WNT10A variants: following the pattern of inheritance in tooth agenesis and self-reported family history of cancer

Clinical Oral Investigations - The aim of this study was the analysis of WNT10A variants in seven families of probands with various forms of tooth agenesis and self-reported family history of...     

Model-Based Evaluation of Drying Kinetics and Solvent Diffusion in Pharmaceutical Thin Film Coatings

Pharmaceutical Research - Fluid-bed coating processes make it possible to manufacture pharmaceutical products with tuneable properties. The choice of polymer type and coating thickness provides...     

The metabolism of flubendazole in human liver and cancer cell lines

Flubendazole (FLU), a benzimidazole anthelmintic drug widely used in veterinary medicine, has been approved for the treatment of gut‐residing nematodes in humans. In addition, FLU is now considered a promising anti‐cancer agent. Despite this, information about biotransformation of this compound in human is lacking. Moreover, there is no information regarding whether cancer cells are able to metabolize FLU in order to deactivate it. For these reasons, the present study was designed to identify all metabolites of Phase I and Phase II of FLU in human liver and in various cancer cells using ultra high‐performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) analysis. Precision‐cut human liver slices and 9 cell lines of different origin (breast, colon, oral cavity) were used as in vitro model systems. Our study showed that FLU with a reduced carbonyl group (FLUR) is the only FLU metabolite formed in the human liver. All human cancer cell lines were able to form FLUR. In addition, methylated FLUR was detected in breast cells MCF7 and intestinal SW480 cells. The accumulation of FLU and its reduction to FLUR markedly differed among cells. The extent of FLU reduction was in a good correlation with the detected expression level of carbonyl reductase 1. In most cases, FLU entered in a higher amount and was reduced to a lesser extent in proliferating (metastatic) cells than in differentiated (non‐cancerous, non‐metastatic) ones. These results support the promising potential of FLU in anti‐cancer therapy.     

The influence of orthognathic surgery on ventilation during sleep

Orthognathic surgery has varying effects on respiratory parameters. The authors undertook a prospective study of patients requiring mandibular advancement, mandibular setback and maxillary Le Fort I advancement, and surgically assisted rapid maxillary expansion (SARME). Breathing parameters were monitored in a sleep laboratory the night before the operation and in a mean of 9.5 months after the operation. In patients treated with mandibular advancement, the respiratory disturbance index (RDI), oxygen desaturation index (ODI), and number of obstructive apnoeas (OAs) improved significantly. In patients treated with mandibular setback and maxillary Le Fort I advancement, the RDI, ODI, index of flow limitations (IFL), number of obstructive hypopnoeas (OHs), OA, and oxygen saturation deteriorated. In contrast, patients treated with SARME improved only mildly. These results indicate that bimaxillary surgery for Class III malocclusion increased upper airway resistance, probably because of a more dorsal positioning of the base of the tongue, representing an iatrogenic obstructive sleep apnoea (OSA). A young person would probably be able to balance such a decline in respiratory function using different adaptative mechanisms. Mandibular advancement significantly improved respiratory parameters during sleep. The possible effect of orthognathic surgery on the upper airways should be incorporated into the treatment plan.     

Acoustical enrichment during early postnatal development changes response properties of inferior colliculus neurons in rats

The structure and function of the auditory system may be influenced by acoustic stimulation, especially during the early postnatal period. This study explores the effects of an acoustically enriched environment applied during the third and fourth week of life on the responsiveness of inferior colliculus neurons in rats. The enrichment comprised a spectrally and temporally modulated complex sound reinforced with several target acoustic stimuli, one of which triggered a reward release. The exposure permanently influenced neuronal representation of the sound frequency and intensity, resulting in lower excitatory thresholds at neuronal characteristic frequency, an increased frequency selectivity, larger response magnitudes, steeper rate–intensity functions and an increased spontaneous activity. The effect was general and non‐specific, spanning the entire hearing range – no changes specific to the frequency band of the target stimuli were found. The alterations depended on the activity of animals during the enrichment – a higher activity of rats in the stimulus–reward paradigm led to more profound changes compared with the treatment when the stimulus–reward paradigm was not used. Furthermore, the exposure in early life led to permanent changes in response parameters, whereas the application of the same environment in adulthood influenced only a subset of the examined parameters and had only a temporary effect. These findings indicate that a rich and stimulating acoustic environment during early development, particularly when reinforced by positive feedback, may permanently affect signal processing in the subcortical auditory nuclei, including the excitatory thresholds of neurons and their frequency and intensity resolution.