DNA damage in circulating leukocytes measured with the comet assay may predict the risk of death

The comet assay or single cell gel electrophoresis, is the most common method used to measure strand breaks and a variety of other DNA lesions in human populations. To estimate the risk of overall mortality, mortality by cause, and cancer incidence associated to DNA damage, a cohort of 2,403 healthy individuals (25,978 person-years) screened in 16 laboratories using the comet assay between 1996 and 2016 was followed-up. Kaplan-Meier analysis indicated a worse overall survival in the medium and high tertile of DNA damage (p < 0.001). The effect of DNA damage on survival was modelled according to Cox proportional hazard regression model. The adjusted hazard ratio (HR) was 1.42 (1.06-1.90) for overall mortality, and 1.94 (1.04-3.59) for diseases of the circulatory system in subjects with the highest tertile of DNA damage. The findings of this study provide epidemiological evidence encouraging the implementation of the comet assay in preventive strategies for non-communicable diseases

Acupuncture for the treatment of severe acute pain in Herpes Zoster: results of a nested, open-label, randomized trial in the VZV Pain Study

<p>Abstract</p> <p>Background</p> <p>Data on the potential efficacy of acupuncture (AC) in controlling intense or very intense pain in patients with Herpes Zoster (HZ) has not been so far adequately assessed in comparison with standard pharmacological treatment (ST) by a controlled trial design.</p> <p>Methods</p> <p>Within the VZV Pescara study, pain was assessed in HZ patients on a Visual Analogue Scale (VAS) and by the McGill Pain Questionnaire (MPQ) both at the beginning and at the end of treatment. Response rates, mean changes in pain intensity, differences in total pain burden with an area-under-the-curve (AUC) method over a 1-year follow-up and differences in the incidence of Post-Herpetic Neuralgia (PHN) were evaluated.</p> <p>Results</p> <p>One hundred and two patients were randomized to receive either AC (n = 52) or ST (n = 50) for 4 weeks. Groups were comparable regarding age, sex, pain intensity at presentation and missed antiviral prescription. Both interventions were largely effective. No significant differences were observed in response rates (81.6% vs 89.2%, p = 0.8), mean reduction of VAS (4.1 +/- 2.3 vs 4.9 +/- 1.9, p = 0.12) and MPQ scores (1.3 +/- 0.9 vs 1.3 +/- 0.9, p = 0.9), incidence of PHN after 3 months (48.4% vs 46.8%, p = 0.5), and mean AUC during follow-up (199 +/- 136 vs 173 +/- 141, p = 0.4). No serious treatment-related adverse event was observed in both groups.</p> <p>Conclusions</p> <p>This controlled and randomized trial provides the first evidence of a potential role of AC for the treatment of acute herpetic pain.</p> <p>Trial registration</p> <p>ChiCTR-TRC-10001146.</p

European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS).

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.The EU-ROS consortium (COST Action BM1203) was supported by the European Cooperation in Science and Technology (COST). The present overview represents the final Action dissemination summarizing the major achievements of COST Action BM1203 (EU-ROS) as well as research news and personal views of its members. Some authors were also supported by COST Actions BM1005 (ENOG) and BM1307 (PROTEOSTASIS), as well as funding from the European Commission FP7 and H2020 programmes, and several national funding agencies

In vivo electron paramagnetic resonance spectroscopy/imaging in experimental oncology: the hope and the reality

Purpose: Low frequency (280 MHz) electron paramagnetic resonance imaging is a new magnetic resonance technique, still being developed, that can map the in vivo spatial distribution of paramagnetic species such as nitroxide free radicals. The reduction rate of these molecules is affected by oxygen concentration. This paper gives some examples of the use of electron paramagnetic resonance imaging methodology in whole rats in the framework of its possible use in experimental oncology. Methods and Materials: The 280 MHz apparatus based on a cylindrical 16 pole magnet was developed and designed specifically for 50-200 g laboratory animals. It generates the main field and the three field gradients required for three-dimensional (3-D) projections. A pyrrolidine nitroxyl (2,2,5,5,-tetramethylpyrrolidine- 1-oxyl-3-carboxylic acid) was injected intravenously in rats to provide an electron paramagnetic resonance signal for in vivo measurements. Electron paramagnetic resonance X-band spectrometer was used to monitor pyrrolidine nitroxyl decay in an external blood circuit during normoxia and moderate hypoxia (15% O-2). Results and Conclusion: One-dimensional (1-D) transversal and longitudinal mapping of this nitroxide free radical distribution in rat whole body was obtained 7-9 min after injection. In circulating blood, nitroxide half-life decreased significantly during hypoxia. The present sensitivity (10(-4)-10(-5) M), spatial resolution (3-10 mm) and collection time (3-5 min) could be drastically improved by narrow linewidth paramagnetic probes and pulsed techniques

pH-sensitive imaging by low-frequency EPR: a model study for biological applications

The use of pH-sensitive nitroxides, in conjunction with low-frequency EPR, offers a unique opportunity for non-invasive;assessment of pH values (in the range 0 to 14) in living animals. In the present study, we have investigated the potential use of pH-sensitive nitroxide free radicals in conjunction with EPR imaging techniques at low and very low frequencies (280 MHz-2.1 GHz). In particular, vie have measured the hyperfine splitting (hfs) of a pH-sensitive probe at three different EPR frequencies: 280 MHz, 1.1 GHz and 2.1 GHz. We have also developed EPR imaging experiments with phantoms simulating in vivo conditions, using pH-sensitive probes at 280 MHz (spatial-spatial) and 1.1 GHz (spectral-spatial). Finally, we discuss the actual sensitivity/resolution limits of the EPR imaging techniques at low frequencies. Practical applications of this method in the biomedical field are suggested for the continuous and non-invasive localization of pH in vivo