Bromelain down-regulates myofibroblast differentiation in an in vitro wound healing assay.

Bromelain, a pineapple-derived enzyme mixture, is a widely used drug to improve tissue regeneration. Clinical and experimental data indicate a better outcome of soft tissue healing under the influence of bromelain. Proteolytic, anti-bacterial, anti-inflammatory, and anti-oedematogenic effects account for this improvement on the systemic level. It remains unknown, whether involved tissue cells are directly influenced by bromelain. In order to gain more insight into those mechanisms by which bromelain modulates tissue regeneration at the cellular level, we applied a well-established in vitro wound healing assay. Two main players of soft tissue healing--fibroblasts and microvascular endothelial cells--were used as mono- and co-cultures. Cell migration, proliferation, apoptosis, and the differentiation of fibroblasts to myofibroblasts as well as interleukin-6 were quantified in response to bromelain (36 × 10(-3) IU/ml) under normoxia and hypoxia. Bromelain attenuated endothelial cell and fibroblast proliferation in a moderate way. This proliferation decrease was not caused by apoptosis, rather, by driving cells into the resting state G0 of the cell cycle. Endothelial cell migration was not influenced by bromelain, whereas fibroblast migration was clearly slowed down, especially under hypoxia. Bromelain led to a significant decrease of myofibroblasts under both normoxic (from 19 to 12 %) and hypoxic conditions (from 22 to 15 %), coincident with higher levels of interleukin-6. Myofibroblast differentiation, a clear sign of fibrotic development, can be attenuated by the application of bromelain in vitro. Usage of bromelain as a therapeutic drug for chronic human wounds thus remains a very promising concept for the future.

Physical training during intrahepatic chemotherapy.

OBJECTIVE: To evaluate the role of strength and endurance training for the muscular, cardiac, respiratory, and immune systems and the quality of life (QOL) during intrahepatic chemotherapy (folinic acid, 5-fluorouracil). DESIGN: Single case. SETTING: Teaching hospital in Germany. PARTICIPANT: An elderly athlete with liver metastasis after resection of a carcinoma of the rectum (pT3, N0, M-liver, G2). INTERVENTION: Strength and endurance training during chemotherapy. MAIN OUTCOME MEASURES: During the intervals between training cycles (14d), beginning in postoperative week 6, a strength and endurance training regimen was performed twice weekly for 13 weeks, with an intensity of 40% to 60% of the maximum postoperative individual power and endurance. Before and after chemotherapy, we checked echocardiograms, resting and exercise electrocardiograms, lung function, natural killer (NK) cells, and the Gastrointestinal Quality of Life Index (GIQLI) scores. RESULTS: The increase in strength was between 0% and 144%. The improvement in endurance expressed by reduction of heart rate and lactate concentration was 10% and 21.5%, respectively. Lung function also improved with regard to forced expiratory volume in 1 second (12.9%), forced vital capacity (11.3%), and inspiratory vital capacity (11.4%). The relative count of the NK cells increased to 27.2%. An improvement in the GIQLI was observed from 109 points (pathologic) to 129 points. CONCLUSION: Strength and endurance training was associated with an increase of physical strength and endurance with positive influence on illness-related QOL. Postoperative physical exercise during regional chemotherapy is beneficial.