The role of nanotoxicology in realizing the ‘helping without harm’ paradigm of nanomedicine: lessons from studies of pulmonary effects of single‐walled carbon nanotubes

Nano‐sized materials and nano‐scaled processes are widely used in many industries. They are being actively introduced as diagnostic and therapeutic in biomedicine and they are found in numerous consumer products. The small size of nanoparticles, comparable with molecular machinery of cells, may affect normal physiological functions of cells and cause cytotoxicity. Their toxic potential cannot be extrapolated from studies of larger particles due to unique physicochemical properties of nanomaterials. Therefore, the use of nanomaterials may pose unknown risks to human health and the environment. This review discusses several important issues relevant to pulmonary toxicity of nanoparticles, especially single‐walled carbon nanotubes (SWCNT), their direct cytotoxic effects, their ability to cause an inflammatory response, and induce oxidative stress upon pharyngeal aspiration or inhalation. Further, recognition and engulfment of nanotubes by macrophages as they relate to phagocytosis and bio‐distribution of nanotubes in tissues and circulation are discussed. The immunosuppressive effects of CNT and their significance in increased sensitivity of exposed individuals to microbial infections are summarized. Finally, data on biodegradation of SWCNT by oxidative enzymes of inflammatory cells are presented in lieu of their persistence and distribution in the body.     

Mass spectrometric analysis of tobacco-specific nitrosamine-DNA adducts in smokers and nonsmokers

A gas chromatography, negative ion chemical ionization mass spectrometry (GC-NICI-MS) based assay for tobacco-specific nitrosamine adducts of DNA is described. The assay is based on the observation that acid hydrolysis of DNA from animals treated with tobacco-specific nitrosamines releases 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB). HPB and the internal standard [4,4-D2]HPB are derivatized with pentafluorobenzoyl chloride and the resulting HPB-pentafluorobenzoate is purified by high-performance liquid chromatography prior to GC-NICI-MS analysis. DNA from human peripheral lung and tracheobronchial tissue, collected at autopsy, was analyzed for acid-released HPB. The mean HPB level (fmol/mg of DNA) for peripheral lung DNA was 11 +/- 16 (SD, n = 9) for smokers and 0.9 +/- 2.3 (n = 8) for nonsmokers. Mean adduct levels in tracheobronchus were 16 +/- 18 (n = 4) for smokers and 0.9 +/- 1.7 (n = 4) for nonsmokers. These are the first measurements of tobacco-specific nitrosamine-DNA adducts in humans. Further studies comparing the levels of DNA and globin adducts will provide a better understanding of the metabolic activation of tobacco-specific nitrosamines in humans and may provide a more accurate indication of an individual's risk of developing tobacco-related cancer.     

Experimenteller und epidemiologischer Beitrag zur aktiven Immunisierung gegen die Frühling-Sommer-Zeckenencephalitis

Ohne Zusammenfassung     

Visceral pleural thickening in asbestos exposure: the occurrence and implications of thickened interlobar fissures

We evaluated fissural (ie, visceral pleural) thickening on radiographs in two asbestos-exposed study populations and a control group. Asbestos workers had an incidence of fissural thickening of 54.5% compared with 16.0% in the unexposed control group, with a strong positive statistical effect due to asbestos exposure beyond that attributable to age. Fissural thickening occurred in 85% of workers with parietal plaques and in 36% without pleural plaques. Fissural thickening occurred in 45% without radiographic evidence of pulmonary fibrosis, but it was very common (85%) in those with pulmonary fibrosis. Data analysis showed that fissural thickening responds more strongly to asbestos exposure than does plaque formation, with 21 years of asbestos exposure needed for a 50% chance of developing fissural thickening, while 31 years of exposure were needed for a 50% chance of forming pleural plaques. From a second group of 57 asbestos workers evaluated clinically, 8 were diagnosed as having asbestosis with radiographically clear lungs and fissural thickening. We conclude that visceral pleural thickening is common in asbestos exposure, that it is related to the years since first asbestos exposure, and that its presence may indicate the presence of pulmonary asbestosis, even with radiographically normal lungs.     

A neurosurgical view of anatomical evaluation of anterior C1–C2 for safer transoral odontoidectomy

An anatomical study for evaluation of anterior C1–C2. To provide essential anatomic data for safer transoral odontoidectomy. The surface dimensions of the atlas vertebra and the transoral approach for odontoidectomy have been described in detail. Anterior arcus of C1 must be drilled out to reach odontoid process for transoral odontoidectomy. The thickness of anterior ring of C1 has not been studied before. Sixty, dried adult atlas and 60 axis vertebrae and ten cadaveric craniocervical specimens were measured for the following: (1) bony drilling depth (BDD), the distance from the anterior wall of anterior ring of C1 to anterior wall of odontoid; (2) minimum drilling diameter (MDD), distance of minimum C1 anterior ring removal for odontoid resection on horizontal plane; (3) maximum bony drilling diameter (MBDD), distance of maximum C1 anterior ring removal for odontoid resection on horizontal plane. Lateral border of this diameter is limited by medial borders of the lateral mass; (4) the widest odontoid diameters (WOD) on coronal sections were measured. On 60 atlas and axis vertebrae, the BDD was 7.0 ± 1.2 mm on dry bones, the distance between the medial borders of the lateral mass (MBDD) was 16.1 ± 1.5 mm, and the WOD on coronal sections (WOD) was 9.8 ± 0.8 mm. On cadavers, the distance between the two edges of C1 anterior ring removal for odontoid resection (MDD) was 10.8 ± 1.1 mm and the WOD on coronal sections (WOD) was 10.1 ± 1.4 mm. An odontoid surgery through transoral approach is safe and feasible. A quantitative understanding of the anterior anatomy of C-1 and C-2 is necessary when considering transoral odontoid resection. In this study the authors define safe zones for anterior atlas and axis.     

Rhinocerebral mucormycosis in patients with burns: case report and review of the literature.

Mucormycosis is an opportunistic infection most commonly occurring in patients with impaired host defenses or diabetes mellitus. In patients with burns the rhinocerebral form is rare, and mucormycotic infections more commonly involve the cutaneous burn wound. Both forms are associated with a high mortality rate that increases with delays in treatment. The initial management of these types of infections includes vigorous glucose control, correction of acidosis, and the administration of systemic antifungal agents such as amphotericin B. The rhinocerebral form of mucormycosis is extremely virulent and may warrant the use of interstitial and intraventricular antifungal therapy. Despite these measures, the mainstay of treatment for both forms of mucormycosis is the extensive surgical débridement of all infected and necrotic tissue.