Pharmacokinetic study of nerisopam and its n-acetyl metabolite in rats

Three doses were administered to the rats during the pharmacokinetic study of nerisopam and the plasma concentrations of nerisopam and its N-acetyl metabolite were determined parallelly by means of validated SPE-HPLC method developed by the authors. The pharmacokinetics of nerisopam could be described by a two-compartment open model in rats, it was absorbed rapidly and could be measured in plasma for about 8 hours. The peak plasma concentration of the N-acetyl metabolite was reached rapidly a little bit later than that of the parent compound, similarly to the human plasma, and it could be measured for about 12 hours. The pharmacokinetics of N-acetyl metabolite could be described by an one-compartment open model. The fast appearance of the metabolite and the Cmax and AUC 0-infinity values higher than those of nerisopam refer to an intensive "first-pass" metabolism. The AUC-dose curves indicate that supposingly the mechanism transforming the N-acetyl metabolites are not as fast as the acetylation.     

Catalysts for selective hydrogenation of soybean oil.1 II. Commercial catalysts

A survey of commercial hydrogenation catalysts demonstrated the higher selectivity (S_L= 2.4\s-2.7) of certain platinum, palladium and rhodium catalysts for hydrogenating linolenic components in soybean oil. Nickel catalysts generally showed selectivities below S_L=2.0 although skeletal nickel achieved higher values.Trans-isomers were in the range 7.8\s-15.4% for the above noble metal catalysts. Nickel catalysts provide a lesser degree of isomerization, 5.2\s-7.4% oftrans-isomers for the most selective catalysts. Presented at the AOCS Meeting at Toronto, 1962.     

Thermal decomposition of InP surfaces: volatile component loss, morphological changes, and pattern formation

The thermal decomposition of bulk and heteroepitaxial InP surfaces is studied by in-situ scanning electron microscopy combined with mass spectrometry and atomic force microscopy. Correlation is established between the evaporation of phosphorous and the formation of thermal etch pits. The formation of the pattern that the In droplets constitute is analysed using fractal mathematics. Only negligible roughening is induced by annealing outside the pits.     

Quantifying key uncertainties in the costs of nuclear power

In power system portfolio decisions, cost risk (uncertainty over cost) should be an important consideration, in addition to central estimates of cost. This study quantifies the uncertainty in each of the cost components for nuclear power, and combines them using a Monte Carlo analysis, allowing a direct assessment of cost risk for this technology. This can be used as an input to sophisticated portfolio optimisation modelling tools that take cost risk into account. Levelised cost of energy (LCOE) estimates are also provided here to allow an indicative comparison of the scale of cost risk, compared with other technologies. The most important contributors to cost risk for nuclear power generation are identified to be overnight capital cost (OCC) estimates, the degree of cost escalation over the construction and pre‐construction periods and the duration of those periods. In the absence of cost escalation, the mean LCOE of nuclear power is found to be AU$145/MWh in jurisdictions excluding Asia (or AU$130/MWh if Asian plant costs are included in the distributions), with a standard deviation of AU$62/MWh. However, when cost escalation over construction and pre‐construction periods is included at rates observed during nuclear build programs in France and the USA, the mean LCOE increases to AU$515/MWh, with a standard deviation of AU$2646/MWh. These results indicate that nuclear power costs have an 80% probability of exceeding AU$170/MWh, and a 50% probability of exceeding AU$278/MWh, based upon Monte Carlo analysis. This suggests that for OECD jurisdictions without an established nuclear industry (such as Australia), nuclear power may be comparable in cost with ‘dispatchable’, synchronous renewable alternatives such as concentrating solar thermal. Furthermore, the considerable cost risk associated with nuclear power is a significant disadvantage. Copyright © 2016 John Wiley & Sons, Ltd.     

Effect of gas-containing microspheres and echo contrast agents on free radical formation by ultrasound

Stabilized microbubbles (microspheres) are widely used to enhance the contrast of ultrasound imaging. Our data provide direct evidence that the contrast agents, Levovist, PVC-AN (polyvinylidene chloride-acrylonitryl copolymer), and Albunex (compared to 5% human albumin), at concentrations comparable to those used for ultrasound imaging, enhance H2O2 production (through the superoxide-dependent pathway) in air-saturated aqueous solutions exposed to 47 kHz ultrasound above the cavitation threshold. These agents also act as scavengers of .H atoms and .OH radicals, thus lowering H2O2 formation (by recombination of .OH radicals) in argon-saturated solutions. EPR spin trapping also reveals that secondary radicals derived from the contrast agents are produced by reactions with .H and .OH which are formed by pyrolysis of water inside cavitation bubbles. In addition, the contrast agents themselves undergo pyrolysis reactions in the cavitation bubbles as demonstrated by formation of methyl radicals. Possible deleterious consequences of the formation of sonochemical intermediates may have to be assessed, particularly since some of the echo contrast agents have been shown to lower the cavitation threshold of diagnostic ultrasound. Unlike the microspheres formed from organic molecules, inorganic microspheres, Eccospheres, because of their stability and inert nature with respect to participation in free radical processes, appear to be suitable tools for enhancing the yields of aqueous sonochemical reactions.     

Ion implantation modified stainless steel as a substrate for hydroxyapatite deposition. Part I. Surface modification and characterization

Material surfaces play critical role in biology and medicine since most biological reactions occur on surfaces and interfaces. There are many examples showing that the surface properties of the materials control and are directly involved in biological reactions and processes in-vitro like blood compatibility, protein absorption, cell development, etc. The rules that govern the diversity of biological surface phenomenon are fundamental physical laws. Stainless steel doped with Cr, Ni and Mo is widely used material in medicine and dentistry due to its excellent corrosion resistance and mechanical properties. The interest in this material has stimulated extensive studies on improving its bone-bonding properties. This paper describes the surface modification of Cr-Ni stainless steel (AISI 316) by a whole surface sequential implantation of Ca and P ions (the basic ions of hydroxyapatite). Three groups of stainless steel samples are prepared: (i) ion-implanted, (ii) ion-implanted and thermally treated at 600^∘C in air for 1 h and (iii) initials. The surface chemistry and topography before and after the surface modification are characterized by X-ray photoelectron spectroscopy, Auger electron spectroscopy, magic mirror method, atomic force microscopy and contact angle measurements.     

Nitric oxide formation from hydroxylamine by myoglobin and hydrogen peroxide

Hydroxylamine (HA), which is a natural product of mammalian cells, has been shown to possess vasodilatory properties in several model systems. In this study, HA and methyl-substituted hydroxylamines, N-methylhydroxylamine (NMHA) and N,N-dimethylhydroxylamine (NDMHA), have been tested for their ability to generate free diffusible nitric oxide (NO) in the presence of myoglobin (Mb) and hydrogen peroxide. A NO-specific conversion of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) to 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl (carboxy-PTI), measured by electron spin resonance (ESR) spectroscopy, along with nitrite and nitrate production, was observed for HA but not for NMHA and NDMHA. ESR measurements at 77 K showed the formation of the ferrous nitrosyl myoglobin, Mb-NO, in the reaction mixtures containing Mb, H2O2 and HA. Our data also demonstrate that Mb-NO is an end product of the reaction pathway involving Mb, H2O2 and HA, rather than a reaction intermediate in the formation of NO. In summary, our results demonstrate a possible pathway of NO formation from HA, however, the significance of this mechanism for bioactivation of HA in vivo is unknown at the present time.     

The life of Wilhelm Conrad Roentgen

This year, 1995, marks the centennial of the discovery of X-rays by Wilhelm Conrad Roentgen on the historical date of that discovery, November 8, 1895 [1]. After completing my radiology residency at Brooke General Hospital, I was assigned to the U.S. Army 5th General Hospital in Stuttgart Bad Cannstatt, West Germany. This period of payback was from October 1966 to August 1969. During these memorable years, the opportunity presented itself for me to make a pilgrimage to every location associated with the life of Roentgen. It is my pleasure to share that pilgrimage with you.