Acrylamide: Increased concentrations in homemade food and first evidence of its variable absorption from food, variable metabolism and placental and breast milk transfer in humans

We have developed a liquid chromatography/mass spectrometry (LC-MS/MS) assay to determine acrylamide in various body fluids. The assay also allows the reliable quantitation of acrylamide in food. In a total of 11 healthy male and female subjects, we were able to show that acrylamide from food given to humans is in fact absorbed from the gut. The half-lives determined in two male subjects were 2.2 and 7 h. Acrylamide was found in human breast milk and penetrated the human placenta (n = 3). The variability of acrylamide concentrations found in this investigation is most likely caused by variable intersubject bioavailability and metabolism. This may be an important indication that the assessment of the risk from acrylamide for the individual may be very difficult without knowing the concentrations of acrylamide in the body. This should be considered in the design of any risk assessment study or post hoc analysis of earlier studies. At this time, we suggest that pregnant women and breast-feeding mothers avoid acrylamide-containing food. Copyright (C) 2002 S. Karger AG, Basel

Is Ciprofloxacin a Substrate of P-glycoprotein?

INTRODUCTION: Studies using MDCKII and LLC-PK1 cells transfected with MDR1 cDNA indicate that ciprofloxacin is not a substrate of P-glycoprotein. However, our data has shown that transport studies done using different P-gp overexpressing cell lines (MDCKI-MDR1, MDCKII-MDR1 and L-MDR1), could lead to contradictory conclusion on whether a compound is a substrate of P-gp. The aim of our study was to determine if ciprofloxacin is indeed not a P-glycoprotein substrate using MDCKI cells transfected with human MDR1 cDNA. METHODS: Semi-quantitative RT-PCR was used to determine the mRNA level of MDR1 while Western blot was performed to determine the protein expression level of P-gp, MRP1 and MRP2 in various cells. Ciprofloxacin bidirectional transport studies were performed in MDCKI, MDCKI-MDR1, MDCKII, MDCKII-MDR1, MDCKII-MRP2, LLC-PK1, L-MRP1 and L-MDR1 cells. RESULTS: Ciprofloxacin showed net secretion in MDCKI-MDR1 but net absorption in MDCKI cells. Various P-gp inhibitors decreased the B to A and increased the A to B transport of ciprofloxacin in MDCKI-MDR1 cells while having no effect in MDCKI cells. The B to A transport of ciprofloxacin in MDCKI-MDR1 cells was not affected by non-P-gp inhibitors. In the presence of indomethacin, ciprofloxacin showed net secretion instead of net absorption in MDCKI cells while in the presence of probenecid and sulfinpyrazone, there was no net secretion and absorption. There was no difference in ciprofloxacin transport between MDCKII and MDCKII-MDR1, LLC-PK1 and L-MDR1, LLC-PK1 and L-MRP1 and MDCKII and MDCKII-MRP2. CONCLUSIONS: Transport data in MDCKI and MDCKI-MDR1 cells indicate that ciprofloxacin is a substrate of P-gp but data from MDCKII, MDCKII-MDR1, LLC-PK1 and L-MDR1 cells indicate that ciprofloxacin is not a substrate of P-gp. Vinblastine, a well-known P-gp substrate, also did not show differences between LLC-PK1 and L-MDR1 cells. Further studies need to be performed to characterize these P-gp overexpressing cell lines and the transport of ciprofloxacin

Spin dynamics of frustrated easy-axis triangular antiferromagnet 2H-AgNiO2 explored by inelastic neutron scattering

We report inelastic neutron scattering measurements of the spin dynamics in the layered hexagonal magnet 2H-AgNiO2 which has stacked triangular layers of antiferromagnetically-coupled Ni2+ spins (S=1) ordered in a collinear alternating stripe pattern. We observe a broad band of magnetic excitations above a small gap of 1.8 meV and extending up to 7.5 meV, indicating strongly dispersive excitations. The measured dispersions of the boundaries of the powder-averaged spectrum can be quantitatively explained by a linear spin-wave dispersion for triangular layers with antiferromagnetic nearest- and weak next-nearest neighbor couplings, a strong easy-axis anisotropy and additional weak inter-layer couplings. The resulting dispersion relation has global minima not at magnetic Bragg wavevectors but at symmetry-related soft points and we attribute this anomalous feature to the strong competition between the easy-axis anisotropy and the frustrated antiferromagnetic couplings. We have also calculated the quantum corrections to the dispersion relation to order 1/S in spin-wave theory by extending the work of Chubukov and Jolicoeur [Phys. Rev. B v46, 11137 (1992)] and find that the presence of easy-axis anisotropy significantly reduces the quantum renormalizations predicted for the isotropic model.Comment: 17 pages and 15 figures. To appear in Physical Review

Mean-field Study of Charge, Spin, and Orbital Orderings in Triangular-lattice Compounds ANiO2 (A=Na, Li, Ag)

We present our theoretical results on the ground states in layered triangular-lattice compounds ANiO2 (A=Na, Li, Ag). To describe the interplay between charge, spin, orbital, and lattice degrees of freedom in these materials, we study a doubly-degenerate Hubbard model with electron-phonon couplings by the Hartree-Fock approximation combined with the adiabatic approximation. In a weakly-correlated region, we find a metallic state accompanied by \sqroot3x\sqroot3 charge ordering. On the other hand, we obtain an insulating phase with spin-ferro and orbital-ferro ordering in a wide range from intermediate to strong correlation. These phases share many characteristics with the low-temperature states of AgNiO2 and NaNiO2, respectively. The charge-ordered metallic phase is stabilized by a compromise between Coulomb repulsions and effective attractive interactions originating from the breathing-type electronphonon coupling as well as the Hund's-rule coupling. The spin-orbital-ordered insulating phase is stabilized by the cooperative effect of electron correlations and the Jahn-Teller coupling, while the Hund's-rule coupling also plays a role in the competition with other orbital-ordered phases. The results suggest a unified way of understanding a variety of low-temperature phases in ANiO2. We also discuss a keen competition among different spin-orbital-ordered phases in relation to a puzzling behavior observed in LiNiO2

Interplay between localized and itinerant d electrons in a frustrated metallic antiferromagnet, 2H-AgNiO2

We report the electronic and magnetic behaviour of the frustrated triangular metallic antiferromagnet 2H-AgNiO2 in high magnetic fields (54 T) using thermodynamic and transport measurements. Here localized d electrons are arranged on an antiferromagnetic triangular lattice nested inside a honeycomb lattice with itinerant d electrons. When the magnetic field is along the easy axis we observe a cascade of field-induced transitions, attributed to the competition between easy-axis anisotropy, geometrical frustration and coupling of the localized and itinerant system. The quantum oscillations data suggest that the Fermi surface is reconstructed by the magnetic order but in high fields magnetic breakdown orbits are possible. The itinerant electrons are extremely sensitive to scattering by spin fluctuations and a significant mass enhancement (~ 3) is found.Comment: 4 page

Recovery of cefazolin and clindamycin in in vitro pediatric CPB systems

Cardiopulmonary bypass (CPB) is often necessary for congenital cardiac surgery, but CPB can alter drug pharmacokinetic parameters resulting in underdosing. Inadequate plasma levels of antibiotics could lead to postoperative infections with increased morbidity. The influence of pediatric CPB systems on cefazolin and clindamycin plasma levels is not kn

In Vitro Recovery of Sufentanil, Midazolam, Propofol, and Methylprednisolone in Pediatric Cardiopulmonary Bypass Systems

Objectives: To evaluate in vitro drug recovery in cardiopulmonary bypass (CPB) systems used for pediatric cardiac surgery. Design: Observational in vitro study. Setting: Single-center university hospital. Participants: In vitro CPB systems used for pediatric cardiac surgery. Interventions: Three full neonatal, infant, and pediatric CPB systems were primed according to hospital protocol and kept running for 6 hours. Midazolam, propofol, sufentanil, and methylprednisolone were added to the venous side of the systems in doses commonly used for induction of general anesthesia. Blood samples were taken from the postoxygenator side of the circuit immediately after injection of the drugs and after 2, 5, 7, 10, 30, 60, 180, and 300 minutes. Measurements and Main Results: Linear mixed model analyses were performed to assess the relationship between log-transformed drug concentration (dependent variable) and type of CPB system and sample time point (independent variables). The mean percentage of drug recovery after 60 and 180 minutes compared with T1 was 41.7% (95% confidence interval [CI] 35.9-47.4) and 23.0% (95% CI 9.2-36.8) for sufentanil, 87.3% (95% CI 64.9-109.7) and 82.0% (95% CI 64.6-99.4) for midazolam, 41.3% (95% CI 15.5-67.2) and 25.0% (95% CI 4.7-45.3) for propofol, and 119.3% (95% CI 101.89-136.78) and 162.0% (95% CI 114.09-209.91) for methylprednisolone, respectively. Conclusions: The present in vitro experiment with neonatal, infant, and pediatric CPB systems shows a variable recovery of routinely used drugs with significant differences between drugs, but not between system categories (with the exception of propofol). The decreased recovery of mainly sufentanil and propofol could lead to suboptimal dosing of patients during cardiac surgery with CPB