A model of gallbladder motility.

Impaired gallbladder motility leads to some clinical manifestations associated with its muscle contraction and/or the rate of filling with bile. To gain a better understanding of the possible reasons for different filling/emptying patterns we developed a mathematical model of the gallbladder that takes into account the kinetics of its filling and emptying and changes in the concentration of the accumulated bile. The model is based on four parameters responsible for the maximum speed of bile evacuation (Mg), pulsation of contractions (ω), the kinetic filling rate (kg) and the maximum bile mass accumulated in the gallbladder (mtotal). The model results were fitted to different clinical results describing gallbladder motility depending on the meal composition, patient's age and health condition (obesity and gallstones). Compatibility of the model results with the experimental data allows us to draw physiological conclusions. We found that different gallbladder emptying patterns may result from differences in the amplitude of contraction of gallbladder muscles (e.g. for various meal composition), differences in the rate of bile inflow (e.g. for obese patients during filling), and differences in gallbladder muscle pulsations (e.g. for lean patients during early gallbladder emptying). The model of gallbladder motility can facilitate identification of causes of disorders, help to explore complicated physiological pathways, and can be applied in etiology analysis or studies of observable clinical indicators.

A preliminary investigation of the role of the transcription co-activators YAP/TAZ of the Hippo signalling pathway in canine and feline mammary tumours.

Breast cancer is the most common cancer in women worldwide. Cancer metastases are responsible for the high mortality rate. A small but distinct subset of cells, cancer stem cells (CSCs), have the capacity to self-renew, initiate tumour formation, and develop metastases. The CSC content in human breast cancer correlates with the Hippo tumour suppressor signalling pathway. Specifically, the activity of YAP/TAZ, transcription co-activators of the Hippo pathway, sustains the self-renewal and tumour-initiation capacities of CSCs. Little is known about YAP/TAZ in canine and feline mammary tumours, which are very common tumours. The preliminary aim of the study was to investigate the expression of YAP/TAZ in canine and feline mammary tumours by Western blot and immunohistochemistry. Increased cytoplasmic and nuclear expression of YAP/TAZ was observed in all carcinomas compared to normal tissues, indicating neoplastic deregulation of the Hippo pathway. Nuclear expression significantly increased in grade III (high grade carcinomas) compared to grade I (low grade carcinomas) tumours, suggesting that YAP/TAZ play a role in the increased aggressiveness of these tumours. Moreover, different scoring systems for immunohistochemical analyses were compared and the H index and the Allred scores were the most significant. In conclusion, YAP/TAZ are expressed in aggressive canine and feline mammary tumours as reported in some human cancers. Further studies might better elucidate the role of the Hippo pathway in prognosis and as a target for new therapies. In addition, tumours in dogs and cats may be a useful model to study this pathway.