One health in history

This chapter historicizes "One Health" as a concept and approach. It explores the changing constellation of ideas, practices and conditions that brought human and animal health into alignment in different historical contexts, the people and institutions involved and the factors of change over time. The first section shows how deeply animals and animal health were embedded within human medicine in the pre-modern period. The second section extends from the late 18th-century foundation of the veterinary profession to the turn of the 20th century. It tracks the evolving relationship between the veterinary and medical professions, and how, as scientific knowledge and practices changed, new conceptual links were forged between humans, animals and the environment. The third section extends this analysis into the 20th century, focusing particularly on the changing status of animals within medical research, and on international efforts to develop comparative medicine and veterinary public health. The conclusion challenges the idea that the historical record can provide straightforward lessons or guides for "One Health" today

One Health in History

Introduction The purpose of this chapter is to outline the history of One Health. This task immediately raises the question of how to approach the history of a subject that only became known as "One Health" a few years ago, and is still evolving..

COX-2 induction by unconjugated bile acids involves reactive oxygen speciesmediated signalling pathways in Barrett's oesophagus and oesophageal adenocarcinoma

Objectives: Bile reflux contributes to oesophageal injury and neoplasia. COX-2 is involved in both inflammation and carcinogenesis; however, the precise mechanisms by which bile acids promote COX-2 expression in the oesophagus are largely unknown. We analysed the molecular mechanisms that govern bile acid-mediated expression of COX-2 in Barrett's oesophagus and oesophageal adenocarcinoma (OA). Design: The effects of bile acids on COX-2 expression were analysed in immortalised Barrett's oesophagus and OA cells using immunoblotting and transient transfections. Pharmacological inhibitors, phospho-specific antibodies, dominant-negative mutants and siRNA techniques were used to identify relevant signalling pathways. Flow cytometry and reactive oxygen species (ROS) scavengers were used to examine ROS involvement. Immunohistochemistry was performed on oesophageal mucosa obtained from an established rat model of bile reflux. Results: Unconjugated bile acids potently stimulated COX-2 expression and induced AKT and ERK1/2 phosphorylation in concert with COX-2 induction. These findings were mimicked in the in vivo rat model. Dominant-negative (DN) AKT and LY294002 (PI3K inhibitor) or U0126 (MEK-1/2 inhibitor) blocked chenodeoxycholic acid (CD) and deoxycholic acid (DC) mediated COX-2 induction. CD and DC also induced CREB phosphorylation and AP-1 activity. CREB-specific siRNA and DN AP-1 blocked CD and DC-induced COX-2 induction. Finally, CD and DC increased intracellular ROS, while ROS scavengers blocked COX-2 induction and the signalling pathways involved. Conclusions: Unconjugated bile acids induce CREB and AP-1-dependent COX-2 expression in Barrett's oesophagus and OA through ROS-mediated activation of PI3K/AKT and ERK1/2. This study enhances our understanding of the molecular mechanisms by which bile acids promote the development of oesophageal adenocarcinoma

Chapitre 1 - One Health dans l’histoire

Introduction Ce chapitre présente l’histoire de One Health. Cette tâche soulève d’emblée la question de savoir comment aborder l’histoire d’un sujet qui n’a pris le nom de « One Health » qu’il y a quelques années, et qui évolue encore conceptuellement sous l’influence des défis de la santé, des avancées scientifiques et des priorités politiques, économiques, environnementales et professionnelles. Bien qu’il y ait eu de nombreux ..

Off-Label Promotion, On-Target Sales

Adriane Fugh-Berman and Douglas Melnick describe techniques by which pharmaceutical companies covertly promote off-label drug use even where such promotion is illegal

Rethinking Statistical Approaches to Evaluating Drug Safety

[[abstract]]The current methods used to evaluate the efficacy of drug products are inadequate. We propose a non-inferiority approach to prove the safety of drugs. Materials and Methods: Traditional hypotheses for the evaluation of the safety of drugs are based on proof of hazard, which have proven to be inadequate. Therefore, based on the concept of proof of safety, the non-inferiority hypothesis is employed to prove that the risk of new drugs does not exceed a pre-specified allowable safety margin, hence proving that a drug has no excessive risk. The results from papers published on Vioxx (R) and Avandia (R) are used to illustrate the difference between the traditional approach for proof of hazard and the non-inferiority approach for proof of safety. Results: The p-values from traditional hypotheses were greater than 0.05, and failed to demonstrate that Vioxx (R) and Avandia (R) are of cardiovascular hazard. However, these results cannot prove that both Vioxx (R) and Avandia (R) are of no cardiovascular risk. On the other hand, the non-inferiority approach can prove that they are of excessive cardiovascular risk. Conclusion: The non-inferiority approach is appropriate to prove the safety of drugs