Compatibility and activity of aldesleukin (recombinant interleukin-2) in presence of selected drugs during simulated Y-site administration: evaluation of three methods

The compatibility and biological activity of aldesleukin (a form of recombinant interleukin-2) in the presence of selected i.v. drugs during simulated Y-site administration was studied. Five milliliters of aldesleukin 33,800 IU/mL in 5% dextrose injection was mixed in glass test tubes with 5 mL of each of 19 i.v. drugs prepared at concentrations used in routine clinical practice. The compatibility of the combinations was assessed by visual examination and spectrophotometry at 0, 0.5, 1, and 2 hours after preparation, and bioassays were conducted to determine the activity of aldesleukin in the combinations. Lorazepam was the only drug visually incompatible with aldesleukin. All the secondary drugs were spectrophotometrically compatible with aldesleukin. However, the bioassays showed that the following drugs reduced the activity of aldesleukin: ganciclovir sodium, lorazepam, pentamidine isethionate, prochlorperazine edisylate, and promethazine hydrochloride. Thus, aldesleukin became less biologically active when combined with four drugs for which visual examination suggested compatibility and when combined with five drugs for which spectrophotometry indicated compatibility. Aldesleukin 33,800 IU/mL in 5% dextrose injection lost significant biological activity in the presence of prochlorperazine edisylate, promethazine hydrochloride, lorazepam, ganciclovir sodium, and pentamidine isethionate during simulated Y-site administration. Visual assessment and spectrophotometry may not be valid methods for assessing possible changes in the biological activity of aldesleukin when combined with other agents.     

Individual differences in vulnerability to inescapable shock in rats.

The present study determined whether individual differences in neophobia during an open-field pretest predict vulnerability to inescapable electric shock, as measured by 2 tests of learned helplessness in rats. Shuttle-escape latencies and saccharin finickiness increased across groups that had received increasing numbers of inescapable shocks 24 hr earlier. Dispersion in the test measure as well as the percentage of variance explained by pretest neophobia were greater when no or few shocks were delivered in the interpolated stress phase. Pretest neophobia was positively related to stress vulnerability in both tests under these conditions. Further increments in stressor severity overwhelmed even the most stress-resistant rats, thereby decreasing dispersion in the test measure and eliminating the predictive value of pretest neophobia. This pattern of outcomes was more robust for the shuttle-escape measure of helplessness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rapid determination of the membrane potential of mitochondria in small biopsy specimens of the liver

In liver transplantation, graft viability is ideally to be determined before implantation. Integrity of mitochondria may be a prerequisite to a viable graft. A new method is presented, which allows for the determination of the membrane potential of mitochondria (MPM; mV) in state 4 respiration within 50 min in 40-mg specimens, employing rhodamine 123 as a probe. Normal control showed a MPM of 239.2 mV. Storage in saline at 37 degrees C yielded an impaired MPM of 153.5 mV within 3 h. The cold storage at 1 degree C could preserve MPM at quasi-normal after 3 h but reduced it significantly after 24 h to 222.2 mV in saline (p < 0.005 vs. control) and 231.0 mV in UW solution (p < 0.05 vs. control): the difference between the 24-hour values was significant (p < 0.05).     

Enhancement of endogenous cyclic AMP signal: a new approach to allow for cold preservation of rat livers from non-heart-beating donors?

BACKGROUND: The organ donor shortage has led to a reconsideration of the use of non-heart-beating donors (NHBDs). However, graft injury due to warm ischemia in NHBD livers strongly affects posttransplant outcome. The present study was aimed at investigating the role of the cellular cyclic (c)AMP second messenger signal with regard to hepatic viability after cold preservation of NHBD livers. METHODS: Cardiac arrest was induced in Wistar rats by frenotomy of the anesthetized nonheparinized animal. After 30 min, the livers were excised and flushed with 20 ml of heparinized saline solution, rinsed with 10 ml of University of Wisconsin (UW) solution, and stored submerged in UW solution at 4 degrees C for 24 hr. In half of the experiments, UW solution was supplemented with glucagon (0.5 microg/ml) to increase the cAMP signal in the liver. Reperfusion was carried out in vitro after all livers were incubated at 25 degrees C in saline solution to replicate the period of slow rewarming during surgical implantation in vivo. RESULTS: Hepatic levels of cAMP (nmol/g dry weight) declined from 1.21+/-0.05 to 0.53+/-0.03 (P<0.01) at 30 min after cardiac arrest. Subsequent storage in UW solution resulted in a further decline to 0.35+/-0.04 after 24 hr in group A, whereas glucagon treatment enhanced cellular cAMP signal to 0.64+/-0.06 (P<0.01). Upon reperfusion, liver integrity was significantly improved after glucagon administration, with 66% reduction in alanine aminotransferase release and a threefold increase in hepatic bile production as compared with untreated livers. Moreover, liver ATP tissue levels were restored to only 2.19+/-0.51 micromol/g in the untreated group but reached 4.97+/-0.41 micromol/g (P<0.05) after treatment with glucagon. CONCLUSIONS: Posthoc conditioning of predamaged livers by glucagon enhances cAMP tissue levels during ischemic preservation and improves hepatic integrity upon reperfusion. This may represent a promising approach for the use of livers from non-heart-beating donors in clinical transplantation.     

Crystallization of Fe-Si-B metallic glasses studied by X-ray synchrotron radiation

We have studied the crystallization kinetics of Fe_90-x Si _x B₁₀ amorphous alloys withx ranging from 7 to 21, by synchrotron X-ray radiation. Using energy- dispersive X-ray diffraction, the kinetics of the different crystalline phases evolving during isothermal annealing were followed. These crystalline phases were identified as precipitation of-Fe(Si) and/or Fe₃Si in the amorphous matrix. At a later time or at a higher temperature, Fe₂B starts to crystallize (x < 21 ). Only at low iron concentration (x = 21) was the second phase different, namely Fe₅SiB₂ The hypo- and hyper-eutectic Fe-Si-B glasses were found to crystallize differently. The crystallization processes are discussed in some detail.     

Terrain‐inclination‐based Three‐dimensional Localization for Mobile Robots in Outdoor Environments

A new terrain‐inclination‐based localization technique is proposed in this paper to enable a robot to identify its three‐dimensional location relative to measurable terrain inclinations. Given a topographical map and a planned path, a robot‐terrain‐inclination model (RTI model) is extracted along the path on the terrain upon which the robot is operating. A particle filter is then used to fuse the measurement data with the robot motion based on the extracted RTI model for either a three‐wheeled or a four‐wheeled mobile robot. Experiments were carried out in four outdoor scenarios: one short path with different initial conditions and map resolution, another short path with different surface roughness and sensor accuracy, and two long paths with different types of rigid terrains and multiple loops. Experimental results show that the proposed method could achieve good localization performance on inclined outdoor terrains.     

The effect of twin plane spacing on the deformation of copper containing a high density of growth twins

In-situ tensile straining in a transmission electron microscope was used to investigate the role of twin plane spacing on the deformation and fracture mechanism of pure copper containing a high density of nanoscale growth twins. Real-time and post-mortem observations clearly reveal that twin plane spacing plays a key role in determining the operative deformation mechanism and therefore the subsequent crack propagation path. The deformation mechanism transition, which results from changes in the twin plane spacing, has implications for interpreting the unusual mechanical behavior of the copper with a high density of nanoscale growth twins.