Hiromasa Yamashita

2,2'-Azobis (4-methoxy-2,4-dimethylvaleronitrile), a new lipid-soluble azo initiator: application to oxidations of lipids and low-density lipoprotein in solution and in aqueous dispersions.

Both hydrophilic and hydrophobic azo radical initiators are useful for in vitro studies on lipid peroxidation and its inhibition by antioxidants. In the present study, a new lipophilic azo compound, 2,2-azobis(4-methoxy-2,4-dimethylvaleronitrile) (MeO-AMVN), was introduced and its action as an initiator of lipid peroxidation was examined. MeO-AMVN decomposed about 15 times as fast as 2,2-azobis(2,4-dimethylvaleronitrile) (AMVN), a widely used lipophilic azo initiator, and MeO-AMVN-initiated free radical-mediated peroxidations of lipids in organic solution and in micelles, membranes, and low-density lipoprotein in aqueous dispersions with much smaller concentration than AMVN. The rate of chain initiation by MeO-AMVN varied significantly with the medium and decreased with increasing viscosity of the medium. The advantage and cautions for using MeO-AMVN as a lipophilic radical source have been discussed and it has been concluded that MeO-AMVN, when properly used, is a useful radical initiator of lipid peroxidations especially in micelles, membranes, and lipoproteins.

Multi-slider linkage mechanism for endoscopic forceps manipulator

This paper proposes a new endoscopic hand-held forceps manipulator for endoscopic surgery using two bending mechanisms by multi-slider linkage mechanisms to achieve high mechanical performance and applicability. A bending mechanism consisted of three outer frames, two rotating joints and two sliding linkages for drive and restraint. Two pin-joints could rotate /spl plusmn/45 degrees respectively, enabling rotation of /spl plusmn/90 degrees. The rotation of the joint was available by pulling/pushing the adjacent element by sliding linkage in order. We connected two bending mechanisms, one was for the horizontal plane bending and the other was for the vertical plane bending, enabling 2-DOFs independent motions between -90 degrees and +90 degrees. The 2-DOFs bending mechanism and 1-DOF forceps mechanism were driven by three brushless DC-servomotors. A personal computer-based control unit determined displacement of sliding two linkages and of pulling one wire by the target angle of each DOF mechanism. We examined the actual angle of 2-DOFs bending mechanism, obtaining repeatability of /spl plusmn/0.87 degrees in the horizontal plane bending and /spl plusmn/0.91 degrees in the vertical plane bending. In vivo experiment, this manipulator performed endoscopic surgical tasks under pneumoperitoneum. In conclusion, we were sure of a usefulness of multi-slider linkage mechanism for the new handheld forceps manipulator for clinical application, which showed high repeatability of less 1.0 mm and large workspace with sufficient holding power of 0.55 kgf.

The specificity of lipoxygenase-catalyzed lipid peroxidation and the effects of radical-scavenging antioxidants

Abstract The oxidation of low density lipoprotein (LDL) by lipoxygenase has been implicated in the pathogenesis of atherosclerosis. It has been known that lipoxygenasemediated lipid peroxidation proceeds in general via regio, stereo and enantiospecific mechanisms, but that it is sometimes accompanied by a share of random hydroperoxides as side reaction products. In this study we investigated the oxidation of various substrates (linoleic acid, methyl linoleate, phosphatidylcholine, isolated LDL, and human plasma) by the arachidonate 15-lipoxygenases from rabbit reticulocytes and soybeans aiming at elucidating the effects of substrate, lipoxygenase and reaction milieu on the contribution and mechanism of random oxidation and also the effect of antioxidant. The specific character of the rabbit 15-lipoxygenase reaction was confirmed under all conditions employed here. However, the specificity by soybean lipoxygenase was markedly dependent on the conditions. When phosphatidylcholine liposomes and LDL were oxygenated by soybean lipoxygenase, the product pattern was found to be exclusively regio, stereo, and enantiorandom. When free linoleic acid was incorporated into PC liposomes and oxidized by soybean lipoxygenase, the free acid was specifically oxygenated, whereas esterified linoleate gave random oxidation products exclusively. Radicalscavenging antioxidants such as αtocopherol, ascorbic acid and 2-carboxy-2,5,7,8-tetramethyl-6-chromanol selectively inhibited the random oxidation but did not influence specific product formation. It is assumed that the random reaction products originate from free radical intermediates, which have escaped the active site of the enzyme and thus may be accessible to radical scavengers. These data indicate that the specificity of lipoxygenasecatalyzed lipid oxidation and the inhibitory effects of antioxidants depend on the physicochemical state of the substrate and type of lipoxygenase and that they may change completely depending on the conditions.

Oxidation of low density lipoprotein and plasma by 15-lipoxygenase and free radicals

It is generally accepted that the oxidation of pentadiene structures of polyunsaturated lipids by lipoxygenase (LOX) is regio‐ and enantio‐specific, while the free radical‐mediated lipid peroxidation gives stereo‐random racemic products. It was confirmed that the oxidation of human low density lipoprotein (LDL) by 15‐LOX from rabbit reticulocytes gave phosphatidylcholine (PC) and cholesteryl ester (CE) hydroperoxides regio‐, stereo‐ and enantio‐specifically. 15‐LOX also oxidized human plasma to give specific PC and CE hydroperoxides in spite of the presence of high concentrations of antioxidants. More CE hydroperoxides were formed than PC hydroperoxides from LDL, but the reverse order was observed for plasma oxidation. The S/R ratio of the hydroperoxides decreased during long time incubation but remained significantly larger than one, while free radical‐mediated oxidation of LDL and plasma gave racemic products.

Handheld Laparoscopic Forceps Manipulator Using Multi-slider Linkage Mechanisms

This paper proposes a new handheld laparoscopic forceps manipulator using 2-DOFs bending mechanism by multi-slider linkage mechanisms and 1-DOF wire-driven grasping mechanism. Careful design of the linkage channels enables unique and independent bending procedure from –90 to 90 degrees on the horizontal and vertical plane to secure large workspace. The manipulator consists of multi-DOFs end-effector, linear-drive unit, dial-type interface and computer-based control unit. In mechanical performance analyses, 2-DOFs bending mechanism enabled high accuracy of less 1.0 mm manipulation and high bending power of up to 0.85 kgf. In vivo experiments, this manipulator performed laparoscopic surgical tasks, such as raising the liver and the stomach, and suturing the stomach surface tissue in 22.3 ± 5.4 seconds per suture. Furthermore, we operated cholecystectomy with an animal within 45 minutes. In conclusion we were sure of a usefulness of a new handheld laparoscopic forceps manipulator for speedy and dexterous laparoscopic surgery.

Action of 21-aminosteroid U74006F as an antioxidant against lipid peroxidation.

The dynamics of the action of the 21-aminosteroid U74006F as an antioxidant against lipid peroxidation were studied in organic solution and membranes. It was confirmed that the reactivities of this compound toward stable phenoxyl radical and peroxyl radical were quite low. In fact, U74006F did not exert appreciable antioxidant effect against the free radical-driven oxidation of methyl linoleate in acetonitrile solution. However, it suppressed the oxidation of phosphatidylcholine liposomal membranes into which it was incorporated in a concentration-dependent manner. The 21-aminosteroid U74006F did not exert any sparing effect on the rate of alpha-tocopherol consumption in the oxidation of methyl linoleate in solution, but when they were simultaneously incorporated into the membrane, U74006F spared alpha-tocopherol and exerted a synergistic effect against the oxidation of liposomal membranes. This suggests that lipophilic U74006F acts as an antioxidant against lipid peroxidation through a physicochemical and not a pure chemical mechanism, and that a physical interaction with the liposomal membrane may facilitate the inhibition of lipid peroxidation with U74006F.

Distance Measuring Navigation for Fetoscopic Laser Photocoagulation to Treat Twin-to-Twin Transfusion Syndrome: Feasibility Evaluations

This paper reports feasibility evaluations of a distance measuring navigation for fetoscopic laser photocoagulation (FLP) of placental anastmotic communicating vessels between twin fetuses to treat twin-to-twin transfusion syndrome (TTTS) in intrauterine fetal surgery. This navigation uses only a laser fiber for photocoagulation and a fiberscope for a fetoscope, which are usually used in conventional FLP, and a computer to analyzing the fetoscopic view including a laser fiber tip and a guide-spot of red diode-laser. From fiberscopic view, pixels between center of the fetoscopic circular view and center of the guide-spot irradiated from a laser fiber are automatically detected. These pixels can be converted to the real distance between fetoscope tip and target according to geometric and optical relation of a laser fiber and a fetoscope including warping correction. In distance measuring evaluation, measuring errors between the fiberscope tip and target plates were under ± 1 mm around 10-mm distance from the target regardless of target angles (0 ~ 40 degrees) and colors. In conclusion, accuracy of our distance measuring navigation can provide more secure FLP in clinical use with minimum instruments.

Endoscope system with plasma flushing and separator for off-pump cardiac surgery

The purpose of this study is to develop a new endoscope for performing simple surgical tasks inside a cardiac atrium/chamber filled with blood, that is in “off-pump” cardiac surgeries. In general, it is very difficult to observe the inner side of the vessels containing circulating blood because the light of the endoscope is scattered by the red blood cells. The “plasma flushing” system is invented to observe the inner side of the heart filled with blood, to remove blood cells in front of the tip of the endoscope. We developed an endoscope with the separator to observe ϕ5-mm circle at 5.5-mm distant from endoscope.

Specificity and inhibition by antioxidant of lipid peroxidation by lipoxygenase: effects of substrate, lipoxygenase and milieu

Abstract Although lipid peroxidation by lipoxygenases usually results in a site-, stereo- and enantio-specific mechanism, it was found that the oxidation of phospholipids incorporated into the liposomal membrane by soybean lipoxygenase, but not by rabbit reticulocyte 15-lipoxygenase, was proceeded entirely by a nonspecific mechanism. The radical-scavenging antioxidants such as α-tocopherol did not inhibit specific oxidation; however, they did suppress the nonspecific oxidation.