Search

Therapeutic regimens using monoclonal antibodies have been implemented in clinical daily practice for various gastroenterological diseases, for therapeutic strategies in gastrointestinal (GI) oncology, and infectious diseases of the gastrointestinal tract. The main indications remain the therapy of chronic inflammatory bowel disease and in GI oncology. A new field has opened for targeted therapy with monoclonal antibodies of recurrent Clostridium difficile infection. In the nomenclature of monoclonal antibodies, the endings of the substances indicate the production or degree of "humanization" of the respective antibodies ("umab": fully human, recombinant antibody; "ximab": chimeric antibody with variable murine domain). For chronic inflammatory bowel disease, monoclonal antibodies has been developed to interfere with molecular targets of the inflammatory cascade in the underlying pathogenesis (tumor necrosis factor‑α, interleukin-12 and -23; α4β7-integrins). The development of targeted therapies in the treatment of GI malignancies, monoclonal antibodies has been developed to interfere with substantial pathways of proliferation and apoptosis as well as neoplastic vascularization and neovascularization (e.g., vascular endothelial growth factor [VEGF] and VEGF receptor antibodies, epidermal growth factor receptor antibodies, HER2/neu antibodies). In the current review, we provide a summary of the current applications of monoclonal antibodies in the therapeutic treatment of gastroenterological diseases.

Previous and more recent studies show that cholinesterase inhibitors (ChE-Is) are an important possibility for therapeutic intervention in Alzheimer's Disease, sepsis and other inflammatory syndromes. ChE-Is maintain high levels of acetylcholine (ACh) determining beneficial effects on the disease process. Despite numerous efforts to identify the appropriate choice of agents and dose of ChE-Is, a common protocol regarding concentration- and species-dependent differences in inhibitory potency (IC 50) of clinical relevant ChE-Is is still not available. To evaluate the in vitro sensitivity of Acetyl- and Butyrylcholinesterase (AChE, BChE), we compared the concentration-response effects of physostigmine and neostigmine on cholinesterases in whole blood from rat and human. A spectrophotometrical test system based on in vitro Ellman's reagent has been used to determine the kinetic properties of clinical relevant ChE-Is. In vitro, the enzyme activity of human AChE and BChE was inhibited in a concentration-dependent manner until a residual activity of 4-6% for AChE and 20-30% for BChE (IC 50 human AChE: 0.117 ± 0.007 μM physostigmine, 0.062 ± 0.003 μM neostigmine; IC 50 human BChE: 0.373 ± 0.089 μM neostigmine; 0.059 ± 0.012 μM physostigmine). The inhibition curve of rat BChE in contrast showed no concentration-dependency for physostigmine and neostigmine (87% residual activity even at high inhibitor concentrations). Rat AChE was inhibited in a concentration-dependent manner until a residual activity of 53%. The results suggest that cholinesterases from human and rat show marked species- and inhibitor-dependent differences in sensitivity to physostigmine and neostigmine. Knowledge of such differences may be critical in assessing the possible therapeutic effects of ChE-Is in both species and may guide researchers in the optimal design of future experiments regarding the application of ChE-Is.