Hepatic Arterial Infusion Therapy with Cisplatin using Protein Binding Inhibition : Pharmacokinetics and Antineoplastic Effects of Cisplatin Combined with L-Cysteine in Rats

Cisplatin の蛋白結合には共有結合が関与しており、L-cysteine はcisplatin の共有結合を低下させる。そこで、この蛋白結合阻害を利用してcisplatin の肝動注療法の応用性について検討を行った。実験では、Donryu系雄性ラットにおけるL-cysteine 併用時におけるcisplatin の体内動態と抗腫瘍効果の影響について検討した。その結果、L-cysteine 併用においてcisplatin のtotal とfree 濃度に有意な差はみられなかった。また肝癌ラットを使用したin vivo 実験系において、L-cysteine を併用したcisplatin の肝動注はcisplatin のみの投与に比べ、腫瘍増殖率が抑えられる傾向であることを示した。さらに肝組織中における腫瘍部と非腫瘍部におけるcisplatin 濃度において、L-cysteine 併用により腫瘍部と非腫瘍部に有意な差を認めることができた (p<0.01)。以上の結果より、L-cysteine の併用はcisplatin の肝動注療法へ応用できると考えられる。Covalent binding is involved in the protein binding of cisplatin. L-cysteine reduces the covalent binding of cisplatin. We investigated hepatic arterial infusion therapy with cisplatin using protein binding inhibition. In the present experiment, the pharmacokinetics and antineoplastic effects of cisplatin combined with L-cysteine in male Donryu rats were investigated. As a result, no significant difference was noted in the total and free concentrations of cisplatin combined with L-cysteine. In an in vivo experiment using rats with liver cancer, the hepatic arterial infusion of cisplatin combined with L-cysteine showed that it was the tendency that tumor growth rate was inhibited in comparison with administration only for cisplatin. In addition, concentrations of cisplatin increased significantly between tumor and non-tumor regions in liver tissue when combined with L-cysteine (p<0.01). Thus, L-cysteine can be combined with cisplatin for hepatic arterial infusion therapy

Performance of a 3Â kW wind turbine generator with variable pitch control system

A prototype 3 kW horizontal upwind type wind turbine generator of 4 m in diameter has been designed and examined under real wind conditions. The machine was designed based on the concept that even small wind turbines should have a variable pitch control system just as large wind turbines, especially in Japan where typhoons occur at least once a year. A characteristic of the machine is the use of a worm and gear system with a stepping motor installed in the center of the hub, and the rotational main shaft. The machine is constructed with no mechanical breaking system so as to avoid damage from strong winds. In a storm, the wind turbine is slowed down by adjusting the pitch angle and the maximum electrical load. Usually the machine is controlled at several stages depending on the rotational speed of the blades. Two control methods have been applied: the variable pitch angle, and regulation of the generator field current. The characteristics of the generator under each rotational speed and field current are first investigated in the laboratory. This paper describes the performances of the wind turbine in terms of the functions of wind turbine rotational speed, generated outputs, and its stability for wind speed changes. The expected performances of the machine have been confirmed under real wind conditions and compared with numerical simulation results. The wind turbine showed a power coefficient of 0.257 under the average wind speed of 7.3 m/s.Renewable energy Wind turbine generator Variable pitch control Field current control

FLOW AROUND A SUDDENLY START ROTATING CIRCULAR CYLINDER AND INTRODUCE A NEW PARADOX

ABSTRACT There have been many misunderstanding about the flow around vortices for example a stationary and/or moving vortex pair. The authors have pointed out that no fluid dynamics textbooks have accepted the existence of stationary or arbitral speed moving vortices. About the vortex flow, recently the authors have found a new analytic solution of the Navier-Stokes equations for twodimensional flow around a suddenly start rotating circular cylinder. This analytic solution explains the velocity distribution, vorticity distribution with change in time, and boundary layer thickness close to a vortex filament because of the action of viscosity. The resulting solutions are involved simple exponential function. Authors present a new construction for the solution of the Navier-Stokes equations for suddenly start rotating circular cylinder. New solution is based on the concept of the similarity solution approach using similarity variable, dimensional analysis, initial, &amp; boundary conditions. A brief theoretical discussion is presented about the suddenly start rotating circular cylinder. The second part of the paper deals with the analytic solution being compared with experimental results in various Reynolds number. A typical measurement is that of relaxation of rotational velocities when the cylinder is subjected only to the viscous resistance. To measure the velocity distribution of the flow the experiments were made with the help of tracer particle (aluminum powder and 150-grain diameter meshes) for water and oil (Super Mulpus 68). The effects of the Reynolds number on the laminar asymmetric flow structure in the flow region are studied. The induced speed distribution in the rotation of cylinder (diameter 10 mm) circumference has examined about the Reynolds number from 26 to 522 for water consequent cylinder rpm 10, 25, 50, 75, 100 and 0.12 to 2.32 for Super Mulpus 68 Oil consequent cylinder rpm 5, 10, 25, 50, 75, 100. The relation between the induced speeds after the time had passed enough and the various cylinder rotational speeds for both analytical and experimental results are shown. At lower Reynolds number experimental results are closer to theoretical results for a finite time condition, at that time there is exist vorticity around the cylinder. We can also establish that more difference between experimental and theoretical results with higher Reynolds number. An interesting phenomenon has been observed in the flow patterns at various Reynolds number and is discussed. Finally, authors have explained the significant difference between experimental and theoretical results and a new paradox has been introduced

Human-specific mutations in VMAT1 confer functional changes and multi-directional evolution in the regulation of monoamine circuits

Abstract Background Neurochemicals like serotonin and dopamine play crucial roles in human cognitive and emotional functions. Vesicular monoamine transporter 1 (VMAT1) transports monoamine neurotransmitters, and its variant (136Thr) is associated with various psychopathological symptoms and reduced monoamine uptake relative to 136Ile. We previously showed that two human-specific amino acid substitutions (Glu130Gly and Asn136Thr/Ile) of VMAT1 were subject to positive natural selection. However, the potential functional alterations caused by these substitutions (Glu130Gly and Asn136Thr) remain unclear. To assess functional changes in VMAT1 from an evolutionary perspective, we reconstructed ancestral residues and examined the role of these substitutions in monoamine uptake in vitro using fluorescent false neurotransmitters (FFN), which are newly developed substances used to quantitatively assay VMATs. Results Immunoblotting confirmed that all the transfected YFP-VMAT1 variants are properly expressed in HEK293T cells at comparable levels, and no significant difference was seen in the density and the size of vesicles among them. Our fluorescent assays revealed a significant difference in FFN206 uptake among VMAT1 variants: 130Glu/136Asn, 130Glu/136Thr, and 130Gly/136Ile showed significantly higher levels of FFN206 uptake than 130Gly/136Asn and 130Gly/136Thr, indicating that both 130Glu and 136Ile led to increased neurotransmitter uptake, for which 136Thr and 136Asn were comparable by contrast. Conclusions These findings suggest that monoamine uptake by VMAT1 initially declined (from 130Glu/136Asn to 130Gly/136Thr) in human evolution, possibly resulting in higher susceptibility to the external environment of our ancestors