Environmental Tobacco Smoke in Occupational Settings: Effect and Susceptibility Biomarkers in Workers From Lisbon Restaurants and Bars.

Environmental tobacco smoke (ETS) has been recognized as a major health hazard by environmental and public health authorities worldwide. In Portugal, smoke-free laws are in force for some years, banning smoking in most indoor public spaces. However, in hospitality venues such as restaurants and bars, owners can still choose between a total smoke-free policy or a partial smoking restriction with designated smoking areas, if adequate reinforced ventilation systems are implemented. Despite that, a previous study showed that workers remained continuously exposed to higher ETS pollution in Lisbon restaurants and bars where smoking was still allowed, comparatively to total smoke-free venues. This was assessed by measurements of indoor PM2.5 and urinary cotinine, a biomarkers of tobacco smoke exposure, demonstrating that partial smoking restrictions do not effectively protect workers from ETS. The aim of the present work was to characterize effect and susceptibility biomarkers in non-smokers from those hospitality venues occupationally exposed to ETS comparatively to non-exposed ones. A group of smokers was also included for comparison. The sister chromatid exchange (SCE), micronucleus (MN) and comet assays in whole peripheral blood lymphocytes (PBLs) and the micronucleus assay in exfoliated buccal cells, were used as biomarkers of genotoxicity. Furthermore, a comet assay after ex vivo challenge of leukocytes with an alkylating agent, ethyl methanesulfonate (EMS), was used to analyze the repair capacity of those cells. Genetic polymorphisms in genes associated with metabolism and DNA repair were also included. The results showed no clear association between occupational exposure to ETS and the induction of genotoxicity. Interestingly, the leukocytes from non-smoking ETS-exposed individuals displayed lower DNA damage levels in response to the ex vivo EMS challenge, in comparison to those from non-exposed workers, suggesting a possible adaptive response. The contribution of individual susceptibility to the effect biomarkers studied was unclear, deserving further investigation.

ICD defibrillation failure solved in an unusual fashion.

An implantable cardioverter defibrillator (ICD) is designed to sense life-threatening ventricular arrhythmias and terminate them, either by rapid pacing or by delivering an electrical shock. Nowadays it is a proven therapy for both primary and secondary prevention of sudden cardiac death. The typical configuration of an ICD consists of a right ventricular sensing/defibrillator lead with two coils (one distal, located in the right ventricle, and one proximal, located at the superior vena cava-right atrium junction) and an active can, the so-called "ventricular triad". Although effective in the vast majority of patients, it could be argued that this is not the most rational arrangement in electrical terms, since the main shock vector is anteriorly displaced in relation to the greater portion of the left ventricular mass. We describe a case of an ICD defibrillation failure that was solved by placing an additional defibrillator lead in a tributary of the coronary sinus.

Utility of Pacemaker With Sleep Apnea Monitor to Predict Left Ventricular Overload and Acute Decompensated Heart Failure.

Pacemakers with sleep apnea monitor (SAM) provide an easy tool to assess obstructive sleep apnea over long periods of time. The link between respiratory disturbances at night and the incidence of acute decompensated heart failure (ADHF) is not well established. We aimed at (1) determining the ability of SAM pacemakers to evaluate the extent of left ventricular overload and (2) assess the impact of respiratory disturbances at night on the occurrence of ADHF over 1-year of follow-up. We conducted a single-center prospective study. Consecutive patients with SAM pacemakers were comprehensively assessed. SAM automatically computes a respiratory disturbance index (RDI, apneas/hypopneas per hour - AH/h) in the previous night and the percentage of nights with RDI >20 AH/h in the previous 6 months. Thirty-seven patients were included (79.3 ± 11.2 years, 46% males). A high RDI in the previous night and a higher %nights with increased RDI were associated with increased NT-proBNP values (p = 0.008 and p = 0.013, respectively) and were the sole predictors of increased noninvasive pulmonary capillary wedge pressures (PCWP) in the morning of assessment (p = 0.031 and p = 0.044, respectively). Receiver operating characteristic curve analysis revealed an area under the curve of 0.804 (95% confidence interval 0.656 to 0.953, p = 0.002) for %nights with RDI >20 AH/h in the prediction of high PCWP. Patients with >12.5% of nights with RDI >20AH/h tended to have more ADHF during follow-up (log-rank p = 0.067). In conclusion, a high burden of apneas/hypopneas at night is associated with elevated NT-proBNP and PCWP values and an increased risk of ADHF over 1 year. These patients might benefit from early tailored clinical management.

Genotoxicity of microcystin-LR in in vitro and in vivo experimental models.

Microcystin-LR (MCLR) is a cyanobacterial toxin known for its acute hepatotoxicity. Despite being recognized as tumour promoter, its genotoxicity is far from being completely clarified, particularly in organs other than liver. In this work, we used the comet and/or the micronucleus (MN) assays to study the genotoxicity of MCLR in kidney- (Vero-E6) and liver-derived (HepG2) cell lines and in blood cells from MCLR-exposed mice. MCLR treatment (5 and 20 µM) caused a significant induction in the MN frequency in both cell lines and, interestingly, a similar positive effect was observed in mouse reticulocytes (37.5 µg MCLR/kg, i.p. route). Moreover, the FISH-based analysis of the MN content (HepG2 cells) suggested that MCLR induces both chromosome breaks and loss. On the other hand, the comet assay results were negative in Vero-E6 cells and in mouse leukocytes, with the exception of a transient increase in the level of DNA damage 30 minutes after mice exposure. Overall, the present findings contributed to increase the weight of evidence in favour of MCLR genotoxicity, based on its capacity to induce permanent genetic damage either in vitro or in vivo. Moreover, they suggest a clastogenic and aneugenic mode of action that might underlie a carcinogenic effect.

Genotoxicity evaluation of nanosized titanium dioxide, synthetic amorphous silica and multi-walled carbon nanotubes in human lymphocytes.

Toxicological characterization of manufactured nanomaterials (NMs) is essential for safety assessment, while keeping pace with innovation from their development and application in consumer products. The specific physicochemical properties of NMs, including size and morphology, might influence their toxicity and have impact on human health. The present work aimed to evaluate the genotoxicity of nanosized titanium dioxide (TiO2), synthetic amorphous silica (SAS) and multiwalled carbon nanotubes (MWCNTs), in human lymphocytes. The morphology and size of those NMs were characterized by transmission electron microscopy, while the hydrodynamic particle size-distributions were determined by dynamic light scattering. Using a standardized procedure to ensure the dispersion of the NMs and the cytokinesis-block micronucleus assay (without metabolic activation), we observed significant increases in the frequencies of micronucleated binucleated cells (MNBCs) for some TiO2 NMs and for two MWCNTs, although no clear dose-response relationships could be disclosed. In contrast, all forms of SAS analyzed in this study were unable to induce micronuclei. The present findings increase the weight of evidence towards a genotoxic effect of some forms of TiO2 and some MWCNTs. Regarding safety assessment, the differential genotoxicity observed for closely related NMs highlights the importance of investigating the toxic potential of each NM individually, instead of assuming a common mechanism and equal genotoxic effects for a set of similar NMs.