TiO2 NPs Induce DNA Damage in Lymphocytes from Healthy Individuals and Patients with Respiratory Diseases-An Ex Vivo/In Vitro Study.

Little is known of the effects of nanoparticles in human systems, let alone in diseased individuals and nanotechnology has preceded nanotoxicology. Therefore, the effects of titanium dioxide (TiO2) nanoparticles in peripheral blood lymphocytes from patients with respiratory diseases [lung cancer, chronic obstructive pulmonary disease (COPD) and asthma] were compared with those in healthy Individuals, to determine differences in sensitivity to nanochemical insult. The Comet assay was performed according to recommended guidelines. The micronucleus assay and ras oncoprotein detection were conducted according to published standard methods. The results showed statistically significant concentration-dependent genotoxic effects of TiO2 NPs in both respiratory patient and control groups in the Comet assay. The TiO2 NPs caused DNA damage in a concentration dependent manner in both groups (respiratory and healthy controls) with the exception of the lowest TiO2 concentration (10 µg/ml) which did not induce significant damage in healthy controls (n.s). When OTM data were used to compare the whole patient group and the control group, the patient group had more DNA damage (p > 0.001) with the exception of 10 µg/ml of TiO2 that caused less significant damage to patient lymphocytes (p < 0.05). Similarly, there was an increase in the pattern of cytogenetic damage measured in the MN assay without statistical significance except when compared to the negative control of healthy individuals. Furthermore, when modulation of ras p21 expression was investigated, regardless of TiO2 treatment, only lung cancer and COPD patients expressed measurable ras p21 levels. Results were achieved in the absence of cytotoxicity.

The effect of sepsis on breathing pattern and weaning outcomes in patients recovering from respiratory failure.

OBJECTIVE: To determine the effects of sepsis on breathing pattern and weaning outcome in medical patients recovering from respiratory failure. DESIGN: Prospective, observational study. SETTING: Medical ICU of a 300-bed community teaching hospital. MEASUREMENTS: Patients were classified as having sepsis or not having sepsis on the first day of weaning. The respiratory rate:tidal volume ratio (RVR), maximal inspiratory pressure (MIP), respiratory system mechanics, minute volume, WBC count, and maximal temperature (Tmax) were recorded for the first day of weaning. Weaning was then conducted by the patients' primary physicians; weaning outcomes and days spent receiving mechanical ventilation were recorded. RESULTS: Sixty patients were studied over 64 separate ICU admissions. Twenty-five patients met criteria for sepsis and had a higher mean APACHE II (acute physiology and chronic health evaluation) score than patients without sepsis (mean+/-SE: 23.4+/-1.3 vs 18.7+/-1.0; p<0.05). Respiratory mechanics, age, and minute volumes were not different between patients with and without sepsis. Patients with sepsis had a higher RVR than patients without sepsis (94.3+/-10.1 vs 66.6+/-6.4 breaths/min/L; p<0.05) and tended to have a lower MIP (25.0+/-2.0 vs 31.0+/-2.3 cm H2O; p=0.055). The MIP and RVR were moderately correlated (r=0.50, p<0.001). WBC count and Tmax did not correlate with RVR in the total population or in sepsis/nonsepsis subpopulations. First-day weaning success was higher in patients without sepsis (17/39=44%) than patients with sepsis (6/25=24%; odds ratio=2.4; 95% confidence interval=0.8 to 7.3). Patients with sepsis tended to require a longer duration of weaning (3.8+/-0.6 vs 2.5+/-0.5 days; p=0.1) and mechanical ventilation (7.4+/-1.0 vs 5.6+/-1.0 days; p=0.2) than patients without sepsis. Differences were not significant when patients were stratified by ICU admission APACHE II scores. CONCLUSIONS: Patients recovering from sepsis breathe with a higher RVR, tend to have a lower MIP, and tend to be more likely to encounter first-day weaning failure compared to patients without sepsis. Our data also suggest that the severity of illness on ICU admission could explain some of these differences.