The use of animal models in homeopathic research--a review of 2010-2014 PubMed indexed papers.

BACKGROUND: In the 1990s, a study was performed on the effects of highly diluted thyroxine on frog metamorphosis. This model represented one of the most discussed examples of the biological effects of high dilutions over the next two decades. In 2010, another critical conceptual review of the use of animal models in homeopathy and high-dilution research was published. The main contribution of these studies was the elucidation of the biological features and phenomenology of the effects of high dilutions on living systems, representing an important step forward in our understanding of the mechanisms of action of homeopathic medicines. METHODS: We performed a further review of this line of investigation using the same methods. Fifty-three articles that were indexed in the PubMed database and used 12 different animal species were systematically evaluated. Only a fraction of the studies (29/53) reported herein were performed with "ultra high" dilutions. The other studies were performed with dilutions in ranges below 10(-23) (14/53 articles) or commercial complexes (10/53 articles). RESULTS: Only two articles reported negative results; both used in vivo protocols to test commercial complexes, one in fish and one in bees. The quality of the employed techniques improved in 2010-2014 compared with the studies that were reviewed previously in 2010, with the inclusion of more ethically refined protocols, including in vitro primary cell cultures and ex vivo studies (10/53 articles), often with three or more replicates and analyses of epigenetic mechanisms that were previously unknown in 2010. CONCLUSION: In our updated review of the past 5 years, we found further demonstrations of the biological effects of homeopathy using more refined animal models and in vitro techniques.

High-diluted thymulin on Ehrlich tumor growth in mice and the importance of tumor microenvironment

Introduction: The aim of the present study was to describe different biological aspects of Ehrlich tumor in mice, such as body weight evolution, tumor growth rate, histological organization and systemic immune response after treatment with high-diluted thymulin (10-9 M, named 5CH). Methods: Tumor assessment was focused on macro- and microscopic aspects; parameters included occurrence of necrosis, embolism and tumor development, in addition to quantitative analysis of apoptosis (caspase-3), cell proliferation (Ki-67) and angiogenesis (vascular endothelial growth factor - VEGF) by means of specific immunohistochemistry markers. Spleen cell populations were evaluated by flow cytometry analysis. Results: Mice treated with thymulin 5CH exhibited changes in the tumor microenvironment, such as reduced micro-embolism incidence and cytokeratin expression, with increased caspase-3 expression in the tumor cells. These findings indicate some apoptotic activity by the tumor cells induced by the treatment, even though no reduction of the macroscopic tumor mass occurred. No changes in the systemic immune response were detected, as the balance among spleen cell populations remained unchanged. Conclusions: The results indicate that treatment of mice bearing Ehrlich tumor with thymulin 5CH induces some specific changes in the tumor environment. However, it did not influence systemic immunity parameters. Adjuvant use of thymulin 5CH in oncological clinical practice is still a matter of discussion. (AU)