Paradoxical regulation of Bcl-2 family proteins by 17β-oestradiol in human breast cancer cells MCF-7

Tumorigenesis is related to the dysregulation of cell growth or cell death pathways. Hence, elucidation of the mechanisms involved in the modulation of pro- or anti-apoptotic proteins is important in furthering understanding of breast cancer aetiology and may aid in designing prevention and treatment strategies. In the present study, we examined the role of 17β-oestradiol on the regulation of apoptosis in the breast cancer cell line MCF-7. Using multi-probe RNAase protection assays, we found changes in the mRNA levels of several Bcl-2 family proteins upon treatment of MCF-7 cells with 17β-oestradiol. Unexpectedly, we found a paradoxical effects of 17β-oestradiol on two anti-apoptotic proteins Bcl-2 and Bcl-x. Treatment with 17β-oestradiol resulted in up-regulation of Bcl-2 mRNA and protein, but down-regulated Bcl-x(L) mRNA and protein. The effect of 17β-oestradiol on Bcl-x(L) occurred at concentration-dependent fashion. The effect was specific to 17β-oestradiol since other steroid hormones exert no effect on Bcl-x(L). Tamoxifen, an anti-oestrogen, blocked the down-regulation of Bcl-x(L) by 17β-oestradiol demonstrating this effect is oestrogen receptor-dependent. We speculate that different members of the Bcl-2 family proteins may be regulated through different pathway and these pathways may be modulated by 17β-oestradiol. © 1999 Cancer Research Campaig

Rôle potentiel de la noradrénaline dans la dysfonction immune du sepsis [Potential role of norepinephrine in the immune dysfunction associated with sepsis]

Septic shock may be complicated by a state of immune suppression, with ominous prognosis significance. Although the underlying pathophysiological mechanisms are poorly understood, it is possible that norepinephrine, used to treat circulatory failure during septic shock, plays a significant contributing role. Indeed, besides its hemodynamic effects, norepinephrine exerts multiple immunosuppressive actions, which are primarily mediated by beta-2 adrenergic receptors expressed by immune cells. Furthermore, norepinephrine has the ability to promote the growth of numerous bacteria, and could thereby foster the development of nosocomial infections. Norepinephrine being one of the most prescribed drugs in intensive care medicine, knowledge of these particular immunological effects is essential for the intensive care physicians

Integrated Design and Control of Active Aerodynamic Features for High Performance Electric Vehicles

Aerodynamics plays a major role in the design of all kinds of vehicles throughout automotive history. Initially the main topic under investigation was the aerodynamic drag reduction to achieve high-energy efficiency, however in the late '60s the vertical aerodynamic forces gained traction, particularly in high performance cars. The automotive market usually treats design, aerodynamics and vehicle dynamics in different departments. This paper proposes an integrated approach for the aerodynamics development in which a sport car is defined as reference vehicle. The objective of the concurrent engineering operation is to control the aerodynamic forces by implementing active surfaces control finally improving vehicle lap time. The vehicle dynamics analysis is carried out in cooperation with vehicle aerodynamics in order to perform the hardware and software design of the active system. The paper presents a case study in which an active aerodynamics control system is designed and successfully simulated numerically, with a co-simulation between MATLAB/Simulink and VI-Grade CarRealTime. The development process of the control system with fuzzy logic is described and relevant results are presented. Furthermore, to assess the vehicle dynamics improvements, a specific maneuver and a tailored track were developed to highlight the phenomena induced by the active aero surfaces. A final validation, through a static simulator testing session, is performed and presented and the overall conclusions in terms of objective and subjective performance improvements are presented