Antinociceptive effects of Cremophor EL orally administered to mice

Surfactants are frequently used to improve solubilization of lipophilic drugs. Cremophor EL (CrEL) is a polyoxyethylated castor oil surfactant used to solubilize water-insoluble drugs such as anesthetic, antineoplastic, immunosuppressive and analgesic drugs, vitamins and new synthetic compounds, including potential analgesics. The antinociceptive effect of CrEL (3.2, 6.4 and 10.6 g/kg, in 10 ml/kg body weight, by gavage) on the abdominal writhing response induced by intraperitoneal administration of acetic acid (0.8%, 10 ml/kg body weight) and on the tail immersion test was investigated in mice. Control animals received castor oil (10 ml/kg body weight) or saline (0.9% NaCl, 10 ml/kg body weight). CrEL reduced nociception in a dose-dependent manner in both tests. At 10.6 g/kg, CrEL caused antinociception similar to that induced by dipyrone (300 mg/kg, by gavage) in the abdominal writhing test, and antinociception similar to that induced by morphine (20 mg/kg, by gavage) in the tail immersion test. The effect of castor oil was similar to that of saline in both assays. These data indicate that the appropriate controls should be used when evaluating the effects of potential antinociceptive agents dissolved in CrEL

Geodesics dynamics in the Linet–Tian spacetime with Λ<0\Lambda <0

We investigate the geodesics' kinematics and dynamics in the Linet-Tian metric with $\Lambda<0$ and compare with the results for the Levi-Civita metric, when $\Lambda=0$. This is used to derive new stability results about the geodesics' dynamics in static vacuum cylindrically symmetric spacetimes with respect to the introduction of $\Lambda<0$. In particular, we find that increasing $|\Lambda|$ always increases the minimum and maximum radial distances to the axis of any spatially confined planar null geodesic. Furthermore, we show that, in some cases, the inclusion of any $\Lambda<0$ breaks the geodesics' orbit confinement of the $\Lambda=0$ metric, for both planar and non-planar null geodesics, which are therefore unstable. Using the full system of geodesics' equations, we provide numerical examples which illustrate our results.IB and FM thank CMAT, Univ. Minho, for support through the FEDER Funds-COMPETE and FCT Project Est-C/MAT/UI0013/2011. FM is also supported by FCT projects PTDC/MAT/108921/2008 and CERN/FP/123609/2011 and thanks the warm hospitality from Instituto de Fisica, UERJ, Rio de Janeiro, where this work was completed. MFAdaSilva acknowledges the financial support from FAPERJ (Nos. E-26/171.754/2000, E-26/171.533.2002, E-26/170.951/2006, E-26/110.432/2009 and E-26/111.714/2010), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq-Brazil (Nos. 450572/2009-9, 301973/2009-1 and 477268/2010-2) and Financiadora de Estudos e Projetos-FINEP-Brazil