Genotoxicity of synthetic amorphous silica nanoparticles in rats following short‐term exposure. Part 1: Oral route

Synthetic amorphous silica (SAS) in its nanosized form is now used in food applications although the potential risks for human health have not been evaluated. In this study, genotoxicity and oxidative DNA damage of two pyrogenic (NM‐202 and 203) and two precipitated (NM‐200 and ‐201) nanosized SAS were investigated in vivo in rats following oral exposure. Male Sprague Dawley rats were exposed to 5, 10, or 20 mg/kg b.w./day for three days by gavage. DNA strand breaks and oxidative DNA damage were investigated in seven tissues (blood, bone marrow from femur, liver, spleen, kidney, duodenum, and colon) with the alkaline and the (Fpg)‐modified comet assays, respectively. Concomitantly, chromosomal damage was investigated in bone marrow and in colon with the micronucleus assay. Additionally, malondialdehyde (MDA), a lipid peroxidation marker, was measured in plasma. When required, a histopathological examination was also conducted. The results showed neither obvious DNA strand breaks nor oxidative damage with the comet assay, irrespective of the dose and the organ investigated. Similarly, no increases in chromosome damage in bone marrow or lipid peroxidation in plasma were detected. However, although the response was not dose‐dependent, a weak increase in the percentage of micronucleated cells was observed in the colon of rats treated with the two pyrogenic SAS at the lowest dose (5 mg/kg b.w./day). Additional data are required to confirm this result, considering in particular, the role of agglomeration/aggregation of SAS NMs in their uptake by intestinal cells. Environ. Mol. Mutagen. 56:218–227, 2015. © 2014 Wiley Periodicals, Inc.     

Prognostic index to identify patients who may not benefit from whole brain radiotherapy for multiple brain metastases from lung cancer

Palliative whole brain radiotherapy (WBRT) is often recommended in the management of multiple brain metastases. Allowing for WBRT waiting time, duration of the WBRT course and time to clinical response, it may take 6 weeks from the point of initial assessment for a benefit from WBRT to manifest. Patients who die within 6 weeks (‘early death’) may not benefit from WBRT and may instead experience a decline in quality of life. This study aimed to develop a prognostic index (PI) that identifies the subset of patients with lung cancer with multiple brain metastases who may not benefit from WBRT because of ‘early death’. The medical records of patients with lung cancer who had WBRT recommended for multiple brain metastases over a 10-year period were retrospectively reviewed. Patients were classified as either having died within 6 weeks or having lived beyond 6 weeks. Potential prognostic indicators were evaluated for correlation with ‘early death’. A PI was constructed by modelling the survival classification to determine the contribution of these factors towards shortened survival. Of the 275 patients recommended WBRT, 64 (23.22%) died within 6 weeks. The main prognostic factor predicting early death was Eastern Cooperative Oncology Group (ECOG) status >2. Patients with a high PI score (>13) were at higher risk of ‘early death’. Twenty-three per cent of patients died prior to benefit from WBRT. ECOG status was the most predictive for ‘early death’. Other factors may also contribute towards a poor outcome. With further refinement and validation, the PI could be a valuable clinical decision tool.     

Bariatric surgery and the gut-brain communication—The state of the art three years later

ObjectiveThis review analyzes the literature concerning gut peptides and bariatric surgery, from 2005 to July 2009. In particular, we are interested in whether, and how, gastrointestinal peptide alterations following surgery interfere with appetite/satiety, and what role they might play in the resolution of comorbidities.Research methods and procedurePubMed/MEDLINE and ISI Web of Knowledge were used to search for human studies concerning gut peptides profiles after any bariatric operation technique.ResultsMost of the studies reviewed had longitudinal design, short follow-up, and low statistical power. The diversity of study results may be partially explained by methodological aspects. Glucagon-like peptide-1, gastric inhibitory peptide, and peptide YY alterations may contribute to the excellent results in glycemic control of diabetics. Results do vary depending on bariatric operation technique; this is particularly evident in the case of ghrelin, which has been much studied in recent years. Ghrelin suppression has been linked to increased satiety, alterations in energy homeostasis, and better glucose metabolism.ConclusionsThere is a lack of long-term data on gastrointestinal hormone profiles after bariatric surgery and the studies have many methodological pitfalls. We still need prospective, long-term, good methodological studies in this area.     

Non-cultured cell transplantation in an ovine model of non-ischemic heart failure.

OBJECTIVE: Cell therapy may be a promising alternative or adjunct to current treatment modalities for ischemic heart failure. But little is known on the impact of myogenic cell transplantation in large animal models of non-ischemic cardiomyopathy. The aim of the present study was to explore whether an ovine model of toxin-induced heart disease could benefit from non-cultured skeletal muscle cell transplantation. METHODS: Sequential intracoronary injections of doxorubicin (0.75 mg/kg) were carried out every 2 weeks until echocardiographic detection of myocardial dysfunction. Sheep were then randomly assigned to either non-cultured cell transplantation (n=8) or placebo injection (n=5). For the cell therapy group, a skeletal muscle biopsy (about 10 g) was explanted from each animal approximately 3h before grafting. After thoracotomy, 20 epicardial injections were carried out. The animals were assessed one last time before sacrifice, 2 months after the thoracotomy. Cells were tracked with cmDiI (red fluorescence) and characterized with immunohistochemistry with monoclonal antibodies to a fast skeletal isoform of myosin heavy chain. RESULTS: Two months after intramyocardial grafting, tissue Doppler imaging and conventional echocardiographic assessment of the groups showed a marked improvement in the non-cultured cell therapy group. Ejection fraction (EF) (p<0.05) as well as systolic endocardial velocities (p<0.01) improved versus the placebo group. CmDiI and skeletal myosin heavy chain expression was detected in all animals at 2 months after implantation confirming engraftment of skeletal muscle cells. CONCLUSIONS: In conclusion, our data indicate that non-cultured muscle cell transplantation is feasible and may translate into a functional benefit in an ovine model of dilated heart failure.     

Paediatric medulloblastoma: Patterns of care and radiotherapy quality assurance in Australia

The purpose of this study was to document how children in Australia with medulloblastoma are being treated and to evaluate the quality of radiotherapy (RT) delivered. The Radiotherapy Database of the Australian and New Zealand Children’s Haematology and Oncology Group was used to identify 46 children with medulloblastoma younger than the age of 15 years treated with radical intent by craniospinal irradiation between 1997 and 1999 inclusively. Twenty‐six patients had completely resected disease without evidence of disease spread. Of these, 16 patients received a craniospinal RT dose of <25 Gy in addition to chemotherapy. RT treatment immobilization methods varied, as did planning methods. RT dose to critical structures was recorded on treatment plans for only 15% of patients. The average systematic error in shield placement at the posterior orbit was 5.2 mm, and two‐thirds of patients were ‘overshielded’ at this site. Adequate coverage of the distal end of the thecal sac was achieved in fewer than 50% of on‐treatment verification films for 21 of 45 patients. With a reduction in RT dose to the craniospinal axis for paediatric medulloblastoma, greater attention is needed for patient immobilization, documentation of RT dose to critical structures and the placement and reproducibility of shielding.     

Gadoteridol dose dependence in MR imaging of a liver abscess model

A necrotic liver abscess model was studied with magnetic resonance (MR) imaging at 1.5 T before and after intravenous administration of gadoteridol at doses of 0.1, 0.25, and 0.5 mmol/kg in 24 rabbits. Enhancement characteristics and lesion delineation were assessed with both breath-hold and non-breath-hold imaging techniques. Lesion delineation, as assessed both by signal intensity measurements and evaluations by two image readers blinded to imaging technique, was greatest on high-dose (0.5 mmol/kg) breath-hold images. Lesion rim enhancement was seen consistently only on postcontrast images obtained at a dose of 0.5 mmol/kg and progressed with time after injection of contrast material.