Cardiac oxidative stress and inflammatory cytokines response after myocardial infarction

Oxidative stress in heart failure or during ischemia/reperfusion occurs as a result of the excessive generation or accumulation of free radicals or their oxidation products. Free radicals formed during oxidative stress can initiate lipid peroxidation, oxidize proteins to inactive states and cause DNA strand breaks. Oxidative stress is a condition in which oxidant metabolites exert toxic effects because of their increased production or an altered cellular mechanism of protection. In the early phase of acute heart ischemia cytokines have the feature to be functional pleiotropy and redundancy, moreover, several cytokines exert similar and overlapping actions on the same cell type and one cytokine shows a wide range of biological effects on various cell types. Activation of cytokine cascades in the infarcted myocardium was established in numerous studies. In experimental models of myocardial infarction, induction and release of the pro-inflammatory cytokines like TNF-&alpha (Tumor Necrosis Factor &alpha), IL-1&beta (Interleukin- 1&beta) and IL-6 (Interleukin-6) and chemokines are steadily described. The current review examines the role of oxidative stress and pro-inflammatory cytokines response following acute myocardial infarction and explores the inflammatory mechanisms of cardiac injur

Antioxidant Effect of the Castanea sativa Mill. Leaf Extract on Oxidative Stress Induced upon Human Spermatozoa

This study was aimed at evaluating in vitro the effects of a 75% v/v ethanolic extract of leaves of Castanea sativa Mill. (var. Bastarda Rossa, Mount Amiata, Tuscany, Italy) on ejaculated human sperm. Total polyphenols and total flavonoids contained in the extract were determined by a colorimetric assay and HPLC-DAD. The DPPH test and electrochemistry were utilized to study the antioxidant activity of the extract. Swim-up-selected sperm from 8 healthy men were treated with the C. sativa leaf extract at different dilutions (1: 100, 1: 200, and 1: 500), and sperm motility was assessed following the WHO guidelines. Swim-up-selected spermatozoa were incubated with 100 μM H2O2 to induce lipid peroxidation (LPO) and with H2O2 and the leaf extract (1: 100, 1: 200, and 1: 500) to test the antioxidant activity of the extract. The levels of LPO were determined by measuring malondialdehyde (MDA) concentrations. The treated samples were also analyzed by transmission electron microscopy (TEM) for ultrastructural evaluation. The chemical analysis showed that one-third ca. of the polyphenols in the C. sativa extract were made up of flavonoids, with hyperoside present in high concentration. A good antioxidant activity was demonstrated by both the DPPH test and electrochemical analysis. The C. sativa leaf extract did not decrease sperm motility at all tested dilutions. Treatment with H2O2 alone caused a significant increment in MDA levels (P=0.006993), while the treatment with H2O2 plus C. sativa extract diluted to 1: 100 and 1: 200 significantly reduced MDA levels (P=0.01476 and P=0.01571, respectively), with respect to H2O2 alone. TEM analysis confirmed the protective effect of the extract on damage induced by LPO, in particular that occurring at the plasma membrane level. The C. sativa leaf extract could be used in human and farm animal protocols for gamete handling, such as techniques of assisted reproduction and cryopreservation of semen, all conditions in which oxidative stress is exacerbated

PRELIMINARY CHEMICAL CHARACTERIZATION OF TUNISIN MONOVARIETAL VIRGIN OLIVE OILS AND COMPARISON WITH SICILIAN ONES.

Work was carried out on the characterization of monovarietal virgin olive oils (VOO) from Tunisia and Sicily (Italy). The two main Tunisian VOO (cvv. Ch\ue9toui of the North and cv. Chemlali grown in the Center and some regions of the South) and three principal Sicilian VOO (cvv. Nocellara del Belice, Biancolilla and Cerasuola) were studied. Moreover, the Ch\ue9toui oils were tested in a rain-fed control and an irrigation regime. All olive samples were picked at three different stages of ripeness. Analyses of major components (fatty acids and triacylglycerols) and minor ones (squalene, tocopherols and phenolic compounds) were carried out. Ch\ue9toui oils had a higher level of phenolic compounds followed by Chemlali. Generally, in the Sicilian oils these natural antioxidant contents were lower. These preliminary results indicate that it was possible to classify the Tunisian and Sicilian oils tested in their original growing area based on their chemical composition

Different renal phenotypes in related adult males with Fabry disease with the same classic genotype

BACKGROUND: Fabry disease related patients with classical mutation usually exhibit similar severe phenotype especially concerning renal manifestation. METHODS: A dry blood spot screening (DBS) and the DNA analysis has been performed in a 48-year-old man (Patient 1) because of paresthesia. RESULTS: The DBS revealed absent leukocyte \u3b1-Gal A enzyme activity while DNA analysis identified the I354K mutation. Serum creatinine and e-GFR were in normal range and also albuminuria and proteinuria were absent. The brain MRI showed ischemic lesions and a diffuse focus of gliosis in the white matter, while the echocardiogram showed a left ventricular hypertrophy. The renal biopsy performed in the case index showed a massive deposition of zebra bodies. By a familiar investigation, it was recognized that his brother (Patient 2) died 2 years before from sudden death syndrome at the age of 49. He had suffered sporadic and undiagnosed pain at the extremities, a prior cataract, bilateral neurosensorial hearing loss and left ventricular hypertrophy on Echocardiogram. His previous laboratory examinations revealed a normal serum creatinine and the absence of proteinuria. Pedigree analysis of the brothers revealed a high disease burden among family members, with an affected cousin (Patient 3) who progressed early to end-stage renal disease (ESRD) that required renal transplantation. CONCLUSIONS: Here we describe the clinical history of three adult male members of the same family with the same genotype who manifested different presentation and progression of the disease, particularly concerning the renal involvement

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

A novel biweekly pancreatic cancer treatment schedule with gemcitabine, 5-fluorouracil and folinic acid

Pancreatic adenocarcinoma is a common disease considered to be poorly responsive to antiblastic treatment. Recent clinical and preclinical results suggest that a combined treatment of gemcitabine (GEM), 5-flurouracil (5-FU) and folinic acid (FA) offers a clinical benefit in patients with advanced pancreas adenocarcinoma. The aim of this phase II clinical trial was to evaluate the antitumour activity and toxicity of a novel biweekly schedule of this combination in patients with pancreatic adenocarcinoma. A total of 42 patients received a 30 min infusion of FA (100 mgm2) and 5-FU (400 mgm2) (FUFA) on days 1–3, and GEM 1000 mgm2 on day 1 every 15 days. We observed 13 objective responses (two complete, 11 partial) and 23 stable diseases. The median time to progression was 9.75 months (95% Confidence Interval (CI), 6.88–12.62) and the median overall survival was 13.10 months (95% CI 9.64–16.56). There were seven cases of each grade III gastroenteric and haematological toxicity. The GEM plus FUFA combination appears to be well tolerated and very active in patients with pancreatic carcinoma

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands

A Standard Siren Measurement of the Hubble Constant from GW170817 without the Electromagnetic Counterpart

We perform a statistical standard siren analysis of GW170817. Our analysis does not utilize knowledge of NGC 4993 as the unique host galaxy of the optical counterpart to GW170817. Instead, we consider each galaxy within the GW170817 localization region as a potential host; combining the redshifts from all of the galaxies with the distance estimate from GW170817 provides an estimate of the Hubble constant, H 0. Considering all galaxies brighter than $0.626{L}_{B}^{\star }$ as equally likely to host a binary neutron star merger, we find ${H}_{0}={77}_{-18}^{+37}$ km s−1 Mpc−1 (maximum a posteriori and 68.3% highest density posterior interval; assuming a flat H 0 prior in the range $\left[10,220\right]$ km s−1 Mpc−1). We explore the dependence of our results on the thresholds by which galaxies are included in our sample, and we show that weighting the host galaxies by stellar mass or star formation rate provides entirely consistent results with potentially tighter constraints. By applying the method to simulated gravitational-wave events and a realistic galaxy catalog we show that, because of the small localization volume, this statistical standard siren analysis of GW170817 provides an unusually informative (top 10%) constraint. Under optimistic assumptions for galaxy completeness and redshift uncertainty, we find that dark binary neutron star measurements of H 0 will converge as $40 \% /\sqrt{(N)}$, where N is the number of sources. While these statistical estimates are inferior to the value from the counterpart standard siren measurement utilizing NGC 4993 as the unique host, ${H}_{0}={76}_{-13}^{+19}$ km s−1 Mpc−1 (determined from the same publicly available data), our analysis is a proof-of-principle demonstration of the statistical approach first proposed by Bernard Schutz over 30 yr ago

First measurement of the Hubble Constant from a Dark Standard Siren using the Dark Energy Survey Galaxies and the LIGO/Virgo Binary–Black-hole Merger GW170814

International audienceWe present a multi-messenger measurement of the Hubble constant H 0 using the binary–black-hole merger GW170814 as a standard siren, combined with a photometric redshift catalog from the Dark Energy Survey (DES). The luminosity distance is obtained from the gravitational wave signal detected by the Laser Interferometer Gravitational-Wave Observatory (LIGO)/Virgo Collaboration (LVC) on 2017 August 14, and the redshift information is provided by the DES Year 3 data. Black hole mergers such as GW170814 are expected to lack bright electromagnetic emission to uniquely identify their host galaxies and build an object-by-object Hubble diagram. However, they are suitable for a statistical measurement, provided that a galaxy catalog of adequate depth and redshift completion is available. Here we present the first Hubble parameter measurement using a black hole merger. Our analysis results in , which is consistent with both SN Ia and cosmic microwave background measurements of the Hubble constant. The quoted 68% credible region comprises 60% of the uniform prior range [20, 140] km s−1 Mpc−1, and it depends on the assumed prior range. If we take a broader prior of [10, 220] km s−1 Mpc−1, we find (57% of the prior range). Although a weak constraint on the Hubble constant from a single event is expected using the dark siren method, a multifold increase in the LVC event rate is anticipated in the coming years and combinations of many sirens will lead to improved constraints on H 0