness of the beta-glucan in women with abnormal cytology, including the women with a positive screening for ASCUS-LSIL furtherly divided in women with positive cytology (ASCUS or LSIL) and negative colposcopy and women with abnormal cytology, positive colposcopy and human papilloma virus (HPV)-CIN1 hystology who opted for follow-up. METHODS: From September 2007 to December 2008, 60 women with ASCUS-LSIL diagnosis were recruited at the ambulatory of Lasersurgery and Cervico-Vaginal Patology, Department of Gynecology and Obstetrics of Policlinico Umberto I of Rome. The women was subdivided in two groups: 1) women with cytological diagnosis of ASCUS or LSIL and negative colposcopy; 2) women with abnormal cytology, positive colposcopy and HPV-CIN1 histology, who opted for follow-up. All the women were treated with two cycles of a daily topical application of beta-glucan for 20 consecutive days with a suspension of 10 days. The effects of beta-glucan were analyzed with colposcopy and cytology at 3.6 and 12 months from the beginning of the therapy. RESULTS: After 3 months of treatment, of the 30 women with positive cytology and negative colposcopy, 80% with ASCUS diagnosis resulted negative, 35% with LSIL diagnosis resulted negative; after 6 months 100% with ASCUS diagnosis resulted negative, 70% with LSIL diagnosis resulted negative; after 12 months 85% with LSIL diagnosis resulted negative. Of the 30 women with positive cytology, positive colposcopy and HPV-CIN1 histology after 3 months 20% resulted negative, after 6 months 60% resulted negative and after 12 months 80% resulted negative. The persistence of the HPV-CIN1 histology was verified in the 13% of the women. For these women the definitive treatment was the TFD. CONCLUSION: Our study demonstrate the effectiveness of the treatment with beta-glucan in the women with ASCUS-LSIL lesions and HPV-CIN1 lesions, increasing of the regressions rate after 12 months of the treatment of the 15-20%.

Estimates of lifetime attributable risk of cancer after a single radiation exposure from 64-slice computed tomographic coronary angiography.

AIMS: To estimate the life attributable risk (LAR) of cancer incidence over a wide range of dose radiation exposure and a large spectrum of possible diagnostic computed tomographic coronary angiography (CTCA) scenarios. METHODS: This study included 561 consecutive patients who underwent a successful prospective ECG-gating CTCA protocol (low-dose group) 64-slice CTCA and 188 patients who underwent retrospective ECG-gating CTCA with ECG-triggered dose modulation CTCA (high-dose group). LAR was computed, given the organ equivalent dose, for all cancers in both sexes. LAR was tabulated for each decile of dose-length product by 10-year age classes, separately for each sex. RESULTS: Estimates of LAR of any cancer for an exposure at age < or =40 year were lower in males than in females for any given quantile. At age >/ or =50 years, LAR was similar between sexes only at the lowest exposure doses, whereas at higher dosage, it was, in general, higher for women. At the median age of this case series (62 years) and for a radiation exposure ranging from 1.33 to 3.81 mSv, LAR was 1 in 4329 (or 23.1 per 10(5) persons exposed) and 1 in 4629 (or 21.6 per 10(5) persons) in men and women, respectively. For an exposure ranging from 10.34 to 18.97 mSv at the same median age, the LAR of cancer incidence was 1 in 1336 (or 74.8 per 10(5) persons) in men and doubled (1 in 614 or 162.8 per 10(5) persons) in women. CONCLUSIONS: This study provided an estimate of the LAR of cancer in middle-aged patients of both sexes after a single diagnostic CTCA, providing an easy-to-read table.

Influence of a new slow-release GnRH analogue implant on reproduction in the Budgerigar (Melopsittacus undulatus, Shaw 1805).

The neuroendocrine conditioning of reproduction in birds could perform a very important role in captive breeding, especially in endangered species. Whereas in domestic and wild mammals pharmacological reproductive conditioning is well developed, in birds an effective method is not available. The aim of this study was to test the influence of a new slow-release GnRH analogue (buserelin acetate) implant on the reproductive activity of the Budgerigar (Melopsittacus undulatus), used as model species for captive-bred endangered birds. The effects were assessed by looking at reproductive parameters (egg-laying rate, egg fertility rate) and measuring excreted sex steroid metabolite concentrations in male and female birds. Modification of reproductive parameters and steroid metabolites excretion patterns were observed among birds administered with a GnRH analogue implant and maintained under artificial photoperiod (group I; 16L:8D). Implanted birds showed higher rates of egg-laying, potentially a higher proportion of fertile eggs and higher excreted steroid metabolite concentrations than birds maintained under natural photoperiod (group II; 10L:14D) and birds maintained under artificial photoperiod (group III; 16L:8D). Thus, it is concluded that the new slow-release GnRH analogue implant may represent an innovative and practicable treatment to rapidly induce reproductive activity in the Budgerigar, and that excreted sex hormone metabolites detection permits to monitor male and female gonadal activity.

Direct measurement of the 7Be solar neutrino flux with 192 days of borexino data.

We report the direct measurement of the 7Be solar neutrino signal rate performed with the Borexino detector at the Laboratori Nazionali del Gran Sasso. The interaction rate of the 0.862 MeV 7Be neutrinos is 49+/-3stat+/-4syst counts/(day.100 ton). The hypothesis of no oscillation for 7Be solar neutrinos is inconsistent with our measurement at the 4sigma C.L. Our result is the first direct measurement of the survival probability for solar nu(e) in the transition region between matter-enhanced and vacuum-driven oscillations. The measurement improves the experimental determination of the flux of 7Be, pp, and CNO solar nu(e), and the limit on the effective neutrino magnetic moment using solar neutrinos.

Temporally controlled modulation of antihydrogen production and the temperature scaling of antiproton-positron recombination.

We demonstrate temporally controlled modulation of cold antihydrogen production by periodic RF heating of a positron plasma during antiproton-positron mixing in a Penning trap. Our observations have established a pulsed source of atomic antimatter, with a rise time of about 1 s, and a pulse length ranging from 3 to 100 s. Time-sensitive antihydrogen detection and positron plasma diagnostics, both capabilities of the ATHENA apparatus, allowed detailed studies of the pulsing behavior, which in turn gave information on the dependence of the antihydrogen production process on the positron temperature T. Our data are consistent with power law scaling T (-1.1+/-0.5) for the production rate in the high temperature regime from approximately 100 meV up to 1.5 eV. This is not in accord with the behavior accepted for conventional three-body recombination.

Measurement of the elastic constants of a columnar SiC thin film.

The technique of resonant ultrasound spectroscopy was used to measure the elastic properties of a polycrystalline cubic silicon carbide (3C-SiC) thin film. The film, grown on a silicon (100) substrate, was 1.69 microns thick with columnar crystalline grains and a (111) texture. The substrate with the film was placed between two transducers and the resonant frequencies were measured; measurements were repeated after selective, timed dry etching of the film, allowing a determination of the elastic constants of the film alone. The film elastic constants, c(11)=371 and c(12)=146 GPa, were within a few percent of the literature values (c(11)=386, c(12)=136 GPa) of crystalline 3C-SiC. However, the film elastic constant c(44), 111 GPa, was significantly smaller than the bulk literature value, 254 GPa. For the film, c44 approximately (c(11)-c(12))/2, indicating that, quite unlike a bulk 3C-SiC crystal, the thin film is elastically isotropic.

Evidence for the production of slow antiprotonic hydrogen in vacuum.

We present evidence showing how antiprotonic hydrogen, the quasistable antiproton (p)-proton bound system, has been synthesized following the interaction of antiprotons with the molecular ion H2+ in a nested Penning trap environment. From a careful analysis of the spatial distributions of antiproton annihilation events, evidence is presented for antiprotonic hydrogen production with sub-eV kinetic energies in states around n=70, and with low angular momenta. The slow antiprotonic hydrogen may be studied using laser spectroscopic techniques.

Search for laser-induced formation of antihydrogen atoms.

Antihydrogen can be synthesized by mixing antiprotons and positrons in a Penning trap environment. Here an experiment to stimulate the formation of antihydrogen in the n = 11 quantum state by the introduction of light from a CO2 continuous wave laser is described. An overall upper limit of 0.8% with 90% C.L. on the laser-induced enhancement of the recombination has been found. This result strongly suggests that radiative recombination contributes negligibly to the antihydrogen formed in the experimental conditions used by the ATHENA Collaboration.

Soy isoflavones, lactobacilli, Magnolia bark extract, vitamin D3 and calcium. Controlled clinical study in menopause.

AIM: Affective and behavioural disorders possibly concomitant to the vasomotor menopausal symptoms worsen quality of life. A rational formulation containing soy isoflavones (60 mg), lactobacilli (500 millions spores), calcium (141 mg) and vitamin D3 (5 microg) was added of Magnolia bark extract (60 mg) and magnesium (50 mg) (Estromineral serena, ES). The Magnolia extract active principles interact with GABA system and exhibit a sedative central action. Magnesium intervenes in enzymatic reactions of the energetic metabolism and protects the bone integrity. Aim of this controlled study was to compare the clinical activity and safety of ES versus calcium+vitamin D3 (Ca+D) in menopause. METHODS: A controlled, randomised, multicentre study was carried out in symptomatic menopausal women with sleep or mood alterations. Women received 1 tablet/day of ES or Ca+D for 24 weeks. Symptoms during the treatment and final judgements on efficacy and acceptability were evaluated. RESULTS: Eighty-nine women (44 ES and 45 Ca+D, mean age 53.8 years, in menopause since 56.6 months) participated to the study. Flushing, nocturnal sweating, palpitations, insomnia, asthenia, anxiety, mood depression, irritability, vaginal dryness, dyspareunia, and libido loss, significantly decreased in severity and frequency during ES versus Ca+D treatment even since the fourth week. Woman wellbeing (good/very good 66.7% vs 20%) judgement on efficacy (72.7% vs 17.1%) and acceptability (93.9% vs 31.4%) were significantly better for ES. CONCLUSIONS: The controlled study showed the efficacy of Magnolia extract and magnesium on psycho-affective and sleep disturbances in menopause, in addition to the effects of isoflavones on vasomotor symptoms. A global natural approach to menopause with ES evidenced its therapeutic usefulness and safety.

New source of dense, cryogenic positron plasmas.

We have developed a new method, based on the ballistic transfer of preaccumulated plasmas, to obtain large and dense positron plasmas in a cryogenic environment. The method involves transferring plasmas emanating from a region with a low magnetic field (0.14 T) and relatively high pressure (10(-9) mbar) into a 15 K Penning-Malmberg trap immersed in a 3 T magnetic field with a base pressure better than 10(-13) mbar. The achieved positron accumulation rate in the high field cryogenic trap is more than one and a half orders of magnitude higher than the previous most efficient UHV compatible scheme. Subsequent stacking resulted in a plasma containing more than 1.2 x 10(9) positrons, which is a factor 4 higher than previously reported. Using a rotating wall electric field, plasmas containing about 20 x 10(6) positrons were compressed to a density of 2.6 x 10(10) cm(-3). This is a factor of 6 improvement over earlier measurements.

Spatial distribution of cold antihydrogen formation.

Antihydrogen is formed when antiprotons are mixed with cold positrons in a nested Penning trap. We present experimental evidence, obtained using our antihydrogen annihilation detector, that the spatial distribution of the emerging antihydrogen atoms is independent of the positron temperature and axially enhanced. This indicates that antihydrogen is formed before the antiprotons are in thermal equilibrium with the positron plasma. This result has important implications for the trapping and spectroscopy of antihydrogen.