Oral brush biopsy analysis by matrix assisted laser desorption/ionisation-time of flight mass spectrometry profiling--a pilot study

Oral squamous cell carcinomas (OSCCs) often present as advanced tumours requiring aggressive local and regional therapy and result in significant functional impairment. The objective is to develop pre-symptomatic screening detection of OSCC by a brush biopsy method which is less invasive than the conventional biopsy for histology. Given the molecular heterogeneity of oral cancer, it is unlikely that even a panel of tumour markers would provide accurate diagnosis. Therefore, approaches such as the matrix-assisted-laser-desorption/ionisation-time-of-flight-mass-spectrometry (MALDI-TOF-MS) allow several biomarkers or peptide profile patterns to be simultaneously assessed. Brush biopsies from 27 patients with histology-proven OSCCs plus 40 biopsies from 10 healthy controls were collected. MALDI-TOF-MS profiling was performed and additional statistical analysis of the data was used to classify the disease status according to the biological behaviour of the lesion. For classification a support vector machine algorithm was trained using spectra of brush biopsy samples to distinguish healthy control patients from patients with histology-proven OSCC. MALDI-TOF-MS was able to distinguish between healthy patients and OSCC patients with a sensitivity of 100% and specificity of 93%. In summary, MALDI-TOF-MS in combination with sophisticated bioinformatic methods can distinguish OSCC patients from non-cancer controls with excellent sensitivity and specificity. Further improvement and validation of this approach is necessary to determine its feasibility to assist the pre-symptomatic detection of head and neck cancer screening in routine daily practice.     

Mesenchymal stem cells and inorganic bovine bone mineral in sinus augmentation: comparison with augmentation by autologous bone in adult sheep

Our aim was to compare the osteogenic potential of mononuclear cells harvested from the iliac crest combined with bovine bone mineral (BBM) (experimental group) with that of autogenous cancellous bone alone (control group). We studied bilateral augmentations of the sinus floor in 6 adult sheep. BBM and mononuclear cells (MNC) were mixed and placed into one side and autogenous bone in the other side. Animals were killed after 8 and 16 weeks. Sites of augmentation were analysed radiographically and histologically. The mean (SD) augmentation volume was 3.0 (1.0) cm³ and 2.7 (0.3) cm³ after 8 and 16 weeks in the test group, and 2.8 (0.3) cm³ (8 weeks) and 2.8 (1.2) cm³ (16 weeks) in the control group, respectively. After 8 weeks, histomorphometric analysis showed 24 (3)% BBM, and 19 (11)% of newly formed bone in the test group. The control group had 20 (13%) of newly formed bone. Specimens after 16 weeks showed 29 (12%) of newly formed bone and 19 (3%) BBM in the test group. The amount of newly formed bone in the control group was 16 (6%). The results show that mononuclear cells, including mesenchymal stem cells, in combination with BBM as the biomaterial, have the potential to form bone.     

Importance of microcracks in etiology of bisphosphonate-related osteonecrosis of the jaw: a possible pathogenetic model of symptomatic and non-symptomatic osteonecrosis of the jaw based on scanning electron microscopy findings

The aim of this study was to evaluate a possible role of microcracks in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (ONJ) and to discuss an etiological model. Bone samples from 35 patients with ONJ were analyzed. Control samples were taken from five patients with osteomyelitis (OM), ten patients with osteoradionecrosis, seven patients with osteoporosis and bisphosphonate medication without signs of ONJ, and six osteoporotic elderly patients. Samples were examined using scanning electron microscopy. In 54% of the bone samples of patients with ONJ, microcracks were seen. Inflammatory and connective tissue reactions within the microcracks were evident in 82% of the cases, indicating that these cracks were not artificial. In contrast, only 29% of samples from patients with oral bisphosphonate medication without ONJ, no sample from patients with OM, none of the osteoradionecrosis group, and only 17% from patients with osteoporosis showed microcracks. Statistically significant differences could be found between the ONJ group and the group after irradiation and the group with OM, respectively. The evidence of microcracks could be a first step in the pathogenesis of bisphosphonate-related ONJ. The accumulation of these microcracks leads to a situation that could be named “non-symptomatic ONJ”. Disruptions of the mucosal integrity may then allow bacterial invasion, leading to jawbone infection with exposed bone, fistulas, and pain. This state could be called “symptomatic ONJ”. Furthermore, an assumed local immunosuppression as indicated by various studies could explain the severe courses of therapy-resistant ONJ as regularly observed.     

Spontaneous generation of mammalian prions

Prions are transmissible agents that cause lethal neurodegeneration in humans and other mammals. Prions bind avidly to metal surfaces such as steel wires and, when surface-bound, can initiate infection of brain or cultured cells with remarkable efficiency. While investigating the properties of metal-bound prions by using the scrapie cell assay to measure infectivity, we observed, at low frequency, positive assay results in control groups in which metal wires had been coated with uninfected mouse brain homogenate. This phenomenon proved to be reproducible in rigorous and exhaustive control experiments designed to exclude prion contamination. The infectivity generated in cell culture could be readily transferred to mice and had strain characteristics distinct from the mouse-adapted prion strains used in the laboratory. The apparent ”spontaneous generation” of prions from normal brain tissue could result if the metal surface, possibly with bound cofactors, catalyzed de novo formation of prions from normal cellular prion protein. Alternatively, if prions were naturally present in the brain at levels not detectable by conventional methods, metal surfaces might concentrate them to the extent that they become quantifiable by the scrapie cell assay.     

Narrow band imaging (NBI) during medical thoracoscopy: first impressions

Background  

This is the first ever evaluation of narrow band imaging (NBI), an innovative endoscopic imaging procedure, for the visualisation of pleural processes.     

Collation, assessment and analysis of literature in vitro data on hERG receptor blocking potency for subsequent modeling of drugs' cardiotoxic properties

The assessment of the torsadogenic potency of a new chemical entity is a crucial issue during lead optimization and the drug development process. It is required by the regulatory agencies during the registration process. In recent years, there has been a considerable interest in developing in silico models, which allow prediction of drug-hERG channel interaction at the early stage of a drug development process. The main mechanism underlying an acquired QT syndrome and a potentially fatal arrhythmia called torsades de pointes is the inhibition of potassium channel encoded by hERG (the human ether-a-go-go-related gene). The concentration producing half-maximal block of the hERG potassium current (IC(50)) is a surrogate marker for proarrhythmic properties of compounds and is considered a test for cardiac safety of drugs or drug candidates. The IC(50) values, obtained from data collected during electrophysiological studies, are highly dependent on experimental conditions (i.e. model, temperature, voltage protocol). For the in silico models' quality and performance, the data quality and consistency is a crucial issue. Therefore the main objective of our work was to collect and assess the hERG IC(50) data available in accessible scientific literature to provide a high-quality data set for further studies.