Perturbation of cytochrome P450, generation of oxidative stress and induction of DNA damage in Cyprinus carpio exposed in situ to potable surface water

Epidemiological evidence suggests a link between consumption of chlorinated drinking water and various cancers. Chlorination of water rich in organic chemicals produces carcinogenic organochlorine by-products (OBPs) such as trihalomethanes and haloacetic acids. Since the discovery of the first OBP in the 1970s, there have been several investigations designed to determine the biological effects of single chemicals or small artificial OBP combinations. However, there is still insufficient information regarding the general biological response to these compounds, and further studies are still needed to evaluate their potential genotoxic effects. In the current study, we evaluated the effect of three drinking water disinfectants on the activity of cytochrome P450 (CYP)-linked metabolizing enzymes and on the generation of oxidative stress in the livers of male and female Cyprinus carpio fish (carp). The fish were exposed in situ for up 20 days to surface water obtained from the Trasmene lake in Italy. The water was treated with 1-2 mg/L of either sodium hypochlorite (NaClO) or chlorine dioxide (ClO2) as traditional disinfectants or with a relatively new disinfectant product, peracetic acid (PAA). Micronucleus (MN) frequencies in circulating erythrocytes from the fish were also analysed as a biomarker of genotoxic effect. In the CYP-linked enzyme assays, a significant induction (up to a 57-fold increase in the deethylation of ethoxyresorufin with PAA treatment) and a notable inactivation (up to almost a 90% loss in hydroxylation of p-nitrophenol with all disinfectants, and of testosterome 2 beta-hydroxylation with NaClO) was observed in subcellular liver preparations from exposed fish. Using the electron paramagnetic resonance (EPR) spectroscopy radical-probe technique, we also observed that CYP-modulation was associated with the production of reactive oxygen species (ROS). In addition, we found a significant increase in MN frequency in circulating erythrocytes after 10 days of exposure of fish to water treated with ClO2, while a non-significant six-fold increase in MN frequency was observed with NaClO, but not with PAA. Our data suggest that the use of ClO2 and NaClO to disinfect drinking water could generate harmful OBP mixtures that are able to perturb CYP-mediated reactions, generate oxidative stress and induce genetic damage. These data may provide a mechanistic explanation for epidemiological studies linking consumption of chlorinated drinking water to increased risk of urinary, gastrointestinal and bladder cancers. (c) 2006 Elsevier B.V. All rights reserved

Haemodynamics and oxygenation improvement induced by high frequency percussive ventilation in a patient with hypoxia following cardiac surgery: a case report

<p>Abstract</p> <p>Introduction</p> <p>High frequency percussive ventilation is a ventilatory technique that delivers small bursts of high flow respiratory gas into the lungs at high rates. It is classified as a pneumatically powered, pressure-regulated, time-cycled, high-frequency flow interrupter modality of ventilation. High frequency percussive ventilation improves the arterial partial pressure of oxygen with the same positive end expiratory pressure and fractional inspiratory oxygen level as conventional ventilation using a minor mean airway pressure in an open circuit. It reduces the barotraumatic events in a hypoxic patient who has low lung-compliance. To the best of our knowledge, there have been no papers published about this ventilation modality in patients with severe hypoxaemia after cardiac surgery.</p> <p>Case presentation</p> <p>A 75-year-old Caucasian man with an ejection fraction of 27 percent, developed a lung infection with severe hypoxaemia [partial pressure of oxygen/fractional inspiratory oxygen of 90] ten days after cardiac surgery. Conventional ventilation did not improve the gas exchange. He was treated with high frequency percussive ventilation for 12 hours with a low conventional respiratory rate (five per minute). His cardiac output and systemic and pulmonary pressures were monitored.</p> <p>Compared to conventional ventilation, high frequency percussive ventilation gives an improvement of the partial pressure of oxygen from 90 to 190 mmHg with the same fractional inspiratory oxygen and positive end expiratory pressure level. His right ventricular stroke work index was lowered from 19 to seven g-m/m²/beat; his pulmonary vascular resistance index from 267 to 190 dynes•seconds/cm⁵/m²; left ventricular stroke work index from 28 to 16 gm-m/m²/beat; and his pulmonary arterial wedge pressure was lowered from 32 to 24 mmHg with a lower mean airway pressure compared to conventional ventilation. His cardiac index (2.7 L/min/m²) and ejection fraction (27 percent) did not change.</p> <p>Conclusion</p> <p>Although the high frequency percussive ventilation was started ten days after the conventional ventilation, it still improved the gas exchange. The reduction of right ventricular stroke work index, left ventricular stroke work index, pulmonary vascular resistance index and pulmonary arterial wedge pressure is directly related to the lower respiratory mean airway pressure and the consequent afterload reduction.</p

A combined analysis technique for the search for fast magnetic monopoles with the MACRO detector

We describe a search method for fast moving ($\beta > 5 \times 10^{-3}$) magnetic monopoles using simultaneously the scintillator, streamer tube and track-etch subdetectors of the MACRO apparatus. The first two subdetectors are used primarily for the identification of candidates while the track-etch one is used as the final tool for their rejection or confirmation. Using this technique, a first sample of more than two years of data has been analyzed without any evidence of a magnetic monopole. We set a 90% CL upper limit to the local monopole flux of $1.5 \times 10^{-15} cm^{-2} s^{-1} sr^{-1}$ in the velocity range $5 \times 10^{-3} \le \beta \le 0.99$ and for nucleon decay catalysis cross section smaller than $\sim 1 mb$.Comment: 29 pages (12 figures). Accepted by Astroparticle Physic

Final results of magnetic monopole searches with the MACRO experiment

We present the final results obtained by the MACRO experiment in the search for GUT magnetic monopoles in the penetrating cosmic radiation, for the range $4\times 10^{-5}< \beta < 1$. Several searches with all the MACRO sub-detectors (i.e. scintillation counters, limited streamer tubes and nuclear track detectors) were performed, both in stand alone and combined ways. No candidates were detected and a 90% Confidence Level (C.L.) upper limit to the local magnetic monopole flux was set at the level of $1.4\times 10^{-16}$ cm$^{-2}$ s$^{-1}$ sr$^{-1}$. This result is the first experimental limit obtained in direct searches which is well below the Parker bound in the whole $\beta$ range in which GUT magnetic monopoles are expected.Comment: 12 pages, Latex, 9 figures and 2 Table

The Observation of Up-going Charged Particles Produced by High Energy Muons in Underground Detectors

An experimental study of the production of up-going charged particles in inelastic interactions of down-going underground muons is reported, using data obtained from the MACRO detector at the Gran Sasso Laboratory. In a sample of 12.2 10^6 single muons, corresponding to a detector livetime of 1.55 y, 243 events are observed having an up-going particle associated with a down-going muon. These events are analysed to determine the range and emission angle distributions of the up-going particle, corrected for detection and reconstruction efficiency. Measurements of the muon neutrino flux by underground detectors are often based on the observation of through-going and stopping muons produced in $\nu_\mu$ interactions in the rock below the detector. Up-going particles produced by an undetected down-going muon are a potential background source in these measurements. The implications of this background for neutrino studies using MACRO are discussed.Comment: 18 pages, 9 figures. Accepted by Astrop. Physic

Nuclearite search with the MACRO detector at Gran Sasso

In this paper we present the results of a search for nuclearites in the penetrating cosmic radiation using the scintillator and track-etch subdetectors of the MACRO apparatus. The analyses cover the beta =v/c range at the detector depth (3700 hg/cm^2) 10^-5 < beta < 1; for beta = 2 x 10^-3 the flux limit is 2.7 x 10^-16 cm^-2 s^-1 sr^-1 for an isotropic flux of nuclearites, and twice this value for a flux of downgoing nuclearites.Comment: 16 pages, 4 Encapsulated Postscript figures, uses article.sty. Submitted to The European Physical Journal

Atmospheric neutrino induced muons in the MACRO detector

A measurement of the flux of neutrino-induced muons using the MACRO detector is presented. Different event topologies, corresponding to different neutrino parent energies can be detected. The upward throughgoing muon sample is the larger event sample. The observed upward-throughgoing muons are 26% fewer than expected and the zenith angle distribution does not fit with the expected one. Assuming neutrino oscillations, both measurements suggest maximum mixing and Dm2 of a few times 10-3 eV2. The other samples are due to the internally produced events and to upward-going stopping muons. These data show a regular deficit of observed events in each angular bin, as expected assuming neutrino oscillations with maximum mixing, in agreement with the analysis of the upward-throughgoing muon sample.Comment: 7 pages 6 figures to appear in the proceedings of XVIII International Conference on Neutrino Physics and Astrophysics (Neutrino'98), Takayama, Japan 4-9 June, 199

New MACRO results on atmospheric neutrino oscillations

The final results of the MACRO experiment on atmospheric neutrino oscillations are presented and discussed. The data concern different event topologies with average neutrino energies of ~3 and ~50 GeV. Multiple Coulomb Scattering of the high energy muons in absorbers was used to estimate the neutrino energy of each event. The angular distributions, the L/E_nu distribution, the particle ratios and the absolute fluxes all favour nu_mu --> nu_tau oscillations with maximal mixing and Delta m^2 =0.0023 eV^2. A discussion is made on the Monte Carlos used for the atmospheric neutrino flux. Some results on neutrino astrophysics are also briefly discussed.Comment: Invited Paper at the NANP03 Int. Conf., Dubna, 200

The Conselice Study of Brain Ageing

Among the age-related diseases, the development of cognitive impairments, in particular dementia, is the most devastating for the individual and has great social and healthcare costs. Accurate information is needed about the prevalence and incidence of cognitive disorders and the physiology of the ageing brain. In particular, only scant data are available about the relationship between ageing, cognitive status and nutritional factors. In order to address these issues we planned the Conselice Study of Brain Ageing, a longitudinal study of physiologic and pathologic brain ageing. The center involved in the study was the municipality of Conselice, Ravenna province, in the Northern Italian region Emilia-Romagna. A total of 1016 subjects aged 65 and over was enrolled at baseline. Information about cognitive status at 4-years of follow-up was collected for 940 of them. These data have been used to estimate prevalence and incidence of dementia in the elderly Italian population and to investigate the possible role of baseline blood homocysteine as risk factors for dementia