Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists

PURPOSE: The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT(3) receptor antagonists to assess its translational validity. METHODS: A systematic review identified available evidence and was used to perform meta-analyses. RESULTS: Of 182 potentially relevant publications, 115 reported cisplatin-induced emesis in ferrets and 68 were included in the analysis. The majority (n = 53) used a 10 mg kg(−1) dose to induce acute emesis, which peaked after 2 h. More recent studies (n = 11) also used 5 mg kg(−1), which induced a biphasic response peaking at 12 h and 48 h. Overall, 5-HT(3) receptor antagonists reduced cisplatin (5 mg kg(−1)) emesis by 68% (45–91%) during the acute phase (day 1) and by 67% (48–86%) and 53% (38–68%, all P < 0.001), during the delayed phase (days 2, 3). In an analysis focused on the acute phase, the efficacy of ondansetron was dependent on the dosage and observation period but not on the dose of cisplatin. CONCLUSION: Our analysis enabled novel findings to be extracted from the literature including factors which may impact on the applicability of preclinical results to humans. It reveals that the efficacy of ondansetron is similar against low and high doses of cisplatin. Additionally, we showed that 5-HT(3) receptor antagonists have a similar efficacy during acute and delayed emesis, which provides a novel insight into the pharmacology of delayed emesis in the ferret

Effects of phenyl saligenin phosphate on cell viability and transglutaminase activity in N2a neuroblastoma and HepG2 hepatoma cell lines

We derive upper bounds for the number of degrees of freedom of two-dimensional Navier--Stokes turbulence freely decaying from a smooth initial vorticity field $\omega(x,y,0)=\omega_0$. This number, denoted by $N$, is defined as the minimum dimension such that for $n\ge N$, arbitrary $n$-dimensional balls in phase space centred on the solution trajectory $\omega(x,y,t)$, for $t>0$, contract under the dynamics of the system linearized about $\omega(x,y,t)$. In other words, $N$ is the minimum number of greatest Lyapunov exponents whose sum becomes negative. It is found that $N\le C_1R_e$ when the phase space is endowed with the energy norm, and $N\le C_2R_e(1+\ln R_e)^{1/3}$ when the phase space is endowed with the enstrophy norm. Here $C_1$ and $C_2$ are constant and $R_e$ is the Reynolds number defined in terms of $\omega_0$, the system length scale, and the viscosity $\nu$. The linear (or nearly linear) dependence of $N$ on $R_e$ is consistent with the estimate for the number of active modes deduced from a recent mathematical bound for the viscous dissipation wave number. This result is in a sharp contrast to the forced case, for which well-known estimates for the Hausdorff dimension $D_H$ of the global attractor scale highly superlinearly with $\nu^{-1}$. We argue that the "extra" dependence of $D_H$ on $\nu^{-1}$ is not an intrinsic property of the turbulent dynamics. Rather, it is a "removable artifact," brought about by the use of a time-independent forcing as a model for energy and enstrophy injection that drives the turbulence.Comment: 7 journal pages, to appear in PR