To evaluate the in vitro effects of resveratrol (RSV) incubation on platelets from compensated and decompensated diabetic patients in order to use it as an adjuvant therapy. The study was performed ...on 77 diabetic patients and divided into two phases: 29 compensated and 48 decompensated diabetic platelets were analyzed at recruitment (
T
0
) and after in vitro RSV incubation (20 μg/ml) for 3 h at 37 °C (
T
1
). Lipoperoxide and nitric oxide (NO) levels, superoxide dismutase (SOD) and Na
+
/K
+
ATPase activities, total antioxidant capacity (TAC), and membrane fluidity tested by anisotropy of fluorescent probes TMA-DPH and DPH were determined. In vitro RSV incubation counteracts oxidative damage associated with diabetes and its complications; it is able to improve platelet function through augmented membrane fluidity and Na
+
/K
+
ATPase activity; it enhances antioxidant systems’ functionality by increasing NO levels, SOD activity, and TAC and by decreasing lipoperoxide levels in both compensated and decompensated patients. Such platelet functionality enhancement suggests a new method of secondary prevention of complications associated with platelet dysfunction. Being free from one of the major risks associated with many antidiabetic agents, it can be assumed that RSV utilization in the diabetic diet may have a preventive and protective role in the progression of diabetic oxidative damage.
Production of reactive oxygen species after cerebral blood flow disruption may enhance tissue damage through multiple molecular pathways. Changes in nitric oxide (NO) metabolism and oxidative stress ...status were investigated in 47 patients with ischemic stroke by measuring plasma nitric oxide (NO) and peroxynitrite (ONOO
–
) levels.A correlation was sought between these two parameters and i) baseline stroke severity based on the National Institute of Health stroke scale (NIHSS) and ii) neurological outcome in terms of NIHSS changes from entry (T
0
) to 30 days after symptom onset (T
1
). The control group consisted of 30 age- and sex-matched healthy subjects. Mean plasma levels of ONOO
–
(arbitrary fluorescence number ± SD) were significantly higher in patients (7.70 ± 1.71 vs 5.35 ± 0.69, p < 0.001), whereas mean NO levels (nmol/mg protein) were significantly higher in controls (115.40 ± 12.40 vs. 51.10 ± 12.50, p < 0.001). Plasma ONOO
–
was significantly higher among patients with non-lacunar stroke (8.48 ± 1.50 vs. 6.95 ± 1.58 in those with lacunar stroke; p = 0.001), whereas NO levels were significantly higher among lacunar stroke patients (60.00 ± 7.86, vs. 41.77 ± 9.29 in patients with nonlacunar stroke; p < 0.001). Nitric oxide plasma levels were also associated with an unfavorable evolution in non-lacunar stroke, since a 10 unit increase in NO predicted a 1 point reduction in the NIHSS score at T1. Findings show that changes in NO metabolism may be considered as markers of brain injury in patients with ischemic stroke. Further work is needed to establish whether the amount of biochemical changes related to oxidative stress may influence outcome in these patients.
The design of the MEG II experiment Baldini, A. M.; Baracchini, E.; Bemporad, C. ...
The European physical journal. C, Particles and fields,
05/2018, Volume:
78, Issue:
5
Journal Article
Peer reviewed
Open access
The MEG experiment, designed to search for the
μ
+
→
e
+
γ
decay, completed data-taking in 2013 reaching a sensitivity level of
5.3
×
10
-
13
for the branching ratio. In order to increase the ...sensitivity reach of the experiment by an order of magnitude to the level of
6
×
10
-
14
, a total upgrade, involving substantial changes to the experiment, has been undertaken, known as MEG II. We present both the motivation for the upgrade and a detailed overview of the design of the experiment and of the expected detector performance.
The final results of the search for the lepton flavour violating decay
μ
+
→
e
+
γ
based on the full dataset collected by the MEG experiment at the Paul Scherrer Institut in the period 2009–2013 and ...totalling
7.5
×
10
14
stopped muons on target are presented. No significant excess of events is observed in the dataset with respect to the expected background and a new upper limit on the branching ratio of this decay of
B
(
μ
+
→
e
+
γ
)
<
4.2
×
10
-
13
(90 % confidence level) is established, which represents the most stringent limit on the existence of this decay to date.
Letter of intent for KM3NeT 2.0 Adrián-Martínez, S; Aharonian, F; Aiello, S ...
Journal of physics. G, Nuclear and particle physics,
08/2016, Volume:
43, Issue:
8
Journal Article
Peer reviewed
Open access
The main objectives of the KM3NeT Collaboration are (i) the discovery and subsequent observation of high-energy neutrino sources in the Universe and (ii) the determination of the mass hierarchy of ...neutrinos. These objectives are strongly motivated by two recent important discoveries, namely: (1) the high-energy astrophysical neutrino signal reported by IceCube and (2) the sizable contribution of electron neutrinos to the third neutrino mass eigenstate as reported by Daya Bay, Reno and others. To meet these objectives, the KM3NeT Collaboration plans to build a new Research Infrastructure consisting of a network of deep-sea neutrino telescopes in the Mediterranean Sea. A phased and distributed implementation is pursued which maximises the access to regional funds, the availability of human resources and the synergistic opportunities for the Earth and sea sciences community. Three suitable deep-sea sites are selected, namely off-shore Toulon (France), Capo Passero (Sicily, Italy) and Pylos (Peloponnese, Greece). The infrastructure will consist of three so-called building blocks. A building block comprises 115 strings, each string comprises 18 optical modules and each optical module comprises 31 photo-multiplier tubes. Each building block thus constitutes a three-dimensional array of photo sensors that can be used to detect the Cherenkov light produced by relativistic particles emerging from neutrino interactions. Two building blocks will be sparsely configured to fully explore the IceCube signal with similar instrumented volume, different methodology, improved resolution and complementary field of view, including the galactic plane. One building block will be densely configured to precisely measure atmospheric neutrino oscillations.
The next generation of water Cherenkov neutrino telescopes in the Mediterranean Sea are under construction offshore France (KM3NeT/ORCA) and Sicily (KM3NeT/ARCA). The KM3NeT/ORCA detector features an ...energy detection threshold which allows to collect atmospheric neutrinos to study flavour oscillation. This paper reports the KM3NeT/ORCA sensitivity to this phenomenon. The event reconstruction, selection and classification are described. The sensitivity to determine the neutrino mass ordering was evaluated and found to be 4.4
σ
if the true ordering is normal and 2.3
σ
if inverted, after 3 years of data taking. The precision to measure
Δ
m
32
2
and
θ
23
were also estimated and found to be
85
.
10
-
6
eV
2
and
(
-
3.1
+
1.9
)
∘
for normal neutrino mass ordering and,
75
.
10
-
6
eV
2
and
(
-
7.0
+
2.0
)
∘
for inverted ordering. Finally, a unitarity test of the leptonic mixing matrix by measuring the rate of tau neutrinos is described. Three years of data taking were found to be sufficient to exclude
event rate variations larger than 20% at
3
σ
level.
Background This study was performed to understand the metabolic effects of raloxifene, a selective oestrogen receptor modulator, on platelets in healthy non‐obese postmenopausal women. The data were ...compared to untreated subjects.
Materials and methods Platelet nitric oxide activity (NO) and peroxynitrite level, platelet inducible and endothelial nitric oxide synthase expression and plasma lipids were evaluated at baseline and after 12 months of raloxifene or placebo treatment.
Results A significant increase of platelet NO and reduction of platelet peroxynitrite levels, as well as a decrease of inducible nitric oxide synthase expression, was observed 12 months after raloxifene therapy as compared to baseline or placebo treatment. Moreover, raloxifene treatment caused a significant increase in high‐density lipoprotein cholesterol and a decrease of total cholesterol and low‐density lipoprotein cholesterol were observed versus baseline values (P < 0·05). A significant positive correlation was observed between high‐density lipoprotein cholesterol and platelet NO (r = 0·76, P < 0·005) in the raloxifene group.
Conclusion Our results showed that raloxifene improves platelet metabolism in healthy postmenopausal women through an increase of the bioavailability of platelet NO by a reduction of iNOS and the beneficial effects on lipid metabolism. This mechanism of action of raloxifene on platelet activity may explain some cardiovascular protective effects of this selective oestrogen receptor modulator.
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