A novel brain-derived member of the epidermal growth factor family that interacts with ErbB3 and ErbB4

The availability of an analgesic compound devoid of the side effects associated with the commonly used opioid and nonsteroidal antiinflammatory drugs would be useful during the perioperative period. Although adenosine has analgesic and anesthetic-sparing properties, it also produces dose-dependent cardiovascular depression. Inhibitors of adenosine kinase may be able to provide analgesia without producing acute cardiovascular or respiratory depression. This preliminary study investigated the effects of a novel adenosine kinase-inhibiting drug, GP683, on the minimum alveolar anesthetic concentration (MAC) of desflurane in dogs. Seven mongrel dogs were administered one of three different GP683 dose regimens (or the solvent) by intravenous infusion on separate occasions according to a cross-over study design. After determining the baseline desflurane MAC value, GP683 was infused at 75, 150, or 300 microg x kg(-1) x min(-1) for 5 min as a loading dose, followed by 15, 30, or 60 microg x kg(-1) x min(-1) for an additional 85 min to maintain a stable plasma drug level. The desflurane MAC was redetermined 30-90 min after starting the study drug or vehicle infusion, and 30-90 min and 120-180 min after termination of the infusion. Cardiovascular variables and plasma concentrations of GP683 were determined at specific intervals before, during, and after the MAC determinations. The three GP683 dose regimens produced 22%, 31%, and 50% decreases in the desflurane MAC, respectively. In addition, there was good correlation between the decrease in desflurane MAC and the plasma GP683 concentration (r = -0.78). Although the mean arterial pressure (MAP) was decreased up to 25% by the highest infusion rate of GP683, adjustments in the desflurane concentration to an equi-MAC value resulted in normalization of the MAP values. Furthermore, GP683 produced no changes in heart rate. In conclusion, the adenosine kinase-inhibiting drug, GP683, produced dose-dependent decreases in the desflurane MAC of dogs without producing untoward hemodynamic changes. IMPLICATIONS: An investigational drug (GP683) that can increase the levels of an important endogenous substance in the body (adenosine) has been found to decrease the anesthetic requirement in dogs without producing adverse effects on the cardiovascular system.     

A study of suppression of vapor explosions by adding inversely soluble polymers

The mechanism of the suppression of vapor explosions by adding inversely soluble polymers in water is studied. Vapor explosion experiments and quench experiment are conducted using a silver test piece. Polymetric solution (polyethylene oxide), of concentrations from 0 to 500 wppm, whose normalized viscosity (by water) varies from 1.00 to 2.00, is used. No vapor explosion is observed in the aqueous polymer solution at a concentration higher than 200 wppm. Quench experiments using the silver test piece submerged in the polymer solution and water are performed in order to examine the stability of film boiling. The suppression of the vapor film collapse is attributed to the precipitation of polyethylene as a gel around the vapor film. © 2002 Wiley Periodicals, Inc. Heat Trans Asian Res, 31(4): 297–306, 2002; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/htj.10037     

Cyclic Nigerosyl-Nigerose as Oxygen Nanocarrier to Protect Cellular Models from Hypoxia/Reoxygenation Injury: Implications from an In Vitro Model

Heart failure (HF) prevalence is increasing among the aging population, and the mortality rate remains unacceptably high despite improvements in therapy. Myocardial ischemia (MI) and, consequently, ischemia/reperfusion injury (IRI), are frequently the basis of HF development. Therefore, cardioprotective strategies to limit IRI are mandatory. Nanocarriers have been proposed as alternative therapy for cardiovascular disease. Controlled reoxygenation may be a promising strategy. Novel nanocarriers, such as cyclic nigerosyl-nigerose (CNN), can be innovative tools for oxygen delivery in a controlled manner. In this study we analyzed new CNN-based formulations as oxygen nanocarriers (O₂-CNN), and compared them with nitrogen CNN (N₂-CNN). These different CNN-based formulations were tested using two cellular models, namely, cardiomyoblasts (H9c2), and endothelial (HMEC) cell lines, at different concentrations. The effects on the growth curve during normoxia (21% O₂, 5% CO₂ and 74% N₂) and their protective effects during hypoxia (1% O₂, 5% CO₂ and 94% N₂) and reoxygenation (21% O₂, 5% CO₂ and 74% N₂) were studied. Neither O₂-CNN nor N₂-CNN has any effect on the growth curve during normoxia. However, O₂-CNN applied before hypoxia induces a 15–30% reduction in cell mortality after hypoxia/re-oxygenation when compared to N₂-CNN. O₂-CNN showed a marked efficacy in controlled oxygenation, which suggests an interesting potential for the future medical application of soluble nanocarrier systems for MI treatment.     

Prolonged degradation of end-capped polyelectrolyte multilayer films

Cationic chitosan (CT) and anionic dextran sulfate (Dex) were layer-by-layer (LbL) assembled from aqueous solutions containing 1 M NaCl on a quartz crystal microbalance (QCM) substrate, and the original films ((CT-Dex)₃-CT)) were end-capped with LbL assembly from CT solutions containing 1 M NaCl and Dex solutions without NaCl. The enzymatic degradation of films by chitosanase was quantitatively analyzed by QCM in terms of numbers of end-capping steps. The degradation of films end-capped with (Dex-CT)₃ was considerably prolonged when compared to those end-capped with other end-capping steps. A mechanism for the prolonged degradation was proposed by quantitative QCM data and zeta potential results.     

Syngas production by biomass gasification using Rh/CeO2/SiO2 catalysts and fluidized bed reactor

We have been developed novel catalysts for gasification of biomass with much higher energy efficiency than conventional methods (non-catalyst, dolomite, commercial steam reforming Ni catalyst). From the result of the gasification of cellulose over novel Rh/CeO₂/SiO₂ catalysts, it is found that the gasification process consists of the reforming of tar and the combustion of solid carbon. We also tested novel Rh/CeO₂/SiO₂ in the gasification with air, pyrogasification, and steam reforming of cedar wood. As a result, Rh/CeO₂/SiO₂ gave higher yield of syngas than the conventional steam reforming Ni catalyst. Furthermore, we compared the performance between single and dual bed reactors. Single bed reactor was effective in the gasification of cedar, however, it was not suitable for the gasification of rice straw since a rapid deactivation was observed. Gasification of rice straw, jute stick, baggase using the fluidized dual-bed reactor and Rh/CeO₂/SiO₂ was also investigated. Especially, the catalyst stability in the gasification of rice straw clearly was enhanced by using the fluidized dual bed reactor.     

Resistance to sulfur poisoning of hot gas cleaning catalysts for the removal of tar from the pyrolysis of cedar wood

In the partial oxidation of tar derived from the pyrolysis of cedar wood, the effect of H₂S addition was investigated over non-catalyst, steam reforming Ni catalyst, and Rh/CeO₂/SiO₂ using a fluidized bed reactor. In the non-catalytic gasification, the product distribution was not influenced by the presence of H₂S. Steam reforming Ni catalyst was effective for the tar removal without H₂S addition, however, the addition of H₂S deactivated drastically. In contrast, Rh/CeO₂/SiO₂ exhibited higher and more stable activity than the Ni catalyst even under the presence of high concentration of H₂S (280 ppm). On the Ni catalyst, the adsorption of sulfur was observed by XPS and Ni species was oxidized during the partial oxidation of tar. In the case of Rh/CeO₂/SiO₂, the adsorption of sulfur was below the detection limit of XPS. This can be related to the self-cleaning of catalyst surface during the circulation in the fluidized bed reactor for the partial oxidation of tar derived from cedar pyrolysis.     

Catalyst Design of Pt-Modified Ni/Al2O3 Catalyst with Flat Temperature Profile in Methane Reforming with CO2 and O2

Pt(0.3)/Ni(10)/Al₂O₃, prepared by a sequential impregnation method, exhibited a more excellent performance in methane reforming with CO₂ and O₂ in terms of the catalytic activity and the temperature profile of the catalyst bed than Pt(0.3) + Ni(10)/Al₂O₃ prepared by a coimpregnation method, Ni(10)/Al₂O₃, Pt(0.3)/Al₂O₃, and Pt(10)/Al₂O₃. It is thought that this is because the surface Pt atoms on Ni catalyst can contribute to the enhancement of the catalyst reducibility.     

Effectiveness of polyamidoamine dendrimers modified with tripeptide growth factor, glycyl-L-histidyl-L-lysine, for enhancement of function of hepatoma cells

Cationic polyamidoamine dendrimers are known to be highly branched cascade polymers. Tripeptide growth factor, glycyl-L-histidyl-L-lysine (GHK), was employed as a ligand for activation or attachment of cells from a rat hepatoma cell line, H4-H-E-C3, and immobilized at the terminus of the dendrimer (GHK-dendrimer) to develop a suitable surface for use as a culture substratum in the bioartificial liver support system (BAL). The growth of cells was inhibited by increasing the number of generations of GHK-dendrimers. On the other hand, urea synthesis and lidocaine clearance of the cells adhered on fifth generation GHK-dendrimers were enhanced much more than on first generation GHK-dendrimers. GHK was shown to act as a growth inhibitor and an activator of hepatoma cells. These properties of GHK are advantageous for the utilization of hepatoma cells in BAL. Ligand-modified dendrimers are very promising for the creation of a high-performance substratum for cell culture and high performance bioartificial organs, as well as for high-performance bioartificial liver systems. GHK may have the potential to be a highly useful ligand.     

Dietary eritadenine-induced alteration of molecular species composition of phospholipids in rats

The effect of dietary eritadenine, a hypocholesterolemic compound found in the mushroomLentinus edodes, on the fatty acid and molecular species profiles of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in the plasma and liver microsomes was investigated in relation to the hypocholesterolemic action of the compound in rats. Animals were fed the control or eritadenine-supplemented (50 mg/kg diet) diet for 14 d. Eritadenine supplementation significantly decreased the plasma concentrations of cholesterol and phospholipids, but not triglycerides. The PC/PE ratio of liver microsomes, but not plasma, was also markedly decreased by eritadenine. Eritadenine supplementation was found to increase the proportion of 18:2n-6 and, inversely, to decrease the proportion of 20:4n-6 and 22:5n-6 in plasma PC and liver microsomal PC and PE, indicating that eritadenine depressed the metabolism of linoleic acid. The effect of eritadenine on the profile of n-3 fatty acids was dissimilar in PC and PE. These changes in fatty acid composition were selectively reflected in the molecular species composition of both PC and PE; the extent of increase in 16:0–18:2 molecular species or decrease in 18:0–20:4 molecular species was apparently greater than that of other molecular species containing 18:2 or 20:4 in the sn-2 position. These results suggest that, in addition to the decrease in liver microsomal PC/PE ratio, the alteration of plasma PC molecular species composition might also participate in the hypocholesterolemic action of eritadenine.     

Elevation of plasma levels of L-dopa in transdermal administration of L-dopa-butylester in rats

To increase delivery of L-dopa in its transdermal absorption, a new lipophilic derivative of L-dopa, L-dopa-butylester, was synthesized. An in-vitro study employing two-chamber diffusion cells, in which the excised rat abdominal skin was mounted, revealed that, in the presence of L-menthol and ethanol, L-dopa-butylester penetrated in its original form more effectively than L-dopa. L-Dopa-butylester sheets were made by immersing wiper sheets in methanol containing the compound, and then evaporating the methanol. An extraction study of the compound from the sheets revealed that its stability was maintained for at least 12 weeks. In an in-vivo cutaneous absorption study, an L-dopa-butylester sheet was attached to the shaved rat abdominal skin. A hydrogel containing L-menthol and ethanol was spread on vinyl tape, and this sheet was placed over it. In plasma, the L-dopa level rose linearly between 30 and 180 min after the cutaneous application; L-dopa-butylester was not detected. The L-dopa level was higher than that in which L-dopa was applied. These findings indicated that the lipophilic nature of L-dopa-butylester further increased its penetration through the skin, and that L-dopa-butylester that was taken up into the general circulation system was rapidly converted to L-dopa by hydrolysis in the body.