Suppressive effects of the endothelin receptor (ETA) antagonist BQ-123 on ET-1-induced reduction of lipoprotein lipase activity in 3T3-L1 adipocytes

Endothelin (ET)-1 reduced heparin-releasable lipoprotein lipase (LPL) activity in 3T3-L1 adipocytes in a concentration-dependent manner. However, a selective ETB receptor agonist, [Ala1,3,11,15]ET-1, did not act like ET-1. The ET-1-induced decrease in LPL activity was suppressed by a selective ETA receptor antagonist, BQ-123: the concentration-response curve for the ET-1 reduction of LPL activity was shifted to the right in the presence of BQ-123 in a concentration-dependent manner. This antagonistic effect of BQ-123 clarifies that the ETA receptor is responsible for the ET-1-induced reduction of LPL activity in 3T3-L1 adipocytes, which suggests that there is therapeutic potential for ETA antagonists in LPL-related lipoprotein disorders.     

Endogenous 7-oxocholesterol is an enzymatic product: characterization of 7 alpha-hydroxycholesterol dehydrogenase activity of hamster liver microsomes

Previously, we described a new metabolite derived from endogenous cholesterol in the presence of hamster liver microsomal protein and NADPH (Song et al., 1991, Biochem. Pharmacol. 41, 1439-1447). Through gas chromatography/mass spectral analysis of the metabolite and its methoxime-3-dimethyl-t-butylsilyl ether derivative, this metabolite has been definitively identified as 7-oxocholesterol. Isotope incorporation experiments using molecular 18O2 demonstrated that no oxygen atoms from molecular oxygen were incorporated into the product, 7-oxocholesterol, when 7 alpha-hydroxycholesterol was used as substrate. In contrast, one atom of 18O was incorporated into cholesterol from 18O2 during its metabolism to form 7 alpha-hydroxycholesterol. Formation of 7-oxocholesterol was dependent upon the presence of NADP+, 7 alpha-hydroxycholesterol, and hamster liver microsomes. This enzyme appears to be a membrane-bound protein and its activity was most abundant in liver microsomal fractions and to a lesser extent in mitochondrial fractions; little or no activity was observed in nuclei or cytosol. The enzyme activity was present in highest content in the livers of hamsters and was also observed in human and bovine liver microsomes, but not those of mouse, rabbit, or rat. The reaction was inhibited by 2'-AMP, but not by anti-NADPH:cytochrome-P450 oxidoreductase globulin, carbon monoxide, metyrapone, nor miconazole. In contrast to the previously characterized 3 beta-hydroxy-delta 5-C27-steroid oxidoreductase activity, NAD+ did not serve as an effective cofactor for 7-oxocholesterol formation. The ability of NADPH to partially serve as a cofactor in this reaction was shown to be due to a high NADPH-oxidase activity of hamster liver microsomes, thereby providing sufficient NADP+ to serve as the oxidizing pyridine nucleotide for the reaction. These results document the existence of a non-P450, NADP(+)-dependent 7 alpha-hydroxycholesterol dehydrogenase in liver microsomes which catalyzes this reaction. The product, 7-oxocholesterol, is produced enzymatically in the livers of hamsters and other mammals and may regulate bile acid metabolism or other processes due to its action as an oxysterol.     

A new method of endoscopic mucosal resection of neoplastic lesions in the stomach: its technical features and results

BACKGROUND/AIMS: In gastric cancer, endoscopic treatment can be expected to provide an absolute cure only if the lesion is mucosal and not accompanied by metastatic lymph nodes. To further evaluate such possibly curable lesions, we retrospectively reviewed 208 cases of early gastric cancer surgically resected over the past 20 years. METHODOLOGY: Our new method of endoscopic mucosal resection using a cap-fitted panendoscope, which is called EMRC, has been employed in the treatment of 73 gastric neoplastic lesions. RESULTS: It was found that curable lesions would, as the primary condition, be histologically well-differentiated carcinomas and measure 2 cm or less of the elevated type and less than 1 cm of the depressed type. The lesions were consequently identified as 49 early cancers (46 mucosal, 3 submucosal), 23 adenomas and 1 carcinoid. Although resection was completed in a single session of EMRC treatment in all cases, approximately 40% of them required fractionated resection, leaving an ulcer measuring 3 cm or more in approximately 30%. Bleeding or muscle resection occurred in 7 patients, in whom conservative treatment was effective. No recurrence has been found in any of the 73 lesions, demonstrating a favorable outcome. CONCLUSIONS: This method is advantageous in that it is simple and relatively easily applied at almost any location within the stomach. In addition, the size of the specimen obtained by en bloc resection is approximately 2 cm. The method is thus fairly likely to come into widespread use.     

Effect of altering filling pattern on diastolic pressure-volume curve

BACKGROUND: The early-to-late ventricular filling ratio (E:A) is widely used to index diastolic function. While filling patterns reflect diastolic properties, they can also modulate chamber pressures due to myocardial viscoelasticity. We hypothesized that such feedback can potentially temper effects of delayed relaxation and/or volume loading on diastolic pressures. METHODS AND RESULTS: Six isolated blood-perfused canine left ventricles were studied with ejection and filling controlled by an intracavitary volume servo-pump. Diastolic filling was determined by a simulated atrial pressure source that was either constant or varied to yield dual-phase filling at a specified E:A ratio. E:A ratio was randomly set to 3:1, 1:3, or 1:1, and data were recorded at each ratio at three different preloads. With principally early filling (E:A=3:1), diastolic pressure rise from viscosity increased in proportion with the relaxation time constant (r=.91, P<.0001). However, this dependence was lost as E:A ratio declined (eg, P=.63 for E:A 1:3). Furthermore, E:A=3:1 yielded 37% to 50% lower end-diastolic pressures at similar volumes (versus E:A=1:3) as initial viscous forces decayed. Offsetting early and late filling effects led to little net change in mean diastolic pressure independent of E:A ratio or preload. CONCLUSIONS: Diastolic filling pattern itself influences chamber pressures early and late in diastole due to viscoelasticity, with larger net effects on end-diastolic pressure. Since E:A ratio normally falls with delayed relaxation but rises with higher preload or reduced compliance, the present results suggest that changes in filling pattern may modulate direct effects of such factors on elevating diastolic pressure.     

Transition to an optimal periodic gait by simultaneous input and parameter optimization method of Hamiltonian systems

This paper is concerned with a gait transition to an optimal periodic gait by a simultaneous input and parameter optimization technique of Hamiltonian systems. First, a continuous-time dynamics of a passive walking/running robot between the touchdown and lift-off is considered as a Hamiltonian system. Then, the control input and some robot parameters, such as the mass, inertia, link length, and so on, are optimized using learning optimal control of Hamiltonian systems, which has been developed by the authors. This method allows one to simultaneously obtain an optimal feedforward input and optimal parameters, which (at least locally) minimize a given cost function. The main advantage is that the precise model of the dynamics of the plant system is not required using a symmetric property of Hamiltonian systems, called variational symmetry. We formulate an optimal gait generation scheme via the learning optimal control, where the robot keeps walking and the gait is optimized with respect to the control input and some adjustable robot parameters simultaneously. As a result, the gait transition to an optimal periodic one is achieved.     

Chemical transport rate of titanium disulfide

The chemical transport rate has been measured for various compositions of the nonstoichiometric titanium sulfide within the TiS₂ phase region using iodine as transport agent, with the result that the transport rate depends on the composition of the starting materials. The result was interpreted in terms of equilibrium pressure determined by the total pressure measurements on the TiS and TiSI systems.     

Studies of ethylene chlorohydrin formation in a bubble column reactor

An experimental study of the reactions of ethylene, chlorine, and water in a bubble column reactor, on a laboratory scale, has been carried out. The effect of gas flow rates on the yield of the products in an unbaffled reactor is reported. Baffles were introduced into the column to reduce axial mixing. A significant improvement in the conversion and yield of ethylene to ethylene chlorohydrin was observed.     

Model predictive tracking control for a linear system under time‐varying input constraints

In this paper, we propose a tracking control law for a linear dynamical system under time‐varying input constraints. The proposed control law consists of a dual‐mode model predictive control (MPC) law and a target recalculation mechanism. As the terminal controller of the dual‐mode MPC, we propose a saturation‐level‐dependent gain‐scheduled feedback control law that ensures closed‐loop stability against arbitrary change of the position limit of the actuators. We also present conditions that guarantee feasibility and stability of the control algorithm under time‐varying input constraints. The control algorithm is reduced to an online optimization problem under linear matrix inequality constraints. Copyright © 2012 John Wiley & Sons, Ltd.     

Noble metal catalysts highly-dispersed on Sm-doped ceria for the application to internal reforming solid oxide fuel cells operated at medium temperature

The synthesis of MTBE was studied in the gas phase at elevated temperatures (up to 175°C) and low pressures (150 kPa) where the MTBE formation rate is limited by thermodynamic equilibrium, using various solid acid catalysts (Amberlyst-15 resin, silica-alumina, HY and H-ZSM-5 zeolites). All the zeolites studied were found to exhibit better selectivities to MTBE than the commercially used Amberlyst-15 resin catalyst. The formation of byproducts increased with increasing temperature and appeared to have a strong enhancing effect on catalyst deactivation. H-ZSM-5 seems to be more suitable for high temperature formation of MTBE because of its excellent selectivity towards MTBE and low deactivation behavior.